Sample records for tissue-specific conditional ccm2

  1. The eHealth Enhanced Chronic Care Model: a theory derivation approach.

    PubMed

    Gee, Perry M; Greenwood, Deborah A; Paterniti, Debora A; Ward, Deborah; Miller, Lisa M Soederberg

    2015-04-01

    Chronic illnesses are significant to individuals and costly to society. When systematically implemented, the well-established and tested Chronic Care Model (CCM) is shown to improve health outcomes for people with chronic conditions. Since the development of the original CCM, tremendous information management, communication, and technology advancements have been established. An opportunity exists to improve the time-honored CCM with clinically efficacious eHealth tools. The first goal of this paper was to review research on eHealth tools that support self-management of chronic disease using the CCM. The second goal was to present a revised model, the eHealth Enhanced Chronic Care Model (eCCM), to show how eHealth tools can be used to increase efficiency of how patients manage their own chronic illnesses. Using Theory Derivation processes, we identified a "parent theory", the Chronic Care Model, and conducted a thorough review of the literature using CINAHL, Medline, OVID, EMBASE PsychINFO, Science Direct, as well as government reports, industry reports, legislation using search terms "CCM or Chronic Care Model" AND "eHealth" or the specific identified components of eHealth. Additionally, "Chronic Illness Self-management support" AND "Technology" AND several identified eHealth tools were also used as search terms. We then used a review of the literature and specific components of the CCM to create the eCCM. We identified 260 papers at the intersection of technology, chronic disease self-management support, the CCM, and eHealth and organized a high-quality subset (n=95) using the components of CCM, self-management support, delivery system design, clinical decision support, and clinical information systems. In general, results showed that eHealth tools make important contributions to chronic care and the CCM but that the model requires modification in several key areas. Specifically, (1) eHealth education is critical for self-care, (2) eHealth support needs to be placed within the context of community and enhanced with the benefits of the eCommunity or virtual communities, and (3) a complete feedback loop is needed to assure productive technology-based interactions between the patient and provider. The revised model, eCCM, offers insight into the role of eHealth tools in self-management support for people with chronic conditions. Additional research and testing of the eCCM are the logical next steps.

  2. Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development.

    PubMed

    He, Yun; Zhang, Haifeng; Yu, Luyang; Gunel, Murat; Boggon, Titus J; Chen, Hong; Min, Wang

    2010-04-06

    Cerebral cavernous malformations (CCMs) are human vascular malformations caused by mutations in three genes of unknown function: CCM1, CCM2, and CCM3. CCM3, also known as PDCD10 (programmed cell death 10), was initially identified as a messenger RNA whose abundance was induced by apoptotic stimuli in vitro. However, the in vivo function of CCM3 has not been determined. Here, we describe mice with a deletion of the CCM3 gene either ubiquitously or specifically in the vascular endothelium, smooth muscle cells, or neurons. Mice with global or endothelial cell-specific deletion of CCM3 exhibited defects in embryonic angiogenesis and died at an early embryonic stage. CCM3 deletion reduced vascular endothelial growth factor receptor 2 (VEGFR2) signaling in embryos and endothelial cells. In response to VEGF stimulation, CCM3 was recruited to and stabilized VEGFR2, and the carboxyl-terminal domain of CCM3 was required for the stabilization of VEGFR2. Indeed, the CCM3 mutants found in human patients lacking the carboxyl-terminal domain were labile and were unable to stabilize and activate VEGFR2. These results demonstrate that CCM3 promotes VEGFR2 signaling during vascular development.

  3. Stabiliztin of VEGFR2 Signaling by Cerebral Cavernous Malformation 3 is Critical for Vascular Development

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Y He; H Zhang; L Yu

    2011-12-31

    Cerebral cavernous malformations (CCMs) are human vascular malformations caused by mutations in three genes of unknown function: CCM1, CCM2, and CCM3. CCM3, also known as PDCD10 (programmed cell death 10), was initially identified as a messenger RNA whose abundance was induced by apoptotic stimuli in vitro. However, the in vivo function of CCM3 has not been determined. Here, we describe mice with a deletion of the CCM3 gene either ubiquitously or specifically in the vascular endothelium, smooth muscle cells, or neurons. Mice with global or endothelial cell-specific deletion of CCM3 exhibited defects in embryonic angiogenesis and died at an earlymore » embryonic stage. CCM3 deletion reduced vascular endothelial growth factor receptor 2 (VEGFR2) signaling in embryos and endothelial cells. In response to VEGF stimulation, CCM3 was recruited to and stabilized VEGFR2, and the carboxyl-terminal domain of CCM3 was required for the stabilization of VEGFR2. Indeed, the CCM3 mutants found in human patients lacking the carboxyl-terminal domain were labile and were unable to stabilize and activate VEGFR2. These results demonstrate that CCM3 promotes VEGFR2 signaling during vascular development.« less

  4. The eHealth Enhanced Chronic Care Model: A Theory Derivation Approach

    PubMed Central

    Greenwood, Deborah A; Paterniti, Debora A; Ward, Deborah; Miller, Lisa M Soederberg

    2015-01-01

    Background Chronic illnesses are significant to individuals and costly to society. When systematically implemented, the well-established and tested Chronic Care Model (CCM) is shown to improve health outcomes for people with chronic conditions. Since the development of the original CCM, tremendous information management, communication, and technology advancements have been established. An opportunity exists to improve the time-honored CCM with clinically efficacious eHealth tools. Objective The first goal of this paper was to review research on eHealth tools that support self-management of chronic disease using the CCM. The second goal was to present a revised model, the eHealth Enhanced Chronic Care Model (eCCM), to show how eHealth tools can be used to increase efficiency of how patients manage their own chronic illnesses. Methods Using Theory Derivation processes, we identified a “parent theory”, the Chronic Care Model, and conducted a thorough review of the literature using CINAHL, Medline, OVID, EMBASE PsychINFO, Science Direct, as well as government reports, industry reports, legislation using search terms “CCM or Chronic Care Model” AND “eHealth” or the specific identified components of eHealth. Additionally, “Chronic Illness Self-management support” AND “Technology” AND several identified eHealth tools were also used as search terms. We then used a review of the literature and specific components of the CCM to create the eCCM. Results We identified 260 papers at the intersection of technology, chronic disease self-management support, the CCM, and eHealth and organized a high-quality subset (n=95) using the components of CCM, self-management support, delivery system design, clinical decision support, and clinical information systems. In general, results showed that eHealth tools make important contributions to chronic care and the CCM but that the model requires modification in several key areas. Specifically, (1) eHealth education is critical for self-care, (2) eHealth support needs to be placed within the context of community and enhanced with the benefits of the eCommunity or virtual communities, and (3) a complete feedback loop is needed to assure productive technology-based interactions between the patient and provider. Conclusions The revised model, eCCM, offers insight into the role of eHealth tools in self-management support for people with chronic conditions. Additional research and testing of the eCCM are the logical next steps. PMID:25842005

  5. Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin.

    PubMed

    Retta, Saverio Francesco; Glading, Angela J

    2016-12-01

    Cerebral Cavernous Malformation (CCM) is a vascular disease of proven genetic origin, which may arise sporadically or is inherited as an autosomal dominant condition with incomplete penetrance and highly variable expressivity. CCM lesions exhibit a range of different phenotypes, including wide inter-individual differences in lesion number, size, and susceptibility to intracerebral hemorrhage (ICH). Lesions may remain asymptomatic or result in pathological conditions of various type and severity at any age, with symptoms ranging from recurrent headaches to severe neurological deficits, seizures, and stroke. To date there are no direct therapeutic approaches for CCM disease besides the surgical removal of accessible lesions. Novel pharmacological strategies are particularly needed to limit disease progression and severity and prevent de novo formation of CCM lesions in susceptible individuals. Useful insights into innovative approaches for CCM disease prevention and treatment are emerging from a growing understanding of the biological functions of the three known CCM proteins, CCM1/KRIT1, CCM2 and CCM3/PDCD10. In particular, accumulating evidence indicates that these proteins play major roles in distinct signaling pathways, including those involved in cellular responses to oxidative stress, inflammation and angiogenesis, pointing to pathophysiological mechanisms whereby the function of CCM proteins may be relevant in preventing vascular dysfunctions triggered by these events. Indeed, emerging findings demonstrate that the pleiotropic roles of CCM proteins reflect their critical capacity to modulate the fine-tuned crosstalk between redox signaling and autophagy that govern cell homeostasis and stress responses, providing a novel mechanistic scenario that reconciles both the multiple signaling pathways linked to CCM proteins and the distinct therapeutic approaches proposed so far. In addition, recent studies in CCM patient cohorts suggest that genetic susceptibility factors related to differences in vascular sensitivity to oxidative stress and inflammation contribute to inter-individual differences in CCM disease susceptibility and severity. This review discusses recent progress into the understanding of the molecular basis and mechanisms of CCM disease pathogenesis, with specific emphasis on the potential contribution of altered cell responses to oxidative stress and inflammatory events occurring locally in the microvascular environment, and consequent implications for the development of novel, safe, and effective preventive and therapeutic strategies. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  6. Does the chronic care model meet the emerging needs of people living with multimorbidity? A systematic review and thematic synthesis

    PubMed Central

    Abu Dabrh, Abd Moain; Gionfriddo, Michael R.; Erwin, Patricia; Montori, Victor M.

    2018-01-01

    Background The Chronic Care Model (CCM) emerged in the 1990s as an approach to re-organize primary care and implement critical elements that enable it to proactively attend to patients with chronic conditions. The chronic care landscape has evolved further, as most patients now present with multiple chronic conditions and increasing psychosocial complexity. These patients face accumulating and overwhelming complexity resulting from the sum of uncoordinated responses to each of their problems. Minimally Disruptive Medicine (MDM) was proposed to respond to this challenge, aiming at improving outcomes that matter to patients with the smallest burden of treatment. We sought to critically appraise the extent to which MDM constructs (e.g., reducing patient work, improving patients’ capacity) have been adopted within CCM implementations. Methods We conducted a systematic review and qualitative thematic synthesis of reports of CCM implementations published from 2011–2016. Results CCM implementations were mostly aligned with the healthcare system’s goals, condition-specific, and targeted disease-specific outcomes or healthcare utilization. No CCM implementation addressed patient work. Few reduced treatment workload without adding additional tasks. Implementations supported patient capacity by offering information, but rarely offered practical resources (e.g., financial assistance, transportation), helped patients reframe their biography with chronic illness, or assisted them in engaging with a supportive social network. Few implementations aimed at improving functional status or quality of life, and only one-third of studies were targeted for patients of low socioeconomic status. Conclusion MDM provides a lens to operationalize how to care for patients with multiple chronic conditions, but its constructs remain mostly absent from how implementations of the CCM are currently reported. Improvements to the primary care of patients with multimorbidity may benefit from the application of MDM, and the current CCM implementations that do apply MDM constructs should be considered exemplars for future implementation work. PMID:29420543

  7. Expression Profiling-Based Identification of CO2-Responsive Genes Regulated by CCM1 Controlling a Carbon-Concentrating Mechanism in Chlamydomonas reinhardtii1

    PubMed Central

    Miura, Kenji; Yamano, Takashi; Yoshioka, Satoshi; Kohinata, Tsutomu; Inoue, Yoshihiro; Taniguchi, Fumiya; Asamizu, Erika; Nakamura, Yasukazu; Tabata, Satoshi; Yamato, Katsuyuki T.; Ohyama, Kanji; Fukuzawa, Hideya

    2004-01-01

    Photosynthetic acclimation to CO2-limiting stress is associated with control of genetic and physiological responses through a signal transduction pathway, followed by integrated monitoring of the environmental changes. Although several CO2-responsive genes have been previously isolated, genome-wide analysis has not been applied to the isolation of CO2-responsive genes that may function as part of a carbon-concentrating mechanism (CCM) in photosynthetic eukaryotes. By comparing expression profiles of cells grown under CO2-rich conditions with those of cells grown under CO2-limiting conditions using a cDNA membrane array containing 10,368 expressed sequence tags, 51 low-CO2 inducible genes and 32 genes repressed by low CO2 whose mRNA levels were changed more than 2.5-fold in Chlamydomonas reinhardtii Dangeard were detected. The fact that the induction of almost all low-CO2 inducible genes was impaired in the ccm1 mutant suggests that CCM1 is a master regulator of CCM through putative low-CO2 signal transduction pathways. Among low-CO2 inducible genes, two novel genes, LciA and LciB, were identified, which may be involved in inorganic carbon transport. Possible functions of low-CO2 inducible and/or CCM1-regulated genes are discussed in relation to the CCM. PMID:15235119

  8. Rubisco small-subunit α-helices control pyrenoid formation in Chlamydomonas

    PubMed Central

    Meyer, Moritz T.; Genkov, Todor; Skepper, Jeremy N.; Jouhet, Juliette; Mitchell, Madeline C.; Spreitzer, Robert J.; Griffiths, Howard

    2012-01-01

    The pyrenoid is a subcellular microcompartment in which algae sequester the primary carboxylase, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). The pyrenoid is associated with a CO2-concentrating mechanism (CCM), which improves the operating efficiency of carbon assimilation and overcomes diffusive limitations in aquatic photosynthesis. Using the model alga Chlamydomonas reinhardtii, we show that pyrenoid formation, Rubisco aggregation, and CCM activity relate to discrete regions of the Rubisco small subunit (SSU). Specifically, pyrenoid occurrence was shown to be conditioned by the amino acid composition of two surface-exposed α-helices of the SSU: higher plant-like helices knock out the pyrenoid, whereas native algal helices establish a pyrenoid. We have also established that pyrenoid integrity was essential for the operation of an active CCM. With the algal CCM being functionally analogous to the terrestrial C4 pathway in higher plants, such insights may offer a route toward transforming algal and higher plant productivity for the future. PMID:23112177

  9. Convergent cross-mapping and pairwise asymmetric inference.

    PubMed

    McCracken, James M; Weigel, Robert S

    2014-12-01

    Convergent cross-mapping (CCM) is a technique for computing specific kinds of correlations between sets of times series. It was introduced by Sugihara et al. [Science 338, 496 (2012).] and is reported to be "a necessary condition for causation" capable of distinguishing causality from standard correlation. We show that the relationships between CCM correlations proposed by Sugihara et al. do not, in general, agree with intuitive concepts of "driving" and as such should not be considered indicative of causality. It is shown that the fact that the CCM algorithm implies causality is a function of system parameters for simple linear and nonlinear systems. For example, in a circuit containing a single resistor and inductor, both voltage and current can be identified as the driver depending on the frequency of the source voltage. It is shown that the CCM algorithm, however, can be modified to identify relationships between pairs of time series that are consistent with intuition for the considered example systems for which CCM causality analysis provided nonintuitive driver identifications. This modification of the CCM algorithm is introduced as "pairwise asymmetric inference" (PAI) and examples of its use are presented.

  10. Transformation of Strontium during formation of biogenic calcium carbonate

    NASA Astrophysics Data System (ADS)

    Ohnuki, T.; Kozai, N.; Sakamoto, F.; Yamashita, M.; Horiieke, T.; Utsunomiya, S.

    2016-12-01

    Some amounts of radionuclides contaminated water containing 90Sr generated in the Fukushima Daiichi Nuclear Power Plant were leaked to sea water in the port. One of the possible method to eliminate 90Sr is co-precipitated with biogenic carbonates minerals (CCM). Specific bacteria are known to form biogenic CCM in groundwater. In the present study, we have screened specific bacterium to form CCM in saline water, and studied transformation of Sr during biogenic CCM. A marine microbe of strain TK2d, which is screened from Tokyo bay to form CCM in saline solution, was grown in the medium solution contained urea and Sr. The concentratuion of Sr2+ in the solution was monitored by ICP-OES (ICP-OES; 720 Agilent Technologies, Inc., USA) during the formation of biogenic CCM. The precipitates were analyzed by SEM, TEM, and XAFS. When 1.0 mM Sr was dissolved in the medium solution, the concentration of Sr decreased up to 0.02 mM within 10 days, indicating that most of Sr in the solution was eliminated within 10 days. SEM and TEM analyses showed that needle shaped CCM containing Ca and Sr were formed. The CCM was not single crystalline, but poly-crystalline of calcite and aragonite. The elemental mapping showed that Sr was present at the same position of Ca, indicating that Sr was coprecipitated with Ca. The XANES analysis of Sr in the precipitates showed that the XANES spectrum was not the same as that of Sr coprecipitated with an abiotic Ca carbonates. Linear combination fitting of XANES spectra by those of SrCl2 and SrCO3 showed that both Sr2+ and SrCO3 were present in CCM. Longer contact time resulted in higher content of SrCO3, indicating that Sr was incorporated gradually with time into CCM structure. Thus, Sr was changed its chemical species from adsorbed one to the incorporated one in biogenic CCM in saline solution. This work was partially supported by a research grant from the Japan Science and Technology Agency, Japan (research grant No. 260502).

  11. Curcumin-incorporated albumin nanoparticles and its tumor image

    NASA Astrophysics Data System (ADS)

    Gong, Guangming; Pan, Qinqin; Wang, Kaikai; Wu, Rongchun; Sun, Yong; Lu, Ying

    2015-01-01

    Albumin is an ideal carrier for hydrophobic drugs. This paper reports a facile route to develop human serum albumin (HSA)-curcumin (CCM) nanoparticles, in which β-mercaptoethanol (β-ME) acted as an inducer and CCM acted as a bridge. Fluorescence quenching and conformational changes in HSA-CCM nanoparticles occurred during assembly. Disulfide bonds and hydrophobic interactions may play a key role in assembly. HSA-CCM nanoparticles were about 130 nm in size, and the solubility of CCM increased by more than 500 times. The HSA-CCM nanoparticles could accumulate at the cytoplasm of tumor cells and target the tumor tissues. Therefore, HSA nanoparticles fabricated by β-ME denaturation are promising nanocarriers for hydrophobic substances from chemotherapy drugs to imaging probes.

  12. Curcumin-incorporated albumin nanoparticles and its tumor image.

    PubMed

    Gong, Guangming; Pan, Qinqin; Wang, Kaikai; Wu, Rongchun; Sun, Yong; Lu, Ying

    2015-01-30

    Albumin is an ideal carrier for hydrophobic drugs. This paper reports a facile route to develop human serum albumin (HSA)-curcumin (CCM) nanoparticles, in which β-mercaptoethanol (β-ME) acted as an inducer and CCM acted as a bridge. Fluorescence quenching and conformational changes in HSA-CCM nanoparticles occurred during assembly. Disulfide bonds and hydrophobic interactions may play a key role in assembly. HSA-CCM nanoparticles were about 130 nm in size, and the solubility of CCM increased by more than 500 times. The HSA-CCM nanoparticles could accumulate at the cytoplasm of tumor cells and target the tumor tissues. Therefore, HSA nanoparticles fabricated by β-ME denaturation are promising nanocarriers for hydrophobic substances from chemotherapy drugs to imaging probes.

  13. Beneficial effects of the naturally occurring flavonoid silibinin on the prostate cancer microenvironment: role of monocyte chemotactic protein-1 and immune cell recruitment.

    PubMed

    Ting, Harold; Deep, Gagan; Kumar, Sushil; Jain, Anil K; Agarwal, Chapla; Agarwal, Rajesh

    2016-06-01

    Tumor microenvironment plays an essential role in prostate carcinogenesis and offers novel opportunities to prevent and treat prostate cancer (PCA). Here, we investigated the ability of cancer-associated fibroblasts (CAFs) to promote PCA progression, and silibinin efficacy to target this response. We collected conditioned media from CAFs treated with vehicle or silibinin, and labeled as control conditioned media (CCM) or silibinin-treatment conditioned media (SBCM), respectively. Next, we characterized the effect of CCM and SBCM treatment in several PCA cell lines (RWPE-1, WPE-1 NA-22, WPE-1 NB-14 and PC3). Result showed that compared with SBCM, CCM significantly reduces E-cadherin expression and increases invasiveness and clonogenicity in PCA cells. Further molecular studies identified monocyte chemotactic protein-1 (MCP-1) as the key component of CCM that promotes PCA invasiveness, whereas silibinin treatment strongly reduced MCP-1 expression in CAFs by inhibiting the DNA-binding activity of MCP-1 transcriptional regulators-nuclear factor-kappaB and AP-1. In vivo, silibinin feeding (200mg/kg body weight) strongly reduced TRAMPC1 allografts growth (by 68%) in syngeneic C57Bl/6 mice. TRAMPC1 tumor analysis showed that silibinin reduced MCP-1 and CAFs' biomarkers (fibroblast activation protein, α-smooth muscle actin, transforming growth factor beta 2, vimentin etc.) and significantly modulated the recruitment of immune cells in the tumor microenvironment. Similar inhibitory effects of silibinin on MCP-1 and immune cells recruitment were also observed in TRAMP PCA tissues with reported silibinin efficacy. Overall, our data suggest that silibinin can target CAF-mediated invasiveness in PCA by inhibiting MCP-1 secretion. This, in turn, was associated with a reduction in immune cell recruitment in vivo along with a marked reduction in tumor growth. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Beneficial effects of the naturally occurring flavonoid silibinin on the prostate cancer microenvironment: role of monocyte chemotactic protein-1 and immune cell recruitment

    PubMed Central

    Ting, Harold; Deep, Gagan; Kumar, Sushil; Jain, Anil K.; Agarwal, Chapla; Agarwal, Rajesh

    2016-01-01

    Tumor microenvironment plays an essential role in prostate carcinogenesis and offers novel opportunities to prevent and treat prostate cancer (PCA). Here, we investigated the ability of cancer-associated fibroblasts (CAFs) to promote PCA progression, and silibinin efficacy to target this response. We collected conditioned media from CAFs treated with vehicle or silibinin, and labeled as control conditioned media (CCM) or silibinin-treatment conditioned media (SBCM), respectively. Next, we characterized the effect of CCM and SBCM treatment in several PCA cell lines (RWPE-1, WPE-1 NA-22, WPE-1 NB-14 and PC3). Result showed that compared with SBCM, CCM significantly reduces E-cadherin expression and increases invasiveness and clonogenicity in PCA cells. Further molecular studies identified monocyte chemotactic protein-1 (MCP-1) as the key component of CCM that promotes PCA invasiveness, whereas silibinin treatment strongly reduced MCP-1 expression in CAFs by inhibiting the DNA-binding activity of MCP-1 transcriptional regulators—nuclear factor-kappaB and AP-1. In vivo, silibinin feeding (200mg/kg body weight) strongly reduced TRAMPC1 allografts growth (by 68%) in syngeneic C57Bl/6 mice. TRAMPC1 tumor analysis showed that silibinin reduced MCP-1 and CAFs’ biomarkers (fibroblast activation protein, α-smooth muscle actin, transforming growth factor beta 2, vimentin etc.) and significantly modulated the recruitment of immune cells in the tumor microenvironment. Similar inhibitory effects of silibinin on MCP-1 and immune cells recruitment were also observed in TRAMP PCA tissues with reported silibinin efficacy. Overall, our data suggest that silibinin can target CAF-mediated invasiveness in PCA by inhibiting MCP-1 secretion. This, in turn, was associated with a reduction in immune cell recruitment in vivo along with a marked reduction in tumor growth. PMID:27207648

  15. Reducing agent-free synthesis of curcumin-loaded albumin nanoparticles by self-assembly at room temperature.

    PubMed

    Safavi, Maryam Sadat; Shojaosadati, Seyed Abbas; Yang, Hye Gyeong; Kim, Yejin; Park, Eun Ji; Lee, Kang Choon; Na, Dong Hee

    2017-08-30

    The purpose of this study was to prepare curcumin-loaded bovine serum albumin nanoparticles (CCM-BSA-NPs) by reducing agent-free self-assembly at room temperature. A 2 4 factorial design approach was used to investigate the CCM-BSA-NP preparation process at different pH values, temperatures, dithiothreitol amounts, and CCM/BSA mass ratios. Increasing the ionic strength enabled preparation of CCM-BSA-NPs at 25°C without reducing agent. CCM-BSA-NPs prepared under the optimized conditions at 25°C showed a particle size of 110±6nm, yield of 88.5%, and drug loading of 7.1%. The CCM-BSA-NPs showed strong antioxidant activity and neuroprotective effects in glutamate-induced mouse hippocampal neuronal HT22 cells. This study suggests that ionic strength can be a key parameter affecting the preparation of albumin-based NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Dynamics of Carbon-Concentrating Mechanism Induction and Protein Relocalization during the Dark-to-Light Transition in Synchronized Chlamydomonas reinhardtii1[W][OPEN

    PubMed Central

    Mitchell, Madeline C.; Meyer, Moritz T.; Griffiths, Howard

    2014-01-01

    In the model green alga Chlamydomonas reinhardtii, a carbon-concentrating mechanism (CCM) is induced under low CO2 in the light and comprises active inorganic carbon transport components, carbonic anhydrases, and aggregation of Rubisco in the chloroplast pyrenoid. Previous studies have focused predominantly on asynchronous cultures of cells grown under low versus high CO2. Here, we have investigated the dynamics of CCM activation in synchronized cells grown in dark/light cycles compared with induction under low CO2. The specific focus was to undertake detailed time course experiments comparing physiology and gene expression during the dark-to-light transition. First, the CCM could be fully induced 1 h before dawn, as measured by the photosynthetic affinity for inorganic carbon. This occurred in advance of maximum gene transcription and protein accumulation and contrasted with the coordinated induction observed under low CO2. Between 2 and 1 h before dawn, the proportion of Rubisco and the thylakoid lumen carbonic anhydrase in the pyrenoid rose substantially, coincident with increased CCM activity. Thus, other mechanisms are likely to activate the CCM before dawn, independent of gene transcription of known CCM components. Furthermore, this study highlights the value of using synchronized cells during the dark-to-light transition as an alternative means of investigating CCM induction. PMID:25106822

  17. Identification of a Novel Gene, CIA6, Required for Normal Pyrenoid Formation in Chlamydomonas reinhardtii1[C][W][OA

    PubMed Central

    Ma, Yunbing; Pollock, Steve V.; Xiao, Ying; Cunnusamy, Khrishen; Moroney, James V.

    2011-01-01

    Chlamydomonas reinhardtii possesses a CO2-concentrating mechanism (CCM) that allows the alga to grow at low CO2 concentrations. One common feature seen in photosynthetic organisms possessing a CCM is the tight packaging of Rubisco within the cell. In many eukaryotic algae, Rubisco is localized to the pyrenoid, an electron-dense structure within the chloroplast. In order to identify genes required for a functional CCM, insertional Bleomycin resistance (BleR) mutants were generated and screened for growth on minimal medium under high CO2 conditions (5% CO2 in air) but only slow or no growth under very low CO2 conditions (0.01% CO2 in air). One mutant identified from this screen was named cia6. Physiological studies established that cia6 grows poorly on low levels of CO2 and has an impaired ability to accumulate inorganic carbon. The inserted BleR disrupted a gene encoding a protein with sequence similarity to proteins containing SET domain methyltransferase, although experiments using overexpressed CIA6 failed to demonstrate the methyltransferase activity. Electron microscopy revealed that the pyrenoid of cia6 mutant cells is highly disorganized. Complementation of the mutant restored the pyrenoid, the ability to grow under low-CO2 conditions, and the ability to concentrate inorganic carbon. Quantitative reverse transcription-polymerase chain reaction data from a low-CO2 induction time-course experiment demonstrated that the up-regulation of several CCM components is slower in cia6 compared with the wild type. This slow induction was further confirmed at the protein level using western blots. These results indicated that CIA6 is required for the formation of the pyrenoid and further supported the notion that the pyrenoid is required for a functional CCM in C. reinhardtii. PMID:21527423

  18. Collaborative Chronic Care Models for Mental Health Conditions: Cumulative Meta-Analysis and Meta-Regression to Guide Future Research and Implementation

    PubMed Central

    Grogan-Kaylor, Andrew; Perron, Brian E.; Kilbourne, Amy M.; Woltmann, Emily; Bauer, Mark S.

    2013-01-01

    Objective Prior meta-analysis indicates that collaborative chronic care models (CCMs) improve mental and physical health outcomes for individuals with mental disorders. This study aimed to investigate the stability of evidence over time and identify patient and intervention factors associated with CCM effects in order to facilitate implementation and sustainability of CCMs in clinical practice. Method We reviewed 53 CCM trials that analyzed depression, mental quality of life (QOL), or physical QOL outcomes. Cumulative meta-analysis and meta-regression were supplemented by descriptive investigations across and within trials. Results Most trials targeted depression in the primary care setting, and cumulative meta-analysis indicated that effect sizes favoring CCM quickly achieved significance for depression outcomes, and more recently achieved significance for mental and physical QOL. Four of six CCM elements (patient self-management support, clinical information systems, system redesign, and provider decision support) were common among reviewed trials, while two elements (healthcare organization support and linkages to community resources) were rare. No single CCM element was statistically associated with the success of the model. Similarly, meta-regression did not identify specific factors associated with CCM effectiveness. Nonetheless, results within individual trials suggest that increased illness severity predicts CCM outcomes. Conclusions Significant CCM trials have been derived primarily from four original CCM elements. Nonetheless, implementing and sustaining this established model will require healthcare organization support. While CCMs have typically been tested as population-based interventions, evidence supports stepped care application to more severely ill individuals. Future priorities include developing implementation strategies to support adoption and sustainability of the model in clinical settings while maximizing fit of this multi-component framework to local contextual factors. PMID:23938600

  19. Systems analysis of the CO2 concentrating mechanism in cyanobacteria

    PubMed Central

    Mangan, Niall M; Brenner, Michael P

    2014-01-01

    Cyanobacteria are photosynthetic bacteria with a unique CO2 concentrating mechanism (CCM), enhancing carbon fixation. Understanding the CCM requires a systems level perspective of how molecular components work together to enhance CO2 fixation. We present a mathematical model of the cyanobacterial CCM, giving the parameter regime (expression levels, catalytic rates, permeability of carboxysome shell) for efficient carbon fixation. Efficiency requires saturating the RuBisCO reaction, staying below saturation for carbonic anhydrase, and avoiding wasteful oxygenation reactions. We find selectivity at the carboxysome shell is not necessary; there is an optimal non-specific carboxysome shell permeability. We compare the efficacy of facilitated CO2 uptake, CO2 scavenging, and HCO3− transport with varying external pH. At the optimal carboxysome permeability, contributions from CO2 scavenging at the cell membrane are small. We examine the cumulative benefits of CCM spatial organization strategies: enzyme co-localization and compartmentalization. DOI: http://dx.doi.org/10.7554/eLife.02043.001 PMID:24842993

  20. Crystal Structure of CCM3, a Cerebral Cavernous Malformation Protein Critical for Vascular Integrity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, X.; Zhang, R; Zhang, H

    CCM3 mutations are associated with cerebral cavernous malformation (CCM), a disease affecting 0.1-0.5% of the human population. CCM3 (PDCD10, TFAR15) is thought to form a CCM complex with CCM1 and CCM2; however, the molecular basis for these interactions is not known. We have determined the 2.5 {angstrom} crystal structure of CCM3. This structure shows an all {alpha}-helical protein containing two domains, an N-terminal dimerization domain with a fold not previously observed, and a C-terminal focal adhesion targeting (FAT)-homology domain. We show that CCM3 binds CCM2 via this FAT-homology domain and that mutation of a highly conserved FAK-like hydrophobic pocket (HP1)more » abrogates CCM3-CCM2 interaction. This CCM3 FAT-homology domain also interacts with paxillin LD motifs using the same surface, and partial CCM3 co-localization with paxillin in cells is lost on HP1 mutation. Disease-related CCM3 truncations affect the FAT-homology domain suggesting a role for the FAT-homology domain in the etiology of CCM.« less

  1. Genome-Wide Identification of Regulatory Elements and Reconstruction of Gene Regulatory Networks of the Green Alga Chlamydomonas reinhardtii under Carbon Deprivation

    PubMed Central

    Vischi Winck, Flavia; Arvidsson, Samuel; Riaño-Pachón, Diego Mauricio; Hempel, Sabrina; Koseska, Aneta; Nikoloski, Zoran; Urbina Gomez, David Alejandro; Rupprecht, Jens; Mueller-Roeber, Bernd

    2013-01-01

    The unicellular green alga Chlamydomonas reinhardtii is a long-established model organism for studies on photosynthesis and carbon metabolism-related physiology. Under conditions of air-level carbon dioxide concentration [CO2], a carbon concentrating mechanism (CCM) is induced to facilitate cellular carbon uptake. CCM increases the availability of carbon dioxide at the site of cellular carbon fixation. To improve our understanding of the transcriptional control of the CCM, we employed FAIRE-seq (formaldehyde-assisted Isolation of Regulatory Elements, followed by deep sequencing) to determine nucleosome-depleted chromatin regions of algal cells subjected to carbon deprivation. Our FAIRE data recapitulated the positions of known regulatory elements in the promoter of the periplasmic carbonic anhydrase (Cah1) gene, which is upregulated during CCM induction, and revealed new candidate regulatory elements at a genome-wide scale. In addition, time series expression patterns of 130 transcription factor (TF) and transcription regulator (TR) genes were obtained for cells cultured under photoautotrophic condition and subjected to a shift from high to low [CO2]. Groups of co-expressed genes were identified and a putative directed gene-regulatory network underlying the CCM was reconstructed from the gene expression data using the recently developed IOTA (inner composition alignment) method. Among the candidate regulatory genes, two members of the MYB-related TF family, Lcr1 (Low-CO 2 response regulator 1) and Lcr2 (Low-CO 2 response regulator 2), may play an important role in down-regulating the expression of a particular set of TF and TR genes in response to low [CO2]. The results obtained provide new insights into the transcriptional control of the CCM and revealed more than 60 new candidate regulatory genes. Deep sequencing of nucleosome-depleted genomic regions indicated the presence of new, previously unknown regulatory elements in the C. reinhardtii genome. Our work can serve as a basis for future functional studies of transcriptional regulator genes and genomic regulatory elements in Chlamydomonas. PMID:24224019

  2. Effects of seven antifouling compounds on photosynthesis and inorganic carbon use in sugar kelp Saccharina latissima (Linnaeus).

    PubMed

    Johansson, Per; Eriksson, Karl Martin; Axelsson, Lennart; Blanck, Hans

    2012-10-01

    Macroalgae depend on carbon-concentrating mechanisms (CCMs) to maintain a high photosynthetic activity under conditions of low carbon dioxide (CO(2)) availability. Because such conditions are prevalent in marine environments, CCMs are important for upholding the macroalgal primary productivity in coastal zones. This study evaluated the effects of seven antifouling compounds-chlorothalonil, DCOIT, dichlofluanid, diuron, irgarol, tolylfluanid, and zinc pyrithione (ZnTP)-on the photosynthesis and CCM of sugar kelp (Saccharina latissima (L.)). Concentration-response curves of these toxicants were established using inhibition of carbon incorporation, whereas their effects over time and their inhibition of the CCM were studied using inhibition of O(2) evolution. We demonstrate that exposure to all compounds except ZnTP (< 1000 nM) resulted in toxicity to photosynthesis of S. latissima. However, carbon incorporation and O(2) evolution differed in their ability to detect toxicity from some of the compounds. Diuron, irgarol, DCOIT, tolylfluanid, and, to some extent, dichlofluanid inhibited carbon incorporation. Chlorothalonil did not inhibit carbon incorporation but clearly inhibited oxygen (O(2)) evolution. Photosynthesis showed only little recovery during the 2-h postexposure period. Inhibition of photosynthesis even increased after the end of exposure to chlorothalonil and tolylfluanid. Through changes in pH of the medium, toxic effects on the CCM could be studied isolated from photosynthesis effects. The CCM of S. latissima was inhibited by chlorothalonil, DCOIT, dichlofluanid, and tolylfluanid. Such inhibition of the CCM, or the absence thereof, deepens the understanding the mechanism of action of the studied compounds.

  3. RNA Editing Responses to Oxidative Stress between a Wild Abortive Type Male-Sterile Line and Its Maintainer Line

    PubMed Central

    Xiong, Jie; Tao, Tao; Luo, Zhi; Yan, Shuaigang; Liu, Yi; Yu, Xinqiao; Liu, Guolan; Xia, Hui; Luo, Lijun

    2017-01-01

    RNA editing of mitochondrial gene transcripts plays a central role during plant development and evolutionary adaptation. RNA editing has previously been reported to differ between the rice cytoplasmic male sterile (CMS) line and its maintainer line, which has been suggested as a cause for their different performances under environmental stress. To specifically test this hypothesis, a wild abortive (WA) CMS line (Huhan-1A) and its maintainer line (Huhan-1B) were utilized to investigate performances in response to oxidative stress, as well as RNA editing efficiencies on transcripts of six selected mitochondrial genes. Compared to the maintainer line, Huhan-1A represented both lower plant height and total antioxidant capacity, possessed higher total soluble protein and chlorophyll contents, accumulated less H2O2 content on the 3rd day after treatment (DAT), and exhibited higher survival ratio after re-watering. Furthermore, a total of 90 editing sites were detected on transcripts of six mitochondrial genes (atp9, nad2, nad7, nad9, ccmB, and ccmC) in both Huhan-1A and Huhan-1B on the 0, 1st, and 3rd DAT. Forty-eight sites were furthermore determined as stress-responsive sites (SRS). Generally, in response to oxidative stress, SRS in Huhan-1A increased the resulting editing efficiencies, while SRS in Huhan-1B decreased the resulting editing efficiencies. In addition, 33 and 22 sites at ccmB and ccmC were differentially edited between Huhan-1A and Huhan-1B, respectively, on the 0, 1st, and 3rd DAT. Editing efficiencies of ccmB and ccmC were generally lower in Huhan-1A (ccmB, 37.3–47.8%; ccmC, 41.2–52.3%) than those in Huhan-1B (ccmB, 82.6–86.5%; ccmC, 81.0–82.9%). Deficiencies of RNA editing in Huhan-1A at ccmB and ccmC could lead to the loss of transmembrane domains in their protein structures. Consequently, differences in RNA editing at ccmB and ccmC between the WA-CMS line and its maintainer line partially explained their different performances under stress. Moreover, we detected differences in expressions of pentatricopeptide repeat (PPR) genes between both lines, as well as significant correlations with RNA editing. Our study indicated potential associations of RNA editing and PPR genes in rice tolerance to abiotic stresses. However, the underlying molecular mechanisms of stress-adaptation, which are attributed to RNA editing on transcripts of mitochondrial genes, require further investigation. PMID:29234339

  4. Assembling Components with Aspect-Oriented Modeling/Specification

    DTIC Science & Technology

    2003-10-01

    2 COM: Component Object Mod 3 EJB: Enterprise Java Beans, h 4 CCM: CORBA® Component M 5 http...nt (GM of the co mbly of ct weav el, http: ttp:// java odel, htFigure 2: Connector as a Containertructure in the form of framework, which...assembles components in EJB3 , CCM4; or a package, using such way as manifest file to JavaBeans5. Also such connector in some cases plays the role as

  5. Transcriptome-Wide Changes in Chlamydomonas reinhardtii Gene Expression Regulated by Carbon Dioxide and the CO2-Concentrating Mechanism Regulator CIA5/CCM1[W][OA

    PubMed Central

    Fang, Wei; Si, Yaqing; Douglass, Stephen; Casero, David; Merchant, Sabeeha S.; Pellegrini, Matteo; Ladunga, Istvan; Liu, Peng; Spalding, Martin H.

    2012-01-01

    We used RNA sequencing to query the Chlamydomonas reinhardtii transcriptome for regulation by CO2 and by the transcription regulator CIA5 (CCM1). Both CO2 and CIA5 are known to play roles in acclimation to low CO2 and in induction of an essential CO2-concentrating mechanism (CCM), but less is known about their interaction and impact on the whole transcriptome. Our comparison of the transcriptome of a wild type versus a cia5 mutant strain under three different CO2 conditions, high CO2 (5%), low CO2 (0.03 to 0.05%), and very low CO2 (<0.02%), provided an entry into global changes in the gene expression patterns occurring in response to the interaction between CO2 and CIA5. We observed a massive impact of CIA5 and CO2 on the transcriptome, affecting almost 25% of all Chlamydomonas genes, and we discovered an array of gene clusters with distinctive expression patterns that provide insight into the regulatory interaction between CIA5 and CO2. Several individual clusters respond primarily to either CIA5 or CO2, providing access to genes regulated by one factor but decoupled from the other. Three distinct clusters clearly associated with CCM-related genes may represent a rich source of candidates for new CCM components, including a small cluster of genes encoding putative inorganic carbon transporters. PMID:22634760

  6. Can increased leaf photosynthesis be converted into higher crop mass production? A simulation study for rice using the crop model GECROS

    PubMed Central

    Struik, Paul C.

    2017-01-01

    Abstract Various genetic engineering routes to enhance C3 leaf photosynthesis have been proposed to improve crop productivity. However, their potential contribution to crop productivity needs to be assessed under realistic field conditions. Using 31 year weather data, we ran the crop model GECROS for rice in tropical, subtropical, and temperate environments, to evaluate the following routes: (1) improving mesophyll conductance (gm); (2) improving Rubisco specificity (Sc/o); (3) improving both gm and Sc/o; (4) introducing C4 biochemistry; (5) introducing C4 Kranz anatomy that effectively minimizes CO2 leakage; (6) engineering the complete C4 mechanism; (7) engineering cyanobacterial bicarbonate transporters; (8) engineering a more elaborate cyanobacterial CO2-concentrating mechanism (CCM) with the carboxysome in the chloroplast; and (9) a mechanism that combines the low ATP cost of the cyanobacterial CCM and the high photosynthetic capacity per unit leaf nitrogen. All routes improved crop mass production, but benefits from Routes 1, 2, and 7 were ≤10%. Benefits were higher in the presence than in the absence of drought, and under the present climate than for the climate predicted for 2050. Simulated crop mass differences resulted not only from the increased canopy photosynthesis competence but also from changes in traits such as light interception and crop senescence. The route combinations gave larger effects than the sum of the effects of the single routes, but only Route 9 could bring an advantage of ≥50% under any environmental conditions. To supercharge crop productivity, exploring a combination of routes in improving the CCM, photosynthetic capacity, and quantum efficiency is required. PMID:28379522

  7. Micro-CT Imaging Reveals Mekk3 Heterozygosity Prevents Cerebral Cavernous Malformations in Ccm2-Deficient Mice

    PubMed Central

    Choi, Jaesung P.; Foley, Matthew; Zhou, Zinan; Wong, Weng-Yew; Gokoolparsadh, Naveena; Arthur, J. Simon C.; Li, Dean Y.; Zheng, Xiangjian

    2016-01-01

    Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation in humans. Mouse models of CCM disease have been established by deleting Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. However, the full value of these animal models is limited by the lack of an accurate and quantitative method to assess lesion burden and progression. In the present study we have established a refined and detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in mouse brains. As this study utilized a voxel dimension of 9.5μm (leading to a minimum feature size of approximately 25μm), it is therefore sufficient to measure CCM lesion volume and number globally and accurately, and provide high-resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the mouse hindbrain with similar total volume and number. This quantitative approach also demonstrated a rescue of CCM lesions with simultaneous deletion of one allele of Mekk3. This method would enhance the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases. PMID:27513872

  8. High-throughput sequencing of the entire genomic regions of CCM1/KRIT1, CCM2 and CCM3/PDCD10 to search for pathogenic deep-intronic splice mutations in cerebral cavernous malformations.

    PubMed

    Rath, Matthias; Jenssen, Sönke E; Schwefel, Konrad; Spiegler, Stefanie; Kleimeier, Dana; Sperling, Christian; Kaderali, Lars; Felbor, Ute

    2017-09-01

    Cerebral cavernous malformations (CCM) are vascular lesions of the central nervous system that can cause headaches, seizures and hemorrhagic stroke. Disease-associated mutations have been identified in three genes: CCM1/KRIT1, CCM2 and CCM3/PDCD10. The precise proportion of deep-intronic variants in these genes and their clinical relevance is yet unknown. Here, a long-range PCR (LR-PCR) approach for target enrichment of the entire genomic regions of the three genes was combined with next generation sequencing (NGS) to screen for coding and non-coding variants. NGS detected all six CCM1/KRIT1, two CCM2 and four CCM3/PDCD10 mutations that had previously been identified by Sanger sequencing. Two of the pathogenic variants presented here are novel. Additionally, 20 stringently selected CCM index cases that had remained mutation-negative after conventional sequencing and exclusion of copy number variations were screened for deep-intronic mutations. The combination of bioinformatics filtering and transcript analyses did not reveal any deep-intronic splice mutations in these cases. Our results demonstrate that target enrichment by LR-PCR combined with NGS can be used for a comprehensive analysis of the entire genomic regions of the CCM genes in a research context. However, its clinical utility is limited as deep-intronic splice mutations in CCM1/KRIT1, CCM2 and CCM3/PDCD10 seem to be rather rare. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Effect of Curcumin Supplementation on Physiological Fatigue and Physical Performance in Mice

    PubMed Central

    Huang, Wen-Ching; Chiu, Wan-Chun; Chuang, Hsiao-Li; Tang, Deh-Wei; Lee, Zon-Min; Wei, Li; Chen, Fu-An; Huang, Chi-Chang

    2015-01-01

    Curcumin (CCM) is a well-known phytocompound and food component found in the spice turmeric and has multifunctional bioactivities. However, few studies have examined its effects on exercise performance and physical fatigue. We aimed to evaluate the potential beneficial effects of CCM supplementation on fatigue and ergogenic function following physical challenge in mice. Male ICR mice were divided into four groups to receive vehicle or CCM (180 μg/mL) by oral gavage at 0, 12.3, 24.6, or 61.5 mL/kg/day for four weeks. Exercise performance and anti-fatigue function were evaluated after physical challenge by forelimb grip strength, exhaustive swimming time, and levels of physical fatigue-associated biomarkers serum lactate, ammonia, blood urea nitrogen (BUN), and glucose and tissue damage markers such as aspartate transaminase (AST), alanine transaminase (ALT), and creatine kinase (CK). CCM supplementation dose-dependently increased grip strength and endurance performance and significantly decreased lactate, ammonia, BUN, AST, ALT, and CK levels after physical challenge. Muscular glycogen content, an important energy source for exercise, was significantly increased. CCM supplementation had few subchronic toxic effects. CCM supplementation may have a wide spectrum of bioactivities for promoting health, improving exercise performance and preventing fatigue. PMID:25647661

  10. Provider Experiences with Chronic Care Management (CCM) Services and Fees: A Qualitative Research Study.

    PubMed

    O'Malley, Ann S; Sarwar, Rumin; Keith, Rosalind; Balke, Patrick; Ma, Sai; McCall, Nancy

    2017-12-01

    Support for ongoing care management and coordination between office visits for patients with multiple chronic conditions has been inadequate. In January 2015, Medicare introduced the Chronic Care Management (CCM) payment policy, which reimburses providers for CCM activities for Medicare beneficiaries occurring outside of office visits. To explore the experiences, facilitators, and challenges of practices providing CCM services, and their implications going forward. Semi-structured telephone interviews from January to April 2016 with 71 respondents. Sixty billing and non-billing providers and practice staff knowledgeable about their practices' CCM services, and 11 professional society representatives. Practice respondents noted that most patients expressed positive views of CCM services. Practice respondents also perceived several patient benefits, including improved adherence to treatment, access to care team members, satisfaction, care continuity, and care coordination. Facilitators of CCM provision included having an in-practice care manager, patient-centered medical home recognition, experience developing care plans, patient trust in their provider, and supplemental insurance to cover CCM copayments. Most billing practices reported few problems obtaining patients' consent for CCM, though providers felt that CMS could better facilitate consent by marketing CCM's goals to beneficiaries. Barriers reported by professional society representatives and by billing and non-billing providers included inadequacy of CCM payments to cover upfront investments for staffing, workflow modification, and time needed to manage complex patients. Other barriers included inadequate infrastructure for health information exchange with other providers and limited electronic health record capabilities for documenting and updating care plans. Practices owned by hospital systems and large medical groups faced greater bureaucracy in implementing CCM than did smaller, independent practices. Improving providers' experiences with and uptake of CCM will require addressing several challenges, including the upfront investment for CCM set-up and the time required to provide CCM to more complex patients.

  11. Calcium absorption from apple and orange juice fortified with calcium citrate malate (CCM).

    PubMed

    Andon, M B; Peacock, M; Kanerva, R L; De Castro, J A

    1996-06-01

    Determine calcium (Ca) absorption from Ca fortified orange and apple juice. Absorbability was assessed by measuring 45Ca absorption in healthy women (mean age 57 years, n = 57/group) and whole body 47Ca retention in adult female beagle dogs (n = 6/group) and young adult male rats (n = 6/group). Women received 6.24 mmol (250 mg) Ca as calcium citrate malate fortified orange juice (CCM-OJ) or apple juice (CCM-AJ). Dogs received 3.12 mmol (125 mg) Ca as CCM-OJ or CCM-AJ. Rats were administered 0.15 mmol (6 mg) Ca as either milk, CCM-OJ, or CCM-AJ. Additional 47Ca whole body retention experiments in rats measured the effects of differences in the carbohydrate and organic acid contents of the juices on Ca absorption. Mean +/- SEM percent Ca fractional absorption was greater (p < 0.003) in women who consumed CCM-AJ (42 +/- 2%) than those who consumed CCM-OJ (36 +/- 1%). Ca retention in dogs was 15 +/- 1% for CCM-OJ and 29 +/- 2% for CCM-AJ (p < 0.001). Ca retention was significantly different (p < 0.05) in rats administered milk (42 +/- 2%), CCM-OJ (52 +/- 2%), or CCM-AJ (61 +/- 2%). By manipulating the carbohydrate and organic acid concentrations of test solutions to mimic the composition of Ca fortified juices, we found that the greater fructose and lower organic acid content of apple juice accounted for its greater Ca absorbability. CCM fortified versions of orange and apple juice have high Ca absorbability and are potentially important vehicles for increasing dietary Ca intake. The greater Ca absorption from CCM-AJ compared with CCM-OJ is accounted for by differences in the carbohydrate and organic acid content of the juices. These data suggest that by modifying common beverage ingredients, products with even greater Ca absorbability could be formulated.

  12. Contemporary commercial music (CCM) survey: who's teaching what in nonclassical music.

    PubMed

    LoVetri, Jeannette L; Weekly, Edrie Means

    2003-06-01

    Currently, there is an increasing interest in and demand for training in a wide variety of nonclassical music--contemporary commercial music (CCM)--and most particularly for music theater. A survey of singing teachers was completed to elucidate their training, education, and experience with and methods of teaching CCM. Teachers were at colleges, universities, and conservatories as well as in private studios, both nationally and in several foreign countries. A substantial percentage of those teaching CCM had neither formal education in teaching it nor professional experience. Many of the respondents indicated conflict between classical and CCM styles. Respondents were generally familiar with voice science and voice medicine as well as certain CCM terminology. Teachers expressed an interest in obtaining more information, with an emphasis on healthy vocal production. These results are discussed, as well as implications for the singing teacher who desires specific training to teach CCM.

  13. P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces

    PubMed Central

    Plutoni, Cédric; Bazellieres, Elsa; Le Borgne-Rochet, Maïlys; Comunale, Franck; Brugues, Agusti; Séveno, Martial; Planchon, Damien; Thuault, Sylvie; Morin, Nathalie; Bodin, Stéphane; Trepat, Xavier

    2016-01-01

    Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell–cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-PIX, which is specifically recruited at cell–cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through β-PIX–mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM. PMID:26783302

  14. Child contact management in high tuberculosis burden countries: A mixed-methods systematic review.

    PubMed

    Szkwarko, Daria; Hirsch-Moverman, Yael; Du Plessis, Lienki; Du Preez, Karen; Carr, Catherine; Mandalakas, Anna M

    2017-01-01

    Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. Considering the World Health Organization recommendation to implement child contact management (CCM) for TB, we conducted a mixed-methods systematic review to summarize CCM implementation, challenges, predictors, and recommendations. We searched the electronic databases of PubMed/MEDLINE, Scopus, and Web of Science for studies published between 1996-2017 that reported CCM data from high TB-burden countries. Protocol details for this systematic review were registered on PROSPERO: International prospective register of systematic reviews (#CRD42016038105). We formulated a search strategy to identify all available studies, published in English that specifically targeted a) population: child contacts (<15 years) exposed to TB in the household from programmatic settings in high burden countries (HBCs), b) interventions: CCM strategies implemented within the CCM cascade, c) comparisons: CCM strategies studied and compared in HBCs, and d) outcomes: monitoring and evaluation of CCM outcomes reported in the literature for each CCM cascade step. We included any quantitative, qualitative, mixed-methods study design except for randomized-controlled trials, editorials or commentaries. Thirty-seven studies were reviewed. Child contact losses varied greatly for screening, isoniazid preventive therapy initiation, and completion. CCM challenges included: infrastructure, knowledge, attitudes, stigma, access, competing priorities, and treatment. CCM recommendations included: health system strengthening, health education, and improved preventive therapy. Identified predictors included: index case and clinic characteristics, perceptions of barriers and risk, costs, and treatment characteristics. CCM lacks standardization resulting in common challenges and losses throughout the CCM cascade. Prioritization of a CCM-friendly healthcare environment with improved CCM processes and tools; health education; and active, evidence-based strategies can decrease barriers. A focused approach toward every aspect of the CCM cascade will likely diminish losses throughout the CCM cascade and ultimately decrease TB related morbidity and mortality in children.

  15. Child contact management in high tuberculosis burden countries: A mixed-methods systematic review

    PubMed Central

    Du Plessis, Lienki; Du Preez, Karen; Carr, Catherine; Mandalakas, Anna M.

    2017-01-01

    Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. Considering the World Health Organization recommendation to implement child contact management (CCM) for TB, we conducted a mixed-methods systematic review to summarize CCM implementation, challenges, predictors, and recommendations. We searched the electronic databases of PubMed/MEDLINE, Scopus, and Web of Science for studies published between 1996–2017 that reported CCM data from high TB-burden countries. Protocol details for this systematic review were registered on PROSPERO: International prospective register of systematic reviews (#CRD42016038105). We formulated a search strategy to identify all available studies, published in English that specifically targeted a) population: child contacts (<15 years) exposed to TB in the household from programmatic settings in high burden countries (HBCs), b) interventions: CCM strategies implemented within the CCM cascade, c) comparisons: CCM strategies studied and compared in HBCs, and d) outcomes: monitoring and evaluation of CCM outcomes reported in the literature for each CCM cascade step. We included any quantitative, qualitative, mixed-methods study design except for randomized-controlled trials, editorials or commentaries. Thirty-seven studies were reviewed. Child contact losses varied greatly for screening, isoniazid preventive therapy initiation, and completion. CCM challenges included: infrastructure, knowledge, attitudes, stigma, access, competing priorities, and treatment. CCM recommendations included: health system strengthening, health education, and improved preventive therapy. Identified predictors included: index case and clinic characteristics, perceptions of barriers and risk, costs, and treatment characteristics. CCM lacks standardization resulting in common challenges and losses throughout the CCM cascade. Prioritization of a CCM-friendly healthcare environment with improved CCM processes and tools; health education; and active, evidence-based strategies can decrease barriers. A focused approach toward every aspect of the CCM cascade will likely diminish losses throughout the CCM cascade and ultimately decrease TB related morbidity and mortality in children. PMID:28763500

  16. Update on Novel CCM Gene Mutations in Patients with Cerebral Cavernous Malformations.

    PubMed

    Scimone, Concetta; Bramanti, Placido; Alafaci, Concetta; Granata, Francesca; Piva, Francesco; Rinaldi, Carmela; Donato, Luigi; Greco, Federica; Sidoti, Antonina; D'Angelo, Rosalia

    2017-02-01

    Cerebral cavernous malformations (CCMs) are lesions affecting brain microvessels. The pathogenesis is not clearly understood. Conventional classification criterion is based on genetics, and thus, familial and sporadic forms can be distinguished; however, classification of sporadic cases with multiple lesions still remains uncertain. To date, three CCM causative genes have been identified: CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10. In our previous mutation screening, performed in a cohort of 95 Italian patients, with both sporadic and familial cases, we identified several mutations in CCM genes. This study represents further molecular screening in a cohort of 19 Italian patients enrolled by us in the few last years and classified into familial, sporadic and sporadic with multiple lesions cases. Direct sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis were performed to detect point mutations and large genomic rearrangements, respectively. Effects of detected mutations and single-nucleotide polymorphisms (SNPs) were evaluated by an in silico approach and by western blot analysis. A novel nonsense mutation in CCM1 and a novel missense mutation in CCM2 were detected; moreover, several CCM2 gene polymorphisms in sporadic CCM patients were reported. We believe that these data enrich the mutation spectrum of CCM genes, which is useful for genetic counselling to identify both familial and sporadic CCM cases, as early as possible.

  17. Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

    PubMed Central

    Zhang, Yumin; Zhou, Junhui; Yang, Cuihong; Wang, Weiwei; Chu, Liping; Huang, Fan; Liu, Qiang; Deng, Liandong; Kong, Deling; Liu, Jianfeng; Liu, Jinjian

    2016-01-01

    Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation. PMID:27051287

  18. Structure and vascular function of MEKK3–cerebral cavernous malformations 2 complex

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fisher, Oriana S.; Deng, Hanqiang; Liu, Dou

    Cerebral cavernous malformations 2 (CCM2) loss is associated with the familial form of CCM disease. The protein kinase MEKK3 (MAP3K3) is essential for embryonic angiogenesis in mice and interacts physically with CCM2, but how this interaction is mediated and its relevance to cerebral vasculature are unknown. Here we report that Mekk3 plays an intrinsic role in embryonic vascular development. Inducible endothelial Mekk3 knockout in neonatal mice is lethal due to multiple intracranial haemorrhages and brain blood vessels leakage. We discover direct interaction between CCM2 harmonin homology domain (HHD) and the N terminus of MEKK3, and determine a 2.35 Å cocrystalmore » structure. We find Mekk3 deficiency impairs neurovascular integrity, which is partially dependent on Rho–ROCK signalling, and that disruption of MEKK3:CCM2 interaction leads to similar neurovascular leakage. We conclude that CCM2:MEKK3-mediated regulation of Rho signalling is required for maintenance of neurovascular integrity, unravelling a mechanism by which CCM2 loss leads to disease.« less

  19. Improvement to the Convergence-Confinement Method: Inclusion of Support Installation Proximity and Stiffness

    NASA Astrophysics Data System (ADS)

    Oke, Jeffrey; Vlachopoulos, Nicholas; Diederichs, Mark

    2018-05-01

    The convergence-confinement method (CCM) is a method that has been introduced in tunnel construction that considers the ground response to the advancing tunnel face and the interaction with installed support. One limitation of the CCM is due to the numerically or empirically driven nature of the longitudinal displacement profile and the incomplete consideration of the longitudinal arching effect that occurs during tunnelling operations as part of the face effect. In this paper, the authors address the issue associated with when the CCM is used within squeezing ground conditions at depth. Based on numerical analysis, the authors have proposed a methodology and solution to improving the CCM in order to allow for more accurate results for squeezing ground conditions for three different excavation cases involving various excavation-support increments and distances from the face to the supported front. The tunnelling methods of consideration include: tunnel boring machine, mechanical (conventional), and drill and blast.

  20. Strategy for Identifying Repurposed Drugs for the Treatment of Cerebral Cavernous Malformation

    PubMed Central

    Gibson, Christopher C.; Zhu, Weiquan; Davis, Chadwick T.; Bowman-Kirigin, Jay A.; Chan, Aubrey C.; Ling, Jing; Walker, Ashley E.; Goitre, Luca; Monache, Simona Delle; Retta, Saverio Francesco; Shiu, Yan-Ting E.; Grossmann, Allie H.; Thomas, Kirk R.; Donato, Anthony J.; Lesniewski, Lisa A.; Whitehead, Kevin J.; Li, Dean Y.

    2014-01-01

    Background Cerebral cavernous malformation (CCM) is a hemorrhagic stroke disease affecting up to 0.5% of North Americans with no approved non-surgical treatment. A subset of patients have a hereditary form of the disease due primarily to loss-of-function mutations in KRIT1, CCM2, or PDCD10. We sought to identify known drugs that could be repurposed to treat CCM. Methods and Results We developed an unbiased screening platform based on both cellular and animal models of loss-of-function of CCM2. Our discovery strategy consisted of four steps: an automated immunofluorescence and machine-learning-based primary screen of structural phenotypes in human endothelial cells deficient in CCM2; a secondary screen of functional changes in endothelial stability in these same cells; a rapid in vivo tertiary screen of dermal microvascular leak in mice lacking endothelial Ccm2; and finally a quaternary screen of CCM lesion burden in these same mice. We screened 2,100 known drugs and bioactive compounds, and identified two candidates for further study, cholecalciferol (Vitamin D3) and tempol (a scavenger of superoxide). Each drug decreased lesion burden in a mouse model of CCM vascular disease by approximately 50%. Conclusions By identifying known drugs as potential therapeutics for CCM, we have decreased the time, cost, and risk of bringing treatments to patients. Each drug also prompts additional exploration of biomarkers of CCM disease. We further suggest that the structure-function screening platform presented here may be adapted and scaled to facilitate drug discovery for diverse loss-of-function genetic vascular disease. PMID:25486933

  1. Sensitivity of temporal heart rate variability in Poincaré plot to changes in parasympathetic nervous system activity.

    PubMed

    Karmakar, Chandan K; Khandoker, Ahsan H; Voss, Andreas; Palaniswami, Marimuthu

    2011-03-03

    A novel descriptor (Complex Correlation Measure (CCM)) for measuring the variability in the temporal structure of Poincaré plot has been developed to characterize or distinguish between Poincaré plots with similar shapes. This study was designed to assess the changes in temporal structure of the Poincaré plot using CCM during atropine infusion, 70° head-up tilt and scopolamine administration in healthy human subjects. CCM quantifies the point-to-point variation of the signal rather than gross description of the Poincaré plot. The physiological relevance of CCM was demonstrated by comparing the changes in CCM values with autonomic perturbation during all phases of the experiment. The sensitivities of short term variability (SD1), long term variability (SD2) and variability in temporal structure (CCM) were analyzed by changing the temporal structure by shuffling the sequences of points of the Poincaré plot. Surrogate analysis was used to show CCM as a measure of changes in temporal structure rather than random noise and sensitivity of CCM with changes in parasympathetic activity. CCM was found to be most sensitive to changes in temporal structure of the Poincaré plot as compared to SD1 and SD2. The values of all descriptors decreased with decrease in parasympathetic activity during atropine infusion and 70° head-up tilt phase. In contrast, values of all descriptors increased with increase in parasympathetic activity during scopolamine administration. The concordant reduction and enhancement in CCM values with parasympathetic activity indicates that the temporal variability of Poincaré plot is modulated by the parasympathetic activity which correlates with changes in CCM values. CCM is more sensitive than SD1 and SD2 to changes of parasympathetic activity.

  2. Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition.

    PubMed

    Strickland, Corinne D; Eberhardt, Steven C; Bartlett, Mary R; Nelson, Jeffrey; Kim, Helen; Morrison, Leslie A; Hart, Blaine L

    2017-08-01

    Purpose To determine if adrenal calcifications seen at computed tomography (CT) are associated with familial cerebral cavernous malformations (fCCMs) in carriers of the CCM1 Common Hispanic Mutation. Materials and Methods This study was approved by the institutional review board. The authors retrospectively reviewed abdominal CT scans in 38 patients with fCCM, 38 unaffected age- and sex-matched control subjects, and 13 patients with sporadic, nonfamilial cerebral cavernous malformation (CCM). The size, number, and laterality of calcifications and the morphologic characteristics of the adrenal gland were recorded. Brain lesion count was recorded from brain magnetic resonance (MR) imaging in patients with fCCM. The prevalence of adrenal calcifications in patients with fCCM was compared with that in unaffected control subjects and those with sporadic CCM by using the Fisher exact test. Additional analyses were performed to determine whether age and brain lesion count were associated with adrenal findings in patients with fCCM. Results Small focal calcifications (SFCs) (≤5 mm) were seen in one or both adrenal glands in 19 of the 38 patients with fCCM (50%), compared with 0 of the 38 unaffected control subjects (P < .001) and 0 of the 13 subjects with sporadic CCM (P = .001). Adrenal calcifications in patients with fCCM were more frequently left sided, with 17 of 19 patients having more SFCs in the left adrenal gland than the right adrenal gland and 50 of the 61 observed SFCs (82%) found in the left adrenal gland. No subjects had SFCs on the right side only. In patients with fCCM, the presence of SFCs showed a positive correlation with age (P < .001) and number of brain lesions (P < .001). Conclusion Adrenal calcifications identified on CT scans are common in patients with fCCM and may be a clinically silent manifestation of disease. © RSNA, 2017.

  3. Cancer cell membrane-coated magnetic nanoparticles for MR/NIR fluorescence dual-modal imaging and photodynamic therapy.

    PubMed

    Li, Jiong; Wang, Xuandong; Zheng, Dongye; Lin, Xinyi; Wei, Zuwu; Zhang, Da; Li, Zhuanfang; Zhang, Yun; Wu, Ming; Liu, Xiaolong

    2018-05-22

    Theranostic nanoprobes integrated with dual-modal imaging and therapeutic functions, such as photodynamic therapy (PDT), have exhibited significant potency in cancer treatments due to their high imaging accuracy and non-invasive advantages for cancer elimination. However, biocompatibility and highly efficient accumulation of these nanoprobes in tumor are still unsatisfactory for clinical application. In this study, a photosensitizer -loaded magnetic nanobead with surface further coated with a layer of cancer cell membrane (SSAP-Ce6@CCM) was designed to improve the biocompatibility and cellular uptake and ultimately achieve enhanced MR/NIR fluorescence imaging and PDT efficacy. Compared with similar nanobeads without CCM coating, SSAP-Ce6@CCM showed significantly enhanced cellular uptake, as evidenced by Prussian blue staining, confocal laser scanning microscopy (CLSM) and flow cytometric analysis. Consequently, SSAP-Ce6@CCM displayed a more distinct MR/NIR imaging ability and more obvious photo-cytotoxicity towards cancer cells under 670 nm laser irradiation. Furthermore, the enhanced PDT effect benefited from the surface coating of cancer cell membrane was demonstrated in SMMC-7721 tumor-bearing mice through tumor growth observation and tumor tissue pathological examination. Therefore, this CCM-disguised nanobead that integrated the abilities of MR/NIR fluorescence dual-modal imaging and photodynamic therapy might be a promising theranostic platform for tumor treatment.

  4. Time to Remission for Depression with Collaborative Care Management (CCM) in Primary Care.

    PubMed

    Garrison, Gregory M; Angstman, Kurt B; O'Connor, Stephen S; Williams, Mark D; Lineberry, Timothy W

    2016-01-01

    Collaborative care management (CCM) has been shown to have superior outcomes to usual care (UC) for depressed patients with a fixed end point. This study was a survival analysis over time comparing CCM with UC using remission (9-item Patient Health Questionnaire [PHQ-9] score <5) and persistent depressive symptoms (PDSs; PHQ-9 score ≥10) as end points. A retrospective cohort study of 7340 patients with depression cared for at 4 outpatient primary care clinics was conducted from March 2008 through June 2013. All adult patients diagnosed with depression (International Classification of Diseases, 9th Revision [ICD-9], codes 296.2-3) or dysthymia (ICD-9 code 300.4) with an initial PHQ-9 score ≥10 were included. CCM was implemented at all clinics between 2008 and 2010. Kaplan-Meyer survival curves for time to remission and PDSs were plotted. A Cox proportional hazards model was used to adjust for expected differences between patients choosing CCM versus UC. Median time to remission was 86 days (95% confidence interval [CI], 81-91 days) for the CCM group versus 614 days (95% CI, 565-692 days) for the UC group. Likewise, median duration of PDSs was 31 days (95% CI, 30-33 days) for the CCM group versus 154 days (95% CI, 138-182 days) for the UC group. In the Cox proportional hazards model, which controlled for covariates such as age, sex, race, diagnosis, and initial PHQ-9 score, CCM was associated with faster remission (hazard ratio of the CCM group [HRCCM], 2.48; 95% CI, 2.31-2.65). This study demonstrated that patients enrolled in CCM have a faster rate of remission and a shorter duration of PDSs than patients choosing UC. © Copyright 2016 by the American Board of Family Medicine.

  5. Individual and social variables and their effect on Case/Care Manager Job Satisfaction: an exploratory study.

    PubMed

    Cosentino, Chiara; Bettuzzi, Morena; Campioli, Giulia; Di Marco, Valeria; Giacopuzzi, Giulia; Marinoni, Ivana; Orlandini, Lorenzo; Palermo, Angelo; Pattacini, Siria; Artioli, Giovanna

    2017-07-18

    The Case/Care Manager (CCM) is a new position for in the Italian National Health Service scenario. Job satisfaction plays a key role for the CCM to engage in his work, accomplishing it in a complete. Nurses' job satisfaction is a complex construct and many different variables can influence it: personal characteristics, cultural characteristic, social characteristic, organizational characteristic, and environmental characteristic. The main aim of this study is to assess the job satisfaction in a sample of CCM and to assess if and how Social Variables (organizational climate and health) and Individual (socio-demographic variables, coping strategies, emotion regulation) relate to the CCM job satisfaction. This study has a quantitative exploratory cross-sectional design. Participants were Nurse CCM with or without specific training who filled a battery of questionnaires : Job Satisfaction Survey (JSS) , section three of ICONAS questionnaire, section five of the Multidimensional Organizational Health Questionnaire (MOHQ), anamnestic sheet, Coping Orientation to the Problems Experienced (COPE-NVI-25), and Emotion Regulation Questionnaire (ERQ). The battery was administered online on the website of Italian Case Manager, Italian Association of Care Manager, and IPASVI Colleges. It was also distributed during the National Congress for Case Manager in Padua. 103 participants took part in the study. The total mean score of JSS was 117,28 (S.D.=21,12). The emotional regulation strategy most used was the "Cognitive Response", and the most used Coping strategy was "Problem Oriented". There were significant correlations between JSS and Social variables in the total score (ICONAS r=.574 p<0.01; MOHQ (positive indicators) r=.608 p<0.01; MOHQ (negative indicators) r=-.634 p <0.01) and in its subscales. There were also significant correlations between JSS subscales and Individual variables (COPE and ERQ). Participants with a specific training tend to use the emotion regulation strategy "Negative interpretation self-oriented" (U 910.500 p<0.005) and "Distraction" (U 885.000 p<0.005) more than those without specific training. The same significant difference was found in JSS pay (t=-2,48 per p<0.05) and JSS Fringe Benefits (t=-2,07 per p<0.05). The CCM job satisfaction seems to be ambivalent. It seems to be not entirely polarized on presence/absence, but rather still in a gray area. organizational climate and health influence significantly the overall perception of job satisfaction and its different areas. The most "avoiding" emotional regulation strategies, seem to negatively affect the perception of satisfaction. Emotional regulation and coping strategies related to challenges focusing and management, along with the individual perception of collaboration, positively influence satisfaction. Participants who underwent a specific CCM training, committing themselves financially and personally, perceive less job satisfaction when their role is not recognized in terms of pay. This study showed that that the main strategies used to regulate emotions are the Cognitive Response and the Social Contact. We suggest that further studies could be made to define the links between individual strategies and the presence of chronic distress and we suggest that a specific training on coping and emotion regulation may be implemented in graduation and post-graduation courses.

  6. GLYOXALASE I A111E, PARAOXONASE 1 Q192R AND L55M POLYMORPHISMS IN ITALIAN PATIENTS WITH SPORADIC CEREBRAL CAVERNOUS MALFORMATIONS: A PILOT STUDY.

    PubMed

    Rinaldi, C; Bramanti, P; Famà, A; Scimone, C; Donato, L; Antognelli, C; Alafaci, C; Tomasello, F; D'Angelo, R; Sidoti, A

    2015-01-01

    It is already known that the conditions of increased oxidative stress are associated to a greater susceptibility to vascular malformations including cerebral cavernous malformations (CCMs). These are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities that can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1(Krit1), CCM2 (MGC4607) and CCM3 (PDCD10). Polymorphisms in the genes encoding for enzymes involved in the antioxidant systems such as glyoxalase I (GLO I) and paraoxonase I (PON I) could influence individual susceptibility to the vascular malformations. A single nucleotide polymorphism was identified in the exon 4 of GLO 1 gene that causes an amino acid substitution of Ala for Glu (Ala111Glu). Two common polymorphisms have been described in the coding region of PON1, which lead to glutamine → arginine substitution at 192 (Q192R) and a leucine → methionine substitution at 55 (L55M). The polymorphisms were characterized in 59 patients without mutations in the CCM genes versus 213 healthy controls by PCR/RFLP methods using DNA from lymphocytes. We found that the frequency of patients carrying the GLO1 A/E genotype among the case group (56%) was four-fold higher than among the controls (14.1%). In the cohort of CCM patients, an increase in the frequency of PON192 Q/R genotype was observed (39% in the CCM group versus 3.7% in the healthy controls). Similarly, an increase was observed in the proportion of individuals with the genotype R/R in the disease group (5%) in respect to the normal healthy cohort (0.5%). Finally, the frequency of the PON55 heterozygotes L/M genotype was 29% in patients with CCMs and 4% in the healthy controls. The same trend was observed in PON55 homozygous M/M genotype frequency (CCMs 20% vs controls 10%). The present study aimed to investigate the possible association of GLO1 A111E, PON1 Q192R and L55M polymorphisms with the risk of CCMs. We found that individuals with the GLO1 A /E genotype, PON192/QR-RR genotypes and PON55/LM-MM genotypes had a significantly higher risk of CCMs compared with the other genotypes. However, because CCM is a heterogeneous disease, other additional factors might be involved in the initiation and progression of CCM disease.

  7. The Comparative Studies of Binding Activity of Curcumin and Didemethylated Curcumin with Selenite: Hydrogen Bonding vs Acid-Base Interactions.

    PubMed

    Liao, Jiahn-Haur; Wu, Tzu-Hua; Chen, Ming-Yi; Chen, Wei-Ting; Lu, Shou-Yun; Wang, Yi-Hsuan; Wang, Shao-Pin; Hsu, Yen-Min; Huang, Yi-Shiang; Huang, Zih-You; Lin, Yu-Ching; Chang, Ching-Ming; Huang, Fu-Yung; Wu, Shih-Hsiung

    2015-12-04

    In this report, the in vitro relative capabilities of curcumin (CCM) and didemethylated curcumin (DCCM) in preventing the selenite-induced crystallin aggregation were investigated by turbidity tests and isothermal titration calorimetry (ITC). DCCM showed better activity than CCM. The conformers of CCM/SeO3(2-) and DCCM/SeO3(2-) complexes were optimized by molecular orbital calculations. Results reveal that the selenite anion surrounded by CCM through the H-bonding between CCM and selenite, which is also observed via IR and NMR studied. For DCCM, the primary driving force is the formation of an acid-base adduct with selenite showing that the phenolic OH group of DCCM was responsible for forming major conformer of DCCM. The formation mechanisms of selenite complexes with CCM or DCCM explain why DCCM has greater activity than CCM in extenuating the toxicity of selenite as to prevent selenite-induced lens protein aggregation.

  8. Algal evolution in relation to atmospheric CO2: carboxylases, carbon-concentrating mechanisms and carbon oxidation cycles

    PubMed Central

    Raven, John A.; Giordano, Mario; Beardall, John; Maberly, Stephen C.

    2012-01-01

    Oxygenic photosynthesis evolved at least 2.4 Ga; all oxygenic organisms use the ribulose bisphosphate carboxylase-oxygenase (Rubisco)–photosynthetic carbon reduction cycle (PCRC) rather than one of the five other known pathways of autotrophic CO2 assimilation. The high CO2 and (initially) O2-free conditions permitted the use of a Rubisco with a high maximum specific reaction rate. As CO2 decreased and O2 increased, Rubisco oxygenase activity increased and 2-phosphoglycolate was produced, with the evolution of pathways recycling this inhibitory product to sugar phosphates. Changed atmospheric composition also selected for Rubiscos with higher CO2 affinity and CO2/O2 selectivity correlated with decreased CO2-saturated catalytic capacity and/or for CO2-concentrating mechanisms (CCMs). These changes increase the energy, nitrogen, phosphorus, iron, zinc and manganese cost of producing and operating Rubisco–PCRC, while biosphere oxygenation decreased the availability of nitrogen, phosphorus and iron. The majority of algae today have CCMs; the timing of their origins is unclear. If CCMs evolved in a low-CO2 episode followed by one or more lengthy high-CO2 episodes, CCM retention could involve a combination of environmental factors known to favour CCM retention in extant organisms that also occur in a warmer high-CO2 ocean. More investigations, including studies of genetic adaptation, are needed. PMID:22232762

  9. Cost-effectiveness analysis of the national implementation of integrated community case management and community-based health planning and services in Ghana for the treatment of malaria, diarrhoea and pneumonia.

    PubMed

    Escribano Ferrer, Blanca; Hansen, Kristian Schultz; Gyapong, Margaret; Bruce, Jane; Narh Bana, Solomon A; Narh, Clement T; Allotey, Naa-Korkor; Glover, Roland; Azantilow, Naa-Charity; Bart-Plange, Constance; Sagoe-Moses, Isabella; Webster, Jayne

    2017-07-05

    Ghana has developed two main community-based strategies that aim to increase access to quality treatment for malaria, diarrhoea and suspected pneumonia: the integrated community case management (iCCM) and the community-based health planning and services (CHPS). The aim of the study was to assess the cost-effectiveness of these strategies under programme conditions. A cost-effectiveness analysis was conducted. Appropriate diagnosis and treatment given was the effectiveness measure used. Appropriate diagnosis and treatment data was obtained from a household survey conducted 2 and 8 years after implementation of iCCM in the Volta and Northern Regions of Ghana, respectively. The study population was carers of children under-5 years who had fever, diarrhoea and/or cough in the last 2 weeks prior to the interview. Costs data was obtained mainly from the National Malaria Control Programme (NMCP), the Ministry of Health, CHPS compounds and from a household survey. Appropriate diagnosis and treatment of malaria, diarrhoea and suspected pneumonia was more cost-effective under the iCCM than under CHPS in the Volta Region, even after adjusting for different discount rates, facility costs and iCCM and CHPS utilization, but not when iCCM appropriate treatment was reduced by 50%. Due to low numbers of carers visiting a CBA in the Northern Region it was not possible to conduct a cost-effectiveness analysis in this region. However, the cost analysis showed that iCCM in the Northern Region had higher cost per malaria, diarrhoea and suspected pneumonia case diagnosed and treated when compared to the Volta Region and to the CHPS strategy in the Northern Region. Integrated community case management was more cost-effective than CHPS for the treatment of malaria, diarrhoea and suspected pneumonia when utilized by carers of children under-5 years in the Volta Region. A revision of the iCCM strategy in the Northern Region is needed to improve its cost-effectiveness. Long-term financing strategies should be explored including potential inclusion in the National Health Insurance Scheme (NHIS) benefit package. An acceptability study of including iCCM in the NHIS should be conducted.

  10. Integrated community case management for childhood illnesses: explaining policy resistance in Kenya.

    PubMed

    Juma, Pamela A; Owuor, Karen; Bennett, Sara

    2015-12-01

    There has been a re-emphasis recently on community health workers to provide child health care services including integrated community case management for childhood illness (iCCM). This research analysed iCCM policy development in Kenya and in particular the types of decision-making criteria used by Kenyan policy-makers in considering whether to advance iCCM policy. Data were collected through document reviews (n = 41) and semi-structured interviews (n = 19) with key stakeholders in iCCM policy including government officials, development partners, bilateral donors, and civil society organizations. Initial analysis was guided by the policy triangle with further analysis of factors affecting policy decision-making drawing upon a simple framework developed by Grindle and Thomas (Policy makers, policy choices and policy outcomes: the political economy of reform in developing countries. 1989; Policy Sci 22: :213-48.). Policy development for iCCM has been slow in Kenya, compared with other Sub-Saharan African countries. At the time of the study, the Government had just completed the Community Health Training Manual which incorporated iCCM as a module, but this was the only formal expression of iCCM in Kenya. We found technical considerations, notably concerns about community health workers dispensing antibiotics to be a key factor slowing iCCM policy development, but this also overlapped with bureaucratic considerations, such as how the development of community health worker cadres may affect clinicians, as well as initial concerns about how an integrated approach might affect vertically oriented programs. International actors through agreements such as the Millennium Development Goals helped to get child survival onto the national policy agenda and such actors were active promoters of iCCM policy change. However international funders had not committed funding to scale-up iCCM policy, and this probably constrained their influence over iCCM policy debate. Kenyan actors' concerns about iCCM underline the importance of adapting global policies to local conditions, and also generating local evidence to inform decision-making. © The Author 2015. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Independent Evaluation of the integrated Community Case Management of Childhood Illness Strategy in Malawi Using a National Evaluation Platform Design.

    PubMed

    Amouzou, Agbessi; Kanyuka, Mercy; Hazel, Elizabeth; Heidkamp, Rebecca; Marsh, Andrew; Mleme, Tiope; Munthali, Spy; Park, Lois; Banda, Benjamin; Moulton, Lawrence H; Black, Robert E; Hill, Kenneth; Perin, Jamie; Victora, Cesar G; Bryce, Jennifer

    2016-03-01

    We evaluated the impact of integrated community case management of childhood illness (iCCM) on careseeking for childhood illness and child mortality in Malawi, using a National Evaluation Platform dose-response design with 27 districts as units of analysis. "Dose" variables included density of iCCM providers, drug availability, and supervision, measured through a cross-sectional cellular telephone survey of all iCCM-trained providers. "Response" variables were changes between 2010 and 2014 in careseeking and mortality in children aged 2-59 months, measured through household surveys. iCCM implementation strength was not associated with changes in careseeking or mortality. There were fewer than one iCCM-ready provider per 1,000 under-five children per district. About 70% of sick children were taken outside the home for care in both 2010 and 2014. Careseeking from iCCM providers increased over time from about 2% to 10%; careseeking from other providers fell by a similar amount. Likely contributors to the failure to find impact include low density of iCCM providers, geographic targeting of iCCM to "hard-to-reach" areas although women did not identify distance from a provider as a barrier to health care, and displacement of facility careseeking by iCCM careseeking. This suggests that targeting iCCM solely based on geographic barriers may need to be reconsidered. © The American Society of Tropical Medicine and Hygiene.

  12. Facilitators and barriers of implementing the chronic care model in primary care: a systematic review.

    PubMed

    Kadu, Mudathira K; Stolee, Paul

    2015-02-06

    The Chronic Care Model (CCM) is a framework developed to redesign care delivery for individuals living with chronic diseases in primary care. The CCM and its various components have been widely adopted and evaluated, however, little is known about different primary care experiences with its implementation, and the factors that influence its successful uptake. The purpose of this review is to synthesize findings of studies that implemented the CCM in primary care, in order to identify facilitators and barriers encountered during implementation. This study identified English-language, peer-reviewed research articles, describing the CCM in primary care settings. Searches were performed in three data bases: Web of Knowledge, Pubmed and Scopus. Article abstracts and titles were read based on whether they met the following inclusion criteria: 1) studies published after 2003 that described or evaluated the implementation of the CCM; 2) the care setting was primary care; 3) the target population of the study was adults over the age of 18 with chronic conditions. Studies were categorized by reference, study design and methods, participants and setting, study objective, CCM components used, and description of the intervention. The next stage of data abstraction involved qualitative analysis of cited barriers and facilitators using the Consolidating Framework for Research Implementation. This review identified barriers and facilitators of implementation across various primary care settings in 22 studies. The major emerging themes were those related to the inner setting of the organization, the process of implementation and characteristics of the individual healthcare providers. These included: organizational culture, its structural characteristics, networks and communication, implementation climate and readiness, presence of supportive leadership, and provider attitudes and beliefs. These findings highlight the importance of assessing organizational capacity and needs prior to and during the implementation of the CCM, as well as gaining a better understanding of health care providers' and organizational perspective.

  13. Biocompatibility of metal injection molded versus wrought ASTM F562 (MP35N) and ASTM F1537 (CCM) cobalt alloys.

    PubMed

    Chen, Hao; Sago, Alan; West, Shari; Farina, Jeff; Eckert, John; Broadley, Mark

    2011-01-01

    We present a comparative analysis between biocompatibility test results of wrought and Metal Injection Molded (MIM) ASTM F562-02 UNS R30035 (MP35N) and F1537 UNS R31538 (CCM) alloy samples that have undergone the same generic orthopedic implant's mechanical, chemical surface pre-treatment, and a designed pre-testing sample preparation method. Because the biocompatibility properties resulting from this new MIM cobalt alloy process are not well understood, we conducted tests to evaluate cytotoxicity (in vitro), hemolysis (in vitro), toxicity effects (in vivo), tissue irritation level (in vivo), and pyrogenicity count (in vitro) on such samples. We show that our developed MIM MP35N and CCM materials and treatment processes are biocompatible, and that both the MIM and wrought samples, although somewhat different in microstructure and surface, do not show significant differences in biocompatibility.

  14. Final report on the torque key komparison CCM.T-K1.2 measurand torque: 0 N.m, 500 N.m, 1000 N.m

    NASA Astrophysics Data System (ADS)

    Röske, Dirk

    2015-01-01

    The purpose of the CIPM subsequent bilateral comparison CCM.T-K1.2 was to link another participant, namely the National Institute of Metrology (Thailand), in short NIMT, to the CCM.T-K1 torque key comparison. The measuring capabilities up to 1000 N.m of dead-weight torque standard machines with supported lever were investigated. The pilot laboratory was the same in both comparisons—it was the Physikalisch-Technische Bundesanstalt (PTB, Braunschweig, Germany). The same two very stable torque transducers with well-known properties were used as travelling standards. The measurements at the participating laboratory were carried out between November 2007 and February 2008. According to the technical protocol, torque steps of 500 N.m and 1000 N.m had to be measured both in clockwise and anticlockwise directions. Corrections had to be applied to the results reported by the participants taking into account the use of different amplifiers, the creep (due to different loading times of the machines) and the environmental conditions in the laboratories (temperature and relative humidity of the ambient air). The results of the pilot laboratory in this bilateral comparison are in very good agreement with the same results obtained in the CCM.T-K1 comparison. For each of the transducers, the two torque steps and both senses of direction of the torque vector, the key comparison reference value of the CCM.T-K1 was taken, and the results of participant NIMT were calculated with respect to these values. The agreement between the results is very good. The smallest expanded (k = 2) relative uncertainty of the machine stated by the participant is 1 × 10-4. The results of the comparison support this uncertainty statement. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  15. Mandatory labeling requirements and over-the-counter cough and cold medication use in early childhood.

    PubMed

    DeGroot, Julie; Anderson, Laura N; Chen, Yang; Birken, Catherine S; Parkin, Patricia C; Carsley, Sarah; Khovratovich, Marina; Mamdani, Muhammad; Maguire, Jonathon L

    2016-03-16

    Due to rare but severe adverse events, Health Canada in October 2009 required manufacturers to relabel over-the-counter (OTC) cough and cold medication (CCM) to state that the products should not be used in children <6 years of age. The main objective of this study was to determine whether this labeling standard decreased OTC CCM use among young children with a recent cough, cold or flu. An interrupted time series study was conducted using data from the TARGet Kids! practice-based research network. A total of 3,515 healthy children 1-5 years of age were recruited from 2008-2011; of these, 1,072 had a cough, cold or flu in the previous month. Parents completed a standardized survey instrument. For the primary analysis, use of OTC CCMs prior to and after October 1, 2009 was compared using time series analyses. For the secondary analysis, multivariable logistic regression was used to identify predictors of recent OTC CCM use. OTC CCM use was reported in 222 of 1,072 (20.7%) children with a cough, cold or flu within the previous month. OTC CCM use declined from 22.2% to 17.8% following the October 2009 Health Canada labeling standard (p = 0.014). Maternal age <35 years (OR 1.49; 95% CI: 1.05-2.13) and having older siblings (OR 1.65; 95% CI: 1.16-2.35) were independently associated with OTC CCM use. Labeling legislation against OTC CCM use for children <6 years resulted in a small decrease in OTC CCM use. Stronger measures may be needed to curtail OTC CCM use, particularly for younger parents and those with multiple children.

  16. Magnetic Resonance Thermometry-Guided Stereotactic Laser Ablation of Cavernous Malformations in Drug-Resistant Epilepsy: Imaging and Clinical Results

    PubMed Central

    McCracken, D. Jay; Willie, Jon T.; Fernald, Brad; Saindane, Amit M.; Drane, Daniel L.; Barrow, Daniel L.; Gross, Robert E.

    2016-01-01

    BACKGROUND Surgery is indicated for cerebral cavernous malformations (CCM) that cause medically refractory epilepsy. Real-time magnetic resonance thermography (MRT)-guided stereotactic laser ablation (SLA) is a minimally invasive approach to treating focal brain lesions. SLA of CCM has not previously been described. OBJECTIVE To describe MRT-guided SLA, a novel approach to treating CCM-related epilepsy, with respect to feasibility, safety, imaging, and seizure control in 5 consecutive patients. METHODS Five patients with medically refractory epilepsy undergoing standard presurgical evaluation were found to have corresponding lesions fulfilling imaging characteristics of CCM and were prospectively enrolled. Each underwent stereotactic placement of a saline-cooled cannula containing an optical fiber to deliver 980-nm diode laser energy via twist drill craniostomy. MR anatomic imaging was used to evaluate targeting prior to ablation. MR imaging provided evaluation of targeting and near real-time feedback regarding extent of tissue thermocoagulation. Patients maintained seizure diaries, and remote imaging (6–21 months post-ablation) was obtained in all patients. RESULTS Imaging revealed no evidence of acute hemorrhage following fiber placement within presumed CCM. MRT during treatment and immediate post-procedure imaging confirmed desired extent of ablation. We identified no adverse events or neurological deficits. Four of 5 (80%) patients achieved freedom from disabling seizures after SLA alone (Engel class 1 outcome), with follow-up ranging 12–28 months. Reimaging of all subjects (6–21 months) indicated lesion diminution with surrounding liquefactive necrosis, consistent with the surgical goal of extended lesionotomy. CONCLUSION Minimally invasive MRT-guided SLA of epileptogenic CCM is a potentially safe and effective alternative to open resection. Additional experience and longer follow-up are needed. PMID:27959970

  17. Causative impact of air pollution on evapotranspiration in the North China Plain.

    PubMed

    Yao, Ling

    2017-10-01

    Atmospheric dispersion conditions strongly impact air pollution under identical surface emissions. The degree of air pollution in the Jing-Jin-Ji region is so severe that it may impose feedback on local climate. Reference evapotranspiration (ET 0 ) plays a significant role in the estimation of crop water requirements, as well as in studies on climate variation and change. Since the traditional correlation analysis cannot capture the causality, we apply the convergent cross mapping method (CCM) in this study to observationally investigate whether the air pollution impacts ET 0 . The results indicate that southwest regions of Jing-Jin-Ji always suffer higher PM 2.5 concentration than north regions through the whole year, and correlation analysis suggests that PM 2.5 concentration has a significant negative effect on ET 0 in most cities. The causality detection with CCM quantitatively demonstrates the significantly causative influence of PM 2.5 concentration on ET 0 , higher PM 2.5 concentration decreasing ET 0 . However, CCM analysis suggests that PM 2.5 concentration has a relatively weak causal influence on ET 0 while the correlation analysis gives the near zero correlation coefficient in Zhangjiakou city, indicating that the causative influence of PM 2.5 concentration on ET 0 is better revealed with CCM method than the correlation analysis. Considering that ET 0 is strongly associated with crop water requirement, the amount of water for agricultural irrigation could be reduced at high PM 2.5 concentrations. These findings can be utilized to improve the efficiency of water resources utilization, and reduce the exploiting amount of groundwater in the Jing-Jin-Ji region, although PM 2.5 is detrimental to human health. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Thermal responses of Symbiodinium photosynthetic carbon assimilation

    NASA Astrophysics Data System (ADS)

    Oakley, Clinton A.; Schmidt, Gregory W.; Hopkinson, Brian M.

    2014-06-01

    The symbiosis between hermatypic corals and their dinoflagellate endosymbionts, genus Symbiodinium, is based on carbon exchange. This symbiosis is disrupted by thermally induced coral bleaching, a stress response in which the coral host expels its algal symbionts as they become physiologically impaired. The disruption of the dissolved inorganic carbon (DIC) supply or the thermal inactivation of Rubisco have been proposed as sites of initial thermal damage that leads to the bleaching response. Symbiodinium possesses a highly unusual Form II ribulose bisphosphate carboxylase/oxygenase (Rubisco), which exhibits a lower CO2:O2 specificity and may be more thermally unstable than the Form I Rubiscos of other algae and land plants. Components of the CO2 concentrating mechanism (CCM), which supplies inorganic carbon for photosynthesis, may also be temperature sensitive. Here, we examine the ability of four cultured Symbiodinium strains to acquire and fix DIC across a temperature gradient. Surprisingly, the half-saturation constant of photosynthesis with respect to DIC concentration ( K P), an index of CCM function, declined with increasing temperature in three of the four strains, indicating a greater potential for photosynthetic carbon acquisition at elevated temperatures. In the fourth strain, there was no effect of temperature on K P. Finding no evidence for thermal inhibition of the CCM, we conclude that CCM components are not likely to be the primary sites of thermal damage. Reduced photosynthetic quantum yields, a hallmark of thermal bleaching, were observed at low DIC concentrations, leaving open the possibility that reduced inorganic carbon availability is involved in bleaching.

  19. A “Coiled-Coil” Motif Is Important for Oligomerization and DNA Binding Properties of Human Cytomegalovirus Protein UL77

    PubMed Central

    Dittmer, Alexandra; Lapp, Sara; Bogner, Elke

    2011-01-01

    Human cytomegalovirus (HCMV) UL77 gene encodes the essential protein UL77, its function is characterized in the present study. Immunoprecipitation identified monomeric and oligomeric pUL77 in HCMV infected cells. Immunostaining of purified virions and subviral fractions showed that pUL77 is a structural protein associated with capsids. In silico analysis revealed the presence of a coiled-coil motif (CCM) at the N-terminus of pUL77. Chemical cross-linking of either wild-type pUL77 or CCM deletion mutant (pUL77ΔCCM) implicated that CCM is critical for oligomerization of pUL77. Furthermore, co-immunoprecipitations of infected and transfected cells demonstrated that pUL77 interacts with the capsid-associated DNA packaging motor components, pUL56 and pUL104, as well as the major capsid protein. The ability of pUL77 to bind dsDNA was shown by an in vitro assay. Binding to certain DNA was further confirmed by an assay using biotinylated 36-, 250-, 500-, 1000-meric dsDNA and 966-meric HCMV-specific dsDNA designed for this study. The binding efficiency (BE) was determined by image processing program defining values above 1.0 as positive. While the BE of the pUL56 binding to the 36-mer bio-pac1 containing a packaging signal was 10.0±0.63, the one for pUL77 was only 0.2±0.03. In contrast to this observation the BE of pUL77 binding to bio-500 bp or bio-1000 bp was 2.2±0.41 and 4.9±0.71, respectively. By using pUL77ΔCCM it was demonstrated that this protein could not bind to dsDNA. These data indicated that pUL77 (i) could form homodimers, (ii) CCM of pUL77 is crucial for oligomerization and (iii) could bind to dsDNA in a sequence independent manner. PMID:21998635

  20. Controlled synthesis, formation mechanism, and carbon oxidation properties of Ho2Cu2O5 nanoplates prepared with a coordination-complex method

    NASA Astrophysics Data System (ADS)

    Guo, Rui; You, Junhua; Han, Fei; Li, Chaoyang; Zheng, Guiyuan; Xiao, Weicheng; Liu, Xuanwen

    2017-02-01

    Ho2Cu2O5 nanoplates with perovskite structures were synthesized via a simple solution method (SSM) and a coordination-complex method (CCM) using [HoCu(3,4-pdc)2(OAc)(H2O)3]·8H2O (L = 3,4-pyridinedicarboxylic acid) as a precursor. The CCM was also performed in an N2 environment (CCMN) under various calcination conditions. The crystallization processes were characterized using X-ray diffraction, scanning electron microscopy, and high-resolution transmission electron microscopy. Ho2Cu2O5 formed through the diffusion of CuO into Ho2O3 particles. Cu2+ diffused faster than Ho3+ during this process. The initial products of CCMN (along with the thermal decomposition products) were initially laminarized in the N2 atmosphere, which prevented the growth of CuO particles and decreased the size of the Ho2Cu2O5 particles. The final Ho2Cu2O5 particles from CCMN had a nanoplate morphology with an average thickness of 75 nm. The decomposition of organic molecules and protection from N2 played important roles in determining the morphology of the resulting Ho2Cu2O5. The catalytic oxidation activity of Ho2Cu2O5 samples for carbon was characterized using a specific surface area measurement and thermogravimetric analysis, which revealed that the samples produced by CCMN had the highest catalytic activity.

  1. Examination of tracer transport in the NCAR CCM2 by comparison of CFCl3 simulations with ALE/GAGE observations

    NASA Technical Reports Server (NTRS)

    Hartley, Dana E.; Williamson, David L.; Rasch, Philip J.; Prinn, Ronald G.

    1994-01-01

    The latest version of the National Center for Atmospheric Research (NCAR) community climate model (CCM2) contains a semi-Lagrangian tracer transport scheme for the purpose of advecting water vapor and for including chemistry in the climate model. One way to diagnose the CCM2 transport is to simulate CFCl3 in the CCM2 since it has a well-known industry-based source distribution and a photochemical sink and to compare the model results to Atmospheric Lifetime Experiment/Global Atmospheric Gases Experiment ALE/GAGE observations around the globe. In this paper we focus on this comparison and discuss the synoptic scale issues of tracer transport where appropriate. We compare the model and observations on both 12-hour and monthly timescales. The higher-frequency events allow us to diagnose the synoptic scale transport in the CCM2 associated with the observational sites and to determine uncertainties in our high-resolution source distribution. We find that the CCM2 does simulate many of the key features such as pollution events and some seasonal transports, but there are still some dynamical features of tracer transport such as the storm track dynamics and cross-equatorial flow that merit further study in both the model and the real atmosphere.

  2. Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data.

    PubMed

    Horne, Margaret A; Flemming, Kelly D; Su, I-Chang; Stapf, Christian; Jeon, Jin Pyeong; Li, Da; Maxwell, Susanne S; White, Philip; Christianson, Teresa J; Agid, Ronit; Cho, Won-Sang; Oh, Chang Wan; Wu, Zhen; Zhang, Jun-Ting; Kim, Jeong Eun; Ter Brugge, Karel; Willinsky, Robert; Brown, Robert D; Murray, Gordon D; Al-Shahi Salman, Rustam

    2016-02-01

    Cerebral cavernous malformations (CCMs) can cause symptomatic intracranial haemorrhage (ICH), but the estimated risks are imprecise and predictors remain uncertain. We aimed to obtain precise estimates and predictors of the risk of ICH during untreated follow-up in an individual patient data meta-analysis. We invited investigators of published cohorts of people aged at least 16 years, identified by a systematic review of Ovid MEDLINE and Embase from inception to April 30, 2015, to provide individual patient data on clinical course from CCM diagnosis until first CCM treatment or last available follow-up. We used survival analysis to estimate the 5-year risk of symptomatic ICH due to CCMs (primary outcome), multivariable Cox regression to identify baseline predictors of outcome, and random-effects models to pool estimates in a meta-analysis. Among 1620 people in seven cohorts from six studies, 204 experienced ICH during 5197 person-years of follow-up (Kaplan-Meier estimated 5-year risk 15·8%, 95% CI 13·7-17·9). The primary outcome of ICH within 5 years of CCM diagnosis was associated with clinical presentation with ICH or new focal neurological deficit (FND) without brain imaging evidence of recent haemorrhage versus other modes of presentation (hazard ratio 5·6, 95% CI 3·2-9·7) and with brainstem CCM location versus other locations (4·4, 2·3-8·6), but age, sex, and CCM multiplicity did not add independent prognostic information. The 5-year estimated risk of ICH during untreated follow-up was 3·8% (95% CI 2·1-5·5) for 718 people with non-brainstem CCM presenting without ICH or FND, 8·0% (0·1-15·9) for 80 people with brainstem CCM presenting without ICH or FND, 18·4% (13·3-23·5) for 327 people with non-brainstem CCM presenting with ICH or FND, and 30·8% (26·3-35·2) for 495 people with brainstem CCM presenting with ICH or FND. Mode of clinical presentation and CCM location are independently associated with ICH within 5 years of CCM diagnosis. These findings can inform decisions about CCM treatment. UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association. Copyright © 2016 Horne et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

  3. CASL VMA FY16 Milestone Report (L3:VMA.VUQ.P13.07) Westinghouse Mixing with COBRA-TF

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gordon, Natalie

    2016-09-30

    COBRA-TF (CTF) is a low-resolution code currently maintained as CASL's subchannel analysis tool. CTF operates as a two-phase, compressible code over a mesh comprised of subchannels and axial discretized nodes. In part because CTF is a low-resolution code, simulation run time is not computationally expensive, only on the order of minutes. Hi-resolution codes such as STAR-CCM+ can be used to train lower-fidelity codes such as CTF. Unlike STAR-CCM+, CTF has no turbulence model, only a two-phase turbulent mixing coefficient, β. β can be set to a constant value or calculated in terms of Reynolds number using an empirical correlation. Resultsmore » from STAR-CCM+ can be used to inform the appropriate value of β. Once β is calibrated, CTF runs can be an inexpensive alternative to costly STAR-CCM+ runs for scoping analyses. Based on the results of CTF runs, STAR-CCM+ can be run for specific parameters of interest. CASL areas of application are CIPS for single phase analysis and DNB-CTF for two-phase analysis.« less

  4. The ins and outs of CO2

    PubMed Central

    Raven, John A.; Beardall, John

    2016-01-01

    It is difficult to distinguish influx and efflux of inorganic C in photosynthesizing tissues; this article examines what is known and where there are gaps in knowledge. Irreversible decarboxylases produce CO2, and CO2 is the substrate/product of enzymes that act as carboxylases and decarboxylases. Some irreversible carboxylases use CO2; others use HCO3 –. The relative role of permeation through the lipid bilayer versus movement through CO2-selective membrane proteins in the downhill, non-energized, movement of CO2 is not clear. Passive permeation explains most CO2 entry, including terrestrial and aquatic organisms with C3 physiology and biochemistry, terrestrial C4 plants and all crassulacean acid metabolism (CAM) plants, as well as being part of some mechanisms of HCO3 – use in CO2 concentrating mechanism (CCM) function, although further work is needed to test the mechanism in some cases. However, there is some evidence of active CO2 influx at the plasmalemma of algae. HCO3 – active influx at the plasmalemma underlies all cyanobacterial and some algal CCMs. HCO3 – can also enter some algal chloroplasts, probably as part of a CCM. The high intracellular CO2 and HCO3 – pools consequent upon CCMs result in leakage involving CO2, and occasionally HCO3 –. Leakage from cyanobacterial and microalgal CCMs involves up to half, but sometimes more, of the gross inorganic C entering in the CCM; leakage from terrestrial C4 plants is lower in most environments. Little is known of leakage from other organisms with CCMs, though given the leakage better-examined organisms, leakage occurs and increases the energetic cost of net carbon assimilation. PMID:26466660

  5. Elevated CO2 causes changes in the photosynthetic apparatus of a toxic cyanobacterium, Cylindrospermopsis raciborskii.

    PubMed

    Pierangelini, Mattia; Stojkovic, Slobodanka; Orr, Philip T; Beardall, John

    2014-07-15

    We studied the physiological acclimation of growth, photosynthesis and CO2-concentrating mechanism (CCM) in Cylindrospermopsis raciborskii exposed to low (present day; L-CO2) and high (1300ppm; H-CO2) pCO2. Results showed that under H-CO2 the cell specific division rate (μc) was higher and the CO2- and light-saturated photosynthetic rates (Vmax and Pmax) doubled. The cells' photosynthetic affinity for CO2 (K0.5CO2) was halved compared to L-CO2 cultures. However, no significant differences were found in dark respiration rates (Rd), pigment composition and light harvesting efficiency (α). In H-CO2 cells, non-photochemical quenching (NPQ), associated with state transitions of the electron transport chain (ETC), was negligible. Simultaneously, a reorganisation of PSII features including antenna connectivity (JconPSIIα), heterogeneity (PSIIα/β) and effective absorption cross sectional area (σPSIIα/β) was observed. In relation to different activities of the CCM, our findings suggest that for cells grown under H-CO2: (1) there is down-regulation of CCM activity; (2) the ability of cells to use the harvested light energy is altered; (3) the occurrence of state transitions is likely to be associated with changes of electron flow (cyclic vs linear) through the ETC; (4) changes in PSII characteristics are important in regulating state transitions. Copyright © 2014 Elsevier GmbH. All rights reserved.

  6. Performance of Versions 1,2 and 3 of the Goddard Earth Observing System (GEOS) Chemistry-Climate Model (CCM)

    NASA Technical Reports Server (NTRS)

    Pawson, Steven; Stolarski, Richard S.; Nielsen, J. Eric; Duncan, Bryan N.

    2008-01-01

    Version 1 of the Goddard Earth Observing System Chemistry-Climate Model (GEOS CCM) was used in the first CCMVa1 model evaluation and forms the basis for several studies of links between ozone and the circulation. That version of the CCM was based on the GEOS-4 GCM. Versions 2 and 3 of the GEOS CCM are based on the GEOS-5 GCM, which retains the "Lin-Rood" dynamical core but has a totally different set of physical parameterizatiOns to GEOS-4. In Version 2 of the GEOS CCM the Goddard stratospheric chemistry module is retained. Difference between Versions 1 and 2 thus reflect the physics changes of the underlying GCMs. Several comparisons between these two models are made, several of which reveal improvements in Version 2 (including a more realistic representation of the interannual variability of the Antarctic vortex). In Version 3 of the GEOS CCM, the stratospheric chemistry mechanism is replaced by the "GMI COMBO" code that includes tropospheric chemistry and different computational approaches. An advantage of this model version. is the reduction of high ozone biases that prevail at low chlorine loadings in Versions 1 and 2. This poster will compare and contrast various aspects of the three model versions that are relevant for understanding interactions between ozone and climate.

  7. Heg1 and Ccm1/2 proteins control endocardial mechanosensitivity during zebrafish valvulogenesis

    PubMed Central

    Otten, Cécile; Renz, Marc

    2018-01-01

    Endothelial cells respond to different levels of fluid shear stress through adaptations of their mechanosensitivity. Currently, we lack a good understanding of how this contributes to sculpting of the cardiovascular system. Cerebral cavernous malformation (CCM) is an inherited vascular disease that occurs when a second somatic mutation causes a loss of CCM1/KRIT1, CCM2, or CCM3 proteins. Here, we demonstrate that zebrafish Krit1 regulates the formation of cardiac valves. Expression of heg1, which encodes a binding partner of Krit1, is positively regulated by blood-flow. In turn, Heg1 stabilizes levels of Krit1 protein, and both Heg1 and Krit1 dampen expression levels of klf2a, a major mechanosensitive gene. Conversely, loss of Krit1 results in increased expression of klf2a and notch1b throughout the endocardium and prevents cardiac valve leaflet formation. Hence, the correct balance of blood-flow-dependent induction and Krit1 protein-mediated repression of klf2a and notch1b ultimately shapes cardiac valve leaflet morphology. PMID:29364115

  8. Absorption mechanism of whey-protein-delivered curcumin using Caco-2 cell monolayers.

    PubMed

    Li, Ming; Cui, Jie; Ngadi, Michael O; Ma, Ying

    2015-08-01

    Curcumin (CCM) is a bioactive polyphenolic compound that suffers a low bioavailability because of its low water solubility. In this work β-lactoglobulin (β-Lg) and nanoemulsion were used as carriers to deliver curcumin. The pH stability of β-Lg-CCM was investigated. The digestion of β-Lg-CCM and the nanoemulsion was studied using an in vitro gastrointestinal model. The effect of different carriers on the permeability of curcumin was assessed using the Caco-2 cell monolayer model. The results revealed that the water solubility and the pH stability of curcumin significantly increased by binding with β-Lg. In SDS-PAGE experiments the β-Lg-CCM complex and nanoemulsion were found to be resistant to pepsin digestion but sensitive to trypsin. In the permeability experiment it was shown that the digested nanoemulsion and β-Lg-CCM improved significantly the permeation rate of curcumin. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Identification and characterization of a carboxysomal γ-carbonic anhydrase from the cyanobacterium Nostoc sp. PCC 7120.

    PubMed

    de Araujo, Charlotte; Arefeen, Dewan; Tadesse, Yohannes; Long, Benedict M; Price, G Dean; Rowlett, Roger S; Kimber, Matthew S; Espie, George S

    2014-09-01

    Carboxysomes are proteinaceous microcompartments that encapsulate carbonic anhydrase (CA) and ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco); carboxysomes, therefore, catalyze reversible HCO3 (-) dehydration and the subsequent fixation of CO2. The N- and C-terminal domains of the β-carboxysome scaffold protein CcmM participate in a network of protein-protein interactions that are essential for carboxysome biogenesis, organization, and function. The N-terminal domain of CcmM in the thermophile Thermosynechococcus elongatus BP-1 is also a catalytically active, redox regulated γ-CA. To experimentally determine if CcmM from a mesophilic cyanobacterium is active, we cloned, expressed and purified recombinant, full-length CcmM from Nostoc sp. PCC 7120 as well as the N-terminal 209 amino acid γ-CA-like domain. Both recombinant proteins displayed ethoxyzolamide-sensitive CA activity in mass spectrometric assays, as did the carboxysome-enriched TP fraction. NstCcmM209 was characterized as a moderately active and efficient γ-CA with a k cat of 2.0 × 10(4) s(-1) and k cat/K m of 4.1 × 10(6) M(-1) s(-1) at 25 °C and pH 8, a pH optimum between 8 and 9.5 and a temperature optimum spanning 25-35 °C. NstCcmM209 also catalyzed the hydrolysis of the CO2 analog carbonyl sulfide. Circular dichroism and intrinsic tryptophan fluorescence analysis demonstrated that NstCcmM209 was progressively and irreversibly denatured above 50 °C. NstCcmM209 activity was inhibited by the reducing agent tris(hydroxymethyl)phosphine, an effect that was fully reversed by a molar excess of diamide, a thiol oxidizing agent, consistent with oxidative activation being a universal regulatory mechanism of CcmM orthologs. Immunogold electron microscopy and Western blot analysis of TP pellets indicated that Rubisco and CcmM co-localize and are concentrated in Nostoc sp. PCC 7120 carboxysomes.

  10. A randomized comparison of 5 versus 12 hours per day of cardiac contractility modulation treatment for heart failure patients: A preliminary report.

    PubMed

    Kloppe, Axel; Mijic, Dejan; Schiedat, Fabian; Bogossian, Harilaos; Mügge, Andreas; Rousso, Benny; Lemke, Bernd

    2016-01-01

    Cardiac contractility modulation (CCM) signals are non-excitatory electrical signals delivered during the absolute refractory period intended to improve contraction and cardiac function. Clinical trials have shown that CCM treatment significantly improves exercise tolerance and quality of life in symptomatic heart failure patients. Studies with CCM therapy typically include CCM delivery for 3, 5 or 7 h per day, although other configurations are also commonly used. Each has been associated with improved outcomes in heart failure, but it is not clear whether different application durations are associated with the various degrees of benefit. The purpose of the current pilot evaluation study was to evaluate the quality of life, exercise tolerance, and cardiac function, over a 6-month period when CCM was delivered for 5 h/day vs. 12 h/day. Increasing the daily CCM therapy duration is safe and as good as the standard CCM periods of application per day. This single center pilot evaluation study involved 19 medically refractory symptomatic patients with heart failure and reduced left ventricular function who underwent implantation of an Optimizer™ system (Impulse Dynamics, Orangeburg, NY, USA). Patients were randomized into one of two treatment groups; 5 h/day CCM treatment or 12 h/day CCM treatment. Subjects and evaluating physicians were blinded to the study group. Subjects returned to the hospital after 12 and 24 weeks. Efficacy evaluations included changes from baseline to 24 weeks in Minnesota Living With Heart Failure Questionnaire score (MLWHFQ), maximal oxygen consumption in the cardio-pulmonary stress test (peak VO2), New York Heart Association classification (NYHA), 6-min walk distance (6MWD), and ejection fraction (EF). At the end of 24 weeks, clinical improvement was observed in the entire cohort in all efficacy measures (mean change from baseline of -17.1 in MLWHFQ, -0.86 in NYHA, and improvement trend of 1.48 mL O2/kg/min in peak VO2, 31.3 m in 6MWD, and 2.25% in EF). There were no significant differences, either clinically or statistically, between the groups receiving CCM for 5 h/day vs. 12 h/day. Three subjects were voluntarily withdrawn before completing the study. One subject died from pneumonia after 125 days, and 6 serious adverse events were reported, none of which was classified as related to either the device or the procedure. Together with previously reported experience with CCM, delivery of CCM therapy is equally safe and appears similarly effective over the range of shorter (5 h) to longer (12 h) daily periods of application. Given the small sample size, further studies are warranted.

  11. Curcumin inhibits vasculogenic mimicry through the downregulation of erythropoietin-producing hepatocellular carcinoma-A2, phosphoinositide 3-kinase and matrix metalloproteinase-2

    PubMed Central

    LIANG, YIMING; HUANG, MIN; LI, JIANWEN; SUN, XINLIN; JIANG, XIAODAN; LI, LIANGPING; KE, YIQUAN

    2014-01-01

    Glioblastomas (GBMs) are the most common and aggressive malignant primary brain tumors found in humans. In high-grade gliomas, vasculogenic mimicry (VM) is often detected. VM is the formation of de novo vascular networks by highly invasive tumor cells, instead of endothelial cells. An understanding of the mechanisms of VM formation will contribute to the targeted therapy of GBMs. In the present study, the efficacy of curcumin (CCM) on VM formation and its mechanisms were investigated. It was found that CCM inhibits the VM formation, proliferation, migration and invasion of human glioma U251 cells in a dose-dependent manner. Furthermore, CCM downregulated the protein and mRNA expression of erythropoietin-producing hepatocellular carcinoma-A2, phosphoinositide 3-kinase and matrix metalloproteinase-2, indicating that CCM may function through these factors for the inhibition of VM formation. These data provide novel insights into the use of CCM to antagonize VM, and may contribute to the angiogenesis-targeted therapy of malignant glioma. PMID:25202424

  12. Outcome after surgical or conservative management of cerebral cavernous malformations.

    PubMed

    Moultrie, Fiona; Horne, Margaret A; Josephson, Colin B; Hall, Julie M; Counsell, Carl E; Bhattacharya, Jo J; Papanastassiou, Vakis; Sellar, Robin J; Warlow, Charles P; Murray, Gordon D; Al-Shahi Salman, Rustam

    2014-08-12

    There have been few comparative studies of microsurgical excision vs conservative management of cerebral cavernous malformations (CCM) and none of them has reliably demonstrated a statistically and clinically significant difference. We conducted a prospective, population-based study to identify and independently validate definite CCM diagnoses first made in 1999-2003 in Scottish adult residents. We used multiple sources of prospective follow-up to assess adults' dependence and to identify and independently validate outcome events. We used univariate and multivariable survival analyses to test the influence of CCM excision on outcome, adjusted for prognostic factors and baseline imbalances. Of 134 adults, 25 underwent CCM excision; these adults were younger (34 vs 43 years at diagnosis, p = 0.004) and more likely to present with symptomatic intracranial hemorrhage or focal neurologic deficit than adults managed conservatively (48% vs 26%; odds ratio 2.7, 95% confidence interval [CI] 1.1-6.5). During 5 years of follow-up, CCM excision was associated with a deterioration to an Oxford Handicap Scale score 2-6 sustained over at least 2 successive years (adjusted hazard ratio [HR] 2.2, 95% CI 1.1-4.3) and the occurrence of symptomatic intracranial hemorrhage or new focal neurologic deficit (adjusted HR 3.6, 95% CI 1.3-10.0). CCM excision was associated with worse outcomes over 5 years compared to conservative management. Long-term follow-up will determine whether this difference is sustained over patients' lifetimes. Meanwhile, a randomized controlled trial appears justified. This study provides Class III evidence that CCM excision worsens short-term disability scores and increases the risk of symptomatic intracranial hemorrhage and new focal neurologic deficits. © 2014 American Academy of Neurology.

  13. Convergent Cross Mapping: Basic concept, influence of estimation parameters and practical application.

    PubMed

    Schiecke, Karin; Pester, Britta; Feucht, Martha; Leistritz, Lutz; Witte, Herbert

    2015-01-01

    In neuroscience, data are typically generated from neural network activity. Complex interactions between measured time series are involved, and nothing or only little is known about the underlying dynamic system. Convergent Cross Mapping (CCM) provides the possibility to investigate nonlinear causal interactions between time series by using nonlinear state space reconstruction. Aim of this study is to investigate the general applicability, and to show potentials and limitation of CCM. Influence of estimation parameters could be demonstrated by means of simulated data, whereas interval-based application of CCM on real data could be adapted for the investigation of interactions between heart rate and specific EEG components of children with temporal lobe epilepsy.

  14. A New Water-Soluble Nanomicelle Formed through Self-Assembly of Pectin-Curcumin Conjugates: Preparation, Characterization, and Anticancer Activity Evaluation.

    PubMed

    Bai, Feng; Diao, Jiajing; Wang, Ying; Sun, Shixin; Zhang, Hongmei; Liu, Yunyun; Wang, Yanqing; Cao, Jian

    2017-08-16

    Curcumin is a dominating active component of Curcuma longa and has been studied widely because of its prominent biological activities. The extremely low aqueous solubility, stability, and bioavailability of curcumin limit its application in the field of medicine. In this study, we developed pectin-curcumin (PEC-CCM) conjugates that could self-assemble water-soluble nanomicelles in aqueous solution. The structure of PEC-CCM conjugates was characterized by ultraviolet-visible spectra, fluorescence spectra, Fourier transform infrared spectroscopy, and 1 H nuclear magnetic resonance spectroscopy. The thermal property of PEC-CCM conjugates was investigated by thermogravimetric analysis. It was found that PEC-CCM conjugates had formed nanomicelles in aqueous medium via self-assembly. These nanomicelles were observed as small spheres or ellipsoids and aggregated with a size range of 70-190 nm by transmission electron microscopy analysis. In a solution of nanomicelles, the stability of curcumin was improved, and its antioxidant property was preserved. The anticancer activity of PEC-CCM conjugates was quantified by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay using a hepatic cancer cell line (HepG2), a breast cancer cell line (MCF-7), a cervical cancer cell line (HeLa), and a human normal kidney cell line (293A). It was found that the curcumin of PEC-CCM conjugates had a more significant inhibitory effect on cancer cells and was less cytotoxic to normal cells than free curcumin was. PEC-CCM conjugates have great potential for some food and pharmaceutical applications.

  15. Strategies of dissolved inorganic carbon use in macroalgae across a gradient of terrestrial influence: implications for the Great Barrier Reef in the context of ocean acidification

    NASA Astrophysics Data System (ADS)

    Diaz-Pulido, Guillermo; Cornwall, Christopher; Gartrell, Patrick; Hurd, Catriona; Tran, Dien V.

    2016-12-01

    Macroalgae are generally used as indicators of coral reef status; thus, understanding the drivers and mechanisms leading to increased macroalgal abundance are of critical importance. Ocean acidification (OA) due to elevated carbon dioxide (CO2) concentrations has been suggested to stimulate macroalgal growth and abundance on reefs. However, little is known about the physiological mechanisms by which reef macroalgae use CO2 from the bulk seawater for photosynthesis [i.e., (1) direct uptake of bicarbonate (HCO3 -) and/or CO2 by means of carbon concentrating mechanisms (CCM) and (2) the diffusive uptake of CO2], which species could benefit from increased CO2 or which habitats may be more susceptible to acidification-induced algal proliferations. Here, we provide the first quantitative examination of CO2-use strategies in coral reef macroalgae and provide information on how the proportion of species and the proportional abundance of species utilising each of the carbon acquisition strategies varies across a gradient of terrestrial influence (from inshore to offshore reefs) in the Great Barrier Reef (GBR). Four macroalgal groups were identified based on their carbon uptake strategies: (1) CCM-only (HCO3 - only users); (2) CCM-HCO3 -/CO2 (active uptake HCO3 - and/or CO2 use); (3) Non-CCM species (those relying on diffusive CO2 uptake); and (4) Calcifiers. δ13C values of macroalgae, confirmed by pH drift assays, show that diffusive CO2 use is more prevalent in deeper waters, possibly due to low light availability that limits activity of CCMs. Inshore shallow reefs had a higher proportion of CCM-only species, while reefs further away from terrestrial influence and exposed to better water quality had a higher number of non-CCM species than inshore and mid-shelf reefs. As non-CCM macroalgae are more responsive to increased seawater CO2 and OA, reef slopes of the outer reefs are probably the habitats most vulnerable to the impacts of OA. Our results suggest a potentially important role of carbon physiology in structuring macroalgal communities in the GBR.

  16. A Model and Satellite-Based Analysis of the Tropospheric Ozone Distribution in Clear Versus Convectively Cloudy Conditions

    NASA Technical Reports Server (NTRS)

    Strode, Sarah A.; Douglass, Anne R.; Ziemke, Jerald R.; Manyin, Michael; Nielsen, J. Eric; Oman, Luke D.

    2017-01-01

    Satellite observations of in-cloud ozone concentrations from the Ozone Monitoring Instrument and Microwave Limb Sounder instruments show substantial differences from background ozone concentrations. We develop a method for comparing a free-running chemistry-climate model (CCM) to in-cloud and background ozone observations using a simple criterion based on cloud fraction to separate cloudy and clear-sky days. We demonstrate that the CCM simulates key features of the in-cloud versus background ozone differences and of the geographic distribution of in-cloud ozone. Since the agreement is not dependent on matching the meteorological conditions of a specific day, this is a promising method for diagnosing how accurately CCMs represent the relationships between ozone and clouds, including the lower ozone concentrations shown by in-cloud satellite observations. Since clouds are associated with convection as well as changes in chemistry, we diagnose the tendency of tropical ozone at 400 hPa due to chemistry, convection and turbulence, and large-scale dynamics. While convection acts to reduce ozone concentrations at 400 hPa throughout much of the tropics, it has the opposite effect over highly polluted regions of South and East Asia.

  17. Profiles of cardiovascular biomarkers according to severity stages of Chagas cardiomyopathy.

    PubMed

    Echeverría, Luis E; Rojas, Lyda Z; Calvo, Lauren S; Roa, Zayne M; Rueda-Ochoa, Oscar L; Morillo, Carlos A; Muka, Taulant; Franco, Oscar H

    2017-01-15

    Up 30 to 40% of Chagas patients exhibit cardiomyopathy with different degrees of cardiac involvement. Biomarkers may help in differentiation of the severity of Chagas cardiomyopathy (CCM). This study sought to examine the diagnostic value of a panel of biomarkers to distinguish the severity of (CCM). 100 patients with CCM were included in this cross-sectional study. Based on electrocardiogram and echocardiogram, CCM patients were classified in three stages according to disease's severity. Levels of high-sensitivity cardiac troponin T (Hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), soluble ST2 (sST2) and cystatin-c (Cys-c) were measured. Logistic regression models were used to assess the association between levels of natural log-transformed values of biomarkers and stages C/D versus B. We also calculated the area under curve (AUC) for each of the models. In models adjusted for age, sex, body mass index, kidney function and medication use, increased levels of NT-proBNP (per 1 unit natural log-transformed values, odds ratio (OR)=5.55; 95CI%:1.65-18.72) and Hs-cTnT (per 1 unit natural log-transformed values, OR=7.11; 95CI%:1.41-35.90) showed significant association with the severity of CCM per 1 unit increase of biomarkers. The accuracy of NT-proBNP and Hs-cTnT for diagnosis of the severity of CCM was high: AUC of 0.968 and 0.956 respectively. No significant difference was found in the AUC between NT-proBNP and Hs-cTnT. No association was found between Gal-3, NGAL, sST2 and Cys-C and severity of CCM. NT-proBNP and Hs-cTnT have both same diagnostic value in distinguishing severity of CCM. Copyright © 2016. Published by Elsevier Ireland Ltd.

  18. Cardiac contractility modulation in heart failure patients: Randomized comparison of signal delivery through one vs. two ventricular leads.

    PubMed

    Röger, Susanne; Said, Samir; Kloppe, Axel; Lawo, Thomas; Emig, Ulf; Rousso, Benny; Gutterman, David; Borggrefe, Martin; Kuschyk, Jürgen

    2017-01-01

    Cardiac contractility modulation (CCM) is an electrical stimulation treatment for symptomatic heart failure (HF) patients. The procedure involves implantation of two ventricular leads for delivery of CCM impulses. The purpose of this study is to compare the efficacy and safety of CCM when the signal is delivered through one vs. two ventricular leads. This prospective blinded randomized trial enrolled 48 patients. Eligible subjects had symptoms despite optimal HF medications, left ventricular ejection fraction <40% and peakVO 2 ≥9ml O 2 /kg/min. All patients received a CCM system with two ventricular leads, and were randomized to CCM active through both or just one ventricular lead; 25 patients were randomized to receive signal delivery through two leads (Group A) and 23 patients to signal delivery through one lead (Group B). The study compared the mean changes from baseline to 6 months follow-up in peakVO 2 , New York Heart Association (NYHA) classification, and quality of life (by MLWHFQ). Following 6 months, similar and significant (p<0.05) improvements from baseline in NYHA (-0.7±0.5 vs. -0.9±0.7) and MLWHFQ (-14±20 vs. -16±22) were observed in Group A and in Group B. PeakVO 2 showed improvement trends in both groups (0.34±1.52 vs. 0.10±2.21ml/kg/min; p=ns). No patient died. Serious adverse event rates (20 events in 10 subjects) were not different between groups. No statistically significant difference was found in any of the study endpoints. The efficacy and safety of CCM in this study were similar when the signal was delivered through either one or two ventricular leads. These results support the potential use of a single ventricular lead for delivery of CCM. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  19. A comparison of observed (HALOE) and modeled (CCM2) methane and stratospheric water vapor

    NASA Technical Reports Server (NTRS)

    Mote, Philip W.; Holton, James R.; Russell, James M., III; Boville, Byron A.

    1993-01-01

    Recent measurements (21 September-15 October 1992) of methane and water vapor by the Halogen Occultation Experiment (HALOE) on the Upper Atmosphere Research Satellite (UARS) are compared with model results for the same season from a troposphere-middle atmosphere version of the National Center for Atmospheric Research (NCAR) Community Climate Model (CCM2). Several important features of the two constituent fields are well reproduced by the CCM2, despite the use of simplified methane photochemistry in the CCM2 and some notable differences between the model's zonal mean circulation and climatology. Observed features simulated by the model include the following: 1) subsidence over a deep layer in the Southern Hemisphere polar vortex; 2) widespread dehydration in the polar vortex; and 3) existence of a region of low water vapor mixing ratios extending from the Antarctic into the Northern Hemisphere tropics, which suggests that Antarctic dehydration contributes to midlatitude and tropical dryness in the stratosphere.

  20. The Chronic Care Model and Technological Research and Innovation: A Scoping Review at the Crossroads

    PubMed Central

    Berntsen, Gro Karine Rosvold; Koricho, Absera Teshome; Sygna, Karin; Ruland, Cornelia

    2015-01-01

    Background Information and communication technologies (ICT) are key to optimizing the outcomes of the Chronic Care Model (CCM), currently acknowledged as the best synthesis of available evidence for chronic illness prevention and management. At the same time, CCM can offer a needed framework for increasing the relevance and feasibility of ICT innovation and research in health care. Little is known about how and to what extent CCM and ICT research inform each other to leverage mutual strengths. The current study examines: What characterizes work being done at the crossroads of CCM and ICT research and innovation? Objective Our aim is identify the gaps and potential that lie between the research domains CCM and ICT, thus enabling more substantive questions and opportunities for accelerating improvements in ICT-supported chronic care. Methods Using a scoping study approach, we developed a search strategy applied to medical and technical databases resulting in 1054 titles and abstracts that address CCM and ICT. After iteratively adapting our inclusion/exclusion criteria to balance between breadth and feasibility, 26 publications from 20 studies were found to fulfill our criteria. Following initial coding of each article according to predefined categories (eg, type of article, CCM component, ICT, health issue), a 1st level analysis was conducted resulting in a broad range of categories. These were gradually reduced by constantly comparing them for underlying commonalities and discrepancies. Results None of the studies included were from technical databases and interventions relied mostly on “old-fashioned” technologies. Technologies supporting “productive interactions” were often one-way (provider to patient), and it was sometimes difficult to decipher how CCM was guiding intervention design. In particular, the major focus on ICT to support providers did not appear unique to the challenges of chronic care. Challenges in facilitating CCM components through ICT included poorly designed user interfaces, digital divide issues, and lack of integration with existing infrastructure. Conclusions The CCM is a highly influential guide for health care development, which recognizes the need for alignment of system tools such as ICT. Yet, there seem to be alarmingly few touch points between the subject fields of “health service development” and “ICT-innovation”. Bridging these gaps needs explicit and urgent attention as the synergies between these domains have enormous potential. Policy makers and funding agencies need to facilitate the joining of forces between high-tech innovative expertise and experts in the chronic care system redesign that is required for tackling the current epidemic of long-term multiple conditions. PMID:25677200

  1. The chronic care model and technological research and innovation: a scoping review at the crossroads.

    PubMed

    Gammon, Deede; Berntsen, Gro Karine Rosvold; Koricho, Absera Teshome; Sygna, Karin; Ruland, Cornelia

    2015-02-06

    Information and communication technologies (ICT) are key to optimizing the outcomes of the Chronic Care Model (CCM), currently acknowledged as the best synthesis of available evidence for chronic illness prevention and management. At the same time, CCM can offer a needed framework for increasing the relevance and feasibility of ICT innovation and research in health care. Little is known about how and to what extent CCM and ICT research inform each other to leverage mutual strengths. The current study examines: What characterizes work being done at the crossroads of CCM and ICT research and innovation? Our aim is identify the gaps and potential that lie between the research domains CCM and ICT, thus enabling more substantive questions and opportunities for accelerating improvements in ICT-supported chronic care. Using a scoping study approach, we developed a search strategy applied to medical and technical databases resulting in 1054 titles and abstracts that address CCM and ICT. After iteratively adapting our inclusion/exclusion criteria to balance between breadth and feasibility, 26 publications from 20 studies were found to fulfill our criteria. Following initial coding of each article according to predefined categories (eg, type of article, CCM component, ICT, health issue), a 1st level analysis was conducted resulting in a broad range of categories. These were gradually reduced by constantly comparing them for underlying commonalities and discrepancies. None of the studies included were from technical databases and interventions relied mostly on "old-fashioned" technologies. Technologies supporting "productive interactions" were often one-way (provider to patient), and it was sometimes difficult to decipher how CCM was guiding intervention design. In particular, the major focus on ICT to support providers did not appear unique to the challenges of chronic care. Challenges in facilitating CCM components through ICT included poorly designed user interfaces, digital divide issues, and lack of integration with existing infrastructure. The CCM is a highly influential guide for health care development, which recognizes the need for alignment of system tools such as ICT. Yet, there seem to be alarmingly few touch points between the subject fields of "health service development" and "ICT-innovation". Bridging these gaps needs explicit and urgent attention as the synergies between these domains have enormous potential. Policy makers and funding agencies need to facilitate the joining of forces between high-tech innovative expertise and experts in the chronic care system redesign that is required for tackling the current epidemic of long-term multiple conditions.

  2. CCM-AMI, a Polyethylene Glycol Micelle with Amifostine, as an Acute Radiation Syndrome Protectant in C57BL/6 Mice.

    PubMed

    Chen, Chia-Hung; Kuo, Min-Liang; Wang, Jen-Ling; Liao, Wei-Chuan; Chang, Li-Ching; Chan, Leong-Perng; Lin, Johnson

    2015-09-01

    Acute radiation syndrome results from radiation exposure, such as in accidental nuclear disasters. Safe and effective radioprotectants, mitigators, and treatment drugs must be developed as medical countermeasures against radiation exposure. Here, the authors evaluated CCM-Ami, a novel polyethylene glycol micelle encapsulated with amifostine, for its radioprotective properties after total-body irradiation from a 60Co source. Male C57BL/6 mice (6-8 wk old) were intravenously injected with 45 mg kg(-1) of CCM-Ami 90 min before exposure to 7.2 and 8.5 Gy irradiation at a dose rate of 0.04 Gy min(-1). Both survival benefit and hematopoietic protection were observed after prophylactic CCM-Ami administration when compared with the effects measured in excipient control and amifostine groups. Pharmacokinetic results showed that after the intravenous injection, the plasma concentration of WR-1065, the active form of amifostine, was higher in CCM-Ami-treated mice than in amifostine-treated mice. These findings suggest that CCM-Ami-mediated hematopoietic protection plays a key role in enhancing survival of mice exposed to radiation toxicity and thus indicate that CCM-Ami is a radioprotectant that can be used safely and effectively in nuclear disasters.

  3. pH determines the energetic efficiency of the cyanobacterial CO2 concentrating mechanism.

    PubMed

    Mangan, Niall M; Flamholz, Avi; Hood, Rachel D; Milo, Ron; Savage, David F

    2016-09-06

    Many carbon-fixing bacteria rely on a CO2 concentrating mechanism (CCM) to elevate the CO2 concentration around the carboxylating enzyme ribulose bisphosphate carboxylase/oxygenase (RuBisCO). The CCM is postulated to simultaneously enhance the rate of carboxylation and minimize oxygenation, a competitive reaction with O2 also catalyzed by RuBisCO. To achieve this effect, the CCM combines two features: active transport of inorganic carbon into the cell and colocalization of carbonic anhydrase and RuBisCO inside proteinaceous microcompartments called carboxysomes. Understanding the significance of the various CCM components requires reconciling biochemical intuition with a quantitative description of the system. To this end, we have developed a mathematical model of the CCM to analyze its energetic costs and the inherent intertwining of physiology and pH. We find that intracellular pH greatly affects the cost of inorganic carbon accumulation. At low pH the inorganic carbon pool contains more of the highly cell-permeable H2CO3, necessitating a substantial expenditure of energy on transport to maintain internal inorganic carbon levels. An intracellular pH ≈8 reduces leakage, making the CCM significantly more energetically efficient. This pH prediction coincides well with our measurement of intracellular pH in a model cyanobacterium. We also demonstrate that CO2 retention in the carboxysome is necessary, whereas selective uptake of HCO3 (-) into the carboxysome would not appreciably enhance energetic efficiency. Altogether, integration of pH produces a model that is quantitatively consistent with cyanobacterial physiology, emphasizing that pH cannot be neglected when describing biological systems interacting with inorganic carbon pools.

  4. pH determines the energetic efficiency of the cyanobacterial CO2 concentrating mechanism

    PubMed Central

    Flamholz, Avi; Hood, Rachel D.; Milo, Ron

    2016-01-01

    Many carbon-fixing bacteria rely on a CO2 concentrating mechanism (CCM) to elevate the CO2 concentration around the carboxylating enzyme ribulose bisphosphate carboxylase/oxygenase (RuBisCO). The CCM is postulated to simultaneously enhance the rate of carboxylation and minimize oxygenation, a competitive reaction with O2 also catalyzed by RuBisCO. To achieve this effect, the CCM combines two features: active transport of inorganic carbon into the cell and colocalization of carbonic anhydrase and RuBisCO inside proteinaceous microcompartments called carboxysomes. Understanding the significance of the various CCM components requires reconciling biochemical intuition with a quantitative description of the system. To this end, we have developed a mathematical model of the CCM to analyze its energetic costs and the inherent intertwining of physiology and pH. We find that intracellular pH greatly affects the cost of inorganic carbon accumulation. At low pH the inorganic carbon pool contains more of the highly cell-permeable H2CO3, necessitating a substantial expenditure of energy on transport to maintain internal inorganic carbon levels. An intracellular pH ≈8 reduces leakage, making the CCM significantly more energetically efficient. This pH prediction coincides well with our measurement of intracellular pH in a model cyanobacterium. We also demonstrate that CO2 retention in the carboxysome is necessary, whereas selective uptake of HCO3− into the carboxysome would not appreciably enhance energetic efficiency. Altogether, integration of pH produces a model that is quantitatively consistent with cyanobacterial physiology, emphasizing that pH cannot be neglected when describing biological systems interacting with inorganic carbon pools. PMID:27551079

  5. High-Order Coupled Cluster Method (CCM) Calculations for Quantum Magnets with Valence-Bond Ground States

    NASA Astrophysics Data System (ADS)

    Farnell, D. J. J.; Richter, J.; Zinke, R.; Bishop, R. F.

    2009-04-01

    In this article, we prove that exact representations of dimer and plaquette valence-bond ket ground states for quantum Heisenberg antiferromagnets may be formed via the usual coupled cluster method (CCM) from independent-spin product (e.g. Néel) model states. We show that we are able to provide good results for both the ground-state energy and the sublattice magnetization for dimer and plaquette valence-bond phases within the CCM. As a first example, we investigate the spin-half J 1- J 2 model for the linear chain, and we show that we are able to reproduce exactly the dimerized ground (ket) state at J 2/ J 1=0.5. The dimerized phase is stable over a range of values for J 2/ J 1 around 0.5, and results for the ground-state energies are in good agreement with the results of exact diagonalizations of finite-length chains in this regime. We present evidence of symmetry breaking by considering the ket- and bra-state correlation coefficients as a function of J 2/ J 1. A radical change is also observed in the behavior of the CCM sublattice magnetization as we enter the dimerized phase. We then consider the Shastry-Sutherland model and demonstrate that the CCM can span the correct ground states in both the Néel and the dimerized phases. Once again, very good results for the ground-state energies are obtained. We find CCM critical points of the bra-state equations that are in agreement with the known phase transition point for this model. The results for the sublattice magnetization remain near to the "true" value of zero over much of the dimerized regime, although they diverge exactly at the critical point. Finally, we consider a spin-half system with nearest-neighbor bonds for an underlying lattice corresponding to the magnetic material CaV4O9 (CAVO). We show that we are able to provide excellent results for the ground-state energy in each of the plaquette-ordered, Néel-ordered, and dimerized regimes of this model. The exact plaquette and dimer ground states are reproduced by the CCM ket state in their relevant limits. Furthermore, we estimate the range over which the Néel order is stable, and we find the CCM result is in reasonable agreement with the results obtained by other methods. Our new approach has the dual advantages that it is simple to implement and that existing CCM codes for independent-spin product model states may be used from the outset. Furthermore, it also greatly extends the range of applicability to which the CCM may be applied. We believe that the CCM now provides an excellent choice of method for the study of systems with valence-bond quantum ground states.

  6. Seasonal and interannual variability of carbon monoxide based on MOZAIC observations, MACC reanalysis, and model simulations over an urban site in India

    NASA Astrophysics Data System (ADS)

    Sheel, Varun; Sahu, L. K.; Kajino, M.; Deushi, M.; Stein, O.; Nedelec, P.

    2014-07-01

    The spatial and temporal variations of carbon monoxide (CO) are analyzed over a tropical urban site, Hyderabad (17°27'N, 78°28'E) in central India. We have used vertical profiles from the Measurement of ozone and water vapor by Airbus in-service aircraft (MOZAIC) aircraft observations, Monitoring Atmospheric Composition and Climate (MACC) reanalysis, and two chemical transport model simulations (Model for Ozone And Related Tracers (MOZART) and MRI global Chemistry Climate Model (MRI-CCM2)) for the years 2006-2008. In the lower troposphere, the CO mixing ratio showed strong seasonality, with higher levels (>300 ppbv) during the winter and premonsoon seasons associated with a stable anticyclonic circulation, while lower CO values (up to 100 ppbv) were observed in the monsoon season. In the planetary boundary layer (PBL), the seasonal distribution of CO shows the impact of both local meteorology and emissions. While the PBL CO is predominantly influenced by strong winds, bringing regional background air from marine and biomass burning regions, under calm conditions CO levels are elevated by local emissions. On the other hand, in the free troposphere, seasonal variation reflects the impact of long-range transport associated with the Intertropical Convergence Zone and biomass burning. The interannual variations were mainly due to transition from El Niño to La Niña conditions. The overall modified normalized mean biases (normalization based on the observed and model mean values) with respect to the observed CO profiles were lower for the MACC reanalysis than the MOZART and MRI-CCM2 models. The CO in the PBL region was consistently underestimated by MACC reanalysis during all the seasons, while MOZART and MRI-CCM2 show both positive and negative biases depending on the season.

  7. Characteristics of stratosphere-troposphere exchange in a general circulation model

    NASA Technical Reports Server (NTRS)

    Mote, Philip W.; Holton, James R.; Boville, Byron A.

    1994-01-01

    In this study we examine mass exchange, water vapor exchange, and the behavior of idealized tracers and parcels to diagnose Stratosphere-Troposphere Exchange (STE) in the National Center for Atmospheric Research (NCAR) General Circulation Model (GCM), the Community Climate Model (CCM2). The CCM2 correctly represents the seasonality of mass exchange across 100 hPa, but values are uniformly too strong. Water vapor, however, indicates that tropical STE is not well represented in the CCM2; even though mean tropopause temperatures are colder than observed, the lower stratosphere is too moist. Most net mass flux occurs at water vapor mixing ratios of about 4-5 parts per million by volume (ppmv), about 1 ppmv too moist. Vertical resolution has little impact on the nature of tropical STE. In midlatitudes, CCM2 more successfully represents STE, which occurs in developing baroclinic waves and stationary anticyclones. Exchange from troposphere to stratosphere does occur but only influences the lowest few kilometers of the extratropical stratosphere, even for tracers with large vertical gradients.

  8. Final Report: Comparison of the primary (national) standards of low-pressure gas flow

    NASA Astrophysics Data System (ADS)

    Benková, Miroslava; Makovnik, Stefan; Mickan, Bodo

    2015-01-01

    The EURAMET.M.FF-K6 comparison was organized for the purpose of determination of the degree of equivalence of the primary (national) standards for low-pressure gas flow measurement over the range (2 to 100) m3/h and was performed simultaneously with CCM.FF-K6.2011 with the same transfer standard. A rotary gas meter G65 was used as a transfer standard. The measurements were provided by prescribed reference conditions. Fifteen laboratories from EURAMET participated in this key comparison - SMU, Slovakia; PTB, Germany; CEM, Spain; LNE-LADG, France; VSL, Netherlands; CMI, Czech Republic; BEV, Austria; MKEH, Hungary; GUM Poland; SP, Sweden; METAS, Switzerland; DMDM, Serbia; TUBITAK-UME, Turkey; EIM, Greece; IMBiH, Bosnia-Herzegovina. The EURAMET.M.FF-K6 is linked to the CCM.FF-K6.2011 by correcting the results of three linking laboratories (Slovakia SMU, Germany PTB and France LNE LADG). This correction provides an estimate of what would have been the result from the EURAMET.M-FF-K6 participants, if they had actually participated in CCM.FF-K6.2011. According to the evaluation 93.7 % of the results were consistent with KCRV, 3.4 % of the results were in the warning level and 2.9 % of the results were inconsistent. The results of this comparison can be used for review of the CMC tables. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  9. Quality of care in integrated community case management services in Bugoye, Uganda: a retrospective observational study.

    PubMed

    Miller, James S; English, Lacey; Matte, Michael; Mbusa, Rapheal; Ntaro, Moses; Bwambale, Shem; Kenney, Jessica; Siedner, Mark J; Reyes, Raquel; Lee, Patrick T; Mulogo, Edgar; Stone, Geren S

    2018-02-27

    Village health workers (VHWs) in five villages in Bugoye subcounty (Kasese District, Uganda) provide integrated community case management (iCCM) services, in which VHWs evaluate and treat malaria, pneumonia, and diarrhoea in children under 5 years of age. VHWs use a "Sick Child Job Aid" that guides them through the evaluation and treatment of these illnesses. A retrospective observational study was conducted to measure the quality of iCCM care provided by 23 VHWs in 5 villages in Bugoye subcounty over a 2-year period. Patient characteristics and clinical services were summarized using existing aggregate programme data. Lot quality assurance sampling of individual patient records was used to estimate adherence to the iCCM algorithm, VHW-level quality (based on adherence to the iCCM protocol), and change over time in quality of care (using generalized estimating equations regression modelling). For each of 23 VHWs, 25 patient visits were randomly selected from a 2-year period after iCCM care initiation. In these visits, 97% (150) of patients with diarrhoea were treated with oral rehydration and zinc, 95% (216) of patients with pneumonia were treated with amoxicillin, and 94% (240) of patients with malaria were treated with artemisinin-based combination therapy or rectal artesunate. However, only 44% (44) of patients with a negative rapid test for malaria were appropriately referred to a health facility. Overall, 75% (434) of patients received all the correct evaluation and management steps. Only 9 (39%) of the 23 VHWs met the pre-determined LQAS threshold for high-quality care over the 2-year observation period. Quality of care increased significantly in the first 6 months after initiation of iCCM services (p = 0.003), and then plateaued during months 7-24. Quality of care was high for uncomplicated malaria, pneumonia and diarrhoea. Overall quality of care was lower, in part because VHWs often did not follow the guidelines to refer patients with fever who tested negative for malaria. Quality of care appears to improve in the initial months after iCCM implementation, as VHWs gain initial experience in iCCM care.

  10. Chronic care model implementation in the California State Prison System.

    PubMed

    Ha, Betsy Chang; Robinson, Greg

    2011-04-01

    The chronic care model (CCM) deployed through a learning collaborative strategy, such as the Institute for Healthcare Improvement's Breakthrough Series (BTS), is a widely adopted approach to improve care that has guided clinical quality initiatives nationally and internationally. The BTS collaborative approach has been used to improve chronic conditions at national and state levels and in single health care delivery systems but not in correctional health care. Combining the CCM with a learning collaborative strategy in prison health care is a new frontier. This article describes the adoption of the CCM using a learning collaborative approach in the California prison system under the mandate of a federal receivership and elucidates some barriers to implementation. Results from the first phase of a pilot study were positive in terms of benefit/ cost analysis and suggest financial and political viability to continue the program.

  11. Applying Reflective Middleware Techniques to Optimize a QoS-enabled CORBA Component Model Implementation

    NASA Technical Reports Server (NTRS)

    Wang, Nanbor; Parameswaran, Kirthika; Kircher, Michael; Schmidt, Douglas

    2003-01-01

    Although existing CORBA specifications, such as Real-time CORBA and CORBA Messaging, address many end-to-end quality-of service (QoS) properties, they do not define strategies for configuring these properties into applications flexibly, transparently, and adaptively. Therefore, application developers must make these configuration decisions manually and explicitly, which is tedious, error-prone, and open sub-optimal. Although the recently adopted CORBA Component Model (CCM) does define a standard configuration framework for packaging and deploying software components, conventional CCM implementations focus on functionality rather than adaptive quality-of-service, which makes them unsuitable for next-generation applications with demanding QoS requirements. This paper presents three contributions to the study of middleware for QoS-enabled component-based applications. It outlines rejective middleware techniques designed to adaptively (1) select optimal communication mechanisms, (2) manage QoS properties of CORBA components in their contain- ers, and (3) (re)con$gure selected component executors dynamically. Based on our ongoing research on CORBA and the CCM, we believe the application of rejective techniques to component middleware will provide a dynamically adaptive and (re)configurable framework for COTS software that is well-suited for the QoS demands of next-generation applications.

  12. Applying Reflective Middleware Techniques to Optimize a QoS-enabled CORBA Component Model Implementation

    NASA Technical Reports Server (NTRS)

    Wang, Nanbor; Kircher, Michael; Schmidt, Douglas C.

    2000-01-01

    Although existing CORBA specifications, such as Real-time CORBA and CORBA Messaging, address many end-to-end quality-of-service (QoS) properties, they do not define strategies for configuring these properties into applications flexibly, transparently, and adaptively. Therefore, application developers must make these configuration decisions manually and explicitly, which is tedious, error-prone, and often sub-optimal. Although the recently adopted CORBA Component Model (CCM) does define a standard configuration frame-work for packaging and deploying software components, conventional CCM implementations focus on functionality rather than adaptive quality-of service, which makes them unsuitable for next-generation applications with demanding QoS requirements. This paper presents three contributions to the study of middleware for QoS-enabled component-based applications. It outlines reflective middleware techniques designed to adaptively: (1) select optimal communication mechanisms, (2) man- age QoS properties of CORBA components in their containers, and (3) (re)configure selected component executors dynamically. Based on our ongoing research on CORBA and the CCM, we believe the application of reflective techniques to component middleware will provide a dynamically adaptive and (re)configurable framework for COTS software that is well-suited for the QoS demands of next-generation applications.

  13. Is the Chronic Care Model Integrated Into Research Examining Culturally Competent Interventions for Ethnically Diverse Adults With Type 2 Diabetes Mellitus? A Review.

    PubMed

    Dauvrin, Marie; Lorant, Vincent; d'Hoore, William

    2015-12-01

    The chronic care model (CCM) concerns both the medical and the cultural and linguistic needs of patients through the inclusion of cultural competence in the delivery system design. This literature review attempted to@@ identify the domains of the CCM culturally competent (CC) interventions that the adults from ethnic minorities suffering from type 2 diabetes mellitus report. We identified the CCM and the CC components in the relevant studies published between 2005 and 2014. Thirty-two studies were included. Thirty-one articles focused on self-management and 20 on community resources. Twenty-three interventions integrated cultural norms from the patients' backgrounds. CC interventions reported the CCM at the individual level but need to address the organizational level more effectively. The scope of CC interventions should be expanded to transform health care organizations and systems. © The Author(s) 2015.

  14. A variant System I for cytochrome c biogenesis in archaea and some bacteria has a novel CcmE and no CcmH.

    PubMed

    Allen, James W A; Harvat, Edgar M; Stevens, Julie M; Ferguson, Stuart J

    2006-09-04

    C-type cytochromes are characterized by post-translational covalent attachment of heme to thiols that occur in a Cys-Xxx-Xxx-Cys-His motif. Three distinct biogenesis systems are known for this heme attachment. Archaea are now shown to contain a significantly modified form of cytochrome c maturation System I (the Ccm system). The most notable adaptation relative to the well-studied apparatus from proteobacteria and plants is a novel form of the heme chaperone CcmE, lacking the highly conserved histidine that covalently binds heme and is essential for function in Escherichia coli. In most archaeal CcmEs this histidine, normally found in a His-Xxx-Xxx-Xxx-Tyr motif, is replaced by a cysteine residue that occurs in a Cys-Xxx-Xxx-Xxx-Tyr motif. The CcmEs from two halobacteria contain yet another form of CcmE, having HxxxHxxxH approximately corresponding in alignment to the H/CxxxY motif. The CxxxY-type of CcmE is, surprisingly, also found in some bacterial genomes (including Desulfovibrio species). All of the modified CcmEs cluster together in a phylogenetic tree, as do other Ccm proteins from the same organisms. Significantly, CcmH is absent from all of the complete archaeal genomes we have studied, and also from most of the bacterial genomes that have CxxxY-type CcmE.

  15. 75 FR 31419 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-03

    ... Person Interview (PI) and CCM PFU have been added. These are to be conducted as part of a CCM evaluation... CCM PI OMB package. The CCM program will provide estimates of net coverage error and components of... (PI) and CCM PFU will be conducted. The purpose of the respondent debriefings is to obtain a...

  16. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gilkey, Lindsay

    This milestone presents a demonstration of the High-to-Low (Hi2Lo) process in the VVI focus area. Validation and additional calculations with the commercial computational fluid dynamics code, STAR-CCM+, were performed using a 5x5 fuel assembly with non-mixing geometry and spacer grids. This geometry was based on the benchmark experiment provided by Westinghouse. Results from the simulations were compared to existing experimental data and to the subchannel thermal-hydraulics code COBRA-TF (CTF). An uncertainty quantification (UQ) process was developed for the STAR-CCM+ model and results of the STAR UQ were communicated to CTF. Results from STAR-CCM+ simulations were used as experimental design pointsmore » in CTF to calibrate the mixing parameter β and compared to results obtained using experimental data points. This demonstrated that CTF’s β parameter can be calibrated to match existing experimental data more closely. The Hi2Lo process for the STAR-CCM+/CTF code coupling was documented in this milestone and closely linked L3:VVI.H2LP15.01 milestone report.« less

  17. Combinatorial interaction between CCM pathway genes precipitates hemorrhagic stroke.

    PubMed

    Gore, Aniket V; Lampugnani, Maria Grazia; Dye, Louis; Dejana, Elisabetta; Weinstein, Brant M

    2008-01-01

    Intracranial hemorrhage (ICH) is a particularly severe form of stroke whose etiology remains poorly understood, with a highly variable appearance and onset of the disease (Felbor et al., 2006; Frizzell, 2005; Lucas et al., 2003). In humans, mutations in any one of three CCM genes causes an autosomal dominant genetic ICH disorder characterized by cerebral cavernous malformations (CCM). Recent evidence highlighting multiple interactions between the three CCM gene products and other proteins regulating endothelial junctional integrity suggests that minor deficits in these other proteins could potentially predispose to, or help to initiate, CCM, and that combinations of otherwise silent genetic deficits in both the CCM and interacting proteins might explain some of the variability in penetrance and expressivity of human ICH disorders. Here, we test this idea by combined knockdown of CCM pathway genes in zebrafish. Reducing the function of rap1b, which encodes a Ras GTPase effector protein for CCM1/Krit1, disrupts endothelial junctions in vivo and in vitro, showing it is a crucial player in the CCM pathway. Importantly, a minor reduction of Rap1b in combination with similar reductions in the products of other CCM pathway genes results in a high incidence of ICH. These findings support the idea that minor polygenic deficits in the CCM pathway can strongly synergize to initiate ICH.

  18. Acclimation to Very Low CO2: Contribution of Limiting CO2 Inducible Proteins, LCIB and LCIA, to Inorganic Carbon Uptake in Chlamydomonas reinhardtii1[OPEN

    PubMed Central

    Spalding, Martin H.

    2014-01-01

    The limiting-CO2 inducible CO2-concentrating mechanism (CCM) of microalgae represents an effective strategy to capture CO2 when its availability is limited. At least two limiting-CO2 acclimation states, termed low CO2 and very low CO2, have been demonstrated in the model microalga Chlamydomonas reinhardtii, and many questions still remain unanswered regarding both the regulation of these acclimation states and the molecular mechanism underlying operation of the CCM in these two states. This study examines the role of two proteins, Limiting CO2 Inducible A (LCIA; also named NAR1.2) and LCIB, in the CCM of C. reinhardtii. The identification of an LCIA-LCIB double mutant based on its inability to survive in very low CO2 suggests that both LCIA and LCIB are critical for survival in very low CO2. The contrasting effects of individual mutations in LCIB and LCIA compared with the effects of LCIB-LCIA double mutations on growth and inorganic carbon-dependent photosynthetic O2 evolution reveal distinct roles of LCIA and LCIB in the CCM. Although both LCIA and LCIB are essential for very low CO2 acclimation, LCIB appears to function in a CO2 uptake system, whereas LCIA appears to be associated with a HCO3− transport system. The contrasting and complementary roles of LCIA and LCIB in acclimation to low CO2 and very low CO2 suggest a possible mechanism of differential regulation of the CCM based on the inhibition of HCO3− transporters by moderate to high levels of CO2. PMID:25336519

  19. Critical Care Medicine and Infectious Diseases: An Emerging Combined Subspecialty in the United States

    PubMed Central

    Kadri, Sameer S.; Rhee, Chanu; Fortna, Gregory S.; O'Grady, Naomi P.

    2015-01-01

    The recent rise in unfilled training positions among infectious diseases (ID) fellowship programs nationwide indicates that ID is declining as a career choice among internal medicine residency graduates. Supplementing ID training with training in critical care medicine (CCM) might be a way to regenerate interest in the specialty. Hands-on patient care and higher salaries are obvious attractions. High infection prevalence and antibiotic resistance in intensive care units, expanding immunosuppressed host populations, and public health crises such as the recent Ebola outbreak underscore the potential synergy of CCM-ID training. Most intensivists receive training in pulmonary medicine and only 1% of current board-certified intensivists are trained in ID. While still small, this cohort of CCM-ID certified physicians has continued to rise over the last 2 decades. ID and CCM program leadership nationwide must recognize these trends and the merits of the CCM-ID combination to facilitate creation of formal dual-training opportunities. PMID:25944345

  20. Rapid, automated mosaicking of the human corneal subbasal nerve plexus.

    PubMed

    Vaishnav, Yash J; Rucker, Stuart A; Saharia, Keshav; McNamara, Nancy A

    2017-11-27

    Corneal confocal microscopy (CCM) is an in vivo technique used to study corneal nerve morphology. The largest proportion of nerves innervating the cornea lie within the subbasal nerve plexus, where their morphology is altered by refractive surgery, diabetes and dry eye. The main limitations to clinical use of CCM as a diagnostic tool are the small field of view of CCM images and the lengthy time needed to quantify nerves in collected images. Here, we present a novel, rapid, fully automated technique to mosaic individual CCM images into wide-field maps of corneal nerves. We implemented an OpenCV image stitcher that accounts for corneal deformation and uses feature detection to stitch CCM images into a montage. The method takes 3-5 min to process and stitch 40-100 frames on an Amazon EC2 Micro instance. The speed, automation and ease of use conferred by this technique is the first step toward point of care evaluation of wide-field subbasal plexus (SBP) maps in a clinical setting.

  1. Generation of a mouse with conditionally activated signaling through the BMP receptor, ALK2.

    PubMed

    Fukuda, Tomokazu; Scott, Gregory; Komatsu, Yoshihiro; Araya, Runa; Kawano, Masako; Ray, Manas K; Yamada, Masahisa; Mishina, Yuji

    2006-04-01

    BMP signaling plays pleiotropic roles in various tissues. Transgenic mouse lines that overexpress BMP signaling in a tissue-specific manner would be beneficial; however, production of each tissue-specific transgenic mouse line is labor-intensive. Here, using a Cre-loxP system, we generated a conditionally overexpressing mouse line for BMP signaling through the type I receptor ALK2 (alternatively known as AVCRI, ActRI, or ActRIA). By mating this line with Cre-expression mouse lines, Cre-mediated recombination removes an intervening floxed lacZ expression cassette and thereby permits the expression of a constitutively active form of Alk2 (caAlk2) driven by a ubiquitous promoter, CAG. Tissue specificity of Cre recombination was monitored by a bicistronically expressed EGFP following Alk2 cDNA. Increased BMP signaling was confirmed by ectopic phosphorylation of SMAD1/5/8 in the areas where Cre recombination had occurred. The conditional overexpression system described here provides versatility in investigating gene functions in a tissue-specific manner without having to generate independent tissue-specific transgenic lines. Published 2006 Wiley-Liss, Inc.

  2. Zinc Deficiency Impacts CO2 Assimilation and Disrupts Copper Homeostasis in Chlamydomonas reinhardtii*

    PubMed Central

    Malasarn, Davin; Kropat, Janette; Hsieh, Scott I.; Finazzi, Giovanni; Casero, David; Loo, Joseph A.; Pellegrini, Matteo; Wollman, Francis-André; Merchant, Sabeeha S.

    2013-01-01

    Zinc is an essential nutrient because of its role in catalysis and in protein stabilization, but excess zinc is deleterious. We distinguished four nutritional zinc states in the alga Chlamydomonas reinhardtii: toxic, replete, deficient, and limited. Growth is inhibited in zinc-limited and zinc-toxic cells relative to zinc-replete cells, whereas zinc deficiency is visually asymptomatic but distinguished by the accumulation of transcripts encoding ZIP family transporters. To identify targets of zinc deficiency and mechanisms of zinc acclimation, we used RNA-seq to probe zinc nutrition-responsive changes in gene expression. We identified genes encoding zinc-handling components, including ZIP family transporters and candidate chaperones. Additionally, we noted an impact on two other regulatory pathways, the carbon-concentrating mechanism (CCM) and the nutritional copper regulon. Targets of transcription factor Ccm1 and various CAH genes are up-regulated in zinc deficiency, probably due to reduced carbonic anhydrase activity, validated by quantitative proteomics and immunoblot analysis of Cah1, Cah3, and Cah4. Chlamydomonas is therefore not able to grow photoautotrophically in zinc-limiting conditions, but supplementation with 1% CO2 restores growth to wild-type rates, suggesting that the inability to maintain CCM is a major consequence of zinc limitation. The Crr1 regulon responds to copper limitation and is turned on in zinc deficiency, and Crr1 is required for growth in zinc-limiting conditions. Zinc-deficient cells are functionally copper-deficient, although they hyperaccumulate copper up to 50-fold over normal levels. We suggest that zinc-deficient cells sequester copper in a biounavailable form, perhaps to prevent mismetallation of critical zinc sites. PMID:23439652

  3. Novel functions of CCM1 delimit the relationship of PTB/PH domains.

    PubMed

    Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed

    2017-10-01

    Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and relationship of PTB, PH and FERM domains has been proposed, which extends the importance of the NPXY-PTB/PH interaction on the CSC signaling and/or other cell receptors with great potential pointing to new therapeutic strategies. The study provides new insight into the structural characteristics of PTB/PH domains, essential structural elements of PTB/PH domain required for NPXY motif-binding, and function and relationship among PTB, PH and FERM domains. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Red-pink pigmented Hymenobacter coccineus sp. nov., Hymenobacter lapidarius sp. nov. and Hymenobacter glacialis sp. nov., isolated from rocks in Antarctica.

    PubMed

    Sedláček, Ivo; Králová, Stanislava; Kýrová, Kamila; Mašlaňová, Ivana; Busse, Hans-Jürgen; Staňková, Eva; Vrbovská, Veronika; Němec, Miroslav; Barták, Miloš; Holochová, Pavla; Švec, Pavel; Pantůček, Roman

    2017-06-01

    Four rod-shaped and Gram-stain-negative bacterial strains, CCM 8647, CCM 8649T, CCM 8643T and CCM 8648T, were isolated from rock samples collected on James Ross Island, Antarctica. Extensive biotyping, fatty acid profiling, chemotaxonomy, 16S rRNA gene sequencing and whole-genome sequencing was applied to isolates to clarify their taxonomic position. Phylogenetic analysis based on 16S rRNA gene sequencing indicated that all four isolates belonged to the genus Hymenobacter. Strains CCM 8649T and CCM 8647 were most closely related to Hymenobacter arizonensis OR362-8T (94.4 % 16S rRNA gene sequence similarity), strain CCM 8643T to Hymenobacter terrae DG7AT (96.3 %) and strain CCM 8648T to Hymenobacter glaciei VUG-A130T (96.3 %). The predominant fatty acids of CCM 8649T and CCM 8647 were summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), C16 : 1ω5c and iso-C15 : 0, whereas those of CCM 8643T and CCM 8648T were summed feature 3 (C16 : 1ω7c/C16 : 1ω6c) and C16 : 1ω5c. The quinone systems contained exclusively menaquinone MK-7. The major polyamine was sym-homospermidine. All four strains contained the major polar lipid phosphatidylethanolamine. The G+C content of genomic DNA ranged from 60-63 mol%. Whole-genome sequencing data supported the finding that isolates represented distinct species of the genus Hymenobacter. On the basis of the results obtained, three novel species are proposed for which the names Hymenobacter coccineus sp. nov., Hymenobacter lapidarius sp. nov. and Hymenobacter glacialis sp. nov. are suggested, with the type strains CCM 8649T (=LMG 29441T=P5239T), CCM 8643T (=LMG 29435T=P3150T) and CCM 8648T (=LMG 29440T=P5086T), respectively.

  5. Knowledge and power in policy-making for child survival in Niger.

    PubMed

    Dalglish, Sarah L; Rodríguez, Daniela C; Harouna, Abdoutan; Surkan, Pamela J

    2017-03-01

    Calls to enhance the use of scientific evidence in international health and development policy have increased in recent years; however, analytic frameworks for understanding evidence use focus narrowly on scientific research and were created using data and observations nearly exclusively from Western countries. We examine processes of health policy development in a case study of Niger, a low-income West African country that adopted integrated community case management of childhood illness (iCCM) beginning in 2007, resulting in measurable declines in child mortality. Data collection included in-depth interviews with policy actors in Niger (N = 32), document review (N = 103) and direct observation of policy forums (N = 3). Data analysis used process tracing methodology and applied an Aristotelian definition of "knowledge" as 1) episteme (facts), 2) techne (skills) and 3) phronesis (practical wisdom), while also using a critical perspective to understand issues of power. We found sharp differentials in policy-makers' possession and use of codified forms of knowledge (episteme), with Nigerien policy officers' access highly mediated by actors at international agencies. Government policy-makers possessed skills and capacities (techne) to negotiate with donors and deliberate and weigh conflicting considerations; however they lacked capacity and resources to formally evaluate and document programs and thus reliably draw lessons from them. Practical wisdom (phronesis) emerged as key to the iCCM policy enterprise, particularly among Nigerien government actors, who used logical and ethical arguments to make decisions later found to be critical to iCCM's success. While codified knowledge confers power on members of policy discussions who can access it, this represents only one form of knowledge used in the policy process and perhaps not the most important. Future research on evidence-based policy should use broader definitions of evidence or knowledge, examine on how power conditions the use of knowledge, and examine challenges specific to low-resource policy environments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Category Captain Management: a new approach for healthcare suppliers to partner with their hospital customers.

    PubMed

    Trombetta, Bill

    2007-01-01

    Hospitals represent a substantial market for pharmaceutical and medical device companies. The typical approach by healthcare manufacturers and suppliers to hospitals is to send representatives or detailers to hospitals and meet with representatives of hospital formularies and purchasing officials. Classic channels systems, and specifically, Category Captain Management ("CCM") may provide more of a sustainable competitive advantage than traditional hospital detailing. The purpose of this article is to discuss how CCM might apply as an approach for healthcare suppliers to truly partner with their hospital customers.

  7. Functions, Compositions, and Evolution of the Two Types of Carboxysomes: Polyhedral Microcompartments That Facilitate CO2 Fixation in Cyanobacteria and Some Proteobacteria

    PubMed Central

    Rae, Benjamin D.; Long, Benedict M.; Badger, Murray R.

    2013-01-01

    SUMMARY Cyanobacteria are the globally dominant photoautotrophic lineage. Their success is dependent on a set of adaptations collectively termed the CO2-concentrating mechanism (CCM). The purpose of the CCM is to support effective CO2 fixation by enhancing the chemical conditions in the vicinity of the primary CO2-fixing enzyme, d-ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO), to promote the carboxylase reaction and suppress the oxygenase reaction. In cyanobacteria and some proteobacteria, this is achieved by encapsulation of RubisCO within carboxysomes, which are examples of a group of proteinaceous bodies called bacterial microcompartments. Carboxysomes encapsulate the CO2-fixing enzyme within the selectively permeable protein shell and simultaneously encapsulate a carbonic anhydrase enzyme for CO2 supply from a cytoplasmic bicarbonate pool. These bodies appear to have arisen twice and undergone a process of convergent evolution. While the gross structures of all known carboxysomes are ostensibly very similar, with shared gross features such as a selectively permeable shell layer, each type of carboxysome encapsulates a phyletically distinct form of RubisCO enzyme. Furthermore, the specific proteins forming structures such as the protein shell or the inner RubisCO matrix are not identical between carboxysome types. Each type has evolutionarily distinct forms of the same proteins, as well as proteins that are entirely unrelated to one another. In light of recent developments in the study of carboxysome structure and function, we present this review to summarize the knowledge of the structure and function of both types of carboxysome. We also endeavor to cast light on differing evolutionary trajectories which may have led to the differences observed in extant carboxysomes. PMID:24006469

  8. Proteomic and Mutant Analysis of the CO 2 Concentrating Mechanism of Hydrothermal Vent Chemolithoautotroph Thiomicrospira crunogena

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mangiapia, Mary; Brown, Terry-René W.; Chaput, Dale

    Many autotrophic microorganisms are likely to adapt to scarcity in dissolved inorganic carbon (DIC; CO 2+ HCO 3 -+ CO 3 2-) with CO 2 concentrating mechanisms (CCM) that actively transport DIC across the cell membrane to facilitate carbon fixation. Surprisingly, DIC transport has been well studied among cyanobacteria and microalgae only. The deep-sea vent gammaproteobacterial chemolithoautotrophThiomicrospira crunogenahas a low-DIC inducible CCM, though the mechanism for uptake is unclear, as homologs to cyanobacterial transporters are absent. To identify the components of this CCM, proteomes ofT. crunogenacultivated under low- and high-DIC conditions were compared. Fourteen proteins, including those comprising carboxysomes, weremore » at least 4-fold more abundant under low-DIC conditions. One of these proteins was encoded byTcr_0854; strains carrying mutated copies of this gene, as well as the adjacent Tcr_0853, required elevated DIC for growth. Strains carrying mutated copies of Tcr_0853 and Tcr_0854 overexpressed carboxysomes and had diminished ability to accumulate intracellular DIC. Based on reverse transcription (RT)-PCR, Tcr_0853 and Tcr_0854 were cotranscribed and upregulated under low-DIC conditions. The Tcr_0853 -encoded protein was predicted to have 13 transmembrane helices. Given the mutant phenotypes described above, Tcr_0853 and Tcr_0854 may encode a two-subunit DIC transporter that belongs to a previously undescribed transporter family, though it is widespread among autotrophs from multiple phyla.DIC uptake and fixation by autotrophs are the primary input of inorganic carbon into the biosphere. The mechanism for dissolved inorganic carbon uptake has been characterized only for cyanobacteria despite the importance of DIC uptake by autotrophic microorganisms from many phyla among theBacteriaandArchaea. In this work, proteins necessary for dissolved inorganic carbon utilization in the deep-sea vent chemolithoautotrophT. crunogenawere identified, and two of these may be able to form a novel transporter. Homologs of these proteins are present in 14 phyla inBacteriaand also in one phylum ofArchaea, theEuryarchaeota. Many organisms carrying these homologs are autotrophs, suggesting a role in facilitating dissolved inorganic carbon uptake and fixation well beyond the genusThiomicrospira.« less

  9. Proteomic and Mutant Analysis of the CO 2 Concentrating Mechanism of Hydrothermal Vent Chemolithoautotroph Thiomicrospira crunogena

    DOE PAGES

    Mangiapia, Mary; Brown, Terry-René W.; Chaput, Dale; ...

    2017-01-23

    Many autotrophic microorganisms are likely to adapt to scarcity in dissolved inorganic carbon (DIC; CO 2+ HCO 3 -+ CO 3 2-) with CO 2 concentrating mechanisms (CCM) that actively transport DIC across the cell membrane to facilitate carbon fixation. Surprisingly, DIC transport has been well studied among cyanobacteria and microalgae only. The deep-sea vent gammaproteobacterial chemolithoautotrophThiomicrospira crunogenahas a low-DIC inducible CCM, though the mechanism for uptake is unclear, as homologs to cyanobacterial transporters are absent. To identify the components of this CCM, proteomes ofT. crunogenacultivated under low- and high-DIC conditions were compared. Fourteen proteins, including those comprising carboxysomes, weremore » at least 4-fold more abundant under low-DIC conditions. One of these proteins was encoded byTcr_0854; strains carrying mutated copies of this gene, as well as the adjacent Tcr_0853, required elevated DIC for growth. Strains carrying mutated copies of Tcr_0853 and Tcr_0854 overexpressed carboxysomes and had diminished ability to accumulate intracellular DIC. Based on reverse transcription (RT)-PCR, Tcr_0853 and Tcr_0854 were cotranscribed and upregulated under low-DIC conditions. The Tcr_0853 -encoded protein was predicted to have 13 transmembrane helices. Given the mutant phenotypes described above, Tcr_0853 and Tcr_0854 may encode a two-subunit DIC transporter that belongs to a previously undescribed transporter family, though it is widespread among autotrophs from multiple phyla.DIC uptake and fixation by autotrophs are the primary input of inorganic carbon into the biosphere. The mechanism for dissolved inorganic carbon uptake has been characterized only for cyanobacteria despite the importance of DIC uptake by autotrophic microorganisms from many phyla among theBacteriaandArchaea. In this work, proteins necessary for dissolved inorganic carbon utilization in the deep-sea vent chemolithoautotrophT. crunogenawere identified, and two of these may be able to form a novel transporter. Homologs of these proteins are present in 14 phyla inBacteriaand also in one phylum ofArchaea, theEuryarchaeota. Many organisms carrying these homologs are autotrophs, suggesting a role in facilitating dissolved inorganic carbon uptake and fixation well beyond the genusThiomicrospira.« less

  10. The added value of a mobile application of Community Case Management on referral, re-consultation and hospitalization rates of children aged under 5 years in two districts in Northern Malawi: study protocol for a pragmatic, stepped-wedge cluster-randomized controlled trial.

    PubMed

    Hardy, Victoria; O'Connor, Yvonne; Heavin, Ciara; Mastellos, Nikolaos; Tran, Tammy; O'Donoghue, John; Fitzpatrick, Annette L; Ide, Nicole; Wu, Tsung-Shu Joseph; Chirambo, Griphin Baxter; Muula, Adamson S; Nyirenda, Moffat; Carlsson, Sven; Andersson, Bo; Thompson, Matthew

    2017-10-11

    There is evidence to suggest that frontline community health workers in Malawi are under-referring children to higher-level facilities. Integrating a digitized version of paper-based methods of Community Case Management (CCM) could strengthen delivery, increasing urgent referral rates and preventing unnecessary re-consultations and hospital admissions. This trial aims to evaluate the added value of the Supporting LIFE electronic Community Case Management Application (SL eCCM App) compared to paper-based CCM on urgent referral, re-consultation and hospitalization rates, in two districts in Northern Malawi. This is a pragmatic, stepped-wedge cluster-randomized trial assessing the added value of the SL eCCM App on urgent referral, re-consultation and hospitalization rates of children aged 2 months and older to up to 5 years, within 7 days of the index visit. One hundred and two health surveillance assistants (HSAs) were stratified into six clusters based on geographical location, and clusters randomized to the timing of crossover to the intervention using simple, computer-generated randomization. Training workshops were conducted prior to the control (paper-CCM) and intervention (paper-CCM + SL eCCM App) in assigned clusters. Neither participants nor study personnel were blinded to allocation. Outcome measures were determined by abstraction of clinical data from patient records 2 weeks after recruitment. A nested qualitative study explored perceptions of adherence to urgent referral recommendations and a cost evaluation determined the financial and time-related costs to caregivers of subsequent health care utilization. The trial was conducted between July 2016 and February 2017. This is the first large-scale trial evaluating the value of adding a mobile application of CCM to the assessment of children aged under 5 years. The trial will generate evidence on the potential use of mobile health for CCM in Malawi, and more widely in other low- and middle-income countries. ClinicalTrials.gov, ID: NCT02763345 . Registered on 3 May 2016.

  11. Formation of Fe-Mn crusts within a continental margin environment

    USGS Publications Warehouse

    Conrad, Tracey A.; Hein, James R.; Paytan, Adina; Clague, David A.

    2017-01-01

    This study examines Fe-Mn crusts that form on seamounts along the California continental-margin (CCM), within the United States 200 nautical mile exclusive economic zone. The study area extends from approximately 30° to 38° North latitudes and from 117° to 126° West longitudes. The area of study is a tectonically active northeast Pacific plate boundary region and is also part of the North Pacific Subtropical Gyre with currents dominated by the California Current System. Upwelling of nutrient-rich water results in high primary productivity that produces a pronounced oxygen minimum zone. Hydrogenetic Fe-Mn crusts forming along the CCM show distinct chemical and mineral compositions compared to open-ocean crusts. On average, CCM crusts contain more Fe relative to Mn than open-ocean Pacific crusts. The continental shelf and slope release both Fe and Mn under low-oxygen conditions. Silica is also enriched relative to Al compared to open-ocean crusts. This is due to the North Pacific silica plume and enrichment of Si along the path of deep-water circulation, resulting in Si enrichment in bottom and intermediate waters of the eastern Pacific.The CCM Fe-Mn crusts have a higher percentage of birnessite than open-ocean crusts, reflecting lower dissolved seawater oxygen that results from the intense coastal upwelling and proximity to zones of continental slope pore-water anoxia. Carbonate fluorapatite (CFA) is not present and CCM crusts do not show evidence of phosphatization, even in the older sections. The mineralogy indicates a suboxic environment under which birnessite forms, but in which pH is not high enough to facilitate CFA deposition. Growth rates of CCM crusts generally increase with increasing water depth, likely due to deep-water Fe sources mobilized from reduced shelf and slope sediments.Many elements of economic interest including Mn, Co, Ni, Cu, W, and Te have slightly or significantly lower concentrations in CCM crusts relative to crusts from the Pacific Prime Crust Zone and other open-ocean basins. However, concentrations of total rare earth elements and yttrium average only slightly lower contents and in the future may be a strategic resource for the U.S.

  12. Training Internists to Meet Critical Care Needs in the United States: A Consensus Statement from the Critical Care Societies Collaborative (CCSC)

    PubMed Central

    Pastores, Stephen M.; Martin, Greg S.; Baumann, Michael H.; Curtis, J. Randall; Farmer, J. Christopher; Fessler, Henry E.; Gupta, Rakesh; Hill, Nicholas S.; Hyzy, Robert C.; Kvetan, Vladimir; MacGregor, Drew A.; O’Grady, Naomi P.; Ognibene, Frederick P.; Rubenfeld, Gordon D.; Sessler, Curtis N.; Siegal, Eric; Simpson, Steven Q.; Spevetz, Antoinette; Ward, Nicholas S.; Zimmerman, Janice L.

    2014-01-01

    Objectives Multiple training pathways are recognized by the Accreditation Council for Graduate Medical Education (ACGME) for internal medicine (IM) physicians to certify in critical care medicine (CCM) via the American Board of Internal Medicine. While each involves 1 year of clinical fellowship training in CCM, substantive differences in training requirements exist among the various pathways. The Critical Care Societies Collaborative convened a task force to review these CCM pathways and to provide recommendations for unified and coordinated training requirements for IM-based physicians. Participants A group of CCM professionals certified in pulmonary-CCM and/or IM-CCM from ACGME-accredited training programs who have expertise in education, administration, research, and clinical practice. Data Sources and Synthesis Relevant published literature was accessed through a MEDLINE search and references provided by all task force members. Material published by the ACGME, American Board of Internal Medicine, and other specialty organizations was also reviewed. Collaboratively and iteratively, the task force reached consensus using a roundtable meeting, electronic mail, and conference calls. Main Results Internal medicine-CCM–based fellowships have disparate program requirements compared to other internal medicine subspecialties and adult CCM fellowships. Differences between IM-CCM and pulmonary-CCM programs include the ratio of key clinical faculty to fellows and a requirement to perform 50 therapeutic bronchoscopies. Competency-based training was considered uniformly desirable for all CCM training pathways. Conclusions The task force concluded that requesting competency-based training and minimizing variations in the requirements for IM-based CCM fellowship programs will facilitate effective CCM training for both programs and trainees. PMID:24637881

  13. CCM-3/STRIPAK promotes seamless tube extension through endocytic recycling.

    PubMed

    Lant, Benjamin; Yu, Bin; Goudreault, Marilyn; Holmyard, Doug; Knight, James D R; Xu, Peter; Zhao, Linda; Chin, Kelly; Wallace, Evan; Zhen, Mei; Gingras, Anne-Claude; Derry, W Brent

    2015-03-06

    The mechanisms governing apical membrane assembly during biological tube development are poorly understood. Here, we show that extension of the C. elegans excretory canal requires cerebral cavernous malformation 3 (CCM-3), independent of the CCM1 orthologue KRI-1. Loss of ccm-3 causes canal truncations and aggregations of canaliculular vesicles, which form ectopic lumen (cysts). We show that CCM-3 localizes to the apical membrane, and in cooperation with GCK-1 and STRIPAK, promotes CDC-42 signalling, Golgi stability and endocytic recycling. We propose that endocytic recycling is mediated through the CDC-42-binding kinase MRCK-1, which interacts physically with CCM-3-STRIPAK. We further show canal membrane integrity to be dependent on the exocyst complex and the actin cytoskeleton. This work reveals novel in vivo roles of CCM-3·STRIPAK in regulating tube extension and membrane integrity through small GTPase signalling and vesicle dynamics, which may help explain the severity of CCM3 mutations in patients.

  14. Carbon-concentrating mechanisms in seagrasses.

    PubMed

    Larkum, Anthony William D; Davey, Peter A; Kuo, John; Ralph, Peter J; Raven, John A

    2017-06-01

    Seagrasses are unique angiosperms that carry out growth and reproduction submerged in seawater. They occur in at least three families of the Alismatales. All have chloroplasts mainly in the cells of the epidermis. Living in seawater, the supply of inorganic carbon (Ci) to the chloroplasts is diffusion limited, especially under unstirred conditions. Therefore, the supply of CO2 and bicarbonate across the diffusive boundary layer on the outer side of the epidermis is often a limiting factor. Here we discuss the evidence for mechanisms that enhance the uptake of Ci into the epidermal cells. Since bicarbonate is plentiful in seawater, a bicarbonate pump might be expected; however, the evidence for such a pump is not strongly supported. There is evidence for a carbonic anhydrase outside the outer plasmalemma. This, together with evidence for an outward proton pump, suggests the possibility that local acidification leads to enhanced concentrations of CO2 adjacent to the outer tangential epidermal walls, which enhances the uptake of CO2, and this could be followed by a carbon-concentrating mechanism (CCM) in the cytoplasm and/or chloroplasts. The lines of evidence for such an epidermal CCM are discussed, including evidence for special 'transfer cells' in some but not all seagrass leaves in the tangential inner walls of the epidermal cells. It is concluded that seagrasses have a CCM but that the case for concentration of CO2 at the site of Rubisco carboxylation is not proven. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Training, supervision and quality of care in selected integrated community case management (iCCM) programmes: A scoping review of programmatic evidence.

    PubMed

    Bosch-Capblanch, Xavier; Marceau, Claudine

    2014-12-01

    To describe the training, supervision and quality of care components of integrated Community Case Management (iCCM) programmes and to draw lessons learned from existing evaluations of those programmes. Scoping review of reports from 29 selected iCCM programmes purposively provided by stakeholders containing any information relevant to understand quality of care issues. The number of people reached by iCCM programmes varied from the tens of thousands to more than a million. All programmes aimed at improving access of vulnerable populations to health care, focusing on the main childhood illnesses, managed by Community Health Workers (CHW), often selected bycommunities. Training and supervision were widely implemented, in different ways and intensities, and often complemented with tools (eg, guides, job aids), supplies, equipment and incentives. Quality of care was measured using many outcomes (eg, access or appropriate treatment). Overall, there seemed to be positive effects for those strategies that involved policy change, organisational change, standardisation of clinical practices and alignment with other programmes. Positive effects were mostly achieved in large multi-component programmes. Mild or no effects have been described on mortality reduction amongst the few programmes for which data on this outcome was available to us. Promising strategies included teaming-up of CHW, micro-franchising or social franchising. On-site training and supervision of CHW have been shown to improve clinical practices. Effects on caregivers seemed positive, with increases in knowledge, care seeking behaviour, or caregivers' basic disease management. Evidence on iCCM is often of low quality, cannot relate specific interventions or the ways they are implemented with outcomes and lacks standardisation; this limits the capacity to identify promising strategies to improve quality of care. Large, multi-faceted, iCCM programmes, with strong components of training, supervision, which included additional support of equipment and supplies, seemed to improve selected quality of care outcomes. However, current evaluation and reporting practices need to be revised in a new research agenda to address the methodological challenges of iCCM evaluations.

  16. Monitoring intensive care unit performance—impact of a novel individualised performance scorecard in critical care medicine: a mixed-methods study protocol

    PubMed Central

    Neilipovitz, David; Sarti, Aimee J; Rosenberg, Erin; Ishaq, Rabia; Thornton, Mary; Kim, John

    2018-01-01

    Introduction Patients admitted to a critical care medicine (CCM) environment, including an intensive care unit (ICU), are susceptible to harm and significant resource utilisation. Therefore, a strategy to optimise provider performance is required. Performance scorecards are used by institutions for the purposes of driving quality improvement. There is no widely accepted or standardised scorecard that has been used for overall CCM performance. We aim to improve quality of care, patient safety and patient/family experience in CCM practice through the utilisation of a standardised, repeatable and multidimensional performance scorecard, designed to provide a continuous review of ICU physician and nurse practice, as well as departmental metrics. Methods and analysis This will be a mixed-methods, controlled before and after study to assess the impact of a CCM-specific quality scorecard. Scorecard metrics were developed through expert consensus and existing literature. The study will include 19 attending CCM physicians and approximately 300 CCM nurses. Patient data for scorecard compilation are collected daily from bedside flow sheets. Preintervention baseline data will be collected for 6 months for each participant. After this, each participant will receive their scorecard measures. Following a 3-month washout period, postintervention data will be collected for 6 months. The primary outcome will be change in performance metrics following the provision of scorecard feedback to subjects. A cost analysis will also be performed, with the purpose of comparing total ICU costs prior to implementation of the scorecard with total ICU costs following implementation of the scorecard. The qualitative portion will include interviews with participants following the intervention phase. Interviews will be analysed in order to identify recurrent themes and subthemes, for the purposes of driving scorecard improvement. Ethics and dissemination This protocol has been approved by the local research ethics board. Publication of results is anticipated in 2019. If this intervention is found to improve patient- and unit-directed outcomes, with evidence of cost-effectiveness, it would support the utilisation of such a scorecard as a quality standard in CCM. PMID:29358441

  17. Training, supervision and quality of care in selected integrated community case management (iCCM) programmes: A scoping review of programmatic evidence

    PubMed Central

    Bosch–Capblanch, Xavier; Marceau, Claudine

    2014-01-01

    Aim To describe the training, supervision and quality of care components of integrated Community Case Management (iCCM) programmes and to draw lessons learned from existing evaluations of those programmes. Methods Scoping review of reports from 29 selected iCCM programmes purposively provided by stakeholders containing any information relevant to understand quality of care issues. Results The number of people reached by iCCM programmes varied from the tens of thousands to more than a million. All programmes aimed at improving access of vulnerable populations to health care, focusing on the main childhood illnesses, managed by Community Health Workers (CHW), often selected bycommunities. Training and supervision were widely implemented, in different ways and intensities, and often complemented with tools (eg, guides, job aids), supplies, equipment and incentives. Quality of care was measured using many outcomes (eg, access or appropriate treatment). Overall, there seemed to be positive effects for those strategies that involved policy change, organisational change, standardisation of clinical practices and alignment with other programmes. Positive effects were mostly achieved in large multi–component programmes. Mild or no effects have been described on mortality reduction amongst the few programmes for which data on this outcome was available to us. Promising strategies included teaming–up of CHW, micro–franchising or social franchising. On–site training and supervision of CHW have been shown to improve clinical practices. Effects on caregivers seemed positive, with increases in knowledge, care seeking behaviour, or caregivers’ basic disease management. Evidence on iCCM is often of low quality, cannot relate specific interventions or the ways they are implemented with outcomes and lacks standardisation; this limits the capacity to identify promising strategies to improve quality of care. Conclusion Large, multi–faceted, iCCM programmes, with strong components of training, supervision, which included additional support of equipment and supplies, seemed to improve selected quality of care outcomes. However, current evaluation and reporting practices need to be revised in a new research agenda to address the methodological challenges of iCCM evaluations. PMID:25520793

  18. Regulatory components of carbon concentrating mechanisms in aquatic unicellular photosynthetic organisms.

    PubMed

    Tomar, Vandana; Sidhu, Gurpreet Kaur; Nogia, Panchsheela; Mehrotra, Rajesh; Mehrotra, Sandhya

    2017-11-01

    This review provides an insight into the regulation of the carbon concentrating mechanisms (CCMs) in lower organisms like cyanobacteria, proteobacteria, and algae. CCMs evolved as a mechanism to concentrate CO 2 at the site of primary carboxylating enzyme Ribulose-1, 5-bisphosphate carboxylase oxygenase (Rubisco), so that the enzyme could overcome its affinity towards O 2 which leads to wasteful processes like photorespiration. A diverse set of CCMs exist in nature, i.e., carboxysomes in cyanobacteria and proteobacteria; pyrenoids in algae and diatoms, the C 4 system, and Crassulacean acid metabolism in higher plants. Prime regulators of CCM in most of the photosynthetic autotrophs belong to the LysR family of transcriptional regulators, which regulate the activity of the components of CCM depending upon the ambient CO 2 concentrations. Major targets of these regulators are carbonic anhydrase and inorganic carbon uptake systems (CO 2 and HCO 3 - transporters) whose activities are modulated either at transcriptional level or by changes in the levels of their co-regulatory metabolites. The article provides information on the localization of the CCM components as well as their function and participation in the development of an efficient CCM. Signal transduction cascades leading to activation/inactivation of inducible CCM components on perception of low/high CO 2 stimuli have also been brought into picture. A detailed study of the regulatory components can aid in identifying the unraveled aspects of these mechanisms and hence provide information on key molecules that need to be explored to further provide a clear understanding of the mechanism under study.

  19. Anticancer drug-based multifunctional nanogels through self-assembly of dextran-curcumin conjugates toward cancer theranostics.

    PubMed

    Nagahama, Koji; Sano, Yoshinori; Kumano, Takayuki

    2015-06-15

    Curcumin (CCM) has been received much attention in cancer theranostics because CCM exhibits both anticancer activity and strong fluorescence available for bio-imaging. However, CCM has never been utilized in clinical mainly due to its extremely low water solubility and its low cellular uptake into cancer cells. We fabricated novel CCM-based biodegradable nanoparticles through self-assembly of amphiphilic dextran-CCM conjugates. Significantly high CCM loading contents in the nanoparticles and the high water solubility were achieved. Importantly, the dextran-CCMs nanoparticles were effectively delivered into HeLa cells and exhibited strong fluorescence available for live-cell imaging, although the nanoparticles were not delivered into normal cells. Thus, the dextran-CCMs nanoparticles could be a promising for creation of novel CCM-based cancer theranostics with high efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Tract-Specific Diffusion Tensor Imaging Reveals Laterality of Neurological Symptoms in Patients with Cervical Compression Myelopathy.

    PubMed

    Maki, Satoshi; Koda, Masao; Saito, Junya; Takahashi, Sho; Inada, Taigo; Kamiya, Koshiro; Ota, Mitsutoshi; Iijima, Yasushi; Masuda, Yoshitada; Matsumoto, Koji; Kojima, Masatoshi; Takahashi, Kazuhisa; Obata, Takayuki; Yamazaki, Masashi; Furuya, Takeo

    2016-12-01

    Patients with cervical compression myelopathy (CCM) generally present bilateral neurological symptoms in their extremities. However, a substantial portion of patients with CCM exhibit laterality of neurological symptoms. The aim of this study was to assess the correlation between intrinsic structural damage and laterality of symptoms using spinal cord diffusion tensor imaging (DTI) of the corticospinal tract. We enrolled 10 healthy volunteers and 40 patients with CCM in this study. We evaluated motor function using the American Spinal Injury Association (ASIA) motor score for left and right extremities. For DTI acquisitions, a 3.0-T magnetic resonance imaging system with diffusion-weighted spin-echo sequence was used. Regions-of-interest in the lateral column tracts were determined. We determined the correlations between fractional anisotropy (FA) and ASIA motor scores. An FA asymmetry index was calculated using left and right regions-of-interest. Four patients exhibited laterality of symptoms in their extremities, for which left and right ASIA scores correlated moderately with FA in the left and right lateral columns, respectively (left: ρ = 0.64, P < 0.001; right: ρ = 0.67, P < 0.001). The area under the receiver-operator characteristic curve showed that the FA asymmetry index indicated laterality of symptoms. Using tract-specific DTI, we demonstrated that microstructural damages in the left and right corticospinal tracts correlated with corresponding neurological symptoms in the ipsilateral side and the FA asymmetry index could indicate laterality in neurological symptoms of patients with CCM. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Conventional and microwave combustion synthesis of optomagnetic CuFe2O4 nanoparticles for hyperthermia studies

    NASA Astrophysics Data System (ADS)

    Kombaiah, K.; Vijaya, J. Judith; Kennedy, L. John; Bououdina, M.; Al-Najar, Basma

    2018-04-01

    Nanosized copper ferrite (CuFe2O4) nanoparticles have been prepared by conventional (CCM) and microwave (MCM) combustion methods using Hibiscus rosa sinensis plant extract as a fuel. XRD and rietveld analysis confirmed the formation of single cubic phase and with crystallite size varying from 25 to 62 nm owing to grain growth after calcination. FT-IR analysis confirms the modes of the cubic CuFe2O4 phase, due to the stretching and bending vibrations. Spherical shaped particles are observed by scanning electron microscopy and the average particle size is found to be in the range of 50-200 nm. The chemical composition is confirmed by energy dispersive X-ray analysis. The optical band gap energy estimated using Kubelka-Munk function with the help of UV-Visible diffused reflectance spectroscopy, is found to be 2.34 and 2.22 eV for CCM and MCM respectively. Photoluminescence analysis indicates that both samples absorb light in the UV-visible region and exhibit emissions at 360, 376, and 412 nm. Magnetic measurements indicate a ferromagnetic behavior, where both magnetic properties very much influenced by the preparation method and calcination temperature: both saturation magnetization and coercivity are found higher when using CCM and MCM; from 29.40 to 34.09 emu/g while almost double from 224.4 to 432.2 Oe. The observed changes in physical properties are mainly associated with crystallinity, particle size, better chemical homogeneity, and cations distribution among tetrahedral/octahedral sites. The maximum specific absorption rate obtained was 14.63 W/g, which can be considered suitable and favorable for magnetic hyperthermia. This study highlighted the benefits of green synthesis of CuFe2O4 nanoparticles providing better magnetic properties for the platform of hyperthermia application.

  2. Probabilistic Analysis of a Composite Crew Module

    NASA Technical Reports Server (NTRS)

    Mason, Brian H.; Krishnamurthy, Thiagarajan

    2011-01-01

    An approach for conducting reliability-based analysis (RBA) of a Composite Crew Module (CCM) is presented. The goal is to identify and quantify the benefits of probabilistic design methods for the CCM and future space vehicles. The coarse finite element model from a previous NASA Engineering and Safety Center (NESC) project is used as the baseline deterministic analysis model to evaluate the performance of the CCM using a strength-based failure index. The first step in the probabilistic analysis process is the determination of the uncertainty distributions for key parameters in the model. Analytical data from water landing simulations are used to develop an uncertainty distribution, but such data were unavailable for other load cases. The uncertainty distributions for the other load scale factors and the strength allowables are generated based on assumed coefficients of variation. Probability of first-ply failure is estimated using three methods: the first order reliability method (FORM), Monte Carlo simulation, and conditional sampling. Results for the three methods were consistent. The reliability is shown to be driven by first ply failure in one region of the CCM at the high altitude abort load set. The final predicted probability of failure is on the order of 10-11 due to the conservative nature of the factors of safety on the deterministic loads.

  3. Expanding the chronic care framework to improve diabetes management: the REACH case study.

    PubMed

    Jenkins, Carolyn; Pope, Charlene; Magwood, Gayenell; Vandemark, Lisa; Thomas, Virginia; Hill, Karen; Linnen, Florene; Beck, Lorna Shelton; Zapka, Jane

    2010-01-01

    Reducing the burden of chronic conditions among minorities requires novel approaches to prevent and manage disease. This paper describes the expansion of the Chronic Care Model (CCM) to include a community focus for improving diabetes self-management and reducing health disparities. The literature review assesses the concept of "community" in improving outcomes as viewed by proponents of the CCM for chronic disease. The CCM was then modified and informed by experiences of a major community-based participatory action initiative to improve diabetes outcomes, the Racial and Ethnic Approaches to Community Health (REACH) Charleston and Georgetown Diabetes Coalition. Based on our experiences with community-based and health systems diabetes interventions, we present examples of improvements within both health delivery practice sites and other community systems that are essential for improving diabetes outcomes and reducing disparities. Building on the Centers for Disease Control and Prevention's (CDC) principles of community involvement, our coalition activities provide examples of working with community partners to frame this enhanced ecologically grounded Community CCM (CCCM). The resulting CCCM integrates expanded conceptual frameworks, evidence-based practice, community-based evidence and participatory actions, and highlights the possibilities and challenges for improving chronic disease outcomes and reducing disparities via community programs that foster individual, systems, community, and policy change.

  4. Evidence Suggesting that the Cardiomyocyte Circadian Clock Modulates Responsiveness of the Heart to Hypertrophic Stimuli in Mice

    PubMed Central

    Durgan, David J.; Tsai, Ju-Yun; Grenett, Maximiliano H.; Pat, Betty M.; Ratcliffe, William F.; Villegas-Montoya, Carolina; Garvey, Merissa E.; Nagendran, Jeevan; Dyck, Jason R.B.; Bray, Molly S.; Gamble, Karen L.; Gimble, Jeffrey M.; Young, Martin E.

    2011-01-01

    Circadian dyssynchrony of an organism (at the whole body level) with its environment, either through light/dark cycle or genetic manipulation of clock genes, augments various cardiometabolic diseases. The cardiomyocyte circadian clock has recently been shown to influence multiple myocardial processes, ranging from transcriptional regulation and energy metabolism, to contractile function. We therefore reasoned that chronic dyssychrony of the cardiomyocyte circadian clock with its environment would precipitate myocardial maladaptation to a circadian challenge (simulated shift work; SSW). To test this hypothesis, 2 and 20 month old wild-type and CCM (Cardiomyocyte Clock Mutant; a model with genetic temporal suspension of the cardiomyocyte circadian clock at the active-to-sleep phase transition) mice were subjected to chronic (16-wks) bi-weekly 12-hr phase shifts in the light/dark cycle (i.e., SSW). Assessment of adaptation/maladaptation at whole body homeostatic, gravimetric, humoral, histological, transcriptional, and cardiac contractile function levels revealed essentially identical responses between wild-type and CCM littermates. However, CCM hearts exhibit increased bi-ventricular weight, cardiomyocyte size, and molecular markers of hypertrophy (anf, mcip1) independent of aging and/or SSW. Similarly, a second genetic model of selective temporal suspension of the cardiomyocyte circadian clock (Cardiomyocyte-specific BMAL1 Knockout [CBK] mice) exhibits increased bi-ventricular weight and mcip1 expression. Wild-type mice exhibit 5-fold greater cardiac hypertrophic growth (and 6-fold greater anf mRNA induction) when challenged with the hypertrophic agonist isoproterenol at the active-to-sleep phase transition, relative to isoproterenol administration at the sleep-to-active phase transition. This diurnal variation was absent in CCM mice. Collectively, these data suggest that the cardiomyocyte circadian clock likely influences responsiveness of the heart to hypertrophic stimuli. PMID:21452915

  5. Proteomic and Mutant Analysis of the CO2 Concentrating Mechanism of Hydrothermal Vent Chemolithoautotroph Thiomicrospira crunogena

    PubMed Central

    Mangiapia, Mary; Brown, Terry-René W.; Chaput, Dale; Haller, Edward; Harmer, Tara L.; Hashemy, Zahra; Keeley, Ryan; Leonard, Juliana; Mancera, Paola; Nicholson, David; Stevens, Stanley; Wanjugi, Pauline; Zabinski, Tania; Pan, Chongle

    2017-01-01

    ABSTRACT Many autotrophic microorganisms are likely to adapt to scarcity in dissolved inorganic carbon (DIC; CO2 + HCO3− + CO32−) with CO2 concentrating mechanisms (CCM) that actively transport DIC across the cell membrane to facilitate carbon fixation. Surprisingly, DIC transport has been well studied among cyanobacteria and microalgae only. The deep-sea vent gammaproteobacterial chemolithoautotroph Thiomicrospira crunogena has a low-DIC inducible CCM, though the mechanism for uptake is unclear, as homologs to cyanobacterial transporters are absent. To identify the components of this CCM, proteomes of T. crunogena cultivated under low- and high-DIC conditions were compared. Fourteen proteins, including those comprising carboxysomes, were at least 4-fold more abundant under low-DIC conditions. One of these proteins was encoded by Tcr_0854; strains carrying mutated copies of this gene, as well as the adjacent Tcr_0853, required elevated DIC for growth. Strains carrying mutated copies of Tcr_0853 and Tcr_0854 overexpressed carboxysomes and had diminished ability to accumulate intracellular DIC. Based on reverse transcription (RT)-PCR, Tcr_0853 and Tcr_0854 were cotranscribed and upregulated under low-DIC conditions. The Tcr_0853-encoded protein was predicted to have 13 transmembrane helices. Given the mutant phenotypes described above, Tcr_0853 and Tcr_0854 may encode a two-subunit DIC transporter that belongs to a previously undescribed transporter family, though it is widespread among autotrophs from multiple phyla. IMPORTANCE DIC uptake and fixation by autotrophs are the primary input of inorganic carbon into the biosphere. The mechanism for dissolved inorganic carbon uptake has been characterized only for cyanobacteria despite the importance of DIC uptake by autotrophic microorganisms from many phyla among the Bacteria and Archaea. In this work, proteins necessary for dissolved inorganic carbon utilization in the deep-sea vent chemolithoautotroph T. crunogena were identified, and two of these may be able to form a novel transporter. Homologs of these proteins are present in 14 phyla in Bacteria and also in one phylum of Archaea, the Euryarchaeota. Many organisms carrying these homologs are autotrophs, suggesting a role in facilitating dissolved inorganic carbon uptake and fixation well beyond the genus Thiomicrospira. PMID:28115547

  6. The Comparative Studies of Binding Activity of Curcumin and Didemethylated Curcumin with Selenite: Hydrogen Bonding vs Acid-Base Interactions

    NASA Astrophysics Data System (ADS)

    Liao, Jiahn-Haur; Wu, Tzu-Hua; Chen, Ming-Yi; Chen, Wei-Ting; Lu, Shou-Yun; Wang, Yi-Hsuan; Wang, Shao-Pin; Hsu, Yen-Min; Huang, Yi-Shiang; Huang, Zih-You; Lin, Yu-Ching; Chang, Ching-Ming; Huang, Fu-Yung; Wu, Shih-Hsiung

    2015-12-01

    In this report, the in vitro relative capabilities of curcumin (CCM) and didemethylated curcumin (DCCM) in preventing the selenite-induced crystallin aggregation were investigated by turbidity tests and isothermal titration calorimetry (ITC). DCCM showed better activity than CCM. The conformers of CCM/SeO32- and DCCM/SeO32- complexes were optimized by molecular orbital calculations. Results reveal that the selenite anion surrounded by CCM through the H-bonding between CCM and selenite, which is also observed via IR and NMR studied. For DCCM, the primary driving force is the formation of an acid-base adduct with selenite showing that the phenolic OH group of DCCM was responsible for forming major conformer of DCCM. The formation mechanisms of selenite complexes with CCM or DCCM explain why DCCM has greater activity than CCM in extenuating the toxicity of selenite as to prevent selenite-induced lens protein aggregation.

  7. Bifurcating effects of hope and support in short- and long-term health outcomes among primary care patients without mental illness.

    PubMed

    Katerndahl, David

    2014-08-01

    Adverse life events and stressors can lead to symptoms, increased alcohol intake, and impaired functional status, while hope and social support can mitigate such adverse effects. Yet, there is reason to question such simple, linear relationships among healthy adults. The purpose of this study was to assess whether short-term or long-term changes in alcohol intake, psychological symptoms or functional status were better modelled as cusp catastrophic or linear processes among primary care patients without mental illness. This secondary analysis of a study on the stability of psychological symptoms among primary care patients without mental disorders included 38 subjects who completed baseline, and 2-month and/or 6-month assessments of psychological symptoms, functional status and stressors as well as hope and social support. The analyses modelled short-term and long-term changes in alcohol intake, psychological symptoms and functional status using cusp catastrophe (CCM) and linear modelling. Overall, four of the nine 2-month analyses found CCM superior to linear models; however, only one 6-month analysis (alcohol intake) found that CCM was superior. The 2-month cusp phenomena included both symptomatology and functional status. The asymmetry variables were often not significant in the CCM models; in fact, only distress was significant at all. While hope was a significant bifurcation variable at both the 2-month and 6-month levels, social support was a significant bifurcation variable for three of the four 2-month CCMs. In conclusion, while 6-month outcomes were rarely explained through CCM, half of 2-month outcomes were. Hope and support demonstrated bifurcation effects. © 2013 John Wiley & Sons, Ltd.

  8. Under-Five Child Mortality and Morbidity Associated with Consanguineous Child Marriage in Pakistan: Retrospective Analysis using Pakistan Demographic and Health Surveys, 1990-91, 2006-07, 2012-13.

    PubMed

    Mustafa, Mudasir; Zakar, Rubeena; Zakar, Muhammad Zakria; Chaudhry, Ashraf; Nasrullah, Muazzam

    2017-05-01

    Objective To assess the combined effect of consanguineous and child marriages (CCM) on children health, which has not previously been explored, either globally or locally. Methods We analyzed secondary data from a series of cross-sectional, nationally representative Pakistan Demographic and Health Surveys 1990-91, 2006-07, and 2012-13. A total of 5406 mothers with 10,164 children were included in the analysis. Child health was assessed by variables such as history of diarrhea, acute respiratory infection (ARI), ARI with fever, Under-5 child mortality (U5CM) and small-size birth (SSB). Associations among variables were assessed by calculating unadjusted Odd Ratios (OR) and adjusted OR (AOR). Results A majority (n = 6,247, 61%) of the births were to mothers having CCM as compare to non-CCM (3917, 39%). There was a significant association between CCM and U5CM during 1990-91 (AOR 1.24, 95% CI 1.03-1.49) and 2006-07 (AOR 1.25, 95% CI 1.05-1.51), and infant mortality in 1990-91 (AOR 1.39, 95% CI 1.05-1.85) and 2006-07 (AOR 1.61, 95% CI 1.17-2.21). A significant association was also found between CCM and SSB infants in the period 2006-07 (AOR 1.19, 95% CI 1.01-1.42) and 2012-13 (AOR 1.22, 95% CI 1.02-1.46). We noted no effect of CCM on diarrhea, ARI, and ARI with fever. Conclusion CCM increases the likelihood of U5CM, infant mortality and SSB infants. Further quantitative and qualitative research should be conducted to assess the effects of environmental, congenital and genetic factors on the health of children born to mothers in CCM.

  9. Nonlinear Directed Interactions Between HRV and EEG Activity in Children With TLE.

    PubMed

    Schiecke, Karin; Pester, Britta; Piper, Diana; Benninger, Franz; Feucht, Martha; Leistritz, Lutz; Witte, Herbert

    2016-12-01

    Epileptic seizure activity influences the autonomic nervous system (ANS) in different ways. Heart rate variability (HRV) is used as indicator for alterations of the ANS. It was shown that linear, nondirected interactions between HRV and EEG activity before, during, and after epileptic seizure occur. Accordingly, investigations of directed nonlinear interactions are logical steps to provide, e.g., deeper insight into the development of seizure onsets. Convergent cross mapping (CCM) investigates nonlinear, directed interactions between time series by using nonlinear state space reconstruction. CCM is applied to simulated and clinically relevant data, i.e., interactions between HRV and specific EEG components of children with temporal lobe epilepsy (TLE). In addition, time-variant multivariate Autoregressive model (AR)-based estimation of partial directed coherence (PDC) was performed for the same data. Influence of estimation parameters and time-varying behavior of CCM estimation could be demonstrated by means of simulated data. AR-based estimation of PDC failed for the investigation of our clinical data. Time-varying interval-based application of CCM on these data revealed directed interactions between HRV and delta-related EEG activity. Interactions between HRV and alpha-related EEG activity were visible but less pronounced. EEG components mainly drive HRV. The interaction pattern and directionality clearly changed with onset of seizure. Statistical relevant interactions were quantified by bootstrapping and surrogate data approach. In contrast to AR-based estimation of PDC CCM was able to reveal time-courses and frequency-selective views of nonlinear interactions for the further understanding of complex interactions between the epileptic network and the ANS in children with TLE.

  10. Large variation in the Rubisco kinetics of diatoms reveals diversity among their carbon-concentrating mechanisms.

    PubMed

    Young, Jodi N; Heureux, Ana M C; Sharwood, Robert E; Rickaby, Rosalind E M; Morel, François M M; Whitney, Spencer M

    2016-05-01

    While marine phytoplankton rival plants in their contribution to global primary productivity, our understanding of their photosynthesis remains rudimentary. In particular, the kinetic diversity of the CO2-fixing enzyme, Rubisco, in phytoplankton remains unknown. Here we quantify the maximum rates of carboxylation (k cat (c)), oxygenation (k cat (o)), Michaelis constants (K m) for CO2 (K C) and O2 (K O), and specificity for CO2 over O2 (SC/O) for Form I Rubisco from 11 diatom species. Diatom Rubisco shows greater variation in K C (23-68 µM), SC/O (57-116mol mol(-1)), and K O (413-2032 µM) relative to plant and algal Rubisco. The broad range of K C values mostly exceed those of C4 plant Rubisco, suggesting that the strength of the carbon-concentrating mechanism (CCM) in diatoms is more diverse, and more effective than previously predicted. The measured k cat (c) for each diatom Rubisco showed less variation (2.1-3.7s(-1)), thus averting the canonical trade-off typically observed between K C and k cat (c) for plant Form I Rubisco. Uniquely, a negative relationship between K C and cellular Rubisco content was found, suggesting variation among diatom species in how they allocate their limited cellular resources between Rubisco synthesis and their CCM. The activation status of Rubisco in each diatom was low, indicating a requirement for Rubisco activase. This work highlights the need to better understand the correlative natural diversity between the Rubisco kinetics and CCM of diatoms and the underpinning mechanistic differences in catalytic chemistry among the Form I Rubisco superfamily. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  11. Large variation in the Rubisco kinetics of diatoms reveals diversity among their carbon-concentrating mechanisms

    PubMed Central

    Young, Jodi N.; Heureux, Ana M.C.; Sharwood, Robert E.; Rickaby, Rosalind E.M.; Morel, François M.M.; Whitney, Spencer M.

    2016-01-01

    While marine phytoplankton rival plants in their contribution to global primary productivity, our understanding of their photosynthesis remains rudimentary. In particular, the kinetic diversity of the CO2-fixing enzyme, Rubisco, in phytoplankton remains unknown. Here we quantify the maximum rates of carboxylation (k cat c), oxygenation (k cat o), Michaelis constants (K m) for CO2 (K C) and O2 (K O), and specificity for CO2 over O2 (SC/O) for Form I Rubisco from 11 diatom species. Diatom Rubisco shows greater variation in K C (23–68 µM), SC/O (57–116mol mol−1), and K O (413–2032 µM) relative to plant and algal Rubisco. The broad range of K C values mostly exceed those of C4 plant Rubisco, suggesting that the strength of the carbon-concentrating mechanism (CCM) in diatoms is more diverse, and more effective than previously predicted. The measured k cat c for each diatom Rubisco showed less variation (2.1–3.7s−1), thus averting the canonical trade-off typically observed between K C and k cat c for plant Form I Rubisco. Uniquely, a negative relationship between K C and cellular Rubisco content was found, suggesting variation among diatom species in how they allocate their limited cellular resources between Rubisco synthesis and their CCM. The activation status of Rubisco in each diatom was low, indicating a requirement for Rubisco activase. This work highlights the need to better understand the correlative natural diversity between the Rubisco kinetics and CCM of diatoms and the underpinning mechanistic differences in catalytic chemistry among the Form I Rubisco superfamily. PMID:27129950

  12. A Flow Perfusion Bioreactor System for Vocal Fold Tissue Engineering Applications

    PubMed Central

    Heris, Hossein K.; Thomson, Scott L.; Taher, Rani; Kazemirad, Siavash; Sheibani, Sara; Li-Jessen, Nicole Y.K.; Vali, Hojatollah; Mongeau, Luc

    2016-01-01

    The human vocal folds (VFs) undergo complex biomechanical stimulation during phonation. The aim of the present study was to develop and validate a phono-mimetic VF flow perfusion bioreactor, which mimics the mechanical microenvironment of the human VFs in vitro. The bioreactor uses airflow-induced self-oscillations, which have been shown to produce mechanical loading and contact forces that are representative of human phonation. The bioreactor consisted of two synthetic VF replicas within a silicone body. A cell-scaffold mixture (CSM) consisting of human VF fibroblasts, hyaluronic acid, gelatin, and a polyethylene glycol cross-linker was injected into cavities within the replicas. Cell culture medium (CCM) was perfused through the scaffold by using a customized secondary flow loop. After the injection, the bioreactor was operated with no stimulation over a 3-day period to allow for cell adaptation. Phonation was subsequently induced by using a variable speed centrifugal blower for 2 h each day over a period of 4 days. A similar bioreactor without biomechanical stimulation was used as the nonphonatory control. The CSM was harvested from both VF replicas 7 days after the injection. The results confirmed that the phono-mimetic bioreactor supports cell viability and extracellular matrix proteins synthesis, as expected. Many scaffold materials were found to degrade because of challenges from phonation-induced biomechanical stimulation as well as due to biochemical reactions with the CCM. The bioreactor concept enables future investigations of the effects of different phonatory characteristics, that is, voice regimes, on the behavior of the human VF cells. It will also help study the long-term functional outcomes of the VF-specific biomaterials before animal and clinical studies. PMID:27537192

  13. A Flow Perfusion Bioreactor System for Vocal Fold Tissue Engineering Applications.

    PubMed

    Latifi, Neda; Heris, Hossein K; Thomson, Scott L; Taher, Rani; Kazemirad, Siavash; Sheibani, Sara; Li-Jessen, Nicole Y K; Vali, Hojatollah; Mongeau, Luc

    2016-09-01

    The human vocal folds (VFs) undergo complex biomechanical stimulation during phonation. The aim of the present study was to develop and validate a phono-mimetic VF flow perfusion bioreactor, which mimics the mechanical microenvironment of the human VFs in vitro. The bioreactor uses airflow-induced self-oscillations, which have been shown to produce mechanical loading and contact forces that are representative of human phonation. The bioreactor consisted of two synthetic VF replicas within a silicone body. A cell-scaffold mixture (CSM) consisting of human VF fibroblasts, hyaluronic acid, gelatin, and a polyethylene glycol cross-linker was injected into cavities within the replicas. Cell culture medium (CCM) was perfused through the scaffold by using a customized secondary flow loop. After the injection, the bioreactor was operated with no stimulation over a 3-day period to allow for cell adaptation. Phonation was subsequently induced by using a variable speed centrifugal blower for 2 h each day over a period of 4 days. A similar bioreactor without biomechanical stimulation was used as the nonphonatory control. The CSM was harvested from both VF replicas 7 days after the injection. The results confirmed that the phono-mimetic bioreactor supports cell viability and extracellular matrix proteins synthesis, as expected. Many scaffold materials were found to degrade because of challenges from phonation-induced biomechanical stimulation as well as due to biochemical reactions with the CCM. The bioreactor concept enables future investigations of the effects of different phonatory characteristics, that is, voice regimes, on the behavior of the human VF cells. It will also help study the long-term functional outcomes of the VF-specific biomaterials before animal and clinical studies.

  14. Evidence-informed policymaking in practice: country-level examples of use of evidence for iCCM policy

    PubMed Central

    Rodríguez, Daniela C; Shearer, Jessica; Mariano, Alda RE; Juma, Pamela A; Dalglish, Sarah L; Bennett, Sara

    2015-01-01

    Integrated Community Case Management of Childhood Illness (iCCM) is a policy for providing treatment for malaria, diarrhoea and pneumonia for children below 5 years at the community level, which is generating increasing evidence and support at the global level. As countries move to adopt iCCM, it becomes important to understand how this growing evidence base is viewed and used by national stakeholders. This article explores whether, how and why evidence influenced policy formulation for iCCM in Niger, Kenya and Mozambique, and uses Carol Weiss’ models of research utilization to further explain the use of evidence in these contexts. A documentary review and in-depth stakeholder interviews were conducted as part of retrospective case studies in each study country. Findings indicate that all three countries used national monitoring data to identify the issue of children dying in the community prior to reaching health facilities, whereas international research evidence was used to identify policy options. Nevertheless, policymakers greatly valued local evidence and pilot projects proved critical in advancing iCCM. World Health Organization and United Nations Children's Fund (UNICEF) functioned as knowledge brokers, bringing research evidence and experiences from other countries to the attention of local policymakers as well as sponsoring site visits and meetings. In terms of country-specific findings, Niger demonstrated both Interactive and Political models of research utilization by using iCCM to capitalize on the existing health infrastructure. Both Mozambique and Kenya exhibit Problem-Solving research utilization with different outcomes. Furthermore, the persistent quest for additional evidence suggests a Tactical use of research in Kenya. Results presented here indicate that while evidence from research studies and other contexts can be critical to policy development, local evidence is often needed to answer key policymaker questions. In the end, evidence may not be enough to overcome resistance if the policy is viewed as incompatible with national goals. PMID:26516149

  15. Modeling the "Year without summer 1816" with the CCM SOCOL

    NASA Astrophysics Data System (ADS)

    Arfeuille, Florian; Rozanov, Eugene; Peter, Thomas; Fischer, Andreas. M.; Weisenstein, Debra; Brönnimann, Stefan

    2010-05-01

    The "Year without summer" 1816 had profound social and environmental effects, and although the cataclysmic eruption of Mt Tambora is now commonly known to have largely contributed to the negative temperature anomalies of the summer 1816 in Europe and North America, lots of uncertainties remain. The eruption of Mt. Tambora in April 1815 is the largest within the last 500 years. A crucial parameter to assess in order to simulate this eruption is the aerosol size distribution, which strongly influences the radiative impact of the aerosols (changes in albedo and residence time in the stratosphere, among others) and the impacts on dynamics and chemistry. The representation of this major forcing is done by using the AER-2D aerosol model which calculates the size distribution of the aerosols formed after the eruption. The modeling of the climatic impacts is then done by the state-of-the-art Chemistry-Climate model (CCM) SOCOL. The importance of stratospheric processes for the study of the "Year without summer" 1816 justifies the choice of a CCM which allows a precise analysis of the radiative, dynamical and chemical impacts of the Tambora eruption. The 1810's decade is an interesting period as it combines both a strong signal to noise ratio for the study of the impacts of the volcanic forcing, and an availability of several high resolution climate proxies allowing a credible reconstruction of interesting climatic components like Sea Surface Temperatures (SST) which are forced in the CCM . This can particularly provide a realistic description of the inter-annual variability linked to the major atmosphere/ocean coupled oscillations such as ENSO. Reconstructions based on inland natural proxies and early instrumental records can then be used to validate the simulated climate. I will present the characteristics of the Tambora eruption and show some results from simulations made using the aerosol model/CCM, with an emphasis on the radiative and chemical implications of the large aerosol sizes produced by the Mt. Tambora 60-80MT SO2 release. For instance, the specific absorption/scattering ratio of Mt.Tambora aerosols induced a very large stratospheric warming which will be analyzed. The climatic impacts will also be discussed in regards of the high sedimentation rate of Mt. Tambora aerosols, leading to a fast decrease of the atmospheric optical depth in the first two years after the eruption.

  16. The potential for co-evolution of CO2-concentrating mechanisms and Rubisco in diatoms.

    PubMed

    Young, Jodi N; Hopkinson, Brian M

    2017-06-01

    Diatoms are a diverse group of unicellular algae that contribute significantly to global photosynthetic carbon fixation and export in the modern ocean, and are an important source of microfossils for paleoclimate reconstructions. Because of their importance in the environment, diatoms have been a focus of study on the physiology and ecophysiology of carbon fixation, in particular their CO2-concentrating mechanisms (CCMs) and Rubisco characteristics. While carbon fixation in diatoms is not as well understood as in certain model aquatic photoautotrophs, a greater number of species have been examined in diatoms. Recent work has highlighted a large diversity in the function, physiology, and kinetics of both the CCM and Rubisco between different diatom species. This diversity was unexpected since it has generally been assumed that CCMs and Rubiscos were similar within major algal lineages as the result of selective events deep in evolutionary history, and suggests a more recent co-evolution between the CCM and Rubisco within diatoms. This review explores our current understanding of the diatom CCM and highlights the diversity of both the CCM and Rubisco kinetics. We will suggest possible environmental, physiological, and evolutionary drivers for the co-evolution of the CCM and Rubisco in diatoms. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. Costs of implementing integrated community case management (iCCM) in six African countries: implications for sustainability.

    PubMed

    Daviaud, Emmanuelle; Besada, Donnela; Leon, Natalie; Rohde, Sarah; Sanders, David; Oliphant, Nicholas; Doherty, Tanya

    2017-06-01

    Sub-Saharan Africa still reports the highest rates of under-five mortality. Low cost, high impact interventions exist, however poor access remains a challenge. Integrated community case management (iCCM) was introduced to improve access to essential services for children 2-59 months through diagnosis, treatment and referral services by community health workers for malaria, pneumonia and diarrhea. This paper presents the results of an economic analysis of iCCM implementation in regions supported by UNICEF in six countries and assesses country-level scale-up implications. The paper focuses on costs to provider (health system and donors) to inform planning and budgeting, and does not cover cost-effectiveness. The analysis combines annualised set-up costs and 1 year implementation costs to calculate incremental economic and financial costs per treatment from a provider perspective. Affordability is assessed by calculating the per capita financial cost of the program as a percentage of the public health expenditure per capita. Time and financial implications of a 30% increase in utilization were modeled. Country scale-up is modeled for all children under 5 in rural areas. Utilization of iCCM services varied from 0.05 treatment/y/under-five in Ethiopia to over 1 in Niger. There were between 10 and 603 treatments/community health worker (CHW)/y. Consultation cost represented between 93% and 22% of economic costs per treatment influenced by the level of utilization. Weighted economic cost per treatment ranged from US$ 13 (2015 USD) in Ghana to US$ 2 in Malawi. CHWs spent from 1 to 9 hours a week on iCCM. A 30% increase in utilization would add up to 2 hours a week, but reduce cost per treatment (by 20% in countries with low utilization). Country scale up would amount to under US$ 0.8 per capita total population (US$ 0.06-US$0.74), between 0.5% and 2% of public health expenditure per capita but 8% in Niger. iCCM addresses unmet needs and impacts on under 5 mortality. An economic cost of under US$ 1/capita/y represents a sound investment. Utilization remains low however, and strategies must be developed as a priority to improve demand. Continued donor support is required to sustain iCCM services and strengthen its integration within national health systems.

  18. Costs of implementing integrated community case management (iCCM) in six African countries: implications for sustainability

    PubMed Central

    Daviaud, Emmanuelle; Besada, Donnela; Leon, Natalie; Rohde, Sarah; Sanders, David; Oliphant, Nicholas; Doherty, Tanya

    2017-01-01

    Background Sub–Saharan Africa still reports the highest rates of under–five mortality. Low cost, high impact interventions exist, however poor access remains a challenge. Integrated community case management (iCCM) was introduced to improve access to essential services for children 2–59 months through diagnosis, treatment and referral services by community health workers for malaria, pneumonia and diarrhea. This paper presents the results of an economic analysis of iCCM implementation in regions supported by UNICEF in six countries and assesses country–level scale–up implications. The paper focuses on costs to provider (health system and donors) to inform planning and budgeting, and does not cover cost–effectiveness. Methods The analysis combines annualised set–up costs and 1 year implementation costs to calculate incremental economic and financial costs per treatment from a provider perspective. Affordability is assessed by calculating the per capita financial cost of the program as a percentage of the public health expenditure per capita. Time and financial implications of a 30% increase in utilization were modeled. Country scale–up is modeled for all children under 5 in rural areas. Results Utilization of iCCM services varied from 0.05 treatment/y/under–five in Ethiopia to over 1 in Niger. There were between 10 and 603 treatments/community health worker (CHW)/y. Consultation cost represented between 93% and 22% of economic costs per treatment influenced by the level of utilization. Weighted economic cost per treatment ranged from US$ 13 (2015 USD) in Ghana to US$ 2 in Malawi. CHWs spent from 1 to 9 hours a week on iCCM. A 30% increase in utilization would add up to 2 hours a week, but reduce cost per treatment (by 20% in countries with low utilization). Country scale up would amount to under US$ 0.8 per capita total population (US$ 0.06–US$0.74), between 0.5% and 2% of public health expenditure per capita but 8% in Niger. Conclusions iCCM addresses unmet needs and impacts on under 5 mortality. An economic cost of under US$ 1/capita/y represents a sound investment. Utilization remains low however, and strategies must be developed as a priority to improve demand. Continued donor support is required to sustain iCCM services and strengthen its integration within national health systems. PMID:28702174

  19. Emotion Recognition From Singing Voices Using Contemporary Commercial Music and Classical Styles.

    PubMed

    Hakanpää, Tua; Waaramaa, Teija; Laukkanen, Anne-Maria

    2018-02-22

    This study examines the recognition of emotion in contemporary commercial music (CCM) and classical styles of singing. This information may be useful in improving the training of interpretation in singing. This is an experimental comparative study. Thirteen singers (11 female, 2 male) with a minimum of 3 years' professional-level singing studies (in CCM or classical technique or both) participated. They sang at three pitches (females: a, e1, a1, males: one octave lower) expressing anger, sadness, joy, tenderness, and a neutral state. Twenty-nine listeners listened to 312 short (0.63- to 4.8-second) voice samples, 135 of which were sung using a classical singing technique and 165 of which were sung in a CCM style. The listeners were asked which emotion they heard. Activity and valence were derived from the chosen emotions. The percentage of correct recognitions out of all the answers in the listening test (N = 9048) was 30.2%. The recognition percentage for the CCM-style singing technique was higher (34.5%) than for the classical-style technique (24.5%). Valence and activation were better perceived than the emotions themselves, and activity was better recognized than valence. A higher pitch was more likely to be perceived as joy or anger, and a lower pitch as sorrow. Both valence and activation were better recognized in the female CCM samples than in the other samples. There are statistically significant differences in the recognition of emotions between classical and CCM styles of singing. Furthermore, in the singing voice, pitch affects the perception of emotions, and valence and activity are more easily recognized than emotions. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  20. The carbonic anhydrase CAH1 is an essential component of the carbon-concentrating mechanism in Nannochloropsis oceanica.

    PubMed

    Gee, Christopher W; Niyogi, Krishna K

    2017-04-25

    Aquatic photosynthetic organisms cope with low environmental CO 2 concentrations through the action of carbon-concentrating mechanisms (CCMs). Known eukaryotic CCMs consist of inorganic carbon transporters and carbonic anhydrases (and other supporting components) that culminate in elevated [CO 2 ] inside a chloroplastic Rubisco-containing structure called a pyrenoid. We set out to determine the molecular mechanisms underlying the CCM in the emerging model photosynthetic stramenopile, Nannochloropsis oceanica , a unicellular picoplanktonic alga that lacks a pyrenoid. We characterized CARBONIC ANHYDRASE 1 ( CAH1 ) as an essential component of the CCM in N. oceanica CCMP1779. We generated insertions in this gene by directed homologous recombination and found that the cah1 mutant has severe defects in growth and photosynthesis at ambient CO 2 We identified CAH1 as an α-type carbonic anhydrase, providing a biochemical role in CCM function. CAH1 was found to localize to the lumen of the epiplastid endoplasmic reticulum, with its expression regulated by the external inorganic carbon concentration at both the transcript and protein levels. Taken together, these findings show that CAH1 is an indispensable component of what may be a simple but effective and dynamic CCM in N. oceanica .

  1. Critical Care Medicine and Infectious Diseases: An Emerging Combined Subspecialty in the United States.

    PubMed

    Kadri, Sameer S; Rhee, Chanu; Fortna, Gregory S; O'Grady, Naomi P

    2015-08-15

    The recent rise in unfilled training positions among infectious diseases (ID) fellowship programs nationwide indicates that ID is declining as a career choice among internal medicine residency graduates. Supplementing ID training with training in critical care medicine (CCM) might be a way to regenerate interest in the specialty. Hands-on patient care and higher salaries are obvious attractions. High infection prevalence and antibiotic resistance in intensive care units, expanding immunosuppressed host populations, and public health crises such as the recent Ebola outbreak underscore the potential synergy of CCM-ID training. Most intensivists receive training in pulmonary medicine and only 1% of current board-certified intensivists are trained in ID. While still small, this cohort of CCM-ID certified physicians has continued to rise over the last 2 decades. ID and CCM program leadership nationwide must recognize these trends and the merits of the CCM-ID combination to facilitate creation of formal dual-training opportunities. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Internet search and krokodil in the Russian Federation: an infoveillance study.

    PubMed

    Zheluk, Andrey; Quinn, Casey; Meylakhs, Peter

    2014-09-18

    Krokodil is an informal term for a cheap injectable illicit drug domestically prepared from codeine-containing medication (CCM). The method of krokodil preparation may produce desomorphine as well as toxic reactants that cause extensive tissue necrosis. The first confirmed report of krokodil use in Russia took place in 2004. In 2012, reports of krokodil-related injection injuries began to appear beyond Russia in Western Europe and the United States. This exploratory study had two main objectives: (1) to determine if Internet search patterns could detect regularities in behavioral responses to Russian CCM policy at the population level, and (2) to determine if complementary data sources could explain the regularities we observed. First, we obtained krokodil-related search pattern data for each Russia subregion (oblast) between 2011 and 2012. Second, we analyzed several complementary data sources included krokodil-related court cases, and related search terms on both Google and Yandex to evaluate the characteristics of terms accompanying krokodil-related search queries. In the 6 months preceding CCM sales restrictions, 21 of Russia's 83 oblasts had search rates higher than the national average (mean) of 16.67 searches per 100,000 population for terms associated with krokodil. In the 6 months following restrictions, mean national searches dropped to 9.65 per 100,000. Further, the number of oblasts recording a higher than average search rate dropped from 30 to 16. Second, we found krokodil-related court appearances were moderately positively correlated (Spearman correlation=.506, P≤.001) with behaviors consistent with an interest in the production and use of krokodil across Russia. Finally, Google Trends and Google and Yandex related terms suggested consistent public interest in the production and use of krokodil as well as for CCM as analgesic medication during the date range covered by this study. Illicit drug use data are generally regarded as difficult to obtain through traditional survey methods. Our analysis suggests it is plausible that Yandex search behavior served as a proxy for patterns of krokodil production and use during the date range we investigated. More generally, this study demonstrates the application of novel methods recently used by policy makers to both monitor illicit drug use and influence drug policy decision making.

  3. Attitudes of anesthesiology residents toward critical care medicine training.

    PubMed

    Durbin, C G; McLafferty, C L

    1993-09-01

    The number of anesthesiology residents pursuing critical care medicine (CCM) fellowship training has been decreasing in recent years. A significant number of training positions remain unfilled each year. Possible causes of this decline were evaluated by surveying residents regarding their attitudes toward practice and training in CCM. All 38 anesthesiology programs having accredited CCM fellowships were surveyed. Four of these and one program without CCM fellowships were used to develop the survey instrument. Four programs without CCM fellowships and 34 programs with CCM fellowships make up the survey group. Returned were 640 surveys from 37 (97%) programs accounting for over 30% of the possible residents. Resident interest in pursuing CCM training decreased as year of residency increased (P < 0.0001). Residents in programs with little patient care responsibility during intensive care unit (ICU) rotations expressed less interest in CCM training (P < 0.012). The administrative role of the anesthesiology department in the ICU also influenced resident interest (P < 0.014). Written responses to open-ended questions suggested resident concerns with the following: stress of chronic care, financial consequences of additional year of training, ICU call frequency and load, ICU role ambiguity, and shared decision-making in the ICU. A recurring question was, "Are there jobs (outside of academics) for anesthesiologist intensivists?" Most residents knew a CCM anesthesiologist they admired and knew that there were unfilled fellowship positions available. Defining the job market, improving curriculum and teaching, supporting deferment of student loans, and introducing residents and medical students to the ICU earlier may increase the interest in CCM practice among anesthesiology residents.

  4. Social Determinants of Health, the Chronic Care Model, and Systemic Lupus Erythematosus

    PubMed Central

    Williams, Edith M.; Ortiz, Kasim; Browne, Teri

    2014-01-01

    Systemic lupus erythematosus (SLE) is a chronic inflammatory rheumatic disease that disproportionately affects African Americans and other minorities in the USA. Public health attention to SLE has been predominantly epidemiological. To better understand the effects of this cumulative disadvantage and ultimately improve the delivery of care, specifically in the context of SLE, we propose that more research attention to the social determinants of SLE is warranted and more transdisciplinary approaches are necessary to appropriately address identified social determinants of SLE. Further, we suggest drawing from the chronic care model (CCM) for an understanding of how community-level factors may exacerbate disparities explored within social determinant frameworks or facilitate better delivery of care for SLE patients. Grounded in social determinants of health (SDH) frameworks and the CCM, this paper presents issues relative to accessibility to suggest that more transdisciplinary research focused on the role of place could improve care for SLE patients, particularly the most vulnerable patients. It is our hope that this paper will serve as a springboard for future studies to more effectively connect social determinants of health with the chronic care model and thus more comprehensively address adverse health trajectories in SLE and other chronic conditions. PMID:26464854

  5. Causal Relationships Among Time Series of the Lange Bramke Catchment (Harz Mountains, Germany)

    NASA Astrophysics Data System (ADS)

    Aufgebauer, Britta; Hauhs, Michael; Bogner, Christina; Meesenburg, Henning; Lange, Holger

    2016-04-01

    Convergent Cross Mapping (CCM) has recently been introduced by Sugihara et al. for the identification and quantification of causal relationships among ecosystem variables. In particular, the method allows to decide on the direction of causality; in some cases, the causality might be bidirectional, indicating a network structure. We extend this approach by introducing a method of surrogate data to obtain confidence intervals for CCM results. We then apply this method to time series from stream water chemistry. Specifically, we analyze a set of eight dissolved major ions from three different catchments belonging to the hydrological monitoring system at the Bramke valley in the Harz Mountains, Germany. Our results demonstrate the potentials and limits of CCM as a monitoring instrument in forestry and hydrology or as a tool to identify processes in ecosystem research. While some networks of causally linked ions can be associated with simple physical and chemical processes, other results illustrate peculiarities of the three studied catchments, which are explained in the context of their special history.

  6. Evaluation of the reactive nitrogen budget of the remote atmosphere in global models using airborne measurements

    NASA Astrophysics Data System (ADS)

    Murray, L. T.; Strode, S. A.; Fiore, A. M.; Lamarque, J. F.; Prather, M. J.; Thompson, C. R.; Peischl, J.; Ryerson, T. B.; Allen, H.; Blake, D. R.; Crounse, J. D.; Brune, W. H.; Elkins, J. W.; Hall, S. R.; Hintsa, E. J.; Huey, L. G.; Kim, M. J.; Moore, F. L.; Ullmann, K.; Wennberg, P. O.; Wofsy, S. C.

    2017-12-01

    Nitrogen oxides (NOx ≡ NO + NO2) in the background atmosphere are critical precursors for the formation of tropospheric ozone and OH, thereby exerting strong influence on surface air quality, reactive greenhouse gases, and ecosystem health. The impact of NOx on atmospheric composition and climate is sensitive to the relative partitioning of reactive nitrogen between NOx and longer-lived reservoir species of the total reactive nitrogen family (NOy) such as HNO3, HNO4, PAN and organic nitrates (RONO2). Unfortunately, global chemistry-climate models (CCMs) and chemistry-transport models (CTMs) have historically disagreed in their reactive nitrogen budgets outside of polluted continental regions, and we have lacked in situ observations with which to evaluate them. Here, we compare and evaluate the NOy budget of six global models (GEOS-Chem CTM, GFDL AM3 CCM, GISS E2.1 CCM, GMI CTM, NCAR CAM CCM, and UCI CTM) using new observations of total reactive nitrogen and its member species from the NASA Atmospheric Tomography (ATom) mission. ATom has now completed two of its four planned deployments sampling the remote Pacific and Atlantic basins of both hemispheres with a comprehensive suite of measurements for constraining reactive photochemistry. All six models have simulated conditions climatologically similar to the deployments. The GMI and GEOS-Chem CTMs have in addition performed hindcast simulations using the MERRA-2 reanalysis, and have been sampled along the flight tracks. We evaluate the performance of the models relative to the observations, and identify factors contributing to their disparate behavior using known differences in model oxidation mechanisms, heterogeneous loss pathways, lightning and surface emissions, and physical loss processes.

  7. Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease.

    PubMed

    Girard, Romuald; Zeineddine, Hussein A; Orsbon, Courtney; Tan, Huan; Moore, Thomas; Hobson, Nick; Shenkar, Robert; Lightle, Rhonda; Shi, Changbin; Fam, Maged D; Cao, Ying; Shen, Le; Neander, April I; Rorrer, Autumn; Gallione, Carol; Tang, Alan T; Kahn, Mark L; Marchuk, Douglas A; Luo, Zhe-Xi; Awad, Issam A

    2016-09-15

    Cerebral cavernous malformations (CCMs) are hemorrhagic brain lesions, where murine models allow major mechanistic discoveries, ushering genetic manipulations and preclinical assessment of therapies. Histology for lesion counting and morphometry is essential yet tedious and time consuming. We herein describe the application and validations of X-ray micro-computed tomography (micro-CT), a non-destructive technique allowing three-dimensional CCM lesion count and volumetric measurements, in transgenic murine brains. We hereby describe a new contrast soaking technique not previously applied to murine models of CCM disease. Volumetric segmentation and image processing paradigm allowed for histologic correlations and quantitative validations not previously reported with the micro-CT technique in brain vascular disease. Twenty-two hyper-dense areas on micro-CT images, identified as CCM lesions, were matched by histology. The inter-rater reliability analysis showed strong consistency in the CCM lesion identification and staging (K=0.89, p<0.0001) between the two techniques. Micro-CT revealed a 29% greater CCM lesion detection efficiency, and 80% improved time efficiency. Serial integrated lesional area by histology showed a strong positive correlation with micro-CT estimated volume (r(2)=0.84, p<0.0001). Micro-CT allows high throughput assessment of lesion count and volume in pre-clinical murine models of CCM. This approach complements histology with improved accuracy and efficiency, and can be applied for lesion burden assessment in other brain diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Evaluating data-driven causal inference techniques in noisy physical and ecological systems

    NASA Astrophysics Data System (ADS)

    Tennant, C.; Larsen, L.

    2016-12-01

    Causal inference from observational time series challenges traditional approaches for understanding processes and offers exciting opportunities to gain new understanding of complex systems where nonlinearity, delayed forcing, and emergent behavior are common. We present a formal evaluation of the performance of convergent cross-mapping (CCM) and transfer entropy (TE) for data-driven causal inference under real-world conditions. CCM is based on nonlinear state-space reconstruction, and causality is determined by the convergence of prediction skill with an increasing number of observations of the system. TE is the uncertainty reduction based on transition probabilities of a pair of time-lagged variables. With TE, causal inference is based on asymmetry in information flow between the variables. Observational data and numerical simulations from a number of classical physical and ecological systems: atmospheric convection (the Lorenz system), species competition (patch-tournaments), and long-term climate change (Vostok ice core) were used to evaluate the ability of CCM and TE to infer causal-relationships as data series become increasingly corrupted by observational (instrument-driven) or process (model-or -stochastic-driven) noise. While both techniques show promise for causal inference, TE appears to be applicable to a wider range of systems, especially when the data series are of sufficient length to reliably estimate transition probabilities of system components. Both techniques also show a clear effect of observational noise on causal inference. For example, CCM exhibits a negative logarithmic decline in prediction skill as the noise level of the system increases. Changes in TE strongly depend on noise type and which variable the noise was added to. The ability of CCM and TE to detect driving influences suggest that their application to physical and ecological systems could be transformative for understanding driving mechanisms as Earth systems undergo change.

  9. Developing measures of educational change for academic health care teams implementing the chronic care model in teaching practices.

    PubMed

    Bowen, Judith L; Stevens, David P; Sixta, Connie S; Provost, Lloyd; Johnson, Julie K; Woods, Donna M; Wagner, Edward H

    2010-09-01

    The Chronic Care Model (CCM) is a multidimensional framework designed to improve care for patients with chronic health conditions. The model strives for productive interactions between informed, activated patients and proactive practice teams, resulting in better clinical outcomes and greater satisfaction. While measures for improving care may be clear, measures of residents' competency to provide chronic care do not exist. This report describes the process used to develop educational measures and results from CCM settings that used them to monitor curricular innovations. Twenty-six academic health care teams participating in the national and California Academic Chronic Care Collaboratives. Using successive discussion groups and surveys, participants engaged in an iterative process to identify desirable and feasible educational measures for curricula that addressed educational objectives linked to the CCM. The measures were designed to facilitate residency programs' abilities to address new accreditation requirements and tested with teams actively engaged in redesigning educational programs. Field notes from each discussion and lists from work groups were synthesized using the CCM framework. Descriptive statistics were used to report survey results and measurement performance. Work groups generated educational objectives and 17 associated measurements. Seventeen (65%) teams provided feasibility and desirability ratings for the 17 measures. Two process measures were selected for use by all teams. Teams reported variable success using the measures. Several teams reported use of additional measures, suggesting more extensive curricular change. Using an iterative process in collaboration with program participants, we successfully defined a set of feasible and desirable education measures for academic health care teams using the CCM. These were used variably to measure the results of curricular changes, while simultaneously addressing requirements for residency accreditation.

  10. Antarctic Phytoplankton down-regulate Their Carbon-Concentrating Mechanisms under High CO2 with no Change in Growth Rates

    NASA Astrophysics Data System (ADS)

    Kranz, S. A.; Young, J. N.; Goldman, J.; Tortell, P. D.; Morel, F. M.

    2016-02-01

    High-latitude oceans, in particular the coastal Western Antarctic Peninsula (WAP) region of the Southern Ocean, are experiencing a rapidly changing environment due to rising surface ocean temperatures and CO2 concentrations. However, the direct effect of increasing CO2 on polar ocean primary production is unclear, with a number of experiments showing conflicting results. It has been hypothesized that increased CO2 may cause a reduction of the energy-intensive carbon concentrating mechanism (CCM) in phytoplankton, and these energy savings may lead to increased productivity. To test this hypothesis, we incubated natural phytoplankton communities in the WAP under high (800 ppm), current (400 ppm) and low (100 ppm) CO2 for 2 to 3 wk during the austral spring-summer of 2012/2013. In 2 incubations with diatom-dominated phytoplankton assemblages, high CO2 led to a clear down-regulation of CCM activity, as evidenced by an increase in half-saturation constants for CO2, a decrease in external carbonic anhydrase activity and a higher biological fractionation of stable carbon isotopes. In a third incubation, there was no observable regulation of the CCM. We did not observe a significant effect of CO2 on growth rates or community composition in the diatom-dominated communities. The lack of a measureable effect on growth despite CCM down-regulation is likely explained by a very small energetic requirement to concentrate CO2 and saturate Rubisco at low temperatures.

  11. NCAR CCM2 simulation of the modern Antarctic climate

    NASA Technical Reports Server (NTRS)

    Tzeng, Ren-Yow; Bromwich, David H.; Parish, Thomas R.; Chen, Biao

    1994-01-01

    The National Center for Atmospheric Research (NCAR) community climate model version 2 (CCM2) simulation of the circumpolar trough, surface air temperature, the polar vortex, cloudiness, winds, and atmospheric moisture and energy budgets are examined to validate the model's representation of the present-day Antarctic climate. The results show that the CCM2 can well simulate many important climate features over Antarctica, such as the location and intensity of the circumpolar trough, the coreless winter over the plateau, the intensity and horizontal distribution of the surface inversion, the speed and streamline pattern of the katabatic winds, the double jet stream feature over the southern Indian and Pacific oceans, and the arid climate over the continent. However, there are also some serious errors in the model. Some are due to old problems but some are caused by the new parameterizations in the model. The model errors over high southern latitudes can be summarized as follows: The circumpolar trough, the polar vertex, and the westerlies in midlatitudes are too strong; the semiannual cycle of the circumpolar trough is distorted compared to the observations; the low centers of the circumpolar trough and the troughs in the middle and upper troposphere are shifted eastward by 15 deg - 40 deg longitude; the surface temperatures are too cold over the plateau in summer and over the coastline in winter; the polar tropopause continues to have a cold bias; and the cloudiness is too high over the continent. These biases are induced by two major factors: (1) the cloud optical properties in tropical and middle latitudes, which cause the eastward shift of troughs and surface low centers and the error in the semiannual cycle, and (2) the cold bias of the surface air temperature, which is attributed to the oversimulation of cloudiness over the continent, especially during summer, and the uniform 2-m-thick sea ice. The constant thickness of sea ice suppresses the energy flux from the ocean to the atmosphere and hence reduces the air temperature near the coast during winter. Finally, although the simulated Antarctic climate still suffers these biases, the overall performance of the CCM2 is much better than that of the CCM1-T42. Therefore the CCM2 is good enough to be used for climate change studies, especially over Antarctica.

  12. Policy challenges facing integrated community case management in Sub-Saharan Africa.

    PubMed

    Bennett, Sara; George, Asha; Rodriguez, Daniela; Shearer, Jessica; Diallo, Brahima; Konate, Mamadou; Dalglish, Sarah; Juma, Pamela; Namakhoma, Ireen; Banda, Hastings; Chilundo, Baltazar; Mariano, Alda; Cliff, Julie

    2014-07-01

    To report an in-depth analysis of policy change for integrated community case management of childhood illness (iCCM) in six sub-Saharan African countries. We analysed how iCCM policies developed and the barriers and facilitators to policy change. Qualitative retrospective case studies drawing from document reviews, semi-structured interviews and in-country validation workshops were conducted in Burkina Faso, Kenya, Malawi, Mali, Mozambique and Niger. These countries were selected to maximise variation in iCCM policy status, community health worker (CHW) models and different African regions. Country iCCM policies evolved in an ad hoc fashion, but were substantially influenced by the history of primary health care and the nature of CHW programmes. Technical officers within Ministries of Health led iCCM policy change with support from international donors, but neither communities nor political leadership was mobilised. Concerns about achieving the Millennium Development Goals, together with recognition of the shortcomings of existing child health programmes, led to the adoption of iCCM policies. Availability of external financing played a critical role in facilitating policy change. iCCM policy change has been promoted by international agencies, but national governments have struggled to align iCCM with country health systems. Greater investment is needed in tailoring global policy initiatives to match country needs. High-level, political ownership of iCCM policies could facilitate policy change, as could clearer strategies for ensuring the long-term sustainability of such policies. © 2014 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  13. Policy challenges facing integrated community case management in Sub-Saharan Africa

    PubMed Central

    Bennett, Sara; George, Asha; Rodriguez, Daniela; Shearer, Jessica; Diallo, Brahima; Konate, Mamadou; Dalglish, Sarah; Juma, Pamela; Namakhoma, Ireen; Banda, Hastings; Chilundo, Baltazar; Mariano, Alda; Cliff, Julie

    2014-01-01

    Objective To report an in-depth analysis of policy change for integrated community case management of childhood illness (iCCM) in six sub-Saharan African countries. We analysed how iCCM policies developed and the barriers and facilitators to policy change. Methods Qualitative retrospective case studies drawing from document reviews, semi-structured interviews and in-country validation workshops were conducted in Burkina Faso, Kenya, Malawi, Mali, Mozambique and Niger. These countries were selected to maximise variation in iCCM policy status, community health worker (CHW) models and different African regions. Results Country iCCM policies evolved in an ad hoc fashion, but were substantially influenced by the history of primary health care and the nature of CHW programmes. Technical officers within Ministries of Health led iCCM policy change with support from international donors, but neither communities nor political leadership was mobilised. Concerns about achieving the Millennium Development Goals, together with recognition of the shortcomings of existing child health programmes, led to the adoption of iCCM policies. Availability of external financing played a critical role in facilitating policy change. Conclusions iCCM policy change has been promoted by international agencies, but national governments have struggled to align iCCM with country health systems. Greater investment is needed in tailoring global policy initiatives to match country needs. High-level, political ownership of iCCM policies could facilitate policy change, as could clearer strategies for ensuring the long-term sustainability of such policies. PMID:24750516

  14. Ultralow-frequency collective compression mode and strong interlayer coupling in multilayer black phosphorus

    DOE PAGES

    Dong, Shan; Zhang, Anmin; Liu, Kai; ...

    2016-02-26

    The recent renaissance of black phosphorus (BP) as a two-dimensional (2D) layered material has generated tremendous interest, but its unique structural characters underlying many of its outstanding properties still need elucidation. Here we report Raman measurements that reveal an ultralow-frequency collective compression mode (CCM) in BP, which is unprecedented among similar 2D layered materials. This novel CCM indicates an unusually strong interlayer coupling, and this result is quantitatively supported by a phonon frequency analysis and first-principles calculations. Moreover, the CCM and another branch of low-frequency Raman modes shift sensitively with changing number of layers, allowing an accurate determination of themore » thickness up to tens of atomic layers, which is considerably higher than previously achieved by using high-frequency Raman modes. Lastly, these findings offer fundamental insights and practical tools for further exploration of BP as a highly promising new 2D semiconductor.« less

  15. Dosimetric evaluation of high-dose-rate interstitial brachytherapy boost treatments for localized prostate cancer.

    PubMed

    Fröhlich, Georgina; Agoston, Péter; Lövey, József; Somogyi, András; Fodor, János; Polgár, Csaba; Major, Tibor

    2010-07-01

    To quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk. Treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose-volume parameters for target (V90, V100, V150, V200, D90, D(min)) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D(r)) and urethra (D(u)), dose to volume of 2 cm(3) of the rectum (D(2ccm)), and 0.1 cm(3) and 1% of the urethra (D(0.1ccm) and D1) were determined. Nonparametric correlation analysis was performed between these parameters. The median number of needles was 16, the mean prostate volume (V(p)) was 27.1 cm(3). The mean V90, V100, V150, and V200 were 99%, 97%, 39%, and 13%, respectively. The mean D90 was 109%, and the D(min) was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D(2ccm) = 49% for the rectum, D(0.1ccm) = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D(r),D(2ccm)) = 0.69, R(D(u),D0.(1ccm)) = 0.64, R(D(u),D1) = 0.23. US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose-volume parameters. For urethra dose characterization, the use of D1 volumetric parameter is recommended.

  16. Crystal Growth Control

    NASA Technical Reports Server (NTRS)

    Duval, Walter M. B.; Batur, Celal; Bennett, Robert J.

    1997-01-01

    We present an innovative design of a vertical transparent multizone furnace which can operate in the temperature range of 25 C to 750 C and deliver thermal gradients of 2 C/cm to 45 C/cm for the commercial applications to crystal growth. The operation of the eight zone furnace is based on a self-tuning temperature control system with a DC power supply for optimal thermal stability. We show that the desired thermal profile over the entire length of the furnace consists of a functional combination of the fundamental thermal profiles for each individual zone obtained by setting the set-point temperature for that zone. The self-tuning system accounts for the zone to zone thermal interactions. The control system operates such that the thermal profile is maintained under thermal load, thus boundary conditions on crystal growth ampoules can be predetermined prior to crystal growth. Temperature profiles for the growth of crystals via directional solidification, vapor transport techniques, and multiple gradient applications are shown to be easily implemented. The unique feature of its transparency and ease of programming thermal profiles make the furnace useful for scientific and commercial applications for the determination of process parameters to optimize crystal growth conditions.

  17. Changing fluvial styles in volcaniclastic successions: A cretaceous example from the Cerro Barcino Formation, Patagonia

    NASA Astrophysics Data System (ADS)

    Umazano, A. Martín; Krause, J. Marcelo; Bellosi, Eduardo S.; Perez, Mariano; Visconti, Graciela; Melchor, Ricardo N.

    2017-08-01

    The Cretaceous Puesto La Paloma (PLPM) and Cerro Castaño (CCM) members (Cerro Barcino Formation, Chubut Group) are pyroclastic-rich, alluvial successions deposited in the Somuncurá-Cañadón Asfalto Basin during sag and endorheic conditions. The PLPM comprises sheet-like tuffaceous sandstone strata, whereas the overlying CCM includes sheet-to ribbon-channel sandstone bodies intercalated within tuffaceous and fine-grained sediments. In this context, the goals of this contribution were: i) to make a detailed documentation of the contrasting sedimentary palaeonvironments; and ii) to infer the allocyclic controls that governed the sedimentation of both units. The study area is located in the western sector of the basin, where six localities, which were studied. Six facies associations were defined including ash-falls, sheet-floods, shallow lakes, aeolian, fluvial channel-belts, and reworked debris-flows. We defined four stratigraphic intervals for the studied sections, denominated 1 to 4 in chronological order of deposition, which increase their thicknesses toward the Puesto Mesa-Cerro León site. The interval 1 (18-42 m thick) corresponds to the PLPM and includes numerous pedogenized sheet-flood deposits, carbonate-rich lacustrine, aeolian sandy facies, and ash-fall beds. The interval 1 is interpreted as an ephemeral and unconfined alluvial system that interacted with aeolian dunes and dry interdune zones. The interval 2 (20-47 m thick) represents the lower part of the CCM. It shows an alternation of fluvial channel-belt deposits and vegetated floodplain facies with sediments originated from sheet-floods, lakes, and few ash-falls and debris-flows. The mean palaeoflow was toward E-SE, except in the northernmost locality where the drainage was towards SW. Proportion of channel-belt bodies ranges from 10 to 36%, reaching higher values in the northern part of the study area, where they are also thicker. The interval 2 represents a permanent, meandering or locally low-sinuosity, fluvial system, and displays both an increase of lacustrine facies and a decrease of ash-fall deposits. The interval 3 (7.5-27 m thick) corresponds to the middle part of the CCM, and lacks channel-belt bodies. It has the highest participation of sheet-flood and ash-fall deposits. This interval entirely records a pedogenized floodplain setting. In relation to the interval 2, participation of debris-flow deposits remains constant and lacustrine facies subtly increases. The interval 4 (18-148 m thick) represents the upper part of the CCM. It comprises an alternation of channel-belt bodies and pedogenized floodplain facies, the last characterized by sheet-flood, lake, debris-flow, and volcanic ash rain deposits. The mean palaeoflow was toward E-SE, except in the two localities positioned further north where the drainage was towards NE and SSE. Proportion of channel-belt deposits ranges from 6 to 32%. It represents channelized and perennial fluvial systems with meandering and locally low-sinuosity styles. Increase in channel proportion and thicker channel bodies are in the northern part of the study area. Particularly, in Puesto Mesa-Cerro León locality this interval is the thickest and has the highest proportion of thicker channel-belt bodies. We interpret these changes in facies architecture as the response to alternated periods of high (intervals 1 and 3) and low (intervals 2 and 4) primary pyroclastic sediment supply. Moreover, there was a climatic change to wetter conditions (intervals 1 to 2-4); as well as intrabasinal tectonic activity in northern area for intervals 2 and 4 inferred from palaeocurrent data.

  18. In Science Students Must Also Play Their Part.

    ERIC Educational Resources Information Center

    Brekke, Stewart E.

    1993-01-01

    Argues that very little is being done to improve the environmental conditions that cause poor student performance such as gang behavior, violence in children's lives, behavior problems, and the detrimental effects of poverty. (CCM)

  19. A supermolecular curcumin for enhanced antiproliferative and proapoptotic activities: molecular characteristics, computer modeling and in vivo pharmacokinetics

    NASA Astrophysics Data System (ADS)

    Tan, Qunyou; Wu, Jianyong; Li, Yi; Mei, Hu; Zhao, Chunjing; Zhang, Jingqing

    2013-01-01

    The supermolecular curcumin (SMCCM) exhibiting remarkably improved solubility and release characteristics was fabricated to increase the oral bioavailability in rat as well as the antiproliferative and proapoptotic activities of curcumin (CCM) against human lung adenocarcinoma cell A549. SMCCM was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, morphology and structure, aqueous solubility, and release behavior in vitro. Computer modeling of the supermolecular structure was performed. The pharmacokinetics, antiproliferative and proapoptotic activities of SMCCM were evaluated. The mechanisms by which SMCCM inhibited proliferation and induced apoptosis were identified. The formation of SMCCM was testified and the supermolecular structure was studied by a computer modeling technique. Compared to free CCM, SMCCM with much higher aqueous solubility exhibited obviously enhanced release and more favorable pharmacokinetic profiles, and, furthermore, SMCCM showed higher anticancer efficacy, enhanced induction of G2/M-phase arrest and apoptosis in A549 cells, which might be involved with the increases in reactive oxygen species production and intracellular Ca2+ accumulation, and a decrease in mitochondrial membrane potential. SMCCM remarkably enhanced not only the oral bioavailability but also the antiproliferative and proapoptotic activities of CCM along with improved solubility and release characteristics of CCM.

  20. A supermolecular curcumin for enhanced antiproliferative and proapoptotic activities: molecular characteristics, computer modeling and in vivo pharmacokinetics.

    PubMed

    Tan, Qunyou; Wu, Jianyong; Li, Yi; Mei, Hu; Zhao, Chunjing; Zhang, Jingqing

    2013-01-25

    The supermolecular curcumin (SMCCM) exhibiting remarkably improved solubility and release characteristics was fabricated to increase the oral bioavailability in rat as well as the antiproliferative and proapoptotic activities of curcumin (CCM) against human lung adenocarcinoma cell A549. SMCCM was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, morphology and structure, aqueous solubility, and release behavior in vitro. Computer modeling of the supermolecular structure was performed. The pharmacokinetics, antiproliferative and proapoptotic activities of SMCCM were evaluated. The mechanisms by which SMCCM inhibited proliferation and induced apoptosis were identified. The formation of SMCCM was testified and the supermolecular structure was studied by a computer modeling technique. Compared to free CCM, SMCCM with much higher aqueous solubility exhibited obviously enhanced release and more favorable pharmacokinetic profiles, and, furthermore, SMCCM showed higher anticancer efficacy, enhanced induction of G2/M-phase arrest and apoptosis in A549 cells, which might be involved with the increases in reactive oxygen species production and intracellular Ca(2+) accumulation, and a decrease in mitochondrial membrane potential. SMCCM remarkably enhanced not only the oral bioavailability but also the antiproliferative and proapoptotic activities of CCM along with improved solubility and release characteristics of CCM.

  1. Curcumin-loaded chitosan-cholesterol micelles: evaluation in monolayers and 3D cancer spheroid model.

    PubMed

    Muddineti, Omkara Swami; Kumari, Preeti; Ray, Eupa; Ghosh, Balaram; Biswas, Swati

    2017-06-02

    To improve the bioavailability and anticancer potential of curcumin by using a cholesterol-conjugated chitosan micelle. Methods & methods: Cholesterol was conjugated to chitosan (15 kDa) to form self-assembled micelles, which loaded curcumin. Physicochemical characterization and formulation optimization of the drug-loaded micelles (curcumin-loaded chitosan-cholesterol micelles [C-CCM]) were performed. In vitro cellular uptake and viability of C-CCM were investigated in melanoma and breast cancer cell lines. The antitumor efficacy was evaluated in 3D lung cancer spheroid model. The optimized C-CCM had size of approximately 162 nm with loading efficiency of approximately 36%. C-CCM was taken up efficiently by the cells, and it reduced cancer cell viability significantly compared with free curcumin. C-CCM enhanced the antitumor efficacy in spheroids, suggesting that C-CCM could be used as an effective chemotherapy in cancer.

  2. Monitoring iCCM referral systems: Bugoye Integrated Community Case Management Initiative (BIMI) in Uganda.

    PubMed

    English, Lacey; Miller, James S; Mbusa, Rapheal; Matte, Michael; Kenney, Jessica; Bwambale, Shem; Ntaro, Moses; Patel, Palka; Mulogo, Edgar; Stone, Geren S

    2016-04-29

    In Uganda, over half of under-five child mortality is attributed to three infectious diseases: malaria, pneumonia and diarrhoea. Integrated community case management (iCCM) trains village health workers (VHWs) to provide in-home diagnosis and treatment of these common childhood illnesses. For severely ill children, iCCM relies on a functioning referral system to ensure timely treatment at a health facility. However, referral completion rates vary widely among iCCM programmes and are difficult to monitor. The Bugoye Integrated Community Case Management Initiative (BIMI) is an iCCM programme operating in Bugoye sub-county, Uganda. This case study describes BIMI's experience with monitoring referral completion at Bugoye Health Centre III (BHC), and outlines improvements to be made within iCCM referral systems. This study triangulated multiple data sources to evaluate the strengths and gaps in the BIMI referral system. Three quantitative data sources were reviewed: (1) VHW report of referred patients, (2) referral forms found at BHC, and (3) BHC patient records. These data sources were collated and triangulated from January-December 2014. The goal was to determine if patients were completing their referrals and if referrals were adequately documented using routine data sources. From January-December 2014, there were 268 patients referred to BHC, as documented by VHWs. However, only 52 of these patients had referral forms stored at BHC. Of the 52 referral forms found, 22 of these patients were also found in BHC register books recorded by clinic staff. Thus, the study found a mismatch between VHW reports of patient referrals and the referral visits documented at BHC. This discrepancy may indicate several gaps: (1) referred patients may not be completing their referral, (2) referral forms may be getting lost at BHC, and, (3) referred patients may be going to other health facilities or drug shops, rather than BHC, for their referral. This study demonstrates the challenges of effectively monitoring iCCM referral completion, given identified limitations such as discordant data sources, incomplete record keeping and lack of unique identifiers. There is a need to innovate and improve the ways by which referral compliance is monitored using routine data, in order to improve the percentage of referrals completed. Through research and field experience, this study proposes programmatic and technological solutions to rectify these gaps within iCCM programmes facing similar challenges. With improved monitoring, VHWs will be empowered to increase referral completion, allowing critically ill children to access needed health services.

  3. Implementing collaborative care for depression treatment in primary care: A cluster randomized evaluation of a quality improvement practice redesign

    PubMed Central

    2011-01-01

    Background Meta-analyses show collaborative care models (CCMs) with nurse care management are effective for improving primary care for depression. This study aimed to develop CCM approaches that could be sustained and spread within Veterans Affairs (VA). Evidence-based quality improvement (EBQI) uses QI approaches within a research/clinical partnership to redesign care. The study used EBQI methods for CCM redesign, tested the effectiveness of the locally adapted model as implemented, and assessed the contextual factors shaping intervention effectiveness. Methods The study intervention is EBQI as applied to CCM implementation. The study uses a cluster randomized design as a formative evaluation tool to test and improve the effectiveness of the redesign process, with seven intervention and three non-intervention VA primary care practices in five different states. The primary study outcome is patient antidepressant use. The context evaluation is descriptive and uses subgroup analysis. The primary context evaluation measure is naturalistic primary care clinician (PCC) predilection to adopt CCM. For the randomized evaluation, trained telephone research interviewers enrolled consecutive primary care patients with major depression in the evaluation, referred enrolled patients in intervention practices to the implemented CCM, and re-surveyed at seven months. Results Interviewers enrolled 288 CCM site and 258 non-CCM site patients. Enrolled intervention site patients were more likely to receive appropriate antidepressant care (66% versus 43%, p = 0.01), but showed no significant difference in symptom improvement compared to usual care. In terms of context, only 40% of enrolled patients received complete care management per protocol. PCC predilection to adopt CCM had substantial effects on patient participation, with patients belonging to early adopter clinicians completing adequate care manager follow-up significantly more often than patients of clinicians with low predilection to adopt CCM (74% versus 48%%, p = 0.003). Conclusions Depression CCM designed and implemented by primary care practices using EBQI improved antidepressant initiation. Combining QI methods with a randomized evaluation proved challenging, but enabled new insights into the process of translating research-based CCM into practice. Future research on the effects of PCC attitudes and skills on CCM results, as well as on enhancing the link between improved antidepressant use and symptom outcomes, is needed. Trial Registration ClinicalTrials.gov: NCT00105820 PMID:22032247

  4. Development of clinical contents model markup language for electronic health records.

    PubMed

    Yun, Ji-Hyun; Ahn, Sun-Ju; Kim, Yoon

    2012-09-01

    To develop dedicated markup language for clinical contents models (CCM) to facilitate the active use of CCM in electronic health record systems. Based on analysis of the structure and characteristics of CCM in the clinical domain, we designed extensible markup language (XML) based CCM markup language (CCML) schema manually. CCML faithfully reflects CCM in both the syntactic and semantic aspects. As this language is based on XML, it can be expressed and processed in computer systems and can be used in a technology-neutral way. CCML HAS THE FOLLOWING STRENGTHS: it is machine-readable and highly human-readable, it does not require a dedicated parser, and it can be applied for existing electronic health record systems.

  5. Access to integrated community case management of childhood illnesses services in rural Ethiopia: a qualitative study of the perspectives and experiences of caregivers

    PubMed Central

    Shaw, Bryan; Amouzou, Agbessi; Miller, Nathan P; Tafesse, Mengistu; Bryce, Jennifer; Surkan, Pamela J

    2016-01-01

    Background: In 2010, Ethiopia began scaling up the integrated community case management (iCCM) of childhood illness strategy throughout the country allowing health extension workers (HEWs) to treat children in rural health posts. After 2 years of iCCM scale up, utilization of HEWs remains low. Little is known about factors related to the use of health services in this setting. This research aimed to elicit perceptions and experiences of caregivers to better understand reasons for low utilization of iCCM services. Methods: A rapid ethnographic assessment was conducted in eight rural health post catchment areas in two zones: Jimma and West Hararghe. In total, 16 focus group discussions and 78 in-depth interviews were completed with mothers, fathers, HEWs and community health volunteers. Results: In spite of the HEW being a core component of iCCM, we found that the lack of availability of HEWs at the health post was one of the most common barriers to the utilization of iCCM services mentioned by caregivers. Financial and geographic challenges continue to influence caregiver decisions despite extension of free child health services in communities. Acceptability of HEWs was often low due to a perceived lack of sensitivity of HEWs and concerns about medicines given at the health post. Social networks acted both to facilitate and hinder use of HEWs. Many mothers stated a preference for using the health post, but some were unable to do so due to objections or alternative care-seeking preferences of gatekeepers, often mothers-in-law and husbands. Conclusion: Caregivers in Ethiopia face many challenges in using HEWs at the health post, potentially resulting in low demand for iCCM services. Efforts to minimize barriers to care seeking and to improve demand should be incorporated into the iCCM strategy in order to achieve reductions in child mortality and promote equity in access and child health outcomes. PMID:26608585

  6. A multi-institutional quality improvement initiative to transform education for chronic illness care in resident continuity practices.

    PubMed

    Stevens, David P; Bowen, Judith L; Johnson, Julie K; Woods, Donna M; Provost, Lloyd P; Holman, Halsted R; Sixta, Constance S; Wagner, Ed H

    2010-09-01

    There is a gap between the need for patient-centered, evidence-based primary care for the large burden of chronic illness in the US, and the training of resident physicians to provide that care. To improve training for residents who provide chronic illness care in teaching practice settings. US teaching hospitals were invited to participate in one of two 18-month Breakthrough Series Collaboratives-either a national Collaborative, or a subsequent California Collaborative-to implement the Chronic Care Model (CCM) and related curriculum changes in resident practices. Most practices focused on patients with diabetes mellitus. Educational redesign strategies with related performance measures were developed for curricular innovations anchored in the CCM. In addition, three clinical measures-HbA1c <7%, LDL <100 mg/dL, and blood pressure

  7. A Multi-Institutional Quality Improvement Initiative to Transform Education for Chronic Illness Care in Resident Continuity Practices

    PubMed Central

    Bowen, Judith L.; Johnson, Julie K.; Woods, Donna M.; Provost, Lloyd P.; Holman, Halsted R.; Sixta, Constance S.; Wagner, Ed H.

    2010-01-01

    BACKGROUND There is a gap between the need for patient-centered, evidence-based primary care for the large burden of chronic illness in the US, and the training of resident physicians to provide that care. OBJECTIVE To improve training for residents who provide chronic illness care in teaching practice settings. DESIGN US teaching hospitals were invited to participate in one of two 18-month Breakthrough Series Collaboratives—either a national Collaborative, or a subsequent California Collaborative—to implement the Chronic Care Model (CCM) and related curriculum changes in resident practices. Most practices focused on patients with diabetes mellitus. Educational redesign strategies with related performance measures were developed for curricular innovations anchored in the CCM. In addition, three clinical measures—HbA1c <7%, LDL <100 mg/dL, and blood pressure ≤130/80—and three process measures—retinal and foot examinations, and patient self-management goals—were tracked. PARTICIPANTS Fifty-seven teams from 37 self-selected teaching hospitals committed to implement the CCM in resident continuity practices; 41 teams focusing on diabetes improvement participated over the entire duration of one of the Collaboratives. INTERVENTIONS Teaching-practice teams—faculty, residents and staff—participated in Collaboratives by attending monthly calls and regular 2-day face-to-face meetings with the other teams. The national Collaborative faculty led calls and meetings. Each team used rapid cycle quality improvement (PDSA cycles) to implement the CCM and curricular changes. Teams reported education and clinical performance measures monthly. RESULTS Practices underwent extensive redesign to establish CCM elements. Education measures tracked substantial development of CCM-related learning. The clinical and process measures improved, however inconsistently, during the Collaboratives. CONCLUSIONS These initiatives suggest that systematic practice redesign for implementing the CCM along with linked educational approaches are achievable in resident continuity practices. Improvement of clinical outcomes in such practices is daunting but achievable. PMID:20737232

  8. Contour Connection Method for automated identification and classification of landslide deposits

    NASA Astrophysics Data System (ADS)

    Leshchinsky, Ben A.; Olsen, Michael J.; Tanyu, Burak F.

    2015-01-01

    Landslides are a common hazard worldwide that result in major economic, environmental and social impacts. Despite their devastating effects, inventorying existing landslides, often the regions at highest risk of reoccurrence, is challenging, time-consuming, and expensive. Current landslide mapping techniques include field inventorying, photogrammetric approaches, and use of bare-earth (BE) lidar digital terrain models (DTMs) to highlight regions of instability. However, many techniques do not have sufficient resolution, detail, and accuracy for mapping across landscape scale with the exception of using BE DTMs, which can reveal the landscape beneath vegetation and other obstructions, highlighting landslide features, including scarps, deposits, fans and more. Current approaches to landslide inventorying with lidar to create BE DTMs include manual digitizing, statistical or machine learning approaches, and use of alternate sensors (e.g., hyperspectral imaging) with lidar. This paper outlines a novel algorithm to automatically and consistently detect landslide deposits on a landscape scale. The proposed method is named as the Contour Connection Method (CCM) and is primarily based on bare earth lidar data requiring minimal user input such as the landslide scarp and deposit gradients. The CCM algorithm functions by applying contours and nodes to a map, and using vectors connecting the nodes to evaluate gradient and associated landslide features based on the user defined input criteria. Furthermore, in addition to the detection capabilities, CCM also provides an opportunity to be potentially used to classify different landscape features. This is possible because each landslide feature has a distinct set of metadata - specifically, density of connection vectors on each contour - that provides a unique signature for each landslide. In this paper, demonstrations of using CCM are presented by applying the algorithm to the region surrounding the Oso landslide in Washington (March 2014), as well as two 14,000 ha DTMs in Oregon, which were used as a comparison of CCM and manually delineated landslide deposits. The results show the capability of the CCM with limited data requirements and the agreement with manual delineation but achieving the results at a much faster time.

  9. Supplement to CCM.D-K4 'Hydrometer' report: linkage of EURAMET.M.D-K4 comparison, SIM.M.D-K4 comparison and the supplementary SIM.M.D-S2 to CCM.D-K4 'Hydrometer'

    NASA Astrophysics Data System (ADS)

    Lorefice, S.; Becerra, L. O.

    2017-01-01

    Evaluation of different types of comparisons to a common set of reference values of a CIPM key comparison is essential to satisfy the concept of the CIPM Mutual Recognition Arrangement (CIPM MRA), where the DoEs of any participant who took part in comparisons should be within the Calibration and Measurement Capability (CMC) section of the CIPM MRA Key Comparison Data Base. The subject of this supplementary report is therefore to present the equivalence of each National Metrological Institute (NMI) participant in the CCM.D-K4 'Hydrometer' key comparison, which was performed in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20 °C, and the linkage of the European and Inter-American NMI results performed in the RMO.M.D-K4 comparisons as well as those of the supplementary SIM.M.D-S2 to the common set of KCRVs of the CCM.D-K4 'Hydrometer'. The linking procedure has been obtained by numerical simulation, based on the Monte Carlo method, in which the differences in the results of the different comparison between the intended laboratory and one or more linking laboratory/ies, which took part in both comparisons, are correlated with a continuous function describing the DoEs of the linking laboratory/ies with respect to the common set of KCRVs of the CCM.D-K4. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  10. Coordinate Axes and Mental Rotation Tasks: A Solomon Four Group Design.

    ERIC Educational Resources Information Center

    Branoff, Theodore J.

    1999-01-01

    Studies the effectiveness of adding coordinate axes to mental rotations tasks. Assesses the effect of the coordinate axes, the effect of pretest sensitization, and interaction between the pretest and posttest conditions. (Author/CCM)

  11. Physician involvement in disease management as part of the CCM.

    PubMed

    Wallace, Paul J

    2005-01-01

    Phase I of the voluntary chronic care improvement (CCI-I) under traditional fee-for-service Medicare initiative seeks to extend the benefits of disease management to an elderly population with comorbid chronic medical conditions. Active, sustained involvement of treating physicians, a historical deficit of disease management programs, is a CCI-I program goal. During the last decade, Kaiser Permanente, an integrated health care delivery system with more than 60 years of experience in managing the care of individuals and populations, has applied the chronic care model (CCM) to develop care management strategies for populations of patients with chronic medical conditions. Physician leadership and involvement have been key to successfully incorporating these practices into care. The scope of physician involvement in leading, developing, and delivering chronic illness care management at Kaiser Permanente is described as a basis for identifying opportunities to involve practicing physicians in the CCI-I.

  12. Physician Involvement in Disease Management as Part of the CCM

    PubMed Central

    Wallace, Paul J.

    2005-01-01

    Phase I of the voluntary chronic care improvement (CCI-I) under traditional fee-for-service Medicare initiative seeks to extend the benefits of disease management to an elderly population with comorbid chronic medical conditions. Active, sustained involvement of treating physicians, a historical deficit of disease management programs, is a CCI-I program goal. During the last decade, Kaiser Permanente, an integrated health care delivery system with more than 60 years of experience in managing the care of individuals and populations, has applied the chronic care model (CCM) to develop care management strategies for populations of patients with chronic medical conditions. Physician leadership and involvement have been key to successfully incorporating these practices into care. The scope of physician involvement in leading, developing, and delivering chronic illness care management at Kaiser Permanente is described as a basis for identifying opportunities to involve practicing physicians in the CCI-I. PMID:17288075

  13. Detection of coupling delay: A problem not yet solved

    NASA Astrophysics Data System (ADS)

    Coufal, David; Jakubík, Jozef; Jajcay, Nikola; Hlinka, Jaroslav; Krakovská, Anna; Paluš, Milan

    2017-08-01

    Nonparametric detection of coupling delay in unidirectionally and bidirectionally coupled nonlinear dynamical systems is examined. Both continuous and discrete-time systems are considered. Two methods of detection are assessed—the method based on conditional mutual information—the CMI method (also known as the transfer entropy method) and the method of convergent cross mapping—the CCM method. Computer simulations show that neither method is generally reliable in the detection of coupling delays. For continuous-time chaotic systems, the CMI method appears to be more sensitive and applicable in a broader range of coupling parameters than the CCM method. In the case of tested discrete-time dynamical systems, the CCM method has been found to be more sensitive, while the CMI method required much stronger coupling strength in order to bring correct results. However, when studied systems contain a strong oscillatory component in their dynamics, results of both methods become ambiguous. The presented study suggests that results of the tested algorithms should be interpreted with utmost care and the nonparametric detection of coupling delay, in general, is a problem not yet solved.

  14. Chronic care model for the management of depression: synthesis of barriers to, and facilitators of, success.

    PubMed

    Holm, Anne Lise; Severinsson, Elisabeth

    2012-12-01

    Depression is a socially- and physically-disabling condition. The Chronic Care Model (CCM) was developed to promote better management of long-term conditions, such as depression, in primary care settings. The aim of the study was to identify barriers to, and facilitators of, success when implementing the CCM for the management of depression in primary care. A systematic search was conducted in electronic databases from January 2005 to December 2011. Thirteen articles met the inclusion criteria and were reviewed by means of a thematic analysis. The barriers were categorized under two themes: lack of organizational, administrative, and professional ability to change and implement the components of the CCM; and lack of clarity pertaining to the responsibility inherent in the role of care manager (often a nurse) when it comes to promoting the patient's self-management ability. In terms of the facilitators of success, two themes emerged: leadership support and vision, and redesigning the delivery system. When shaping an environment for organizational change, leadership and professionals must work towards a common goal and vision. Such processes require a care manager with a clear role and responsibilities in order for the health-care system to meet the needs of the person with depression. © 2012 The Authors. International Journal of Mental Health Nursing © 2012 Australian College of Mental Health Nurses Inc.

  15. Medicare Chronic Care Management Payments and Financial Returns to Primary Care Practices: A Modeling Study.

    PubMed

    Basu, Sanjay; Phillips, Russell S; Bitton, Asaf; Song, Zirui; Landon, Bruce E

    2015-10-20

    Physicians have traditionally been reimbursed for face-to-face visits. A new non-visit-based payment for chronic care management (CCM) of Medicare patients took effect in January 2015. To estimate financial implications of CCM payment for primary care practices. Microsimulation model incorporating national data on primary care use, staffing, expenditures, and reimbursements. National Ambulatory Medical Care Survey and other published sources. Medicare patients. 10 years. Practice-level. Comparison of CCM delivery approaches by staff and physicians. Net revenue per full-time equivalent (FTE) physician; time spent delivering CCM services. If nonphysician staff were to deliver CCM services, net revenue to practices would increase despite opportunity and staffing costs. Practices could expect approximately $332 per enrolled patient per year (95% CI, $234 to $429) if CCM services were delivered by registered nurses (RNs), approximately $372 (CI, $276 to $468) if services were delivered by licensed practical nurses, and approximately $385 (CI, $286 to $485) if services were delivered by medical assistants. For a typical practice, this equates to more than $75 ,00 of net annual revenue per FTE physician and 12 hours of nursing service time per week if 50% of eligible patients enroll. At a minimum, 131 Medicare patients (CI, 115 to 140 patients) must enroll for practices to recoup the salary and overhead costs of hiring a full-time RN to provide CCM services. If physicians were to deliver all CCM services, approximately 25% of practices nationwide could expect net revenue losses due to opportunity costs of face-to-face visit time. The CCM program may alter long-term primary care use, which is difficult to predict. Practices that rely on nonphysician team members to deliver CCM services will probably experience substantial net revenue gains but must enroll a sufficient number of eligible patients to recoup costs. None.

  16. Assessment of the monitoring and evaluation system for integrated community case management (ICCM) in Ethiopia: a comparison against global benchmark indicators.

    PubMed

    Mamo, Dereje; Hazel, Elizabeth; Lemma, Israel; Guenther, Tanya; Bekele, Abeba; Demeke, Berhanu

    2014-10-01

    Program managers require feasible, timely, reliable, and valid measures of iCCM implementation to identify problems and assess progress. The global iCCM Task Force developed benchmark indicators to guide implementers to develop or improve monitoring and evaluation (M&E) systems. To assesses Ethiopia's iCCM M&E system by determining the availability and feasibility of the iCCM benchmark indicators. We conducted a desk review of iCCM policy documents, monitoring tools, survey reports, and other rele- vant documents; and key informant interviews with government and implementing partners involved in iCCM scale-up and M&E. Currently, Ethiopia collects data to inform most (70% [33/47]) iCCM benchmark indicators, and modest extra effort could boost this to 83% (39/47). Eight (17%) are not available given the current system. Most benchmark indicators that track coordination and policy, human resources, service delivery and referral, supervision, and quality assurance are available through the routine monitoring systems or periodic surveys. Indicators for supply chain management are less available due to limited consumption data and a weak link with treatment data. Little information is available on iCCM costs. Benchmark indicators can detail the status of iCCM implementation; however, some indicators may not fit country priorities, and others may be difficult to collect. The government of Ethiopia and partners should review and prioritize the benchmark indicators to determine which should be included in the routine M&E system, especially since iCCMdata are being reviewed for addition to the HMIS. Moreover, the Health Extension Worker's reporting burden can be minimized by an integrated reporting approach.

  17. Development of Clinical Contents Model Markup Language for Electronic Health Records

    PubMed Central

    Yun, Ji-Hyun; Kim, Yoon

    2012-01-01

    Objectives To develop dedicated markup language for clinical contents models (CCM) to facilitate the active use of CCM in electronic health record systems. Methods Based on analysis of the structure and characteristics of CCM in the clinical domain, we designed extensible markup language (XML) based CCM markup language (CCML) schema manually. Results CCML faithfully reflects CCM in both the syntactic and semantic aspects. As this language is based on XML, it can be expressed and processed in computer systems and can be used in a technology-neutral way. Conclusions CCML has the following strengths: it is machine-readable and highly human-readable, it does not require a dedicated parser, and it can be applied for existing electronic health record systems. PMID:23115739

  18. Representations of the Stratospheric Polar Vortices in Versions 1 and 2 of the Goddard Earth Observing System Chemistry-Climate Model (GEOS CCM)

    NASA Technical Reports Server (NTRS)

    Pawson, S.; Stolarski, R.S.; Nielsen, J.E.; Perlwitz, J.; Oman, L.; Waugh, D.

    2009-01-01

    This study will document the behavior of the polar vortices in two versions of the GEOS CCM. Both versions of the model include the same stratospheric chemistry, They differ in the underlying circulation model. Version 1 of the GEOS CCM is based on the Goddard Earth Observing System, Version 4, general circulation model which includes the finite-volume (Lin-Rood) dynamical core and physical parameterizations from Community Climate Model, Version 3. GEOS CCM Version 2 is based on the GEOS-5 GCM that includes a different tropospheric physics package. Baseline simulations of both models, performed at two-degree spatial resolution, show some improvements in Version 2, but also some degradation, In the Antarctic, both models show an over-persistent stratospheric polar vortex with late breakdown, but the year-to-year variations that are overestimated in Version I are more realistic in Version 2. The implications of this for the interactions with tropospheric climate, the Southern Annular Mode, will be discussed. In the Arctic both model versions show a dominant dynamically forced variabi;ity, but Version 2 has a persistent warm bias in the low stratosphere and there are seasonal differences in the simulations. These differences will be quantified in terms of climate change and ozone loss. Impacts of model resolution, using simulations at one-degree and half-degree, and changes in physical parameterizations (especially the gravity wave drag) will be discussed.

  19. Final report on CIPM key comparison CCM.FF-K6.2011: Comparison of the primary (national) standards of low-pressure gas flow

    NASA Astrophysics Data System (ADS)

    Benková, Miroslava; Makovnik, Stefan; Mickan, Bodo; Arias, Roberto; Chahine, Khaled; Funaki, Tatsuya; Li, Chunhui; Choi, Hae Man; Seredyuk, Denys; Su, Chun-Min; Windenberg, Christophe; Wright, John

    2014-01-01

    The comparison CCM.FF-K6.2011 was organized for the purpose of determination of the degree of equivalence of the national standards for low-pressure gas flow measurement over the range (2 to 100) m3/h. A rotary gas meter was used as a transfer standard. The measurements were provided at prescribed reference conditions. Eleven laboratories from four RMOs participated in this key comparison—EURAMET: PTB, Germany; SMU, Slovakia; LNE-LADG, France; SIM: NIST, USA; CENAM, Mexico; APMP: NMIJ AIST Japan; KRISS, Korea; NMI, Australia; NIM, China; CMS, Chinese Taipei; COOMET: GP GP Ivano-Frankivs'kstandart-metrologia, Ukraine and all participants reported independent traceability chains to the SI. All results were used in the determination of the key comparison reference value (KCRV) and the uncertainty of the KCRV. The reference value was determined at each flow separately following procedure A presented by M G Cox. The degree of equivalence with the KCRV was also calculated for each flow and laboratory. All reported results were consistent with the KCRV. This KCRV can now be used in the further regional comparisons. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  20. Identification of a novel gene cluster in the upstream region of the S-layer gene sbpA involved in cell wall metabolism of Lysinibacillus sphaericus CCM 2177 and characterization of the recombinantly produced autolysin and pyruvyl transferase.

    PubMed

    Pleschberger, Magdalena; Hildner, Florian; Rünzler, Dominik; Gelbmann, Nicola; Mayer, Harald F; Sleytr, Uwe B; Egelseer, Eva M

    2013-05-01

    The S-layer protein SbpA of Lysinibacillus sphaericus CCM 2177 assembles into a square (p4) lattice structure and recognizes a pyruvylated secondary cell wall polymer (SCWP) as the proper anchoring structure to the rigid cell wall layer. Sequencing of 8,004 bp in the 5'-upstream region of the S-layer gene sbpA led to five ORFs-encoding proteins involved in cell wall metabolism. After cloning and heterologous expression of ORF1 and ORF5 in Escherichia coli, the recombinant autolysin rAbpA and the recombinant pyruvyl transferase rCsaB were isolated, purified, and correct folding was confirmed by circular dichroism. Although rAbpA encoded by ORF1 showed amidase activity, it could attack whole cells of Ly. sphaericus CCM 2177 only after complete extraction of the S-layer lattice. Despite the presence of three S-layer-homology motifs on the N-terminal part, rAbpA did not show detectable affinity to peptidoglycan-containing sacculi, nor to isolated SCWP. As the molecular mass of the autolysin lies above the molecular exclusion limit of the S-layer, AbpA is obviously trapped within the rigid cell wall layer by the isoporous protein lattice. Immunogold-labeling of ultrathin-sectioned whole cells of Ly. sphaericus CCM 2177 with a polyclonal rabbit antiserum raised against rCsaB encoded by ORF5, and cell fractionation experiments demonstrated that the pyruvyl transferase was located in the cytoplasm, but not associated with cell envelope components including the plasma membrane. In enzymatic assays, rCsaB clearly showed pyruvyl transferase activity. By using RT-PCR, specific transcripts for each ORF could be detected. Cotranscription could be confirmed for ORF2 and ORF3.

  1. Human severe sepsis cytokine mixture increases β2-integrin-dependent polymorphonuclear leukocyte adhesion to cerebral microvascular endothelial cells in vitro.

    PubMed

    Blom, Chris; Deller, Brittany L; Fraser, Douglas D; Patterson, Eric K; Martin, Claudio M; Young, Bryan; Liaw, Patricia C; Yazdan-Ashoori, Payam; Ortiz, Angelica; Webb, Brian; Kilmer, Greg; Carter, David E; Cepinskas, Gediminas

    2015-04-07

    Sepsis-associated encephalopathy (SAE) is a state of acute brain dysfunction in response to a systemic infection. We propose that systemic inflammation during sepsis causes increased adhesion of leukocytes to the brain microvasculature, resulting in blood-brain barrier dysfunction. Thus, our objectives were to measure inflammatory analytes in plasma of severe sepsis patients to create an experimental cytokine mixture (CM), and to use this CM to investigate the activation and interactions of polymorphonuclear leukocytes (PMN) and human cerebrovascular endothelial cells (hCMEC/D3) in vitro. The concentrations of 41 inflammatory analytes were quantified in plasma obtained from 20 severe sepsis patients and 20 age- and sex-matched healthy controls employing an antibody microarray. Two CMs were prepared to mimic severe sepsis (SSCM) and control (CCM), and these CMs were then used for PMN and hCMEC/D3 stimulation in vitro. PMN adhesion to hCMEC/D3 was assessed under conditions of flow (shear stress 0.7 dyn/cm(2)). Eight inflammatory analytes elevated in plasma obtained from severe sepsis patients were used to prepare SSCM and CCM. Stimulation of PMN with SSCM led to a marked increase in PMN adhesion to hCMEC/D3, as compared to CCM. PMN adhesion was abolished with neutralizing antibodies to either β2 (CD18), αL/β2 (CD11α/CD18; LFA-1) or αM/β2 (CD11β/CD18; Mac-1) integrins. In addition, immune-neutralization of the endothelial (hCMEC/D3) cell adhesion molecule, ICAM-1 (CD54) also suppressed PMN adhesion. Human SSCM up-regulates PMN pro-adhesive phenotype and promotes PMN adhesion to cerebrovascular endothelial cells through a β2-integrin-ICAM-1-dependent mechanism. PMN adhesion to the brain microvasculature may contribute to SAE.

  2. Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study.

    PubMed

    Kass-Iliyya, Lewis; Javed, Saad; Gosal, David; Kobylecki, Christopher; Marshall, Andrew; Petropoulos, Ioannis N; Ponirakis, Georgios; Tavakoli, Mitra; Ferdousi, Maryam; Chaudhuri, Kallol Ray; Jeziorska, Maria; Malik, Rayaz A; Silverdale, Monty A

    2015-12-01

    Autonomic and somatic denervation is well established in Parkinson's disease (PD). (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose. PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Internet Search and Krokodil in the Russian Federation: An Infoveillance Study

    PubMed Central

    2014-01-01

    Background Krokodil is an informal term for a cheap injectable illicit drug domestically prepared from codeine-containing medication (CCM). The method of krokodil preparation may produce desomorphine as well as toxic reactants that cause extensive tissue necrosis. The first confirmed report of krokodil use in Russia took place in 2004. In 2012, reports of krokodil-related injection injuries began to appear beyond Russia in Western Europe and the United States. Objective This exploratory study had two main objectives: (1) to determine if Internet search patterns could detect regularities in behavioral responses to Russian CCM policy at the population level, and (2) to determine if complementary data sources could explain the regularities we observed. Methods First, we obtained krokodil-related search pattern data for each Russia subregion (oblast) between 2011 and 2012. Second, we analyzed several complementary data sources included krokodil-related court cases, and related search terms on both Google and Yandex to evaluate the characteristics of terms accompanying krokodil-related search queries. Results In the 6 months preceding CCM sales restrictions, 21 of Russia's 83 oblasts had search rates higher than the national average (mean) of 16.67 searches per 100,000 population for terms associated with krokodil. In the 6 months following restrictions, mean national searches dropped to 9.65 per 100,000. Further, the number of oblasts recording a higher than average search rate dropped from 30 to 16. Second, we found krokodil-related court appearances were moderately positively correlated (Spearman correlation=.506, P≤.001) with behaviors consistent with an interest in the production and use of krokodil across Russia. Finally, Google Trends and Google and Yandex related terms suggested consistent public interest in the production and use of krokodil as well as for CCM as analgesic medication during the date range covered by this study. Conclusions Illicit drug use data are generally regarded as difficult to obtain through traditional survey methods. Our analysis suggests it is plausible that Yandex search behavior served as a proxy for patterns of krokodil production and use during the date range we investigated. More generally, this study demonstrates the application of novel methods recently used by policy makers to both monitor illicit drug use and influence drug policy decision making. PMID:25236385

  4. In vivo collective cell migration requires an LPAR2-dependent increase in tissue fluidity

    PubMed Central

    Kuriyama, Sei; Theveneau, Eric; Benedetto, Alexandre; Parsons, Maddy; Tanaka, Masamitsu; Charras, Guillaume; Kabla, Alexandre

    2014-01-01

    Collective cell migration (CCM) and epithelial–mesenchymal transition (EMT) are common to cancer and morphogenesis, and are often considered to be mutually exclusive in spite of the fact that many cancer and embryonic cells that have gone through EMT still cooperate to migrate collectively. Here we use neural crest (NC) cells to address the question of how cells that have down-regulated cell–cell adhesions can migrate collectively. NC cell dissociation relies on a qualitative and quantitative change of the cadherin repertoire. We found that the level of cell–cell adhesion is precisely regulated by internalization of N-cadherin downstream of lysophosphatidic acid (LPA) receptor 2. Rather than promoting the generation of single, fully mesenchymal cells, this reduction of membrane N-cadherin only triggers a partial mesenchymal phenotype. This intermediate phenotype is characterized by an increase in tissue fluidity akin to a solid-like–to–fluid-like transition. This change of plasticity allows cells to migrate under physical constraints without abolishing cell cooperation required for collectiveness. PMID:25002680

  5. Chronic care management for dependence on alcohol and other drugs: the AHEAD randomized trial.

    PubMed

    Saitz, Richard; Cheng, Debbie M; Winter, Michael; Kim, Theresa W; Meli, Seville M; Allensworth-Davies, Don; Lloyd-Travaglini, Christine A; Samet, Jeffrey H

    2013-09-18

    People with substance dependence have health consequences, high health care utilization, and frequent comorbidity but often receive poor-quality care. Chronic care management (CCM) has been proposed as an approach to improve care and outcomes. To determine whether CCM for alcohol and other drug dependence improves substance use outcomes compared with usual primary care. The AHEAD study, a randomized trial conducted among 563 people with alcohol and other drug dependence at a Boston, Massachusetts, hospital-based primary care practice. Participants were recruited from September 2006 to September 2008 from a freestanding residential detoxification unit and referrals from an urban teaching hospital and advertisements; 95% completed 12-month follow-up. Participants were randomized to receive CCM (n=282) or no CCM (n=281). Chronic care management included longitudinal care coordinated with a primary care clinician; motivational enhancement therapy; relapse prevention counseling; and on-site medical, addiction, and psychiatric treatment, social work assistance, and referrals (including mutual help). The no CCM (control) group received a primary care appointment and a list of treatment resources including a telephone number to arrange counseling. The primary outcome was self-reported abstinence from opioids, stimulants, or heavy drinking. Biomarkers were secondary outcomes. There was no significant difference in abstinence from opioids, stimulants, or heavy drinking between the CCM (44%) and control (42%) groups (adjusted odds ratio, 0.84; 95% CI, 0.65-1.10; P=.21). No significant differences were found for secondary outcomes of addiction severity, health-related quality of life, or drug problems. No subgroup effects were found except among those with alcohol dependence, in whom CCM was associated with fewer alcohol problems (mean score, 10 vs 13; incidence rate ratio, 0.85; 95% CI, 0.72-1.00; P=.048). Among persons with alcohol and other drug dependence, CCM compared with a primary care appointment but no CCM did not increase self-reported abstinence over 12 months. Whether more intensive or longer-duration CCM is effective requires further investigation. clinicaltrials.gov Identifier: NCT00278447.

  6. An ethical justification for the Chronic Care Model (CCM)

    PubMed Central

    Oprea, Liviu; Braunack‐Mayer, Annette; Rogers, Wendy A.; Stocks, Nigel

    2009-01-01

    Abstract Background:  Chronic diseases are major causes of morbidity and mortality in developed countries. Their effects can be mitigated by high quality evidence‐based care, but this is not the norm in most systems. The Chronic Care Model (CCM) is an evidence‐based policy response to this practice gap, which uses multiple strategies to promote the quality of chronic care. Objective:  To review CCM with an ethical lens. Methods:  We reviewed the published empirical and non‐empirical articles of CCM to analyse the ethical underpinnings of this model. Results and conclusions:  We argue that its principal ethical value lies in the institutional cooperation it builds between the stakeholders involved in health care services. First, we briefly describe CCM and argue that the pathways through which it aims to improve patients’ health outcomes are not made explicit. Second, we argue that the potential of CCM to be more beneficent, compared with traditional health care systems, depends on its capacity to promote mutual trust between health care providers and patients. There is no evidence to date that the implementation of CCM enhances mutual trust between health care professionals and patients. Third, we argue that CCM seeks to enhance human agency, allowing increased expression of individual autonomy and increased respect for individuals thereby expanding human freedom and avoiding social discrimination. However, we review the communication patterns that characterize the model of doctor–patient relationship promoted by this model and argue that these communication patterns raise ethical concerns that may prevent the model from reaching its expected outcomes. PMID:19906213

  7. Relative Influence of Initial Surface and Atmospheric Conditions on Seasonal Water and Energy Balances

    NASA Technical Reports Server (NTRS)

    Oglesby, Robert J.; Marshall, Susan; Roads, John O.; Robertson, Franklin R.; Goodman, H. Michael (Technical Monitor)

    2001-01-01

    We constructed and analyzed wet and dry soil moisture composites for the mid-latitude GCIP region of the central US using long climate model simulations made with the NCAR CCM3 and reanalysis products from NCEP. Using the diagnostic composites as a guide, we have completed a series of predictability experiments in which we imposed soil water initial conditions in CCM3 for the GCIP region for June 1 from anomalously wet and dry years, with atmospheric initial conditions taken from June 1 of a year with 'near-normal' soil water, and initial soil water from the near-normal year and atmospheric initial conditions from the wet and dry years. Preliminary results indicate that the initial state of the atmosphere is more important than the initial state of soil water determining the subsequent late spring and summer evolution of sod water over the GCIP region. Surprisingly, neither the composites or the predictability experiments yielded a strong influence of soil moisture on the atmosphere. To explore this further, we have made runs with extreme dry soil moisture initial anomalies imposed over the GCIP region (the soil close to being completely dry). These runs did yield a very strong effect on the atmosphere that persisted for at least three months. We conclude that the magnitude of the initial soil moisture anomaly is crucial, at least in CCM3, and are currently investigating whether a threshold exists, below which little impact is seen. In a complementary study, we compared the impact of the initial condition of snow cover versus the initial atmospheric state over the western US (corresponding to the westward extension of the GAPP program follow-on to GCIP). In this case, the initial prescription of snow cover is far more important than the initial atmospheric state in determining the subsequent evolution of snow cover. We are currently working to understand the very different soil water and snow cover results.

  8. Stratigraphy, correlation, depositional setting, and geophysical characteristics of the Oligocene Snowshoe Mountain Tuff and Creede Formation in two cored boreholes

    USGS Publications Warehouse

    Larsen, Daniel; Nelson, Philip H.

    2000-01-01

    Core descriptions and geophysical logs from two boreholes (CCM-1 and CCM-2) in the Oligocene Snowshoe Mountain Tuff and Creede Formation, south-central Colorado, are used to interpret sedimentary and volcanic facies associations and their physical properties. The seven facies association include a mixed sequence of intracaldera ash-flow tuffs and breccias, alluvial and lake margin deposits, and tuffaceous lake beds. These deposits represent volcanic units related to caldera collapse and emplacement of the Snowshoe Mountain Tuff, and sediments and pyroclastic material deposited in the newly formed caldera basin, Early sedimentation is interpreted to have been rapid, and to have occurred in volcaniclastic fan environments at CCM-1 and in a variery of volcaniclastic fan, braided stream shallow lacustrine, and mudflat environments at CCM-2. After an initial period of lake-level rise, suspension settling, turbidite, and debris-flow sedimentation occurred in lacustrine slope and basin environments below wave base. Carbonate sedimentation was initially sporadic, but more continuous in the latter part of the recorded lake history (after the H fallout tuff). Sublacustrine-fan deposition occurred at CCM-1 after a pronounced lake-level fall and subsequent rise that preceded the H tuff. Variations in density, neutron, gamma-ray, sonic, and electrical properties of deposits penetrated oin the two holes reflect variations in lithology, porosity, and alteration. Trends in the geophysical properties of the lacustrine strata are linked to downhole changes in authigenic mineralology and a decrease in porosity interpreted to have resulted primarily from diagenesis. Lithological and geophysical characteristics provide a basis for correlation of the cores; however, mineralogical methods of correlation are hampered by the degree of diagenesis and alteration.

  9. Demand generation and social mobilisation for integrated community case management (iCCM) and child health: Lessons learned from successful programmes in Niger and Mozambique.

    PubMed

    Sharkey, Alyssa B; Martin, Sandrine; Cerveau, Teresa; Wetzler, Erica; Berzal, Rocio

    2014-12-01

    We present the approaches used in and outcomes resulting from integrated community case management (iCCM) programmes in Niger and Mozambique with a strong focus on demand generation and social mobilisation. We use a case study approach to describe the programme and contextual elements of the Niger and Mozambique programmes. Awareness and utilisation of iCCM services and key family practices increased following the implementation of the Niger and Mozambique iCCM and child survival programmes, as did care-seeking within 24 hours and care-seeking from appropriate, trained providers in Mozambique. These approaches incorporated interpersonal communication activities and community empowerment/participation for collective change, partnerships and networks among key stakeholder groups within communities, media campaigns and advocacy efforts with local and national leaders. iCCM programmes that train and equip community health workers and successfully engage and empower community members to adopt new behaviours, have appropriate expectations and to trust community health workers' ability to assess and treat illnesses can lead to improved care-seeking and utilisation, and community ownership for iCCM.

  10. Access to integrated community case management of childhood illnesses services in rural Ethiopia: a qualitative study of the perspectives and experiences of caregivers.

    PubMed

    Shaw, Bryan; Amouzou, Agbessi; Miller, Nathan P; Tafesse, Mengistu; Bryce, Jennifer; Surkan, Pamela J

    2016-06-01

    In 2010, Ethiopia began scaling up the integrated community case management (iCCM) of childhood illness strategy throughout the country allowing health extension workers (HEWs) to treat children in rural health posts. After 2 years of iCCM scale up, utilization of HEWs remains low. Little is known about factors related to the use of health services in this setting. This research aimed to elicit perceptions and experiences of caregivers to better understand reasons for low utilization of iCCM services. A rapid ethnographic assessment was conducted in eight rural health post catchment areas in two zones: Jimma and West Hararghe. In total, 16 focus group discussions and 78 in-depth interviews were completed with mothers, fathers, HEWs and community health volunteers. In spite of the HEW being a core component of iCCM, we found that the lack of availability of HEWs at the health post was one of the most common barriers to the utilization of iCCM services mentioned by caregivers. Financial and geographic challenges continue to influence caregiver decisions despite extension of free child health services in communities. Acceptability of HEWs was often low due to a perceived lack of sensitivity of HEWs and concerns about medicines given at the health post. Social networks acted both to facilitate and hinder use of HEWs. Many mothers stated a preference for using the health post, but some were unable to do so due to objections or alternative care-seeking preferences of gatekeepers, often mothers-in-law and husbands. Caregivers in Ethiopia face many challenges in using HEWs at the health post, potentially resulting in low demand for iCCM services. Efforts to minimize barriers to care seeking and to improve demand should be incorporated into the iCCM strategy in order to achieve reductions in child mortality and promote equity in access and child health outcomes. © The Author 2015. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

  11. Synergy, Salary, and Satisfaction: Benefits of Training in Critical Care Medicine and Infectious Diseases Gleaned From a National Pilot Survey of Dually Trained Physicians.

    PubMed

    Kadri, Sameer S; Rhee, Chanu; Magda, Gabriela; Strich, Jeffrey R; Cai, Rongman; Sun, Junfeng; Decker, Brooke K; O'Grady, Naomi P

    2016-10-01

    An increasing number of physicians are seeking dual training in critical care medicine (CCM) and infectious diseases (ID). Understanding experiences and perceptions of CCM-ID physicians could inform career choices and programmatic innovation. All physicians trained and/or certified in both CCM and ID to date in the United States were sent a Web-based questionnaire in 2015. Responses enabled a cross-sectional analysis of physician demographics and training and practice characteristics and satisfaction. Of 202 CCM-ID physicians, 196 were alive and reachable. The response rate was 79%. Forty-six percent trained and 34% practice in the northeastern United States. Only 40% received dual training at the same institution. Eighty-three percent identified as either an intensivist with ID expertise (44%) or as equally an intensivist and ID physician (38%). Median salary was $265 000 (interquartile range [IQR], $215 000-$350 000). Practice settings were split between academic (45%) and community settings (42%). Two-thirds are clinicians but 62% conduct some research and 26% practice outpatient ID. Top reasons to dually specialize included clinical synergy (70%), procedural activity (50%), and less interest in pulmonology (49%). Although 38% cited less proficiency with bronchoscopy as a disadvantage, 87% seldom need pulmonary consultation in the intensive care unit. Median career satisfaction was 4 (IQR, 4-5) out of 5, and 76% would dually train again. CCM-ID graduates prefer the acute care setting, predominantly CCM or a combination of CCM and ID. They find combination training and practice to be synergistic and satisfying, but most have had to seek CCM and ID training independently at separate institutions. Given these findings, avenues for combined training in CCM-ID should be considered. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. Monitoring iCCM: a feasibility study of the indicator guide for monitoring and evaluating integrated community case management.

    PubMed

    Roberton, Timothy; Kasungami, Dyness; Guenther, Tanya; Hazel, Elizabeth

    2016-07-01

    Most countries in sub-Saharan Africa have now adopted integrated community case management (iCCM) of common childhood illnesses as a strategy to improve child health. In March 2014, the iCCM Task Force published an Indicator Guide for Monitoring and Evaluating iCCM: a 'menu' of recommended indicators with globally agreed definitions and methodology, to guide countries in developing robust iCCM monitoring systems. The Indicator Guide was conceived as an evolving document that would incorporate collective experience and learning as iCCM programmes themselves evolve. This article presents findings from two studies that examined the feasibility of collecting the Indicator Guide's 18 routine monitoring indicators with the iCCM monitoring systems that countries currently have in place. We reviewed iCCM monitoring tools, protocols and reports from a purposive sample of 10 countries in sub-Saharan Africa. We developed a scorecard system to assess which of the Indicator Guide's 18 routine monitoring indicators could be calculated with the given monitoring tools, and at which level of the health system the relevant information would be available. We found that the data needed to calculate many of the Indicator Guide's routine monitoring indicators are already being collected through existing monitoring systems, although much of these data are only available at health facility level and not aggregated to district or national levels. Our results highlight challenge of using supervision checklists as a data source, and the need for countries to maintain accurate deployment data for CHWs and CHW supervisors. We suggest that some of the recommended indicators need revising. Routine monitoring will be more feasible, effective and efficient if iCCM programmes focus on a smaller set of high-value indicators that are easy to measure, reliably interpreted and useful both for global and national stakeholders and for frontline health workers themselves. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

  13. An inorganic carbon transport system responsible for acclimation specific to air levels of CO2 in Chlamydomonas reinhardtii.

    PubMed

    Wang, Yingjun; Spalding, Martin H

    2006-06-27

    Many photosynthetic microorganisms acclimate to CO(2) limited environments by induction and operation of CO(2)-concentrating mechanisms (CCMs). Despite their central role in CCM function, inorganic carbon (Ci) transport systems never have been identified in eukaryotic photosynthetic organisms. In the green alga Chlamydomonas reinhardtii, a mutant, pmp1, was described in 1983 with deficiencies in Ci transport, and a Pmp1 protein-associated Ci uptake system has been proposed to be responsible for Ci uptake in low CO(2) (air level)-acclimated cells. However, even though pmp1 represents the only clear genetic link to Ci transport in microalgae and is one of only a very few mutants directly affecting the CCM itself, the identity of Pmp1 has remained unknown. Physiological analyses indicate that C. reinhardtii possesses multiple Ci transport systems responsible for acclimation to different levels of limiting CO(2) and that the Pmp1-associated transport system is required specifically for low (air level) CO(2) acclimation. In the current study, we identified and characterized a pmp1 allelic mutant, air dier 1 (ad1) that, like pmp1, cannot grow in low CO(2) (350 ppm) but can grow either in high CO(2) (5% CO(2)) or in very low CO(2) (<200 ppm). Molecular analyses revealed that the Ad1/Pmp1 protein is encoded by LciB, a gene previously identified as a CO(2)-responsive gene. LciB and three related genes in C. reinhardtii compose a unique gene family that encode four closely related, apparently soluble plastid proteins with no clearly identifiable conserved motifs.

  14. Results and evaluation of key comparison CCM.P-K12.1 for very low helium flow rates (leak rates)

    NASA Astrophysics Data System (ADS)

    Šetina, Janez; Vičar, Martin; Pražák, Dominik

    2015-01-01

    The Czech Metrology Institute (CMI) took part and failed to prove equivalence in the Key Comparison CCM.P-K12 of helium leak artefacts (leak rates) into vacuum. After identifying and eliminating the cause of the failure, the Institute of Metals and Technology (IMT) of Slovenia, a successful participant in CCM.P-K12, volunteered to serve as pilot and link in a following bilateral comparison of IMT and CMI that obtained designation CCM.P-K12.1 in June 2012. It was decided to perform the comparison with a glass permeation helium leak artefact at nominally 3.10-11 mol/s (7.4.10-7 mbar.L.s-1) at 23 °C. Both the laboratory standards took part in CCM.P-K12 and were considered as primary. The comparison measurements were performed in October 2012. CMI proved equivalence both with IMT and with the reference value of the key comparison CCM.P-K12. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  15. Revised Tijeras Arroyo Groundwater Current Conceptual Model and Corrective Measures Evaluation Report - February 2018.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Copland, John R.

    The U.S. Department of Energy (DOE) and the management and operating (M&O) contractor for Sandia National Laboratories beginning on May 1, 2017, National Technology & Engineering Solutions of Sandia, LLC (NTESS), hereinafter collectively referred to as DOE/NTESS, prepared this Revised Tijeras Arroyo Groundwater Current Conceptual Model (CCM) and Corrective Measures Evaluation (CME) Report , referred to as the Revised CCM/CME Report, to meet requirements under the Sandia National Laboratories-New Mexico (SNL/NM) Compliance Order on Consent (Consent Order). The Consent Order became effective on April 29, 2004. The Consent Order identifies the Tijeras Arroyo Groundwater (TAG) Area of Concern (AOC) asmore » an area of groundwater contamination requiring further characterization and corrective action. In November 2004, New Mexico Environment Department (NMED) approved the July 2004 CME Work Plan. In April 2005, DOE and the SNL M&O contractor at the time, Sandia Corporation (Sandia), hereinafter collectively referred to as DOE/Sandia, submitted a CME Report, but NMED did not finalize review of that document. In December 2016, DOE/Sandia submitted a combined and updated CCM/CME Report. NMED issued a disapproval letter in May 2017 that included comments on the December 2016 CCM/CME Report. In August 2017, NMED and DOE/NTESS staff held a meeting to discuss and clarify outstanding issues. This Revised CCM/CME Report addresses (1) the issues presented in the NMED May 2017 disapproval letter and (2) findings from the August 2017 meeting.« less

  16. A Health Systems Approach to Integrated Community Case Management of Childhood Illness: Methods and Tools

    PubMed Central

    McGorman, Laura; Marsh, David R.; Guenther, Tanya; Gilroy, Kate; Barat, Lawrence M.; Hammamy, Diaa; Wansi, Emmanuel; Peterson, Stefan; Hamer, Davidson H.; George, Asha

    2012-01-01

    Integrated community case management (iCCM) of childhood illness is an increasingly popular strategy to expand life-saving health services to underserved communities. However, community health approaches vary widely across countries and do not always distribute resources evenly across local health systems. We present a harmonized framework, developed through interagency consultation and review, which supports the design of CCM by using a systems approach. To verify that the framework produces results, we also suggest a list of complementary indicators, including nine global metrics, and a menu of 39 country-specific measures. When used by program managers and evaluators, we propose that the framework and indicators can facilitate the design, implementation, and evaluation of community case management. PMID:23136280

  17. Circuit to Construct Mapping: A Mathematical Tool for Assisting the Diagnosis and Treatment in Major Depressive Disorder

    PubMed Central

    Bielczyk, Natalia Z.; Buitelaar, Jan K.; Glennon, Jeffrey C.; Tiesinga, Paul H. E.

    2015-01-01

    Major depressive disorder (MDD) is a serious condition with a lifetime prevalence exceeding 16% worldwide. MDD is a heterogeneous disorder that involves multiple behavioral symptoms on the one hand and multiple neuronal circuits on the other hand. In this review, we integrate the literature on cognitive and physiological biomarkers of MDD with the insights derived from mathematical models of brain networks, especially models that can be used for fMRI datasets. We refer to the recent NIH research domain criteria initiative, in which a concept of “constructs” as functional units of mental disorders is introduced. Constructs are biomarkers present at multiple levels of brain functioning – cognition, genetics, brain anatomy, and neurophysiology. In this review, we propose a new approach which we called circuit to construct mapping (CCM), which aims to characterize causal relations between the underlying network dynamics (as the cause) and the constructs referring to the clinical symptoms of MDD (as the effect). CCM involves extracting diagnostic categories from behavioral data, linking circuits that are causal to these categories with use of clinical neuroimaging data, and modeling the dynamics of the emerging circuits with attractor dynamics in order to provide new, neuroimaging-related biomarkers for MDD. The CCM approach optimizes the clinical diagnosis and patient stratification. It also addresses the recent demand for linking circuits to behavior, and provides a new insight into clinical treatment by investigating the dynamics of neuronal circuits underneath cognitive dimensions of MDD. CCM can serve as a new regime toward personalized medicine, assisting the diagnosis and treatment of MDD. PMID:25767450

  18. Running STAR-CCM+ Software on the Peregrine System | High-Performance

    Science.gov Websites

    /bin/lmutil lmstat -c 1999@wind-lms.nrel.gov -a module load star-ccm export TMPDIR="/scratch/$USER + -power -rsh "ssh -oStrictHostKeyChecking=no" -machinefile nodelist -np $(($nodes*$cores , type the commands from the SLURM script and make sure the job runs: module load star-ccm export TMPDIR

  19. Cytochrome P450 and matrix metalloproteinase genetic modifiers of disease severity in Cerebral Cavernous Malformation type 1

    PubMed Central

    Choquet, Hélène; Trapani, Eliana; Goitre, Luca; Trabalzini, Lorenza; Akers, Amy; Fontanella, Marco; Hart, Blaine L.; Morrison, Leslie A.; Pawlikowska, Ludmila; Kim, Helen; Retta, Saverio Francesco

    2016-01-01

    Background Familial Cerebral Cavernous Malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and characterized by multiple brain lesions. CCM lesions manifest across a range of different phenotypes, including wide differences in lesion number, size and susceptibility to intracerebral hemorrhage (ICH). Oxidative stress plays an important role in cerebrovascular disease pathogenesis, raising the possibility that inter-individual variability in genes related to oxidative stress may contribute to the phenotypic differences observed in CCM1 disease. Here, we investigated whether candidate oxidative stress-related cytochrome P450 (CYP) and matrix metalloproteinase (MMP) genetic markers grouped by superfamilies, families or genes, or analyzed individually influence the severity of CCM1 disease. Methods Clinical assessment and cerebral susceptibility-weighted magnetic resonance imaging (SWI) were performed to determine total and large (≥5 mm in diameter) lesion counts as well as ICH in 188 Hispanic CCM1 patients harboring the founder KRIT1/CCM1 ‘common Hispanic mutation’ (CCM1–CHM). Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. We analyzed 1,122 genetic markers (both single nucleotide polymorphisms (SNPs) and insertion/deletions) grouped by CYP and MMP superfamily, family or gene for association with total or large lesion count and ICH adjusted for age at enrollment and gender. Genetic markers bearing the associations were then analyzed individually. Results The CYP superfamily showed a trend toward association with total lesion count (P=0.057) and large lesion count (P=0.088) in contrast to the MMP superfamily. The CYP4 and CYP8 families were associated with either large lesion count or total lesion count (P=0.014), and two other families (CYP46 and the MMP Stromelysins) were associated with ICH (P=0.011 and 0.007, respectively). CYP4F12 rs11085971, CYP8A1 rs5628, CYP46A1 rs10151332, and MMP3 rs117153070 single SNPs, mainly bearing the above-mentioned associations, were also individually associated with CCM1 disease severity. Conclusions Overall, our candidate oxidative stress-related genetic markers set approach outlined CYP and MMP families and identified suggestive SNPs that may impact the severity of CCM1 disease, including the development of numerous and large CCM lesions and ICH. These novel genetic risk factors of prognostic value could serve as early objective predictors of disease outcome and might ultimately provide better options for disease prevention and treatment. PMID:26795600

  20. Cytochrome P450 and matrix metalloproteinase genetic modifiers of disease severity in Cerebral Cavernous Malformation type 1.

    PubMed

    Choquet, Hélène; Trapani, Eliana; Goitre, Luca; Trabalzini, Lorenza; Akers, Amy; Fontanella, Marco; Hart, Blaine L; Morrison, Leslie A; Pawlikowska, Ludmila; Kim, Helen; Retta, Saverio Francesco

    2016-03-01

    Familial Cerebral Cavernous Malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and characterized by multiple brain lesions. CCM lesions manifest across a range of different phenotypes, including wide differences in lesion number, size and susceptibility to intracerebral hemorrhage (ICH). Oxidative stress plays an important role in cerebrovascular disease pathogenesis, raising the possibility that inter-individual variability in genes related to oxidative stress may contribute to the phenotypic differences observed in CCM1 disease. Here, we investigated whether candidate oxidative stress-related cytochrome P450 (CYP) and matrix metalloproteinase (MMP) genetic markers grouped by superfamilies, families or genes, or analyzed individually influence the severity of CCM1 disease. Clinical assessment and cerebral susceptibility-weighted magnetic resonance imaging (SWI) were performed to determine total and large (≥5mm in diameter) lesion counts as well as ICH in 188 Hispanic CCM1 patients harboring the founder KRIT1/CCM1 'common Hispanic mutation' (CCM1-CHM). Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. We analyzed 1,122 genetic markers (both single nucleotide polymorphisms (SNPs) and insertion/deletions) grouped by CYP and MMP superfamily, family or gene for association with total or large lesion count and ICH adjusted for age at enrollment and gender. Genetic markers bearing the associations were then analyzed individually. The CYP superfamily showed a trend toward association with total lesion count (P=0.057) and large lesion count (P=0.088) in contrast to the MMP superfamily. The CYP4 and CYP8 families were associated with either large lesion count or total lesion count (P=0.014), and two other families (CYP46 and the MMP Stromelysins) were associated with ICH (P=0.011 and 0.007, respectively). CYP4F12 rs11085971, CYP8A1 rs5628, CYP46A1 rs10151332, and MMP3 rs117153070 single SNPs, mainly bearing the above-mentioned associations, were also individually associated with CCM1 disease severity. Overall, our candidate oxidative stress-related genetic markers set approach outlined CYP and MMP families and identified suggestive SNPs that may impact the severity of CCM1 disease, including the development of numerous and large CCM lesions and ICH. These novel genetic risk factors of prognostic value could serve as early objective predictors of disease outcome and might ultimately provide better options for disease prevention and treatment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Key comparison of liquid density standards

    NASA Astrophysics Data System (ADS)

    Buchner, Christian; Zelenka, Zoltan; Kajastie, Heikki; Madec, Tanguy; Wolf, Henning; Vámossy, Csilla; Lorefice, Salvatore; Garberg, Torgunn; Lenard, Elżbieta; Spohr, Isabel; Mares, Gabriela; Spurný, Robert; Lumbreras, Angel; Medina, Nieves; Y Akçadağ, Ümit; Perkin, Michael

    2015-01-01

    Hydrostatic density determination for liquids is mainly performed by laboratories to provide means for calibrating liquid density measuring instruments such as oscillation-type density meters. From 2002 to 2005 the CIPM key comparison CCM.D-K2 'comparison of liquid density standards' was carried out piloted by the PTB. The aim was to compare the results of the density determination by the participating laboratories to support entries to the CMC tables in this sub-field. To provide further laboratories the possibility to support their entries to the CMC tables at the meeting of the EUROMET Working Group on Density in 2007 this comparison was agreed on. BEV (Austria) organized the comparison supported by the PTB (Germany). For the comparison samples of pentadecane, water, tetrachloroethylene and of an oil of high viscosity were measured in the temperature range from 5 °C to 60 °C at atmospheric pressure by hydrostatic weighing. The measurements were completed in 2008. The reference values of the first reports based on the draft of the CCM.D-K2. After the official publication of the CCM.D-K2 the reference values were recalculated and the report was finalised in 2015. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  2. Bovine vaginal strain Kocuria kristinae and its characterization.

    PubMed

    Styková, Eva; Nemcová, Radomíra; Gancarčíková, Soňa; Valocký, Igor; Lauková, Andrea

    2016-05-01

    Kocuria spp. are widely distributed in nature. They are Gram-positive, coagulase-negative, coccoid bacteria belonging to the family Micrococcaceae, suborder Micrococcineae, order Actinomycetales, class Actinobacteria. In general, limited knowledge exists concerning the properties associated with the representants of the genus Kocuria, Kocuria kristinae as well. Following our previous results, K. kristinae Kk2014 Biocenol(™) (CCM 8628) was isolated from vagina of a healthy cow. Its taxonomical allottation was confirmed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) identification system and phenotypic characteristics. Kk2014 strain showed strong adherence capability to the vaginal mucus, produced organic acids which can play a role in prevention of unsuitable contamination, and showed in vitro antagonistic/antimicrobial activity against strains Arcanobacterium pyogenes CCM 5753, Fusobacterium necrophorum CCM 5982, Streptococcus equi subsp. zooepidemicus CCM 7316, and Gardnerella vaginalis CCM 6221. Antimicrobial activity ranged from 100 to 200 AU/mL, up to 32 mm in size, respectively.

  3. CCM in the FUV

    NASA Astrophysics Data System (ADS)

    Cartledge, S. I. B.; Clayton, G. C.; Gordon, K. D.

    2005-12-01

    Over 90% of Milky Way extinction curves sampled from IR through UV wavelengths (UV coverage by IUE) conform to the CCM family of curves based on R(V), a single parameter linked to grain size. The far-ultraviolet (FUV) portion of this formulation, however, was based only on a few sight lines observed by Copernicus, and it has recently been shown that in certain cases CCM does not predict extinction in the FUV as accurately as it does at longer wavelengths. In this poster paper, we present preliminary results from our examination of the agreement between all publicly-available FUSE FUV spectra of reddened O and B stars and their corresponding extinction curves inferred from longer wavelength fluxes. The eventual goal of our project is to reformulate CCM, particularly in the FUV where we have compiled more than 90 sight lines observed by FUSE. We are also exploring correlations between bulk sight line properties and the form of the reconstituted CCM curves.

  4. [Development of quality of care indicators to support chronic disease management].

    PubMed

    Beaulieu, Marie-dominique; Pomey, Marie-pascale; Del Grande, Claudio; Côté, Brigitte; Tremblay, Éric; Ghorbel, Monia; Hua, Phuong

    2015-01-01

    This article presents the results of a project conducted by the Institut national d'excellence en santé et en services sociaux of Québec to develop quality of care indicators for the management of six chronic illnesses. Indicators were identified through literature searches and analysis of clinical practice guidelines (CPGs). Interdisciplinary expert panels assessed their validity and the strength of the evidence on which they were based. Representatives of patients (N = 19) and professionals (N = 29) were consulted on their relevance and acceptability. Indicators were categorized according to the Chronic Care Model (CCM). A total of 164 indicators were developed, 126 specific to the illnesses under study and 38 on processes and outcomes generic to the CCM. There was convergence between patients and professionals on the relevance of a majority of indicators. Professionals expressed concerns on the indicators measured by means of patient surveys that they considered to be too subjective. The importance given to CPGs as the main source of indicators resulted in a great number of indicators of the technical quality ofcare. Using the CCM contributed to a broader perspective of quality. The consultation process identified some of the concerns of professionals about indicator measurement, thusguidingfuture implementation initiatives.

  5. Rapid Crop Cover Mapping for the Conterminous United States.

    PubMed

    Dahal, Devendra; Wylie, Bruce; Howard, Danny

    2018-06-05

    Timely crop cover maps with sufficient resolution are important components to various environmental planning and research applications. Through the modification and use of a previously developed crop classification model (CCM), which was originally developed to generate historical annual crop cover maps, we hypothesized that such crop cover maps could be generated rapidly during the growing season. Through a process of incrementally removing weekly and monthly independent variables from the CCM and implementing a 'two model mapping' approach, we found it viable to generate conterminous United States-wide rapid crop cover maps at a resolution of 250 m for the current year by the month of September. In this approach, we divided the CCM model into one 'crop type model' to handle the classification of nine specific crops and a second, binary model to classify the presence or absence of 'other' crops. Under the two model mapping approach, the training errors were 0.8% and 1.5% for the crop type and binary model, respectively, while test errors were 5.5% and 6.4%, respectively. With spatial mapping accuracies for annual maps reaching upwards of 70%, this approach demonstrated a strong potential for generating rapid crop cover maps by the 1 st of September.

  6. Performer's attitudes toward seeking health care for voice issues: understanding the barriers.

    PubMed

    Gilman, Marina; Merati, Albert L; Klein, Adam M; Hapner, Edie R; Johns, Michael M

    2009-03-01

    Contemporary commercial music (CCM) performers rely heavily on their voice, yet may not be aware of the importance of proactive voice care. This investigation intends to identify perceptions and barriers to seeking voice care among CCM artists. This cross-sectional observational study used a 10-item Likert-based response questionnaire to assess current perceptions regarding voice care in a population of randomly selected participants of professional CCM conference. Subjects (n=78) were queried regarding their likelihood to seek medical care for minor medical problems and specifically problems with their voice. Additional questions investigated anxiety about seeking voice care from a physician specialist, speech language pathologist, or voice coach; apprehension regarding findings of laryngeal examination, laryngeal imaging procedures; and the effect of medical insurance on the likelihood of seeking medical care. Eighty-two percent of subjects reported that their voice was a critical part of their profession; 41% stated that they were not likely to seek medical care for problems with their voice; and only 19% were reluctant to seek care for general medical problems (P<0.001). Anxiety about seeking a clinician regarding their voice was not a deterrent. Most importantly, 39% of subjects do not seek medical attention for their voice problems due to medical insurance coverage. The CCM artists are less likely to seek medical care for voice problems compared with general medical problems. Availability of medical insurance may be a factor. Availability of affordable voice care and education about the importance of voice care is needed in this population of vocal performers.

  7. Evolutionary bursts in Euphorbia (Euphorbiaceae) are linked with photosynthetic pathway.

    PubMed

    Horn, James W; Xi, Zhenxiang; Riina, Ricarda; Peirson, Jess A; Yang, Ya; Dorsey, Brian L; Berry, Paul E; Davis, Charles C; Wurdack, Kenneth J

    2014-12-01

    The mid-Cenozoic decline of atmospheric CO2 levels that promoted global climate change was critical to shaping contemporary arid ecosystems. Within angiosperms, two CO2 -concentrating mechanisms (CCMs)-crassulacean acid metabolism (CAM) and C4 -evolved from the C3 photosynthetic pathway, enabling more efficient whole-plant function in such environments. Many angiosperm clades with CCMs are thought to have diversified rapidly due to Miocene aridification, but links between this climate change, CCM evolution, and increased net diversification rates (r) remain to be further understood. Euphorbia (∼2000 species) includes a diversity of CAM-using stem succulents, plus a single species-rich C4 subclade. We used ancestral state reconstructions with a dated molecular phylogeny to reveal that CCMs independently evolved 17-22 times in Euphorbia, principally from the Miocene onwards. Analyses assessing among-lineage variation in r identified eight Euphorbia subclades with significantly increased r, six of which have a close temporal relationship with a lineage-corresponding CCM origin. Our trait-dependent diversification analysis indicated that r of Euphorbia CCM lineages is approximately threefold greater than C3 lineages. Overall, these results suggest that CCM evolution in Euphorbia was likely an adaptive strategy that enabled the occupation of increased arid niche space accompanying Miocene expansion of arid ecosystems. These opportunities evidently facilitated recent, replicated bursts of diversification in Euphorbia. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  8. Final report on key comparison EURAMET.M.P-K13 in the range 50 MPa to 500 MPa of hydraulic gauge pressure

    NASA Astrophysics Data System (ADS)

    Kocas, I.; Sabuga, W.; Bergoglio, M.; Eltaweel, A.; Korasie, C.; Farar, P.; Setina, J.; Waller, B.; Durgut, Y.

    2015-01-01

    The regional key comparison EURAMET.M.P-K13 for pressure measurements in liquid media from 50 MPa to 500 MPa was piloted by the TÜBİTAK UME Pressure Group Laboratories, Turkey. The transfer standard was a DH-Budenberg pressure balance with a free deformation piston-cylinder unit of 2 mm2 nominal effective area. Six laboratories from the EURAMET region, namely PTB, INRIM, SMU, IMT, NPL and UME, and two laboratories from the AFRIMETS region, NIS and NMISA participated in this comparison. Participant laboratories and countries are given in the bottom of the page. PTB participated in this comparison to provide a link to corresponding 500 MPa CCM key comparison CCM.P-K13. The results of all participants excepting NMISA and NPL were found to be consistent with the reference value of the actual comparison and of CCM.P-K13 within their claimed uncertainties (k = 2), at all pressures. Compared in pairs all laboratories with exception of NPL and NMISA demonstrate their agreement with each other within the expanded uncertainties (k = 2) at all pressures. The results are therefore considered to be satisfactory. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  9. Demand generation and social mobilisation for integrated community case management (iCCM) and child health: Lessons learned from successful programmes in Niger and Mozambique

    PubMed Central

    Sharkey, Alyssa B; Martin, Sandrine; Cerveau, Teresa; Wetzler, Erica; Berzal, Rocio

    2014-01-01

    Aim We present the approaches used in and outcomes resulting from integrated community case management (iCCM) programmes in Niger and Mozambique with a strong focus on demand generation and social mobilisation. Methods We use a case study approach to describe the programme and contextual elements of the Niger and Mozambique programmes. Results Awareness and utilisation of iCCM services and key family practices increased following the implementation of the Niger and Mozambique iCCM and child survival programmes, as did care–seeking within 24 hours and care–seeking from appropriate, trained providers in Mozambique. These approaches incorporated interpersonal communication activities and community empowerment/participation for collective change, partnerships and networks among key stakeholder groups within communities, media campaigns and advocacy efforts with local and national leaders. Conclusions iCCM programmes that train and equip community health workers and successfully engage and empower community members to adopt new behaviours, have appropriate expectations and to trust community health workers’ ability to assess and treat illnesses can lead to improved care–seeking and utilisation, and community ownership for iCCM. PMID:25520800

  10. Overcoming roadblocks: current and emerging reimbursement strategies for integrated mental health services in primary care.

    PubMed

    O'Donnell, Allison N; Williams, Mark; Kilbourne, Amy M

    2013-12-01

    The Chronic Care Model (CCM) has been shown to improve medical and psychiatric outcomes for persons with mental disorders in primary care settings, and has been proposed as a model to integrate mental health care in the patient-centered medical home under healthcare reform. However, the CCM has not been widely implemented in primary care settings, primarily because of a lack of a comprehensive reimbursement strategy to compensate providers for day-to-day provision of its core components, including care management and provider decision support. Drawing upon the existing literature and regulatory guidelines, we provide a critical analysis of challenges and opportunities in reimbursing CCM components under the current fee-for-service system, and describe an emerging financial model involving bundled payments to support core CCM components to integrate mental health treatment into primary care settings. Ultimately, for the CCM to be used and sustained over time to integrate physical and mental health care, effective reimbursement models will need to be negotiated across payers and providers. Such payments should provide sufficient support for primary care providers to implement practice redesigns around core CCM components, including care management, measurement-based care, and mental health specialist consultation.

  11. Algal and aquatic plant carbon concentrating mechanisms in relation to environmental change.

    PubMed

    Raven, John A; Giordano, Mario; Beardall, John; Maberly, Stephen C

    2011-09-01

    Carbon dioxide concentrating mechanisms (also known as inorganic carbon concentrating mechanisms; both abbreviated as CCMs) presumably evolved under conditions of low CO(2) availability. However, the timing of their origin is unclear since there are no sound estimates from molecular clocks, and even if there were, there are no proxies for the functioning of CCMs. Accordingly, we cannot use previous episodes of high CO(2) (e.g. the Palaeocene-Eocene Thermal Maximum) to indicate how organisms with CCMs responded. Present and predicted environmental change in terms of increased CO(2) and temperature are leading to increased CO(2) and HCO(3)(-) and decreased CO(3)(2-) and pH in surface seawater, as well as decreasing the depth of the upper mixed layer and increasing the degree of isolation of this layer with respect to nutrient flux from deeper waters. The outcome of these forcing factors is to increase the availability of inorganic carbon, photosynthetic active radiation (PAR) and ultraviolet B radiation (UVB) to aquatic photolithotrophs and to decrease the supply of the nutrients (combined) nitrogen and phosphorus and of any non-aeolian iron. The influence of these variations on CCM expression has been examined to varying degrees as acclimation by extant organisms. Increased PAR increases CCM expression in terms of CO(2) affinity, whilst increased UVB has a range of effects in the organisms examined; little relevant information is available on increased temperature. Decreased combined nitrogen supply generally increases CO(2) affinity, decreased iron availability increases CO(2) affinity, and decreased phosphorus supply has varying effects on the organisms examined. There are few data sets showing interactions amongst the observed changes, and even less information on genetic (adaptation) changes in response to the forcing factors. In freshwaters, changes in phytoplankton species composition may alter with environmental change with consequences for frequency of species with or without CCMs. The information available permits less predictive power as to the effect of the forcing factors on CCM expression than for their overall effects on growth. CCMs are currently not part of models as to how global environmental change has altered, and is likely to further alter, algal and aquatic plant primary productivity.

  12. Evaluation of stability of interface between CCM (Co-Cr-Mo) UCLA abutment and external hex implant.

    PubMed

    Yoon, Ki-Joon; Park, Young-Bum; Choi, Hyunmin; Cho, Youngsung; Lee, Jae-Hoon; Lee, Keun-Woo

    2016-12-01

    The purpose of this study is to evaluate the stability of interface between Co-Cr-Mo (CCM) UCLA abutment and external hex implant. Sixteen external hex implant fixtures were assigned to two groups (CCM and Gold group) and were embedded in molds using clear acrylic resin. Screw-retained prostheses were constructed using CCM UCLA abutment and Gold UCLA abutment. The external implant fixture and screw-retained prostheses were connected using abutment screws. After the abutments were tightened to 30 Ncm torque, 5 kg thermocyclic functional loading was applied by chewing simulator. A target of 1.0 × 10 6 cycles was applied. After cyclic loading, removal torque values were recorded using a driving torque tester, and the interface between implant fixture and abutment was evaluated by scanning electronic microscope (SEM). The means and standard deviations (SD) between the CCM and Gold groups were analyzed with independent t-test at the significance level of 0.05. Fractures of crowns, abutments, abutment screws, and fixtures and loosening of abutment screws were not observed after thermocyclic loading. There were no statistically significant differences at the recorded removal torque values between CCM and Gold groups ( P >.05). SEM analysis revealed that remarkable wear patterns were observed at the abutment interface only for Gold UCLA abutments. Those patterns were not observed for other specimens. Within the limit of this study, CCM UCLA abutment has no statistically significant difference in the stability of interface with external hex implant, compared with Gold UCLA abutment.

  13. Development Challenges of Utilizing a Corner Cube Mechanism Design with Successful IASI Flight Heritage for the Infrared Sounder (IRS) on MTG: Recurrent Mechanical Design not Correlated to Recurrent Development

    NASA Astrophysics Data System (ADS)

    Spanoudakis, Peter; Schwab, Philippe; Kiener, Lionel; Saudan, Herve; Perruchoud, Gerald

    2015-09-01

    The Corner Cube Mechanism (CCM) design for the Infra-Red Sounder (IRS) on MTG is based on the successful mechanism currently in orbit on the Infrared Atmospheric Sounding Interferometers (IASI) on the Metop satellites. The overall CCM performance is described with attention given to the specific design developments for the MTG project. A description is presented of the modifications introduced and challenges encountered to adapt the IASI space heritage design (which is only 15 years old) to meet the MTG specifications. A detailed account is provided regarding the tests performed on the adapted components for the new programme. The major issues encountered and solutions proposed are illustrated concerning the voice- coil actuator development, optical switch design, fatigue life of the flexure components and the adaptation of the launch locking device. Nevertheless, an Engineering Qualification Model was rapidly manufactured and now undergoing a qualification test campaign.

  14. PUPTH Prehospital Air Medical Plasma (PAMP) Trial

    DTIC Science & Technology

    2014-07-01

    collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for...projects. Scott Gunn, MD, is an Associate Professor of CCM and Emergency Medicine and Director , Combined Emergency Medicine/Internal Medicine/CCM...Residency Program. Dr. Gunn is also Director of the CCM Clinical Trials Program. As such, he is experienced in the design and monitoring of clinical trials

  15. Strengthening the primary care workforce to deliver community case management for child health in rural Indonesia.

    PubMed

    Setiawan, Agus; Dawson, Angela

    2017-10-02

    Objectives The aim of the present study was to report on the implementation of community case management (CCM) to reduce infant mortality in a rural district, namely Kutai Timur, Kalimantan Indonesia. Methods An interpretive qualitative methodology was used. In-depth interviews were conducted with 18 primary healthcare workers (PHCWs), and PHCWs were observed during a consultation with mothers to gain insight into the delivery of the new protocol and workforce issues. The field notes and interview transcripts were analysed thematically. Results PHCWs reported that their performance had improved as a result of increased knowledge and confidence. The implementation of CCM had also reportedly enhanced the PHCWs' clinical reasoning. However, the participants noted confusion surrounding their role in prescribing medication. Conclusions CCM is viewed as a useful model of care in terms of enhancing the capacity of rural PHCWs to provide child health care and improve the uptake of life-saving interventions. However, work is needed to strengthen the workforce and to fully integrate CCM into maternal and child health service delivery across Indonesia. What is known about the topic? Indonesia has successfully reduced infant mortality in the past 10 years. However, concerns remain regarding issues related to disparities between districts. The number of infant deaths in rural areas tends to be staggeringly high compared with that in the cities. One of the causes is inadequate access to child health care. What does this paper add? CCM is a model of care that is designed to address childhood illnesses in limited-resource settings. In CCM, PHCWs are trained to deliver life-saving interventions to sick children in rural communities. In the present study, CCM improved the capacity of PHCWs to treat childhood illnesses. What are the implications for practitioners? CCM can be considered to strengthen PHCWs' competence in addressing infant mortality in areas where access to child health care is challenging. Policy regarding task shifting needs to be examined further so that CCM can be integrated into current health service delivery in Indonesia.

  16. Global water cycle

    NASA Technical Reports Server (NTRS)

    Robertson, Franklin R.; Christy, John R.; Goodman, Steven J.; Miller, Tim L.; Fitzjarrald, Dan; Lapenta, Bill; Wang, Shouping

    1991-01-01

    The primary objective is to determine the scope and interactions of the global water cycle with all components of the Earth system and to understand how it stimulates and regulates changes on both global and regional scales. The following subject areas are covered: (1) water vapor variability; (2) multi-phase water analysis; (3) diabatic heating; (4) MSU (Microwave Sounding Unit) temperature analysis; (5) Optimal precipitation and streamflow analysis; (6) CCM (Community Climate Model) hydrological cycle; (7) CCM1 climate sensitivity to lower boundary forcing; and (8) mesoscale modeling of atmosphere/surface interaction.

  17. The Impact of Posttraumatic Stress Disorder on the 6-Month Outcomes in Collaborative Care Management for Depression.

    PubMed

    Angstman, Kurt B; Marcelin, Alberto; Gonzalez, Cesar A; Kaufman, Tara K; Maxson, Julie A; Williams, Mark D

    2016-07-01

    Posttraumatic stress disorder (PTSD) has symptoms that exist along a spectrum that includes depression and the 2 disorders may coexist. Collaborative care management (CCM) has been successfully used in outpatient mental health management (especially depression and anxiety) with favorable outcomes. Despite this, there exist limited data on clinical impact of a diagnosis of PTSD on depression outcomes in CCM. The present study used a retrospective cohort design to examine the association of PTSD with depression outcomes among 2121 adult patients involved in CCM in a primary care setting. Using standardized self-report measures, baseline depression scores and 6-month outcome scores were evaluated. Seventy-six patients had a diagnosis of PTSD documented in their electronic medical record. Patients with PTSD reported more severe depressive symptoms at baseline (Patient Health Questionnaire-9 score of 17.9 vs 15.4, P < .001) than those without PTSD. Controlling for sociodemographic and clinical characteristics, a clinical diagnosis of PTSD was associated with lower odds (AOR = 0.457, CI = 0.274-0.760, P = .003) of remission at 6 months and was also associated with higher odds (AOR = 3.112, CI = 1.921-5.041, P < .001) of persistent depressive symptoms at 6 months after CCM. When coexisting with depression, a diagnosis of PTSD was associated with worse depression outcomes, when managed with CCM in primary care. Opportunities still exist for more aggressive management of depression in these patients to help improve remission as well as reduce persistent depressive symptoms. © The Author(s) 2016.

  18. CCM-C,Collins checks the middeck experiment

    NASA Image and Video Library

    1999-07-24

    S93-E-5016 (23 July 1999) --- Astronaut Eileen M. Collins, mission commander, checks on an experiment on Columbia's middeck during Flight Day 1 activity. The experiment is called the Cell Culture Model, Configuration C. Objectives of it are to validate cell culture models for muscle, bone and endothelial cell biochemical and functional loss induced by microgravity stress; to evaluate cytoskeleton, metabolism, membrane integrity and protease activity in target cells; and to test tissue loss pharmaceuticals for efficacy. The photo was recorded with an electronic still camera (ESC).

  19. Competition between cyanobacteria and green algae at low versus elevated CO2: who will win, and why?

    PubMed

    Ji, Xing; Verspagen, Jolanda M H; Stomp, Maayke; Huisman, Jef

    2017-06-01

    Traditionally, it has often been hypothesized that cyanobacteria are superior competitors at low CO2 and high pH in comparison with eukaryotic algae, owing to their effective CO2-concentrating mechanism (CCM). However, recent work indicates that green algae can also have a sophisticated CCM tuned to low CO2 levels. Conversely, cyanobacteria with the high-flux bicarbonate uptake system BicA appear well adapted to high inorganic carbon concentrations. To investigate these ideas we studied competition between three species of green algae and a bicA strain of the harmful cyanobacterium Microcystis aeruginosa at low (100 ppm) and high (2000 ppm) CO2. Two of the green algae were competitively superior to the cyanobacterium at low CO2, whereas the cyanobacterium increased its competitive ability with respect to the green algae at high CO2. The experiments were supported by a resource competition model linking the population dynamics of the phytoplankton species with dynamic changes in carbon speciation, pH and light. Our results show (i) that competition between phytoplankton species at different CO2 levels can be predicted from species traits in monoculture, (ii) that green algae can be strong competitors under CO2-depleted conditions, and (iii) that bloom-forming cyanobacteria with high-flux bicarbonate uptake systems will benefit from elevated CO2 concentrations. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  20. Eutectic superalloys by edge-defined, film-fed growth

    NASA Technical Reports Server (NTRS)

    Hurley, G. F.

    1975-01-01

    The feasibility of producing directionally solidified eutectic alloy composites by edge-defined, film-fed growth (EFG) was carried out. The three eutectic alloys which were investigated were gamma + delta, gamma/gamma prime + delta, and a Co-base TaC alloy containing Cr and Ni. Investigations into the compatibility and wettability of these metals with various carbides, borides, nitrides, and oxides disclosed that compounds with the largest (negative) heats of formation were most stable but poorest wetting. Nitrides and carbides had suitable stability and low contact angles but capillary rise was observed only with carbides. Oxides would not give capillary rise but would probably fulfill the other wetting requirements of EFG. Tantalum carbide was selected for most of the experimental portion of the program based on its exhibiting spontaneous capillary rise and satisfactory slow rate of degradation in the liquid metals. Samples of all three alloys were grown by EFG with the major experimental effort restricted to gamma + delta and gamma/gamma prime + delta alloys. In the standard, uncooled EFG apparatus, the thermal gradient was inferred from the growth speed and was 150 to 200 C/cm. This value may be compared to typical gradients of less than 100 C/cm normally achieved in a standard Bridgman-type apparatus. When a stream of helium was directed against the side of the bar during growth, the gradient was found to improve to about 250 C/cm. In comparison, a theoretical gradient of 700 C/cm should be possible under ideal conditions, without the use of chills. Methods for optimizing the gradient in EFG are discussed, and should allow attainment of close to the theoretical for a particular configuration.

  1. Evaluation of stability of interface between CCM (Co-Cr-Mo) UCLA abutment and external hex implant

    PubMed Central

    Yoon, Ki-Joon; Park, Young-Bum; Choi, Hyunmin; Cho, Youngsung; Lee, Jae-Hoon

    2016-01-01

    PURPOSE The purpose of this study is to evaluate the stability of interface between Co-Cr-Mo (CCM) UCLA abutment and external hex implant. MATERIALS AND METHODS Sixteen external hex implant fixtures were assigned to two groups (CCM and Gold group) and were embedded in molds using clear acrylic resin. Screw-retained prostheses were constructed using CCM UCLA abutment and Gold UCLA abutment. The external implant fixture and screw-retained prostheses were connected using abutment screws. After the abutments were tightened to 30 Ncm torque, 5 kg thermocyclic functional loading was applied by chewing simulator. A target of 1.0 × 106 cycles was applied. After cyclic loading, removal torque values were recorded using a driving torque tester, and the interface between implant fixture and abutment was evaluated by scanning electronic microscope (SEM). The means and standard deviations (SD) between the CCM and Gold groups were analyzed with independent t-test at the significance level of 0.05. RESULTS Fractures of crowns, abutments, abutment screws, and fixtures and loosening of abutment screws were not observed after thermocyclic loading. There were no statistically significant differences at the recorded removal torque values between CCM and Gold groups (P>.05). SEM analysis revealed that remarkable wear patterns were observed at the abutment interface only for Gold UCLA abutments. Those patterns were not observed for other specimens. CONCLUSION Within the limit of this study, CCM UCLA abutment has no statistically significant difference in the stability of interface with external hex implant, compared with Gold UCLA abutment. PMID:28018564

  2. Costing commodity and human resource needs for integrated community case management in thie differing community health strategies of Ethiopia, Kenya and Zambia.

    PubMed

    Nefdt, Rory; Ribaira, Eric; Diallo, Khassoum

    2014-10-01

    To ensure correct and appropriate funding is available, there is a need to estimate resource needs for improved planning and implementation of integrated Community Case Management (iCCM). To compare and estimate costs for commodity and human resource needs for iCCM, based on treatment coverage rates, bottlenecks and national targets in Ethiopia, Kenya and Zambia from 2014 to 2016. Resource needs were estimated using Ministry of Health (MoH) targets fronm 2014 to 2016 for implementation of case management of pneumonia, diarrhea and malaria through iCCM based on epidemiological, demographic, economic, intervention coverage and other health system parameters. Bottleneck analysis adjusted cost estimates against system barriers. Ethiopia, Kenya and Zambia were chosen to compare differences in iCCM costs in different programmatic implementation landscapes. Coverage treatment rates through iCCM are lowest in Ethiopia, followed by Kenya and Zambia, but Ethiopia had the greatest increases between 2009 and 2012. Deployment of health extension workers (HEWs) in Ethiopia is more advanced compared to Kenya and Zambia, which have fewer equivalent cadres (called commu- nity health workers (CHWs)) covering a smaller proportion of the population. Between 2014 and 2016, the propor- tion of treatments through iCCM compared to health centres are set to increase from 30% to 81% in Ethiopia, 1% to 18% in Kenya and 3% to 22% in Zambia. The total estimated cost of iCCM for these three years are USD 75,531,376 for Ethiopia, USD 19,839,780 for Kenya and USD 33,667,742 for Zambia. Projected per capita expen- diture for 2016 is USD 0.28 for Ethiopia, USD 0.20 in Kenya and USD 0.98 in Zambia. Commodity costs for pneumonia and diarrhea were a small fraction of the total iCCM budget for all three countries (less than 3%), while around 80% of the costs related to human resources. Analysis of coverage, demography and epidemiology data improves estimates of fimding requirements for iCCM. Bottleneck analysis adjusts cost estimates by including system barriers, thus reflecting a more accurate estimate of potential resource utilization. Adding pneumonia and diarrhea interventions to existing large scale community-based malaria case management programs is likely to require relatively small and nationally affordable investments. iCCM can be implemented for USD 0.09 to 0.98 per capita per annum, depending on the stage of scale-up and targets set by the MoH.

  3. [Development of a novel absorbable nanofiber chitosan-collagen membrane by electrospinning and the preliminary study on guided bone regeneration].

    PubMed

    Gao, B; Li, X J; Lin, M; Li, Y Y; Dong, Y

    2018-02-09

    Objective: To evaluate the application effect of nanofiber chitosan-collagen membrane (NCM) on guided bone regeneration (GBR). Methods: The mixture of collagen, chitosan, polyethylene oxide was used to make up the NCM by electrospinning, then the NCM was crosslinked by glutaraldehyde vapor. The physical property of the NCM was measured by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). MC3T3-E1 osteoblasts were cultured on NCM to characterize the biocompatibility. The effectiveness of four groups [contrast group, Bio-gide membrane (BGM), compressed chitosan-collagen menbrane (CCM), NCM/CCM] on bone regeneration were evaluated in critical-sized defects (diameter = 5 mm) in SD rats. Results: When the mixed solution consists of 4.0% collagen, 1.0% chitosan and 3.5% polyethylene oxide, the NCM could be validly fabricated by electrospinning. After cross-linking by glutaraldehyde vapor, the tensile strength and the stability of NCM in damp was enhanced. No cytotoxicity of the NCM was detected on MC3T3-E1 osteoblasts. In vivo study showed that the new bone regeneration ratio of NCM/CCM group was [(43.10±1.49)%], and this was similar to that of the group of BGM [(41.36±2.60)%] ( P> 0.05), but higher than that of the CCM group [(33.10±1.41)%] and the contrast group [(7.22±2.46)%] ( P< 0.05). Conclusions: The NCM can promote new bone regeneration effectively in GBR procedure.

  4. Dehalogenation of Haloalkanes by Mycobacterium tuberculosis H37Rv and Other Mycobacteria

    PubMed Central

    Jesenská, Andrea; Sedlác̆ek, Ivo; Damborský, Jir̆í

    2000-01-01

    Haloalkane dehalogenases convert haloalkanes to their corresponding alcohols by a hydrolytic mechanism. To date, various haloalkane dehalogenases have been isolated from bacteria colonizing environments that are contaminated with halogenated compounds. A search of current databases with the sequences of these known haloalkane dehalogenases revealed the presence of three different genes encoding putative haloalkane dehalogenases in the genome of the human parasite Mycobacterium tuberculosis H37Rv. The ability of M. tuberculosis and several other mycobacterial strains to dehalogenate haloaliphatic compounds was therefore studied. Intact cells of M. tuberculosis H37Rv were found to dehalogenate 1-chlorobutane, 1-chlorodecane, 1-bromobutane, and 1,2-dibromoethane. Nine isolates of mycobacteria from clinical material and four strains from a collection of microorganisms were found to be capable of dehalogenating 1,2-dibromoethane. Crude extracts prepared from two of these strains, Mycobacterium avium MU1 and Mycobacterium smegmatis CCM 4622, showed broad substrate specificity toward a number of halogenated substrates. Dehalogenase activity in the absence of oxygen and the identification of primary alcohols as the products of the reaction suggest a hydrolytic dehalogenation mechanism. The presence of dehalogenases in bacterial isolates from clinical material, including the species colonizing both animal tissues and free environment, indicates a possible role of parasitic microorganisms in the distribution of degradation genes in the environment. PMID:10618227

  5. On the utility of GPU accelerated high-order methods for unsteady flow simulations: A comparison with industry-standard tools

    NASA Astrophysics Data System (ADS)

    Vermeire, B. C.; Witherden, F. D.; Vincent, P. E.

    2017-04-01

    First- and second-order accurate numerical methods, implemented for CPUs, underpin the majority of industrial CFD solvers. Whilst this technology has proven very successful at solving steady-state problems via a Reynolds Averaged Navier-Stokes approach, its utility for undertaking scale-resolving simulations of unsteady flows is less clear. High-order methods for unstructured grids and GPU accelerators have been proposed as an enabling technology for unsteady scale-resolving simulations of flow over complex geometries. In this study we systematically compare accuracy and cost of the high-order Flux Reconstruction solver PyFR running on GPUs and the industry-standard solver STAR-CCM+ running on CPUs when applied to a range of unsteady flow problems. Specifically, we perform comparisons of accuracy and cost for isentropic vortex advection (EV), decay of the Taylor-Green vortex (TGV), turbulent flow over a circular cylinder, and turbulent flow over an SD7003 aerofoil. We consider two configurations of STAR-CCM+: a second-order configuration, and a third-order configuration, where the latter was recommended by CD-adapco for more effective computation of unsteady flow problems. Results from both PyFR and STAR-CCM+ demonstrate that third-order schemes can be more accurate than second-order schemes for a given cost e.g. going from second- to third-order, the PyFR simulations of the EV and TGV achieve 75× and 3× error reduction respectively for the same or reduced cost, and STAR-CCM+ simulations of the cylinder recovered wake statistics significantly more accurately for only twice the cost. Moreover, advancing to higher-order schemes on GPUs with PyFR was found to offer even further accuracy vs. cost benefits relative to industry-standard tools.

  6. On the utility of GPU accelerated high-order methods for unsteady flow simulations: A comparison with industry-standard tools

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vermeire, B.C., E-mail: brian.vermeire@concordia.ca; Witherden, F.D.; Vincent, P.E.

    First- and second-order accurate numerical methods, implemented for CPUs, underpin the majority of industrial CFD solvers. Whilst this technology has proven very successful at solving steady-state problems via a Reynolds Averaged Navier–Stokes approach, its utility for undertaking scale-resolving simulations of unsteady flows is less clear. High-order methods for unstructured grids and GPU accelerators have been proposed as an enabling technology for unsteady scale-resolving simulations of flow over complex geometries. In this study we systematically compare accuracy and cost of the high-order Flux Reconstruction solver PyFR running on GPUs and the industry-standard solver STAR-CCM+ running on CPUs when applied to amore » range of unsteady flow problems. Specifically, we perform comparisons of accuracy and cost for isentropic vortex advection (EV), decay of the Taylor–Green vortex (TGV), turbulent flow over a circular cylinder, and turbulent flow over an SD7003 aerofoil. We consider two configurations of STAR-CCM+: a second-order configuration, and a third-order configuration, where the latter was recommended by CD-adapco for more effective computation of unsteady flow problems. Results from both PyFR and STAR-CCM+ demonstrate that third-order schemes can be more accurate than second-order schemes for a given cost e.g. going from second- to third-order, the PyFR simulations of the EV and TGV achieve 75× and 3× error reduction respectively for the same or reduced cost, and STAR-CCM+ simulations of the cylinder recovered wake statistics significantly more accurately for only twice the cost. Moreover, advancing to higher-order schemes on GPUs with PyFR was found to offer even further accuracy vs. cost benefits relative to industry-standard tools.« less

  7. A causal loop analysis of the sustainability of integrated community case management in Rwanda.

    PubMed

    Sarriot, Eric; Morrow, Melanie; Langston, Anne; Weiss, Jennifer; Landegger, Justine; Tsuma, Laban

    2015-04-01

    Expansion of community health services in Rwanda has come with the national scale up of integrated Community Case Management (iCCM) of malaria, pneumonia and diarrhea. We used a sustainability assessment framework as part of a large-scale project evaluation to identify factors affecting iCCM sustainability (2011). We then (2012) used causal-loop analysis to identify systems determinants of iCCM sustainability from a national systems perspective. This allows us to develop three high-probability future scenarios putting the achievements of community health at risk, and to recommend mitigating strategies. Our causal loop diagram highlights both balancing and reinforcing loops of cause and effect in the national iCCM system. Financial, political and technical scenarios carry high probability for threatening the sustainability through: (1) reduction in performance-based financing resources, (2) political shocks and erosion of political commitment for community health, and (3) insufficient progress in resolving district health systems--"building blocks"--performance gaps. In a complex health system, the consequences of choices may be delayed and hard to predict precisely. Causal loop analysis and scenario mapping make explicit complex cause-and-effects relationships and high probability risks, which need to be anticipated and mitigated. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Resist characteristics with direct-write electron beam and SCALPEL exposure system

    NASA Astrophysics Data System (ADS)

    Sato, Mitsuru; Omori, Katsumi; Ishikawa, Kiyoshi; Nakayama, Toshimasa; Novembre, Anthony E.; Ocola, Leonidas E.

    1999-06-01

    High acceleration voltage electron beam exposure is one of the possible candidates for post-optical lithography. The use of electrons, instead of photons, avoids optical related problems such as the standing wave issues. However, resists must conform to certain needs for the SCALPEL system, such as exposure in a vacuum chamber with 100kv electron beams. Taking into account the challenging requirements of high resolution, high sensitivity, low bake dependency and no outgassing, TOK has been able to develop resists to meet most of the SCALPEL system needs. However, due to the nature of chemical amplification and the PEB dependency, as is the case with DUV resist which varies for different features, we must recommend different resist for multiple features such as dense lines, isolated lines and contact holes. TOK has designed an electron beam negative resist, EN-009, which demonstrate 100nm pattern resolution. The dose to print on the SCALPEL system is 5.0(mu) C/cm2. The electron beam positive resist, EP-004M, has been designed for line and space patterns. The dose to print on the SCALPEL system is 8.25(mu) C/cm2. The processing conditions are standard, using 0.26N developer. These are the lowest exposure energies reported to date for similar resolution on this exposure tools.

  9. In vivo collective cell migration requires an LPAR2-dependent increase in tissue fluidity.

    PubMed

    Kuriyama, Sei; Theveneau, Eric; Benedetto, Alexandre; Parsons, Maddy; Tanaka, Masamitsu; Charras, Guillaume; Kabla, Alexandre; Mayor, Roberto

    2014-07-07

    Collective cell migration (CCM) and epithelial-mesenchymal transition (EMT) are common to cancer and morphogenesis, and are often considered to be mutually exclusive in spite of the fact that many cancer and embryonic cells that have gone through EMT still cooperate to migrate collectively. Here we use neural crest (NC) cells to address the question of how cells that have down-regulated cell-cell adhesions can migrate collectively. NC cell dissociation relies on a qualitative and quantitative change of the cadherin repertoire. We found that the level of cell-cell adhesion is precisely regulated by internalization of N-cadherin downstream of lysophosphatidic acid (LPA) receptor 2. Rather than promoting the generation of single, fully mesenchymal cells, this reduction of membrane N-cadherin only triggers a partial mesenchymal phenotype. This intermediate phenotype is characterized by an increase in tissue fluidity akin to a solid-like-to-fluid-like transition. This change of plasticity allows cells to migrate under physical constraints without abolishing cell cooperation required for collectiveness. © 2014 Kuriyama et al.

  10. Chronic disease management for depression in US medical practices: results from the Health Tracking Physician Survey.

    PubMed

    Zafar, Waleed; Mojtabai, Ramin

    2011-07-01

    Chronic care model (CCM) envisages a multicomponent systematic remodeling of ambulatory care to improve chronic diseases management. Application of CCM in primary care management of depression has traditionally lagged behind the application of this model in management of other common chronic illnesses. In past research, the use of CCM has been operationalized by measuring the use of evidence-based organized care management processes (CMPs). To compare the use of CMPs in treatment of depression with the use of these processes in treatment of diabetes and asthma and to examine practice-level correlates of this use. Using data from the 2008 Health Tracking Physician Survey, a nationally representative sample of physicians in the United States, we compared the use of 5 different CMPs: written guidelines in English and other languages for self-management, availability of staff to educate patients about self-management, availability of nurse care managers for care coordination, and group meetings of patients with staff. We further examined the association of practice-level characteristics with the use of the 5 CMPs for management of depression. CMPs were more commonly used for management of diabetes and asthma than for depression. The use of CMPs for depression was more common in health maintenance organizations [adjusted odds ratios (AOR) ranging from 2.45 to 5.98 for different CMPs], in practices that provided physicians with feedback regarding quality of care to patients (AOR range, 1.42 to 1.69), and in practices with greater use of clinical information technology (AOR range, 1.06 to 1.11). The application of CMPs in management of depression continues to lag behind other common chronic conditions. Feedbacks on quality of care and expanded use of information technology may improve application of CMPs for depression care in general medical settings.

  11. Rapid crop cover mapping for the conterminous United States

    USGS Publications Warehouse

    Dahal, Devendra; Wylie, Bruce K.; Howard, Daniel

    2018-01-01

    Timely crop cover maps with sufficient resolution are important components to various environmental planning and research applications. Through the modification and use of a previously developed crop classification model (CCM), which was originally developed to generate historical annual crop cover maps, we hypothesized that such crop cover maps could be generated rapidly during the growing season. Through a process of incrementally removing weekly and monthly independent variables from the CCM and implementing a ‘two model mapping’ approach, we found it viable to generate conterminous United States-wide rapid crop cover maps at a resolution of 250 m for the current year by the month of September. In this approach, we divided the CCM model into one ‘crop type model’ to handle the classification of nine specific crops and a second, binary model to classify the presence or absence of ‘other’ crops. Under the two model mapping approach, the training errors were 0.8% and 1.5% for the crop type and binary model, respectively, while test errors were 5.5% and 6.4%, respectively. With spatial mapping accuracies for annual maps reaching upwards of 70%, this approach demonstrated a strong potential for generating rapid crop cover maps by the 1st of September.

  12. Hydrogenetic Ferromanganese Crusts of the California Continental Margin

    NASA Astrophysics Data System (ADS)

    Conrad, Tracey A.

    Hydrogenetic Ferromanganese (Fe-Mn) crusts grow from seawater and in doing so sequester elements of economic interest and serve as archives of past seawater chemistry. Ferromanganese crusts have been extensively studied in open-ocean environments. However, few studies have examined continent-proximal Fe-Mn crusts especially from the northeast Pacific. This thesis addresses Fe-Mn crusts within the northeast Pacific California continental margin (CCM), which is a dynamic geological and oceanographic environment. In the first of three studies, I analyzed the chemical and mineralogical composition of Fe-Mn crusts and show that continental-proximal processes greatly influence the chemistry and mineralogy of CCM Fe-Mn crusts. When compared to global open-ocean Fe-Mn crusts, CCM crusts have higher concentrations of iron, silica, and thorium with lower concentrations of many elements of economic interest including manganese, cobalt, and tellurium, among other elements. The mineralogy of CCM Fe-Mn crusts is also unique with more birnessite and todorokite present than found in open-ocean samples. Unlike open-ocean Fe-Mn crusts, carbonate-fluorapatite is not present in CCM crusts. This lack of phosphatization makes CCM Fe-Mn crusts excellent candidates for robust paleoceanography records. The second and third studies in this thesis use isotope geochemistry on select CCM Fe-Mn crusts from four seamounts in the CCM to study past terrestrial inputs into the CCM and sources and behavior of Pb and Nd isotopes over the past 7 million years along the northeast Pacific margin. The second study focuses on riverine inputs into the Monterey Submarine Canyon System and sources of the continental material. Osmium isotopes in the crusts are compared to the Cenozoic Os seawater curve to develop an age model for the samples that show the crusts range in age of initiation of crust growth from approximately 20 to 6 Myr. Lead and neodymium isotopes measured in select Fe-Mn crusts show that large amounts of terrestrial material entered the CCM via the Monterey Canyon from prior to 6.8+/-0.5 until 4.5 +/-0.5 Myr ago. These data combined with reconstructions of the paleo-coastline indicate that incision of the modern Monterey Canyon started around 7 Myr ago. Isotope plots of potential source regions indicate that the source of the material is the border of the southern Sierra Nevada and western Basin and Range. This answers a long-standing and fundamental question about the timing and formation of the Monterey Canyon, the dominant feature of the Monterey Bay. The third study presented here uses the differences in lead and neodymium isotopic values in CCM Fe-Mn crusts over time compared to open-ocean Pacific, North Pacific, and Arctic Ocean Fe-Mn crusts to identify regional time-series trends and sources for these important oceanographic tracers. I found that sediment fluxes and inputs of terrestrial material from North American rivers effects the lead and neodymium isotope composition of regional seawater.

  13. Development of membrane electrode assembly for high temperature proton exchange membrane fuel cell by catalyst coating membrane method

    NASA Astrophysics Data System (ADS)

    Liang, Huagen; Su, Huaneng; Pollet, Bruno G.; Pasupathi, Sivakumar

    2015-08-01

    Membrane electrode assembly (MEA), which contains cathode and anode catalytic layer, gas diffusion layers (GDL) and electrolyte membrane, is the key unit of a PEMFC. An attempt to develop MEA for ABPBI membrane based high temperature (HT) PEMFC is conducted in this work by catalyst coating membrane (CCM) method. The structure and performance of the MEA are examined by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and I-V curve. Effects of the CCM preparation method, Pt loading and binder type are investigated for the optimization of the single cell performance. Under 160 °C and atmospheric pressure, the peak power density of the MEA, with Pt loading of 0.5 mg cm-2 and 0.3 mg cm-2 for the cathode and the anode, can reach 277 mW cm-2, while a current density of 620 A cm-2 is delivered at the working voltage of 0.4 V. The MEA prepared by CCM method shows good stability operating in a short term durability test: the cell voltage maintained at ∼0.45 V without obvious drop when operated at a constant current density of 300 mA cm-2 and 160 °C under ambient pressure for 140 h.

  14. Thallium stimulates ethanol production in immortalized hippocampal neurons

    PubMed Central

    2017-01-01

    Lactate and ethanol (EtOH) were determined in cell culture medium (CCM) of immortalized hippocampal neurons (HN9.10e cell line) before and after incubation with Thallium (Tl). This cell line is a reliable, in vitro model of one of the most vulnerable regions of central nervous system. Cells were incubated for 48 h with three different single Tl doses: 1, 10, 100 μg/L (corresponding to 4.9, 49 and 490 nM, respectively). After 48 h, neurons were “reperfused” with fresh CCM every 24/48 h until 7 days after the treatment and the removed CCM was collected and analysed. Confocal microscopy was employed to observe morphological changes. EtOH was determined by head space—solid phase microextraction -gas chromatography -mass spectrometry (HS-SPME-GCMS), lactate by RP-HPLC with UV detection. Tl exposure had significant effects on neuronal growth rate and morphology. The damage degree was dose-dependent. In not exposed cells, EtOH concentration was 0.18 ± 0.013 mM, which represents about 5% of lactate concentration (3.4 ± 0.10 mM). After Tl exposure lactate and EtOH increased. In CCM of 100 and 10 μg/L Tl-treated cells, lactate increased 24 h after reperfusion up to 2 and 3.3 times the control value, respectively. In CCM of 10 and 100 μg/L Tl-treated cells 24 h after reperfusion, EtOH increased up to 0.3 and 0.58 mmol/L. respectively. These results are consistent with significant alterations in energy metabolism, despite the low doses of Tl employed and the relatively short incubation time. PMID:29161327

  15. Critical care medicine training and certification for emergency physicians.

    PubMed

    Huang, David T; Osborn, Tiffany M; Gunnerson, Kyle J; Gunn, Scott R; Trzeciak, Stephen; Kimball, Edward; Fink, Mitchell P; Angus, Derek C; Dellinger, R Phillip; Rivers, Emanuel P

    2005-09-01

    Demand for critical care services is increasing. Unless the supply of intensivists increases, critically ill patients will not have access to intensivists. Recent critical care society recommendations include increased graduate medical education support and expansion of the J-1 visa waiver program for foreign medical graduates. This article proposes additional recommendations, based on strengthening the relationship between emergency medicine and critical care medicine. Demand for critical care services is increasing. Unless the supply of intensivists increases, critically ill patients will not have access to intensivists. Recent critical care society recommendations include increased graduate medical education support and expansion of the J-1 visa waiver program for foreign medical graduates. This article proposes additional recommendations, based on strengthening the relationship between emergency medicine (EM) and critical care medicine (CCM). Critical care is a continuum that includes prehospital, emergency department (ED), and intensive care unit (ICU) care teams. Both EM and CCM require expertise in treating life-threatening acute illness, with many critically ill patients often presenting first to the ED. Increased patient volumes and acuity have resulted in longer ED lengths of stay and more critical care delivery in the ED. However, the majority of CCM fellowships do not accept EM residents, and those who successfully complete a fellowship do not have access to a U.S. certification exam in CCM. Despite these barriers, interest in CCM training among EM physicians is increasing. Dual EM/CCM-trained physicians not only will help alleviate the intensivist shortage but also will strengthen critical care delivery in the ED and facilitate coordination at the ED-ICU interface. We therefore propose that all accreditation bodies work cooperatively to create a route to CCM certification for emergency physicians who complete a critical care fellowship.

  16. The Chronic Care Model and Diabetes Management in US Primary Care Settings: A Systematic Review

    PubMed Central

    Stellefson, Michael; Stopka, Christine

    2013-01-01

    Introduction The Chronic Care Model (CCM) uses a systematic approach to restructuring medical care to create partnerships between health systems and communities. The objective of this study was to describe how researchers have applied CCM in US primary care settings to provide care for people who have diabetes and to describe outcomes of CCM implementation. Methods We conducted a literature review by using the Cochrane database of systematic reviews, CINAHL, and Health Source: Nursing/Academic Edition and the following search terms: “chronic care model” (and) “diabet*.” We included articles published between January 1999 and October 2011. We summarized details on CCM application and health outcomes for 16 studies. Results The 16 studies included various study designs, including 9 randomized controlled trials, and settings, including academic-affiliated primary care practices and private practices. We found evidence that CCM approaches have been effective in managing diabetes in US primary care settings. Organizational leaders in health care systems initiated system-level reorganizations that improved the coordination of diabetes care. Disease registries and electronic medical records were used to establish patient-centered goals, monitor patient progress, and identify lapses in care. Primary care physicians (PCPs) were trained to deliver evidence-based care, and PCP office–based diabetes self-management education improved patient outcomes. Only 7 studies described strategies for addressing community resources and policies. Conclusion CCM is being used for diabetes care in US primary care settings, and positive outcomes have been reported. Future research on integration of CCM into primary care settings for diabetes management should measure diabetes process indicators, such as self-efficacy for disease management and clinical decision making. PMID:23428085

  17. Analysis of Low-Speed Stall Aerodynamics of a Business Jets Wing Using STAR-CCM+

    NASA Technical Reports Server (NTRS)

    Bui, Trong

    2016-01-01

    Reynolds-Averaged Navier-Stokes (RANS) computational fluid dynamics (CFD) analysis was conducted: to study the low-speed stall aerodynamics of a GIII aircrafts swept wing modified with (1) a laminar-flow wing glove, or (2) a seamless flap. The stall aerodynamics of these two different wing configurations were analyzed and compared with the unmodified baseline wing for low-speed flight. The Star-CCM+ polyhedral unstructured CFD code was first validated for wing stall predictions using the wing-body geometry from the First AIAA CFD High-Lift Prediction Workshop.

  18. On the cradle of CCM research: discovery, development, and challenges ahead.

    PubMed

    Kaplan, Aaron

    2017-06-01

    Herein, 40 years after its discovery, I briefly and critically survey the development of ideas that propelled research on CO2-concentrating mechanisms (CCMs; a term proposed by Dean Price) of phytoplankton, mainly focusing on cyanobacteria. This is not a comprehensive review on CCM research, but a personal view on the past developments and challenges that lie ahead. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Shade compromises the photosynthetic efficiency of NADP-ME less than that of PEP-CK and NAD-ME C4 grasses.

    PubMed

    Sonawane, Balasaheb V; Sharwood, Robert E; Whitney, Spencer; Ghannoum, Oula

    2018-05-25

    The high energy cost and apparently low plasticity of C4 photosynthesis compared with C3 photosynthesis may limit the productivity and distribution of C4 plants in low light (LL) environments. C4 photosynthesis evolved numerous times, but it remains unclear how different biochemical subtypes perform under LL. We grew eight C4 grasses belonging to three biochemical subtypes [NADP-malic enzyme (NADP-ME), NAD-malic enzyme (NAD-ME), and phosphoenolpyruvate carboxykinase (PEP-CK)] under shade (16% sunlight) or control (full sunlight) conditions and measured their photosynthetic characteristics at both low and high light. We show for the first time that LL (during measurement or growth) compromised the CO2-concentrating mechanism (CCM) to a greater extent in NAD-ME than in PEP-CK or NADP-ME C4 grasses by virtue of a greater increase in carbon isotope discrimination (∆P) and bundle sheath CO2 leakiness (ϕ), and a greater reduction in photosynthetic quantum yield (Φmax). These responses were partly explained by changes in the ratios of phosphoenolpyruvate carboxylase (PEPC)/initial Rubisco activity and dark respiration/photosynthesis (Rd/A). Shade induced a greater photosynthetic acclimation in NAD-ME than in NADP-ME and PEP-CK species due to a greater Rubisco deactivation. Shade also reduced plant dry mass to a greater extent in NAD-ME and PEP-CK relative to NADP-ME grasses. In conclusion, LL compromised the co-ordination of the C4 and C3 cycles and, hence, the efficiency of the CCM to a greater extent in NAD-ME than in PEP-CK species, while CCM efficiency was less impacted by LL in NADP-ME species. Consequently, NADP-ME species are more efficient at LL, which could explain their agronomic and ecological dominance relative to other C4 grasses.

  20. Shade compromises the photosynthetic efficiency of NADP-ME less than that of PEP-CK and NAD-ME C4 grasses

    PubMed Central

    2018-01-01

    Abstract The high energy cost and apparently low plasticity of C4 photosynthesis compared with C3 photosynthesis may limit the productivity and distribution of C4 plants in low light (LL) environments. C4 photosynthesis evolved numerous times, but it remains unclear how different biochemical subtypes perform under LL. We grew eight C4 grasses belonging to three biochemical subtypes [NADP-malic enzyme (NADP-ME), NAD-malic enzyme (NAD-ME), and phosphoenolpyruvate carboxykinase (PEP-CK)] under shade (16% sunlight) or control (full sunlight) conditions and measured their photosynthetic characteristics at both low and high light. We show for the first time that LL (during measurement or growth) compromised the CO2-concentrating mechanism (CCM) to a greater extent in NAD-ME than in PEP-CK or NADP-ME C4 grasses by virtue of a greater increase in carbon isotope discrimination (∆P) and bundle sheath CO2 leakiness (ϕ), and a greater reduction in photosynthetic quantum yield (Φmax). These responses were partly explained by changes in the ratios of phosphoenolpyruvate carboxylase (PEPC)/initial Rubisco activity and dark respiration/photosynthesis (Rd/A). Shade induced a greater photosynthetic acclimation in NAD-ME than in NADP-ME and PEP-CK species due to a greater Rubisco deactivation. Shade also reduced plant dry mass to a greater extent in NAD-ME and PEP-CK relative to NADP-ME grasses. In conclusion, LL compromised the co-ordination of the C4 and C3 cycles and, hence, the efficiency of the CCM to a greater extent in NAD-ME than in PEP-CK species, while CCM efficiency was less impacted by LL in NADP-ME species. Consequently, NADP-ME species are more efficient at LL, which could explain their agronomic and ecological dominance relative to other C4 grasses. PMID:29659931

  1. Evaluation of cold chain monitoring in Kelantan, Malaysia.

    PubMed

    Hanjeet, K; Lye, M S; Sinniah, M; Schnur, A

    1996-01-01

    An analysis was carried out on a total of 883 cold chain monitor (CCM) cards, which had been attached to batches of poliomyelitis, measles, DPT (diphtheria, pertussis, tetanus) and hepatitis B vaccines, during their transport and storage from the central store in Kuala Lumpur to Kelantan, a state in north-eastern Malaysia; 234 freeze watches attached to hepatitis B vaccines were also analysed. The monitor cards and freeze watches were observed at six levels between the central store and the periphery during distribution of the vaccines, and a colour change in any of the four windows (A, B, C, D) on the CCM cards or the freeze watches was recorded. In addition, 33 unopened vials of oral poliovirus vaccine (OPV), collected from refrigerators in 29 health facilities in Kelantan, were tested for potency using the tissue culture infective dose 50 (TCID50) method; 14 of them (42%) did not meet the WHO criteria for potent vaccines. The results showed that at the final destination 13.4% of all cards remained white while a colour change to blue was observed in 65% in window A, 16.6% in window B, and 4.4% in window C; none had turned blue in window D indicating that the vaccine had not been subjected to temperatures > or = 34 degrees C for 2 hours. All but 2 of the 234 freeze watches had turned purple, which indicates exposure of the hepatitis B vaccines to temperatures below 0 degree C. These results will assist health planners to correct the weaknesses identified in the cold chain system.

  2. The Design of a Transparent Vertical Multizone Furnace: Application to Thermal Field Tuning and Crystal Growth

    NASA Technical Reports Server (NTRS)

    Duvual, Walter M. B.; Batur, Celal; Bennett, Robert J.

    1998-01-01

    We present an innovative design of a vertical transparent multizone furnace which can operate in the temperature range of 25 C to 750 C and deliver thermal gradients of 2 C/cm to 45 C/cm for the commercial applications to crystal growth. The operation of the eight zone furnace is based on a self-tuning temperature control system with a DC power supply for optimal thermal stability. We show that the desired thermal profile over the entire length of the furnace consists of a functional combination of the fundamental thermal profiles for each individual zone obtained by setting the set-point temperature for that zone. The self-tuning system accounts for the zone to zone thermal interactions. The control system operates such that the thermal profile is maintained under thermal load, thus boundary conditions on crystal growth ampoules can be predetermined prior to crystal growth. Temperature profiles for the growth of crystals via directional solidification, vapor transport techniques, and multiple gradient applications are shown to be easily implemented. The unique feature of its transparency and ease of programming thermal profiles make the furnace useful in scientific and commercial applications for determining the optimized process parameters for crystal growth.

  3. A faster Rubisco with potential to increase photosynthesis in crops.

    PubMed

    Lin, Myat T; Occhialini, Alessandro; Andralojc, P John; Parry, Martin A J; Hanson, Maureen R

    2014-09-25

    In photosynthetic organisms, D-ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the major enzyme assimilating atmospheric CO2 into the biosphere. Owing to the wasteful oxygenase activity and slow turnover of Rubisco, the enzyme is among the most important targets for improving the photosynthetic efficiency of vascular plants. It has been anticipated that introducing the CO2-concentrating mechanism (CCM) from cyanobacteria into plants could enhance crop yield. However, the complex nature of Rubisco's assembly has made manipulation of the enzyme extremely challenging, and attempts to replace it in plants with the enzymes from cyanobacteria and red algae have not been successful. Here we report two transplastomic tobacco lines with functional Rubisco from the cyanobacterium Synechococcus elongatus PCC7942 (Se7942). We knocked out the native tobacco gene encoding the large subunit of Rubisco by inserting the large and small subunit genes of the Se7942 enzyme, in combination with either the corresponding Se7942 assembly chaperone, RbcX, or an internal carboxysomal protein, CcmM35, which incorporates three small subunit-like domains. Se7942 Rubisco and CcmM35 formed macromolecular complexes within the chloroplast stroma, mirroring an early step in the biogenesis of cyanobacterial β-carboxysomes. Both transformed lines were photosynthetically competent, supporting autotrophic growth, and their respective forms of Rubisco had higher rates of CO2 fixation per unit of enzyme than the tobacco control. These transplastomic tobacco lines represent an important step towards improved photosynthesis in plants and will be valuable hosts for future addition of the remaining components of the cyanobacterial CCM, such as inorganic carbon transporters and the β-carboxysome shell proteins.

  4. Age of depressed patient does not affect clinical outcome in collaborative care management.

    PubMed

    Angstman, Kurt B; MacLaughlin, Kathy L; Rasmussen, Norman H; DeJesus, Ramona S; Katzelnick, David J

    2011-09-01

    Clinical response and remission for the treatment of depression has been shown to be improved utilizing collaborative care management (CCM). Prior studies have indicated that the presence of mental health comorbidities noted by self-rated screening tools at the intake for CCM are associated with worsening outcomes; few have examined directly the impact of age on clinical response and remission. The hypothesis was that when controlling for other mental health and demographic variables, the age of the patient at implementation of CCM does not significantly impact clinical outcome, and that CCM shows consistent efficacy across the adult age spectrum. We performed a retrospective chart analysis of a cohort of 574 patients with a clinical diagnosis of major depression (not dysthymia) treated in CCM who had 6 months of follow-up data. Using the age group as a categorical variable in logistic regression models demonstrated that while maintaining control of all other variables, age grouping remained a nonsignificant predictor of clinical response (P ≥ 0.1842) and remission (P ≥ 0.1919) after 6 months of treatment. In both models, a lower Generalized Anxiety Disorder-7 score and a negative Mood Disorder Questionnaire score were predictive of clinical response and remission. However, the initial Patient Health Questionnaire-9 score was a statistically significant predictor only for clinical remission (P = 0.0094), not for response (P = 0.0645), at 6 months. In a subset (n = 295) of the study cohort, clinical remission at 12 months was also not associated with age grouping (P ≥ 0.3355). The variables that were predictive of remission at 12 months were the presence of clinical remission at 6 months (odds ratio [OR], 7.4820; confidence interval [CI], 3.9301-14.0389; P < 0.0001), clinical response (with persistent symptoms) (OR, 2.7722; CI, 1.1950-6.4313; P = 0.0176), and a lower initial Patient Health Questionnaire-9 score (OR, 0.9121; CI, 0.8475-0.9816; P = 0.0140). Our study suggests that using CCM for depression treatment may transcend age-related differences in depression and result in positive outcomes regardless of age.

  5. Functional Traits for Carbon Access in Macrophytes

    PubMed Central

    Pfister, Catherine A.; Wootton, J. Timothy

    2016-01-01

    Understanding functional trait distributions among organisms can inform impacts on and responses to environmental change. In marine systems, only 1% of dissolved inorganic carbon in seawater exists as CO2. Thus the majority of marine macrophytes not only passively access CO2 for photosynthesis, but also actively transport CO2 and the more common bicarbonate (HCO3-, 92% of seawater dissolved inorganic carbon) into their cells. Because species with these carbon concentrating mechanisms (CCMs) are non-randomly distributed in ecosystems, we ask whether there is a phylogenetic pattern to the distribution of CCMs among algal species. To determine macrophyte traits that influence carbon uptake, we assessed 40 common macrophyte species from the rocky intertidal community of the Northeast Pacific Ocean to a) query whether macrophytes have a CCM and b) determine the evolutionary history of CCMs, using ancestral state reconstructions and stochastic character mapping based on previously published data. Thirty-two species not only depleted CO2, but also concentrated and depleted HCO3-, indicative of a CCM. While analysis of CCMs as a continuous trait in 30 families within Phylum Rhodophyta showed a significant phylogenetic signal under a Brownian motion model, analysis of CCMs as a discrete trait (presence or absence) indicated that red algal families are more divergent than expected in their CCM presence or absence; CCMs are a labile trait within the Rhodophyta. In contrast, CCMs were present in each of 18 Ochrophyta families surveyed, indicating that CCMs are highly conserved in the brown algae. The trait of CCM presence or absence was largely conserved within Families. Fifteen of 23 species tested also changed the seawater buffering capacity, or Total Alkalinity (TA), shifting DIC composition towards increasing concentrations of HCO3- and CO2 for photosynthesis. Manipulating the external TA of the local environment may influence carbon availability in boundary layers and areas of low water mixing, offering an additional mechanism to increase CO2 availability. PMID:27415005

  6. An Assessment of the Potential Predictability of Drought Over the United States Based on Climate Model Simulations with Specified SST

    NASA Technical Reports Server (NTRS)

    Schubert, Siegfried; Wang, Hailan; Suarez, Max; Koster, Randal

    2010-01-01

    The USCLIV AR working group on drought recently initiated a series of global climate model simulations forced with idealized SST anomaly patterns, designed to address a number of uncertainties regarding the impact of SST forcing and the role of land-atmosphere feedbacks on regional drought. The runs were done with several global atmospheric models including NASA/NSIPP-l, NCEP/GFS, GFDLlAM2, and NCAR CCM3 and CAM3.5. Specific questions that the runs are designed to address include: What are mechanisms that maintain drought across the seasonal cycle and from one year to the next. To what extent can droughts develop independently of ocean variability due to year-to-year memory that may be inherent to the land. What is the role of the different ocean basins? Here we focus on the potential predictability of drought conditions over the United States. Specific issues addressed include the seasonality and regionality of the signal-to-noise ratios associated with Pacific and Atlantic SST forcing, and the sensitivity of the results to the climatological stationary waves simulated by the different AGCMs.

  7. Universal versus conditional day 3 follow-up for children with non-severe unclassified fever at the community level in the Democratic Republic of the Congo: A cluster-randomized, community-based non-inferiority trial.

    PubMed

    Mullany, Luke C; van Boetzelaer, Elburg W; Gutman, Julie R; Steinhardt, Laura C; Ngoy, Pascal; Barbera Lainez, Yolanda; Wittcoff, Alison; Harvey, Steven A; Ho, Lara S

    2018-04-01

    The World Health Organization's integrated community case management (iCCM) guidelines recommend that all children presenting with uncomplicated fever and no danger signs return for follow-up on day 3 following the initial consultation on day 1. Such fevers often resolve rapidly, however, and previous studies suggest that expectant home care for uncomplicated fever can be safely recommended. We aimed to determine if a conditional follow-up visit was non-inferior to a universal follow-up visit for these children. We conducted a cluster-randomized, community-based non-inferiority trial among children 2-59 months old presenting to community health workers (CHWs) with non-severe unclassified fever in Tanganyika Province, Democratic Republic of the Congo. Clusters (n = 28) of CHWs were randomized to advise caregivers to either (1) return for a follow-up visit on day 3 following the initial consultation on day 1, regardless of illness resolution (as per current WHO guidelines; universal follow-up group) or (2) return for a follow-up visit on day 3 only if illness continued (conditional follow-up group). Children in both arms were assessed again at day 8, and classified as a clinical failure if fever (caregiver-reported), malaria, diarrhea, pneumonia, or decline of health status (development of danger signs, hospitalization, or death) was noted (failure definition 1). Alternative failure definitions were examined, whereby caregiver-reported fever was first restricted to caregiver-reported fever of at least 3 days (failure definition 2) and then replaced with fever measured via axillary temperature (failure definition 3). Study participants, providers, and investigators were not masked. Among 4,434 enrolled children, 4,141 (93.4%) met the per-protocol definition of receipt of the arm-specific advice from the CHW and a timely day 8 assessment (universal follow-up group: 2,210; conditional follow-up group: 1,931). Failure was similar (difference: -0.7%) in the conditional follow-up group (n = 188, 9.7%) compared to the universal follow-up group (n = 230, 10.4%); however, the upper bound of a 1-sided 95% confidence interval around this difference (-∞, 5.1%) exceeded the prespecified non-inferiority margin of 4.0% (non-inferiority p = 0.089). When caregiver-reported fever was restricted to fevers lasting ≥3 days, failure in the conditional follow-up group (n = 159, 8.2%) was similar to that in the universal follow-up group (n = 200, 9.1%) (difference: -0.8%; 95% CI: -∞, 4.1%; p = 0.053). If caregiver-reported fever was replaced by axillary temperature measurement in the definition of failure, failure in the conditional follow-up group (n = 113, 5.9%) was non-inferior to that in the universal follow-up group (n = 160, 7.2%) (difference: -1.4%; 95% CI: -∞, 2.5%; p = 0.012). In post hoc analysis, when the definition of failure was limited to malaria, diarrhea, pneumonia, development of danger signs, hospitalization, or death, failure in the conditional follow-up group (n = 108, 5.6%) was similar to that in the universal follow-up group (n = 147, 6.7%), and within the non-inferiority margin (95% CI: -∞, 2.9%; p = 0.017). Limitations include initial underestimation of the proportion of clinical failures as well as substantial variance in cluster-specific failure rates, reducing the precision of our estimates. In addition, heightened security concerns slowed recruitment in the final months of the study. We found that advising caregivers to return only if children worsened or remained ill on day 3 resulted in similar rates of caregiver-reported fever and other clinical outcomes on day 8, compared to advising all caregivers to return on day 3. Policy-makers could consider revising guidelines for management of uncomplicated fever within the iCCM framework. ClinicalTrials.gov NCT02595827.

  8. Value-based payment in implementing evidence-based care: the Mental Health Integration Program in Washington state.

    PubMed

    Bao, Yuhua; McGuire, Thomas G; Chan, Ya-Fen; Eggman, Ashley A; Ryan, Andrew M; Bruce, Martha L; Pincus, Harold Alan; Hafer, Erin; Unützer, Jürgen

    2017-01-01

    To assess the role of value-based payment (VBP) in improving fidelity and patient outcomes in community implementation of an evidence-based mental health intervention, the Collaborative Care Model (CCM). Retrospective study based on a natural experiment. We used the clinical tracking data of 1806 adult patients enrolled in a large implementation of the CCM in community health clinics in Washington state. VBP was initiated in year 2 of the program, creating a natural experiment. We compared implementation fidelity (measured by 3 process-of-care elements of the CCM) between patient-months exposed to VBP and patient-months not exposed to VBP. A series of regressions were estimated to check robustness of findings. We estimated a Cox proportional hazard model to assess the effect of VBP on time to achieving clinically significant improvement in depression (measured based on changes in depression symptom scores over time). Estimated marginal effects of VBP on fidelity ranged from 9% to 30% of the level of fidelity had there been no exposure to VBP (P <.05 for every fidelity measure). Improvement in fidelity in response to VBP was greater among providers with a larger patient panel and among providers with a lower level of fidelity at baseline. Exposure to VBP was associated with an adjusted hazard ratio of 1.45 (95% confidence interval, 1.04-2.03) for achieving clinically significant improvement in depression. VBP improved fidelity to key elements of the CCM, both directly incentivized and not explicitly incentivized by the VBP, and improved patient depression outcomes.

  9. Effect of different film packaging on microbial growth in minimally processed cactus pear (Opuntia ficus-indica).

    PubMed

    Palma, A; Mangia, N P; Fadda, A; Barberis, A; Schirra, M; D'Aquino, S

    2013-01-01

    Microorganisms are natural contaminants of fresh produce and minimally processed products, and contamination arises from a number of sources, including the environment, postharvest handling and processing. Fresh-cut products are particularly susceptible to microbial contaminations because of the changes occurring in the tissues during processing. In package gas composition of modified atmosphere packaging (MAP) in combination with low storage temperatures besides reducing physiological activity of packaged produce, can also delay pathogen growth. Present study investigated on the effect of MAPs, achieved with different plastic films, on microbial growth of minimally processed cactus pear (Opuntio ficus-indica) fruit. Five different plastic materials were used for packaging the manually peeled fruit. That is: a) polypropylene film (Termoplast MY 40 micron thickness, O2 transmission rate 300 cc/m2/24h); b) polyethylene film (Bolphane BHE, 11 micron thickness, O2 transmission rate 19000 cc/m2/24h); c) polypropylene laser-perforated films (Mach Packaging) with 8, 16 or 32 100-micron holes. Total aerobic psychrophilic, mesophilic microorganisms, Enterobacteriaceae, yeast, mould populations and in-package CO2, O2 and C2H4 were determined at each storage time. Different final gas compositions, ranging from 7.8 KPa to 17.1 KPa O2, and 12.7 KPa to 2.6 KPa CO2, were achieved with MY and micro perforated films, respectively. Differences were detected in the mesophilic, Enterobacteriaceae and yeast loads, while no difference was detected in psychrophilic microorganisms. At the end of storage, microbial load in fruits sealed with MY film was significantly lower than in those sealed with BHE and micro perforated films. Furthermore, fruits packed with micro-perforated films showed the highest microbial load. This occurrence may in part be related to in-package gas composition and in part to a continuous contamination of microorganisms through micro-holes.

  10. [Influence of tissue-specific superoxide dismutase genes expression in brain cells on Drosophila melanogaster sensitivity to oxidative stress and viability].

    PubMed

    Vitushynska, M V; Matiytsiv, N P; Chernyk, Y

    2015-01-01

    The study has shown that both functional gene knockout Sodl and Sod2 and their overexpression in neurons and glial tissue increase the sensitivity of Drosophila melanogaster to oxidative stress (OS) conditions. The lowest survival rate was only 20.5% in insects with Sod2 knockout in neurons. Comparative analysis of the survival curves showed that adults with altered tissue-specific expression of the studied genes had reduced average and maximum life span. Under OS conditions induced by 5% hydrogen peroxide the life spans of wild type Oregon R and transgenic insects were significantly reduced. Altered Sod gene expression in glial tissue leads to degenerative changes in Drosophila brain at the young age. During the aging of insects and the action of pro-oxidants increasing of neurodegenerative phenotype is observed.

  11. Assessment of data quality and reporting systems for underserved populations: the case of integrated community case management programs in Nigeria.

    PubMed

    Nyangara, Florence M; Hai, Tajrina; Zalisk, Kirsten; Ozor, Lynda; Ufere, Joy; Isiguzo, Chinwoke; Abubakar, Ibrahim Ndaliman

    2018-05-01

    Decision makers are searching for reliable data and best practices to support the implementation and scale-up of the integrated community case management (iCCM) programs in underserved areas to reduce under-five mortality in low-income countries. This study assesses data quality and reporting systems of the World Health Organization supported Rapid Access Expansion program implementing iCCM in Abia and Niger States, Nigeria. This cross-sectional study used data from 16 primary health facilities in both states. Data were collected through review of registers and monthly summary reports of 140 community-oriented resource persons (CORPs), assessments of the five dimensions of the data reporting systems and 46 key informant interviews with stakeholders. Data quality was assessed by availability, completeness and consistency. Each component of the reporting system was assessed on a 3-point scale (weak, satisfactory and strong). Results show that both the structure, functions and capabilities, as well as data collection and reporting tools dimensions of the reporting system were strong, scoring (2.80, 2.73) for Abia and (2.88, 2.75) for Niger, respectively. Data management processes and links with national reporting system components scored low 2 s, indicating fair strength. Data availability, completeness and consistency were found to be good, an indication of adequate training and supervision of CORPs and community health extension workers. Indicator definitions and reporting guidelines were the weakest dimension of the system due to lack of data reporting guidelines in both states. In conclusion, the results indicate satisfactory data reporting systems and good quality data during early implementation of iCCM programs in the two states. Hence, countries planning to adopt and implement iCCM programs should first develop structures, establish national standardized tools for collecting and reporting data, provide for adequate training and supervision of community health workers and develop reporting guidelines for all reporting levels to ensure data quality.

  12. Cerebral Cavernous Malformation

    MedlinePlus

    ... and individuals frequently have multiple CCMs found via magnetic resonance imaging. Individuals with CCM are faced with a diagnosis ... and individuals frequently have multiple CCMs found via magnetic resonance imaging. Individuals with CCM are faced with a diagnosis ...

  13. The possible evolution and future of CO2-concentrating mechanisms.

    PubMed

    Raven, John A; Beardall, John; Sánchez-Baracaldo, Patricia

    2017-06-01

    CO2-concentrating mechanisms (CCMs), based either on active transport of inorganic carbon (biophysical CCMs) or on biochemistry involving supplementary carbon fixation into C4 acids (C4 and CAM), play a major role in global primary productivity. However, the ubiquitous CO2-fixing enzyme in autotrophs, Rubisco, evolved at a time when atmospheric CO2 levels were very much higher than today and O2 was very low and, as CO2 and O2 approached (by no means monotonically), today's levels, at some time subsequently many organisms evolved a CCM that increased the supply of CO2 and decreased Rubisco oxygenase activity. Given that CO2 levels and other environmental factors have altered considerably between when autotrophs evolved and the present day, and are predicted to continue to change into the future, we here examine the drivers for, and possible timing of, evolution of CCMs. CCMs probably evolved when CO2 fell to 2-16 times the present atmospheric level, depending on Rubisco kinetics. We also assess the effects of other key environmental factors such as temperature and nutrient levels on CCM activity and examine the evidence for evolutionary changes in CCM activity and related cellular processes as well as limitations on continuity of CCMs through environmental variations. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Developing a medication communication framework across continuums of care using the Circle of Care Modeling approach.

    PubMed

    Kitson, Nicole A; Price, Morgan; Lau, Francis Y; Showler, Grey

    2013-10-17

    Medication errors are a common type of preventable errors in health care causing unnecessary patient harm, hospitalization, and even fatality. Improving communication between providers and between providers and patients is a key aspect of decreasing medication errors and improving patient safety. Medication management requires extensive collaboration and communication across roles and care settings, which can reduce (or contribute to) medication-related errors. Medication management involves key recurrent activities (determine need, prescribe, dispense, administer, and monitor/evaluate) with information communicated within and between each. Despite its importance, there is a lack of conceptual models that explore medication communication specifically across roles and settings. This research seeks to address that gap. The Circle of Care Modeling (CCM) approach was used to build a model of medication communication activities across the circle of care. CCM positions the patient in the centre of his or her own healthcare system; providers and other roles are then modeled around the patient as a web of relationships. Recurrent medication communication activities were mapped to the medication management framework. The research occurred in three iterations, to test and revise the model: Iteration 1 consisted of a literature review and internal team discussion, Iteration 2 consisted of interviews, observation, and a discussion group at a Community Health Centre, and Iteration 3 consisted of interviews and a discussion group in the larger community. Each iteration provided further detail to the Circle of Care medication communication model. Specific medication communication activities were mapped along each communication pathway between roles and to the medication management framework. We could not map all medication communication activities to the medication management framework; we added Coordinate as a separate and distinct recurrent activity. We saw many examples of coordination activities, for instance, Medical Office Assistants acting as a liaison between pharmacists and family physicians to clarify prescription details. Through the use of CCM we were able to unearth tacitly held knowledge to expand our understanding of medication communication. Drawing out the coordination activities could be a missing piece for us to better understand how to streamline and improve multi-step communication processes with a goal of improving patient safety.

  15. Developing a medication communication framework across continuums of care using the Circle of Care Modeling approach

    PubMed Central

    2013-01-01

    Background Medication errors are a common type of preventable errors in health care causing unnecessary patient harm, hospitalization, and even fatality. Improving communication between providers and between providers and patients is a key aspect of decreasing medication errors and improving patient safety. Medication management requires extensive collaboration and communication across roles and care settings, which can reduce (or contribute to) medication-related errors. Medication management involves key recurrent activities (determine need, prescribe, dispense, administer, and monitor/evaluate) with information communicated within and between each. Despite its importance, there is a lack of conceptual models that explore medication communication specifically across roles and settings. This research seeks to address that gap. Methods The Circle of Care Modeling (CCM) approach was used to build a model of medication communication activities across the circle of care. CCM positions the patient in the centre of his or her own healthcare system; providers and other roles are then modeled around the patient as a web of relationships. Recurrent medication communication activities were mapped to the medication management framework. The research occurred in three iterations, to test and revise the model: Iteration 1 consisted of a literature review and internal team discussion, Iteration 2 consisted of interviews, observation, and a discussion group at a Community Health Centre, and Iteration 3 consisted of interviews and a discussion group in the larger community. Results Each iteration provided further detail to the Circle of Care medication communication model. Specific medication communication activities were mapped along each communication pathway between roles and to the medication management framework. We could not map all medication communication activities to the medication management framework; we added Coordinate as a separate and distinct recurrent activity. We saw many examples of coordination activities, for instance, Medical Office Assistants acting as a liaison between pharmacists and family physicians to clarify prescription details. Conclusions Through the use of CCM we were able to unearth tacitly held knowledge to expand our understanding of medication communication. Drawing out the coordination activities could be a missing piece for us to better understand how to streamline and improve multi-step communication processes with a goal of improving patient safety. PMID:24134454

  16. CCM.FF-K3.2011: Final report for the CIPM key comparison of air speed, 0.5 m/s to 40 m/s

    NASA Astrophysics Data System (ADS)

    Müller, Harald; Caré, Isabelle; Lucas, Peter; Pachinger, Dietmar; Kurihara, Noboru; Lishui, Cui; Su, Chun-Min; Shinder, Iosif; Spazzini, Pier Giorgio

    2017-01-01

    The CCM.FF-K3.2011 comparison was organized for the purpose of determination of the degree of equivalence of the national standards for air speed over the range 0.5 m/s to 40 m/s. An ultrasonic anemometer and a Laser Doppler anemometer were used as transfer standards. Nine laboratories from three RMOs participated between July 2013 and July 2015—EURAMET: PTB, Germany; LNE-CETIAT, France; INRIM, Italy; VSL, The Netherlands; E+E, Austria; SIM: NIST, USA; APMP: NMIJ/AIST, Japan; NIM, China; CMS/ITRI, Chinese Taipei. The measurements were provided at ambient conditions. All results of independent participants were used in the determination of the key comparison reference value (KCRV) and the uncertainty of the KCRV. The reference value was determined at each air speed separately following `procedure A' presented by M G Cox. The degree of equivalence with the KCRV was calculated for each air speed and laboratory. Almost all reported results were consistent with the KCRV. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  17. Metabolomic Analysis of Key Central Carbon Metabolism Carboxylic Acids as Their 3-Nitrophenylhydrazones by UPLC/ESI-MS

    PubMed Central

    Han, Jun; Gagnon, Susannah; Eckle, Tobias; Borchers, Christoph H.

    2014-01-01

    Multiple hydroxy-, keto-, di-, and tri-carboxylic acids are among the cellular metabolites of central carbon metabolism (CCM). Sensitive and reliable analysis of these carboxylates is important for many biological and cell engineering studies. In this work, we examined 3-nitrophenylhydrazine as a derivatizing reagent and optimized the reaction conditions for the measurement of ten CCM related carboxylic compounds, including glycolate, lactate, malate, fumarate, succinate, citrate, isocitrate, pyruvate, oxaloacetate, and α-ketoglutarate as their 3-nitrophenylhydrazones using LC/MS with electrospray ionization. With the derivatization protocol which we have developed, and using negative-ion multiple reaction monitoring on a triple-quadrupole instrument, all of the carboxylates showed good linearity within a dynamic range of ca. 200 to more than 2000. The on-column limits of detection and quantitation were from high femtomoles to low picomoles. The analytical accuracies for eight of the ten analytes were determined to be between 89.5 to 114.8% (CV≤7.4%, n=6). Using a quadrupole time-of-flight instrument, the isotopic distribution patterns of these carboxylates, extracted from a 13C-labeled mouse heart, were successfully determined by UPLC/MS with full-mass detection, indicating the possible utility of this analytical method for metabolic flux analysis. In summary, this work demonstrates an efficient chemical derivatization LC/MS method for metabolomic analysis of these key CCM intermediates in a biological matrix. PMID:23580203

  18. The association between chronic care management and the quality of thrombosis care

    PubMed Central

    Drewes, H.W.; Baan, C.A.; Westert, G.P.; Meijboom, B.R.; Lambooij, M.

    2010-01-01

    Introduction The oral anticoagulant therapy (OAT), used to prevent thrombosis, is associated with substantial avoidable hospitalization. Aim Identify the associations between chronic care management and the quality of OAT as suggested by the chronic care model (CCM) of Wagner. Methods Regression analysis with data of 61 thrombosis clinics and inductive analysis with 63 interviews with health care professionals of 23 thrombosis clinics. Results Results show substantial differences between regions in the quality of thrombosis care and the CCM activities. However, the variation in quality of care was not associated with the differences in CCM activities. The inductive analysis indicates that there are problems in the cooperation between caregivers. Several preferred CCM activities (e.g., multidisciplinary protocol) as well as the barriers to implement these activities (e.g., conflicting interests) were put forward by the health care professionals. Conclusion It can be concluded that there is variation in quality of thrombosis care between regions. This variation could not be explained by the observed differences in CCM activities. However, fragmentation is a major source of inefficiency according to health care professionals. The paper concludes with suggestions to improve chronic care management for thrombosis.

  19. Flyback CCM inverter for AC module applications: iterative learning control and convergence analysis

    NASA Astrophysics Data System (ADS)

    Lee, Sung-Ho; Kim, Minsung

    2017-12-01

    This paper presents an iterative learning controller (ILC) for an interleaved flyback inverter operating in continuous conduction mode (CCM). The flyback CCM inverter features small output ripple current, high efficiency, and low cost, and hence it is well suited for photovoltaic power applications. However, it exhibits the non-minimum phase behaviour, because its transfer function from control duty to output current has the right-half-plane (RHP) zero. Moreover, the flyback CCM inverter suffers from the time-varying grid voltage disturbance. Thus, conventional control scheme results in inaccurate output tracking. To overcome these problems, the ILC is first developed and applied to the flyback inverter operating in CCM. The ILC makes use of both predictive and current learning terms which help the system output to converge to the reference trajectory. We take into account the nonlinear averaged model and use it to construct the proposed controller. It is proven that the system output globally converges to the reference trajectory in the absence of state disturbances, output noises, or initial state errors. Numerical simulations are performed to validate the proposed control scheme, and experiments using 400-W AC module prototype are carried out to demonstrate its practical feasibility.

  20. Comparison of manually produced and automated cross country movement maps using digital image processing techniques

    NASA Technical Reports Server (NTRS)

    Wynn, L. K.

    1985-01-01

    The Image-Based Information System (IBIS) was used to automate the cross country movement (CCM) mapping model developed by the Defense Mapping Agency (DMA). Existing terrain factor overlays and a CCM map, produced by DMA for the Fort Lewis, Washington area, were digitized and reformatted into geometrically registered images. Terrain factor data from Slope, Soils, and Vegetation overlays were entered into IBIS, and were then combined utilizing IBIS-programmed equations to implement the DMA CCM model. The resulting IBIS-generated CCM map was then compared with the digitized manually produced map to test similarity. The numbers of pixels comprising each CCM region were compared between the two map images, and percent agreement between each two regional counts was computed. The mean percent agreement equalled 86.21%, with an areally weighted standard deviation of 11.11%. Calculation of Pearson's correlation coefficient yielded +9.997. In some cases, the IBIS-calculated map code differed from the DMA codes: analysis revealed that IBIS had calculated the codes correctly. These highly positive results demonstrate the power and accuracy of IBIS in automating models which synthesize a variety of thematic geographic data.

  1. Effectiveness of two community-based strategies on disease knowledge and health behaviour regarding malaria, diarrhoea and pneumonia in Ghana.

    PubMed

    Escribano-Ferrer, Blanca; Gyapong, Margaret; Bruce, Jane; Narh Bana, Solomon A; Narh, Clement T; Allotey, Naa-Korkor; Glover, Roland; Azantilow, Charity; Bart-Plange, Constance; Sagoe-Moses, Isabella; Webster, Jayne

    2017-12-12

    Ghana has developed two community-based strategies that aim to increase access to quality treatment for malaria, diarrhoea and suspected pneumonia, and to improve household and family practices: integrated Community Case Management (iCCM) and Community-based Health Planning and Services (CHPS). The objective of the study was to assess the effectiveness of iCCM and CHPS on disease knowledge and health behaviour regarding malaria, diarrhoea and pneumonia. A household survey was conducted two and eight years after implementation of iCCM in the Volta and Northern Regions of Ghana respectively, and more than ten years of CHPS implementation in both regions. The study population included 1356 carers of children under- five years of age who had fever, diarrhoea and/or cough in the two weeks prior to the interview. Disease knowledge was assessed based on the knowledge of causes and identification of signs of severe disease and its association with the sources of health education messages received. Health behaviour was assessed based on reported prompt care seeking behaviour, adherence to treatment regime, utilization of mosquito nets and having improved sanitation facilities, and its association with the sources of health education messages received. Health education messages from community-based agents (CBAs) in the Northern Region were associated with the identification of at least two signs of severe malaria (adjusted Odds Ratio (OR) 1.8, 95%CI 1.0, 3.3, p = 0.04), two practices that can cause diarrhoea (adjusted OR 4.7, 95%CI 1.4, 15.5, p = 0.02) 0and two signs of severe pneumonia (adjusted OR 7.7, 95%CI2.2, 26.5, p = 0.01)-the later also associated with prompt care seeking behaviour (p = 0.04). In the Volta Region, receiving messages on diarrhoea from CHPS was associated with the identification of at least two signs of severe diarrhoea (adjusted OR 3.6, 95%CI 1.4, 9.0), p = 0.02). iCCM was associated with prompt care seeking behaviour in the Volta Region and CHPS with prompt care seeking behaviour in the Northern Region (p < 0.5). Both iCCM and CHPS were associated with disease knowledge and health behaviour, but this was more pronounced for iCCM and in the Northern Region. HBC should continue to be considered as the strategy through which community-IMCI is implemented.

  2. Transgenic tobacco plants with improved cyanobacterial Rubisco expression but no extra assembly factors grow at near wild-type rates if provided with elevated CO2

    PubMed Central

    Occhialini, Alessandro; Lin, Myat T.; Andralojc, P. John; Hanson, Maureen R.; Parry, Martin A. J.

    2015-01-01

    SUMMARY Introducing a carbon concentrating mechanism and a faster Rubisco from cyanobacteria into higher plant chloroplasts could improve photosynthetic performance by increasing the rate of CO2 fixation while decreasing losses caused by photorespiration. We previously demonstrated that tobacco plants will grow photoautotrophically using Synechococcus elongatus Rubisco, although the plants exhibited considerably slower growth than wild-type and required supplementary CO2. Because of concerns that vascular plant assembly factors might not be adequate for assembly of a cyanobacterial Rubisco, prior transgenic plants included the cyanobacterial chaperone RbcX or the carboxysomal protein CcmM35. Here we show that neither RbcX nor CcmM35 is needed for assembly of active cyanobacterial Rubisco. Furthermore, by altering the gene regulatory sequences on the Rubisco transgenes, cyanobacterial Rubisco expression was enhanced and the transgenic plants grew at near wild-type growth rates, though still requiring elevated CO2. We performed detailed kinetic characterization of the enzymes produced with and without the RbcX and CcmM35 cyanobacterial proteins. These transgenic plants exhibit photosynthetic characteristics that confirm the predicted benefits of non-native forms of Rubisco with higher carboxylation rate constants in vascular plants and the potential nitrogen use efficiency that may be gained provided that adequate CO2 can be concentrated near the enzyme. PMID:26662726

  3. Final report on EURAMET.M.P-K4.2010: Key and supplementary comparison of national pressure standards in the range 1 Pa to 15 kPa of absolute and gauge pressure

    NASA Astrophysics Data System (ADS)

    Krajíček, Zdeněk; Bergoglio, Mercede; Jousten, Karl; Otal, Pierre; Sabuga, Wladimir; Saxholm, Sari; Pražák, Dominik; Vičar, Martin

    2014-01-01

    This report describes a EURAMET comparison of five European National Metrology Institutes in low gauge and absolute pressure in gas (nitrogen), denoted as EURAMET.M.P-K4.2010. Its main intention is to state equivalence of the pressure standards, in particular those based on the technology of force-balanced piston gauges such as e.g. FRS by Furness Controls, UK and FPG8601 by DHI-Fluke, USA. It covers the range from 1 Pa to 15 kPa, both gauge and absolute. The comparison in absolute mode serves as a EURAMET Key Comparison which can be linked to CCM.P-K4 and CCM.P-K2 via PTB. The comparison in gauge mode is a supplementary comparison. The comparison was carried out from September 2008 till October 2012. The participating laboratories were the following: CMI, INRIM, LNE, MIKES, PTB-Berlin (absolute pressure 1 kPa and below) and PTB-Braunschweig (absolute pressure 1 kPa and above and gauge pressure). CMI was the pilot laboratory and provided a transfer standard for the comparison. This transfer standard was also the laboratory standard of CMI at the same time, which resulted in a unique and logistically difficult star comparison. Both in gauge and absolute pressures all the participating institutes successfully proved their equivalence with respect to the reference value and all also proved mutual bilateral equivalences in all the points. All the participating laboratories are also equivalent with the reference values of CCM.P-K4 and CCM.P-K2 in the relevant points. The comparison also proved the ability of FPG8601 to serve as a transfer standard. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  4. Nationwide implementation of integrated community case management of childhood illness in Rwanda

    PubMed Central

    Mugeni, Catherine; Levine, Adam C; Munyaneza, Richard M; Mulindahabi, Epiphanie; Cockrell, Hannah C; Glavis-Bloom, Justin; Nutt, Cameron T; Wagner, Claire M; Gaju, Erick; Rukundo, Alphonse; Habimana, Jean Pierre; Karema, Corine; Ngabo, Fidele; Binagwaho, Agnes

    2014-01-01

    ABSTRACT Background: Between 2008 and 2011, Rwanda introduced integrated community case management (iCCM) of childhood illness nationwide. Community health workers in each of Rwanda's nearly 15,000 villages were trained in iCCM and equipped for empirical diagnosis and treatment of pneumonia, diarrhea, and malaria; for malnutrition surveillance; and for comprehensive reporting and referral services. Methods: We used data from the Rwanda health management information system (HMIS) to calculate monthly all-cause under-5 mortality rates, health facility use rates, and community-based treatment rates for childhood illness in each district. We then compared a 3-month baseline period prior to iCCM implementation with a seasonally matched comparison period 1 year after iCCM implementation. Finally, we compared the actual changes in all-cause child mortality and health facility use over this time period with the changes that would have been expected based on baseline trends in Rwanda. Results: The number of children receiving community-based treatment for diarrhea and pneumonia increased significantly in the 1-year period after iCCM implementation, from 0.83 cases/1,000 child-months to 3.80 cases/1,000 child-months (P = .01) and 0.25 cases/1,000 child-months to 5.28 cases/1,000 child-months (P<.001), respectively. On average, total under-5 mortality rates declined significantly by 38% (P<.001), and health facility use declined significantly by 15% (P = .006). These decreases were significantly greater than would have been expected based on baseline trends. Conclusions: This is the first study to demonstrate decreases in both child mortality and health facility use after implementing iCCM of childhood illness at a national level. While our study design does not allow for direct attribution of these changes to implementation of iCCM, these results are in line with those of prior studies conducted at the sub-national level in other low-income countries. PMID:25276592

  5. A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation in patients with systolic heart failure: rationale, design, and baseline patient characteristics.

    PubMed

    Abraham, William T; Burkhoff, Daniel; Nademanee, Koonlawee; Carson, Peter; Bourge, Robert; Ellenbogen, Kenneth A; Parides, Michael; Kadish, Alan

    2008-10-01

    Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the cardiac absolute refractory period that enhance the strength of cardiac muscular contraction. Prior research in experimental and human heart failure has shown that CCM signals normalize phosphorylation of key proteins and expression of genes coding for proteins involved in regulation of calcium cycling and contraction. The results of prior clinical studies of CCM have supported its safety and efficacy. A large-scale clinical study, the FIX-HF-5 study, is currently underway to test the safety and efficacy of this treatment. In this article, we provide an overview of the system used to deliver CCM signals, the implant procedure, and the details and rationale of the FIX-HF-5 study design. Baseline characteristics for patients randomized in this trial are also presented.

  6. Present-day Antarctic climatology of the NCAR Community Climate Model Version 1

    NASA Technical Reports Server (NTRS)

    Tzeng, Ren-Yow; Bromwich, David H.; Parish, Thomas R.

    1993-01-01

    The ability of the NCAR Community Climate Model Version 1 (CCM1) with R 15 resolution to simulate the present-day climate of Antarctica was evaluated using the five-year seasonal cycle output produced by the CCM1 and comparing the model results with observed horizontal syntheses and point data. The results showed that the CCM1 with R 15 resolution can simulate to some extent the dynamics of Antarctic climate on the synoptic scale as well as some mesoscale features. The model can also simulate the phase and the amplitude of the annual and semiannual variation of the temperature, sea level pressure, and zonally averaged zonal (E-W) wind. The main shortcomings of the CCM1 model are associated with the model's anomalously large precipitation amounts at high latitudes, due to the tendency of the scheme to suppress negative moisture values.

  7. Applying the chronic care model to an employee benefits program: a qualitative inquiry.

    PubMed

    Schauer, Gillian L; Wilson, Mark; Barrett, Barbara; Honeycutt, Sally; Hermstad, April K; Kegler, Michelle C

    2013-12-01

    To assess how employee benefits programs may strengthen and/or complement elements of the chronic care model (CCM), a framework used by health systems to improve chronic illness care. A qualitative inquiry consisting of semi-structured interviews with employee benefit administrators and partners from a self-insured, self-administered employee health benefits program was conducted at a large family-owned business in southwest Georgia. Results indicate that the employer adapted and used many health system-related elements of the CCM in the design of their benefit program. Data also suggest that the employee benefits program contributed to self-management skills and to informing and activating patients to interact with the health system. Findings suggest that employee benefits programs can use aspects of the CCM in their own benefit design, and can structure their benefits to contribute to patient-related elements from the CCM.

  8. The LDIFLARE and CCM methods demonstrate early nerve fibre abnormalities in untreated hypothyroidism: a prospective study.

    PubMed

    Sharma, Sanjeev; Tobin, Victoria; Vas, Prashant R J; Rayman, Gerry

    2018-05-31

    Recent studies using skin biopsy suggest presence of small fibre neuropathy in subclinical hypothyroidism. This study uses two novel non-invasive methods - the Laser Doppler imager (LDIFLARE) and Corneal confocal microscopy (CCM) - to assess small fibre function (SFF) and structure (SFS) respectively in newly diagnosed hypothyroidism (HT) before and after adequate treatment. Single-center, prospective, intervention-based cohort study. 20 patients with newly diagnosed HT- 15 primary and 5 post-radioiodine - along with 20 age-matched healthy controls (HC). Both HT and HC were assessed neurologically at diagnosis and baseline respectively. The HT group was reassessed after optimal replacement (defined as TSH:0.27-4.20mIU/L) with levothyroxine (LT4) while HC were reviewed at 1-year interval. Neurological assessment for small fibres was performed using the LDIFLARE for SFF and CCM for SFS while large fibres were studied by sural nerve conduction velocity (SNCV) and amplitude (SNAP). At baseline, compared to HC, both LDIFLARE (mean±SD) (6.74±1.20vs.8.90±1.75cm2; p=0.0002) and CCM-nerve fibre density (CNFD) (50.77±6.54vs.58.32±6.54no/mm2;p=0.002) were significantly reduced in HT whereas neither SNCV nor SNAP were different (p=>0.05). Following optimal LT4 treatment, both LDIFLARE (7.72±1.12vs.6.74±1.20 cm2; p=<0.0001) and CNFD (54.43±5.70vs.50.77±6.54no/mm2; p=0.02) improved significantly but remained significantly reduced compared to HC (p=0.008 and p=0.01 respectively) despite normalization of TSH. This study demonstrates that dysfunction of small fibres precedes large neural fibres in early hypothyroidism. This can be reversed by replacement therapy to achieve a biochemically euthyroid state but small fibres neural outcomes continued to be remain low when compared to HC.

  9. Comparison in gas media (absolute and gauge mode)in the range from 25 kPa TO 200 kPa (EURAMET.M.P-K8)

    NASA Astrophysics Data System (ADS)

    Wuethrich, C.; Alisic, S.; Altintas, A.; van Andel, I.; C, In­Mook; Eltawil, A. A.; Farár, P.; Hetherington, P.; Koçaş, I.; Lefkopoulos, A.; Otal, P.; Prazak, D.; Sabuga, W.; Salustiano, R.; Sandu, I.; Sardi, M.; Saxholm, S.; Setina, J.; Spohr, I.; Steindl, D.; Testa, N.; Vámossy, C.; Grgec Bermanec, L.

    2016-01-01

    It was decided at the EURAMET TC-M meeting in Torino in 2006 to realize a comparison in gauge and absolute pressure up to 200 kPa as it would allow a link to the CCM.P-K6 and CCM.P-K2 comparisons to be established. This project interested a lot of laboratories from the beginning with 23 participants, 22 of which have submitted results. The circulation of the transfer standard began in July 2009 and lasted until January 2012. No major problems occurred during the transport. The measurand of the comparison is the effective area of a piston-cylinder determined in gauge and absolute pressure from 25 kPa to 200 kPa with pressure steps of 25 kPa. The transfer standard is a gas lubricated tungsten carbide piston-cylinder with an effective area of ~9.8 cm2, fabricated by DH Instruments and compatible with a PG-7601 pressure balance. Some participants used their own pressure balance while a pressure balance with a reference vacuum sensor has been circulated for the participants not equipped with this system. One participant (SMU, Slovakia) has never provided the measurement results and another participant (FORCE Technology, Denmark) submitted a revised set of measurement results after the pilot laboratory mentioned that the equivalence was not met. After the determination of the reference value, all the 22 participants who delivered the results in gauge pressure demonstrated equivalence respective to the reference value on most of the range. In absolute pressure the equivalence is demonstrated, for all nominal pressures, by all 17 participants who submitted results. The comparison is linked to the CCM.P-K6 for gauge pressure and to CCM.P-K2 for absolute pressure. The link does not strongly affect the equivalence of the results and an excellent degree of equivalence is achieved in gauge and absolute pressure. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  10. Final report on the key comparison, CCM.M.P-K15.1 in the pressure range from 1.0 × 10-4 Pa to 1.0 Pa

    NASA Astrophysics Data System (ADS)

    Wuethrich, Christian; Hongyan, Yu

    2017-01-01

    At the CCM WG-LP meeting in Berlin in April 2011 the National Institute of Metrology of the people's republic of China asked for an opportunity to be linked to the CCM.M.P-K15 comparison which just ended. METAS, which had been active as pilot for the CCM.M.P-K15, agreed to make a link with NIM. The NIM introduced a new static expansion system in his laboratory. Two spinning rotor gauges and a control electronic are used as transfer standard. The circulation of the transfer standard was made in spring 2012. The drift of the accommodation coefficient of the two SRG was measured by the pilot before and after the comparison. The stability of the transfer standards was excellent and the equivalence between METAS and NIM has been demonstrated. A link to the CCM.M.P­K15 has been established using the results from METAS. It has been possible to achieve a link with a small uncertainty due to the strong correlation of the measurements of METAS in the two comparisons. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  11. Factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of congenital choledochal malformation: a retrospective case study in Southeast China

    PubMed Central

    Guo, Wan-liang; Zhan, Yang; Fang, Fang; Deng, Yan-bing; Zhao, Jun-gang

    2018-01-01

    Objective The aim of this study was to evaluate factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of congenital choledochal malformation (CCM). Design A 3-year retrospective study was undertaken between January 2013 and December 2015 in four centres in China. Setting This involved a retrospective chart review of paediatric patients with CCM in four large hospitals in Southeast China. Participants Sixty-five paediatric patients with CCM were included in this study. We derived all available information on patient demographics, clinical characteristics, preoperative complications and surgical methods from the charts of all these patients. Interventions Univariate and multivariate logistic regression analyses were used to evaluate factors significantly affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of CCM. Results Twenty-three of the 65 case surgeries were performed using laparoscopic technique, and 42 surgeries were performed by conventional open surgery. The median operating time was 215 min (range 120–430 min). The morphological subtype of CCM and the presence of cholecystitis or cholangitis were the only factors found to affect the operating time (p<0.05). Logistic regression analysis confirmed cholangitis as an independent risk factor. Conclusions The morphological subtype of CMM and the presence of cholecystitis or cholangitis are factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of CCM, whereas cholangitis is an independent risk factor. PMID:29804066

  12. Circle of care modelling: an approach to assist in reasoning about healthcare change using a patient-centric system.

    PubMed

    Price, Morgan

    2016-10-04

    Many health system and health Information and Communication Technology (ICT) projects do not achieve their expected benefits. This paper presents an approach to exploring changes in the healthcare system to better understand the expected improvements and other changes by using a patient-centric modelling approach. Circle of care modeling (CCM) was designed to assist stakeholders in considering healthcare system changes using a patient centric approach. The CCM approach is described. It includes four steps, based on soft systems methodology: finding out, conceptual modelling, structured discussion, and describing potential improvements. There are four visualizations that are used though this process: patient-persona based rich pictures of care flows (as part of finding out), and three models: provider view, communication view, and information repository view (as part of conceptual modelling). Three case studies are presented where CCM was applied to different real-world healthcare problems: 1. Seeking improvements in continuity of care for end of life patients. 2. Exploring current practices for medication communication for ambulatory patients prior to an update of a jurisdictional drug information system. 3. Deciding how to improve attachment of patients to primary care. The cases illustrate how CCM helped stakeholders reason from a patient centered approach about gaps and improvements in care such as: data fragmentation (in 1), coordination efforts of medication management (in 2), and deciding to support a community health centre for unattached patients (in 3). The circle of care modelling approach has proved to be a useful tool in assisting stakeholders explore health system change in a patient centric approach. It is one way to instantiate the important principle of being patient centered into practice when considering health system changes.

  13. Introducing an algal carbon-concentrating mechanism into higher plants: location and incorporation of key components.

    PubMed

    Atkinson, Nicky; Feike, Doreen; Mackinder, Luke C M; Meyer, Moritz T; Griffiths, Howard; Jonikas, Martin C; Smith, Alison M; McCormick, Alistair J

    2016-05-01

    Many eukaryotic green algae possess biophysical carbon-concentrating mechanisms (CCMs) that enhance photosynthetic efficiency and thus permit high growth rates at low CO2 concentrations. They are thus an attractive option for improving productivity in higher plants. In this study, the intracellular locations of ten CCM components in the unicellular green alga Chlamydomonas reinhardtii were confirmed. When expressed in tobacco, all of these components except chloroplastic carbonic anhydrases CAH3 and CAH6 had the same intracellular locations as in Chlamydomonas. CAH6 could be directed to the chloroplast by fusion to an Arabidopsis chloroplast transit peptide. Similarly, the putative inorganic carbon (Ci) transporter LCI1 was directed to the chloroplast from its native location on the plasma membrane. CCP1 and CCP2 proteins, putative Ci transporters previously reported to be in the chloroplast envelope, localized to mitochondria in both Chlamydomonas and tobacco, suggesting that the algal CCM model requires expansion to include a role for mitochondria. For the Ci transporters LCIA and HLA3, membrane location and Ci transport capacity were confirmed by heterologous expression and H(14) CO3 (-) uptake assays in Xenopus oocytes. Both were expressed in Arabidopsis resulting in growth comparable with that of wild-type plants. We conclude that CCM components from Chlamydomonas can be expressed both transiently (in tobacco) and stably (in Arabidopsis) and retargeted to appropriate locations in higher plant cells. As expression of individual Ci transporters did not enhance Arabidopsis growth, stacking of further CCM components will probably be required to achieve a significant increase in photosynthetic efficiency in this species. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  14. The Effects of an Integrated Community Case Management Strategy on the Appropriate Treatment of Children and Child Mortality in Kono District, Sierra Leone: A Program Evaluation.

    PubMed

    Ratnayake, Ruwan; Ratto, Jeffrey; Hardy, Colleen; Blanton, Curtis; Miller, Laura; Choi, Mary; Kpaleyea, John; Momoh, Pheabean; Barbera, Yolanda

    2017-09-01

    Integrated community case management (iCCM) aims to reduce child mortality in areas with poor access to health care. iCCM was implemented in 2009 in Kono district, Sierra Leone, a postconflict area with high under-five mortality rates (U5MRs). We evaluated iCCM's impact and effects on child health using cluster surveys in 2010 (midterm) and 2013 (endline) to compare indicators on child mortality, coverage of appropriate treatment, timely access to care, quality of care, and recognition of community health workers (CHWs). The sample size was powered to detect a 28% decline in U5MR. Clusters were selected proportional to population size. All households were sampled to measure mortality and systematic random sampling was used to measure coverage in a subset of households. We used program data to evaluate utilization and access; 5,257 (2010) and 3,649 (2013) households were surveyed. U5MR did not change significantly (4.54 [95% confidence interval [CI]: 3.47-5.60] to 3.95 [95% CI: 3.06-4.83] deaths per 1,000 per month ( P = 0.4)) though a relative change smaller than 28% could not be detected. CHWs were the first source of care for 52% (2010) and 50.9% (2013) of children. Coverage of appropriate treatment of fever by CHWs or peripheral health units increased from 45.5% [95% CI: 39.2-52.0] to 58.2% [95% CI: 50.5-65.5] ( P = 0.01); changes for diarrhea and pneumonia were not significant. The continued reliance on the CHW as the first source of care and improved coverage for the appropriate treatment of fever support iCCM's role in Kono district.

  15. Impact of Amazon deforestation on climate simulations using the NCAR CCM2/BATS model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hahmann, A.N.; Dickinson, R.E.

    Model validation and results are briefly presented for a simulation of deforestation of the Amazon rainforest. This initial study is made using assumptions regarding deforestation similar to those in earlier studies with several versions of the NCAR Community Climate Model (CCM) couples to the Biosphere-Atmosphere Transfer Scheme (BATS). The model used is a revised version of the NCAR CCM Version 2 coupled to BATS Version 1e. This paper discusses the portion of validation dealing with the distribution of precipitation; the simulation displays very good agreement with observed rainfall rates for the austral summer. Preliminary results from an 8-year simulation ofmore » deforestation are similar to that of previous studies. Annual precipitation and evaporation are reduced, while surface air temperatures show a slight increase. A substantial bimodal pattern appears in the results, with the Amazon decrease of precipitation and temperature increase accompanied by changes in the opposite sign to the southeast of the Amazon. Similar patterns have occurred in other studies, but not always in exactly the same locations. Evidently, how much of the region of rainfall increase occurs in the deforested area over the Amazon strongly affects the inferred statistics. It is likely that this pattern depends on the model control climatology and possibly other features. 16 refs., 2 figs., 2 tabs.« less

  16. Modeling and Observational Study of the Global Atmospheric Impacts of Antarctic Sea Ice Anomalies

    NASA Technical Reports Server (NTRS)

    Bromwich, David H.; Hines, Keith M.

    2004-01-01

    A combined observational and modeling study considers the linkage between Antarctic sea ice and the climate of non-local latitudes. The observational component is based upon analyses of monthly station observations and the National Centers for Environmental Prediction (NCEP)/National Center for Atmospheric Research (NCAR) Reanalysis (NNR). The modeling component consists of simulations of the NCAR Community Climate Model versions 2 (CCM2) and 3 (CCM3) and the recent Community Atmosphere Model (CAM2). A convenient mechanism for communication between the Antarctic region (particularly the Ross Sea area) and the tropics and Northern Hemisphere is examined. The first evidence of this teleconnection came from CCM2 simulations performed during an earlier NASA supported project. Annual-cycle simulations with and without Antarctic sea ice show statistically- significant responses in monsoon precipitation over central and northern China during the month of September. The changes in monsoon precipitation are physically consistent with an intensified southwest Pacific (Northern Hemisphere) subtropical high in response to all Antarctic sea ice being removed and replaced with open water at -1.9"C. The intensified high is the northernmost component of three primary anomalies. The southernmost anomaly includes the Ross Sea area, where sea ice has been removed. An earlier study by Peng and Domros had also found a link between Antarctic sea ice and the East Asian monsoon circulation. The current project has helped to understand the teleconnection.

  17. Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPβ-regulated atrogin1 expression in cancer cachexia.

    PubMed

    Sun, Rulin; Zhang, Santao; Hu, Wenjun; Lu, Xing; Lou, Ning; Yang, Zhende; Chen, Shaoyong; Zhang, Xiaoping; Yang, Hongmei

    2016-07-01

    Muscle wasting is the hallmark of cancer cachexia and is associated with poor quality of life and increased mortality. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has important biological effects in the treatment of muscular dystrophy. To verify whether VPA could ameliorate muscle wasting induced by cancer cachexia, we explored the role of VPA in two cancer cachectic mouse models [induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)] and atrophied C2C12 myotubes [induced by C26 cell conditioned medium (CCM) or LLC cell conditioned medium (LCM)]. Our data demonstrated that treatment with VPA increased the mass and cross-sectional area of skeletal muscles in tumor-bearing mice. Furthermore, treatment with VPA also increased the diameter of myotubes cultured in conditioned medium. The skeletal muscles in cachectic mice or atrophied myotubes treated with VPA exhibited reduced levels of CCAAT/enhancer binding protein beta (C/EBPβ), resulting in atrogin1 downregulation and the eventual alleviation of muscle wasting and myotube atrophy. Moreover, atrogin1 promoter activity in myotubes was stimulated by CCM via activating the C/EBPβ-responsive cis-element and subsequently inhibited by VPA. In contrast to the effect of VPA on the levels of C/EBPβ, the levels of inactivating forkhead box O3 (FoxO3a) were unaffected. In summary, VPA attenuated muscle wasting and myotube atrophy and reduced C/EBPβ binding to atrogin1 promoter locus in the myotubes. Our discoveries indicate that HDAC inhibition by VPA might be a promising new approach for the preservation of skeletal muscle in cancer cachexia. Copyright © 2016 the American Physiological Society.

  18. Completion of the mitochondrial genome sequence of onion (Allium cepa L.) containing the CMS-S male-sterile cytoplasm and identification of an independent event of the ccmF N gene split.

    PubMed

    Kim, Bongju; Kim, Kyunghee; Yang, Tae-Jin; Kim, Sunggil

    2016-11-01

    Cytoplasmic male-sterility (CMS) conferred by the CMS-S cytoplasm has been most commonly used for onion (Allium cepa L.) F 1 hybrid seed production. We first report the complete mitochondrial genome sequence containing CMS-S cytoplasm in this study. Initially, seven contigs were de novo assembled from 150-bp paired-end raw reads produced from the total genomic DNA using the Illumina NextSeq500 platform. These contigs were connected into a single circular genome consisting of 316,363 bp (GenBank accession: KU318712) by PCR amplification. Although all 24 core protein-coding genes were present, no ribosomal protein-coding genes, except rps12, were identified in the onion mitochondrial genome. Unusual trans-splicing of the cox2 gene was verified, and the cox1 gene was identified as part of the chimeric orf725 gene, which is a candidate gene responsible for inducing CMS. In addition to orf725, two small chimeric genes were identified, but no transcripts were detected for these two open reading frames. Thirteen chloroplast-derived sequences, with sizes of 126-13,986 bp, were identified in the intergenic regions. Almost 10 % of the onion mitochondrial genome was composed of repeat sequences. The vast majority of repeats were short repeats of <100 base pairs. Interestingly, the gene encoding ccmF N was split into two genes. The ccmF N gene split is first identified outside the Brassicaceae family. The breakpoint in the onion ccmF N gene was different from that of other Brassicaceae species. This split of the ccmF N gene was also present in 30 other Allium species. The complete onion mitochondrial genome sequence reported in this study would be fundamental information for elucidation of onion CMS evolution.

  19. Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel

    PubMed Central

    Al-Shahi Salman, Rustam; A. Awad, Issam; Dahlem, Kristen; Flemming, Kelly; Hart, Blaine; Kim, Helen; Jusue-Torres, Ignacio; Kondziolka, Douglas; Lee, Cornelia; Morrison, Leslie; Rigamonti, Daniele; Rebeiz, Tania; Tournier-Lasserve, Elisabeth; Waggoner, Darrel; Whitehead, Kevin

    2017-01-01

    Abstract BACKGROUND: Despite many publications about cerebral cavernous malformations (CCMs), controversy remains regarding diagnostic and management strategies. OBJECTIVE: To develop guidelines for CCM management. METHODS: The Angioma Alliance (www.angioma.org), the patient support group in the United States advocating on behalf of patients and research in CCM, convened a multidisciplinary writing group comprising expert CCM clinicians to help summarize the existing literature related to the clinical care of CCM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and radiology standards, (4) neurosurgical considerations, and (5) neurological considerations. The group reviewed literature, rated evidence, developed recommendations, and established consensus, controversies, and knowledge gaps according to a prespecified protocol. RESULTS: Of 1270 publications published between January 1, 1983 and September 31, 2014, we selected 98 based on methodological criteria, and identified 38 additional recent or relevant publications. Topic authors used these publications to summarize current knowledge and arrive at 23 consensus management recommendations, which we rated by class (size of effect) and level (estimate of certainty) according to the American Heart Association/American Stroke Association criteria. No recommendation was level A (because of the absence of randomized controlled trials), 11 (48%) were level B, and 12 (52%) were level C. Recommendations were class I in 8 (35%), class II in 10 (43%), and class III in 5 (22%). CONCLUSION: Current evidence supports recommendations for the management of CCM, but their generally low levels and classes mandate further research to better inform clinical practice and update these recommendations. The complete recommendations document, including the criteria for selecting reference citations, a more detailed justification of the respective recommendations, and a summary of controversies and knowledge gaps, was similarly peer reviewed and is available on line www.angioma.org/CCMGuidelines. PMID:28387823

  20. Comprehensive gene expression analysis of the NAC gene family under normal growth conditions, hormone treatment, and drought stress conditions in rice using near-isogenic lines (NILs) generated from crossing Aday Selection (drought tolerant) and IR64.

    PubMed

    Nuruzzaman, Mohammed; Sharoni, Akhter Most; Satoh, Kouji; Moumeni, Ali; Venuprasad, Ramiah; Serraj, Rachid; Kumar, Arvind; Leung, Hei; Attia, Kotb; Kikuchi, Shoshi

    2012-05-01

    The NAC (NAM, ATAF1/2 and CUC2) genes are plant-specific transcriptional factors known to play diverse roles in various plant developmental processes. We describe the rice (Oryza sativa) OsNAC genes expression profiles (GEPs) under normal and water-deficit treatments (WDTs). The GEPs of the OsNAC genes were analyzed in 25 tissues covering the entire life cycle of Minghui 63. High expression levels of 17 genes were demonstrated in certain tissues under normal conditions suggesting that these genes may play important roles in specific organs. We determined that 16 genes were differentially expressed under at least 1 phytohormone (NAA, GA3, KT, SA, ABA, and JA) treatment. To investigate the GEPs in the root, leaf, and panicle of three rice genotypes [e.g., 2 near-isogenic lines (NILs) and IR64], we used two NILs from a common genetic combination backcross developed by Aday Selection and IR64. WDTs were applied using the fraction of transpirable soil water at severe, mild, and control conditions. Transcriptomic analysis using a 44K oligoarray from Agilent was performed on all the tissue samples. We identified common and specific genes in all tissues from the two NILs under both WDTs, and the majority of the OsNAC genes that were activated were in the drought-tolerant IR77298-14-1-2-B-10 line compared with the drought-susceptible IR77298-14-1-2-B-13 or IR64. In IR77298-14-1-2-B-10, seventeen genes were very specific in their expression levels. Approximately 70 % of the genes from subgroups SNAC and NAM/CUC3 were activated in the leaf, but 37 % genes from subgroup SND were inactivated in the root compared with the control under severe stress conditions. These results provide a useful reference for the cloning of candidate genes from the specific subgroup for further functional analysis.

  1. Impact of tropical convection and ENSO variability in vertical distributions of CO and O3 over an urban site of India

    NASA Astrophysics Data System (ADS)

    Sahu, L. K.; Sheel, Varun; Kajino, M.; Deushi, M.; Gunthe, Sachin S.; Sinha, P. R.; Yadav, Ravi; Pal, Devendra; Nedelec, P.; Thouret, Valérie; Smit, Herman G.

    2017-07-01

    This study is based on the analysis of the measurement of ozone and water vapor by airbus in-service aircraft (MOZAIC) data of vertical ozone (O3) and carbon monoxide (CO) over Hyderabad during November 2005-March 2009. Measurements in the upper troposphere show highest values of O3 (53-75 ppbv) and CO (80-110 ppbv) during the pre-monsoon and post-monsoon seasons, respectively. The episodes of strong wind shears (>20 ms-1) were frequent during the monsoon/post-monsoon months, while weak shear conditions (<10 ms-1) were prevalent during the winter season. The profiles of both O3 and CO measured under southerly winds showed lower values than under northerly winds in each season. The strong and weak wind shears over the study region were associated with the El Niño and La Niña conditions, respectively. The outgoing long-wave radiation (OLR) and wind shear data indicate enhancement in the convective activity from monsoon to post-monsoon period. Higher levels of O3 were measured under the strong shear conditions, while CO and H2O show enhancements under weak shear conditions. The near surface observation and simulations show increase of O3 with increasing OLR, while insignificant relation in the upper region. In case of CO, the MOZAIC and CCM2 show weaker dependence while MOZART-4 shows rapid increase with OLR indicating large overestimation of convective transport. A modified Tiedtke convective scheme provides better representation compared to the Hack/Zhang-McFarlane schemes for both O3 and CO during the monsoon season. The difference between observation and simulations were particularly large during transition from El Niño to La Niña phases. The different convection scheme and horizontal resolution in the MOZART-4 and CCM2 seem to be the major causes of disagreement between these models. Vertical profiles of both O3 and CO during extreme events such a tropical cyclones (TCs) show strong influence of the convective-dynamics over Bay of Bengal (BOB).

  2. Laboratory Evaluation of Isaria fumosorosea CCM 8367 and Steinernema feltiae Ustinov against Immature Stages of the Colorado Potato Beetle

    PubMed Central

    Hussein, Hany M.; Skoková Habuštová, Oxana; Půža, Vladimír; Zemek, Rostislav

    2016-01-01

    The Colorado potato beetle, Leptinotarsa decemlineata, has developed resistance to most registered pesticides and has become one of the most difficult insect pests to control. Development of new biopesticides targeting this pest might solve the resistance problem and contribute to sustainable crop production. Laboratory experiments were conducted to assess the efficacy of Isaria fumosorosea (syn. Paecilomyces fumosoroseus) strain CCM 8367 against L. decemlineata when applied alone or combined with the entomopathogenic nematode Steinernema feltiae. The last-instar larvae of the Colorado potato beetle showed the highest susceptibility to I. fumosorosea followed by pre-pupae and pupae. The median lethal concentration (LC50) was estimated to be 1.03×106 blastospores/ml. The strain CCM 8367 was more virulent, causing 92.6% mortality of larvae (LT50 = 5.0 days) compared to the reference strain Apopka 97, which caused 54.5% mortality (LT50 = 7.0 days). The combined application of the fungus with the nematodes increased the mortality up to 98.0%. The best results were obtained when S. feltiae was applied simultaneously with I. fumosorosea (LT50 = 2.0 days); later application negatively affected both the penetration rate and the development of the nematodes. We can conclude that the strain CCM 8367 of I. fumosorosea is a prospective biocontrol agent against immature stages of L. decemlineata. For higher efficacy, application together with an entomopathogenic nematode is recommended. PMID:27015633

  3. Evaluation of cranial bone transport distraction with and without adipose grafting.

    PubMed

    Koch, Felix P; Yuhasz, Mikell M; Travieso, Rob; Wong, Kenneth; Clune, James; Zhuang, Zhen W; Van Houten, Joshua; Steinbacher, Derek M

    2014-05-01

    Transport distraction osteogenesis (DO) can be used to autologously reconstitute calvarial defects. The purpose of this study is to histomorphologically interrogate osteogenic formation during cranial transport distraction using a novel device. We also evaluate the effect of fat grafting on the regenerate and soft-tissue stability during distraction. This study was approved by Yale IACUC. Ten male New Zealand white rabbits (3 mo; 3.5 kg) were used (8 treatment, 2 control). A 16 × 16 mm defect was created abutted by a 10 × 16 mm transport disc. The device was fixated anterioposteriorly. Four animals were fat-grafted using 2 mL of subdermal intrascapular fat deposited along the distraction site. Latency (1 d), active distraction (12-14 d) (1.5 mm/d), and consolidation (4 wk) followed. Calcein and xylene orange fluorochromes were injected subcutaneously during and post-distraction to mark sites of bone formation. Following sacrifice, osteogenesis was assessed using microCT, histology, and fluorescence. Treatment animals demonstrated regenerate bone between distracted segments on microCT. MicroCT analysis of non-fat-grafted and fat-grafted animals revealed a mean density of 2271.95 mgHA/ccm and 2254.27 mgHA/ccm (P = 0.967), respectively, and defect bone versus total volume (BV/TV) of 0.0999 and 0.0766 (P = 0.5979), respectively. Controls had minimal reossification. Histologically, mean densities measured 43.63% and 8.19%, respectively. Fluorescence revealed ossification from the callus as well as from dura and periosteum in the cranial defect. Transport distraction is effective to reconstruct critically sized rabbit calvarial defects. Regenerate bone arises predominantly from the callus with contribution from surrounding dura and periosteum. Adipose grafting is well tolerated but does not enhance osseous regeneration.

  4. Description of the NCAR Community Climate Model (CCM3). Technical note

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kiehl, J.T.; Hack, J.J.; Bonan, G.B.

    This repor presents the details of the governing equations, physical parameterizations, and numerical algorithms defining the version of the NCAR Community Climate Model designated CCM3. The material provides an overview of the major model components, and the way in which they interact as the numerical integration proceeds. This version of the CCM incorporates significant improvements to the physic package, new capabilities such as the incorporation of a slab ocean component, and a number of enhancements to the implementation (e.g., the ability to integrate the model on parallel distributed-memory computational platforms).

  5. Validation of Slosh Modeling Approach Using STAR-CCM+

    NASA Technical Reports Server (NTRS)

    Benson, David J.; Ng, Wanyi

    2018-01-01

    Without an adequate understanding of propellant slosh, the spacecraft attitude control system may be inadequate to control the spacecraft or there may be an unexpected loss of science observation time due to higher slosh settling times. Computational fluid dynamics (CFD) is used to model propellant slosh. STAR-CCM+ is a commercially available CFD code. This paper seeks to validate the CFD modeling approach via a comparison between STAR-CCM+ liquid slosh modeling results and experimental, empirically, and analytically derived results. The geometries examined are a bare right cylinder tank and a right cylinder with a single ring baffle.

  6. Devitalization of bacterial and parasitic germs in sewage sludge during aerobic digestion under laboratory conditions.

    PubMed

    Juris, P; Plachý, P; Lauková, A

    1995-05-01

    The survival of 8 bacterial species (Pseudomonas sp., Salmonella sp., Enterobacteriae, Streptococcus sp., Escherichia coli) was detected in municipal sewage sludge up to 37 hours of mesophilic aerobic digestion under laboratory conditions. The model strain Enterococcus faecium CCM 4231 survived almost twice as long as the above-mentioned isolates. Similar findings, regarding the viability of the microorganisms studied, were also determined during thermophilic aerobic digestion of municipal sewage sludges. The final reduction in the total count of bacteria was not directly dependent on the temperature during aerobic digestion. It may be supposed that E. faecium CCM 4231 strain as a bacteriocin-producing strain with a broad antimicrobial spectrum, inoculated into the sludges, could inhibit the growth of microorganisms in the sludges by the way of its bacteriocin activity. Studying the effect of aerobic digestion on the viability of helminth eggs, the observed negative effect of higher temperatures was more expressive in comparison with bacterial strains. During thermophilic digestion process all helminth eggs (Ascaris suum, Toxocara canis) were devitalized. All eggs of T. canis were killed in experiments under mesophilic temperature. However, 32% of nonembryonated A. suum eggs remained viable.

  7. A demonstration of mobile phone deployment to support the treatment of acutely ill children under five in Bushenyi district, Uganda.

    PubMed

    Kabakyenga, Jerome; Barigye, Celestine; Brenner, Jennifer; Maling, Samuel; Buchner, Denise; Nettle-Aquirre, Alberto; Singhal, Nalini; Kyomuhangi, Teddy; Tumusiime, David; Finch, Janet; MacLeod, Stuart

    2016-03-01

    Benefits of mobile phone deployment for children <5 in low-resource settings remain unproven. The target population of the current demonstration study in Bushenyi District, Uganda, presented with acute fever, pneumonia, or diarrhoea and were treated by community health workers (CHWs) providing integrated community case management (iCCM). An observational study was conducted in five parishes (47 villages) served by CHWs well versed in iCCM with supplemental training in mobile phone use. Impact was assessed by quantitative measures and qualitative evaluation through household surveys, focus group discussions, and key informant interviews. CHWs in targeted sites improved child healthcare through mobile phone use coupled with iCCM. Of acutely ill children, 92.6% were correctly managed. Significant improvements in clinical outcomes compared to those obtained by CHWs with enhanced iCCM training alone were unproven in this limited demonstration. Nonetheless, qualitative evaluation showed gains in treatment planning, supply management, and logistical efficiency. Provider confidence and communications were enhanced as was ease and accuracy of record keeping. Mobile phones appear synergistic with iCCM to bolster basic supportive care for acutely ill children provided by CHWs. The full impact of expanded mobile phone deployment warrants further evaluation prior to scaling up in low-resource settings.

  8. [Tuscan Chronic Care Model: a preliminary analysis].

    PubMed

    Barbato, Angelo; Meggiolaro, Angela; Rossi, Luigi; Fioravanti, C; Palermita, F; La Torre, Giuseppe

    2015-01-01

    the aim of this study is to present a preliminary analysis of efficacy and effectiveness of a model of chronically ill care (Chronic Care Model, CCM). the analysis took into account 106 territorial modules, 1016 General Practitioners and 1,228,595 patients. The diagnostic and therapeutic pathways activated (PDTA), involved four chronic conditions, selected according to the prevalence and incidence, in Tuscany Region: Diabetes Mellitus (DM), Heart Failure (SC), Chronic Obstructive Pulmonary Disease (COPD) and stroke. Six epidemiological indicators of process and output were selected, in order to measure the model of care performed, before and after its application: adherence to specific follow-up for each pathology (use of clinical and laboratory indicators), annual average of expenditure per/capita/euro for diagnostic tests, in laboratory and instrumental, average expenditure per/capita/year for specialist visits; hospitalization rate for diseases related to the main pathology, hospitalization rate for long-term complications and rate of access to the emergency department (ED). Data were collected through the database; the differences before and after the intervention and between exposed and unexposed, were analyzed by method "Before-After (Controlled and Uncontrolled) Studies". The impact of the intervention was calculated as DD (difference of the differences). DM management showed an increased adhesion to follow-up (DD: +8.1%), and the use of laboratory diagnostics (DD: +4,9 €/year/pc), less hospitalization for long-term complications and for endocrine related diseases (DD respectively: 5.8/1000 and DD: +1.2/1000), finally a smaller increase of access to PS (DD: -1.6/1000), despite a slight increase of specialistic visits (DD: +0,38 €/year/pc). The management of SC initially showed a rising adherence to follow-up (DD: +2.3%), a decrease of specialist visits (DD:E 1.03 €/year/pc), hospitalization and access to PS for exacerbations (DD: -4.4/1000 and DD: -6.1/100, respectively), compared with a slight increase of diagnostic tests (DD: +2.10 €/year/pc). Stroke showed the following outcomes: increased consumption of instrumental diagnostics and imaging (DD: +1.65 €/year/pc) and growing hospitalizations for related conditions (DD 6.1/1,000). The care of patients with COPD, finally, has produced an increase in overall expenditure on medicines (DD: +39.71/year/pc) associated with the decrease of hospitalization for related conditions (DD: -2.7/1,000). the Tuscany CCM has proven a promising model of integrated management and taking care for chronic patients, can have a positive impact on the quality of life and on the total health expenditure. Additional monitoring studies are desirable in perspective of expanding the model on all over the national territory.

  9. A qualitative study on the experiences and perspectives of public sector patients in Cape Town in managing the workload of demands of HIV and type 2 diabetes multimorbidity.

    PubMed

    Matima, Rangarirai; Murphy, Katherine; Levitt, Naomi S; BeLue, Rhonda; Oni, Tolu

    2018-01-01

    Current South African health policy for chronic disease management proposes integration of chronic services for better outcomes for chronic conditions; that is based on the Integrated Chronic Disease Model (ICDM). However, scant data exist on how patients with chronic multimorbidities currently experience the (re)-organisation of health services and what their perceived needs are in order to enhance the management of their conditions. A qualitative study was conducted in a community health centre treating both HIV and diabetes patients in Cape Town. The study was grounded in the Shippee's Cumulative Complexity Model (CCM) and explored "patient workload" and "patient capacity" to manage chronic conditions. Individual interviews were conducted with 10 adult patient-participants with HIV and type two diabetes (T2D) multimorbidity and 6 healthcare workers who provided health services to these patient-participants. Patient-participants in this study experienced clinic-related workload such as: two separate clinics for HIV and T2D and perceived and experienced power mismatch between patients and healthcare workers. Self-care related workloads were largely around nutritional requirements, pill burden, and stigma. Burden of these demands varied in difficulty among patient-participants due to capacity factors such as: positive attitudes, optimal health literacy, social support and availability of economic resources. Strategies mentioned by participants for improved continuity of care and self-management of multi-morbidities included integration of chronic services, consolidated guidelines for healthcare workers, educational materials for patients, improved information systems and income for patients. Using the CCM to explore multimorbidity captured most of the themes around "patient workload" and "patient capacity", and was thus a suitable framework to explore multimorbidity in this high HIV/T2D burden setting. Integration of chronic services and addressing social determinants of health may be the first steps towards alleviating patient burden and improving their access and utilisation of these services. Further studies are necessary to explore multimorbidity beyond the context of HIV/T2D.

  10. A qualitative study on the experiences and perspectives of public sector patients in Cape Town in managing the workload of demands of HIV and type 2 diabetes multimorbidity

    PubMed Central

    Murphy, Katherine; Levitt, Naomi S.; BeLue, Rhonda; Oni, Tolu

    2018-01-01

    Background Current South African health policy for chronic disease management proposes integration of chronic services for better outcomes for chronic conditions; that is based on the Integrated Chronic Disease Model (ICDM). However, scant data exist on how patients with chronic multimorbidities currently experience the (re)-organisation of health services and what their perceived needs are in order to enhance the management of their conditions. Methods A qualitative study was conducted in a community health centre treating both HIV and diabetes patients in Cape Town. The study was grounded in the Shippee's Cumulative Complexity Model (CCM) and explored “patient workload” and “patient capacity” to manage chronic conditions. Individual interviews were conducted with 10 adult patient-participants with HIV and type two diabetes (T2D) multimorbidity and 6 healthcare workers who provided health services to these patient-participants. Results Patient-participants in this study experienced clinic-related workload such as: two separate clinics for HIV and T2D and perceived and experienced power mismatch between patients and healthcare workers. Self-care related workloads were largely around nutritional requirements, pill burden, and stigma. Burden of these demands varied in difficulty among patient-participants due to capacity factors such as: positive attitudes, optimal health literacy, social support and availability of economic resources. Strategies mentioned by participants for improved continuity of care and self-management of multi-morbidities included integration of chronic services, consolidated guidelines for healthcare workers, educational materials for patients, improved information systems and income for patients. Conclusion Using the CCM to explore multimorbidity captured most of the themes around "patient workload" and "patient capacity”, and was thus a suitable framework to explore multimorbidity in this high HIV/T2D burden setting. Integration of chronic services and addressing social determinants of health may be the first steps towards alleviating patient burden and improving their access and utilisation of these services. Further studies are necessary to explore multimorbidity beyond the context of HIV/T2D. PMID:29538415

  11. Impact of Stratospheric Ozone Zonal Asymmetries on the Tropospheric Circulation

    NASA Technical Reports Server (NTRS)

    Tweedy, Olga; Waugh, Darryn; Li, Feng; Oman, Luke

    2015-01-01

    The depletion and recovery of Antarctic ozone plays a major role in changes of Southern Hemisphere (SH) tropospheric climate. Recent studies indicate that the lack of polar ozone asymmetries in chemistry climate models (CCM) leads to a weaker and warmer Antarctic vortex, and smaller trends in the tropospheric mid-latitude jet and the surface pressure. However, the tropospheric response to ozone asymmetries is not well understood. In this study we report on a series of integrations of the Goddard Earth Observing System Chemistry Climate Model (GEOS CCM) to further examine the effect of zonal asymmetries on the state of the stratosphere and troposphere. Integrations with the full, interactive stratospheric chemistry are compared against identical simulations using the same CCM except that (1) the monthly mean zonal mean stratospheric ozone from first simulation is prescribed and (2) ozone is relaxed to the monthly mean zonal mean ozone on a three day time scale. To analyze the tropospheric response to ozone asymmetries, we examine trends and quantify the differences in temperatures, zonal wind and surface pressure among the integrations.

  12. [Diagnostic performance of surface electrocardiogram in early detection of chagasic cardiomyopathy].

    PubMed

    Bochard-Villanueva, Bruno; Estornell-Erill, Jordi; Fabregat-Andrés, Óscar; García-González, Pilar; Morell-Cabedo, Salvador; Ridocci-Soriano, Francisco

    2015-03-15

    Contrast-enhanced cardiac magnetic resonance imaging (CMR) allows early detection of myocardial involvement by Trypanosoma cruzi infection. The aim of our study was to assess the diagnostic performance of the surface electrocardiogram (ECG) in the early detection of Chagas' cardiomyopathy (CCM) compared with CMR. We included 43 asymptomatic patients (30 women, 42 ± 9.8 years), diagnosed of Chagas disease. The sample was divided into 2 groups according to the presence (n=17) or absence (n=26) of electrocardiographic abnormalities. All patients underwent CMR and late gadolinium enhancement (LGE) was used as a marker of early myocardial involvement. Six (14%) patients had a LGE significantly higher in the group who had electrocardiographic abnormalities (29 vs. 4%, P<.05). With CMR as the method of reference, the ECG had a sensitivity of 83% and a negative predictive value of 96% to detect CCM. ECG is a useful, inexpensive and globally available tool for the screening of CCM in asymptomatic patients but with proven myocardial involvement in CMR. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  13. Continuous esterification to produce biodiesel by SPES/PES/NWF composite catalytic membrane in flow-through membrane reactor: experimental and kinetic studies.

    PubMed

    Shi, Wenying; He, Benqiao; Cao, Yuping; Li, Jianxin; Yan, Feng; Cui, Zhenyu; Zou, Zhiqun; Guo, Shiwei; Qian, Xiaomin

    2013-02-01

    A novel composite catalytic membrane (CCM) was prepared from sulfonated polyethersulfone (SPES) and polyethersulfone (PES) blend supported by non-woven fabrics, as a heterogeneous catalyst to produce biodiesel from continuous esterification of oleic acid with methanol in a flow-through mode. A kinetic model of esterification was established based on a plug-flow assumption. The effects of the CCM structure (thickness, area, porosity, etc.), reaction temperature and the external and internal mass transfer resistances on esterification were investigated. The results showed that the CCM structure had a significant effect on the acid conversion. The external mass transfer resistance could be neglected when the flow rate was over 1.2 ml min(-1). The internal mass transfer resistance impacted on the conversion when membrane thickness was over 1.779 mm. An oleic acid conversion kept over 98.0% for 500 h of continuous running. The conversions obtained from the model are in good agreement with the experimental data. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Final report on RMO Vickers key comparison COOMET M.H-K1

    NASA Astrophysics Data System (ADS)

    Aslanyan, E.; Menelao, F.; Herrmann, K.; Aslanyan, A.; Pivovarov, V.; Galat, E.; Dovzhenko, Y.; Zhamanbalin, M.

    2013-01-01

    This report describes a COOMET key comparison on Vickers hardness scales involving five National Metrology Institutes: PTB (Germany), BelGIM (Belarus), NSC IM (Ukraine), KazInMetr (Kazakhstan) and VNIIFTRI (Russia). The pilot laboratory was VNIIFTRI, and PTB acted as the linking institute to key comparisons CCM.H-K1.b and CCM.H-K1.c conducted for the Vickers hardness scales HV1 and HV30, respectively. The comparison was also conducted for the HV5 Vickers hardness scale, since this scale is most frequently used in practice in Russia and CIS countries that work according to GOST standards. In the key comparison, two sets of hardness reference blocks for the Vickers hardness scales HV1, HV5 and HV30 consisting each of three hardness reference blocks with hardness levels of 450 HV and 750 HV were used. The measurement results and uncertainty assessments for HV1 and HV30 hardness scales, as announced by BelGIM, NSC IM, KazInMetr and VNIIFTRI, are in good agreement with the key comparison reference values of CCM.H-K1.b and CCM.H-K1.c. The comparison results for the HV5 hardness scale are viewed as additional information, since up to today no CCM key comparisons on this scale have yet been carried out. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  15. Guided bone regeneration with asymmetric collagen-chitosan membranes containing aspirin-loaded chitosan nanoparticles

    PubMed Central

    Zhang, Jiayu; Ma, Shiqing; Liu, Zihao; Geng, Hongjuan; Lu, Xin; Zhang, Xi; Li, Hongjie; Gao, Chenyuan; Zhang, Xu; Gao, Ping

    2017-01-01

    Introduction Membranes allowing the sustained release of drugs that can achieve cell adhesion are very promising for guided bone regeneration. Previous studies have suggested that aspirin has the potential to promote bone regeneration. The purpose of this study was to prepare a local drug delivery system with aspirin-loaded chitosan nanoparticles (ACS) contained in an asymmetric collagen-chitosan membrane (CCM). Methods In this study, the ACS were fabricated using different concentrations of aspirin (5 mg, 25 mg, 50 mg, and 75 mg). The drug release behavior of ACS was studied. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to examine the micromorphology of ACS and aspirin-loaded chitosan nanoparticles contained in chitosan-collagen membranes (ACS-CCM). In vitro bone mesenchymal stem cells (BMSCs) were cultured and critical-sized cranial defects on Sprague-Dawley rats were made to evaluate the effect of the ACS-CCM on bone regeneration. Results Drug release behavior results of ACS showed that the nanoparticles fabricated in this study could successfully sustain the release of the drug. TEM showed the morphology of the nanoparticles. SEM images indicated that the asymmetric membrane comprised a loose collagen layer and a dense chitosan layer. In vitro studies showed that ACS-CCM could promote the proliferation of BMSCs, and that the degree of differentiated BMSCs seeded on CCMs containing 50 mg of ACS was higher than that of other membranes. Micro-computed tomography showed that 50 mg of ACS-CCM resulted in enhanced bone regeneration compared with the control group. Conclusion This study shows that the ACS-CCM would allow the sustained release of aspirin and have further osteogenic potential. This membrane is a promising therapeutic approach to guiding bone regeneration. PMID:29276386

  16. Improving Access to Child Health Care in Indonesia Through Community Case Management.

    PubMed

    Setiawan, Agus; Dignam, Denise; Waters, Cheryl; Dawson, Angela

    2016-11-01

    Objectives In order to reduce infant mortality in Indonesia, community case management (CCM) was introduced. CCM is a community-based service delivery model to improve children's wellness and longevity, involving the delivery of lifesaving, curative interventions to address common childhood illnesses, particularly where there are limited facility-based services. This paper reports the findings of a qualitative study that investigated the implementation of CCM in the Kutai Timur district, East Kalimantan Indonesia from the perspective of mothers who received care. Methods Seven mothers and health workers were observed during a consultation and these mothers were interviewed in their home weeks after delivery. Field notes and the interview transcriptions were analysed thematically. Findings Mothers reported that their access to care had improved, along with an increase in their knowledge of infant danger signs and when to seek care. Family compliance with care plans was also found to have improved. Mothers expressed satisfaction with the care provided under the CCM model. The mothers expressed a need for a nurse or midwife to be posted in each village, preferably someone from that village. However two mothers did not wish their children to receive health interventions as they did not believe these to be culturally appropriate. Conclusion CCM is seen by rural Indonesian mothers to be a helpful model of care in terms of increasing access to health care and the uptake of lifesaving interventions for sick children. However there is a need to modify the program to demonstrate cultural sensitivity and meet cultural needs of the target population. While CCM is a potentially effective model of care, further integrative strategies are required to embed this model into maternal and child health service delivery.

  17. Guided bone regeneration with asymmetric collagen-chitosan membranes containing aspirin-loaded chitosan nanoparticles.

    PubMed

    Zhang, Jiayu; Ma, Shiqing; Liu, Zihao; Geng, Hongjuan; Lu, Xin; Zhang, Xi; Li, Hongjie; Gao, Chenyuan; Zhang, Xu; Gao, Ping

    2017-01-01

    Membranes allowing the sustained release of drugs that can achieve cell adhesion are very promising for guided bone regeneration. Previous studies have suggested that aspirin has the potential to promote bone regeneration. The purpose of this study was to prepare a local drug delivery system with aspirin-loaded chitosan nanoparticles (ACS) contained in an asymmetric collagen-chitosan membrane (CCM). In this study, the ACS were fabricated using different concentrations of aspirin (5 mg, 25 mg, 50 mg, and 75 mg). The drug release behavior of ACS was studied. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to examine the micromorphology of ACS and aspirin-loaded chitosan nanoparticles contained in chitosan-collagen membranes (ACS-CCM). In vitro bone mesenchymal stem cells (BMSCs) were cultured and critical-sized cranial defects on Sprague-Dawley rats were made to evaluate the effect of the ACS-CCM on bone regeneration. Drug release behavior results of ACS showed that the nanoparticles fabricated in this study could successfully sustain the release of the drug. TEM showed the morphology of the nanoparticles. SEM images indicated that the asymmetric membrane comprised a loose collagen layer and a dense chitosan layer. In vitro studies showed that ACS-CCM could promote the proliferation of BMSCs, and that the degree of differentiated BMSCs seeded on CCMs containing 50 mg of ACS was higher than that of other membranes. Micro-computed tomography showed that 50 mg of ACS-CCM resulted in enhanced bone regeneration compared with the control group. This study shows that the ACS-CCM would allow the sustained release of aspirin and have further osteogenic potential. This membrane is a promising therapeutic approach to guiding bone regeneration.

  18. TransOmic analysis of forebrain sections in Sp2 conditional knockout embryonic mice using IR-MALDESI imaging of lipids and LC-MS/MS label-free proteomics

    PubMed Central

    Loziuk, Philip; Meier, Florian; Johnson, Caroline

    2016-01-01

    Quantitative methods for detection of biological molecules are needed more than ever before in the emerging age of “omics” and “big data.” Here, we provide an integrated approach for systematic analysis of the “lipidome” in tissue. To test our approach in a biological context, we utilized brain tissue selectively deficient for the transcription factor Specificity Protein 2 (Sp2). Conditional deletion of Sp2 in the mouse cerebral cortex results in developmental deficiencies including disruption of lipid metabolism. Silver (Ag) cationization was implemented for infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) to enhance the ion abundances for olefinic lipids, as these have been linked to regulation by Sp2. Combining Ag-doped and conventional IR-MALDESI imaging, this approach was extended to IR-MALDESI imaging of embryonic mouse brains. Further, our imaging technique was combined with bottom-up shotgun proteomic LC-MS/MS analysis and western blot for comparing Sp2 conditional knockout (Sp2-cKO) and wild-type (WT) cortices of tissue sections. This provided an integrated omics dataset which revealed many specific changes to fundamental cellular processes and biosynthetic pathways. In particular, step-specific altered abundances of nucleotides, lipids, and associated proteins were observed in the cerebral cortices of Sp2-cKO embryos. PMID:26942738

  19. Transgenic tobacco plants with improved cyanobacterial Rubisco expression but no extra assembly factors grow at near wild-type rates if provided with elevated CO2.

    PubMed

    Occhialini, Alessandro; Lin, Myat T; Andralojc, P John; Hanson, Maureen R; Parry, Martin A J

    2016-01-01

    Introducing a carbon-concentrating mechanism and a faster Rubisco enzyme from cyanobacteria into higher plant chloroplasts may improve photosynthetic performance by increasing the rate of CO2 fixation while decreasing losses caused by photorespiration. We previously demonstrated that tobacco plants grow photoautotrophically using Rubisco from Synechococcus elongatus, although the plants exhibited considerably slower growth than wild-type and required supplementary CO2 . Because of concerns that vascular plant assembly factors may not be adequate for assembly of a cyanobacterial Rubisco, prior transgenic plants included the cyanobacterial chaperone RbcX or the carboxysomal protein CcmM35. Here we show that neither RbcX nor CcmM35 is needed for assembly of active cyanobacterial Rubisco. Furthermore, by altering the gene regulatory sequences on the Rubisco transgenes, cyanobacterial Rubisco expression was enhanced and the transgenic plants grew at near wild-type growth rates, although still requiring elevated CO2 . We performed detailed kinetic characterization of the enzymes produced with and without the RbcX and CcmM35 cyanobacterial proteins. These transgenic plants exhibit photosynthetic characteristics that confirm the predicted benefits of introduction of non-native forms of Rubisco with higher carboxylation rate constants in vascular plants and the potential nitrogen-use efficiency that may be achieved provided that adequate CO2 is available near the enzyme. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  20. The LysR-type transcription factor PacR is a global regulator of photosynthetic carbon assimilation in Anabaena.

    PubMed

    Picossi, Silvia; Flores, Enrique; Herrero, Antonia

    2015-09-01

    Cyanobacteria perform water-splitting photosynthesis and are important primary producers impacting the carbon and nitrogen cycles at global scale. They fix CO2 through ribulose-bisphosphate carboxylase/oxygenase (RuBisCo) and have evolved a distinct CO2 concentrating mechanism (CCM) that builds high CO2 concentrations in the vicinity of RuBisCo favouring its carboxylase activity. Filamentous cyanobacteria such as Anabaena fix CO2 in photosynthetic vegetative cells, which donate photosynthate to heterocysts that rely on a heterotrophic metabolism to fix N2 . CCM elements are induced in response to inorganic carbon limitation, a cue that exposes the photosynthetic apparatus to photodamage by over-reduction. An Anabaena mutant lacking the LysR-type transcription factor All3953 grew poorly and dies under high light. The rbcL operon encoding RuBisCo was induced upon carbon limitation in the wild type but not in the mutant. ChIP-Seq analysis was used to globally identify All3953 targets under carbon limitation. Targets include, besides rbcL, genes encoding CCM elements, photorespiratory pathway- photosystem- and electron transport-related components, and factors, including flavodiiron proteins, with a demonstrated or putative function in photoprotection. Quantitative reverse transcription polymerase chain reaction analysis of selected All3953 targets showed regulation in the wild type but not in the mutant. All3953 (PacR) is a global regulator of carbon assimilation in an oxygenic photoautotroph. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  1. Can the GEOS CCM Simulate the Temperature Response to Warm Pool El Nino Events in the Antarctic Stratosphere?

    NASA Technical Reports Server (NTRS)

    Hurwitz, M. M.; Song, I.-S.; Oman, L. D.; Newman, P. A.; Molod, A. M.; Frith, S. M.; Nielsen, J. E.

    2010-01-01

    "Warm pool" (WP) El Nino events are characterized by positive sea surface temperature (SST) anomalies in the central equatorial Pacific. During austral spring. WP El Nino events are associated with an enhancement of convective activity in the South Pacific Convergence Zone, provoking a tropospheric planetary wave response and thus increasing planetary wave driving of the Southern Hemisphere stratosphere. These conditions lead to higher polar stratospheric temperatures and to a weaker polar jet during austral summer, as compared with neutral ENSO years. Furthermore, this response is sensitive to the phase of the quasi-biennial oscillation (QBO): a stronger warming is seen in WP El Nino events coincident with the easterly phase of the quasi-biennial oscillation (QBO) as compared with WP El Nino events coincident with a westerly or neutral QBO. The Goddard Earth Observing System (GEOS) chemistry-climate model (CCM) is used to further explore the atmospheric response to ENSO. Time-slice simulations are forced by composited SSTs from observed WP El Nino and neutral ENSO events. The modeled eddy heat flux, temperature and wind responses to WP El Nino events are compared with observations. A new gravity wave drag scheme has been implemented in the GEOS CCM, enabling the model to produce a realistic, internally generated QBO. By repeating the above time-slice simulations with this new model version, the sensitivity of the WP El Nino response to the phase of the quasi-biennial oscillation QBO is estimated.

  2. Can the GEOS CCM Simulate the Temperature Response to Warm Pool El Nino Events in the Antarctic Stratosphere?

    NASA Technical Reports Server (NTRS)

    Hurwitz, M. M.; Song, I.-S.; Oman, L. D.; Newman, P. A.; Molod, A. M.; Frith, S. M.; Nielsen, J. E.

    2011-01-01

    "Warm pool" (WP) El Nino events are characterized by positive sea surface temperature (SST) anomalies in the central equatorial Pacific. During austral spring, WP El Nino events are associated with an enhancement of convective activity in the South Pacific Convergence Zone, provoking a tropospheric planetary wave response and thus increasing planetary wave driving of the Southern Hemisphere stratosphere. These conditions lead to higher polar stratospheric temperatures and to a weaker polar jet during austral summer, as compared with neutral ENSO years. Furthermore, this response is sensitive to the phase of the quasi-biennial oscillation (QBO): a stronger warming is seen in WP El Nino events coincident with the easterly phase of the quasi-biennial oscillation (QBO) as compared with WP El Nino events coincident with a westerly or neutral QBO. The Goddard Earth Observing System (GEOS) chemistry-climate model (CCM) is used to further explore the atmospheric response to ENSO. Time-slice simulations are forced by composited SSTs from observed NP El Nino and neutral ENSO events. The modeled eddy heat flux, temperature and wind responses to WP El Nino events are compared with observations. A new gravity wave drag scheme has been implemented in the GEOS CCM, enabling the model to produce e realistic, internally generated QBO. By repeating the above time-slice simulations with this new model version, the sensitivity of the WP El Nino response to the phase of the quasi-biennial oscillation QBO is estimated.

  3. Synthesis and Absorption Properties of Hollow-spherical Dy2Cu2O5 via a Coordination Compound Method with [DyCu(3,4-pdc)2(OAc)(H2O)2]•10.5H2O Precursor.

    PubMed

    Liu, Xuanwen; You, Junhua; Wang, Renchao; Ni, Zhiyuan; Han, Fei; Jin, Lei; Ye, Zhiqi; Fang, Zhao; Guo, Rui

    2017-10-12

    Dy 2 Cu 2 O 5 nanoparticles with perovskite structures were synthesized via a simple solution method (SSM) and a coordination compound method (CCM) using [DyCu(3,4-pdc) 2 (OAc)(H 2 O) 2 ]•10.5H 2 O (pdc = 3,4-pyridinedicarboxylic acid) as precursor. The as-prepared samples were structurally characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), x-ray photoelectron spectroscopy (XPS) and standard Brunauer-Emmett-Teller (BET) methods. Compared to the aggregated hexahedral particles prepared by SSM, the Dy 2 Cu 2 O 5 of CCM showed hollow spherical morphology composed of nanoparticles with average diameters of 100-150 nm and a larger special surface area up to 36.5 m 2 /g. The maximum adsorption capacity (Q m ) of CCM for malachite green (MG) determined by the adsorption isotherms with different adsorbent dosages of 0.03-0.07 g, reached 5.54 g/g at room temperature. The thermodynamic parameters of adsorption process were estimated by the fittings of the isotherms at 298, 318, and 338 K, and the kinetic parameters were obtained from the time-dependent adsorption isotherms. The results revealed that the adsorption process followed a pseudo-second-order reaction. Finally, the adsorption mechanism was studied using a competitive ion (CI) experiments, and the highly efficient selective adsorption was achieved due to strong O-Cu and O-Dy coordination bonds between Dy 2 Cu 2 O 5 and MG.

  4. Examination of Daily Weather in the NCAR CCM

    NASA Astrophysics Data System (ADS)

    Cocke, S. D.

    2006-05-01

    The NCAR CCM is one of the most extensively studied climate models in the scientific community. However, most studies focus primarily on the long term mean behavior, typically monthly or longer time scales. In this study we examine the daily weather in the GCM by performing a series of daily or weekly 10 day forecasts for one year at moderate (T63) and high (T126) resolution. The model is initialized with operational "AVN" and ECMWF analyses, and model performance is compared to that of major operational centers, using conventional skill scores used by the major centers. Such a detailed look at the CCM at shorter time scales may lead to improvements in physical parameterizations, which may in turn lead to improved climate simulations. One finding from this study is that the CCM has a significant drying tendency in the lower troposphere compared to the operational analyses. Another is that the large scale predictability of the GCM is competitive with most of the operational models, particularly in the southern hemisphere.

  5. Conjugation of curcumin onto alginate enhances aqueous solubility and stability of curcumin.

    PubMed

    Dey, Soma; Sreenivasan, K

    2014-01-01

    Curcumin is a potential drug for various diseases including cancer. Prime limitations associated with curcumin are low water solubility, rapid hydrolytic degradation and poor bioavailability. In order to redress these issues we developed Alginate-Curcumin (Alg-Ccm) conjugate which was characterized by FTIR and (1)H NMR spectroscopy. The conjugate self-assembled in aqueous solution forming micelles with an average hydrodynamic diameter of 459 ± 0.32 nm and negative zeta potential. The spherical micelles were visualized by TEM. The critical micelle concentration (CMC) of Alg-Ccm conjugate was determined. A significant enhancement in the aqueous solubility of curcumin was observed upon conjugation with alginate. Formation of micelles improved the stability of curcumin in water at physiological pH. The cytotoxic activity of Alg-Ccm was quantified by MTT assay using L-929 fibroblast cells and it was found to be potentially cytotoxic. Hence, Alg-Ccm could be a promising drug conjugate as well as a nanosized delivery vehicle. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Capillary isoelectric focusing and fluorometric detection of proteins and microorganisms dynamically modified by poly(ethylene glycol) pyrenebutanoate.

    PubMed

    Horka, Marie; Ruzicka, Filip; Horký, Jaroslav; Holá, Veronika; Slais, Karel

    2006-12-15

    The nonionogenic pyrene-based tenside, poly(ethylene glycol) pyrenebutanoate, was prepared and applied in capillary isoelectric focusing with fluorometric detection. This dye was used here as a buffer additive in capillary isoelectric focusing for a dynamic modification of the sample of proteins and microorganisms. The values of the isoelectric points of the labeled bioanalytes were calculated with use of the fluorescent pI markers and were found comparable with pI of the native compounds. The mixed cultures of proteins and microorganisms, Escherichia coli CCM 3954, Staphylococcus epidermidis CCM 4418, Proteus vulgaris, Enterococcus faecalis CCM 4224, and Stenotrophomonas maltophilia, the strains of the yeast cells, Candida albicans CCM 8180, Candida krusei, Candida parapsilosis, Candida glabrata, Candida tropicalis, and Saccharomyces cerevisiae were reproducibly focused and separated by the suggested technique. Using UV excitation for the on-column fluorometric detection, the minimum detectable amount was down to 10 cells injected on the separation capillary.

  7. Follow-up Contemporary Commercial Music (CCM) Survey: who's teaching what in nonclassical music.

    PubMed

    Weekly, Edrie Means; Lovetri, Jeannette L

    2009-05-01

    A previous study, published in the Journal of Voice in 2003, revealed that a majority of teachers of Music Theater (MT), a style of Contemporary Commercial Music (CCM), had little professional experience and little formal training in vocal pedagogy for this style. Those who did indicate that they had had training did not describe the training nor quantify it in any manner. To ascertain what type of training was available for CCM in general and MT, in particular, a follow-up study seemed warranted. A new questionnaire was developed which asked for further information from teachers of MT in several areas including performance experience, training methods, teaching philosophy, the use of terminology, knowledge of voice science and medicine, and other parameters. Responses were gathered from 145 singing teachers throughout the United States and several foreign countries. Statistical analysis obtained from the data may lead to both a better understanding of the kind of training available for teachers of CCM repertoire, and of its content and applicability.

  8. Integrated Community Case Management of Childhood Illness in Ethiopia: Implementation Strength and Quality of Care

    PubMed Central

    Miller, Nathan P.; Amouzou, Agbessi; Tafesse, Mengistu; Hazel, Elizabeth; Legesse, Hailemariam; Degefie, Tedbabe; Victora, Cesar G.; Black, Robert E.; Bryce, Jennifer

    2014-01-01

    Ethiopia has scaled up integrated community case management of childhood illness (iCCM) in most regions. We assessed the strength of iCCM implementation and the quality of care provided by health extension workers (HEWs). Data collectors observed HEWs' consultations with sick children and carried out gold standard re-examinations. Nearly all HEWs received training and supervision, and essential commodities were available. HEWs provided correct case management for 64% of children. The proportions of children correctly managed for pneumonia, diarrhea, and malnutrition were 72%, 79%, and 59%, respectively. Only 34% of children with severe illness were correctly managed. Health posts saw an average of 16 sick children in the previous 1 month. These results show that iCCM can be implemented at scale and that community-based HEWs can correctly manage multiple illnesses. However, to increase the chances of impact on child mortality, management of severe illness and use of iCCM services must be improved. PMID:24799369

  9. Understanding Differences in the Response to Composition Change as Simulated by CCMVal Models

    NASA Technical Reports Server (NTRS)

    Douglass, Anne R.; Strahan, Susan E.; Oman, Luke D.

    2012-01-01

    Chemistry climate models (CCMs) have a common conceptual basis. Differences in implementation lead to differences in the stratospheric ozone response to changes in composition and climate. Although evaluation by CCMVal-2 identified strengths and weaknesses of participant models, the evaluation results were not used to discriminate among projections for future ozone evolution, at least in part because the overall diagnostic evaluation did not cleanly relate to the differences in CCM response. Here we use a subset of CCMVal diagnostics and additional analysis to understand the differences in response. In the upper stratosphere, differences in simulated temperature and total odd nitrogen prior to increases in chlorine loading explain the large differences in CCM sensitivity. In the lower atmosphere, there are two principle contributions to differences in CCM sensitivity to chlorine and climate change. First, differences in the lower stratospheric ClO affect simulated sensitivity to chlorine. CCMs with best transport performance match NDACC column HCl measurements at a broad range of latitudes. Other CCMs disagree with observations due to differences in total inorganic chlorine, partitioning between HCl and ClONO2, or both. Differences in ClONO2 are directly related to differences in simulated ClO. Second, although all CCMs predict increased tropical upwelling, the rate of increase varies and contributes to differences in tropical ozone and the 60N-60S column average.

  10. Clinical marginal and internal adaptation of CAD/CAM milling, laser sintering, and cast metal ceramic crowns.

    PubMed

    Tamac, Ece; Toksavul, Suna; Toman, Muhittin

    2014-10-01

    Metal ceramic crowns are widely used in clinical practice, but comparisons of the clinical adaptation of restorations made with different processing techniques are lacking. The purpose of this study was to compare the clinical marginal and internal adaptation of metal ceramic crowns fabricated with 3 different techniques: computer-aided design and computer-aided manufacturing (CAD/CAM) milling (CCM), direct metal laser sintering (DMLS), and traditional casting (TC). Twenty CCM, 20 DMLS, and 20 TC metal ceramic crowns were fabricated for 42 patients. Before luting the crowns, silicone replicas were obtained to measure marginal gap and internal adaptation that was evaluated at 3 regions: axial wall, axio-occlusal angle, and occlusal surface. Measurements were made with a reflected light binocular stereomicroscope at 20× magnification and analyzed with 1-way analysis of variance (ANOVA) and the Bonferroni post hoc test (α=.05). The mean marginal gap values were 86.64 μm for CCM, 96.23 μm for DMLS, and 75.92 μm for TC. The means at the axial wall region were 117.5 μm for the CCM group, 139.02 μm for the DMLS group, and 121.38 μm for the TC group. One-way ANOVA revealed no statistically significant differences among the groups for measurements at the marginal gap (P=.082) and the axial wall region (P=.114). The means at the axio-occlusal region were 142.1 μm for CCM, 188.12 μm for DMLS, and 140.63 μm for TC, and those at the occlusal surface region were 265.73 μm for CCM, 290.39 μm for DMLS, and 201.09 μm for TC. The mean values of group DMLS were significantly higher at the axio-occlusal region and the occlusal surface region than those of other groups (P<.05). CCM, DMLS and TC metal ceramic crowns performed similarly in terms of clinical marginal and axial wall adaptation. The cement film thickness at the occlusal region and axio-occlusal region were higher for DMLS crowns. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  11. [Development and application of component-based Chinese medicine theory].

    PubMed

    Zhang, Jun-Hua; Fan, Guan-Wei; Zhang, Han; Fan, Xiao-Hui; Wang, Yi; Liu, Li-Mei; Li, Chuan; Gao, Yue; Gao, Xiu-Mei; Zhang, Bo-Li

    2017-11-01

    Traditional Chinese medicine (TCM) prescription is the main therapies for disease prevention and treatment in Chinese medicine. Following the guidance of the theory of TCM and developing drug by composing prescriptions of TCM materials and pieces, it is a traditional application mode of TCM, and still widely used in clinic. TCM prescription has theoretical advantages and rich clinical application experience in dealing with multi-factor complex diseases, but scientific research is relatively weak. The lack of scientific cognition of the effective substances and mechanism of Chinese medicine leads to insufficient understanding of the efficacy regularity, which affects the stability of effect and hinders the improvement of quality of Chinese medicinal products. Component-based Chinese medicine (CCM) is an innovation based on inheritance, which breaks through the tradition of experience-based prescription and realize the transformation of compatibility from herbal pieces to components. CCM is an important achievement during the research process of modernization of Chinese medicine. Under the support of three national "973" projects, in order to reveal the scientific connotation of the prescription compatibility theory and develop innovative Chinese drugs, we have launched theoretical innovation and technological innovation around the "two relatively clear", and opened up the research field of CCM. CCM is an innovation based on inheritance, breaking through the tradition of experience based prescription, and realizing the transformation from compatibility of herbal pieces to component compatibility, which is an important achievement of the modernization of traditional Chinese medicine. In the past more than 10 years, with the deepening of research and the expansion of application, the theory and methods of CCM and efficacy-oriented compatibility have been continuously improved. The value of CCM is not only in developing new drug, more important is to build a communication bridge between traditional Chinese medicine and modern science and construct the system of key technologies which meet the need of innovation and development of TCM. This paper focused on the research progress, related concepts and technology development of CCM, as well as its application prospect in the theory research of Chinese medicine, development of innovative Chinese drugs, secondary development of Chinese patent medicine and upgrading of pharmaceutical technology. Copyright© by the Chinese Pharmaceutical Association.

  12. How do we know? An assessment of integrated community case management data quality in four districts of Malawi.

    PubMed

    Yourkavitch, Jennifer; Zalisk, Kirsten; Prosnitz, Debra; Luhanga, Misheck; Nsona, Humphreys

    2016-11-01

    The World Health Organization contracted annual data quality assessments of Rapid Access Expansion (RAcE) projects to review integrated community case management (iCCM) data quality and the monitoring and evaluation (M&E) system for iCCM, and to suggest ways to improve data quality. The first RAcE data quality assessment was conducted in Malawi in January 2014 and we present findings pertaining to data from the health management information system at the community, facility and other sub-national levels because RAcE grantees rely on that for most of their monitoring data. We randomly selected 10 health facilities (10% of eligible facilities) from the four RAcE project districts, and collected quantitative data with an adapted and comprehensive tool that included an assessment of Malawi's M&E system for iCCM data and a data verification exercise that traced selected indicators through the reporting system. We rated the iCCM M&E system across five function areas based on interviews and observations, and calculated verification ratios for each data reporting level. We also conducted key informant interviews with Health Surveillance Assistants and facility, district and central Ministry of Health staff. Scores show a high-functioning M&E system for iCCM with some deficiencies in data management processes. The system lacks quality controls, including data entry verification, a protocol for addressing errors, and written procedures for data collection, entry, analysis and management. Data availability was generally high except for supervision data. The data verification process identified gaps in completeness and consistency, particularly in Health Surveillance Assistants' record keeping. Staff at all levels would like more training in data management. This data quality assessment illuminates where an otherwise strong M&E system for iCCM fails to ensure some aspects of data quality. Prioritizing data management with documented protocols, additional training and approaches to create efficient supervision practices may improve iCCM data quality. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Integrated community case management in Malawi: an analysis of innovation and institutional characteristics for policy adoption.

    PubMed

    Rodríguez, Daniela C; Banda, Hastings; Namakhoma, Ireen

    2015-12-01

    In 2007, Malawi became an early adopter of integrated community case management for childhood illnesses (iCCM), a policy aimed at community-level treatment for malaria, diarrhoea and pneumonia for children below 5 years. Through a retrospective case study, this article explores critical issues in implementation that arose during policy formulation through the lens of the innovation (i.e. iCCM) and of the institutions involved in the policy process. Data analysis is founded on a documentary review and 21 in-depth stakeholder interviews across institutions in Malawi. Findings indicate that the characteristics of iCCM made it a suitable policy to address persistent challenges in child mortality, namely that ill children were not interacting with health workers on a timely basis and consequently were dying in their communities. Further, iCCM was compatible with the Malawian health system due to the ability to build on an existing community health worker cadre of health surveillance assistants (HSAs) and previous experiences with treatment provision at the community level. In terms of institutions, the Ministry of Health (MoH) demonstrated leadership in the overall policy process despite early challenges of co-ordination within the MoH. WHO, United Nations Children's Fund (UNICEF) and implementing organizations played a supportive role in their position as knowledge brokers. Greater challenges were faced in the organizational capacity of the MoH. Regulatory issues around HSA training as well as concerns around supervision and overburdening of HSAs were discussed, though not fully addressed during policy development. Similarly, the financial sustainability of iCCM, including the mechanisms for channelling funding flows, also remains an unresolved issue. This analysis highlights the role of implementation questions during policy development. Despite several outstanding concerns, the compatibility between iCCM as a policy alternative and the local context laid the foundation for Malawi's road to early adoption of iCCM. © The Author 2015. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Identifying organisational principles and management practices important to the quality of health care services for chronic conditions.

    PubMed

    Frølich, Anne

    2012-02-01

    The quality of health care services offered to people suffering from chronic diseases often fails to meet standards in Denmark or internationally. The population consisting of people with chronic diseases is large and accounts for about 70% of total health care expenses. Given that resources are limited, it is necessary to identify efficient methods to improve the quality of care. Comparing health care systems is a well-known method for identifying new knowledge regarding, for instance, organisational methods and principles. Kaiser Permanente (KP), an integrated health care delivery system in the U.S., is recognized as providing high-quality chronic care; to some extent, this is due to KP's implementation of the chronic care model (CCM). This model recommends a range of evidence-based management practices that support the implementation of evidence-based medicine. However, it is not clear which management practices in the CCM are most efficient and in what combinations. In addition, financial incentives and public reporting of performance are often considered effective at improving the quality of health care services, but this has not yet been definitively proved. The aim of this dissertation is to describe the effect of determinants, such as organisational structures and management practices including two selected incentives, on the quality of care in chronic diseases. The dissertation is based on four studies with the following purposes: 1) macro- or healthcare system-level identification of organisational structures and principles that affect the quality of health care services, based on a comparison of KP and the Danish health care system; 2) meso- or organisation-level identification of management practices with positive effects on screening rates for hemoglobin A1c and lipid profile in diabetes; 3) evaluation of the effect of the CCM on quality of health care services and continuity of care in a Danish setting; 4) micro- or practice-level evaluation of the effect of financial incentives and public performance reporting on the behaviour of professionals and quality of care. Using secondary data, KP and the Danish health care system were compared in terms of six central dimensions: population, health care professionals, health care organisations, utilization patterns, quality measurements, and costs. Differences existed between the two systems on all dimensions, complicating the interpretation of findings. For instance, observed differences might be due to similar tendencies in the two health care systems that were observed at different times, rather than true structural differences. The expenses in the two health care systems were corrected for differences in the populations served and the purchasing power of currencies. However, no validated methods existed to correct for observed differences in case-mixes of chronic conditions. Data from a population of about half a million patients with diabetes in a large U.S. integrated health care delivery system affiliated with 41 medical centers employing 15 different CCM management practices was the basis for identifying effective management practices. Through the use of statistical modelling, the management practice of provider alerts was identified as most effective for promoting screening for hemoglobin A1c and lipid profile. The CCM was used as a framework for implementing four rehabilitation programs. The model promoted continuity of care and quality of health care services. New management practices were developed in the study, and known practices were further developed. However, the observational nature of the study limited the generalisability of the findings. In a structured literature survey focusing on the effect of financial incentives and public performance reporting on the quality of health care services, few studies documenting an effect were identified. The results varied, and important program aspects or contextual variables were often omitted. A model describing the effects of the two incentives on the conduct of health care professionals and their interaction with the organisations in which they serve was developed. On the macro-level, organisational differences between KP and the Danish health care system related to the primary care sectors, utilization patterns, and the quality of health care services, supporting a hypothesis that KP's focus on primary care is a beneficial form of organisation. On the meso-level, use of the CCM improved quality of health care services, but the effect is complicated and context dependent. The CCM was found to be useful in the Danish health care system, and the model was also further developed in a Danish setting. On the micro-level, quality was improved by financial incentives and disclosure in a complex interplay with other central factors in the work environment of health care professionals.

  15. Origin of the CMS gene locus in rapeseed cybrid mitochondria: active and inactive recombination produces the complex CMS gene region in the mitochondrial genomes of Brassicaceae.

    PubMed

    Oshima, Masao; Kikuchi, Rie; Imamura, Jun; Handa, Hirokazu

    2010-01-01

    CMS (cytoplasmic male sterile) rapeseed is produced by asymmetrical somatic cell fusion between the Brassica napus cv. Westar and the Raphanus sativus Kosena CMS line (Kosena radish). The CMS rapeseed contains a CMS gene, orf125, which is derived from Kosena radish. Our sequence analyses revealed that the orf125 region in CMS rapeseed originated from recombination between the orf125/orfB region and the nad1C/ccmFN1 region by way of a 63 bp repeat. A precise sequence comparison among the related sequences in CMS rapeseed, Kosena radish and normal rapeseed showed that the orf125 region in CMS rapeseed consisted of the Kosena orf125/orfB region and the rapeseed nad1C/ccmFN1 region, even though Kosena radish had both the orf125/orfB region and the nad1C/ccmFN1 region in its mitochondrial genome. We also identified three tandem repeat sequences in the regions surrounding orf125, including a 63 bp repeat, which were involved in several recombination events. Interestingly, differences in the recombination activity for each repeat sequence were observed, even though these sequences were located adjacent to each other in the mitochondrial genome. We report results indicating that recombination events within the mitochondrial genomes are regulated at the level of specific repeat sequences depending on the cellular environment.

  16. What Case Managers Should Know About Their Roles and Functions: A National Study From the Commission for Case Manager Certification: Part 1.

    PubMed

    Tahan, Hussein M; Watson, Annette C; Sminkey, Patrice V

    2015-01-01

    The purpose of this national role and function study was to identify the essential activities and necessary knowledge areas for effective case manager practice from the perspective of those currently functioning in various care settings and across diverse professional disciplines. The national study covered all case management practices and/or work settings across the full continuum of health care. This cross-sectional descriptive study used the practice analysis method and online survey research design. It employed a purposive sample of case managers, in which 52,370 individuals received an invitation to participate. Data collection completed over a 4-week period, resulting in 7,668 useable survey responses (nearly a 15% response rate). The study identified the common activities and knowledge areas necessary for competent and effective performance of case managers, as is highlighted in this article, which is the first of a 2-part series on the role and function study. The results informed the needed update of the test specifications for the Certified Case Manager (CCM) certification examination, as will be delineated in Part 2 of the article series, to ensure that it continues to be substantiated in current practice. Of special note are the emergence of specific activity and knowledge domains in the area of case management ethical, legal, and practice standards, and an increase in the number of employers requiring certified case managers to fill vacant positions and compensating them financially for such qualifications. This study helps keep the CCM credentialing examination evidence-based and maintain its validity for evaluating competency of case managers. Specifically, the study identified essential activities and knowledge domains that define competent case management practice. Findings can be used for developing programs and curricula for the training and development of case managers. The study instrument also can be used for further research of case management practice.

  17. Asiatic Acid Inhibits Pro-Angiogenic Effects of VEGF and Human Gliomas in Endothelial Cell Culture Models

    PubMed Central

    Kavitha, Chandagirikoppal V.; Agarwal, Chapla; Agarwal, Rajesh; Deep, Gagan

    2011-01-01

    Malignant gliomas are one of the most devastating and incurable tumors. Sustained excessive angiogenesis by glioma cells is the major reason for their uncontrolled growth and resistance toward conventional therapies resulting in high mortality. Therefore, targeting angiogenesis should be a logical strategy to prevent or control glioma cell growth. Earlier studies have shown that Asiatic Acid (AsA), a pentacyclic triterpenoid, is effective against glioma and other cancer cells; however, its efficacy against angiogenesis remains unknown. In the present study, we examined the anti-angiogenic efficacy of AsA using human umbilical vein endothelial cells (HUVEC) and human brain microvascular endothelial cells (HBMEC). Our results showed that AsA (5–20 µM) inhibits HUVEC growth and induces apoptotic cell death by activating caspases (3 and 9) and modulating the expression of apoptosis regulators Bad, survivin and pAkt-ser473. Further, AsA showed a dose-dependent inhibition of HUVEC migration, invasion and capillary tube formation, and disintegrated preformed capillary network. AsA also inhibited the VEGF-stimulated growth and capillary tube formation by HUVEC and HBMEC. Next, we analyzed the angiogenic potential of conditioned media collected from human glioma LN18 and U87-MG cells treated with either DMSO (control conditioned media, CCM) or AsA 20 µM (AsA20 conditioned media, AsA20CM). CCM from glioma cells significantly enhanced the capillary tube formation in both HUVEC and HBMEC, while capillary tube formation in both endothelial cell lines was greatly compromised in the presence of AsA20CM. Consistent with these results, VEGF expression was lesser in AsA20CM compared to CCM, and indeed AsA strongly inhibited VEGF level (both cellular and secreted) in glioma cells. AsA also showed dose-dependent anti-angiogenic efficacy in Matrigel plug assay, and inhibited the glioma cells potential to attract HUVEC/HBMEC. Overall, the present study clearly showed the strong anti-angiogenic potential of AsA and suggests its usefulness against malignant gliomas. PMID:21826202

  18. Bilateral key comparison CCM.P-K3.1 for absolute pressure measurements from 3 × 10-6 Pa to 9 × 10-4 Pa

    NASA Astrophysics Data System (ADS)

    Fedchak, J. A.; Bock, Th; Jousten, K.

    2014-01-01

    This report describes the bilateral key comparison CCM.P-K3.1 between the National Institute of Standards and Technology (NIST) and Physikalisch-Technische Bundesanstalt (PTB) for absolute pressure in the range from 3 × 10-6 Pa to 9 × 10-4 Pa. This comparison was a follow-up to the comparison CCM.P-K3. Two ionization gauges and two spinning rotor gauges (SRGs) were used as the transfer standards for the comparison. The SRGs were used to compare the standards at a pressure of 9 × 10-4 Pa and to normalize the ionization gauge readings. The two ionization gauges were used to compare the standards in the pressure range of from 3 × 10-6 Pa to 3 × 10-4 Pa. Both laboratories used dynamic expansion chambers as standards in the comparison. The two labs showed excellent agreement with each other and with the CCM.P-K3 key comparison reference value (KCRV) over the entire range. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  19. Critical Communicative Methodology: Informing Real Social Transformation through Research

    ERIC Educational Resources Information Center

    Gomez, Aitor; Puigvert, Lidia; Flecha, Ramon

    2011-01-01

    The critical communicative methodology (CCM) is a methodological response to the dialogic turn of societies and sciences that has already had an important impact in transforming situations of inequality and exclusion. Research conducted with the CCM implies continuous and egalitarian dialogue among researchers and the people involved in the…

  20. CCM key comparison CCM.D-K4 'Hydrometer'

    NASA Astrophysics Data System (ADS)

    Lorefice, S.; Becerra, L. O.; Lenard, E.; Lee, Y. J.; Lee, W. G.; Madec, T.; Meury, P. A.; Caceres, J.; Santos, C.; Vamossy, C.; Man, J.; Fen, K.; Toda, K.; Wright, J.; Bettin, H.; Toth, H.

    2016-01-01

    This report presents the comparison philosophy, methodology, analysis and the results of the designed CCM.D-K4 key comparison that covered the calibration of high resolution hydrometers for liquid and alcoholometers in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20°C. The main purpose of this comparison was not only to evaluate the degree of equivalence in the calibration of high accuracy hydrometers between NMI participants, but also to link, were it is possible, the results of previous comparisons to Key Comparison Reference Values (KCRVs) of CCM.D-K4. Eleven NMI laboratories took part in the CCM.D-K4 divided in two groups (petals). With the CCM.D-K4 purpose, two similar sets consisting of three hydrometers for liquid density determinations and an alcoholometer were circulated to the NMI participants as a travelling standard in the time interval from January 2011 to April 2012. Twelve Key Comparison Reference Values (KCRVs) for each petal have been obtained at the density values related to the tested density marks of the transfer standards by the results of participants. The KCRVs and corresponding uncertainties were calculated by the weighted mean in the case of consistent results, otherwise the median was used. The degree of equivalence (DoE) with respect to the corresponding KCRV was determined for each participant and, in this particular comparison, the Weighted Least Squares (WLS) method was used to link the individual DoE of each participant by a continuous function. Significant drift of the transfer standards was not detected. This report also gives instructions on calculating pair-wise degrees of equivalence, with the addition of any information on correlations that may be necessary to estimate more accurately as well as the procedure for linking international comparisons to the CCM.D-K4. Finally an example of linkage to the CCM.D-K4 is given by dealing with the results of the bilateral comparison between INRiM and NMIA, which was added to this comparison so that all participants were engaged after the breakage of the 9340171 artefact. A particularly good agreement was found among the results provided by most of the participants, even if some systematic differences and either underestimated or overestimated uncertainties of the submitted results can be identified with respect to the KCRVs. In general the deviations of the laboratory results to the KCRVs are within of 1/3rd to 1/4th of a scale division and the uncertainty at 95% is usually within half a division. During the analysis of the submitted results, a systematic difference between the first and last immersed mark was also noted, possibly due to a temperature gradient along the stem and/or wetting of the stem around the tested mark, and therefore a corrected claimed uncertainty from each laboratory is expected. However this comparison may help the laboratories to solve some residual or marginal problems as well as to better understand the uncertainty components. The comparison fully supports the calibration measurement capabilities table in the BIPM key comparison database (KCDB). The results can be used to link regional comparisons to this CCM key comparison Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  1. Limits to the Positive Effect of Ocean Acidification on Macroalgal Primary Production, Interactions with Light and Temperature

    NASA Astrophysics Data System (ADS)

    Kubler, J.; Dudgeon, S. R.; Nisumaa, A. M.

    2016-02-01

    About one third of macroalgal species lack any carbon concentrating mechanism (CCM), which prevents carbon limitation under air equilibrium in other seaweed species. It is predicted that those species lacking CCM's will benefit from ongoing ocean acidification in terms of primary productivity and growth. The absolute sizes and pattern of those benefits are not known. Here, we compare the results of a model based on composite data from the literature, with a growth experiment using Plocamium cartilagineum, a broadly distributed rhodophyte species lacking a carbon concentrating mechanism and hypothesized to be carbon limited under current conditions. We grew P. cartilagineum, at 15 and 20°C in seawater aerated with a total of 53 different pCO2s (from 344 to 1053µatm), in 8 multiweek trials over 12 months. We measured growth and photosynthetic rates. A linear mixed model analysis was used to partition the effect sizes of drivers of variation in the experiment. The growth rates and maximum photosynthetic rates responded nonlinearly to OA, increasing with elevated pCO2 from recent atmospheric level to up 450µatm and decreasing at higher pCO2. Light harvesting efficiency was unaffected by pCO2 and inversely related to temperature. We were able to compare the results of the growth experiment directly to the model based on the additive effects of temperature and pCO2 on photosynthetic rates, finding concordance of the pattern of response. The size of the effect of pCO2 on growth rate in the experiment was greater than the effect predicted by the model for net primary productivity. These results predict that the benefit of OA for macroalgal growth may disappear as ocean acidification continues through this century.

  2. Chronic disease management: implementation and coordination of healthcare systems for depressed elderly persons.

    PubMed

    Severinsson, Elisabeth; Holm, Anne Lise

    2014-12-01

    The aim of this study was to evaluate the implementation of the research-based Chronic Care Model (CCM), discuss methods and summarise research recommendations for improving the care of depressed elderly persons. Interviews were conducted and state-of-the-art reviews employed. Three important areas emerged: (1) barriers to and facilitating factors in the implementation of the CCM; (2) the challenges involved in re-designing the delivery system and interdisciplinary team collaboration; and (3) empirical evidence pertaining to self-management support and how older persons manage to live with depressive ill-health. In conclusion, implementation research requires evidence-based knowledge, staff involvement and familiarity with the context in which development occurs.

  3. SpeCond: a method to detect condition-specific gene expression

    PubMed Central

    2011-01-01

    Transcriptomic studies routinely measure expression levels across numerous conditions. These datasets allow identification of genes that are specifically expressed in a small number of conditions. However, there are currently no statistically robust methods for identifying such genes. Here we present SpeCond, a method to detect condition-specific genes that outperforms alternative approaches. We apply the method to a dataset of 32 human tissues to determine 2,673 specifically expressed genes. An implementation of SpeCond is freely available as a Bioconductor package at http://www.bioconductor.org/packages/release/bioc/html/SpeCond.html. PMID:22008066

  4. A Simple Combinatorial Codon Mutagenesis Method for Targeted Protein Engineering.

    PubMed

    Belsare, Ketaki D; Andorfer, Mary C; Cardenas, Frida S; Chael, Julia R; Park, Hyun June; Lewis, Jared C

    2017-03-17

    Directed evolution is a powerful tool for optimizing enzymes, and mutagenesis methods that improve enzyme library quality can significantly expedite the evolution process. Here, we report a simple method for targeted combinatorial codon mutagenesis (CCM). To demonstrate the utility of this method for protein engineering, CCM libraries were constructed for cytochrome P450 BM3 , pfu prolyl oligopeptidase, and the flavin-dependent halogenase RebH; 10-26 sites were targeted for codon mutagenesis in each of these enzymes, and libraries with a tunable average of 1-7 codon mutations per gene were generated. Each of these libraries provided improved enzymes for their respective transformations, which highlights the generality, simplicity, and tunability of CCM for targeted protein engineering.

  5. Tissue- and cell-specific expression of mouse xanthine oxidoreductase gene in vivo: regulation by bacterial lipopolysaccharide.

    PubMed Central

    Kurosaki, M; Li Calzi, M; Scanziani, E; Garattini, E; Terao, M

    1995-01-01

    The expression of the xanthine oxidoreductase gene was studied in various mouse organs and tissues, under basal conditions and on treatment with bacterial lipopolysaccharide. Levels of xanthine oxidoreductase protein and mRNA were compared in order to understand the molecular mechanisms regulating the expression of this enzyme system. The highest amounts of xanthine oxidoreductase and the respective mRNA are observed in the duodenum and jejunum, where the protein is present in an unusual form because of a specific proteolytic cleavage of the primary translation product present in all locations. Under basal conditions, multiple tissue-specific mechanisms of xanthine oxidoreductase regulation are evident. Lipopolysaccharide increases enzyme activity in some, but not all tissues, mainly via modulation of the respective transcript, although translational and post-translational mechanisms are also active. In situ hybridization studies on tissue sections obtained from mice under control conditions or with lipopolysaccharide treatment demonstrate that xanthine oxidoreductase is present in hepatocytes, predominantly in the proximal tubules of the kidney, epithelial layer of the gastrointestinal mucosa, the alveolar compartment of the lung, the pulpar region of the spleen and the vascular component of the heart. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 PMID:7864814

  6. [Screening endophytic bacteria against plant-parasitic nematodes].

    PubMed

    Peng, Shuang; Yan, Shuzhen; Chen, Shuanglin

    2011-03-01

    Plant-parasite nematode is one of the most important pathogens in plant. Our objective is to screen endophytic bacteria against plant-parasitic nematodes from plant. Endophytic bacteria were isolated and screened by testing their metabolite against Bursaphelenchus xylophilus in vitro. Those strains inhibiting B. xylophilus were selected to culture in liquid medium and fermentation conditions were optimized by orthogonal test. The stability of the antinematode substances was evaluated by various. In addition, four strains were identified by 16SrDNA sequence analysis. In total 13 strains of endophytic bacteria secreting antinematode metabolite were isolated from 6 species of plant. The supernatant of the fermentation broth of these endophytic bacteria gave 100% mortality of nematodes after treated as the follows: 1 ml each was mixed with 0.2 ml of the suspension of nematodes (2000 nematodes/ml) then incubated at 250C for 24 h, some of which could led to leakage or dissolution of nematodes. Among them, four strains, BCM2, SZ5, CCM7 and DP1, showed stronger activity than others. The supernatants diluted three times also gave not less than 95% mortality after 24 h treatment, and those from DP1 and SZ5 even gave 100% mortality. The fermentation conditions of the four strains were optimized and the antinematode activity grew up four times after optimization. The antinematode substances of these strains were found stable when treated with protease or heating or stored at 4 degrees C after 100 days, while instable when treated with acid or alkali. DP1 and CCM7 were identified to be Bacillus subtilis, while SZ5 and BCM2 to be Bacillus cereus. Endophytic bacteria secreting antinematode metabolite were found in economic crops. The metabolite of some strains showed strong and stable antinematode activity. Our results indicate the real potential of biocontrol by endophytic bacteria.

  7. 75 FR 1589 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-12

    ... Census Coverage Measurement Recall Bias Panel Study has been added. Two previous notices were published... Reinterview, and Recall Bias Panel Study. OMB Control Number: None. Form Number(s): All data will be collected... different PI enumerator. In addition to the CCM PI Operation, CCM will conduct a Recall Bias Panel Study...

  8. The Effects of Cognitive Conflict Management on Cognitive Development and Science Achievement

    ERIC Educational Resources Information Center

    Budiman, Zainol Badli; Halim, Lilia; Mohd Meerah, Subahan; Osman, Kamisah

    2014-01-01

    Three teaching methods were compared in this study, namely a Cognitive Conflict Management Module (CCM) that is infused into Cognitive Acceleration through Science Education (CASE), (Module A) CASE without CCM (Module B) and a conventional teaching method. This study employed a pre- and post-test quasi-experimental design using non-equivalent…

  9. Coaching, Counseling, and Mentoring: A Strategic Need in Training and Development

    ERIC Educational Resources Information Center

    Demik, Randal J.

    2007-01-01

    Literature within HRD is reviewed that aides in the understanding of Coaching, Counseling, and Mentoring (CCM) as a strategic need. Published case studies are presented where CCM strategies have been put into practice in the workplace to foster an environment of performance improvement. By developing and implementing these approaches,…

  10. Gas Furnace with Pulsed Feeding of the Heating Agent for Volume Precision Heat Treatment of CCM Rolls

    NASA Astrophysics Data System (ADS)

    Moroz, V. I.; Egorova, V. M.; Gusev, S. V.

    2001-05-01

    A standard chamber batch furnace of the Severstal' plant has been modified for precision heat treatment of CCM rolls. The certification tests of a charge of rolls from steel 24KhM1F have shown the technical and economical advantages of the new design.

  11. An Evaluation of Collaborative Interventions to Improve Chronic Illness Care: Framework and Study Design

    ERIC Educational Resources Information Center

    Cretin, Shan; Shortell, Stephen M.; Keeler, Emmett B.

    2004-01-01

    The authors' dual-purpose evaluation assesses the effectiveness of formal collaboratives in stimulating organizational changes to improve chronic illness care (the chronic care model or CCM). Intervention and comparison sites are compared before and after introduction of the CCM. Multiple data sources are used to measure the degree of…

  12. The Community College of Maine Annual Report, Year Two, 1990-1991.

    ERIC Educational Resources Information Center

    Maine Univ., Augusta. Office of Distance Education.

    The Community College of Maine (CCM) makes use of new telecommunications and information technologies to overcome the barriers of geography, cost, and time that have always limited access to higher education for Maine's rural communities. Currently, the Interactive Television System (ITV) is the primary means used to broadcast CCM courses, but…

  13. Improved sampling and analysis of images in corneal confocal microscopy.

    PubMed

    Schaldemose, E L; Fontain, F I; Karlsson, P; Nyengaard, J R

    2017-10-01

    Corneal confocal microscopy (CCM) is a noninvasive clinical method to analyse and quantify corneal nerve fibres in vivo. Although the CCM technique is in constant progress, there are methodological limitations in terms of sampling of images and objectivity of the nerve quantification. The aim of this study was to present a randomized sampling method of the CCM images and to develop an adjusted area-dependent image analysis. Furthermore, a manual nerve fibre analysis method was compared to a fully automated method. 23 idiopathic small-fibre neuropathy patients were investigated using CCM. Corneal nerve fibre length density (CNFL) and corneal nerve fibre branch density (CNBD) were determined in both a manual and automatic manner. Differences in CNFL and CNBD between (1) the randomized and the most common sampling method, (2) the adjusted and the unadjusted area and (3) the manual and automated quantification method were investigated. The CNFL values were significantly lower when using the randomized sampling method compared to the most common method (p = 0.01). There was not a statistical significant difference in the CNBD values between the randomized and the most common sampling method (p = 0.85). CNFL and CNBD values were increased when using the adjusted area compared to the standard area. Additionally, the study found a significant increase in the CNFL and CNBD values when using the manual method compared to the automatic method (p ≤ 0.001). The study demonstrated a significant difference in the CNFL values between the randomized and common sampling method indicating the importance of clear guidelines for the image sampling. The increase in CNFL and CNBD values when using the adjusted cornea area is not surprising. The observed increases in both CNFL and CNBD values when using the manual method of nerve quantification compared to the automatic method are consistent with earlier findings. This study underlines the importance of improving the analysis of the CCM images in order to obtain more objective corneal nerve fibre measurements. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

  14. ACTE Wing Loads Analysis

    NASA Technical Reports Server (NTRS)

    Horn, Nicholas R.

    2015-01-01

    The Adaptive Compliant Trailing Edge (ACTE) project modified a Gulfstream III (GIII) aircraft with a new flexible flap that creates a seamless transition between the flap and the wing. As with any new modification, it is crucial to ensure that the aircraft will not become overstressed in flight. To test this, Star CCM a computational fluid dynamics (CFD) software program was used to calculate aerodynamic data for the aircraft at given flight conditions.

  15. Measuring Coverage in MNCH: Evaluation of Community-Based Treatment of Childhood Illnesses through Household Surveys

    PubMed Central

    Hazel, Elizabeth; Requejo, Jennifer; David, Julia; Bryce, Jennifer

    2013-01-01

    Community case management (CCM) is a strategy for training and supporting workers at the community level to provide treatment for the three major childhood diseases—diarrhea, fever (indicative of malaria), and pneumonia—as a complement to facility-based care. Many low- and middle-income countries are now implementing CCM and need to evaluate whether adoption of the strategy is associated with increases in treatment coverage. In this review, we assess the extent to which large-scale, national household surveys can serve as sources of baseline data for evaluating trends in community-based treatment coverage for childhood illnesses. Our examination of the questionnaires used in Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) conducted between 2005 and 2010 in five sub-Saharan African countries shows that questions on care seeking that included a locally adapted option for a community-based provider were present in all the DHS surveys and in some MICS surveys. Most of the surveys also assessed whether appropriate treatments were available, but only one survey collected information on the place of treatment for all three illnesses. This absence of baseline data on treatment source in household surveys will limit efforts to evaluate the effects of the introduction of CCM strategies in the study countries. We recommend alternative analysis plans for assessing CCM programs using household survey data that depend on baseline data availability and on the timing of CCM policy implementation. PMID:23667329

  16. Final report on key comparison APMP.M.P-K13 in hydraulic gauge pressure from 50 MPa to 500 MPa

    NASA Astrophysics Data System (ADS)

    Kajikawa, Hiroaki; Kobata, Tokihiko; Yadav, Sanjay; Jian, Wu; Changpan, Tawat; Owen, Neville; Yanhua, Li; Hung, Chen-Chuan; Ginanjar, Gigin; Choi, In-Mook

    2015-01-01

    This report describes the results of a key comparison of hydraulic high-pressure standards at nine National Metrology Institutes (NMIs: NMIJ/AIST, NPLI, NMC/A*STAR, NIMT, NMIA, NIM, CMS/ITRI, KIM-LIPI, and KRISS) within the framework of the Asia-Pacific Metrology Programme (APMP) in order to determine their degrees of equivalence in the pressure range from 50 MPa to 500 MPa in gauge mode. The pilot institute was the National Metrology Institute of Japan (NMIJ/AIST). All participating institutes used hydraulic pressure balances as their pressure standards. A set of pressure balance with a free-deformational piston-cylinder assembly was used as the transfer standard. Three piston-cylinder assemblies, only one at a time, were used to complete the measurements in the period from November 2010 to January 2013. Ten participants completed their measurements and reported the pressure-dependent effective areas of the transfer standard at specified pressures with the associated uncertainties. Since one of the participants withdrew its results, the measurement results of the nine participants were finally compared. The results were linked to the CCM.P-K13 reference values through the results of two linking laboratories, NMIJ/AIST and NPLI. The degrees of equivalence were evaluated by the relative deviations of the participants' results from the CCM.P-K13 key comparison reference values, and their associated combined expanded (k=2) uncertainties. The results of all the nine participating NMIs agree with the CCM.P-K13 reference values within their expanded (k=2) uncertainties in the entire pressure range from 50 MPa to 500 MPa. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  17. Association between community management of pneumonia and diarrhoea in high-burden countries and the decline in under-five mortality rates: an ecological analysis.

    PubMed

    Boschi-Pinto, Cynthia; Dilip, Thandassery Ramachandran; Costello, Anthony

    2017-02-14

    The objective of the paper is to explore if the adoption of national policies to use community-based health providers for the management of pneumonia and diarrhoea is associated with the decline in under-five mortality, including achievement of the Millennium Development Goal (MDG)4 target, in high-burden countries. This country level analysis covers 75 high-burden low-income and middle-income countries which accounted for 98% of the 5.9 million global under-five deaths in 2015. One-fourth of these deaths were due to pneumonia and diarrhoea. χ 2 tests and multiple regression analysis were used to examine the association between reduction in under-five mortality rates and community case management of pneumonia and diarrhoea by adjusting for the influence of other possible determinants. No patient or population interviewed/examined for this analysis. Countries were the unit of analysis. Community case management (CCM) of pneumonia and diarrhoea policies. Changes in under-five mortality rates over time. Countries that had adopted both CCM policies were three times more likely to achieve the MDG4 target than countries that did not have both policies in place. This association was further confirmed by the multivariate analysis (β-coefficient=10.4; 95% CI 2.4 to 18.5; p value=0.012). There is a statistically significant association between adoption of CCM policies for treatment of pneumonia and diarrhoea and the rate of decline in child mortality levels. It is important to promote CCM in countries lagging behind to achieve the new target of 25 or fewer deaths per 1000 live births by 2030. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. Biona-C Cell Culture pH Monitoring System

    NASA Technical Reports Server (NTRS)

    Friedericks, C.

    1999-01-01

    Sensors 2000! is developing a system to demonstrate the ability to perform accurate, real-time measurements of pH and CO2 in a cell culture media in Space. The BIONA-C Cell Culture pH Monitoring System consists of S2K! developed ion selective sensors and control electronics integrated with the fluidics of a cell culture system. The integrated system comprises a "rail" in the Cell Culture Module (CCM) of WRAIR (Space Biosciences of Walter Read Army Institute of Research). The CCM is a Space Shuttle mid-deck locker experiment payload. The BIONA-C is displayed along with associated graphics and text explanations. The presentation will stimulate interest in development of sensor technology for real-time cell culture measurements. The transfer of this technology to other applications will also be of interest. Additional information is contained in the original document.

  19. The annual cycle of stratospheric water vapor in a general circulation model

    NASA Technical Reports Server (NTRS)

    Mote, Philip W.

    1995-01-01

    The application of general circulation models (GCM's) to stratospheric chemistry and transport both permits and requires a thorough investigation of stratospheric water vapor. The National Center for Atmospheric Research has redesigned its GCM, the Community Climate Model (CCM2), to enable studies of the chemistry and transport of tracers including water vapor; the importance of water vapor to the climate and chemistry of the stratosphere requires that it be better understood in the atmosphere and well represented in the model. In this study, methane is carried as a tracer and converted to water; this simple chemistry provides an adequate representation of the upper stratospheric water vapor source. The cold temperature bias in the winter polar stratosphere, which the CCM2 shares with other GCM's, produces excessive dehydration in the southern hemisphere, but this dry bias can be ameliorated by setting a minimum vapor pressure. The CCM2's water vapor distribution and seasonality compare favorably with observations in many respects, though seasonal variations including the upper stratospheric semiannual oscillation are generally too small. Southern polar dehydration affects midlatitude water vapor mixing ratios by a few tenths of a part per million, mostly after the demise of the vortex. The annual cycle of water vapor in the tropical and northern midlatitude lower stratosphere is dominated by drying at the tropical tropopause. Water vapor has a longer adjustment time than methane and had not reached equilibrium at the end of the 9 years simulated here.

  20. CCM Continuity Constraint Method: A finite-element computational fluid dynamics algorithm for incompressible Navier-Stokes fluid flows

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Williams, P. T.

    1993-09-01

    As the field of computational fluid dynamics (CFD) continues to mature, algorithms are required to exploit the most recent advances in approximation theory, numerical mathematics, computing architectures, and hardware. Meeting this requirement is particularly challenging in incompressible fluid mechanics, where primitive-variable CFD formulations that are robust, while also accurate and efficient in three dimensions, remain an elusive goal. This dissertation asserts that one key to accomplishing this goal is recognition of the dual role assumed by the pressure, i.e., a mechanism for instantaneously enforcing conservation of mass and a force in the mechanical balance law for conservation of momentum. Provingmore » this assertion has motivated the development of a new, primitive-variable, incompressible, CFD algorithm called the Continuity Constraint Method (CCM). The theoretical basis for the CCM consists of a finite-element spatial semi-discretization of a Galerkin weak statement, equal-order interpolation for all state-variables, a 0-implicit time-integration scheme, and a quasi-Newton iterative procedure extended by a Taylor Weak Statement (TWS) formulation for dispersion error control. Original contributions to algorithmic theory include: (a) formulation of the unsteady evolution of the divergence error, (b) investigation of the role of non-smoothness in the discretized continuity-constraint function, (c) development of a uniformly H 1 Galerkin weak statement for the Reynolds-averaged Navier-Stokes pressure Poisson equation, (d) derivation of physically and numerically well-posed boundary conditions, and (e) investigation of sparse data structures and iterative methods for solving the matrix algebra statements generated by the algorithm.« less

  1. Ocean acidification alleviates low-temperature effects on growth and photosynthesis of the red alga Neosiphonia harveyi (Rhodophyta).

    PubMed

    Olischläger, Mark; Wiencke, Christian

    2013-12-01

    This study aimed to examine interactive effects between ocean acidification and temperature on the photosynthetic and growth performance of Neosiphonia harveyi. N. harveyi was cultivated at 10 and 17.5 °C at present (~380 µatm), expected future (~800 µatm), and high (~1500 µatm) pCO2. Chlorophyll a fluorescence, net photosynthesis, and growth were measured. The state of the carbon-concentrating mechanism (CCM) was examined by pH-drift experiments (with algae cultivated at 10 °C only) using ethoxyzolamide, an inhibitor of external and internal carbonic anhydrases (exCA and intCA, respectively). Furthermore, the inhibitory effect of acetazolamide (an inhibitor of exCA) and Tris (an inhibitor of the acidification of the diffusive boundary layer) on net photosynthesis was measured at both temperatures. Temperature affected photosynthesis (in terms of photosynthetic efficiency, light saturation point, and net photosynthesis) and growth at present pCO2, but these effects decreased with increasing pCO2. The relevance of the CCM decreased at 10 °C. A pCO2 effect on the CCM could only be shown if intCA and exCA were inhibited. The experiments demonstrate for the first time interactions between ocean acidification and temperature on the performance of a non-calcifying macroalga and show that the effects of low temperature on photosynthesis can be alleviated by increasing pCO2. The findings indicate that the carbon acquisition mediated by exCA and acidification of the diffusive boundary layer decrease at low temperatures but are not affected by the cultivation level of pCO2, whereas the activity of intCA is affected by pCO2. Ecologically, the findings suggest that ocean acidification might affect the biogeographical distribution of N. harveyi.

  2. Effects of temperature, pH and NaCl content on in vitro putrescine and cadaverine production through the growth of Serratia marcescens CCM 303.

    PubMed

    Bubelová, Zuzana; Buňka, František; Taťáková, Monika; Štajnochová, Kateřina; Purevdorj, Khatantuul; Buňková, Leona

    2015-01-01

    The aim of this study was to evaluate the combined effect of temperature (10, 20 and 37°C), pH (4, 5, 6, 7 and 8), and NaCl content (0, 1, 3, 4, 5 and 6% w/v) on the growth and putrescine and cadaverine production of Serratia marcescens CCM 303 under model conditions. The decarboxylase activity of S. marcescens was monitored in broth after cultivation. The cultivation medium was enriched with selected amino acids (ornithine, arginine and lysine; 0.2% w/v each) serving as precursors of biogenic amines. Levels of putrescine and cadaverine in broth were analysed by high-performance liquid chromatography after pre-column derivatisation with o-phthalaldehyde reagent. S. marcescens produced higher amounts of putrescine (up to 2096.8 mg L(-1)) compared to cadaverine content (up to 343.3 mg L(-1)) in all cultivation media. The highest putrescine and cadaverine concentrations were reached during cultivation at 10-20°C, pH 5-7 and NaCl content 1-3% w/v. On the other hand, the highest BAs production of individual cell (recalculated based on a cell; so called "yield factor") was observed at 10°C, pH 4 and salt concentration 3-5% w/v as a response to environmental stress.

  3. Automated Means of Identifying Landslide Deposits using LiDAR Data using the Contour Connection Method Algorithm

    NASA Astrophysics Data System (ADS)

    Olsen, M. J.; Leshchinsky, B. A.; Tanyu, B. F.

    2014-12-01

    Landslides are a global natural hazard, resulting in severe economic, environmental and social impacts every year. Often, landslides occur in areas of repeated slope instability, but despite these trends, significant residential developments and critical infrastructure are built in the shadow of past landslide deposits and marginally stable slopes. These hazards, despite their sometimes enormous scale and regional propensity, however, are difficult to detect on the ground, often due to vegetative cover. However, new developments in remote sensing technology, specifically Light Detection and Ranging mapping (LiDAR) are providing a new means of viewing our landscape. Airborne LiDAR, combined with a level of post-processing, enable the creation of spatial data representative of the earth beneath the vegetation, highlighting the scars of unstable slopes of the past. This tool presents a revolutionary technique to mapping landslide deposits and their associated regions of risk; yet, their inventorying is often done manually, an approach that can be tedious, time-consuming and subjective. However, the associated LiDAR bare earth data present the opportunity to use this remote sensing technology and typical landslide geometry to create an automated algorithm that can detect and inventory deposits on a landscape scale. This algorithm, called the Contour Connection Method (CCM), functions by first detecting steep gradients, often associated with the headscarp of a failed hillslope, and initiating a search, highlighting deposits downslope of the failure. Based on input of search gradients, CCM can assist in highlighting regions identified as landslides consistently on a landscape scale, capable of mapping more than 14,000 hectares rapidly (<30 minutes). CCM has shown preliminary agreement with manual landslide inventorying in Oregon's Coast Range, realizing almost 90% agreement with inventorying performed by a trained geologist. The global threat of landslides necessitates new and effective tools for inventorying regions of risk to protect people, infrastructure and the environment from landslide hazards. Use of the CCM algorithm combined with judgment and rapidly developing remote sensing technology may help better define these regions of risk.

  4. Structure/Function of the Novel Proteins LCIB and LCIC in the Chlamydomonas CCM

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martin, Spalding H.

    2017-05-09

    The goal of this project was to investigate the function of two novel proteins, LCIB and LCIC, which together form an essential protein complex that is required for function of a carbon-dioxide-concentrating mechanism (CCM) required by microalgae to grow in environments where carbon dioxide levels are at or below air equilibration levels.

  5. Effective Reading Comprehension in EFL Contexts: Individual and Collaborative Concept Mapping Strategies

    ERIC Educational Resources Information Center

    Riahi, Zahra; Pourdana, Natasha

    2017-01-01

    The present study attempted to investigate the possible impacts of Individual Concept Mapping (ICM) and Collaborative Concept Mapping (CCM) strategies on Iranian EFL learners' reading comprehension. For this purpose, 90 pre-intermediate female language learners ranged between 12 to 17 years of age were selected to randomly assign into ICM, CCM and…

  6. The Canadian Heart Health Strategy and Action Plan: Cardiac rehabilitation as an exemplar of chronic disease management.

    PubMed

    Arthur, H M; Suskin, N; Bayley, M; Fortin, M; Howlett, J; Heckman, G; Lewanczuk, R

    2010-01-01

    In October 2006, federal funding was announced for the development of a national strategy to fight cardiovascular disease (CVD) in Canada. The comprehensive, independent, stakeholder-driven Canadian Heart Health Strategy and Action Plan (CHHS-AP) was delivered to the Minister of Health on February 24, 2009. The mandate of CHHS-AP Theme Working Group (TWG) 6 was to identify the optimal chronic disease management model that incorporated timely access to rehabilitation services and end-of-life planning and care. The purpose of the present paper was to provide an overview of worldwide approaches to CVD and cardiac rehabilitation (CR) strategies and recommendations for CR care in Canada, within the context of the well-known Chronic Care Model (CCM). A separate paper will address end-of-life issues in CVD. TWG 6 was composed of content representatives, primary care representatives and patients. Input in the area of Aboriginal and indigenous cardiovascular health was obtained through individual expert consultation. Information germane to the present paper was gathered from international literature and best practice guidelines. The CCM principles were discussed and agreed on by all. Prioritization of recommendations and overall messaging was discussed and decided on within the entire TWG. The full TWG report was presented to the CHHS-AP Steering Committee and was used to inform the recommendations of the CHHS-AP. Specific actionable recommendations for CR are made in accordance with the key principles of the CCM. The present CR blueprint, as part of the CHHS-AP, will be a first step toward reducing the health care burden of CVD in Canada.

  7. Community dialogues for child health: results from a qualitative process evaluation in three countries.

    PubMed

    Martin, Sandrine; Leitão, Jordana; Muhangi, Denis; Nuwa, Anthony; Magul, Dieterio; Counihan, Helen

    2017-06-05

    Across the developing world, countries are increasingly adopting the integrated community case management of childhood illnesses (iCCM) strategy in efforts to reduce child mortality. This intervention's effectiveness is dependent on community adoption and changes in care-seeking practices. We assessed the implementation process of a theory-driven community dialogue (CD) intervention specifically designed to strengthen the support and uptake of the newly introduced iCCM services and related behaviours in three African countries. A qualitative process evaluation methodology was chosen and used secondary project data and primary data collected in two districts of each of the three countries, in purposefully sampled communities. The final data set included 67 focus group discussions and 57 key informant interviews, totalling 642 respondents, including caregivers, CD facilitators community leaders, and trainers. Thematic analysis of the data followed the 'Framework Approach' utilising both a deduction and induction process. Results show that CDs contribute to triggering community uptake of and support for iCCM services through filling health information gaps and building cooperation within communities. We found it to be an effective approach for addressing social norms around child care practices. This approach was embraced by communities for its flexibility and value in planning individual and collective change. Regular CDs can contribute to the formation of new habits, particularly in relation to seeking timely care in case of child sickness. This study also confirms the value of process evaluation to unwrap the mechanisms of community mobilisation approaches in context and provides key insights for improving the CD approach.

  8. Spatial analysis improves the detection of early corneal nerve fiber loss in patients with recently diagnosed type 2 diabetes

    PubMed Central

    Winter, Karsten; Strom, Alexander; Zhivov, Andrey; Allgeier, Stephan; Papanas, Nikolaos; Ziegler, Iris; Brüggemann, Jutta; Ringel, Bernd; Peschel, Sabine; Köhler, Bernd; Stachs, Oliver; Guthoff, Rudolf F.; Roden, Michael

    2017-01-01

    Corneal confocal microscopy (CCM) has revealed reduced corneal nerve fiber (CNF) length and density (CNFL, CNFD) in patients with diabetes, but the spatial pattern of CNF loss has not been studied. We aimed to determine whether spatial analysis of the distribution of corneal nerve branching points (CNBPs) may contribute to improving the detection of early CNF loss. We hypothesized that early CNF decline follows a clustered rather than random distribution pattern of CNBPs. CCM, nerve conduction studies (NCS), and quantitative sensory testing (QST) were performed in a cross-sectional study including 86 patients recently diagnosed with type 2 diabetes and 47 control subjects. In addition to CNFL, CNFD, and branch density (CNBD), CNBPs were analyzed using spatial point pattern analysis (SPPA) including 10 indices and functional statistics. Compared to controls, patients with diabetes showed lower CNBP density and higher nearest neighbor distances, and all SPPA parameters indicated increased clustering of CNBPs (all P<0.05). SPPA parameters were abnormally increased >97.5th percentile of controls in up to 23.5% of patients. When combining an individual SPPA parameter with CNFL, ≥1 of 2 indices were >99th or <1st percentile of controls in 28.6% of patients compared to 2.1% of controls, while for the conventional CNFL/CNFD/CNBD combination the corresponding rates were 16.3% vs 2.1%. SPPA parameters correlated with CNFL and several NCS and QST indices in the controls (all P<0.001), whereas in patients with diabetes these correlations were markedly weaker or lost. In conclusion, SPPA reveals increased clustering of early CNF loss and substantially improves its detection when combined with a conventional CCM measure in patients with recently diagnosed type 2 diabetes. PMID:28296936

  9. Silibinin prevents prostate cancer cell-mediated differentiation of naïve fibroblasts into cancer-associated fibroblast phenotype by targeting TGF β2.

    PubMed

    Ting, Harold J; Deep, Gagan; Jain, Anil K; Cimic, Adela; Sirintrapun, Joseph; Romero, Lina M; Cramer, Scott D; Agarwal, Chapla; Agarwal, Rajesh

    2015-09-01

    Tumor microenvironment (TM) is an essential element in prostate cancer (PCA), offering unique opportunities for its prevention. TM includes naïve fibroblasts that are recruited by nascent neoplastic lesion and altered into 'cancer-associated fibroblasts' (CAFs) that promote PCA. A better understanding and targeting of interaction between PCA cells and fibroblasts and inhibiting CAF phenotype through non-toxic agents are novel approaches to prevent PCA progression. One well-studied cancer chemopreventive agent is silibinin, and thus, we examined its efficacy against PCA cells-mediated differentiation of naïve fibroblasts into a myofibroblastic-phenotype similar to that found in CAFs. Silibinin's direct inhibitory effect on the phenotype of CAFs derived directly from PCA patients was also assessed. Human prostate stromal cells (PrSCs) exposed to control conditioned media (CCM) from human PCA PC3 cells showed more invasiveness, with increased alpha-smooth muscle actin (α-SMA) and vimentin expression, and differentiation into a phenotype we identified in CAFs. Importantly, silibinin (at physiologically achievable concentrations) inhibited α-SMA expression and invasiveness in differentiated fibroblasts and prostate CAFs directly, as well as indirectly by targeting PCA cells. The observed increase in α-SMA and CAF-like phenotype was transforming growth factor (TGF) β2 dependent, which was strongly inhibited by silibinin. Furthermore, induction of α-SMA and CAF phenotype by CCM were also strongly inhibited by a TGFβ2-neutralizing antibody. The inhibitory effect of silibinin on TGFβ2 expression and CAF-like biomarkers was also observed in PC3 tumors. Together, these findings highlight the potential usefulness of silibinin in PCA prevention through targeting the CAF phenotype in the prostate TM. © 2014 Wiley Periodicals, Inc.

  10. Research in disaster settings: a systematic qualitative review of ethical guidelines.

    PubMed

    Mezinska, Signe; Kakuk, Péter; Mijaljica, Goran; Waligóra, Marcin; O'Mathúna, Dónal P

    2016-10-21

    Conducting research during or in the aftermath of disasters poses many specific practical and ethical challenges. This is particularly the case with research involving human subjects. The extraordinary circumstances of research conducted in disaster settings require appropriate regulations to ensure the protection of human participants. The goal of this study is to systematically and qualitatively review the existing ethical guidelines for disaster research by using the constant comparative method (CCM). We performed a systematic qualitative review of disaster research ethics guidelines to collect and compare existing regulations. Guidelines were identified by a three-tiered search strategy: 1) searching databases (PubMed and Google Scholar), 2) an Internet search (Google), and 3) a search of the references in the included documents from the first two searches. We used the constant comparative method (CCM) for analysis of included guidelines. Fourteen full text guidelines were included for analysis. The included guidelines covered the period 2000-2014. Qualitative analysis of the included guidelines revealed two core themes: vulnerability and research ethics committee review. Within each of the two core themes, various categories and subcategories were identified. Some concepts and terms identified in analyzed guidelines are used in an inconsistent manner and applied in different contexts. Conceptual clarity is needed in this area as well as empirical evidence to support the statements and requirements included in analyzed guidelines.

  11. Effectiveness of comprehensive care programs for patients with multiple chronic conditions or frailty: A systematic literature review.

    PubMed

    Hopman, Petra; de Bruin, Simone R; Forjaz, Maria João; Rodriguez-Blazquez, Carmen; Tonnara, Giuseppe; Lemmens, Lidwien C; Onder, Graziano; Baan, Caroline A; Rijken, Mieke

    2016-07-01

    To describe comprehensive care programs targeting multimorbid and/or frail patients and to estimate their effectiveness regarding improvement of patient and caregiver related outcomes, healthcare utilization and costs. Systematic search in six electronic databases for scientific papers published between January 2011 and March 2014, supplemented by reference tracking. Wagner's Chronic Care Model (CCM) was used to operationalize comprehensive care. The quality of the included studies was assessed, and a best-evidence synthesis was applied. Nineteen publications were included describing effects of eighteen comprehensive care programs for multimorbid or frail patients, of which only one was implemented in a European country. Programs varied in target groups, settings, interventions and number of CCM components addressed. Providing comprehensive care might result in more patient satisfaction, less depressive symptoms, a better health-related quality of life or functioning of multimorbid or frail patients, but the evidence is insufficient. There is no evidence that comprehensive care reduces the number of primary care or GP visits or healthcare costs. Regarding the use of inpatient care, the evidence was insufficient. No evidence was found for a beneficial effect of comprehensive care on caregiver-related outcomes. Despite the fact that over the years several (good-quality) studies have been performed to estimate the value of comprehensive care for multimorbid and/or frail patients, evidence for their effectiveness remains insufficient. More good-quality studies and/or studies allowing meta-analysis are needed to determine which specific target groups at what moment will benefit from comprehensive care. Moreover, evaluation studies could improve by using more appropriate outcome measures, e.g. measures that relate to patient-defined (personal) goals of care. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Implementation of a program for type 2 diabetes based on the Chronic Care Model in a hospital-centered health care system: "the Belgian experience".

    PubMed

    Sunaert, Patricia; Bastiaens, Hilde; Feyen, Luc; Snauwaert, Boris; Nobels, Frank; Wens, Johan; Vermeire, Etienne; Van Royen, Paul; De Maeseneer, Jan; De Sutter, An; Willems, Sara

    2009-08-23

    Most research publications on Chronic Care Model (CCM) implementation originate from organizations or countries with a well-structured primary health care system. Information about efforts made in countries with a less well-organized primary health care system is scarce. In 2003, the Belgian National Institute for Health and Disability Insurance commissioned a pilot study to explore how care for type 2 diabetes patients could be organized in a more efficient way in the Belgian healthcare setting, a setting where the organisational framework for chronic care is mainly hospital-centered. Process evaluation of an action research project (2003-2007) guided by the CCM in a well-defined geographical area with 76,826 inhabitants and an estimated number of 2,300 type 2 diabetes patients. In consultation with the region a program for type 2 diabetes patients was developed. The degree of implementation of the CCM in the region was assessed using the Assessment of Chronic Illness Care survey (ACIC). A multimethod approach was used to evaluate the implementation process. The resulting data were triangulated in order to identify the main facilitators and barriers encountered during the implementation process. The overall ACIC score improved from 1.45 (limited support) at the start of the study to 5.5 (basic support) at the end of the study. The establishment of a local steering group and the appointment of a program manager were crucial steps in strengthening primary care. The willingness of a group of well-trained and motivated care providers to invest in quality improvement was an important facilitator. Important barriers were the complexity of the intervention, the lack of quality data, inadequate information technology support, the lack of commitment procedures and the uncertainty about sustainable funding. Guided by the CCM, this study highlights the opportunities and the bottlenecks for adapting chronic care delivery in a primary care system with limited structure. The study succeeded in achieving a considerable improvement of the overall support for diabetes patients but further improvement requires a shift towards system thinking among policy makers. Currently primary care providers lack the opportunities to take up full responsibility for chronic care. ClinicalTrials.gov Identifier: NCT00824499.

  13. Formation of self-assembled monolayer of curcuminoid molecules on gold surfaces

    NASA Astrophysics Data System (ADS)

    Berlanga, Isadora; Etcheverry-Berríos, Álvaro; Mella, Andy; Jullian, Domingo; Gómez, Victoria Alejandra; Aliaga-Alcalde, Núria; Fuenzalida, Victor; Flores, Marcos; Soler, Monica

    2017-01-01

    We investigated the formation of self-assembled monolayers of two thiophene curcuminoid molecules, 2-thphCCM (1) and 3-thphCCM (2), on polycrystalline gold substrates prepared by immersion of the surfaces in a solution of the molecules during 24 h. The functionalized surfaces were studied by scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy (XPS). Despite the fact that both molecules have the same composition and almost the same structure, these molecules exhibit different behavior on the gold surface, which can be explained by the different positions of the sulfur atoms in the terminal aromatic rings. In the case of molecule 1, the complete formation of a SAM can be observed after 24 h of immersion. In the case of molecule 2, the transition from flat-lying to upright configuration on the surface is still in process after 24 h of immersion. This is attributed to the fact that molecule 2 have the sulfur atoms more exposed than molecule 1.

  14. Sustained Axenic Metabolic Activity by the Obligate Intracellular Bacterium Coxiella burnetii▿ †

    PubMed Central

    Omsland, Anders; Cockrell, Diane C.; Fischer, Elizabeth R.; Heinzen, Robert A.

    2008-01-01

    Growth of Coxiella burnetii, the agent of Q fever, is strictly limited to colonization of a viable eukaryotic host cell. Following infection, the pathogen replicates exclusively in an acidified (pH 4.5 to 5) phagolysosome-like parasitophorous vacuole. Axenic (host cell free) buffers have been described that activate C. burnetii metabolism in vitro, but metabolism is short-lived, with bacterial protein synthesis halting after a few hours. Here, we describe a complex axenic medium that supports sustained (>24 h) C. burnetii metabolic activity. As an initial step in medium development, several biological buffers (pH 4.5) were screened for C. burnetii metabolic permissiveness. Based on [35S]Cys-Met incorporation, C. burnetii displayed optimal metabolic activity in citrate buffer. To compensate for C. burnetii auxotrophies and other potential metabolic deficiencies, we developed a citrate buffer-based medium termed complex Coxiella medium (CCM) that contains a mixture of three complex nutrient sources (neopeptone, fetal bovine serum, and RPMI cell culture medium). Optimal C. burnetii metabolism occurred in CCM with a high chloride concentration (140 mM) while the concentrations of sodium and potassium had little effect on metabolism. CCM supported prolonged de novo protein and ATP synthesis by C. burnetii (>24 h). Moreover, C. burnetii morphological differentiation was induced in CCM as determined by the transition from small-cell variant to large-cell variant. The sustained in vitro metabolic activity of C. burnetii in CCM provides an important tool to investigate the physiology of this organism including developmental transitions and responses to antimicrobial factors associated with the host cell. PMID:18310349

  15. Evaluation of antioxidant and xanthine oxidase inhibitory activity of different solvent extracts of leaves of Citrullus colocynthis

    PubMed Central

    Nessa, Fazilatun; Khan, Saeed A.

    2014-01-01

    Background: Citrullus colocynthis is a folk medicinal plan of United Arab Emirates. Several studies on this plant reported and focused on the biological and toxicological profile of fruits pulp. The present study focused on the antioxidant potency of leaf extract of this plant. Aim: To evaluate the antioxidant and xanthine oxidase (XO) inhibitory activities of C. colocynthis by chemical method. Materials and Methods: Four different solvent extracts (methanol-CCM, methanol: water (1:1)-CCMW, chloroform-CCC and hexane-CCH) of leaves of C. colocynthis were investigated for their free radical scavenging activity using DPPH radical as a substrate, lipid peroxidation (LPO) inhibitory activity using a model system consisting of β-carotene-linoleic acid, superoxide radical scavenging activity (enzymatically/nonenzymatically) and XO inhibitory activity. A dose response curve was plotted for determining SC50 and IC50 values for expressing the results of free radical scavenging activity and XO inhibitory activities respectively. Results: The high polyphenolic content of CCM and CCMW extract showed highest antioxidant activity irrespective the method used for this investigation. The overall results decreased in the order of: CCM > CCMW > CCC > CCH. CCH extract was inactive towards chemically generated superoxide radical and poor DPPH radical scavengers. The results of LPO inhibitory activities of leaves extract (0.1, 0.5 and 1.0 mg/mL) also decreased in the order of: CCM > CCMW > CCC > CCH. Overall 1.0 mg/mL leaves extract showed highest antioxidant potency amongst the studied concentration. Conclusion: CCMW and CCM extract of C. colocynthis exhibited promising antioxidants and XO inhibitory activities. PMID:25002802

  16. Impact of Personality Disorder Cluster on Depression Outcomes Within Collaborative Care Management Model of Care.

    PubMed

    George, Merit P; Garrison, Gregory M; Merten, Zachary; Heredia, Dagoberto; Gonzales, Cesar; Angstman, Kurt B

    2018-01-01

    Previous studies have suggested that having a comorbid personality disorder (PD) along with major depression is associated with poorer depression outcomes relative to those without comorbid PD. However, few studies have examined the influence of specific PD cluster types. The purpose of the current study is to compare depression outcomes between cluster A, cluster B, and cluster C PD patients treated within a collaborative care management (CCM), relative to CCM patients without a PD diagnosis. The overarching goal was to identify cluster types that might confer a worse clinical prognosis. This retrospective chart review study examined 2826 adult patients with depression enrolled in CCM. The cohort was divided into 4 groups based on the presence of a comorbid PD diagnosis (cluster A/nonspecified, cluster B, cluster C, or no PD). Baseline clinical and demographic variables, along with 6-month follow-up Patient Health Questionnaire-9 (PHQ-9) scores were obtained for all groups. Depression remission was defined as a PHQ-9 score <5 at 6 months, and persistent depressive symptoms (PDS) was defined as a PHQ-9 score ≥10 at 6 months. Adjusted odds ratios (AORs) were determined for both remission and PDS using logistic regression modeling for the 6-month PHQ-9 outcome, while retaining all study variables. A total of 59 patients (2.1%) had a cluster A or nonspecified PD diagnosis, 122 patients (4.3%) had a cluster B diagnosis, 35 patients (1.2%) had a cluster C diagnosis, and 2610 patients (92.4%) did not have any PD diagnosis. The presence of a cluster A/nonspecified PD diagnosis was associated with a 62% lower likelihood of remission at 6 months (AOR = 0.38; 95% CI 0.20-0.70). The presence of a cluster B PD diagnosis was associated with a 71% lower likelihood of remission at 6 months (AOR = 0.29; 95% CI 0.18-0.47). Conversely, having a cluster C diagnosis was not associated with a significantly lower likelihood of remission at 6 months (AOR = 0.83; 95% CI 0.42-1.65). Increased odds of having PDS at 6-month follow-up were seen with cluster A/nonspecified PD patients (AOR = 3.35; 95% CI 1.92-5.84) as well as cluster B patients (AOR = 3.66; 95% CI 2.45-5.47). However, cluster C patents did not have significantly increased odds of experiencing persistent depressive symptoms at 6-month follow-up (AOR = 0.95; 95% CI 0.45-2.00). Out of the 3 clusters, the presence of a cluster B PD diagnosis was most significantly associated with poorer depression outcomes at 6-month follow-up, including reduced remission rates and increased risk for PDS. The cluster A/nonspecified PD group also showed poor outcomes; however, the heterogeneity of this subgroup with regard to PD features must be noted. The development of novel targeted interventions for at-risk clusters may be warranted in order to improve outcomes of these patients within the CCM model of care.

  17. Final report on CCM key comparison CCM.D-K2: Comparison of liquid density standards

    NASA Astrophysics Data System (ADS)

    Bettin, Horst; Jacques, Claude; Zelenka, Zoltán; Fujii, Ken-ichi; Kuramoto, Naoki; Chang, Kyung-Ho; Lee, Yong Jae; Becerra, Luis Omar; Domostroeva, Natalia

    2013-01-01

    The results are presented of the key comparison CCM.D-K2 that covered the density measurements of four liquids: the density of water at 20 °C, of pentadecane at 15 °C, 20 °C, 40 °C and 60°C, of tetrachloroethlyene at 5 °C and 20 °C and of a viscous oil at 20 °C. Seven national metrology institutes measured the densities at atmospheric pressure by hydrostatic weighing of solid density standards in the time interval from 27 April 2004 to 28 June 2004. Since the participants were asked not to include components for a possible drift or inhomogeneity of the liquid in their uncertainty budget, these uncertainty contributions are investigated for the final evaluation of the data. For this purpose, results of stability and homogeneity measurements of the pilot laboratory are used. The participants decided not to include a possible drift of the liquid's density since no significant drift could be detected, and the influence of the drift and its uncertainty are negligible. Similarly, the inhomogeneity of the water and pentadecane samples is not significant and has no influence on the evaluation. Thus, it was neglected. Only the inhomogeneities of tetrachloroethylene and of the viscous oil were significant. Consequently, they were included in the evaluation. With one or two exceptions, the results show good agreement among the participants. Only in the case of water are the results clearly discrepant. The key comparison reference values were calculated by the weighted mean (taking into account a small correlation between two participants) in the case of consistent results. Otherwise the Procedure B of Cox was used. The expanded uncertainties of all reference densities are below 1 × 10-5 in relative terms. This satisfies the needs of all customers who wish to calibrate or check liquid density measuring instruments such as oscillation-type density meters. The comparison fully supports the calibration measurement capabilities table in the BIPM key comparison database. The results can be used to link regional comparisons to this CCM key comparison. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  18. Evaluation of Acoustic Emission NDE of Composite Crew Module Service Module/Alternate Launch Abort System (CCM SM/ALAS) Test Article Failure Tests

    NASA Technical Reports Server (NTRS)

    Horne, Michael R.; Madaras, Eric I.

    2010-01-01

    Failure tests of CCM SM/ALAS (Composite Crew Module Service Module / Alternate Launch Abort System) composite panels were conducted during July 10, 2008 and July 24, 2008 at Langley Research Center. This is a report of the analysis of the Acoustic Emission (AE) data collected during those tests.

  19. Final report on COOMET Vickers PTB/VNIIFTRI key comparison (COOMET.M.H-K1.b and COOMET.M.H-K1.c)

    NASA Astrophysics Data System (ADS)

    Aslanyan, E.; Herrmann, K.

    2013-01-01

    This report describes a COOMET key comparison on Vickers hardness scales of two National Metrology Institutes—PTB and VNIIFTRI. The pilot laboratory was PTB, which was the linking institute with the key comparison reference values of CCM.H-K1. In the key comparison two sets of hardness reference blocks for the Vickers hardness scales HV1 and HV30, each consisting of three hardness reference blocks with the hardness levels 240 HV, 540 HV and 840 HV, are used. The same hardness reference blocks were used previously in the key comparison CCM.H-K1. The measurement results and uncertainty assessments, announced by VNIIFTRI, are in good agreement with the key comparison reference values of CCM.H-K1. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  20. Perceived Quality of Care of Community Health Worker and Facility-Based Health Worker Management of Pneumonia in Children Under 5 Years in Western Kenya: A Cross-Sectional Multidimensional Study

    PubMed Central

    Shaw, Brian I.; Asadhi, Elijah; Owuor, Kevin; Okoth, Peter; Abdi, Mohammed; Cohen, Craig R.; Onono, Maricianah

    2016-01-01

    Integrated community case management (iCCM) programs that train lay community health workers (CHWs) in the diagnosis and treatment of diarrhea, malaria, and pneumonia have been increasingly adopted throughout sub-Saharan Africa to provide services in areas where accessibility to formal public sector health services is low. One important aspect of successful iCCM programs is the acceptability and utilization of services provided by CHWs. To understand community perceptions of the quality of care in an iCCM intervention in western Kenya, we used the Primary Care Assessment Survey to compare caregiver attitudes about the diagnosis and treatment of childhood pneumonia as provided by CHWs and facility-based health workers (FBHWs). Overall, caregivers rated CHWs more highly than FBHWs across a set of 10 domains that capture multiple dimensions of the care process. Caregivers perceived CHWs to provide higher quality care in terms of accessibility and patient relationship and equal quality care on clinical aspects. These results argue for the continued implementation and scale-up of iCCM programs as an acceptable intervention for increasing access to treatment of childhood pneumonia. PMID:26976883

  1. The Global Fund: managing great expectations.

    PubMed

    Brugha, Ruairí; Donoghue, Martine; Starling, Mary; Ndubani, Phillimon; Ssengooba, Freddie; Fernandes, Benedita; Walt, Gill

    The Global Fund to fight AIDS, Tuberculosis, and Malaria was created to increase funds to combat these three devastating diseases. We report interim findings, based on interviews with 137 national-level respondents that track early implementation processes in four African countries. Country coordinating mechanisms (CCMs) are country-level partnerships, which were formed quickly to develop and submit grant proposals to the Global Fund. CCM members were often ineffective at representing their constituencies and encountered obstacles in participating in CCM processes. Delay in dissemination of guidelines from the Global Fund led to uncertainty among members about the function of these new partnerships. Respondents expressed most concern about the limited capacity of fund recipients--government and non-government--to meet Global Fund conditions for performance-based disbursement. Delays in payment of funds to implementing agencies have frustrated rapid financing of disease control interventions. The Global Fund is one of several new global initiatives superimposed on existing country systems to finance the control of HIV/AIDS. New and existing donors need to coordinate assistance to developing countries by bringing together funding, planning, management, and reporting systems if global goals for disease control are to be achieved.

  2. Staying Connected: Sustaining Collaborative Care Models with Limited Funding.

    PubMed

    Johnston, Brenda J; Peppard, Lora; Newton, Marian

    2015-08-01

    Providing psychiatric services in the primary care setting is challenging. The multidisciplinary, coordinated approach of collaborative care models (CCMs) addresses these challenges. The purpose of the current article is to discuss the implementation of a CCM at a free medical clinic (FMC) where volunteer staff provide the majority of services. Essential components of CCMs include (a) comprehensive screening and assessment, (b) shared development and communication of care plans among providers and the patient, and (c) care coordination and management. Challenges to implementing and sustaining a CCM at a FMC in Virginia attempting to meet the medical and psychiatric needs of the underserved are addressed. Although the CCM produced favorable outcomes, sustaining the model long-term presented many challenges. Strategies for addressing these challenges are discussed. Copyright 2015, SLACK Incorporated.

  3. Foundation for the redefinition of the kilogram

    NASA Astrophysics Data System (ADS)

    Richard, Philippe; Fang, Hao; Davis, Richard

    2016-10-01

    The redefinition of the kilogram, expected to be approved in the autumn of 2018, will replace the artefact definition of the kilogram by assigning a fixed numerical value to a fundamental constant of physics. While the concept of such a change is pleasing, the mass community as represented by the Consultative Committee for Mass and Related Quantities (CCM) was faced with a number of technical and procedural challenges that needed to be met in order to profit in any meaningful way from the proposed change. In the following, we outline these challenges and how the CCM has met and is meeting them. We focus especially on what the mass community requires of the new definition and the process by which the CCM has sought to ensure that these needs will be met.

  4. An assessment of correlations between chlorinated VOC concentrations in tree tissue and groundwater for phytoscreening applications.

    PubMed

    Duncan, Candice M; Brusseau, Mark L

    2018-03-01

    The majority of prior phytoscreening applications have employed the method as a tool to qualitatively determine the presence of contamination in the subsurface. Although qualitative data is quite useful, this study explores the potential for using phytoscreening quantitatively. The existence of site-specific and non-site-specific (master) correlations between VOC concentrations in tree tissue and groundwater is investigated using data collected from several phytoscreening studies. The aggregated data comprise 100 measurements collected from 12 sites that span a wide range of site conditions. Significant site-specific correlations are observed between tetrachloroethene (PCE) and trichloroethene (TCE) concentrations measured for tree tissue and those measured in groundwater for three sites. A moderately significant correlation (r 2 =0.56) exists for the entire aggregate data set. Parsing the data by groundwater depth produced a highly significant correlation (r 2 =0.88) for sites with shallow (<4m) groundwater. Such a significant correlation for data collected by different investigators from multiple sites with a wide range of tree species and subsurface conditions indicates that groundwater concentration is the predominant factor mediating tree-tissue concentrations for these sites. This may be a result of trees likely directly tapping groundwater for these shallow groundwater conditions. This master correlation may provide reasonable order-of-magnitude estimates of VOC concentrations in groundwater for such sites, thereby allowing the use of phytoscreening in a more quantitative mode. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Experimental Evaluation of the High-Speed Motion Vector Measurement by Combining Synthetic Aperture Array Processing with Constrained Least Square Method

    NASA Astrophysics Data System (ADS)

    Yokoyama, Ryouta; Yagi, Shin-ichi; Tamura, Kiyoshi; Sato, Masakazu

    2009-07-01

    Ultrahigh speed dynamic elastography has promising potential capabilities in applying clinical diagnosis and therapy of living soft tissues. In order to realize the ultrahigh speed motion tracking at speeds of over thousand frames per second, synthetic aperture (SA) array signal processing technology must be introduced. Furthermore, the overall system performance should overcome the fine quantitative evaluation in accuracy and variance of echo phase changes distributed across a tissue medium. On spatial evaluation of local phase changes caused by pulsed excitation on a tissue phantom, investigation was made with the proposed SA signal system utilizing different virtual point sources that were generated by an array transducer to probe each component of local tissue displacement vectors. The final results derived from the cross-correlation method (CCM) brought about almost the same performance as obtained by the constrained least square method (LSM) extended to successive echo frames. These frames were reconstructed by SA processing after the real-time acquisition triggered by the pulsed irradiation from a point source. The continuous behavior of spatial motion vectors demonstrated the dynamic generation and traveling of the pulsed shear wave at a speed of one thousand frames per second.

  6. Project LAUNCH: Bringing Space into Math and Science Classrooms

    NASA Technical Reports Server (NTRS)

    Fauerbach, M.; Henry, D. P.; Schmidt, D. L.

    2005-01-01

    Project LAUNCH is a K-12 teacher professional development program, which has been created in collaboration between the Whitaker Center for Science, Mathematics and Technology Education at Florida Gulf Coast University (FGCU), and the Florida Space Research Institute (FSRI). Utilizing Space as the overarching theme it is designed to improve mathematics and science teaching, using inquiry based, hands-on teaching practices, which are aligned with Florida s Sunshine State Standards. Many students are excited about space exploration and it provides a great venue to get them involved in science and mathematics. The scope of Project LAUNCH however goes beyond just providing competency in the subject area, as pedagogy is also an intricate part of the project. Participants were introduced to the Conceptual Change Model (CCM) [1] as a framework to model good teaching practices. As the CCM closely follows what scientists call the scientific process, this teaching method is also useful to actively engage institute participants ,as well as their students, in real science. Project LAUNCH specifically targets teachers in low performing, high socioeconomic schools, where the need for skilled teachers is most critical.

  7. Estrogen receptor (ER)α-regulated lipocalin 2 expression in adipose tissue links obesity with breast cancer progression.

    PubMed

    Drew, Brian G; Hamidi, Habib; Zhou, Zhenqi; Villanueva, Claudio J; Krum, Susan A; Calkin, Anna C; Parks, Brian W; Ribas, Vicent; Kalajian, Nareg Y; Phun, Jennifer; Daraei, Pedram; Christofk, Heather R; Hewitt, Sylvia C; Korach, Kenneth S; Tontonoz, Peter; Lusis, Aldons J; Slamon, Dennis J; Hurvitz, Sara A; Hevener, Andrea L

    2015-02-27

    Obesity is associated with increased breast cancer (BrCA) incidence. Considering that inactivation of estrogen receptor (ER)α promotes obesity and metabolic dysfunction in women and female mice, understanding the mechanisms and tissue-specific sites of ERα action to combat metabolic-related disease, including BrCA, is of clinical importance. To study the role of ERα in adipose tissue we generated fat-specific ERα knock-out (FERKO) mice. Herein we show that ERα deletion increased adipocyte size, fat pad weight, and tissue expression and circulating levels of the secreted glycoprotein, lipocalin 2 (Lcn2), an adipokine previously associated with BrCA development. Chromatin immunoprecipitation and luciferase reporter studies showed that ERα binds the Lcn2 promoter to repress its expression. Because adipocytes constitute an important cell type of the breast microenvironment, we examined the impact of adipocyte ERα deletion on cancer cell behavior. Conditioned medium from ERα-null adipocytes and medium containing pure Lcn2 increased proliferation and migration of a subset of BrCA cells in culture. The proliferative and promigratory effects of ERα-deficient adipocyte-conditioned medium on BrCA cells was reversed by Lcn2 deletion. BrCA cell responsiveness to exogenous Lcn2 was heightened in cell types where endogenous Lcn2 expression was minimal, but components of the Lcn2 signaling pathway were enriched, i.e. SLC22A17 and 3-hydroxybutyrate dehydrogenase (BDH2). In breast tumor biopsies from women diagnosed with BrCA we found that BDH2 expression was positively associated with adiposity and circulating Lcn2 levels. Collectively these data suggest that reduction of ERα expression in adipose tissue promotes adiposity and is linked with the progression and severity of BrCA via increased adipocyte-specific Lcn2 production and enhanced tumor cell Lcn2 sensitivity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Potential role of vegetation feedback in the climate sensitivity of high-latitude regions: A case study at 6000 years B.P.

    USGS Publications Warehouse

    Kutzbach, J.-E.; Bartlein, P.J.; Foley, J.A.; Harrison, S.P.; Hosteller, S.W.; Liu, Z.; Prentice, I.C.; Webb, T.

    1996-01-01

    Previous climate model simulations have shown that the configuration of the Earth's orbit during the early to mid-Holocene (approximately 10-5 kyr) can account for the generally warmer-than-present conditions experienced by the high latitudes of the northern hemisphere. New simulations for 6 kyr with two atmospheric/mixed-layer ocean models (Community Climate Model, version 1, CCM1, and Global ENvironmental and Ecological Simulation of Interactive Systems, version 2, GENESIS 2) are presented here and compared with results from two previous simulations with GENESIS 1 that were obtained with and without the albedo feedback due to climate-induced poleward expansion of the boreal forest. The climate model results are summarized in the form of potential vegetation maps obtained with the global BIOME model, which facilitates visual comparisons both among models and with pollen and plant macrofossil data recording shifts of the forest-tundra boundary. A preliminary synthesis shows that the forest limit was shifted 100-200 km north in most sectors. Both CCM1 and GENESIS 2 produced a shift of this magnitude. GENESIS 1 however produced too small a shift, except when the boreal forest albedo feedback was included. The feedback in this case was estimated to have amplified forest expansion by approximately 50%. The forest limit changes also show meridional patterns (greatest expansion in central Siberia and little or none in Alaska and Labrador) which have yet to be reproduced by models. Further progress in understanding of the processes involved in the response of climate and vegetation to orbital forcing will require both the deployment of coupled atmosphere-biosphere-ocean models and the development of more comprehensive observational data sets.

  9. Human adipose-derived mesenchymal stromal cell pigment epithelium-derived factor cytotherapy modifies genetic and epigenetic profiles of prostate cancer cells.

    PubMed

    Zolochevska, Olga; Shearer, Joseph; Ellis, Jayne; Fokina, Valentina; Shah, Forum; Gimble, Jeffrey M; Figueiredo, Marxa L

    2014-03-01

    Adipose-derived mesenchymal stromal cells (ASCs) are promising tools for delivery of cytotherapy against cancer. However, ASCs can exert profound effects on biological behavior of tumor cells. Our study aimed to examine the influence of ASCs on gene expression and epigenetic methylation profiles of prostate cancer cells as well as the impact of expressing a therapeutic gene on modifying the interaction between ASCs and prostate cancer cells. ASCs were modified by lentiviral transduction to express either green fluorescent protein as a control or pigment epithelium-derived factor (PEDF) as a therapeutic molecule. PC3 prostate cancer cells were cultured in the presence of ASC culture-conditioned media (CCM), and effects on PC3 or DU145. Ras cells were examined by means of real-time quantitative polymerase chain reaction, EpiTect methyl prostate cancer-focused real-time quantitative polymerase chain reaction arrays, and luciferase reporter assays. ASCs transduced with lentiviral vectors were able to mediate expression of several tumor-inhibitory genes, some of which correlated with epigenetic methylation changes on cocultured PC3 prostate cancer cells. When PC3 cells were cultured with ASC-PEDF CCM, we observed a shift in the balance of gene expression toward tumor inhibition, which suggests that PEDF reduces the potential tumor-promoting activity of unmodified ASCs. These results suggest that ASC-PEDF CCM can promote reprogramming of tumor cells in a paracrine manner. An improved understanding of genetic and epigenetic events in prostate cancer growth in response to PEDF paracrine therapy would enable a more effective use of ASC-PEDF, with the goal of achieving safer yet more potent anti-tumor effects. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  10. Evaluation of Stratospheric Transport in New 3D Models Using the Global Modeling Initiative Grading Criteria

    NASA Technical Reports Server (NTRS)

    Strahan, Susan E.; Douglass, Anne R.; Einaudi, Franco (Technical Monitor)

    2001-01-01

    The Global Modeling Initiative (GMI) Team developed objective criteria for model evaluation in order to identify the best representation of the stratosphere. This work created a method to quantitatively and objectively discriminate between different models. In the original GMI study, 3 different meteorological data sets were used to run an offline chemistry and transport model (CTM). Observationally-based grading criteria were derived and applied to these simulations and various aspects of stratospheric transport were evaluated; grades were assigned. Here we report on the application of the GMI evaluation criteria to CTM simulations integrated with a new assimilated wind data set and a new general circulation model (GCM) wind data set. The Finite Volume Community Climate Model (FV-CCM) is a new GCM developed at Goddard which uses the NCAR CCM physics and the Lin and Rood advection scheme. The FV-Data Assimilation System (FV-DAS) is a new data assimilation system which uses the FV-CCM as its core model. One year CTM simulations of 2.5 degrees longitude by 2 degrees latitude resolution were run for each wind data set. We present the evaluation of temperature and annual transport cycles in the lower and middle stratosphere in the two new CTM simulations. We include an evaluation of high latitude transport which was not part of the original GMI criteria. Grades for the new simulations will be compared with those assigned during the original GMT evaluations and areas of improvement will be identified.

  11. A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation.

    PubMed

    Abraham, William T; Kuck, Karl-Heinz; Goldsmith, Rochelle L; Lindenfeld, JoAnn; Reddy, Vivek Y; Carson, Peter E; Mann, Douglas L; Saville, Benjamin; Parise, Helen; Chan, Rodrigo; Wiegn, Phi; Hastings, Jeffrey L; Kaplan, Andrew J; Edelmann, Frank; Luthje, Lars; Kahwash, Rami; Tomassoni, Gery F; Gutterman, David D; Stagg, Angela; Burkhoff, Daniel; Hasenfuß, Gerd

    2018-05-05

    The authors sought to confirm a subgroup analysis of the prior FIX-HF-5 (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure) study showing that cardiac contractility modulation (CCM) improved exercise tolerance (ET) and quality of life in patients with ejection fractions between 25% and 45%. CCM therapy for New York Heart Association (NYHA) functional class III and IV heart failure (HF) patients consists of nonexcitatory electrical signals delivered to the heart during the absolute refractory period. A total of 160 patients with NYHA functional class III or IV symptoms, QRS duration <130 ms, and ejection fraction ≥25% and ≤45% were randomized to continued medical therapy (control, n = 86) or CCM (treatment, n = 74, unblinded) for 24 weeks. Peak VO 2 (primary endpoint), Minnesota Living With Heart Failure questionnaire, NYHA functional class, and 6-min hall walk were measured at baseline and at 12 and 24 weeks. Bayesian repeated measures linear modeling was used for the primary endpoint analysis with 30% borrowing from the FIX-HF-5 subgroup. Safety was assessed by the percentage of patients free of device-related adverse events with a pre-specified lower bound of 70%. The difference in peak VO 2 between groups was 0.84 (95% Bayesian credible interval: 0.123 to 1.552) ml O 2 /kg/min, satisfying the primary endpoint. Minnesota Living With Heart Failure questionnaire (p < 0.001), NYHA functional class (p < 0.001), and 6-min hall walk (p = 0.02) were all better in the treatment versus control group. There were 7 device-related events, yielding a lower bound of 80% of patients free of events, satisfying the primary safety endpoint. The composite of cardiovascular death and HF hospitalizations was reduced from 10.8% to 2.9% (p = 0.048). CCM is safe, improves exercise tolerance and quality of life in the specified group of HF patients, and leads to fewer HF hospitalizations. (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure; NCT01381172). Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Regional comparison of absolute gravimeters, EURAMET.M.G-K2 key comparison

    NASA Astrophysics Data System (ADS)

    Pálinkáš, V.; Francis, O.; Val'ko, M.; Kostelecký, J.; Van Camp, M.; Castelein, S.; Bilker-Koivula, M.; Näränen, J.; Lothhammer, A.; Falk, R.; Schilling, M.; Timmen, L.; Iacovone, D.; Baccaro, F.; Germak, A.; Biolcati, E.; Origlia, C.; Greco, F.; Pistorio, A.; De Plaen, R.; Klein, G.; Seil, M.; Radinovic, R.; Reudink, R.; Dykowski, P.; Sȩkowski, M.; Próchniewicz, D.; Szpunar, R.; Mojzeš, M.; Jańk, J.; Papčo, J.; Engfeldt, A.; Olsson, P. A.; Smith, V.; van Westrum, D.; Ellis, B.; Lucero, B.

    2017-01-01

    In the framework of the regional EURAMET.M.G-K2 comparison of absolute gravimeters, 17 gravimeters were compared in November 2015. Four gravimeters were from different NMIs and DIs, they were used to link the regional comparison to the CCM.G.K2 by means of linking converter. Combined least-squares adjustments with weighted constraint was used to determine KCRV. Several pilot solutions are presented and compared with the official solution to demonstrate influences of different approaches (e.g. definition of weights and the constraint) on results of the adjustment. In case of the official solution, all the gravimeters are in equivalence with declared uncertainties. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  13. Final report on EUROMET key comparison EUROMET.M.D-K2 (EUROMET 627) "Comparison of density determinations of liquid samples"

    NASA Astrophysics Data System (ADS)

    Bettin, Horst; Heinonen, Martti; Gosset, André; Zelenka, Zoltán; Lorefice, Salvatore; Hellerud, Kristen; Durlik, Hanna; Jordaan, Werner; Field, Ireen

    2016-01-01

    The results of the key comparison EUROMET 627 (EUROMET.M.D-K2) are presented. This project covered the density measurements of three liquids: dodecane, water and an oil of high viscosity measured at 15 °C, 20 °C and 40 °C. Seven European metrology laboratories and the South African laboratory CSIR-NML (now: NMISA) measured the densities at atmospheric pressure by hydrostatic weighing of solid density standards between 04 October 2001 and 18 December 2001. The stability and homogeneity of the liquids were investigated by the pilot laboratory PTB. The results generally show good agreement among the participants. Only for the simple Mohr-Westphal balances do the uncertainties seem to be underestimated by the laboratories. Furthermore, the measurement of high-viscosity oil was difficult for some laboratories. Nevertheless, the five laboratories PTB/DE, BNM/FR (now: LNE/FR), OMH/HU (now: MKEH/HU), IMGC/IT (now: INRIM/IT) and GUM/PL agree with each other for stated uncertainties of 0.05 kg/m3 or less. This satisfies the current needs of customers who wish to calibrate or check liquid density measuring instruments such as oscillation-type density meters. No reference values were calculated since the subsequent CCM key comparison CCM.D-K2 had a different scope and the EUROMET 627 comparison was soon superseded by the EURAMET 1019 (EURAMET.M.D-K2) comparison. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  14. Development, validation, and utility of an instrument to assess core competencies in the Leadership Education in Neurodevelopmental and Related Disabilities (LEND) program.

    PubMed

    Leff, Stephen S; Baum, Katherine T; Bevans, Katherine B; Blum, Nathan J

    2015-02-01

    To describe the development and psychometric evaluation of the Core Competency Measure (CCM), an instrument designed to assess professional competencies as defined by the Maternal Child Health Bureau (MCHB) and targeted by Leadership Education in Neurodevelopmental and Related Disabilities (LEND) programs. The CCM is a 44-item self-report measure comprised of six subscales to assess clinical, interdisciplinary, family-centered/cultural, community, research, and advocacy/policy competencies. The CCM was developed in an iterative fashion through participatory action research, and then nine cohorts of LEND trainees (N = 144) from 14 different disciplines completed the CCM during the first week of the training program. A 6-factor confirmatory factor analysis model was fit to data from the 44 original items. After three items were removed, the model adequately fit the data (comparative fit indices = .93, root mean error of approximation = .06) with all factor loadings exceeding .55. The measure was determined to be quite reliable as adequate internal consistency and test-retest reliability were found for each subscale. The instrument's construct validity was supported by expected differences in self-rated competencies among fellows representing various disciplines, and the convergent validity was supported by the pattern of inter-correlations between subscale scores. The CCM appears to be a reliable and valid measure of MCHB core competencies for our sample of LEND trainees. It provides an assessment of key training areas addressed by the LEND program. Although the measure was developed within only one LEND Program, with additional research it has the potential to serve as a standardized tool to evaluate the strengths and limitations of MCHB training, both within and between programs.

  15. Comparison of fracture resistance between cast, CAD/CAM milling, and direct metal laser sintering metal post systems.

    PubMed

    Bilgin, Mehmet Selim; Erdem, Ali; Dilber, Erhan; Ersoy, İbrahim

    2016-01-01

    The purpose of this study was to compare the fracture resistance of Co-Cr post-cores fabricated with 3 different techniques: traditional casting (TC), computer-aided design and manufacturing (CAD/CAM) milling (CCM) and direct metal laser sintering (DMLS). Forty intact human mandibular premolar were endodontically treated. The roots were then randomly divided into four groups according to the post systems: the control group was only filled with gutta percha. Co-Cr metal posts were fabricated with TC, CCM and DMLS in the other three groups. The posts were luted with a resin cement and subjected to compression test at a crosshead speed of 1mm/min. The statistical analysis of the data was performed using one-way analysis of variance (ANOVA) and multiple comparison post hoc Tukey tests (α=.05). The samples were examined under a stereomicroscope with ×20 magnification for the evaluation of the fracture types. The mean fracture loads were 432.69 N for control, 608.89 N for TC, 689.40 N for DMLS and 959.26 N for CCM. One-way ANOVA revealed significant difference between the groups (p<0.01). In the post hoc Tukey test, there were significant differences between groups except DMLS and TC. While Co-Cr posts fabricated by TC and DMLS systems performed similarly in terms of fracture resistance, posts fabricated by CCM techniques showed higher fracture resistance values. Co-Cr metal posts fabricated by CCM and DMLS could be an alternative to TC processing in daily clinical application. Copyright © 2015 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  16. What influences availability of medicines for the community management of childhood illnesses in central Uganda? Implications for scaling up the integrated community case management programme.

    PubMed

    Bagonza, James; Rutebemberwa, Elizeus; Eckmanns, Tim; Ekirapa-Kiracho, Elizabeth

    2015-11-25

    The integrated Community Case Management (iCCM) of childhood illnesses strategy has been adopted world over to reduce child related ill health and mortality. Community Health workers (CHWs) who implement this strategy need a regular supply of drugs to effectively treat children under 5 years with malaria, pneumonia and diarrhea. In this paper, we report the prevalence and factors influencing availability of medicines for managing malaria, pneumonia and diarrhea in communities in central Uganda. A cross sectional study was conducted among 303 CHWs in Wakiso district in central Uganda. Eligible CHWs from two randomly selected Health Sub Districts (HSDs) were interviewed. Questionnaires, check lists, record reviews were used to collect information on CHW background characteristics, CHW's prescription behaviors, health system support factors and availability of iCCM drugs. Multivariable logistic regression analysis was done to assess factors associated with availability of iCCM drugs. Out of 300 CHWs, 239 (79.9%) were females and mean age was 42.1 (standard deviation =11.1 years). The prevalence of iCCM drug availability was 8.3% and 33 respondents (11%) had no drugs at all. Factors associated with iCCM drug availability were; being supervised within the last month (adjusted OR = 3.70, 95% CI 1.22-11.24), appropriate drug prescriptions (adjusted OR = 3.71, 95% CI 1.38-9.96), regular submission of drug reports (adjusted OR = 4.02, 95% CI 1.62-10.10) and having a respiratory timer as a diagnostic tool (adjusted OR =3.11, 95% CI 1.08-9.00). The low medicine stocks for the community management of childhood illnesses calls for strengthening of CHW supervision, medicine prescription and reporting, and increasing availability of functional diagnostic tools.

  17. The Canadian Heart Health Strategy and Action Plan: Cardiac rehabilitation as an exemplar of chronic disease management

    PubMed Central

    Arthur, Heather M; Suskin, Neville; Bayley, Mark; Fortin, Martin; Howlett, Jonathan; Heckman, George; Lewanczuk, Richard

    2010-01-01

    BACKGROUND: In October 2006, federal funding was announced for the development of a national strategy to fight cardiovascular disease (CVD) in Canada. The comprehensive, independent, stakeholder-driven Canadian Heart Health Strategy and Action Plan (CHHS-AP) was delivered to the Minister of Health on February 24, 2009. OBJECTIVES: The mandate of CHHS-AP Theme Working Group (TWG) 6 was to identify the optimal chronic disease management model that incorporated timely access to rehabilitation services and end-of-life planning and care. The purpose of the present paper was to provide an overview of worldwide approaches to CVD and cardiac rehabilitation (CR) strategies and recommendations for CR care in Canada, within the context of the well-known Chronic Care Model (CCM). A separate paper will address end-of-life issues in CVD. METHODS: TWG 6 was composed of content representatives, primary care representatives and patients. Input in the area of Aboriginal and indigenous cardiovascular health was obtained through individual expert consultation. Information germane to the present paper was gathered from international literature and best practice guidelines. The CCM principles were discussed and agreed on by all. Prioritization of recommendations and overall messaging was discussed and decided on within the entire TWG. The full TWG report was presented to the CHHS-AP Steering Committee and was used to inform the recommendations of the CHHS-AP. RESULTS: Specific actionable recommendations for CR are made in accordance with the key principles of the CCM. CONCLUSIONS: The present CR blueprint, as part of the CHHS-AP, will be a first step toward reducing the health care burden of CVD in Canada. PMID:20101356

  18. Critical Care and Personalized or Precision Medicine: Who needs whom?

    PubMed

    Sugeir, Shihab; Naylor, Stephen

    2018-02-01

    The current paradigm of modern healthcare is a reactive response to patient symptoms, subsequent diagnosis and corresponding treatment of the specific disease(s). This approach is predicated on methodologies first espoused by the Cnidean School of Medicine approximately 2500years ago. More recently escalating healthcare costs and relatively poor disease treatment outcomes have fermented a rethink in how we carry out medical practices. This has led to the emergence of "P-Medicine" in the form of Personalized and Precision Medicine. The terms are used interchangeably, but in fact there are significant differences in the way they are implemented. The former relies on an "N-of-1" model whereas the latter uses a "1-in-N" model. Personalized Medicine is still in a fledgling and evolutionary phase and there has been much debate over its current status and future prospects. A confounding factor has been the sudden development of Precision Medicine, which has currently captured the imagination of policymakers responsible for modern healthcare systems. There is some confusion over the terms Personalized versus Precision Medicine. Here we attempt to define the key differences and working definitions of each P-Medicine approach, as well as a taxonomic relationship tree. Finally, we discuss the impact of Personalized and Precision Medicine on the practice of Critical Care Medicine (CCM). Practitioners of CCM have been participating in Personalized Medicine unknowingly as it takes the protocols of sepsis, mechanical ventilation, and daily awakening trials and applies it to each individual patient. However, the immediate next step for CCM should be an active development of Precision Medicine. This developmental process should break down the silos of modern medicine and create a multidisciplinary approach between clinicians and basic/translational scientists. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Tissue- and environmental response-specific expression of 10 PP2C transcripts in Mesembryanthemum crystallinum.

    PubMed

    Miyazaki, S; Koga, R; Bohnert, H J; Fukuhara, T

    1999-03-01

    Ten transcripts (Mpc1-10) homologous to protein phosphatases of the 2C family have been isolated from the halophyte Mesembryanthemum crystallinum (common ice plant). Transcripts range in size from 1.6 to 2.6 kb, and encode proteins whose catalytic domains are between 24% and 62% identical to that of the Arabidopsis PP2C, ABI1. Transcript expression is tissue specific. Two isoforms are present only in roots (Mpc1 and Mpc5), three in young leaves (Mpc6, 8 and 9), two in old leaves (Mpc6 and Mpc8), and two in post-flowering leaves (Mpc8 and Mpc9). Mpc2 is strongly expressed in roots and also in seeds, meristematic tissues and mature flowers. Mpc3 is specific for leaf meristems, and Mpc4 is found in root and leaf meristems. Mpc7 is restricted to meristematic tissues. Mpc10 is only present in mature flowers. Mpc2 (in roots and leaves), Mpc5 (in roots) and Mpc8 (weakly in leaves) are induced by salinity stress and drought conditions with different kinetics in different tissues, but other Mpcs are downregulated by stress. Cold stress (4 degrees C) leads to a decline in Mpc5 and Mp6, but low temperature provoked a long-term (days) increase in Mpc2 levels in leaves and a transient increase (less than 24 h) in roots. Four full-length transcripts have been obtained. In each case, after over-expression in E. coli, the isolated proteins exhibited (Mg2+-dependent, okadeic acid-insensitive) protein phosphatase activity, although activity against 32P-phosphocasein varied among different PP2Cs. Determination of tissue developmental and stress response specificity of PP2C will facilitate functional studies of signal-transducing enzymes in this halophytic organism.

  20. KEY COMPARISON: Final report of comparison of the calibrations of hydrometers for liquid density determination between SIM laboratories: SIM.M.D-K4

    NASA Astrophysics Data System (ADS)

    Becerra, Luis Omar

    2009-01-01

    This SIM comparison on the calibration of high accuracy hydrometers was carried out within fourteen laboratories in the density range from 600 kg/m3 to 1300 kg/m3 in order to evaluate the degree of equivalence among participant laboratories. This key comparison anticipates the planned key comparison CCM.D-K4, and is intended to be linked with CCM.D-K4 when results are available. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  1. Directional solidification at ultra-high thermal gradient

    NASA Technical Reports Server (NTRS)

    Flemings, M. C.; Lee, D. S.; Neff, M. A.

    1980-01-01

    A high gradient controlled solidification (HGC) furnace was designed and operated at gradients up to 1800 C/cm to continuously produce aluminum alloys. Rubber '0' rings for the water cooling chamber were eliminated, while still maintaining water cooling directly onto the solidified metal. An HGC unit for high temperature ferrous alloys was also designed. Successful runs were made with cast iron, at thermal gradients up to 500 C/cm.

  2. Final report on the key comparison CCM.P-K4.2012 in absolute pressure from 1 Pa to 10 kPa

    NASA Astrophysics Data System (ADS)

    Ricker, Jacob; Hendricks, Jay; Bock, Thomas; Dominik, Pražák; Kobata, Tokihiko; Torres, Jorge; Sadkovskaya, Irina

    2017-01-01

    The report summarizes the Consultative Committee for Mass (CCM) key comparison CCM.P-K4.2012 for absolute pressure spanning the range of 1 Pa to 10 000 Pa. The comparison was carried out at six National Metrology Institutes (NMIs), including National Institute of Standards and Technology (NIST), Physikalisch-Technische Bundesanstalt (PTB), Czech Metrology Institute (CMI), National Metrology Institute of Japan (NMIJ), Centro Nacional de Metrología (CENAM), and DI Mendeleyev Institute for Metrology (VNIIM). The comparison was made via a calibrated transfer standard measured at each of the NMIs facilities using their laboratory standard during the period May 2012 to September 2013. The transfer package constructed for this comparison preformed as designed and provided a stable artifact to compare laboratory standards. Overall the participants were found to be statistically equivalent to the key comparison reference value. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  3. Corneal Confocal Microscopy Detects Early Nerve Regeneration in Diabetic Neuropathy After Simultaneous Pancreas and Kidney Transplantation

    PubMed Central

    Tavakoli, Mitra; Mitu-Pretorian, Maria; Petropoulos, Ioannis N.; Fadavi, Hassan; Asghar, Omar; Alam, Uazman; Ponirakis, Georgios; Jeziorska, Maria; Marshall, Andy; Efron, Nathan; Boulton, Andrew J.; Augustine, Titus; Malik, Rayaz A.

    2013-01-01

    Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas–kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair that is missed by currently advocated assessment techniques. PMID:23002037

  4. Impact of the Chronic Care Model on medication adherence when patients perceive cost as a barrier.

    PubMed

    Mackey, Katherine; Parchman, Michael L; Leykum, Luci K; Lanham, Holly J; Noël, Polly H; Zeber, John E

    2012-07-01

    Cost burdens represent a significant barrier to medication adherence among chronically ill patients, yet financial pressures may be mitigated by clinical or organizational factors, such as treatment aligned with the Chronic Care Model (CCM). This study examines how perceptions of chronic illness care attenuate the relationship between adherence and cost burden. Surveys were administered to patients at 40 small community-based primary care practices. Medication adherence was assessed using the 4-item Morisky scale, while five cost-related items documented recent pharmacy restrictions. CCM experiences were assessed via the 20-item Patient Assessment of Chronic Illness Care (PACIC). Nested random effects models determined if chronic care perceptions modified the association between medication adherence and cost-related burden. Of 1823 respondents reporting diabetes and other chronic diseases, one-quarter endorsed intrapersonal adherence barriers, while 23% restricted medication due of cost. Controlling for age and health status, the relationship between medication cost and CCM with adherence was significant; including PACIC scores attenuated cost-related problems patients with adequate or problematic adherence behavior. Patients experiencing treatment more consistent with the CCM reported better adherence and lower cost-related burden. Fostering highly activated patients and shared clinical decision making may help alleviate medication cost pressures and improve adherence. Published by Elsevier Ltd.

  5. Systematic review; Nutritional therapy in gestational diabetes mellitus.

    PubMed

    Thomaz de Lima, Helaine; Lopes Rosado, Eliane; Ribeiro Neves, Paulo Augusto; Corrêa Monteiro Machado, Raphaela; Mello de Oliveira, Larissa; Saunders, Cláudia

    2013-11-01

    Several methods of dietetic counseling can be used in the nutritional therapy in gestational diabetes mellitus (GDM). The main methods are the traditional method (TM) and the carbohydrate counting (CCM). Presenting a systematic review of the literature on the impact of nutritional therapy in GDM, through TM and CCM, evaluating the results for maternal and child health. We searched databases PubMed, Scopus, Web of Science, Lilacs and CAPES Digital Bank of Thesis. The methodological quality of all the studies included was made using the Jadad score. We have found five studies that evaluated the effects of nutritional therapy, through the TM, on the maternal and child health. None study evaluating the CCM was detected in pregnant women with GDM Nutritional therapy given during antenatal care was effective in reducing pregnancy complications (preeclampsia, excessive gestational weight gain, necessity for cesarean delivery, for insulin therapy and for shoulder dystocia), perinatal complications (macrosomia, neonatal hypoglycemia, and birth weight) and also in better glycemic control. The use of nutritional therapy should be highlighted within the antenatal care for pregnant women with GDM, giving the satisfactory results on metabolic control and on pregnancy outcomes. Studies examining the CCM to GDM patients should be conducted to show its effects on maternal and child health.

  6. Microvasculature of the cerebral cortex: a vascular corrosion cast and immunocytochemical study.

    PubMed

    Scala, Gaetano

    2014-04-01

    In mammals, the cerebral cortex microvasculature (CCM) of the neopallium plays important roles in the physiological and pathological processes of the brain. The aim of the present work is to analyze the CCM by use of the SEM-vascular corrosion cast technique, and to examine the immunocytochemical characteristics of the CCM in adult domestic ruminants (cattle, buffalo, and sheep) by using the SEM-immunogold technique. The CCM originated from the very small, finger-like terminal branches of the macrovasculature of the brain. The superficial cortical arterioles were more numerous than the deep straight arterioles which proceeded toward the white matter. The surface casts of the arterioles and capillaries of the cerebral cortex showed ring-shaped formations in the arterioles and at the origin of the capillaries. All capillaries down-stream from these ring-shaped formations were flaccid. Casts of the capillaries showed wrinkles due to the presence of endothelial folds, which is characteristic of varying blood pressure. Formations having intense anti-GIFAP immunoreactivity were frequently evident along the course of the blood capillaries in the cerebral cortex. These formations were probably astrocytes that might regulate the cerebral microcirculation based on physiological and pathological stimuli, such as neuronal activation. Copyright © 2014 Wiley Periodicals, Inc.

  7. Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia

    PubMed Central

    Oudejans, Linda; He, Xuan; Niesters, Marieke; Dahan, Albert; Brines, Michael; van Velzen, Monique

    2016-01-01

    Cornea confocal microscopy (CCM) is a novel non-invasive method to detect small nerve fiber pathology. CCM generally correlates with outcomes of skin biopsies in patients with small fiber pathology. The aim of this study was to quantify the morphology of small nerve fibers of the cornea of patients with fibromyalgia in terms of density, length and branching and further phenotype these patients using standardized quantitative sensory testing (QST). Small fiber pathology was detected in the cornea of 51% of patients: nerve fiber length was significantly decreased in 44% of patients compared to age- and sex-matched reference values; nerve fiber density and branching were significantly decreased in 10% and 28% of patients. The combination of the CCM parameters and sensory tests for central sensitization, (cold pain threshold, mechanical pain threshold, mechanical pain sensitivity, allodynia and/or windup), yielded four phenotypes of fibromyalgia patients in a subgroup analysis: one group with normal cornea morphology without and with signs of central sensitization, and a group with abnormal cornea morphology parameters without and with signs of central sensitization. In conclusion, half of the tested fibromyalgia population demonstrates signs of small fiber pathology as measured by CCM. The four distinct phenotypes suggest possible differences in disease mechanisms and may require different treatment approaches. PMID:27006259

  8. Replicating DNA by cell factories: roles of central carbon metabolism and transcription in the control of DNA replication in microbes, and implications for understanding this process in human cells

    PubMed Central

    2013-01-01

    Precise regulation of DNA replication is necessary to ensure the inheritance of genetic features by daughter cells after each cell division. Therefore, determining how the regulatory processes operate to control DNA replication is crucial to our understanding and application to biotechnological processes. Contrary to early concepts of DNA replication, it appears that this process is operated by large, stationary nucleoprotein complexes, called replication factories, rather than by single enzymes trafficking along template molecules. Recent discoveries indicated that in bacterial cells two processes, central carbon metabolism (CCM) and transcription, significantly and specifically influence the control of DNA replication of various replicons. The impact of these discoveries on our understanding of the regulation of DNA synthesis is discussed in this review. It appears that CCM may influence DNA replication by either action of specific metabolites or moonlighting activities of some enzymes involved in this metabolic pathway. The role of transcription in the control of DNA replication may arise from either topological changes in nucleic acids which accompany RNA synthesis or direct interactions between replication and transcription machineries. Due to intriguing similarities between some prokaryotic and eukaryotic regulatory systems, possible implications of studies on regulation of microbial DNA replication on understanding such a process occurring in human cells are discussed. PMID:23714207

  9. Ground-state ordering of the J1-J2 model on the simple cubic and body-centered cubic lattices

    NASA Astrophysics Data System (ADS)

    Farnell, D. J. J.; Götze, O.; Richter, J.

    2016-06-01

    The J1-J2 Heisenberg model is a "canonical" model in the field of quantum magnetism in order to study the interplay between frustration and quantum fluctuations as well as quantum phase transitions driven by frustration. Here we apply the coupled cluster method (CCM) to study the spin-half J1-J2 model with antiferromagnetic nearest-neighbor bonds J1>0 and next-nearest-neighbor bonds J2>0 for the simple cubic (sc) and body-centered cubic (bcc) lattices. In particular, we wish to study the ground-state ordering of these systems as a function of the frustration parameter p =z2J2/z1J1 , where z1 (z2) is the number of nearest (next-nearest) neighbors. We wish to determine the positions of the phase transitions using the CCM and we aim to resolve the nature of the phase transition points. We consider the ground-state energy, order parameters, spin-spin correlation functions, as well as the spin stiffness in order to determine the ground-state phase diagrams of these models. We find a direct first-order phase transition at a value of p =0.528 from a state of nearest-neighbor Néel order to next-nearest-neighbor Néel order for the bcc lattice. For the sc lattice the situation is more subtle. CCM results for the energy, the order parameter, the spin-spin correlation functions, and the spin stiffness indicate that there is no direct first-order transition between ground-state phases with magnetic long-range order, rather it is more likely that two phases with antiferromagnetic long range are separated by a narrow region of a spin-liquid-like quantum phase around p =0.55 . Thus the strong frustration present in the J1-J2 Heisenberg model on the sc lattice may open a window for an unconventional quantum ground state in this three-dimensional spin model.

  10. Evaluation of the accuracy, consistency, and stability of measurements of the Planck constant used in the redefinition of the international system of units

    NASA Astrophysics Data System (ADS)

    Possolo, Antonio; Schlamminger, Stephan; Stoudt, Sara; Pratt, Jon R.; Williams, Carl J.

    2018-02-01

    The Consultative Committee for Mass and related quantities (CCM), of the International Committee for weights and measures (CIPM), has recently declared the readiness of the community to support the redefinition of the international system of units (SI) at the next meeting of the General Conference on Weights and Measures (CGPM) scheduled for November, 2018. Such redefinition will replace the international prototype of the Kilogram (IPK), as the definition and sole primary realization of the unit of mass, with a definition involving the Planck constant, h. This redefinition in terms of a fundamental constant of nature will enable widespread primary realizations not only of the kilogram but also of its multiples and sub-multiples, best to address the full range of practical needs in the measurement of mass. We review and discuss the statistical models and statistical data reductions, uncertainty evaluations, and substantive arguments that support the verification of several technical preconditions for the redefinition that the CCM has established, and whose verification the CCM has affirmed. These conditions relate to the accuracy and mutual consistency of qualifying measurement results. We review also an issue that has surfaced only recently, concerning the convergence toward a stable value, of the historical values that the task group on fundamental constants of the committee on Data for Science and Technology CODATA-TGFC has recommended for h over the years, even though the CCM has not deemed this issue to be relevant. We conclude that no statistically significant trend can be substantiated for these recommended values, but note that cumulative consensus values that may be derived from the historical measurement results for h seem to have converged while continuing to exhibit fluctuations that are typical of a process in statistical control. Finally, we argue that the most recent consensus value derived from the best measurements available for h, obtained using either a Kibble balance or the XRCD method, is reliable and has uncertainty no larger than the uncertainties surrounding the current primary and secondary realizations of the unit of mass, hence that no credible technical impediments stand in the way of the redefinition of the unit of mass in terms of a fixed value of h.

  11. Psychiatric consultation in the collaborative care model: The "bipolar sieve" effect.

    PubMed

    Phelps, James R; James, James

    2017-08-01

    Around the world, psychiatrists are in exceptionally short supply. The majority of mental health treatment is delivered in primary care. In the United States, the Collaborative Care Model (CCM) addresses the shortfall of psychiatrists by providing indirect consultation in primary care. A Cochrane meta-analysis affirms the efficacy this model for depression and anxiety. However, our experience with the CCM suggests that most patients referred for consultation have problems far more complex than simple depression and anxiety. Based on preliminary data, we offer five linked hypotheses: (1) in an efficient collaborative care process, the majority of mental illnesses can be handled by providers who are less expensive and more plentiful than psychiatrists. (2) A majority of the remaining cases will be bipolar disorder variations. Differentiating these from PTSD, the most common alternative or comorbid diagnosis, is challenging and often requires a psychiatrist's input. (3) Psychiatric consultants can teach their primary care colleagues that bipolar diagnoses are estimations based on rigorously assessed probabilities, and that cases fall on a spectrum from unipolar to bipolar. (4) All providers must recognize that when bipolarity is missed, antidepressant prescription often follows. Antidepressants can induce bipolar mixed states, with extreme anxiety and potentially dangerous impulsivity and suicidality. (5) Psychiatrists can help develop clinical approaches in primary care that identify bipolarity and differentiate it from (or establish comorbidity with) PTSD; and psychiatrists can facilitate appropriate treatment, including bipolar-specific psychotherapies as well as use of mood stabilizers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. The influence of oceanic basins on drought and ecosystem dynamics in Northeast Brazil

    NASA Astrophysics Data System (ADS)

    Santos Pereira, Marcos Paulo; Justino, Flavio; Mendes Malhado, Ana Claudia; Barbosa, Humberto; Marengo, José

    2014-12-01

    The 2012 drought in Northeast Brazil was the harshest in decades, with potentially significant impacts on the vegetation of the unique semi-arid caatinga biome and on local livelihoods. Here, we use a coupled climate-vegetation model (CCM3-IBIS) to: (1) investigate the role of the Pacific and Atlantic oceans in the 2012 drought, and; (2) evaluate the response of the caatinga vegetation to the 2012 climate extreme. Our results indicate that anomalous sea surface temperatures (SSTs) in the Atlantic Ocean were the primary factor forcing the 2012 drought, with Pacific Ocean SST having a larger role in sustaining typical climatic conditions in the region. The drought strongly influenced net primary production in the caatinga, causing a reduction in annual net ecosystem exchange indicating a reduction in amount of CO2 released to the atmosphere.

  13. A tissue-like culture system using microstructures: influence of extracellular matrix material on cell adhesion and aggregation.

    PubMed

    Knedlitschek, G; Schneider, F; Gottwald, E; Schaller, T; Eschbach, E; Weibezahn, K F

    1999-02-01

    Special microenvironmental conditions are required to induce and/or maintain specific qualities of differentiated cells. An important parameter is the three-dimensional tissue architecture that cannot be reproduced in conventional monolayer systems. Advanced tissue culture systems will meet many of these demands, but may reach their limits, especially when gradients of specific substances over distinct tissue layers must be established for long-term culture. These limitations may be overcome by incorporating microstructures into tissue-like culture systems. The microstructured cell support presented consists of a flat array of 625 cubic microcontainers with porous bottoms, in which cells can be supplied with specific media from both sides of the tissue layer. Permanent cell lines and primary rat hepatocytes have been used to test the culture system. In order to define reproducible conditions for tissue formation and for cell adherence to the structure, several ECM (extracellular matrix) components were tested for coating of microstructured substrata. The described tissue culture system offers great flexibility in adapting the cell support to specific needs.

  14. Modelling an advanced ManPAD with dual band detectors and a rosette scanning seeker head

    NASA Astrophysics Data System (ADS)

    Birchenall, Richard P.; Richardson, Mark A.; Butters, Brian; Walmsley, Roy

    2012-01-01

    Man Portable Air Defence Systems (ManPADs) have been a favoured anti aircraft weapon since their appearance on the military proliferation scene in the mid 1960s. Since this introduction there has been a 'cat and mouse' game of Missile Countermeasures (CMs) and the aircraft protection counter counter measures (CCMs) as missile designers attempt to defeat the aircraft platform protection equipment. Magnesium Teflon Viton (MTV) flares protected the target aircraft until the missile engineers discovered the art of flare rejection using techniques including track memory and track angle bias. These early CCMs relied upon CCM triggering techniques such as the rise rate method which would just sense a sudden increase in target energy and assume that a flare CM had been released by the target aircraft. This was not as reliable as was first thought as aspect changes (bringing another engine into the field of view) or glint from the sun could inadvertently trigger a CCM when not needed. The introduction of dual band detectors in the 1980s saw a major advance in CCM capability allowing comparisons between two distinct IR bands to be made thus allowing the recognition of an MTV flare to occur with minimal false alarms. The development of the rosette scan seeker in the 1980s complemented this advancement allowing the scene in the missile field of view (FOV) to be scanned by a much smaller (1/25) instantaneous FOV (IFOV) with the spectral comparisons being made at each scan point. This took the ManPAD from a basic IR energy detector to a pseudo imaging system capable of analysing individual elements of its overall FOV allowing more complex and robust CCM to be developed. This paper continues the work published in [1,2] and describes the method used to model an advanced ManPAD with a rosette scanning seeker head and robust CCMs similar to the Raytheon Stinger RMP.

  15. Systematic literature review of integrated community case management and the private sector in Africa: Relevant experiences and potential next steps.

    PubMed

    Awor, Phyllis; Miller, Jane; Peterson, Stefan

    2014-12-01

    Despite substantial investments made over the past 40 years in low income countries, governments cannot be viewed as the principal health care provider in many countries. Evidence on the role of the private sector in the delivery of health services is becoming increasingly available. In this study, we set out to determine the extent to which the private sector has been utilized in providing integrated care for sick children under 5 years of age with community-acquired malaria, pneumonia or diarrhoea. We reviewed the published literature for integrated community case management (iCCM) related experiences within both the public and private sector. We searched PubMed and Google/Google Scholar for all relevant literature until July 2014. The search terms used were "malaria", "pneumonia", "diarrhoea", "private sector" and "community case management". A total of 383 articles referred to malaria, pneumonia or diarrhoea in the private sector. The large majority of these studies (290) were only malaria related. Most of the iCCM-related studies evaluated introduction of only malaria drugs and/or diagnostics into the private sector. Only one study evaluated the introduction of drugs and diagnostics for malaria, pneumonia and diarrhoea in the private sector. In contrast, most iCCM-related studies in the public sector directly reported on community case management of 2 or more of the illnesses. While the private sector is an important source of care for children in low income countries, little has been done to harness the potential of this sector in improving access to care for non-malaria-associated fever in children within the community. It would be logical for iCCM programs to expand their activities to include the private sector to achieve higher population coverage. An implementation research agenda for private sector integrated care of febrile childhood illness needs to be developed and implemented in conjunction with private sector intervention programs.

  16. High-CO 2 Requirement as a Mechanism for the Containment of Genetically Modified Cyanobacteria

    DOE PAGES

    Clark, Ryan L.; Gordon, Gina C.; Bennett, Nathaniel R.; ...

    2018-01-10

    As researchers engineer cyanobacteria for biotechnological applications, we must consider potential environmental release of these organisms. Previous theoretical work has considered cyanobacterial containment through elimination of the CO 2-concentrating mechanism (CCM) to impose a high-CO 2 requirement (HCR), which could be provided in the cultivation environment but not in the surroundings. In this work, we experimentally implemented an HCR containment mechanism in Synechococcus sp. strain PCC7002 (PCC7002) through deletion of carboxysome shell proteins and showed that this mechanism contained cyanobacteria in a 5% CO 2 environment. We considered escape through horizontal gene transfer (HGT) and reduced the risk of HGTmore » escape by deleting competence genes. We showed that the HCR containment mechanism did not negatively impact the performance of a strain of PCC7002 engineered for L-lactate production. In conclusion, we showed through coculture experiments of HCR strains with ccm-containing strains that this HCR mechanism reduced the frequency of escape below the NIH recommended limit for recombinant organisms of one escape event in 10 8 CFU.« less

  17. High-CO 2 Requirement as a Mechanism for the Containment of Genetically Modified Cyanobacteria

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Clark, Ryan L.; Gordon, Gina C.; Bennett, Nathaniel R.

    As researchers engineer cyanobacteria for biotechnological applications, we must consider potential environmental release of these organisms. Previous theoretical work has considered cyanobacterial containment through elimination of the CO 2-concentrating mechanism (CCM) to impose a high-CO 2 requirement (HCR), which could be provided in the cultivation environment but not in the surroundings. In this work, we experimentally implemented an HCR containment mechanism in Synechococcus sp. strain PCC7002 (PCC7002) through deletion of carboxysome shell proteins and showed that this mechanism contained cyanobacteria in a 5% CO 2 environment. We considered escape through horizontal gene transfer (HGT) and reduced the risk of HGTmore » escape by deleting competence genes. We showed that the HCR containment mechanism did not negatively impact the performance of a strain of PCC7002 engineered for L-lactate production. In conclusion, we showed through coculture experiments of HCR strains with ccm-containing strains that this HCR mechanism reduced the frequency of escape below the NIH recommended limit for recombinant organisms of one escape event in 10 8 CFU.« less

  18. Evaluation of Tropical Transport in a Global Chemistry and Transport Model

    NASA Technical Reports Server (NTRS)

    Douglass, Anne R.; DaSilva, A. M.; Lin, S.-J.; Pawson, S.; Rood, R. B.; Bhartia, P. K. (Technical Monitor)

    2001-01-01

    Observations of constituents from satellite, aircraft and sondes can be utilized to develop diagnostics of various aspects of tropical transport. These include tropical mid-latitude isolation, the seasonal transport from the upper tropical troposphere to the mid-latitude lowermost stratosphere, the seasonal cycle of the tropical total ozone and its variability. These diagnostics will be applied to constituent fields from an off-line chemistry and transport model (CTM) driven by winds from two sources. These are the Finite Volume Community Climate Model (FV-CCM), a general circulation model that uses the NCAR CCM physics and the Lin and Rood dynamical core, and an assimilation system developed by the Data Assimilation Office at the Goddard Space Flight Center that uses the FV-CCM at its core. Signatures of the quasi-biennial oscillation present in the observations will be emphasized to understand differences between the two model transports and the transport inferred from the observations.

  19. A Finite-Volume "Shaving" Method for Interfacing NASA/DAO''s Physical Space Statistical Analysis System to the Finite-Volume GCM with a Lagrangian Control-Volume Vertical Coordinate

    NASA Technical Reports Server (NTRS)

    Lin, Shian-Jiann; DaSilva, Arlindo; Atlas, Robert (Technical Monitor)

    2001-01-01

    Toward the development of a finite-volume Data Assimilation System (fvDAS), a consistent finite-volume methodology is developed for interfacing the NASA/DAO's Physical Space Statistical Analysis System (PSAS) to the joint NASA/NCAR finite volume CCM3 (fvCCM3). To take advantage of the Lagrangian control-volume vertical coordinate of the fvCCM3, a novel "shaving" method is applied to the lowest few model layers to reflect the surface pressure changes as implied by the final analysis. Analysis increments (from PSAS) to the upper air variables are then consistently put onto the Lagrangian layers as adjustments to the volume-mean quantities during the analysis cycle. This approach is demonstrated to be superior to the conventional method of using independently computed "tendency terms" for surface pressure and upper air prognostic variables.

  20. Final Report on the Key Comparison CCM.P-K4.2012 in Absolute Pressure from 1 Pa to 10 kPa

    PubMed Central

    Ricker, Jacob; Hendricks, Jay; Bock, Thomas; Dominik, Pražák; Kobata, Tokihiko; Torres, Jorge; Sadkovskaya, Irina

    2017-01-01

    The report summarizes the Consultative Committee for Mass (CCM) key comparison CCM.P-K4.2012 for absolute pressure spanning the range of 1 Pa to 10 000 Pa. The comparison was carried out at six National Metrology Institutes (NMIs), including National Institute of Standards and Technology (NIST), Physikalisch-Technische Bundesanstalt (PTB), Czech Metrology Institute (CMI), National Metrology Institute of Japan (NMIJ), Centro Nacional de Metrología (CENAM), and DI Mendeleyev Institute for Metrology (VNIIM). The comparison was made via a calibrated transfer standard measured at each of the NMIs facilities using their laboratory standard during the period May 2012 to September 2013. The transfer package constructed for this comparison preformed as designed and provided a stable artifact to compare laboratory standards. Overall the participants were found to be statistically equivalent to the key comparison reference value. PMID:28216793

  1. A Comparison of Carbon Dioxide Elimination Measurements Between a Portable Indirect Calorimeter and Volumetric Capnography Monitor: An In Vitro Simulation.

    PubMed

    Smallwood, Craig D; Martinez, Enid E; Mehta, Nilesh M

    2016-03-01

    Gas exchange measurements for carbon dioxide elimination (V̇CO2 ) and oxygen consumption (V̇O2 ) have been used to derive resting energy expenditure and guide energy prescription. Volumetric capnography is used in intensive care units and provides V̇CO2 measurements that could be used for titrating respiratory and nutritional support. We have recently suggested that measuring V̇CO2 may be sufficient to obtain a reasonable estimate of energy expenditure. However, data describing the accuracy of gas exchange measurement devices are limited. We used an in vitro simulation model to test the accuracy of gas exchange measurements by 2 devices: the CCM Express indirect calorimeter and the NM3, a volumetric capnography monitor. A Huszczuk gas injection system combined with a high-fidelity lung simulator was used to simulate V̇O2 and V̇CO2 values in the pediatric and adult range. Bland-Altman analysis was used to examine the agreement between the measured and simulated values across a range of tidal volumes and gas exchange values. Additionally, agreement between the 2 devices was examined. During the adult simulation with the CCM Express, the mean bias (95% CI) for V̇CO2 values was -12.6% (-16.4 to -8.8%) and -17.5% (-19.9 to -15.1%) for V̇O2 values. For the pediatric simulation with the CCM Express, mean bias for V̇O2 was -14.7% (-16.4 to -13.0%) and V̇CO2 was -10.9% (-13.5 to -8.3%). For the adult and pediatric simulations with the NM3, the bias for V̇CO2 was -8.2% (-15.7 to -0.7%) and -8.3% (-19.4 to -2.8%), respectively. Between the 2 devices, the mean bias was -4.4% (-10.2 to 1.3%) and -2.3% (-11.4 to 6.8%) for the adult and pediatric V̇CO2 simulations, respectively. Currently available portable gas exchange monitors demonstrated acceptable agreement with reference V̇O2 and V̇CO2 values in an in vitro simulation. The devices demonstrated good agreement with each other. Copyright © 2016 by Daedalus Enterprises.

  2. A Mobile-Based Community Health Management Information System for Community Health Workers and Their Supervisors in 2 Districts of Zambia

    PubMed Central

    Biemba, Godfrey; Chiluba, Boniface; Yeboah-Antwi, Kojo; Silavwe, Vichaels; Lunze, Karsten; Mwale, Rodgers K; Russpatrick, Scott; Hamer, Davidson H

    2017-01-01

    ABSTRACT Introduction: Effective community health management information systems (C-HMIS) are important in low-resource countries that rely heavily on community-based health care providers. Zambia currently lacks a functioning C-HMIS to provide real-time, community-based health information from community health workers (CHWs) to health center staff and higher levels of the health system. Program Description: We developed a C-HMIS mobile platform for use by CHWs providing integrated community case management (iCCM) services and their supervisors to address challenges of frequent stock-outs and inadequate supportive supervision of iCCM-trained CHWs. The platform used simple feature mobile phones on which were loaded the District Health Information System version 2 (DHIS2) software and Java 2 platform micro edition (J2ME) aggregation and tracker applications. This project was implemented in Chipata and Chadiza districts, which supported previous mHealth programs and had cellular coverage from all 3 major network carriers in Zambia. A total of 40 CHWs and 20 CHW supervisors received mobile phones with data bundles and training in the mobile application, after which they implemented the program over a period of 5.5 months, from February to mid-July 2016. CHWs used the mobile phones to submit data on iCCM cases seen, managed, and referred, as well as iCCM medical and diagnostic supplies received and dispensed. Using their mobile phones, the supervisors tracked CHWs' reported cases with medicine consumption, sent CHWs feedback on their referrals, and received SMS reminders to set up mentorship sessions. Observations: CHWs were able to use the mobile application to send weekly reports to health center supervisors on disease caseloads and medical commodities consumed, to make drug and supply requisitions, and to send pre-referral notices to health centers. Health center staff used the mobile system to provide feedback to CHWs on the case outcomes of referred patients and to receive automated monthly SMS reminders to invite CHWs to the facility for mentorship. District- and central-level staff were able to access community-level health data in real time using passwords. Lessons Learned: C-HMIS, using simple feature phones, was feasible and viable for the provision of real-time community-based health information to all levels of the health care system in Zambia, but smartphones, laptops, or desktop computers are needed to perform data analysis and visualization. Ongoing technical support is needed to address the hardware and software challenges CHWs face in their day-to-day interaction with the application on their mobile phones. PMID:28855233

  3. A Mobile-Based Community Health Management Information System for Community Health Workers and Their Supervisors in 2 Districts of Zambia.

    PubMed

    Biemba, Godfrey; Chiluba, Boniface; Yeboah-Antwi, Kojo; Silavwe, Vichaels; Lunze, Karsten; Mwale, Rodgers K; Russpatrick, Scott; Hamer, Davidson H

    2017-09-27

    Effective community health management information systems (C-HMIS) are important in low-resource countries that rely heavily on community-based health care providers. Zambia currently lacks a functioning C-HMIS to provide real-time, community-based health information from community health workers (CHWs) to health center staff and higher levels of the health system. We developed a C-HMIS mobile platform for use by CHWs providing integrated community case management (iCCM) services and their supervisors to address challenges of frequent stock-outs and inadequate supportive supervision of iCCM-trained CHWs. The platform used simple feature mobile phones on which were loaded the District Health Information System version 2 (DHIS2) software and Java 2 platform micro edition (J2ME) aggregation and tracker applications. This project was implemented in Chipata and Chadiza districts, which supported previous mHealth programs and had cellular coverage from all 3 major network carriers in Zambia. A total of 40 CHWs and 20 CHW supervisors received mobile phones with data bundles and training in the mobile application, after which they implemented the program over a period of 5.5 months, from February to mid-July 2016. CHWs used the mobile phones to submit data on iCCM cases seen, managed, and referred, as well as iCCM medical and diagnostic supplies received and dispensed. Using their mobile phones, the supervisors tracked CHWs' reported cases with medicine consumption, sent CHWs feedback on their referrals, and received SMS reminders to set up mentorship sessions. CHWs were able to use the mobile application to send weekly reports to health center supervisors on disease caseloads and medical commodities consumed, to make drug and supply requisitions, and to send pre-referral notices to health centers. Health center staff used the mobile system to provide feedback to CHWs on the case outcomes of referred patients and to receive automated monthly SMS reminders to invite CHWs to the facility for mentorship. District- and central-level staff were able to access community-level health data in real time using passwords. C-HMIS, using simple feature phones, was feasible and viable for the provision of real-time community-based health information to all levels of the health care system in Zambia, but smartphones, laptops, or desktop computers are needed to perform data analysis and visualization. Ongoing technical support is needed to address the hardware and software challenges CHWs face in their day-to-day interaction with the application on their mobile phones. © Biemba et al.

  4. Microseismic source locations with deconvolution migration

    NASA Astrophysics Data System (ADS)

    Wu, Shaojiang; Wang, Yibo; Zheng, Yikang; Chang, Xu

    2018-03-01

    Identifying and locating microseismic events are critical problems in hydraulic fracturing monitoring for unconventional resources exploration. In contrast to active seismic data, microseismic data are usually recorded with unknown source excitation time and source location. In this study, we introduce deconvolution migration by combining deconvolution interferometry with interferometric cross-correlation migration (CCM). This method avoids the need for the source excitation time and enhances both the spatial resolution and robustness by eliminating the square term of the source wavelets from CCM. The proposed algorithm is divided into the following three steps: (1) generate the virtual gathers by deconvolving the master trace with all other traces in the microseismic gather to remove the unknown excitation time; (2) migrate the virtual gather to obtain a single image of the source location and (3) stack all of these images together to get the final estimation image of the source location. We test the proposed method on complex synthetic and field data set from the surface hydraulic fracturing monitoring, and compare the results with those obtained by interferometric CCM. The results demonstrate that the proposed method can obtain a 50 per cent higher spatial resolution image of the source location, and more robust estimation with smaller errors of the localization especially in the presence of velocity model errors. This method is also beneficial for source mechanism inversion and global seismology applications.

  5. Injection of celiac disease patient sera or immunoglobulins to mice reproduces a condition mimicking early developing celiac disease.

    PubMed

    Kalliokoski, Suvi; Caja, Sergio; Frias, Rafael; Laurila, Kaija; Koskinen, Outi; Niemelä, Onni; Mäki, Markku; Kaukinen, Katri; Korponay-Szabó, Ilma R; Lindfors, Katri

    2015-01-01

    Typical features of celiac disease are small-bowel villus atrophy, crypt hyperplasia, and inflammation which develop gradually concomitant with ingestion of gluten. In addition, patients have anti-transglutaminase 2 (TG2) autoantibodies in their serum and tissues. The aim of this study was to establish whether celiac disease can be passively transferred to mice by serum or immunoglobulins. Serum aliquots or purified immunoglobulins (Ig) were intraperitoneally injected into Hsd:Athymic Nude-Foxn1nu mice for 8 or 27 days. As mice do not have proper IgA transport from peritoneum to blood, sera with a high content of IgG class anti-TG2 antibodies from untreated IgA-deficient celiac patients were used. Mouse sera were tested for celiac disease-specific autoantibodies, and several tissues were analyzed for autoantibody deposits targeted to TG2. Morphological assessment was made of the murine small intestinal mucosa. Injection of celiac disease patient sera or total IgG led to a significant delay in weight gain and mild diarrhea in a subset of mice. The mice injected with celiac patient sera or IgG had significantly decreased villus height crypt depth (Vh/CrD) ratios and celiac disease-specific autoantibody deposits targeted to TG2 in several tissues, including the small intestine. None of these features were observed in control mice. We conclude that administration of IgA-deficient celiac disease patient serum or total IgG induces both deterioration of the intestinal mucosa and clinical features of celiac disease in mice. The experimentally induced condition in the mice injected with patient serum or IgG resembles early developing celiac disease in humans. Celiac disease patient sera or total IgG was injected into athymic mice. A significant delay in weight gain and mild diarrhea was observed. Mice evinced significantly decreased villus height crypt depth ratios. Celiac disease-specific autoantibody deposits were present in several tissues. The condition in mice resembles early stage celiac disease in humans.

  6. Is it time for a new classification of mast cells? What do we know about mast cell heterogeneity?

    PubMed

    Frossi, Barbara; Mion, Francesca; Sibilano, Riccardo; Danelli, Luca; Pucillo, Carlo E M

    2018-03-01

    Mast cells (MCs) are derived from committed precursors that leave the hematopoietic tissue, migrate in the blood, and colonize peripheral tissues where they terminally differentiate under microenvironment stimuli. They are distributed in almost all vascularized tissues where they act both as immune effectors and housekeeping cells, contributing to tissue homeostasis. Historically, MCs were classified into 2 subtypes, according to tryptic enzymes expression. However, MCs display a striking heterogeneity that reflects a complex interplay between different microenvironmental signals delivered by various tissues, and a differentiation program that decides their identity. Moreover, tissue-specific MCs show a trained memory, which contributes to shape their function in a specific microenvironment. In this review, we summarize the current state of our understanding of MC heterogeneity that reflects their different tissue experiences. We describe the discovery of unique cell molecules that can be used to distinguish specific MC subsets in vivo, and discuss how the improved ability to recognize these subsets provided new insights into the biology of MCs. These recent advances will be helpful for the understanding of the specific role of individual MC subsets in the control of tissue homeostasis, and in the regulation of pathological conditions such as infection, autoimmunity, and cancer. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Detecting Tie2, an endothelial growth factor receptor, by using immunohistochemistry in mouse lungs.

    PubMed

    Guha, Prajna P; David, Sascha A; Ghosh, Chandra C

    2014-01-01

    Immunohistochemical (IHC) staining is an invaluable, sensitive, and effective method to detect the presence and localization of proteins in the cellular compartment in tissues. The basic concept of IHC is detecting the antigen in tissues by means of specific antibody binding, which is then demonstrated with a colored histochemical reaction that can be observed under a light microscope. The most challenging aspect of IHC techniques is optimizing the precise experimental conditions that are required to get a specific and a strong signal. The critical steps of IHC are specimen acquisition, fixation, permeabilization, detection system, and selection of the antigen specific antibody and its optimization. Here, we elaborate the technique using the endothelial growth factor binding receptor Tie2 in mouse lungs.

  8. Exploring Robust Methods for Evaluating Treatment and Comparison Groups in Chronic Care Management Programs

    PubMed Central

    Hamar, Brent; Bradley, Chastity; Gandy, William M.; Harrison, Patricia L.; Sidney, James A.; Coberley, Carter R.; Rula, Elizabeth Y.; Pope, James E.

    2013-01-01

    Abstract Evaluation of chronic care management (CCM) programs is necessary to determine the behavioral, clinical, and financial value of the programs. Financial outcomes of members who are exposed to interventions (treatment group) typically are compared to those not exposed (comparison group) in a quasi-experimental study design. However, because member assignment is not randomized, outcomes reported from these designs may be biased or inefficient if study groups are not comparable or balanced prior to analysis. Two matching techniques used to achieve balanced groups are Propensity Score Matching (PSM) and Coarsened Exact Matching (CEM). Unlike PSM, CEM has been shown to yield estimates of causal (program) effects that are lowest in variance and bias for any given sample size. The objective of this case study was to provide a comprehensive comparison of these 2 matching methods within an evaluation of a CCM program administered to a large health plan during a 2-year time period. Descriptive and statistical methods were used to assess the level of balance between comparison and treatment members pre matching. Compared with PSM, CEM retained more members, achieved better balance between matched members, and resulted in a statistically insignificant Wald test statistic for group aggregation. In terms of program performance, the results showed an overall higher medical cost savings among treatment members matched using CEM compared with those matched using PSM (-$25.57 versus -$19.78, respectively). Collectively, the results suggest CEM is a viable alternative, if not the most appropriate matching method, to apply when evaluating CCM program performance. (Population Health Management 2013;16:35–45) PMID:22788834

  9. Final report on the key comparison of hydrocarbon liquid flow: CCM.FF-K2.2015

    NASA Astrophysics Data System (ADS)

    Shimada, T.; Bittner-Rohrhofer, K.; Medina López, V. J.; Arias, R.; Su, C.-M.; Chen, I.-C.; Ribere, F.; Rowan, L.; Dignan, S.

    2016-01-01

    Seven laboratories: BEV (Austria), CENAM (Mexico), CMS (Chinese-Taipei), LNE-TRAPIL (France), NEL (United Kingdom), NMIA (Australia), and the pilot lab NMIJ (Japan), participated in the key comparison CCM.FF-K2.2015 for hydrocarbon flow measurement. A screw type positive displacement flow meter was selected as a transfer standard. The calibration stability of the transfer standard was evaluated from repeated measurements by NMIJ and showed standard reproducibility of 0.0035 %. The transfer standard was also thoroughly tested for sensitivity to temperature, viscosity, pressure, and other effects. The uncertainty due to the transfer standard of 0.0080 % was less than the quoted uncertainties of the participants. The key comparison reference values (KCRVs) at Reynolds number of 70 000 and 300 000 were obtained as the weighted mean from the calibration results, and the KCRV at Reynolds number of 100 000 was obtained as the median by using the Monte Carlo method according to Cox's procedure B, since the consistency check at Reynolds number of 100 000 failed at the 95 % confidence level. All participant results selected to determine the KCRVs have En values which show consistency with the evaluated KCRVs. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  10. Assessment of a prototype computer colour matching system to reproduce natural tooth colour on ceramic restorations.

    PubMed

    Kristiansen, Joshua; Sakai, Maiko; Da Silva, John D; Gil, Mindy; Ishikawa-Nagai, Shigemi

    2011-12-01

    The aim of this study was to assess the accuracy of a prototype computer colour matching (CCM) system for dental ceramics targeting the colour of natural maxillary central incisors employing a dental spectrophotometer and the Kubelka-Munk theory. Seventeen human volunteers with natural intact maxillary central incisors were selected to participate in this study. One central incisor from each subject was measured in the body region by a spectrophotometer and the reflectance values were used by the CCM system in order to generate a prescription for a ceramic mixture to reproduce the target tooth's colour. Ceramic discs were fabricated based on these prescriptions and layered on a zirconia ceramic core material of a specified colour. The colour match of each two-layered specimen to the target natural tooth was assessed by CIELAB colour coordinates (ΔE(*), ΔL(*), Δa(*) and Δb(*)). The average colour difference ΔE(*) value was 2.58±84 for the ceramic specimen-natural tooth (CS-NT) pairs. ΔL(*) values ranged from 0.17 to 2.71, Δa(*) values ranged from -1.70 to 0.61, and Δb(*) values ranged from -1.48 to 3.81. There was a moderate inverse correlation (R=-0.44, p-value=0.0721) between L(*) values for natural target teeth and ΔE(*) values; no such correlation was found for a(*) and b(*) values. The newly developed prototype CCM system has the potential to be used as an efficient tool in the reproduction of natural tooth colour. Copyright © 2011. Published by Elsevier Ltd.

  11. Exploring robust methods for evaluating treatment and comparison groups in chronic care management programs.

    PubMed

    Wells, Aaron R; Hamar, Brent; Bradley, Chastity; Gandy, William M; Harrison, Patricia L; Sidney, James A; Coberley, Carter R; Rula, Elizabeth Y; Pope, James E

    2013-02-01

    Evaluation of chronic care management (CCM) programs is necessary to determine the behavioral, clinical, and financial value of the programs. Financial outcomes of members who are exposed to interventions (treatment group) typically are compared to those not exposed (comparison group) in a quasi-experimental study design. However, because member assignment is not randomized, outcomes reported from these designs may be biased or inefficient if study groups are not comparable or balanced prior to analysis. Two matching techniques used to achieve balanced groups are Propensity Score Matching (PSM) and Coarsened Exact Matching (CEM). Unlike PSM, CEM has been shown to yield estimates of causal (program) effects that are lowest in variance and bias for any given sample size. The objective of this case study was to provide a comprehensive comparison of these 2 matching methods within an evaluation of a CCM program administered to a large health plan during a 2-year time period. Descriptive and statistical methods were used to assess the level of balance between comparison and treatment members pre matching. Compared with PSM, CEM retained more members, achieved better balance between matched members, and resulted in a statistically insignificant Wald test statistic for group aggregation. In terms of program performance, the results showed an overall higher medical cost savings among treatment members matched using CEM compared with those matched using PSM (-$25.57 versus -$19.78, respectively). Collectively, the results suggest CEM is a viable alternative, if not the most appropriate matching method, to apply when evaluating CCM program performance.

  12. Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice

    PubMed Central

    Córdoba-Chacón, José; Gahete, Manuel D.; Castaño, Justo P.; Kineman, Rhonda D.

    2011-01-01

    Somatostatin (SST) inhibits growth hormone (GH) secretion and regulates multiple processes by signaling through its receptors sst1–5. Differential expression of SST/ssts may contribute to sex-specific GH pattern and fasting-induced GH rise. To further delineate the tissue-specific roles of SST and sst1–5 in these processes, their expression patterns were evaluated in hypothalamus, pituitary, and stomach of male and female mice under fed/fasted conditions in the presence (wild type) or absence (SST-knockout) of endogenous SST. Under fed conditions, hypothalamic/stomach SST/ssts expression did not differ between sexes, whereas male pituitary expressed more SST and sst2A/2B/3/5A/5TMD2/5TMD1 and less sst1, and male pituitary cell cultures were more responsive to SST inhibitory actions on GH release compared with females. This suggests that local pituitary SST/ssts can contribute to the sexually dimorphic pattern of GH release. Fasting (48 h) reduced stomach sst2A/B and hypothalamic SST/sst2A expression in both sexes, whereas it caused a generalized downregulation of pituitary sst subtypes in male and of sst2A only in females. Thus, fasting can reduce SST sensitivity across tissues and SST input to the pituitary, thereby jointly contributing to enhance GH release. In SST-knockout mice, lack of SST differentially altered sst subtype expression levels in both sexes, supporting an important role for SST in sex-dependent control of GH axis. Evaluation of SST, IGF-I, and glucocorticoid effects on hypothalamic and pituitary cell cultures revealed that these hormones could directly account for alterations in sst2/5 expression in the physiological states examined. Taken together, these results indicate that changes in SST output and sensitivity can contribute critically to precisely define, in a tissue-dependent manner, the sex-specific metabolic regulation of the GH axis. PMID:20943754

  13. Regional comparison of absolute gravimeters SIM.M.G-K1 key comparison

    NASA Astrophysics Data System (ADS)

    Newell, D. B.; van Westrum, D.; Francis, O.; Kanney, J.; Liard, J.; Ramirez, A. E.; Lucero, B.; Ellis, B.; Greco, F.; Pistorio, A.; Reudink, R.; Iacovone, D.; Baccaro, F.; Silliker, J.; Wheeler, R. D.; Falk, R.; Ruelke, A.

    2017-01-01

    Twelve absolute gravimeters were compared during the regional Key Comparison SIM.M.G-K1 of absolute gravimeters. The four gravimeters were from different NMIs and DIs. The comparison was linked to the CCM.G-K2 through EURAMET.M.G-K2 via the DI gravimeter FG5X-216. Overall, the results and uncertainties indicate an excellent agreement among the gravimeters, with a standard deviation of the gravimeters' DoEs better than 1.3 μGal. In the case of the official solution, all the gravimeters are in equivalence well within the declared uncertainties. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  14. Final report on the EURAMET.M.FF-K4.2.2014 volume comparison at 100 μL—calibration of micropipettes

    NASA Astrophysics Data System (ADS)

    Batista, Elsa; Matus, Michael; Metaxiotou, Zoe; Tudor, Maria; Lenard, Elzbieta; Buker, Oliver; Wennergren, Per; Piluri, Erinda; Miteva, Mariana; Vicarova, Martina; Vospĕlová, Alena; Turnsek, Urska; Micic, Ljiljana; Grue, Lise-Lote; Mihailovic, Mirjana; Sarevska, Anastazija

    2017-01-01

    During the EURAMET TC-F meeting of 2014 and following the finalization of CCM.FF-K4.2.2011 comparison, it was agreed to start a Regional Key Comparison (KC) on volume measurements using two 100 μL micropipettes (piston pipettes) allowing the participating laboratories to assess the agreement of their results and uncertainties. Two 100 μL micropipettes were tested by 15 participants. One participant was not a member or associate member of the BIPM and was be removed from this report. The comparison started in July 2015 and ended in March 2016. The Volume and Flow Laboratory of the Portuguese Institute for Quality (IPQ) was the pilot laboratory and performed the initial and final measurements of the micropipettes. The micropipettes showed a stable volume during the whole comparison, which was confirmed by the results from the pilot laboratory. The original results of all participant NMIs were corrected to the standard atmospheric pressure in order to compare results under the same calibration conditions, and the contribution of the 'process-related handling contribution' was added to the uncertainty budget of each participant. In general the declared CMCs are in accordance with the KCDB. For the micropipette 354828Z, two laboratories had inconsistent results. For micropipette 354853Z, three laboratories had inconsistent results. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  15. Transport of Passive Tracers in Baroclinic Wave Life Cycles

    NASA Technical Reports Server (NTRS)

    Stone, Elizabeth M.; Randel, William J.; Stanford, John L.

    1999-01-01

    The transport of passive tracers in idealized baroclinic wave life cycles is studied using output from the National Center for Atmospheric Research Community Climate Model (CCM2). Two life cycles, LCn and LCs, are simulated, starting with baroclinically unstable initial conditions similar to those used by Thorncroft et al. in their study of two life cycle paradigms. The two life cycles LCn and LCs have different initial horizontal wind shear structures that result in distinctive nonlinear development. In terms of potential vorticity-potential temperature (PV-theta) diagnostics, the LCn case is characterized by thinning troughs that are advected anti-cyclonically and equatorward, while the LCs case has broadening troughs that wrap up cyclonically and poleward. Four idealized passive tracers are included in the model to be advected by the semi-Lagrangian transport scheme of the CCM2, and their evolutions are investigated throughout the life cycles. Tracer budgets are analyzed in terms of the transformed Eulerian mean constituent transport formalism in pressure coordinates and also in isentropic coordinates. Results for both LCn and LCs show transport that is downgradient with respect to the background structure of the tracer field, but with a characteristic spatial structure that maximizes in the middle to high latitudes. For the idealized tropospheric tracers in this study, this represents a net upward and poleward transport that enhances concentrations at high latitudes. These results vary little with the initial distribution of the constituent field. The time tendency of the tracer is influenced most strongly by the eddy flux term. with the largest transport occurring during the nonlinear growth stage of the life cycle. The authors also study the transport of a lower-stratospheric tracer, to examine stratosphere-troposphere exchange for baroclinic waves.

  16. Hydrogel-beta-TCP scaffolds and stem cells for tissue engineering bone.

    PubMed

    Weinand, Christian; Pomerantseva, Irina; Neville, Craig M; Gupta, Rajiv; Weinberg, Eli; Madisch, Ijad; Shapiro, Frederic; Abukawa, Harutsugi; Troulis, Maria J; Vacanti, Joseph P

    2006-04-01

    Trabecular bone is a material of choice for reconstruction after trauma and tumor resection and for correction of congenital defects. Autologous bone grafts are available in limited shapes and sizes; significant donor site morbidity is another major disadvantage to this approach. To overcome these limitations, we used a tissue engineering approach to create bone replacements in vitro, combining bone-marrow-derived differentiated mesenchymal stem cells (MSCs) suspended in hydrogels and 3-dimensionally printed (3DP) porous scaffolds made of beta-tricalcium-phosphate (beta-TCP). The scaffolds provided support for the formation of bone tissue in collagen I, fibrin, alginate, and pluronic F127 hydrogels during culturing in oscillating and rotating dynamic conditions. Histological evaluation including toluidine blue, alkaline phosphatase, and von Kossa staining was done at 1, 2, 4, and 6 weeks. Radiographic evaluation and high-resolution volumetric CT (VCT) scanning, expression of bone-specific genes and biomechanical compression testing were performed at 6 weeks. Both culture conditions resulted in similar bone tissue formation. Histologically collagen I and fibrin hydrogels specimens had superior bone tissue, although radiopacities were detected only in collagen I samples. VCT scan revealed density values in all but the Pluronic F127 samples, with Houndsfield unit values comparable to native bone in collagen I and fibrin glue samples. Expression of bone-specific genes was significantly higher in the collagen I samples. Pluronic F127 hydrogel did not support formation of bone tissue. All samples cultured in dynamic oscillating conditions had slightly higher mechanical strength than under rotating conditions. Bone tissue can be successfully formed in vitro using constructs comprised of collagen I hydrogel, MSCs, and porous beta-TCP scaffolds.

  17. Leakage flow simulation in a specific pump model

    NASA Astrophysics Data System (ADS)

    Dupont, P.; Bayeul-Lainé, A. C.; Dazin, A.; Bois, G.; Roussette, O.; Si, Q.

    2014-03-01

    This paper deals with the influence of leakage flow existing in SHF pump model on the analysis of internal flow behaviour inside the vane diffuser of the pump model performance using both experiments and calculations. PIV measurements have been performed at different hub to shroud planes inside one diffuser channel passage for a given speed of rotation and various flow rates. For each operating condition, the PIV measurements have been trigged with different angular impeller positions. The performances and the static pressure rise of the diffuser were also measured using a three-hole probe. The numerical simulations were carried out with Star CCM+ 8.06 code (RANS frozen and unsteady calculations). Comparisons between numerical and experimental results are presented and discussed for three flow rates. The performances of the diffuser obtained by numerical simulation results are compared to the performances obtained by three-hole probe indications. The comparisons show few influence of fluid leakage on global performances but a real improvement concerning the efficiency of the impeller, the pump and the velocity distributions. These results show that leakage is an important parameter that has to be taken into account in order to make improved comparisons between numerical approaches and experiments in such a specific model set up.

  18. Final report on APMP.M.M.K4.1—bilateral comparison of 1 kg stainless steel mass standards between KRISS and A*STAR

    NASA Astrophysics Data System (ADS)

    Chung, J. W.; Lee, S. M.; Lee, S. J.

    2017-01-01

    This report describes a bilateral comparison of 1 kg stainless steel mass standard between the Korea Research Institute of Standards and Science (KRISS), and the National Measurement Centre, Agency for Science, Technology and Research (A*STAR), Singapore, which is registered in the BIPM KCDB as APMP.M.M-K4.1. This nominal value was chosen as it followed the nominal value of CCM.M-K4. This bilateral comparison was piloted by KRISS. The transfer weight was delivered to A*STAR from KRISS in April 2015 and received back from A*STAR in October 2015. A*STAR are aiming to improve their calibration measurement capability (CMC) for mass of 1 kg. KRISS participated in both this comparison and CCM.M-K4, providing a link between the A*STAR result and the KCRV of CCM.M-K4. The final report of this comparison is given in this document. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  19. Factors Affecting Availability of Essential Medicines among Community Health Workers in Ethiopia, Malawi, and Rwanda: Solving the Last Mile Puzzle

    PubMed Central

    Chandani, Yasmin; Noel, Megan; Pomeroy, Amanda; Andersson, Sarah; Pahl, Michelle K.; Williams, Timothy

    2012-01-01

    To understand how supply chain factors affect product availability at the community level, the Improving Supply Chains for Community Case Management of Pneumonia and Other Common Diseases of Childhood Project developed a theory of change (TOC) framework for gathering, organizing, and interpreting evidence about supply constraints to community case management (CCM). Baseline assessments in Ethiopia, Malawi, and Rwanda conducted in 2010 provided information on the strengths and weaknesses of existing CCM supply chains for five main products: antibiotics for pneumonia, oral rehydration solution, ready to use therapeutic food, zinc, and artemether/lumefantrine. The assessments tested the strength and validity of causal pathways identified in the TOC that were believed to influence availability of CCM products among community health workers (CHWs) for treating common childhood illnesses. Results of the assessments showed product availability to be weak in each country, with more than half of CHWs stocked out of at least one tracer product on the day of the assessment. This report will focus on the findings related to three key preconditions of the TOC and how these were used to inform the design of the CCM supply chain improvement strategy in each country. The three key preconditions include product availability at CHW resupply points, supply chain knowledge and capacity among CHWs and their supervisors, and availability of appropriate transportation. PMID:23136287

  20. Multipayer patient-centered medical home implementation guided by the chronic care model.

    PubMed

    Gabbay, Robert A; Bailit, Michael H; Mauger, David T; Wagner, Edward H; Siminerio, Linda

    2011-06-01

    A unique statewide multipayer ini Pennsylvania was undertaken to implement the Patient-Centered Medical Home (PCMH) guided by the Chronic Care Model (CCM) with diabetes as an initial target disease. This project represents the first broad-scale CCM implementation with payment reform across a diverse range of practice organizations and one of the largest PCMH multipayer initiatives. Practices implemented the CCM and PCMH through regional Breakthrough Series learning collaboratives, supported by Improving Performance in Practice (IPIP) practice coaches, with required monthly quality reporting enhanced by multipayer infrastructure payments. Some 105 practices, representing 382 primary care providers, were engaged in the four regional collaboratives. The practices from the Southeast region of Pennsylvania focused on diabetes patients (n = 10,016). During the first intervention year (May 2008-May 2009), all practices achieved at least Level 1 National Committee for Quality Assurance (NCQA) Physician Practice Connections Patient-Centered Medical Home (PPC-PCMH) recognition. There was significant improvement in the percentage of patients who had evidence-based complications screening and who were on therapies to reduce morbidity and mortality (statins, angiotensin-converting enzyme inhibitors). In addition, there were small but statistically significant improvements in key clinical parameters for blood pressure and cholesterol levels, with the greatest absolute improvement in the highest-risk patients. Transforming primary care delivery through implementation of the PCMH and CCM supported by multipayer infrastructure payments holds significant promise to improve diabetes care.

  1. Factors affecting availability of essential medicines among community health workers in Ethiopia, Malawi, and Rwanda: solving the last mile puzzle.

    PubMed

    Chandani, Yasmin; Noel, Megan; Pomeroy, Amanda; Andersson, Sarah; Pahl, Michelle K; Williams, Timothy

    2012-11-01

    To understand how supply chain factors affect product availability at the community level, the Improving Supply Chains for Community Case Management of Pneumonia and Other Common Diseases of Childhood Project developed a theory of change (TOC) framework for gathering, organizing, and interpreting evidence about supply constraints to community case management (CCM). Baseline assessments in Ethiopia, Malawi, and Rwanda conducted in 2010 provided information on the strengths and weaknesses of existing CCM supply chains for five main products: antibiotics for pneumonia, oral rehydration solution, ready to use therapeutic food, zinc, and artemether/lumefantrine. The assessments tested the strength and validity of causal pathways identified in the TOC that were believed to influence availability of CCM products among community health workers (CHWs) for treating common childhood illnesses. Results of the assessments showed product availability to be weak in each country, with more than half of CHWs stocked out of at least one tracer product on the day of the assessment. This report will focus on the findings related to three key preconditions of the TOC and how these were used to inform the design of the CCM supply chain improvement strategy in each country. The three key preconditions include product availability at CHW resupply points, supply chain knowledge and capacity among CHWs and their supervisors, and availability of appropriate transportation.

  2. Materials and Process Activities for NASA's Composite Crew Module

    NASA Technical Reports Server (NTRS)

    Polis, Daniel L.

    2012-01-01

    In January 2007, the NASA Administrator and Associate Administrator for the Exploration Systems Mission Directorate chartered the NASA Engineering and Safety Center (NESC) to design, build, and test a full-scale Composite Crew Module (CCM). The overall goal of the CCM project was to develop a team from the NASA family with hands-on experience in composite design, manufacturing, and testing in anticipation of future space exploration systems being made of composite materials. The CCM project was planned to run concurrently with the Orion project s baseline metallic design within the Constellation Program so that features could be compared and discussed without inducing risk to the overall Program. The materials and process activities were prioritized based on a rapid prototype approach. This approach focused developmental activities on design details with greater risk and uncertainty, such as out-of-autoclave joining, over some of the more traditional lamina and laminate building block levels. While process development and associated building block testing were performed, several anomalies were still observed at the full-scale level due to interactions between process robustness and manufacturing scale-up. This paper describes the process anomalies that were encountered during the CCM development and the subsequent root cause investigations that led to the final design solutions. These investigations highlight the importance of full-scale developmental work early in the schedule of a complex composite design/build project.

  3. Generalized Bondi-Sachs equations for characteristic formalism of numerical relativity

    NASA Astrophysics Data System (ADS)

    Cao, Zhoujian; He, Xiaokai

    2013-11-01

    The Cauchy formalism of numerical relativity has been successfully applied to simulate various dynamical spacetimes without any symmetry assumption. But discovering how to set a mathematically consistent and physically realistic boundary condition is still an open problem for Cauchy formalism. In addition, the numerical truncation error and finite region ambiguity affect the accuracy of gravitational wave form calculation. As to the finite region ambiguity issue, the characteristic extraction method helps much. But it does not solve all of the above issues. Besides the above problems for Cauchy formalism, the computational efficiency is another problem. Although characteristic formalism of numerical relativity suffers the difficulty from caustics in the inner near zone, it has advantages in relation to all of the issues listed above. Cauchy-characteristic matching (CCM) is a possible way to take advantage of characteristic formalism regarding these issues and treat the inner caustics at the same time. CCM has difficulty treating the gauge difference between the Cauchy part and the characteristic part. We propose generalized Bondi-Sachs equations for characteristic formalism for the Cauchy-characteristic matching end. Our proposal gives out a possible same numerical evolution scheme for both the Cauchy part and the characteristic part. And our generalized Bondi-Sachs equations have one adjustable gauge freedom which can be used to relate the gauge used in the Cauchy part. Then these equations can make the Cauchy part and the characteristic part share a consistent gauge condition. So our proposal gives a possible new starting point for Cauchy-characteristic matching.

  4. Immunoreactive Proteins of Bifidobacterium longum ssp. longum CCM 7952 and Bifidobacterium longum ssp. longum CCDM 372 Identified by Gnotobiotic Mono-Colonized Mice Sera, Immune Rabbit Sera and Non-immune Human Sera

    PubMed Central

    Górska, Sabina; Dylus, Ewa; Rudawska, Angelika; Brzozowska, Ewa; Srutkova, Dagmar; Schwarzer, Martin; Razim, Agnieszka; Kozakova, Hana; Gamian, Andrzej

    2016-01-01

    The Bifidobacteria show great diversity in the cell surface architecture which may influence the physicochemical properties of the bacterial cell and strain specific properties. The immunomodulatory role of bifidobacteria has been extensively studied, however studies on the immunoreactivity of their protein molecules are very limited. Here, we compared six different methods of protein isolation and purification and we report identification of immunogenic and immunoreactive protein of two human Bifidobacterium longum ssp. longum strains. We evaluated potential immunoreactive properties of proteins employing polyclonal sera obtained from germ free mouse, rabbit and human. The protein yield was isolation method-dependent and the reactivity of proteins detected by SDS-PAGE and Western blotting was heterogeneous and varied between different serum samples. The proteins with the highest immunoreactivity were isolated, purified and have them sequenced. Among the immunoreactive proteins we identified enolase, aspartokinase, pyruvate kinase, DnaK (B. longum ssp. longum CCM 7952) and sugar ABC transporter ATP-binding protein, phosphoglycerate kinase, peptidoglycan synthethase penicillin-binding protein 3, transaldolase, ribosomal proteins and glyceraldehyde 3-phosphate dehydrogenase (B. longum ssp. longum CCDM 372). PMID:27746766

  5. Immunoreactive Proteins of Bifidobacterium longum ssp. longum CCM 7952 and Bifidobacterium longum ssp. longum CCDM 372 Identified by Gnotobiotic Mono-Colonized Mice Sera, Immune Rabbit Sera and Non-immune Human Sera.

    PubMed

    Górska, Sabina; Dylus, Ewa; Rudawska, Angelika; Brzozowska, Ewa; Srutkova, Dagmar; Schwarzer, Martin; Razim, Agnieszka; Kozakova, Hana; Gamian, Andrzej

    2016-01-01

    The Bifidobacteria show great diversity in the cell surface architecture which may influence the physicochemical properties of the bacterial cell and strain specific properties. The immunomodulatory role of bifidobacteria has been extensively studied, however studies on the immunoreactivity of their protein molecules are very limited. Here, we compared six different methods of protein isolation and purification and we report identification of immunogenic and immunoreactive protein of two human Bifidobacterium longum ssp. longum strains. We evaluated potential immunoreactive properties of proteins employing polyclonal sera obtained from germ free mouse, rabbit and human. The protein yield was isolation method-dependent and the reactivity of proteins detected by SDS-PAGE and Western blotting was heterogeneous and varied between different serum samples. The proteins with the highest immunoreactivity were isolated, purified and have them sequenced. Among the immunoreactive proteins we identified enolase, aspartokinase, pyruvate kinase, DnaK ( B. longum ssp. longum CCM 7952) and sugar ABC transporter ATP-binding protein, phosphoglycerate kinase, peptidoglycan synthethase penicillin-binding protein 3, transaldolase, ribosomal proteins and glyceraldehyde 3-phosphate dehydrogenase ( B. longum ssp. longum CCDM 372).

  6. CONFERENCE NOTE: Comité Consultatif pour la Masse et les grandeurs apparentées (CCM), High Pressure and Medium Pressure Working Groups, Second International Seminar on Pressure Metrology from 1 kPa to 1 GPa

    NASA Astrophysics Data System (ADS)

    1992-01-01

    The seminar will be held from 2 to 4 June 1993, preceding the next meeting of the CCM, at the Laboratoire National d'Essais (LNE), 1 rue Gaston Boissier, 75015 Paris, France. Scope of the Seminar The purpose of the seminar is to review the state of the art of pressure measurements in the 1 kPa to 1 GPa range and to present original and innovative contributions from standards laboratories and industry. Main Topics The seminar will be organized in six sessions as follows: Liquid-column manometers Piston gauge pressure standards Properties of liquids and gases relevant to pressure metrology Pressure transducers and transfer standards Pressure standard comparison (methods and results) Dynamic pressure measurements. Each topic will be introduced by a review paper presented by a session chairman. A final session, coordinated by Dr G F Molinar (IMGC), Chairman of the CCM High Pressure Working Group, and Dr P Stuart (NPL), Chairman of the CCM Medium Pressure Working Group, will deal with: Actual limits of accuracy of static pressure measurements in fluid media Fundamental problems in pressure metrology between I kPa and 1 GPa. Call for Papers Papers should be prepared for oral presentation and will be refereed by the session chairmen. The Proceedings will be published as a special issue of Metrologia. Papers should be written according to the instructions for authors printed on the inside back cover of this journal. A one-page abstract should be sent to Dr Molinar at the IMGC, to arrive before 31 January 1993. A participation fee of 900 FFr (175 US) will be charged. This will cover general expenses and a copy of the Proceedings. Hotel reservations, meals and transport are not included. Organizers For further information please contact: 1993 CCM Pressure Seminar, Dr G F Molinar, Istituto di Metrologia "G Colonnetti", Strada delle Cacce 73, 1-10135 Torino, Italy telephone (39) 11 39771; telex 212209 IMGCTO-I; fax (39) 11 346761. Contact at the LNE: J C Legras, telephone (33) 1 40433700; fax (33) 1 40433737. Scientific Committee The following are responsible for the preparation of the seminar programme: J Bonhoure, BIPM, France V Borovkov, VNIIFTRI, Russia C Ehrlich, NIST, USA J Jäger, PTB, Germany J C Legras, LNE, France G F Molinar, IMGC, Italy P Stuart, NPL, UK C Tilford, NIST, USA S Yamamoto, NRLM, Japan R Wisniewski, Warsaw Univ. of Tech., Poland

  7. Interactive Electronic Decision Trees for the Integrated Primary Care Management of Febrile Children in Low Resource Settings - Review of existing tools.

    PubMed

    Keitel, Kristina; D'Acremont, Valérie

    2018-04-20

    The lack of effective, integrated diagnostic tools pose a major challenge to the primary care management of febrile childhood illnesses. These limitations are especially evident in low-resource settings and are often inappropriately compensated by antimicrobial over-prescription. Interactive electronic decision trees (IEDTs) have the potential to close these gaps: guiding antibiotic use and better identifying serious disease. This narrative review summarizes existing IEDTs, to provide an overview of their degree of validation, as well as to identify gaps in current knowledge and prospects for future innovation. Structured literature review in PubMed and Embase complemented by google search and contact with developers. Six integrated IEDTs were identified: three (eIMCI, REC, and Bangladesh digital IMCI) based on Integrated Management of Childhood Illnesses (IMCI); four (SL eCCM, MEDSINC, e-iCCM, and D-Tree eCCM) on Integrated Community Case Management (iCCM); two (ALMANACH, MSFeCARE) with a modified IMCI content; and one (ePOCT) that integrates novel content with biomarker testing. The types of publications and evaluation studies varied greatly: the content and evidence-base was published for two (ALMANACH and ePOCT), ALMANACH and ePOCT were validated in efficacy studies. Other types of evaluations, such as compliance, acceptability were available for D-Tree eCCM, eIMCI, ALMANACH. Several evaluations are still ongoing. Future prospects include conducting effectiveness and impact studies using data gathered through larger studies to adapt the medical content to local epidemiology, improving the software and sensors, and Assessing factors that influence compliance and scale-up. IEDTs are valuable tools that have the potential to improve management of febrile children in primary care and increase the rational use of diagnostics and antimicrobials. Next steps in the evidence pathway should be larger effectiveness and impact studies (including cost analysis) and continuous integration of clinically useful diagnostic and treatment innovations. Copyright © 2018. Published by Elsevier Ltd.

  8. Surgical Management and Long-Term Seizure Outcome After Surgery for Temporal Lobe Epilepsy Associated with Cerebral Cavernous Malformations.

    PubMed

    Yang, Peng-Fan; Pei, Jia-Sheng; Jia, Yan-Zeng; Lin, Qiao; Xiao, Hui; Zhang, Ting-Ting; Zhong, Zhong-Hui

    2018-02-01

    Operative strategies for cerebral cavernous malformation (CCM)-associated temporal lobe epilepsy and timing of surgical intervention continue to be debated. This study aimed to establish an algorithm to evaluate the efficacy of surgical intervention strategies, to maximize positive surgical outcomes and minimize postsurgical neurologic deficits. 47 patients having undergone operation for CCM-associated temporal lobe epilepsy were retrospectively reviewed. They had received a diagnostic series for seizure localization, including long-term video electroencephalography (vEEG), high-resolution magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT). In patients with mesial temporal lobe CCMs, the involved structures (amygdala, hippocampus, or parahippocampal gyrus) were resected in addition to the lesions. Patients with neocortical epileptogenic CCM underwent extended lesionectomy guided by intraoperative electrocorticography; further performance of amygdalohippocampectomy depended on the extent of hippocampal epileptogenicity. The study cohort contained 28 patients with drug-resistant epilepsy (DRE), 12 with chronic epilepsy (CE), and 7 with sporadic seizure (SS). Normal temporal lobe metabolism was seen in 7/7 patients of the SS group. Hypometabolism was found in all patients with chronic disease except for those with posterior inferior and middle temporal gyrus cavernous malformations (CMs). Of the 31 patients with superficial neocortical CCM, 7 had normal PET without hippocampal sclerosis, 14 had ipsilateral temporal lobe hypometabolism without hippocampal sclerosis, and 10 had obvious hippocampal sclerosis and hypometabolism. Seizure freedom in DRE, CE, and SS was 82.1%, 75%, and 100%, respectively. A significant difference was found between lesion laterality and postoperative seizure control; the rate was lower in left-sided cases because of less aggressive resection. Our study demonstrates that the data from the presurgical evaluation, particularly regarding CM location, responsiveness to antiepileptic drugs, and temporal lobe metabolism, are crucial parameters for choosing surgical approaches to CCM-associated temporal lobe epilepsy. By this operative strategy, patients may receive maximized seizure control and minimized postsurgical neurologic sequelae. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Equatorial waves simulated by the NCAR community climate model

    NASA Technical Reports Server (NTRS)

    Cheng, Xinhua; Chen, Tsing-Chang

    1988-01-01

    The equatorial planetary waves simulated by the NCAR CCM1 general circulation model were investigated in terms of space-time spectral analysis (Kao, 1968; Hayashi, 1971, 1973) and energetic analysis (Hayashi, 1980). These analyses are particularly applied to grid-point data on latitude circles. In order to test some physical factors which may affect the generation of tropical transient planetary waves, three different model simulations with the CCM1 (the control, the no-mountain, and the no-cloud experiments) were analyzed.

  10. Comprehensive care programs for patients with multiple chronic conditions: a systematic literature review.

    PubMed

    de Bruin, Simone R; Versnel, Nathalie; Lemmens, Lidwien C; Molema, Claudia C M; Schellevis, François G; Nijpels, Giel; Baan, Caroline A

    2012-10-01

    To provide insight into the characteristics of comprehensive care programs for patients with multiple chronic conditions and their impact on patients, informal caregivers, and professional caregivers. Systematic literature search in multiple electronic databases for English language papers published between January 1995 and January 2011, supplemented by reference tracking and a manual search on the internet. Wagner's chronic care model (CCM) was used to define comprehensive care. After inclusion, the methodological quality of each study was assessed. A best-evidence synthesis was applied to draw conclusions. Forty-two publications were selected describing thirty-three studies evaluating twenty-eight comprehensive care programs for multimorbid patients. Programs varied in the target patient groups, implementation settings, number of included interventions, and number of CCM components to which these interventions related. Moderate evidence was found for a beneficial effect of comprehensive care on inpatient healthcare utilization and healthcare costs, health behavior of patients, perceived quality of care, and satisfaction of patients and caregivers. Insufficient evidence was found for a beneficial effect of comprehensive care on health-related quality of life in terms of mental functioning, medication use, and outpatient healthcare utilization and healthcare costs. No evidence was found for a beneficial effect of comprehensive care on cognitive functioning, depressive symptoms, functional status, mortality, quality of life in terms of physical functioning, and caregiver burden. Because of the heterogeneity of comprehensive care programs, it is as yet too early to draw firm conclusions regarding their effectiveness. More rigorous evaluation studies are necessary to determine what constitutes best care for the increasing number of people with multiple chronic conditions. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Detecting the causality influence of individual meteorological factors on local PM2.5 concentration in the Jing-Jin-Ji region

    NASA Astrophysics Data System (ADS)

    Chen, Ziyue; Cai, Jun; Gao, Bingbo; Xu, Bing; Dai, Shuang; He, Bin; Xie, Xiaoming

    2017-01-01

    Due to complicated interactions in the atmospheric environment, quantifying the influence of individual meteorological factors on local PM2.5 concentration remains challenging. The Beijing-Tianjin-Hebei (short for Jing-Jin-Ji) region is infamous for its serious air pollution. To improve regional air quality, characteristics and meteorological driving forces for PM2.5 concentration should be better understood. This research examined seasonal variations of PM2.5 concentration within the Jing-Jin-Ji region and extracted meteorological factors strongly correlated with local PM2.5 concentration. Following this, a convergent cross mapping (CCM) method was employed to quantify the causality influence of individual meteorological factors on PM2.5 concentration. The results proved that the CCM method was more likely to detect mirage correlations and reveal quantitative influences of individual meteorological factors on PM2.5 concentration. For the Jing-Jin-Ji region, the higher PM2.5 concentration, the stronger influences meteorological factors exert on PM2.5 concentration. Furthermore, this research suggests that individual meteorological factors can influence local PM2.5 concentration indirectly by interacting with other meteorological factors. Due to the significant influence of local meteorology on PM2.5 concentration, more emphasis should be given on employing meteorological means for improving local air quality.

  12. Preliminary evidences of CCM operation and its down regulation in relation to increasing CO2 levels in natural phytoplankton assemblages from the coastal waters of Bay of Bengal

    NASA Astrophysics Data System (ADS)

    Biswas, Haimanti; Rahman Shaik, Aziz Ur; Bandyopadhyay, Debasmita

    2014-05-01

    Bay of Bengal (BoB), a low productive part of the North Indian Ocean, often possesses low CO2 levels in its surface water and diatoms dominate the phytoplankton communities. Virtually no studies are available from this area reporting how this diatom dominated phytoplankton community would respond any increase in dissolved CO2 levels either naturally or anthopogenically. In most of the marine phytoplankton, the inefficiency of the sole carbon fixing enzyme Rubisco necessitates the need of concentrating dissolved inorganic carbon (DIC) (mostly as HCO3) inside the cell in excess of the ambient water concentrations in order to maintain high rate of photosynthesis under low CO2 levels through an energy consuming carbon concentration mechanisms (CCMs). The ubiquitous enzyme carbonic anhydrase (CA) plays a vital role in CCMs by converting HCO3- to CO2 and usually utilizes the trace metal zinc (Zn) as a cofactor. However, it is evident in many marine phytoplankton species that with increasing external CO2 levels, CCMs can be down-regulated leading to energetic savings which can be reallocated to growth; although exceptions occur. Hence, in order to predict their responses to the projected changes, it is imperative to understand their carbon metabolism patterns. We have conducted a series of incubation experiments in microcosms with natural phytoplankton communities from the coastal waters of BoB under different CO2 levels. Our results revealed that the rate of net photosynthetic oxygen evolution and biomass build-up increased in response to increasing CO2 levels. The depletion in δ13CPOM values were more in the high CO2 treatments relative to the low CO2 treated cells (control), indicating that dissolved CO2 uptake was higher when CO2 levels were increased. When additional Zn was added to the low CO2 treated cells, net photosynthetic oxygen evolution rate was increased significantly than that of the untreated control. It is likely that upon the supply of Zn under low CO2 levels, CA activity was enhanced and accelerated DIC transport and photosynthetic rate. Moreover, δ13CPOM values of low CO2 samples (both Zn treated and untreated) were almost identical, though the rate of photosynthesis was higher in response to Zn addition. This could be because of the fact that under low CO2 levels, DIC was possibly transported as HCO3- and an active HCO3- transport can contribute to low discrimination of 13C compared to diffusive CO2uptake leading to unaltered values of δ13CPOM. Furthermore, under low CO2 treatments, the need of nitrogen resource can be higher to maintain an active CCM (to build-up required proteins, Rubisco and CCM components) and our results showed higher values of δ15NPOMunder low CO2 levels relative to the high CO2treatments suggesting higher nitrogen utilization efficiency in the former case. These observations strengthen the possibility of operating an active CCM under low CO2 levels. HPLC pigment analysis revealed the occurrences of diatoxanthin (DT) [indicator of non-photo-chemical quenching (NPQ)] and high values of photoprotective carotenoid to light harvesting carotenoid ratios (PPC/LHC) in the low CO2 treated cells indicating light stress. This is likely that, when CO2, the only substrate for Rubisco, is low, absorbed light energy within the cell can be surplus leading to photo-damage and to protect the cell from potential damage, DT was produced by energy dissipation via NPQ and PPC were synthesized in excess of LHC. Conversely, in Zn and high CO2 treated cells, the absence of DT and reduced values of PPC/LHC indirectly indicates reduced light stress which was possibly because of enhanced supply of Rubisco substrate either via active bicarbonate transport or diffusive CO2 supply. Thus, we infer that the diatom dominated phytoplankton communities from the study area perform CCMs under low CO2 conditions and the same can be down regulated upon the increasing levels of CO2 and the community may benefit from the increasing CO2 levels followed by increased rate of carbon fixation. These can have large biogeochemical significance.

  13. Equivalent Mass of a Coil Spring.

    ERIC Educational Resources Information Center

    Ruby, Lawrence

    2000-01-01

    Finds that first-year college students can understand in detail the origin of the equivalent mass. Provides both a simple calculation derivation of this result as well as a noncalculus derivation. Argues that for every soft spring, the equivalent mass should be somewhere between m0/3 and m0/2. (CCM)

  14. Enhancing soybean photosynthetic CO2 assimilation using a cyanobacterial membrane protein, ictB

    USDA-ARS?s Scientific Manuscript database

    Soybean C3 photosynthesis can suffer a severe loss in efficiency due to photorespiration and the lack of a carbon concentrating mechanism (CCM) such as those present in other plant species or cyanobacteria. Transgenic soybean (Glycine max cv. Thorne) plants constitutively expressing cyanobacterial i...

  15. a Physical Parameterization of Snow Albedo for Use in Climate Models.

    NASA Astrophysics Data System (ADS)

    Marshall, Susan Elaine

    The albedo of a natural snowcover is highly variable ranging from 90 percent for clean, new snow to 30 percent for old, dirty snow. This range in albedo represents a difference in surface energy absorption of 10 to 70 percent of incident solar radiation. Most general circulation models (GCMs) fail to calculate the surface snow albedo accurately, yet the results of these models are sensitive to the assumed value of the snow albedo. This study replaces the current simple empirical parameterizations of snow albedo with a physically-based parameterization which is accurate (within +/- 3% of theoretical estimates) yet efficient to compute. The parameterization is designed as a FORTRAN subroutine (called SNOALB) which can be easily implemented into model code. The subroutine requires less then 0.02 seconds of computer time (CRAY X-MP) per call and adds only one new parameter to the model calculations, the snow grain size. The snow grain size can be calculated according to one of the two methods offered in this thesis. All other input variables to the subroutine are available from a climate model. The subroutine calculates a visible, near-infrared and solar (0.2-5 μm) snow albedo and offers a choice of two wavelengths (0.7 and 0.9 mu m) at which the solar spectrum is separated into the visible and near-infrared components. The parameterization is incorporated into the National Center for Atmospheric Research (NCAR) Community Climate Model, version 1 (CCM1), and the results of a five -year, seasonal cycle, fixed hydrology experiment are compared to the current model snow albedo parameterization. The results show the SNOALB albedos to be comparable to the old CCM1 snow albedos for current climate conditions, with generally higher visible and lower near-infrared snow albedos using the new subroutine. However, this parameterization offers a greater predictability for climate change experiments outside the range of current snow conditions because it is physically-based and not tuned to current empirical results.

  16. JRmGRN: Joint reconstruction of multiple gene regulatory networks with common hub genes using data from multiple tissues or conditions.

    PubMed

    Deng, Wenping; Zhang, Kui; Liu, Sanzhen; Zhao, Patrick; Xu, Shizhong; Wei, Hairong

    2018-04-30

    Joint reconstruction of multiple gene regulatory networks (GRNs) using gene expression data from multiple tissues/conditions is very important for understanding common and tissue/condition-specific regulation. However, there are currently no computational models and methods available for directly constructing such multiple GRNs that not only share some common hub genes but also possess tissue/condition-specific regulatory edges. In this paper, we proposed a new graphic Gaussian model for joint reconstruction of multiple gene regulatory networks (JRmGRN), which highlighted hub genes, using gene expression data from several tissues/conditions. Under the framework of Gaussian graphical model, JRmGRN method constructs the GRNs through maximizing a penalized log likelihood function. We formulated it as a convex optimization problem, and then solved it with an alternating direction method of multipliers (ADMM) algorithm. The performance of JRmGRN was first evaluated with synthetic data and the results showed that JRmGRN outperformed several other methods for reconstruction of GRNs. We also applied our method to real Arabidopsis thaliana RNA-seq data from two light regime conditions in comparison with other methods, and both common hub genes and some conditions-specific hub genes were identified with higher accuracy and precision. JRmGRN is available as a R program from: https://github.com/wenpingd. hairong@mtu.edu. Proof of theorem, derivation of algorithm and supplementary data are available at Bioinformatics online.

  17. Tissue-specific autophagy responses to aging and stress in C. elegans.

    PubMed

    Chapin, Hannah C; Okada, Megan; Merz, Alexey J; Miller, Dana L

    2015-06-01

    Cellular function relies on a balance between protein synthesis and breakdown. Macromolecular breakdown through autophagy is broadly required for cellular and tissue development, function, and recovery from stress. While Caenorhabditis elegans is frequently used to explore cellular responses to development and stress, the most common assays for autophagy in this system lack tissue-level resolution. Different tissues within an organism have unique functional characteristics and likely vary in their reliance on autophagy under different conditions. To generate a tissue-specific map of autophagy in C. elegans we used a dual fluorescent protein (dFP) tag that releases monomeric fluorescent protein (mFP) upon arrival at the lysosome. Tissue-specific expression of dFP::LGG-1 revealed autophagic flux in all tissues, but mFP accumulation was most dramatic in the intestine. We also observed variable responses to stress: starvation increased autophagic mFP release in all tissues, whereas anoxia primarily increased intestinal autophagic flux. We observed autophagic flux with tagged LGG-1, LGG-2, and two autophagic cargo reporters: a soluble cytoplasmic protein, and mitochondrial TOMM-7. Finally, an increase in mFP in older worms was consistent with an age-dependent shift in proteostasis. These novel measures of autophagic flux in C. elegans reveal heterogeneity in autophagic response across tissues during stress and aging.

  18. Evaluation of Convective Transport in the GEOS-5 Chemistry and Climate Model

    NASA Technical Reports Server (NTRS)

    Pickering, Kenneth E.; Ott, Lesley E.; Shi, Jainn J.; Tao. Wei-Kuo; Mari, Celine; Schlager, Hans

    2011-01-01

    The NASA Goddard Earth Observing System (GEOS-5) Chemistry and Climate Model (CCM) consists of a global atmospheric general circulation model and the combined stratospheric and tropospheric chemistry package from the NASA Global Modeling Initiative (GMI) chemical transport model. The subgrid process of convective tracer transport is represented through the Relaxed Arakawa-Schubert parameterization in the GEOS-5 CCM. However, substantial uncertainty for tracer transport is associated with this parameterization, as is the case with all global and regional models. We have designed a project to comprehensively evaluate this parameterization from the point of view of tracer transport, and determine the most appropriate improvements that can be made to the GEOS-5 convection algorithm, allowing improvement in our understanding of the role of convective processes in determining atmospheric composition. We first simulate tracer transport in individual observed convective events with a cloud-resolving model (WRF). Initial condition tracer profiles (CO, CO2, O3) are constructed from aircraft data collected in undisturbed air, and the simulations are evaluated using aircraft data taken in the convective anvils. A single-column (SCM) version of the GEOS-5 GCM with online tracers is then run for the same convective events. SCM output is evaluated based on averaged tracer fields from the cloud-resolving model. Sensitivity simulations with adjusted parameters will be run in the SCM to determine improvements in the representation of convective transport. The focus of the work to date is on tropical continental convective events from the African Monsoon Multidisciplinary Analyses (AMMA) field mission in August 2006 that were extensively sampled by multiple research aircraft.

  19. Bicarbonate uptake by Southern Ocean phytoplankton

    NASA Astrophysics Data System (ADS)

    Cassar, Nicolas; Laws, Edward A.; Bidigare, Robert R.; Popp, Brian N.

    2004-06-01

    Marine phytoplankton have the potential to significantly buffer future increases in atmospheric carbon dioxide levels. However, in order for CO2 fertilization to have an effect on carbon sequestration to the deep ocean, the increase in dissolved CO2 must stimulate primary productivity; that is, marine phototrophs must be CO2 limited [, 1993]. Estimation of the extent of bicarbonate (HCO3-) uptake in the oceans is therefore required to determine whether the anthropogenic carbon sources will enhance carbon flux to the deep ocean. Using short-term 14CO2-disequilibrium experiments during the Southern Ocean Iron Experiment (SOFeX), we show that HCO3- uptake by Southern Ocean phytoplankton is significant. Since the majority of dissolved inorganic carbon (DIC) in the ocean is in the form of bicarbonate, the biological pump may therefore be insensitive to anthropogenic CO2. Approximately half of the DIC uptake observed was attributable to direct HCO3- uptake, the other half being direct CO2 uptake mediated either by passive diffusion or active uptake mechanisms. The increase in growth rates and decrease in CO2 concentration associated with the iron fertilization did not trigger any noticeable changes in the mode of DIC acquisition, indicating that under most environmental conditions the carbon concentrating mechanism (CCM) is constitutive. A low-CO2 treatment induced an increase in uptake of CO2, which we attributed to increased extracellular carbonic anhydrase activity, at the expense of direct HCO3- transport across the plasmalemma. Isotopic disequilibrium experimental results are consistent with Southern Ocean carbon stable isotope fractionation data from this and other studies. Although iron fertilization has been shown to significantly enhance phytoplankton growth and may potentially increase carbon flux to the deep ocean, an important source of the inorganic carbon taken up by phytoplankton in this study was HCO3-, whose concentration is negligibly affected by the anthropogenic rise in CO2. We conclude that biological productivity in this region of the world's ocean is unlikely to be directly regulated by natural or anthropogenic variations in atmospheric CO2 concentrations because of the presence of a constitutive CCM.

  20. Selection of suitable soybean EF1α genes as internal controls for real-time PCR analyses of tissues during plant development and under stress conditions.

    PubMed

    Saraiva, Kátia D C; Fernandes de Melo, Dirce; Morais, Vanessa D; Vasconcelos, Ilka M; Costa, José H

    2014-09-01

    The EF1α genes were stable in the large majority of soybean tissues during development and in specific tissues/conditions under stress. Quantitative real-time PCR (qPCR) analysis strongly depends on transcript normalization using stable reference genes. Reference genes are generally encoded by multigene families and are used in qPCR normalization; however, little effort has been made to verify the stability of different gene members within a family. Here, the expression stability of members of the soybean EF1α gene family (named EF1α 1a1, 1a2, 1b, 2a, 2b and 3) was evaluated in different tissues during plant development and stress exposure (SA and PEG). Four genes (UKN1, SKIP 16, EF1β and MTP) already established as stably expressed were also used in the comparative analysis. GeNorm analyses revealed different combinations of reference genes as stable in soybean tissues during development. The EF1α genes were the most stable in cotyledons (EF1α 3 and EF1α 1b), epicotyls (EF1α 1a2, EF1α 2b and EF1α 1a1), hypocotyls (EF1α 1a1 and EF1β), pods (EF1α 2a and EF1α 2b) and roots (EF1α 2a and UKN1) and less stable in tissues such as trifoliate and unifoliate leaves and germinating seeds. Under stress conditions, no suitable combination including only EF1α genes was found; however, some genes were relatively stable in leaves (EF1α 1a2) and roots (EF1α 1a1) treated with SA as well as in roots treated with PEG (EF1α 2b). EF1α 2a was the most stably expressed EF1α gene in all soybean tissues under stress. Taken together, our data provide guidelines for the selection of EF1α genes for use as reference genes in qPCR expression analyses during plant development and under stress conditions.

  1. Commensal bacteria-dependent select expression of CXCL2 contributes to periodontal tissue homeostasis.

    PubMed

    Zenobia, Camille; Luo, Xiao Long; Hashim, Ahmed; Abe, Toshiharu; Jin, Lijian; Chang, Yucheng; Jin, Zhi Chao; Sun, Jian Xun; Hajishengallis, George; Curtis, Mike A; Darveau, Richard P

    2013-08-01

    The oral and intestinal host tissues both carry a heavy microbial burden. Although commensal bacteria contribute to healthy intestinal tissue structure and function, their contribution to oral health is poorly understood. A crucial component of periodontal health is the recruitment of neutrophils to periodontal tissue. To elucidate this process, gingival tissues of specific-pathogen-free and germ-free wild-type mice and CXCR2KO and MyD88KO mice were examined for quantitative analysis of neutrophils and CXCR2 chemoattractants (CXCL1, CXCL2). We show that the recruitment of neutrophils to the gingival tissue does not require commensal bacterial colonization but is entirely dependent on CXCR2 expression. Strikingly, however, commensal bacteria selectively upregulate the expression of CXCL2, but not CXCL1, in a MyD88-dependent way that correlates with increased neutrophil recruitment as compared with germ-free conditions. This is the first evidence that the selective use of chemokine receptor ligands contributes to neutrophil homing to healthy periodontal tissue. © 2013 John Wiley & Sons Ltd.

  2. Corneal confocal microscopy detects small fiber neuropathy in CMT1A patients

    PubMed Central

    Tavakoli, Mitra; Marshall, Andy; Banka, Siddharth; Petropoulos, Ioannis N; Fadavi, Hassan; Kingston, Helen; Malik, Rayaz A

    2012-01-01

    Although unmyelinated nerve fibers are affected in CMT1A, they have not been studied in detail due to the invasive nature of the techniques needed to study them. We established alterations in C-fiber bundles of the cornea in patients with CMT1A using non-invasive corneal confocal microscopy (CCM). Twelve patients with CMT1A and twelve healthy control subjects underwent assessment of neuropathic symptoms and deficits, electrophysiology, quantitative sensory testing, corneal sensitivity and corneal confocal microscopy. Corneal sensitivity, corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length and corneal nerve fiber tortuosity were significantly reduced in CMT1A patients compared to controls. There was a significant correlation between corneal sensation and CCM parameters with the severity of painful neuropathic symptoms, cold and warm thresholds and median nerve CMAP amplitude. CCM demonstrates significant damage to C-fiber bundles, which relates to some measures of neuropathy in CMT1A patients. PMID:22996176

  3. Diabetic peripheral neuropathy assessment through texture based analysis of corneal nerve images

    NASA Astrophysics Data System (ADS)

    Silva, Susana F.; Gouveia, Sofia; Gomes, Leonor; Negrão, Luís; João Quadrado, Maria; Domingues, José Paulo; Morgado, António Miguel

    2015-05-01

    Diabetic peripheral neuropathy (DPN) is one common complication of diabetes. Early diagnosis of DPN often fails due to the non-availability of a simple, reliable, non-invasive method. Several published studies show that corneal confocal microscopy (CCM) can identify small nerve fibre damage and quantify the severity of DPN, using nerve morphometric parameters. Here, we used image texture features, extracted from corneal sub-basal nerve plexus images, obtained in vivo by CCM, to identify DPN patients, using classification techniques. A SVM classifier using image texture features was used to identify (DPN vs. No DPN) DPN patients. The accuracies were 80.6%, when excluding diabetic patients without neuropathy, and 73.5%, when including diabetic patients without diabetic neuropathy jointly with healthy controls. The results suggest that texture analysis might be used as a complementing technique for DPN diagnosis, without requiring nerve segmentation in CCM images. The results also suggest that this technique has enough sensitivity to detect early disorders in the corneal nerves of diabetic patients.

  4. Countermeasure effectiveness against a man-portable air-defense system containing a two-color spinscan infrared seeker

    NASA Astrophysics Data System (ADS)

    Jackman, James; Richardson, Mark; Butters, Brian; Walmsley, Roy

    2011-12-01

    Man-portable air-defense (MANPAD) systems have developed sophisticated counter-countermeasures (CCM) to try and defeat any expendable countermeasure that is deployed by an aircraft. One of these is a seeker that is able to detect in two different parts of the electromagnetic spectrum. Termed two-color, the seeker can compare the emissions from the target and a countermeasure in different wavebands and reject the countermeasure. In this paper we describe the modeling process of a two-color infrared seeker using COUNTERSIM, a missile engagement and countermeasure software simulation tool. First, the simulations model a MANPAD with a two-color CCM which is fired against a fast jet model and a transport aircraft model releasing reactive countermeasures. This is then compared to when the aircraft releases countermeasures throughout an engagement up to the hit point to investigate the optimum flare firing time. The results show that the release time of expendable decoys as a countermeasure against a MANPAD with a two-color CCM is critical.

  5. Insulin signaling in various equine tissues under basal conditions and acute stimulation by intravenously injected insulin.

    PubMed

    Warnken, Tobias; Brehm, Ralph; Feige, Karsten; Huber, Korinna

    2017-10-01

    The aim of the study was to analyze key proteins of the equine insulin signaling cascade and their extent of phosphorylation in biopsies from muscle tissue (MT), liver tissue (LT), and nuchal AT, subcutaneous AT, and retroperitoneal adipose tissues. This was investigated under unstimulated (B1) and intravenously insulin stimulated (B2) conditions, which were achieved by injection of insulin (0.1 IU/kg bodyweight) and glucose (150 mg/kg bodyweight). Twelve warmblood horses aged 15 ± 6.8 yr (yr), weighing 559 ± 79 kg, and with a mean body condition score of 4.7 ± 1.5 were included in the study. Key proteins of the insulin signaling cascade were semiquantitatively determined using Western blotting. Furthermore, modulation of the cascade was assessed. The basal expression of the proteins was only slightly influenced during the experimental period. Insulin induced a high extent of phosphorylation of insulin receptor in LT (P < 0.01) but not in MT. Protein kinase B and mechanistic target of rapamycin expressed a higher extent of phosphorylation in all tissues in B2 biopsies. Adenosine monophosphate protein kinase, as a component related to insulin signaling, expressed enhanced phosphorylation in MT (P < 0.05) and adipose tissues (nuchal AT P < 0.05; SCAT P < 0.01; retroperitoneal adipose tissue P < 0.05), but not in LT at B2. Tissue-specific variations in the acute response of insulin signaling to intravenously injected insulin were observed. In conclusion, insulin sensitivity in healthy horses is based on a complex concerted action of different tissues by their variations in the molecular response to insulin. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Sensitivity of a cloud parameterization package in the National Center for Atmospheric Research Community Climate Model

    NASA Astrophysics Data System (ADS)

    Kao, C.-Y. J.; Smith, W. S.

    1999-05-01

    A physically based cloud parameterization package, which includes the Arakawa-Schubert (AS) scheme for subgrid-scale convective clouds and the Sundqvist (SUN) scheme for nonconvective grid-scale layered clouds (hereafter referred to as the SUNAS cloud package), is incorporated into the National Center for Atmospheric Research (NCAR) Community Climate Model, Version 2 (CCM2). The AS scheme is used for a more reasonable heating distribution due to convective clouds and their associated precipitation. The SUN scheme allows for the prognostic computation of cloud water so that the cloud optical properties are more physically determined for shortwave and longwave radiation calculations. In addition, the formation of anvil-like clouds from deep convective systems is able to be simulated with the SUNAS package. A 10-year simulation spanning the period from 1980 to 1989 is conducted, and the effect of the cloud package on the January climate is assessed by comparing it with various available data sets and the National Center for Environmental Protection/NCAR reanalysis. Strengths and deficiencies of both the SUN and AS methods are identified and discussed. The AS scheme improves some aspects of the model dynamics and precipitation, especially with respect to the Pacific North America (PNA) pattern. CCM2's tendency to produce a westward bias of the 500 mbar stationary wave (time-averaged zonal anomalies) in the PNA sector is remedied apparently because of a less "locked-in" heating pattern in the tropics. The additional degree of freedom added by the prognostic calculation of cloud water in the SUN scheme produces interesting results in the modeled cloud and radiation fields compared with data. In general, too little cloud water forms in the tropics, while excessive cloud cover and cloud liquid water are simulated in midlatitudes. This results in a somewhat degraded simulation of the radiation budget. The overall simulated precipitation by the SUNAS package is, however, substantially improved over the original CCM2.

  7. Tissue-Specific Induction of Mouse ZIP8 and ZIP14 Divalent Cation/Bicarbonate Symporters by, and Cytokine Response to, Inflammatory Signals

    PubMed Central

    Gálvez-Peralta, Marina; Wang, Zhifang; Bao, Shengying; Knoell, Daren L; Nebert, Daniel W

    2014-01-01

    Mouse Slc39a8 and Slc39a14 genes encode ZIP8 and ZIP14, respectively, which are ubiquitous divalent cation/(HCO3−)2 symporters responsible for uptake of Zn2+, Fe2+ and Mn2+ into cells. Cd2+ and other toxic nonessential metals can displace essential cations, thereby entering vertebrate cells. Whereas Slc39a8 encodes a single protein, Slc39a14 has two exons 4 which, via alternative splicing, give rise to ZIP14A and ZIP14B; why differences exist in cell-type-specific expression of ZIP14A and ZIP14B remains unknown. Inflammatory stimuli have been associated with ZIP8 and ZIP14 up-regulation, but a systematic study of many tissues simultaneously in a laboratory animal following inflammatory cytokine exposure has not yet been reported. Herein we show that C57BL/6J male mice—treated intraperitoneally with lipopolysaccharide (LPS), or the proinflammatory cytokines tumor necrosis factor (TNF) or interleukin-6 (IL6)—exhibited quantatively very different, highly tissue-specific, and markedly time-dependent up- and down-regulation of ZIP8, ZIP14A and ZIP14B mRNA levels in twelve tissues. Magnitude of the inflammatory response was confirmed by measuring the proinflammatory cytokine TNF, IL6 and interleukin-1β (IL1B) mRNA levels in the same tissues of these animals. Our data suggest that most if not all tissues use ZIP8, ZIP14A and/or ZIP14B) for Zn2+ uptake, some tissues under basal conditions and others moreso when inflammatory stressors are present; collectively, this might lead to substantial alterations in plasma Zn2+ levels, due to Zn2+ redistribution not just in liver, but across many vital organs. In the context of cadmium-mediated toxicity, our data suggest that tissues other than liver, kidney and lung should also be considered. PMID:24728862

  8. Evaluation of the Surface Characteristics of Various Implant Abutment Materials Using Confocal Microscopy and White Light Interferometry.

    PubMed

    Park, Jun-Beom; Yang, Seung-Min; Ko, Youngkyung

    2015-12-01

    The purpose of this study was to evaluate the surface characteristics of various implant abutment materials, such as of titanium alloy (Ti6Al4V; Ma), machined cobalt-chrome-molybdenum alloy (CCM), titanium nitride coating on a titanium alloy disc (TiN), anodic oxidized titanium alloy disc (AO), composite resin coating on a titanium alloy disc (Res), and zirconia disc (Zr), using confocal microscopy and white light interferometry. Measurements from the 2 methods were evaluated to see if these methods would give equivalent results. The precision of measurements were evaluated by the coefficient of variation. Five discs each of Ma, CCM, TiN, AO, Res, and Zr were used. The surface roughness was evaluated by confocal laser microscopy and white light interferometry. Confocal microscopy showed that the Res group showed significantly greater Ra, Rq, Rz, Sa, Sq, and Sz values compared with those of the Ma group (P < 0.05). The white light interferometry results showed that the Res group had significantly higher Ra, Rq, Rz, Rt, Sa, Sq, Sz, and Sdr values compared with the Ma group (P < 0.05). All the roughness parameters obtained from the 2 methods differed, and the Sa values of the Zr group from confocal microscopy were greater by 0.163 μm than those obtained by white light interferometry. Least difference was seen in the TiN group where the difference was 0.058 μm. Roughness parameters of different abutment materials varied significantly. Precision of measurement differed according to the characteristics of the material used. White light interferometry could be recommended for measurement of TiN and AO. Confocal microscopy gave more precise measurements for Ma and CCM groups. The optical characteristics of the surface should be considered before choosing the examination method.

  9. The day/night proteome in the murine heart.

    PubMed

    Podobed, Peter; Pyle, W Glen; Ackloo, Suzanne; Alibhai, Faisal J; Tsimakouridze, Elena V; Ratcliffe, William F; Mackay, Allison; Simpson, Jeremy; Wright, David C; Kirby, Gordon M; Young, Martin E; Martino, Tami A

    2014-07-15

    Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry. Daily variation was considerable, as ∼7.8% (90/1,147) of spots exhibited statistical changes at paired times across the 24-h light- (L) dark (D) cycle. JTK_CYCLE was used to investigate underlying diurnal rhythms in corresponding mRNA. We next revealed that disruption of the L:D cycle altered protein profiles and diurnal variation in cardiac function in Langendorff-perfused hearts, relative to the L:D cycle. To investigate the role of the circadian clock mechanism, we used cardiomyocyte clock mutant (CCM) mice. CCM myofilaments exhibited a loss of time-of-day-dependent maximal calcium-dependent ATP consumption, and altered phosphorylation rhythms. Moreover, the cardiac proteome was significantly altered in CCM hearts, especially enzymes regulating vital metabolic pathways. Lastly, we used a model of pressure overload cardiac hypertrophy to demonstrate the temporal proteome during heart disease. Our studies demonstrate that time of day plays a direct role in cardiac protein abundance and indicate a novel mechanistic contribution of circadian biology to cardiovascular structure and function.

  10. The day/night proteome in the murine heart

    PubMed Central

    Podobed, Peter; Pyle, W. Glen; Ackloo, Suzanne; Alibhai, Faisal J.; Tsimakouridze, Elena V.; Ratcliffe, William F.; Mackay, Allison; Simpson, Jeremy; Wright, David C.; Kirby, Gordon M.; Young, Martin E.

    2014-01-01

    Circadian rhythms are essential to cardiovascular health and disease. Temporal coordination of cardiac structure and function has focused primarily at the physiological and gene expression levels, but these analyses are invariably incomplete, not the least because proteins underlie many biological processes. The purpose of this study was to reveal the diurnal cardiac proteome and important contributions to cardiac function. The 24-h day-night murine cardiac proteome was assessed by two-dimensional difference in gel electrophoresis (2D-DIGE) and liquid chromatography-mass spectrometry. Daily variation was considerable, as ∼7.8% (90/1,147) of spots exhibited statistical changes at paired times across the 24-h light- (L) dark (D) cycle. JTK_CYCLE was used to investigate underlying diurnal rhythms in corresponding mRNA. We next revealed that disruption of the L:D cycle altered protein profiles and diurnal variation in cardiac function in Langendorff-perfused hearts, relative to the L:D cycle. To investigate the role of the circadian clock mechanism, we used cardiomyocyte clock mutant (CCM) mice. CCM myofilaments exhibited a loss of time-of-day-dependent maximal calcium-dependent ATP consumption, and altered phosphorylation rhythms. Moreover, the cardiac proteome was significantly altered in CCM hearts, especially enzymes regulating vital metabolic pathways. Lastly, we used a model of pressure overload cardiac hypertrophy to demonstrate the temporal proteome during heart disease. Our studies demonstrate that time of day plays a direct role in cardiac protein abundance and indicate a novel mechanistic contribution of circadian biology to cardiovascular structure and function. PMID:24789993

  11. Critical care trainees' career goals and needs: A Canadian survey.

    PubMed

    St-Onge, Maude; Mandelzweig, Keren; Marshall, John C; Scales, Damon C; Granton, John

    2014-01-01

    For training programs to meet the needs of trainees, an understanding of their career goals and expectations is required. Canadian critical care medicine (CCM) trainees were surveyed to understand their career goals in terms of clinical work, research, teaching, administration and management; and to identify their perceptions regarding the support they need to achieve their goals. The online survey was sent to all trainees registered in a Canadian adult or pediatric CCM program. It documented the participants' demographics; their career expectations; the perceived barriers and enablers to achieve their career goals; and their perceptions relating to their chances of developing a career in different areas. A response rate of 85% (66 of 78) was obtained. The majority expected to work in an academic centre. Only approximately one-third (31%) estimated their chances of obtaining a position in CCM as >75%. The majority planned to devote 25% to 75% of their time performing clinical work and <25% in education, research or administration. The trainees perceived that there were limited employment opportunities. Networking and having specialized expertise were mentioned as being facilitators for obtaining employment. They expressed a need for more protected time, resources and mentorship for nonclinical tasks during training. CCM trainees perceived having only limited support to help them to achieve their career goals and anticipate difficulties in obtaining successful employment. They identified several gaps that could be addressed by training programs, including more mentoring in the areas of research, education and administration.

  12. STAR-CCM+ Verification and Validation Plan

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pointer, William David

    2016-09-30

    The commercial Computational Fluid Dynamics (CFD) code STAR-CCM+ provides general purpose finite volume method solutions for fluid dynamics and energy transport. This document defines plans for verification and validation (V&V) of the base code and models implemented within the code by the Consortium for Advanced Simulation of Light water reactors (CASL). The software quality assurance activities described herein are port of the overall software life cycle defined in the CASL Software Quality Assurance (SQA) Plan [Sieger, 2015]. STAR-CCM+ serves as the principal foundation for development of an advanced predictive multi-phase boiling simulation capability within CASL. The CASL Thermal Hydraulics Methodsmore » (THM) team develops advanced closure models required to describe the subgrid-resolution behavior of secondary fluids or fluid phases in multiphase boiling flows within the Eulerian-Eulerian framework of the code. These include wall heat partitioning models that describe the formation of vapor on the surface and the forces the define bubble/droplet dynamic motion. The CASL models are implemented as user coding or field functions within the general framework of the code. This report defines procedures and requirements for V&V of the multi-phase CFD capability developed by CASL THM. Results of V&V evaluations will be documented in a separate STAR-CCM+ V&V assessment report. This report is expected to be a living document and will be updated as additional validation cases are identified and adopted as part of the CASL THM V&V suite.« less

  13. Technical Report Series on Global Modeling and Data Assimilation. Volume 20; The Climate of the FVCCM-3 Model

    NASA Technical Reports Server (NTRS)

    Suarez, Max J. (Editor); Chang, Yehui; Schubert, Siegfried D.; Lin, Shian-Jiann; Nebuda, Sharon; Shen, Bo-Wen

    2001-01-01

    This document describes the climate of version 1 of the NASA-NCAR model developed at the Data Assimilation Office (DAO). The model consists of a new finite-volume dynamical core and an implementation of the NCAR climate community model (CCM-3) physical parameterizations. The version of the model examined here was integrated at a resolution of 2 degrees latitude by 2.5 degrees longitude and 32 levels. The results are based on assimilation that was forced with observed sea surface temperature and sea ice for the period 1979-1995, and are compared with NCEP/NCAR reanalyses and various other observational data sets. The results include an assessment of seasonal means, subseasonal transients including the Madden Julian Oscillation, and interannual variability. The quantities include zonal and meridional winds, temperature, specific humidity, geopotential height, stream function, velocity potential, precipitation, sea level pressure, and cloud radiative forcing.

  14. Plausible role for CHW peer support groups in increasing care-seeking in an integrated community case management project in Rwanda: a mixed methods evaluation.

    PubMed

    Langston, Anne; Weiss, Jennifer; Landegger, Justine; Pullum, Thomas; Morrow, Melanie; Kabadege, Melene; Mugeni, Catherine; Sarriot, Eric

    2014-08-01

    The Kabeho Mwana project (2006-2011) supported the Rwanda Ministry of Health (MOH) in scaling up integrated community case management (iCCM) of childhood illness in 6 of Rwanda's 30 districts. The project trained and equipped community health workers (CHWs) according to national guidelines. In project districts, Kabeho Mwana staff also trained CHWs to conduct household-level health promotion and established supervision and reporting mechanisms through CHW peer support groups (PSGs) and quality improvement systems. The 2005 and 2010 Demographic and Health Surveys were re-analyzed to evaluate how project and non-project districts differed in terms of care-seeking for fever, diarrhea, and acute respiratory infection symptoms and related indicators. We developed a logit regression model, controlling for the timing of the first CHW training, with the district included as a fixed categorical effect. We also analyzed qualitative data from the final evaluation to examine factors that may have contributed to improved outcomes. While there was notable improvement in care-seeking across all districts, care-seeking from any provider for each of the 3 conditions, and for all 3 combined, increased significantly more in the project districts. CHWs contributed a larger percentage of consultations in project districts (27%) than in non-project districts (12%). Qualitative data suggested that the PSG model was a valuable sub-level of CHW organization associated with improved CHW performance, supervision, and social capital. The iCCM model implemented by Kabeho Mwana resulted in greater improvements in care-seeking than those seen in the rest of the country. Intensive monitoring, collaborative supervision, community mobilization, and CHW PSGs contributed to this success. The PSGs were a unique contribution of the project, playing a critical role in improving care-seeking in project districts. Effective implementation of iCCM should therefore include CHW management and social support mechanisms. Finally, re-analysis of national survey data improved evaluation findings by providing impact estimates.

  15. Development and testing of an artificial arterial and venous pulse oximeter.

    PubMed

    Cloete, G; Fourie, P R; Scheffer, C

    2013-01-01

    The monitoring of patients healthcare is of a prime importance to ensure their efficient and effective treatment. Monitoring blood oxygen saturation is a field which has grown significantly in recent times and more specifically in tissues affected by diseases or conditions that may negatively affect the function of the tissue. This study involved the development and testing of a highly sensitive non-invasive blood oxygen saturation monitoring device. A device that can be used to continuously monitor the condition of tissue affected by diseases which affect the blood flow through the tissue, and the oxygen usage in tissue. The device's system was designed to specifically monitor occluded tissue which has low oxygen saturations and low perfusion. Although with limitted validation the system was unable to accurately measure the venous oxygenation specifically, but it was able to measure the mixed oxygen saturation. With further research it would be possible to validate the system for measuring both the arterial and venous oxygen saturations.

  16. Supplementary comparisons of COOMET in the field of measurements of liquids kinematical viscosity COOMET.M.V-S2

    NASA Astrophysics Data System (ADS)

    Demyanov, A. A.; Tsurko, A. A.

    2017-01-01

    In the comparisons three Newtonian liquid samples were used with nominal values of 20 mm2/s 100 mm2/s and 1000 mm2/s ('20', '100' and '1000', respectively) at 20 °C. Each NMI presented results of measurements values kinematic viscosity samples, uncertainty and uncertainty budget. The purpose of these comparisons was confirmation of measurement and calibration capabilities (CMC) of the relevant NMI. As a reference the values of kinematic viscosity reference samples were taken as average values of measurement results obtained in the research laboratory of the national standards and research in the field of measurements of viscosity and density of the D I Mendeleev Institute for Metrology (VNIIM, RF), as a participant in international comparisons CCM.V-K1, BIPM. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  17. Isotopic studies of authigenic sulfides, silicates and carbonates, and calcite and pyrite veinlets in the Creede Formation, San Juan Mountains, Southwest Colorado

    USGS Publications Warehouse

    Bethke, Philip M.; Rye, Robert O.; Finkelstein, David B.

    2000-01-01

    Sulfur isotope analysis of authigenic pyrite in the Creede Formation documents its precipitation by the reaction between iron in the volcaniclastic sediments and H2S formed through bacteriogenic reduction of sulfate added to the lake during and immediately following repeated volcanic eruptions during sedimentation. Pyrite veinlets in the underlying Snowshoe Mountain Tuff were formed by the percolation of H2S-bearing pore waters into fractures in the tuff. Conventional analyses of bulk samples of authigenic pyrite range from -20.4% to 34.5% essentially equivalent to the range of -30% to 40% determined using SHRIMP microprobe techniques. Conventional analyses of bulk samples of pyrite from veinlets in the Snowshow Mountain Tiff range from -3.5% to 17.6% much more limited than the ranges of -23% to 111% and -15.6% to 67.0% determined by SHRIMP and laser ablation microbeam techniques, respectively. The extreme range of δ34S for the veinlets is interpreted to be the result of continued fractionation of the already 34S-depleted pore water. Oxygen isotope analysis of authigenic smectite, kaolinite, and K-feldspar together with fluid-inclusion temperatures and oxygen isotope analysis of calcite coexisting with kaolinite indicate that the smectites formed early during burial diagenesis, in accord with petrographic observations. The 40Ar/39Ar dating of K-feldspar, concorfance of K-feldspar, kaolinite, and calcite δ18O values, and fluid-inclusion temperatures in calcite, indicate that the sediments at core hole CCM-1 were subjected to a hydrothermal event at 17.6 Ma. The minerals formed oxygen-shifted meteoric waters with δ18O values of ~-9% Smecities at CCM-1 at least partially exchanged with these waters. Carbon and oxygen isotope analysis of authigenic calcites in the Creede Formation show that they formed over a wide range of temperatures from fluids having a wide range of isotopic composition, presumably over an extended period time. Some of the cements apparently formed very late from unexchanged meteoric water. Concretions and possibly some cements at CCM-1 appear to have exchanged with the 17.6 Ma oxygen-shifted hydrothermal fluids. Such exchange is consistent with evidence that lacustrine carbonates at CCM-1 exchanged with low 18O waters, whereas those at CCM-2 underwent little, if any, exchange. The δ13C-δ18O values for calcite veinlets in the Creede Formation are similar to those for authegenic calcites. Fluid-inclusion temperatures and δ18O indicate that some were deposited during the 17.6 Ma hydrothermal event and others from unexchanged meteoric water at a later date. The isotope studies confirm that part of the model of Rye et al., proposing that the barites in the southern end of the Creede Mining District were formed by mixing of the Creede hydrotermal system with Lake Creede pore of lake waters. The silicate and carbonate isotope data indicate that the pores of the Creede Formation were occupied by at least three isotopically distinct water since the time of deposition. The original pore fluids were probably shifted to lower δ18O values during burial diagensis as a result of the hydrolysis of the volcanic glass to for smectites and other hydrous silicates. During or prior to a 17.6 Ma hydrothermal event in the vicinity of CCM-1, the Creede Formation was flushed with oxygen-shifted meteoric water, possibly related to the breaching of the east side of the caldera wall sometime between 20 and 22 Ma. Later, the Creede Formation was again flushed, this time with unexchanged meteoric water with δD-δ18O values of present-day waters, possibly during the incision of the Rio Grande drainage during uplifting of the southern Rocky Mountains beginning about 5 Ma.

  18. In-plane structuring of proton exchange membrane fuel cell cathodes: Effect of ionomer equivalent weight structuring on performance and current density distribution

    NASA Astrophysics Data System (ADS)

    Herden, Susanne; Riewald, Felix; Hirschfeld, Julian A.; Perchthaler, Markus

    2017-07-01

    Within the active area of a fuel cell inhomogeneous operating conditions occur, however, state of the art electrodes are homogenous over the complete active area. This study uses current density distribution measurements to analyze which ionomer equivalent weight (EW) shows locally the highest current densities. With this information a segmented cathode electrode is manufactured by decal transfer. The segmented electrode shows better performance especially at high current densities compared to homogenous electrodes. Furthermore this segmented catalyst coated membrane (CCM) performs optimal in wet as well as dry conditions, both operating conditions arise in automotive fuel cell applications. Thus, cathode electrodes with an optimized ionomer EW distribution might have a significant impact on future automotive fuel cell development.

  19. The 'Year without summer 1816

    NASA Astrophysics Data System (ADS)

    Arfeuille, F.; Rozanov, E.; Peter, T.; Weisenstein, D.; Hadorn, G.; Bodenmann, T.; Brönnimann, S.

    2010-09-01

    One famous example of an extreme climatic event is the cold summer of 1816 in Europe and North America. This specific year, which was later called the "Year without summer 1816", had profound social and environmental effects. The cataclysmic eruption of Mt Tambora is now commonly known to have largely contributed to the negative temperature anomalies of the summer 1816, but some uncertainties remain. The eruption which occurred in April 1815 is the largest within the last 500 years and this extreme climatic forcing provides a real test for climate models. A crucial parameter to assess in order to simulate this eruption is the aerosol size distribution, which strongly influences the radiative impact of the aerosols (through changes in albedo and residence time in the stratosphere, among others) and the impacts on dynamics and chemistry. The representation of this major forcing is done by using the AER-2D aerosol model which calculates the size distribution of the aerosols formed after the eruption. The modeling of the climatic impacts is then done by the state-of-the-art Chemistry-Climate model (CCM) SOCOL. The characteristics of the Tambora eruption and results from simulations made using the aerosol model/CCM, with an emphasis on the radiative and chemical implications of the large aerosol, will be shown. For instance, the specific absorption/scattering ratio of Mt.Tambora aerosols induced a large stratospheric warming which will be analyzed. The climatic impacts will also be discussed in regards of the high sedimentation rate of Mt. Tambora aerosols, leading to a fast decrease of the atmospheric optical depth in the first two years after the eruption. The link will be made between the modeling results and proxy-reconstructions as well as with available historical daily data from Geneva, Switzerland. Finally, insights on the contemporary response to this climatic extreme will be shown.

  20. Final report of the APMP water flow key comparison: APMP.M.FF-K1

    NASA Astrophysics Data System (ADS)

    Lee, Kwang-Bock; Chun, Sejong; Terao, Yoshiya; Thai, Nguyen Hong; Tsair Yang, Cheng; Tao, Meng; Gutkin, Mikhail B.

    2011-01-01

    The key comparison, APMP.M.FF-K1, was undertaken by APMP/TCFF, the Technical Committee for Fluid Flow (TCFF) under the Asia Pacific Metrology Program (APMP). One objective of the key comparison was to demonstrate the degree of equivalence among six participating laboratories (KRISS, NMIJ, VMI, CMS, NIM and VNIIM) in water flow rate metrology by comparing the results with the key comparison reference value (KCRV) determined from the CCM.FF-K1 key comparison. The other objective of this key comparison was to provide supporting evidence for the calibration and measurement capabilities (CMCs), which had been declared by the participating laboratories during this key comparison. The Transfer Standard Package (TSP) was a Coriolis mass flowmeter, which had been used in the CCM.FF-K1 key comparison. Because the K-factors in the APMP.M.FF-K1 key comparison were slightly lower than the K-factors of the CCM.FF-K1 key comparison due to long-term drifts of the TSP, a correction value D was introduced. The value of D was given by a weighted sum between two link laboratories (NMIJ and KRISS), which participated in both the CCM.FF-K1 and the APMP.M.FF-K1 key comparisons. By this correction, the K-factors were laid between 12.004 and 12.017 at either low (Re = 254 000) or high (Re = 561 000) flow rates. Most of the calibration data were within expected uncertainty bounds. However, some data showed undulations, which gave large fluctuations of the metering factor at Re = 561 000. Calculation of degrees of equivalence showed that all the participating laboratories had deviations between -0.009 and 0.007 pulses/kg from the CCM.FF-K1 KCRV at either the low or the high flow rates. In case of En calculation, all the participating laboratories showed values less than 1, indicating that the corrected K-factors of all the laboratories were equivalent with the KCRV at both Re = 254 000 and 561 000. When the corrected K-factors from two participating laboratories were compared, all the numbers of equivalence showed values less than 1, indicating equivalence. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  1. Seasonal variation in physiological condition of Amblema plicata in the Upper Mississippi River

    USGS Publications Warehouse

    Monroe, E.M.; Newton, T.J.

    2001-01-01

    Measures of physiological condition are being used as sub-lethal endpoints in studies with unionids exposed to a variety of stressors, yet the natural seasonal variation in these measures are largely undocumented. We measured concentrations of glycogen in foot and mantle tissue and a tissue condition index (TCI) in Amblema plicata (Say 1817), about monthly, for 2 years in mussels that were: (1) obtained directly from the Upper Mississippi River (riverine group); and (2) relocated from the river into an artificial pond (relocated group). In both groups, we observed significant seasonal variation in all physiological indicators. Seasonal variation in glycogen was 72% in mantle and 52% in foot tissue and paralleled reproductive activity in this short-term breeder. In the relocated group, most of the variation in glycogen occurred during the first six months after relocation, suggesting that handling stress may have been a contributing factor. The significant seasonal variation in the TCI paralleled glycogen in riverine mussels. We observed tissue-specific differences in glycogen in the riverine group, but not in the relocated group. These data suggest that an interaction of environmental and biological factors influence the energetic status of mussels in natural populations. A better understanding of this variation is needed to interpret changes in physiological condition due to stressors such as relocation.

  2. The logics of metabolic regulation in bacteria challenges biosensor-based metabolic engineering.

    PubMed

    Jules, Matthieu

    2017-12-11

    Synthetic Biology (SB) aims at the rational design and engineering of novel biological functions and systems. By facilitating the engineering of living organisms, SB promises to facilitate the development of many new applications for health, biomanufacturing, and the environment. Over the last decade, SB promoted the construction of libraries of components enabling the fine-tuning of genetic circuits expression and the development of novel genome engineering methodologies for many organisms of interest. SB thus opened new perspectives in the field of metabolic engineering, which was until then mainly limited to (over)producing naturally synthesized metabolic compounds. To engineer efficient cell factories, it is key to precisely reroute cellular resources from the central carbon metabolism (CCM) to the synthetic circuitry. This task is however difficult as there is still significant lack of knowledge regarding both the function of several metabolic components and the regulation of the CCM fluxes for many industrially important bacteria. Pyruvate is a pivotal metabolite at the heart of the CCM and a key precursor for the synthesis of several commodity compounds and fine chemicals. Numerous bacterial species can also use it as a carbon source when present in the environment but bacterial, pyruvate-specific uptake systems were to be discovered. This is an issue for metabolic engineering as one can imagine to make use of pyruvate transport systems to replenish synthetic metabolic pathways towards the synthesis of chemicals of interest. Here we describe a recent study (MBio 8(5): e00976-17), which identified and characterized a pyruvate transport system in the Gram-positive (G +ve ) bacterium Bacillus subtilis , a well-established biotechnological workhorse for the production of enzymes, fine chemicals and antibiotics. This study also revealed that the activity of the two-component system (TCS) responsible for its induction is retro-inhibited by the level of pyruvate influx. Following up on the open question which is whether this retro-inhibition is a generic mechanism for TCSs, we will discuss the implications in metabolic engineering.

  3. Towards eliminating malaria in high endemic countries: the roles of community health workers and related cadres and their challenges in integrated community case management for malaria: a systematic review.

    PubMed

    Sunguya, Bruno F; Mlunde, Linda B; Ayer, Rakesh; Jimba, Masamine

    2017-01-03

    Human resource for health crisis has impaired global efforts against malaria in highly endemic countries. To address this, the World Health Organization (WHO) recommended scaling-up of community health workers (CHWs) and related cadres owing to their documented success in malaria and other disease prevention and management. Evidence is inconsistent on the roles and challenges they encounter in malaria interventions. This systematic review aims to summarize evidence on roles and challenges of CHWs and related cadres in integrated community case management for malaria (iCCM). This systematic review retrieved evidence from PubMed, CINAHL, ISI Web of Knowledge, and WHO regional databases. Terms extracted from the Boolean phrase used for PubMed were also used in other databases. The review included studies with Randomized Control Trial, Quasi-experimental, Pre-post interventional, Longitudinal and cohort, Cross-sectional, Case study, and Secondary data analysis. Because of heterogeneity, only narrative synthesis was conducted for this review. A total of 66 articles were eligible for analysis out of 1380 studies retrieved. CHWs and related cadre roles in malaria interventions included: malaria case management, prevention including health surveillance and health promotion specific to malaria. Despite their documented success, CHWs and related cadres succumb to health system challenges. These are poor and unsustainable finance for iCCM, workforce related challenges, lack of and unsustainable supply of medicines and diagnostics, lack of information and research, service delivery and leadership challenges. Community health workers and related cadres had important preventive, case management and promotive roles in malaria interventions. To enable their effective integration into the health systems, the identified challenges should be addressed. They include: introducing sustainable financing on iCCM programmes, tailoring their training to address the identified gaps, improving sustainable supply chain management of malaria drugs and diagnostics, and addressing regulatory challenges in the local contexts.

  4. The expression of genes involved in myometrial contractility changes during ex situ culture of pregnant human uterine smooth muscle tissue.

    PubMed

    Ilicic, Marina; Butler, Trent; Zakar, Tamas; Paul, Jonathan W

    2017-01-01

    Ex situ analyses of human myometrial tissue has been used to investigate the regulation of uterine quiescence and transition to a contractile phenotype. Following concerns about the validity of cultured primary cells, we examined whether myometrial tissue undergoes culture-induced changes ex situ that may affect the validity of in vitro models. To determine whether human myometrial tissue undergoes culture-induced changes ex situ in Estrogen receptor 1 (ESR1), Prostaglandin-endoperoxide synthase 2 (PTGS2) and Oxytocin receptor (OXTR) expression. Additionally, to determine whether culture conditions approaching the in vivo environment influence the expression of these key genes. Term non-laboring human myometrial tissues were cultured in the presence of specific treatments, including; serum supplementation, progesterone and estrogen, cAMP, PMA, stretch or NF-κB inhibitors. ESR1, PTGS2 and OXTR mRNA abundance after 48 h culture was determined using quantitative RT-PCR. Myometrial tissue in culture exhibited culture-induced up-regulation of ESR1 and PTGS2 and down-regulation of OXTR mRNA expression. Progesterone prevented culture-induced increase in ESR1 expression. Estrogen further up-regulated PTGS2 expression. Stretch had no direct effect, but blocked the effects of progesterone and estrogen on ESR1 and PTGS2 expression. cAMP had no effect whereas PMA further up-regulated PTGS2 expression and prevented decline of OXTR expression. Human myometrial tissue in culture undergoes culture-induced gene expression changes consistent with transition toward a laboring phenotype. Changes in ESR1, PTGS2 and OXTR expression could not be controlled simultaneously. Until optimal culture conditions are determined, results of in vitro experiments with myometrial tissues should be interpreted with caution.

  5. Rheumatic heart disease: infectious disease origin, chronic care approach.

    PubMed

    Katzenellenbogen, Judith M; Ralph, Anna P; Wyber, Rosemary; Carapetis, Jonathan R

    2017-11-29

    Rheumatic heart disease (RHD) is a chronic cardiac condition with an infectious aetiology, causing high disease burden in low-income settings. Affected individuals are young and associated morbidity is high. However, RHD is relatively neglected due to the populations involved and its lower incidence relative to other heart diseases. In this narrative review, we describe how RHD care can be informed by and integrated with models of care developed for priority non-communicable diseases (coronary heart disease), and high-burden communicable diseases (tuberculosis). Examining the four-level prevention model (primordial through tertiary prevention) suggests primordial and primary prevention of RHD can leverage off existing tuberculosis control efforts, given shared risk factors. Successes in coronary heart disease control provide inspiration for similarly bold initiatives for RHD. Further, we illustrate how the Chronic Care Model (CCM), developed for use in non-communicable diseases, offers a relevant framework to approach RHD care. Systems strengthening through greater integration of services can improve RHD programs. Strengthening of systems through integration/linkages with other well-performing and resourced services in conjunction with policies to adopt the CCM framework for the secondary and tertiary prevention of RHD in settings with limited resources, has the potential to significantly reduce the burden of RHD globally. More research is required to provide evidence-based recommendations for policy and service design.

  6. Long interspersed nuclear elements (LINEs) show tissue-specific, mosaic genome and methylation-unrestricted, widespread expression of noncoding RNAs in somatic tissues of the rat

    PubMed Central

    Singh, Deepak K.; Rath, Pramod C.

    2012-01-01

    We report strong somatic and germ line expression of LINE RNAs in eight different tissues of rat by using a novel ~2.8 kb genomic PstI-LINE DNA (P1-LINE) isolated from the rat brain. P1-LINE is present in a 93 kb LINE-SINE-cluster in sub-telomeric region of chromosome 12 (12p12) and as multiple truncated copies interspersed in all rat chromosomes. P1-LINEs occur as inverted repeats at multiple genomic loci in tissue-specific and mosaic patterns. P1-LINE RNAs are strongly expressed in brain, liver, lungs, heart, kidney, testes, spleen and thymus into large to small heterogeneous RNAs (~5.0 to 0.2 kb) in tissue-specific and dynamic patterns in individual rats. P1-LINE DNA is strongly methylated at CpG-dinucleotides in most genomic copies in all the tissues and weakly hypomethylated in few copies in some tissues. Small (700–75 nt) P1-LINE RNAs expressed in all tissues may be possible precursors for small regulatory RNAs (PIWI-interacting/piRNAs) bioinformatically derived from P1-LINE. The strong and dynamic expression of LINE RNAs from multiple chromosomal loci and the putative piRNAs in somatic tissues of rat under normal physiological conditions may define functional chromosomal domains marked by LINE RNAs as long noncoding RNAs (lncRNAs) unrestricted by DNA methylation. The tissue-specific, dynamic RNA expression and mosaic genomic distribution of LINEs representing a steady-state genomic flux of retrotransposon RNAs suggest for biological role of LINE RNAs as long ncRNAs and small piRNAs in mammalian tissues independent of their cellular fate for translation, reverse-transcription and retrotransposition. This may provide evolutionary advantages to LINEs and mammalian genomes. PMID:23064113

  7. Dynamic biochemical tissue analysis detects functional L-selectin ligands on colon cancer tissues

    PubMed Central

    Carlson, Grady E.; Martin, Eric W.; Shirure, Venktesh S.; Malgor, Ramiro; Resto, Vicente A.; Goetz, Douglas J.; Burdick, Monica M.

    2017-01-01

    A growing body of evidence suggests that L-selectin ligands presented on circulating tumor cells facilitate metastasis by binding L-selectin presented on leukocytes. Commonly used methods for detecting L-selectin ligands on tissues, e.g., immunostaining, are performed under static, no-flow conditions. However, such analysis does not assay for functional L-selectin ligands, specifically those ligands that promote adhesion under shear flow conditions. Recently our lab developed a method, termed dynamic biochemical tissue analysis (DBTA), to detect functional selectin ligands in situ by probing tissues with L-selectin-coated microspheres under hemodynamic flow conditions. In this investigation, DBTA was used to probe human colon tissues for L-selectin ligand activity. The detection of L-selectin ligands using DBTA was highly specific. Furthermore, DBTA reproducibly detected functional L-selectin ligands on diseased, e.g., cancerous or inflamed, tissues but not on noncancerous tissues. In addition, DBTA revealed a heterogeneous distribution of functional L-selectin ligands on colon cancer tissues. Most notably, detection of L-selectin ligands by immunostaining using HECA-452 antibody only partially correlated with functional L-selectin ligands detected by DBTA. In summation, the results of this study demonstrate that DBTA detects functional selectin ligands to provide a unique characterization of pathological tissue. PMID:28282455

  8. Dynamic biochemical tissue analysis detects functional L-selectin ligands on colon cancer tissues.

    PubMed

    Carlson, Grady E; Martin, Eric W; Shirure, Venktesh S; Malgor, Ramiro; Resto, Vicente A; Goetz, Douglas J; Burdick, Monica M

    2017-01-01

    A growing body of evidence suggests that L-selectin ligands presented on circulating tumor cells facilitate metastasis by binding L-selectin presented on leukocytes. Commonly used methods for detecting L-selectin ligands on tissues, e.g., immunostaining, are performed under static, no-flow conditions. However, such analysis does not assay for functional L-selectin ligands, specifically those ligands that promote adhesion under shear flow conditions. Recently our lab developed a method, termed dynamic biochemical tissue analysis (DBTA), to detect functional selectin ligands in situ by probing tissues with L-selectin-coated microspheres under hemodynamic flow conditions. In this investigation, DBTA was used to probe human colon tissues for L-selectin ligand activity. The detection of L-selectin ligands using DBTA was highly specific. Furthermore, DBTA reproducibly detected functional L-selectin ligands on diseased, e.g., cancerous or inflamed, tissues but not on noncancerous tissues. In addition, DBTA revealed a heterogeneous distribution of functional L-selectin ligands on colon cancer tissues. Most notably, detection of L-selectin ligands by immunostaining using HECA-452 antibody only partially correlated with functional L-selectin ligands detected by DBTA. In summation, the results of this study demonstrate that DBTA detects functional selectin ligands to provide a unique characterization of pathological tissue.

  9. The functional activity of bone tissue cells under space flight conditions.

    NASA Astrophysics Data System (ADS)

    Rodionova, N. V.; Polkovenko, O. V.; Oganov, V. S.; Nesterenko, O. N.

    The space flight conditions affect considerably the state of bone tissue leading to the development of osteoporosis and osteopenia Many aspects of reactions of bone tissue cells still remain unclear until now With the use of electron microscopy we studied the samples gathered from the femoral bone epiphyses and metaphyses of rats flown on board the space laboratory Spacelab -- 2 during 2 weeks It was established that under microgravity conditions there occur remodelling processes in a spongy bone related with a deficit of support load In this work the main attention is focused on studying the ultrastructure of osteogenetic cells and osteoclasts The degree of differentiation and functional state are evaluated according to the degree of development of organelles for specific biosynthesis rough endoplasmic reticulum RER Golgy complex GC as well as the state of mitochondria and cell nucleus As compared with a synchronous control the population of osteogenetic cells from zones of bone reconstruction shows a decrease in the number of functionally active forms We can judge of this from the reduction of a specific volume of RER GC mitochondria in osteoblasts RER loses architectonics typical for osteoblasts and as against the control is represented by short narrow canaliculi distributed throughout the cytoplasm some canals disintegrate GC is slightly pronounced mitochondria become smaller in size and acquire an optically dark matrix These phenomena are supposed to be associated with the desorganization of microtubules and

  10. Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study.

    PubMed

    Al-Shahi Salman, Rustam; Hall, Julie M; Horne, Margaret A; Moultrie, Fiona; Josephson, Colin B; Bhattacharya, Jo J; Counsell, Carl E; Murray, Gordon D; Papanastassiou, Vakis; Ritchie, Vaughn; Roberts, Richard C; Sellar, Robin J; Warlow, Charles P

    2012-03-01

    Cerebral cavernous malformations (CCMs) are prone to bleeding but the risk of intracranial haemorrhage and focal neurological deficits, and the factors that might predict their occurrence, are unclear. We aimed to quantify these risks and investigate whether they are affected by sex and CCM location. We undertook a population-based study using multiple overlapping sources of case ascertainment (including a Scotland-wide collaboration of neurologists, neurosurgeons, stroke physicians, radiologists, and pathologists, as well as searches of registers of hospital discharges and death certificates) to identify definite CCM diagnoses first made in Scottish residents between 1999 and 2003, which study neuroradiologists independently validated. We used multiple sources of prospective follow-up both to identify outcome events (which were assessed by use of brain imaging, by investigators masked to potential predictive factors) and to assess adults' dependence. The primary outcome was a composite of intracranial haemorrhage or focal neurological deficits (not including epileptic seizure) that were definitely or possibly related to CCM. 139 adults had at least one definite CCM and 134 were alive at initial presentation. During 1177 person-years of follow-up (completeness 97%), for intracranial haemorrhage alone the 5-year risk of a first haemorrhage was lower than the risk of recurrent haemorrhage (2·4%, 95% CI 0·0-5·7 vs 29·5%, 4·1-55·0; p<0·0001). For the primary outcome, the 5-year risk of a first event was lower than the risk of recurrence (9·3%, 3·1-15·4 vs 42·4%, 26·8-58·0; p<0·0001). The annual risk of recurrence of the primary outcome declined from 19·8% (95% CI 6·1-33·4) in year 1 to 5·0% (0·0-14·8) in year 5 and was higher for women than men (p=0·01) but not for adults with brainstem CCMs versus CCMs in other locations (p=0·17). The risk of recurrent intracranial haemorrhage or focal neurological deficit from a CCM is greater than the risk of a first event, is greater for women than for men, and declines over 5 years. This information can be used in clinical practice, but further work is needed to quantify risks precisely in the long term and to understand why women are at greater risk of recurrence than men. UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Introduction of mobile phones for use by volunteer community health workers in support of integrated community case management in Bushenyi District, Uganda: development and implementation process.

    PubMed

    Tumusiime, David Katuruba; Agaba, Gad; Kyomuhangi, Teddy; Finch, Jan; Kabakyenga, Jerome; MacLeod, Stuart

    2014-01-01

    A substantial literature suggests that mobile phones have great potential to improve management and survival of acutely ill children in rural Africa. The national strategy of the Ugandan Ministry of Health calls for employment of volunteer community health workers (CHWs) in implementation of Integrated Community Case Management (iCCM) of common illnesses (diarrhea, acute respiratory infection, pneumonia, fever/malaria) affecting children under five years of age. A mobile phone enabled system was developed within iCCM aiming to improve access by CHWs to medical advice and to strengthen reporting of data on danger signs and symptoms for acutely ill children under five years of age. Herein critical steps in development, implementation, and integration of mobile phone technology within iCCM are described. Mechanisms to improve diagnosis, treatment and referral of sick children under five were defined. Treatment algorithms were developed by the project technical team and mounted and piloted on the mobile phones, using an iterative process involving technical support personnel, health care providers, and academic support. Using a purposefully developed mobile phone training manual, CHWs were trained over an intensive five-day course to make timely diagnoses, recognize clinical danger signs, communicate about referrals and initiate treatment with appropriate essential drugs. Performance by CHWs and the accuracy and completeness of their submitted data was closely monitored post training test period and during the subsequent nine month community trial. In the full trial, the number of referrals and correctly treated children, based on the agreed treatment algorithms, was recorded. Births, deaths, and medication stocks were also tracked. Seven distinct phases were required to develop a robust mobile phone enabled system in support of the iCCM program. Over a nine month period, 96 CHWs were trained to use mobile phones and their competence to initiate a community trial was established through performance monitoring. Local information/communication consultants, working in concert with a university based department of pediatrics, can design and implement a robust mobile phone based system that may be anticipated to contribute to efficient delivery of iCCM by trained volunteer CHWs in rural settings in Uganda.

  12. CauseMap: fast inference of causality from complex time series.

    PubMed

    Maher, M Cyrus; Hernandez, Ryan D

    2015-01-01

    Background. Establishing health-related causal relationships is a central pursuit in biomedical research. Yet, the interdependent non-linearity of biological systems renders causal dynamics laborious and at times impractical to disentangle. This pursuit is further impeded by the dearth of time series that are sufficiently long to observe and understand recurrent patterns of flux. However, as data generation costs plummet and technologies like wearable devices democratize data collection, we anticipate a coming surge in the availability of biomedically-relevant time series data. Given the life-saving potential of these burgeoning resources, it is critical to invest in the development of open source software tools that are capable of drawing meaningful insight from vast amounts of time series data. Results. Here we present CauseMap, the first open source implementation of convergent cross mapping (CCM), a method for establishing causality from long time series data (≳25 observations). Compared to existing time series methods, CCM has the advantage of being model-free and robust to unmeasured confounding that could otherwise induce spurious associations. CCM builds on Takens' Theorem, a well-established result from dynamical systems theory that requires only mild assumptions. This theorem allows us to reconstruct high dimensional system dynamics using a time series of only a single variable. These reconstructions can be thought of as shadows of the true causal system. If reconstructed shadows can predict points from opposing time series, we can infer that the corresponding variables are providing views of the same causal system, and so are causally related. Unlike traditional metrics, this test can establish the directionality of causation, even in the presence of feedback loops. Furthermore, since CCM can extract causal relationships from times series of, e.g., a single individual, it may be a valuable tool to personalized medicine. We implement CCM in Julia, a high-performance programming language designed for facile technical computing. Our software package, CauseMap, is platform-independent and freely available as an official Julia package. Conclusions. CauseMap is an efficient implementation of a state-of-the-art algorithm for detecting causality from time series data. We believe this tool will be a valuable resource for biomedical research and personalized medicine.

  13. Inflammatory cascades mediate synapse elimination in spinal cord compression

    PubMed Central

    2014-01-01

    Background Cervical compressive myelopathy (CCM) is caused by chronic spinal cord compression due to spondylosis, a degenerative disc disease, and ossification of the ligaments. Tip-toe walking Yoshimura (twy) mice are reported to be an ideal animal model for CCM-related neuronal dysfunction, because they develop spontaneous spinal cord compression without any artificial manipulation. Previous histological studies showed that neurons are lost due to apoptosis in CCM, but the mechanism underlying this neurodegeneration was not fully elucidated. The purpose of this study was to investigate the pathophysiology of CCM by evaluating the global gene expression of the compressed spinal cord and comparing the transcriptome analysis with the physical and histological findings in twy mice. Methods Twenty-week-old twy mice were divided into two groups according to the magnetic resonance imaging (MRI) findings: a severe compression (S) group and a mild compression (M) group. The transcriptome was analyzed by microarray and RT-PCR. The cellular pathophysiology was examined by immunohistological analysis and immuno-electron microscopy. Motor function was assessed by Rotarod treadmill latency and stride-length tests. Results Severe cervical calcification caused spinal canal stenosis and low functional capacity in twy mice. The microarray analysis revealed 215 genes that showed significantly different expression levels between the S and the M groups. Pathway analysis revealed that genes expressed at higher levels in the S group were enriched for terms related to the regulation of inflammation in the compressed spinal cord. M1 macrophage-dominant inflammation was present in the S group, and cysteine-rich protein 61 (Cyr61), an inducer of M1 macrophages, was markedly upregulated in these spinal cords. Furthermore, C1q, which initiates the classical complement cascade, was more upregulated in the S group than in the M group. The confocal and electron microscopy observations indicated that classically activated microglia/macrophages had migrated to the compressed spinal cord and eliminated synaptic terminals. Conclusions We revealed the detailed pathophysiology of the inflammatory response in an animal model of chronic spinal cord compression. Our findings suggest that complement-mediated synapse elimination is a central mechanism underlying the neurodegeneration in CCM. PMID:24589419

  14. Integrated community case management of malaria, pneumonia and diarrhoea across three African countries: A qualitative study exploring lessons learnt and implications for further scale up

    PubMed Central

    Strachan, Clare; Wharton–Smith, Alexandra; Sinyangwe, Chomba; Mubiru, Denis; Ssekitooleko, James; Meier, Joslyn; Gbanya, Miatta; Tibenderana, James K.; Counihan, Helen

    2014-01-01

    Numerous studies highlight the effectiveness of an integrated approach for the management of malaria, pneumonia and diarrhoea at the community level. There has however been little study on lessons learnt from implementation in practice and stakeholder experiences which could inform future programmatic planning and evaluation frameworks. A participatory, qualitative evaluation was conducted in the three varied settings of South Sudan, Uganda and Zambia, which have seen the scale up of integrated community case management (iCCM) over the last five years. All key in–country stakeholders were consulted on study design, with a particular focus on scope and methodology. Data collection methods included stakeholder consultations (key informant interviews, focus group discussions), and a review of project and Ministry of Health documentation. Data analysis followed the Framework Approach. Results suggest that iCCM implementation generally followed national pre–agreed guidelines. Overarching key programmatic recommendations included: collaboration with implementing partners in planning stages to positively impact on community acceptance and ownership; adoption of participatory training methods adapted to low literacy populations; development of alternative support supervision methods such as peer support groups; full integration of community level data into the health management information system and emphasizing data analysis, use and feedback at all levels; strengthened supply chains through improved quantification and procurement of commodities in conjunction with the national distribution network; community engagement to establish a support system for community health workers to increase their motivation; enhanced sensitisation and behaviour change communication to raise awareness and usage of appropriate health services; and advocacy at the national level for funding and logistical support for the continuation and integration of iCCM. This qualitative study is a valuable contribution in understanding the ‘hows’ of iCCM implementation with key insights for improved feasibility and acceptability. Main findings show how community support to iCCM and community health workers is necessary for sustained health benefits coupled with a focus on strengthening and ‘enabling’ the public health system. The participatory study design and methodologies used enabled the scope of the research enquiry to effectively capture various stakeholder perspectives. PMID:25520794

  15. Supplementary comparisons of COOMET in the field of measurements of liquids kinematical viscosity COOMET.M.V-S1

    NASA Astrophysics Data System (ADS)

    Demyanov, A. A.; Tsurko, A. A.

    2017-01-01

    In the comparisons three Newtonian liquid samples were used with nominal values of 20 mm2/s 100 mm2/s and 1000 mm2/s ('20', '100' and '1000' respectively) at 20 °C. Each NMI presented results of measurements values kinematic viscosity samples, uncertainty and uncertainty budget. The purpose of these comparisons was confirmation of measurement and calibration capabilities (CMC) of the relevant NMI. As a reference the values of kinematic viscosity reference samples were taken as average values of measurement results obtained in the research laboratory of the national standards and research in the field of measurements of viscosity and density of the D I Mendeleev Institute for Metrology (VNIIM, RF), as a participant in international comparisons CCM.V-K1, BIPM. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  16. Multiplex conditional mutagenesis in zebrafish using the CRISPR/Cas system.

    PubMed

    Yin, L; Maddison, L A; Chen, W

    2016-01-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) system is a powerful tool for genome editing in numerous organisms. However, the system is typically used for gene editing throughout the entire organism. Tissue and temporal specific mutagenesis is often desirable to determine gene function in a specific stage or tissue and to bypass undesired consequences of global mutations. We have developed the CRISPR/Cas system for conditional mutagenesis in transgenic zebrafish using tissue-specific and/or inducible expression of Cas9 and U6-driven expression of sgRNA. To allow mutagenesis of multiple targets, we have isolated four distinct U6 promoters and designed Golden Gate vectors to easily assemble transgenes with multiple sgRNAs. We provide experimental details on the reagents and applications for multiplex conditional mutagenesis in zebrafish. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Calculation of paleohydraulic parameters of a fluvial system under spatially variable subsidence, of the Ericson sandstone, South western Wyoming

    NASA Astrophysics Data System (ADS)

    Snyder, H.; Leva-Lopez, J.

    2017-12-01

    During the late Campanian age in North America fluvial systems drained the highlands of the Sevier orogenic belt and travelled east towards the Western Interior Seaway. One of such systems deposited the Canyon Creek Member (CCM) of the Ericson Formation in south-western Wyoming. At this time the fluvial system was being partially controlled by laterally variable subsidence caused by incipient Laramide uplifts. These uplifts rather than real topographic features were only areas of reduced subsidence at the time of deposition of the CCM. Surface expression at that time must have been minimum, only minute changes in slope and accommodation. Outcrops around these Laramide structures, in particular both flanks of the Rock Springs Uplift, the western side of the Rawlins uplift and the north flank of the Uinta Mountains, have been sampled to study the petrography, grain size, roundness and sorting of the CCM, which along with the cross-bed thickness and bar thickness allowed calculation of the hydraulic parameters of the rivers that deposited the CCM. This study reveals how the fluvial system evolved and responded to the very small changes in subsidence and slope. Furthermore, the petrography will shed light on the provenance of these sandstones and on the relative importance of Sevier sources versus Laramide sources. This work is framed in a larger study that shows how incipient Laramide structural highs modified the behavior, style and architecture of the fluvial system, affecting its thickness, facies characteristics and net-to-gross both down-dip and along strike across the basin.

  18. Device therapy in heart failure with reduced ejection fraction-cardiac resynchronization therapy and more.

    PubMed

    Duncker, D; Veltmann, C

    2018-05-09

    In patients with heart failure with reduced ejection fraction (HFrEF), optimal medical treatment includes beta-blockers, ACE inhibitors/angiotensinreceptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists, and ivabradine when indicated. In device therapy of HFrEF, implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) have been established for many years. CRT is the therapy of choice (class I indication) in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology. However, the vast majority of heart failure patients show a narrow QRS complex or a non-LBBB morphology. These patients are not candidates for CRT and alternative electrical therapies such as baroreflex activation therapy (BAT) and cardiac contractility modulation (CCM) may be considered. BAT modulates vegetative dysregulation in heart failure. CCM improves contractility, functional capacity, and symptoms. Although a broad data set is available for BAT and CCM, mortality data are still lacking for both methods. This article provides an overview of the device-based therapeutic options for patients with HFrEF.

  19. Two-faced property of a market factor in asset pricing and diversification effect

    NASA Astrophysics Data System (ADS)

    Eom, Cheoljun

    2017-04-01

    This study empirically investigates the test hypothesis that a market factor acting as a representative common factor in the pricing models has a negative influence on constructing a well-diversified portfolio from the Markowitz mean-variance optimization function (MVOF). We use the comparative correlation matrix (C-CM) method to control a single eigenvalue among all eigenvalues included in the sample correlation matrix (S-CM), through the random matrix theory (RMT). In particular, this study observes the effect of the largest eigenvalue that has the property of the market factor. According to the results, the largest eigenvalue has the highest explanatory power on the stock return changes. The C-CM without the largest eigenvalue in the S-CM constructs a more diversified portfolio capable of improving the practical applicability of the MVOF. Moreover, the more diversified portfolio constructed from this C-CM has better out-of-sample performance in the future period. These results support the test hypothesis for the two-faced property of the market factor, defined by the largest eigenvalue.

  20. Influence of Desorption Conditions on Analyte Sensitivity and Internal Energy in Discrete Tissue or Whole Body Imaging by IR-MALDESI

    NASA Astrophysics Data System (ADS)

    Rosen, Elias P.; Bokhart, Mark T.; Ghashghaei, H. Troy; Muddiman, David C.

    2015-06-01

    Analyte signal in a laser desorption/postionization scheme such as infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is strongly coupled to the degree of overlap between the desorbed plume of neutral material from a sample and an orthogonal electrospray. In this work, we systematically examine the effect of desorption conditions on IR-MALDESI response to pharmaceutical drugs and endogenous lipids in biological tissue using a design of experiments approach. Optimized desorption conditions have then been used to conduct an untargeted lipidomic analysis of whole body sagittal sections of neonate mouse. IR-MALDESI response to a wide range of lipid classes has been demonstrated, with enhanced lipid coverage received by varying the laser wavelength used for mass spectrometry imaging (MSI). Targeted MS2 imaging (MS2I) of an analyte, cocaine, deposited beneath whole body sections allowed determination of tissue-specific ion response factors, and CID fragments of cocaine were monitored to comment on wavelength-dependent internal energy deposition based on the "survival yield" method.

  1. CASL VMA Milestone Report FY16 (L3:VMA.VUQ.P13.08): Westinghouse Mixing with STAR-CCM+

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gilkey, Lindsay Noelle

    2016-09-30

    STAR-CCM+ (STAR) is a high-resolution computational fluid dynamics (CFD) code developed by CD-adapco. STAR includes validated physics models and a full suite of turbulence models including ones from the k-ε and k-ω families. STAR is currently being developed to be able to do two phase flows, but the current focus of the software is single phase flow. STAR can use imported meshes or use the built in meshing software to create computation domains for CFD. Since the solvers generally require a fine mesh for good computational results, the meshes used with STAR tend to number in the millions of cells,more » with that number growing with simulation and geometry complexity. The time required to model the flow of a full 5x5 Mixing Vane Grid Assembly (5x5MVG) in the current STAR configuration is on the order of hours, and can be very computationally expensive. COBRA-TF (CTF) is a low-resolution subchannel code that can be trained using high fidelity data from STAR. CTF does not have turbulence models and instead uses a turbulent mixing coefficient β. With a properly calibrated β, CTF can be used a low-computational cost alternative to expensive full CFD calculations performed with STAR. During the Hi2Lo work with CTF and STAR, STAR-CCM+ will be used to calibrate β and to provide high-resolution results that can be used in the place of and in addition to experimental results to reduce the uncertainty in the CTF results.« less

  2. Safety Profile of Cough and Cold Medication Use in Pediatrics.

    PubMed

    Green, Jody L; Wang, George Sam; Reynolds, Kate M; Banner, William; Bond, G Randall; Kauffman, Ralph E; Palmer, Robert B; Paul, Ian M; Dart, Richard C

    2017-06-01

    The safety of cough and cold medication (CCM) use in children has been questioned. We describe the safety profile of CCMs in children <12 years of age from a multisystem surveillance program. Cases with adverse events (AEs) after ingestion of at least 1 index CCM ingredient (brompheniramine, chlorpheniramine, dextromethorphan, diphenhydramine, doxylamine, guaifenesin, phenylephrine, and pseudoephedrine) in children <12 years of age were collected from 5 data sources. An expert panel determined relatedness, dose, intent, and risk factors. Case characteristics and AEs are described. Of the 4202 cases reviewed, 3251 (77.4%) were determined to be at least potentially related to a CCM, with accidental unsupervised ingestions (67.1%) and medication errors (13.0%) the most common exposure types. Liquid (67.3%), pediatric (75.5%), and single-ingredient (77.5%) formulations were most commonly involved. AEs occurring in >20% of all cases included tachycardia, somnolence, hallucinations, ataxia, mydriasis, and agitation. Twenty cases (0.6%) resulted in death; most were in children <2 years of age (70.0%) and none involved a therapeutic dose. The overall reported AE rate was 0.573 cases per 1 million units (ie, tablets, gelatin capsules, or liquid equivalent) sold (95% confidence interval, 0.553-0.593) or 1 case per 1.75 million units. The rate of AEs associated with CCMs in children was low. Fatalities occurred even less frequently. No fatality involved a therapeutic dose. Accidental unsupervised ingestions were the most common exposure types and single-ingredient, pediatric liquid formulations were the most commonly reported products. These characteristics present an opportunity for targeted prevention efforts. Copyright © 2017 by the American Academy of Pediatrics.

  3. Dissecting the impact of CO2 and pH on the mechanisms of photosynthesis and calcification in the coccolithophore Emiliania huxleyi.

    PubMed

    Bach, Lennart T; Mackinder, Luke C M; Schulz, Kai G; Wheeler, Glen; Schroeder, Declan C; Brownlee, Colin; Riebesell, Ulf

    2013-07-01

    Coccolithophores are important calcifying phytoplankton predicted to be impacted by changes in ocean carbonate chemistry caused by the absorption of anthropogenic CO2 . However, it is difficult to disentangle the effects of the simultaneously changing carbonate system parameters (CO2 , bicarbonate, carbonate and protons) on the physiological responses to elevated CO2 . Here, we adopted a multifactorial approach at constant pH or CO2 whilst varying dissolved inorganic carbon (DIC) to determine physiological and transcriptional responses to individual carbonate system parameters. We show that Emiliania huxleyi is sensitive to low CO2 (growth and photosynthesis) and low bicarbonate (calcification) as well as low pH beyond a limited tolerance range, but is much less sensitive to elevated CO2 and bicarbonate. Multiple up-regulated genes at low DIC bear the hallmarks of a carbon-concentrating mechanism (CCM) that is responsive to CO2 and bicarbonate but not to pH. Emiliania huxleyi appears to have evolved mechanisms to respond to limiting rather than elevated CO2 . Calcification does not function as a CCM, but is inhibited at low DIC to allow the redistribution of DIC from calcification to photosynthesis. The presented data provides a significant step in understanding how E. huxleyi will respond to changing carbonate chemistry at a cellular level. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  4. Relationship between Trends in Land Precipitation and Tropical SST Gradient

    NASA Technical Reports Server (NTRS)

    Chung, Chul Eddy; Ramanathan, V.

    2007-01-01

    In this study, we examined global zonal/annual mean precipitation trends. Land precipitation trend from 1951 to 2002 shows widespread drying between 10 S to 20 N but the trend from 1977 to 2002 shows partial recovery. Based on general circulation model sensitivity studies, we suggested that these features are driven largely by the meridional SST gradient trend in the tropics. Our idealized CCM3 experiments substantiated that land precipitation is more sensitive to meridional SST gradient than to an overall tropical warming. Various simulations produced for the IPCC 4th assessment report demonstrate that increasing CO2 increases SST in the entire tropics non-uniformly and increases land precipitation only in certain latitude belts, again pointing to the importance of SST gradient change. Temporally varying aerosols in the IPCC simulations alter meridional SST gradient and land precipitation substantially. Anthropogenic aerosol direct solar forcing without its effects on SST is shown by the CCM3 to have weak but non-negligible influence on land precipitation.

  5. Identifying causal linkages between environmental variables and African conflicts

    NASA Astrophysics Data System (ADS)

    Nguy-Robertson, A. L.; Dartevelle, S.

    2017-12-01

    Environmental variables that contribute to droughts, flooding, and other natural hazards are often identified as factors contributing to conflict; however, few studies attempt to quantify these causal linkages. Recent research has demonstrated that the environment operates within a dynamical system framework and the influence of variables can be identified from convergent cross mapping (CCM) between shadow manifolds. We propose to use CCM to identify causal linkages between environmental variables and incidences of conflict. This study utilizes time series data from Climate Forecast System ver. 2 and MODIS satellite sensors processed using Google Earth Engine to aggregate country and regional trends. These variables are then compared to Armed Conflict Location & Event Data Project observations at similar scales. Results provide relative rankings of variables and their linkage to conflict. Being able to identify which factors contributed more strongly to a conflict can allow policy makers to prepare solutions to mitigate future crises. Knowledge of the primary environmental factors can lead to the identification of other variables to examine in the causal network influencing conflict.

  6. SPOT satellite family: Past, present, and future of the operations in the mission and control center

    NASA Technical Reports Server (NTRS)

    Philippe, Pacholczyk

    1993-01-01

    SPOT sun-synchronous remote sensing satellites are operated by CNES since February 1986. Today, the SPOT mission and control center (CCM) operates SPOT1, SPOT2, and is ready to operate SPOT3. During these seven years, the way to operate changed and the CCM, initially designed for the control of one satellite, has been modified and upgraded to support these new operating modes. All these events have shown the performances and the limits of the system. A new generation of satellite (SPOT4) will continue the remote sensing mission during the second half of the 90's. Its design takes into account the experience of the first generation and supports several improvements. A new generation of control center (CMP) has been developed and improves the efficiency, quality, and reliability of the operations. The CMP is designed for operating two satellites at the same time during launching, in-orbit testing, and operating phases. It supports several automatic procedures and improves data retrieval and reporting.

  7. Patient and Nurse Experiences in a Rural Chronic Disease Management Program: A Qualitative Evaluation.

    PubMed

    Davisson, Erica A; Swanson, Elizabeth A

    Rural status confounds chronic disease self-management. The purpose of this qualitative, descriptive study was to evaluate the nurse-led "Living Well" chronic disease management program reporting patient recruitment and retention issues since program initiation in 2013. The Chronic Care Model (CCM) was the guiding framework used to reinforce that interdisciplinary teams must have productive patient interactions for their program(s) to be sustainable. A rural, Midwest county clinic's chronic disease management program. Observations, interviews, and within- and across-case coding were used. Patients' responses were analyzed to identify (1) reasons for recruitment and retention problems and (2) program elements that were viewed as successful or needing improvement. A convenience sample of 6 rural, English-speaking adults (65 years or older, with no severe cognitive impairment) with at least one chronic condition was recruited and interviewed. Themes emerged related to nurse knowledge, availability, and value; peer support; overcoming barriers; adherence enhancement; and family/friends' involvement. Patients reported engagement in self-management activities because of program elements such as support groups and productive nurse-patient interactions. Interdisciplinary communication, commitment, and patient referral processes were identified as reasons for recruitment and retention issues. Findings substantiated that certain elements must be present and improved upon for future rural programs to be successful. Interdisciplinary communication may need to be improved to address recruitment and retention problems. It was clear from patient interviews that the nurse coordinators played a major role in patients' self-management adherence and overall satisfaction with the program. This is important to case management because results revealed the need for programs of this nature that incorporate the vital role of nurse coordinators and align with the CCM value of providing a supportive community health care resource for patients with chronic disease.

  8. Studies on the intracellular Ca2+ concentration of thawed dog spermatozoa: influence of Equex from different sources, two thawing diluents and post-thaw incubation in capacitating conditions.

    PubMed

    Peña, A I; López-Lugilde, L; Barrio, M; Becerra, J J; Quintela, L A; Herradón, P G

    2003-02-01

    The addition of 0.5% (v/v) of Equex STM Paste (Nova Chemical Sales, Scituate Inc., MA, USA), whose active ingredient is sodium dodecyl sulphate (SDS), to a Tris-egg yolk extender was demonstrated to improve the longevity of frozen-thawed dog spermatozoa during in vitro incubation at 38 degrees C. The aim of the first experiment was to compare the effects of two SDS-containing compounds, Equex STM Paste and Equex Pasta (Minitüb, Tiefenbach, Germany), when added to a Tris-egg yolk based extender, on the post-thaw longevity of dog spermatozoa, as well as on the intracellular Ca2+ concentration of spermatozoa, during post-thaw incubation at 38 degrees C. The post-thaw sperm survival and longevity, as well as the quality of the sperm movement, were significantly better when using Equex STM Paste. Such prolonged sperm longevity, however, was associated to a higher intracellular Ca2+ concentration in a large subpopulation of the live spermatozoa. A second experiment was aimed to evaluate the effects of sperm dilution immediately post-thaw with a Tris buffer containing glucose or fructose. The two Tris buffers were no different for any of the sperm parameters studied. The aim of a third experiment was to evaluate the sperm longevity, motility patterns and intracellular Ca2+ concentration of cryopreserved dog spermatozoa during post-thaw incubation in capacitating conditions [canine capacitating medium (CCM) with or without 5 microg/ml of heparin]. Heparin had no significant effects on any of the sperm parameters evaluated. During the first 8 h of incubation, the majority of the live spermatozoa had a high intracellular Ca2+ content. However, after 8-10 h of incubation, it had significantly declined. The highest proportion of fast motile sperm, and the highest curvilinear velocity, average path velocity and amplitude of lateral head displacement for the total motile sperm were observed during the 2-4-h incubation period. It was concluded that: (a) the addition of 0.5% (v/v) of Equex STM Paste to a Tris-egg yolk based extender significantly improved the post-thaw longevity of dog spermatozoa, but the same concentration of Equex Pasta had no significant beneficial effects; (b) sperm dilution after thawing with a Tris buffer containing glucose or fructose made no difference in post-thaw sperm longevity; (c) the addition of 5 microg/ml of heparin to CCM had no significant capacitating effects on frozen-thawed dog spermatozoa.

  9. Coupled-Circulation-Chemistry Studies with the Finite-Volume CCM: Trace Gas Transport in the Tropopause Region

    NASA Technical Reports Server (NTRS)

    Pawson, Steven; Lin, Shian-Jiann; Rood, Richard B.; Nebuda, Sharon; Nielsen, J. Eric; Douglass, Anne R.

    2000-01-01

    A joint project between the Data Assimilation Office at NASA GSFC and NCAR involves linking the physical packages from the Community Climate Model (CCM) with the flux-form semi-Lagrangian dynamical core developed by Lin and Rood in the DAO. A further development of this model includes the implementation of a chemical package developed by Douglass and colleagues in the Atmospheric Chemistry and Dynamics Branch at NASA GSFC. Results from this coupled dynamics-radiation-chemistry model will be presented, focussing on trace gas transport in the tropopause region.

  10. Natural Tissue Microenvironmental Conditions Modulate Adhesive Material Performance

    PubMed Central

    Oliva, Nuria; Shitreet, Sagi; Abraham, Eytan; Stanley, Butch; Edelman, Elazer R.; Artzi, Natalie

    2015-01-01

    We designed and optimized tissue-responsive adhesive materials by matching material and tissue properties. A two-component material based on dextran aldehyde and dendrimer amine provides a cohesive gel through aldehyde–amine cross-linking and an adhesive interface created by a dextran aldehyde-selective reaction with tissue amines. By altering aldehyde–amine chemistry, we examined how variations in tissue surfaces (serosal amine density in the duodenum, jejunum, and ileum) affect interactions with adhesive materials of varied compositions (aldehyde content). Interestingly, the same adhesive formulation reacts differentially with the three regions of the small intestine as a result of variation in the tissue amine density along the intestinal tract, affecting the tissue–material interfacial morphology, adhesion strength, and adhesive mechanical properties. Whereas tissues provide chemical anchors for interaction with materials, we were able to tune the adhesion strength for each section of the small intestine tissue by altering the adhesive formulation using a two-component material with flexible variables aimed at controlling the aldehyde/amine ratio. This tissue-specific approach should be applied to the broad spectrum of biomaterials, taking into account specific microenvironmental conditions in material design. PMID:23046479

  11. SH2 Domain Histochemistry.

    PubMed

    Buhs, Sophia; Nollau, Peter

    2017-01-01

    Among posttranslational modifications, the phosphorylation of tyrosine residues is a key modification in cell signaling. Because of its biological importance, characterization of the cellular state of tyrosine phosphorylation is of great interest. Based on the unique properties of endogenously expressed SH2 domains recognizing tyrosine phosphorylated signaling proteins with high specificity we have developed an alternative approach, coined SH2 profiling, enabling us to decipher complex patterns of tyrosine phosphorylation in various normal and cancerous tissues. So far, SH2 profiling has largely been applied for the analysis of protein extracts with the limitation that information on spatial distribution and intensity of tyrosine phosphorylation within a tissue is lost. Here, we describe a novel SH2 domain based strategy for differential characterization of the state of tyrosine phosphorylation in formaldehyde-fixed and paraffin-embedded tissues. This approach demonstrates that SH2 domains may serve as very valuable tools for the analysis of the differential state of tyrosine phosphorylation in primary tissues fixed and processed under conditions frequently applied by routine pathology laboratories.

  12. Application of multiplex nested methylated specific PCR in early diagnosis of epithelial ovarian cancer.

    PubMed

    Wang, Bi; Yu, Lei; Yang, Guo-Zhen; Luo, Xin; Huang, Lin

    2015-01-01

    To explore the application of multiplex nested methylated specific polymerase chain reaction (PCR) in the early diagnosis of epithelial ovarian carcinoma (EOC). Serum and fresh tissue samples were collected from 114 EOC patients. RUNX3, TFPI2 and OPCML served as target genes. Methylation levels of tissues were assessed by multiplex nested methylated specific PCR, the results being compared with those for carcinoma antigen 125 (CA125). The serum free deoxyribose nucleic acid (DNA) methylation spectrum of EOC patients was completely contained in the DNA spectrum of cancer tissues, providing an accurate reflection of tumor DNA methylation conditions. Serum levels of CA125 and free DNA methylation in the EOC group were evidently higher than those in benign lesion and control groups (p<0.05). Patients with early EOC had markedly lower serum CA125 than those with advanced EOC (p<0.05), but there was no significant difference in free DNA methylation (p>0.05). The sensitivity, specificity and positive predicative value (PPV) of multiplex nested methylated specific PCR were significantly higher for detection of all patients and those with early EOC than those for CA125 (p<0.05). In the detection of patients with advanced EOC, the PPV of CA125 detection was obviously lower than that of multiplex nested methylated specific PCR (p>0.05), but there was no significant difference in sensitivity (p>0.05). Serum free DNA methylation can be used as a biological marker for EOC and multiplex nested methylated specific PCR should be considered for early diagnosis since it can accurately determine tumor methylation conditions.

  13. HIF-2α-induced chemokines stimulate motility of fibroblast-like synoviocytes and chondrocytes into the cartilage-pannus interface in experimental rheumatoid arthritis mouse models.

    PubMed

    Huh, Yun Hyun; Lee, Gyuseok; Lee, Keun-Bae; Koh, Jeong-Tae; Chun, Jang-Soo; Ryu, Je-Hwang

    2015-10-29

    Pannus formation and resulting cartilage destruction during rheumatoid arthritis (RA) depends on the migration of synoviocytes to cartilage tissue. Here, we focused on the role of hypoxia-inducible factor (HIF)-2α-induced chemokines by chondrocytes in the regulation of fibroblast-like synoviocyte (FLS) migration into the cartilage-pannus interface and cartilage erosion. Collagen-induced arthritis (CIA), K/BxN serum transfer, and tumor necrosis factor-α transgenic mice were used as experimental RA models. Expression patterns of HIF-2α and chemokines were determined via immunostaining, Western blotting and RT-PCR. FLS motility was evaluated using transwell migration and invasion assays. The specific role of HIF-2α was determined via local deletion of HIF-2α in joint tissues or using conditional knockout (KO) mice. Cartilage destruction, synovitis and pannus formation were assessed via histological analysis. HIF-2α and various chemokines were markedly upregulated in degenerating cartilage and pannus of RA joints. HIF-2α induced chemokine expression by chondrocytes in both primary culture and cartilage tissue. HIF-2α -induced chemokines by chondrocytes regulated the migration and invasion of FLS. Local deletion of HIF-2α in joint tissues inhibited pannus formation adjacent to cartilage tissue and cartilage destruction caused by K/BxN serum transfer. Furthermore, conditional knockout of HIF-2α in cartilage blocked pannus formation in adjacent cartilage but not bone tissue, along with inhibition of cartilage erosion caused by K/BxN serum transfer. Our findings suggest that chemokines induced by IL-1β or HIF-2α in chondrocytes regulate pannus expansion by stimulating FLS migration and invasion, leading to cartilage erosion during RA pathogenesis.

  14. Tissue Specific Expression Of Sprouty1 In Mice Protects Against High Fat Diet Induced Fat Accumulation, Bone Loss, And Metabolic Dysfunction

    PubMed Central

    Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J.; Liaw, Lucy

    2012-01-01

    We recently characterized Sprouty1 (Spry1), a growth factor signaling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue specific Spry1 expression in mice resulted in increased bone mass and reduced body fat while conditional knockout of Spry1 had the opposite effect with decreased bone and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high fat diet-induced obesity, bone loss, and associated lipid abnormalities and demonstrate that Spry1 has a long-term protective effect on mice fed a high caloric diet. We studied diet-induced obesity in mice with fatty acid binding promoter (aP2)-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1 null mice, high fat diet increased body fat by 40%, impaired glucose regulation, and led to liver steatosis. However, over-expression of Spry1 led to 35% lower body fat, reduced bone loss, and normal metabolic function compared to single transgenics. This protective phenotype was associated with decreased circulating insulin (70%) and leptin (54%) compared to controls on a high fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45%. We show that conditional Spry1 expression in adipose tissue protects against high fat diet-induced obesity and associated bone loss. PMID:22142492

  15. Fabrication of High Performing PEMFC Catalyst-Coated Membranes with a Low Cost Air-Assisted Cylindrical Liquid Jets Spraying System

    DOE PAGES

    Peng, Xiong; Omasta, Travis; Rigdon, William; ...

    2016-11-15

    In this paper, a low cost air-assisted cylindrical liquid jets spraying (ACLJS) system was developed to prepare high-performance catalyst-coated membranes (CCMs) for proton exchange membrane fuel cells (PEMFCs). The catalyst ink was flowed from a cylindrical orifice and was atomized by an air stream fed from a coaxial slit and sprayed directly onto the membrane, which was suctioned to a heated aluminum vacuum plate. The CCM pore architecture including size, distribution and volume can be controlled using various flow parameters, and the impact of spraying conditions on electrode structure and PEMFC performance was investigated. CCMs fabricated in the fiber-type break-upmore » regime by ACLJS achieved very high performance during PEMFC testing, with the top-performing cells having a current density greater than 1900 mA/cm 2 at 0.7 V under H 2/O 2 flows and 700 mA/cm 2 under H 2/Air at 1.5 bar(absolute) pressure and 60% gas RH, and 80°C cell temperature.« less

  16. Fabrication of High Performing PEMFC Catalyst-Coated Membranes with a Low Cost Air-Assisted Cylindrical Liquid Jets Spraying System

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Peng, Xiong; Omasta, Travis; Rigdon, William

    In this paper, a low cost air-assisted cylindrical liquid jets spraying (ACLJS) system was developed to prepare high-performance catalyst-coated membranes (CCMs) for proton exchange membrane fuel cells (PEMFCs). The catalyst ink was flowed from a cylindrical orifice and was atomized by an air stream fed from a coaxial slit and sprayed directly onto the membrane, which was suctioned to a heated aluminum vacuum plate. The CCM pore architecture including size, distribution and volume can be controlled using various flow parameters, and the impact of spraying conditions on electrode structure and PEMFC performance was investigated. CCMs fabricated in the fiber-type break-upmore » regime by ACLJS achieved very high performance during PEMFC testing, with the top-performing cells having a current density greater than 1900 mA/cm 2 at 0.7 V under H 2/O 2 flows and 700 mA/cm 2 under H 2/Air at 1.5 bar(absolute) pressure and 60% gas RH, and 80°C cell temperature.« less

  17. Genetically diagnosed Birt-Hogg-Dubé syndrome and familial cerebral cavernous malformations in the same individual: a case report.

    PubMed

    Whitworth, James; Stausbøl-Grøn, Brian; Skytte, Anne-Bine

    2017-01-01

    When faced with an unusual clinical feature in a patient with a Mendelian disorder, the clinician may entertain the possibilities of either the feature representing a novel manifestation of that disorder or the co-existence of a different inherited condition. Here we describe an individual with a submandibular oncocytoma, pulmonary bullae and renal cysts as well as multiple cerebral cavernous malformations and haemangiomas. Genetic investigations revealed constitutional mutations in FLCN, associated with Birt-Hogg-Dubé syndrome (BHD) and CCM2, associated with familial cerebral cavernous malformation. Intracranial vascular pathologies (but not cerebral cavernous malformation) have recently been described in a number of individuals with BHD (Kapoor et al. in Fam Cancer 14:595-597, 10.1007/s10689-015-9807-y , 2015) but it is not yet clear whether they represent a genuine part of that conditions' phenotypic spectrum. We suggest that in such instances of potentially novel clinical features, more extensive genetic testing to consider co-existing conditions should be considered where available. The increased use of next generation sequencing applications in diagnostic settings is likely to lead more cases such as this being revealed.

  18. Longitudinal changes in seizure outcomes after resection of cerebral cavernous malformations in patients presenting with seizures: a long-term follow-up of 46 patients.

    PubMed

    Kim, Jiha; Kim, Chi Heon; Chung, Chun Kee

    2014-08-01

    Seizure is the most common presentation in patients with cerebral cavernous malformations (CCMs). Although many articles have documented seizure outcomes after resection of CCM, few have conducted long-term follow-ups; thus, the fluctuating seizure outcomes have been neglected. The purpose of this study is to describe long-term postoperative seizure outcomes in patients with CCM and to compare seizure outcomes between patients with sporadic seizures and those with chronic seizures. Forty-six patients with CCM presenting with seizures underwent surgery. The male-to-female ratio was 1:1, and the average age at initial seizure onset was 27.6 years. The mean preoperative seizure duration was 42.7 months. Patients were divided into two groups: a chronic group (N = 20) and a sporadic group (N = 26) according to seizure frequency and duration. The mean postoperative follow-up duration was 96.3 months, and the postoperative seizure outcomes were checked annually based upon Engel's classification. After the first year of follow-up, 80.8 % of the sporadic group and 75.0 % of the chronic group were evaluated as Engel class I. These rates increased to 100.0 % and 90.0 %, respectively, at the eighth year of follow-up. Overall, 29 (63.0 %) of the 46 patients experienced changes in seizure outcomes over the follow-up period. Despite their delayed improvements, the chronic group showed less favorable outcomes throughout follow-up (p = 0.025). Long-term follow-up is indispensable for accurately assessing postoperative seizure outcomes because these outcomes change continuously. We recommend earlier surgery to achieve seizure-free status in patients with CCM. However, even in the chronic group, surgery is recommended, considering the overall delayed improvement.

  19. Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications.

    PubMed

    Grix, Tobias; Ruppelt, Alicia; Thomas, Alexander; Amler, Anna-Klara; Noichl, Benjamin P; Lauster, Roland; Kloke, Lutz

    2018-03-22

    Many tissue models have been developed to mimic liver-specific functions for metabolic and toxin conversion in in vitro assays. Most models represent a 2D environment rather than a complex 3D structure similar to native tissue. To overcome this issue, spheroid cultures have become the gold standard in tissue engineering. Unfortunately, spheroids are limited in size due to diffusion barriers in their dense structures, limiting nutrient and oxygen supply. Recent developments in bioprinting techniques have enabled us to engineer complex 3D structures with perfusion-enabled channel systems to ensure nutritional supply within larger, densely-populated tissue models. In this study, we present a proof-of-concept for the feasibility of bioprinting a liver organoid by combining HepaRG and human stellate cells in a stereolithographic printing approach, and show basic characterization under static cultivation conditions. Using standard tissue engineering analytics, such as immunohistology and qPCR, we found higher albumin and cytochrome P 450 3A4 (CYP3A4) expression in bioprinted liver tissues compared to monolayer controls over a two-week cultivation period. In addition, the expression of tight junctions, liver-specific bile transporter multidrug resistance-associated protein 2 (MRP2), and overall metabolism (glucose, lactate, lactate dehydrogenase (LDH)) were found to be stable. Furthermore, we provide evidence for the perfusability of the organoids' intrinsic channel system. These results motivate new approaches and further development in liver tissue engineering for advanced organ-on-a-chip applications and pharmaceutical developments.

  20. GIANT 2.0: genome-scale integrated analysis of gene networks in tissues.

    PubMed

    Wong, Aaron K; Krishnan, Arjun; Troyanskaya, Olga G

    2018-05-25

    GIANT2 (Genome-wide Integrated Analysis of gene Networks in Tissues) is an interactive web server that enables biomedical researchers to analyze their proteins and pathways of interest and generate hypotheses in the context of genome-scale functional maps of human tissues. The precise actions of genes are frequently dependent on their tissue context, yet direct assay of tissue-specific protein function and interactions remains infeasible in many normal human tissues and cell-types. With GIANT2, researchers can explore predicted tissue-specific functional roles of genes and reveal changes in those roles across tissues, all through interactive multi-network visualizations and analyses. Additionally, the NetWAS approach available through the server uses tissue-specific/cell-type networks predicted by GIANT2 to re-prioritize statistical associations from GWAS studies and identify disease-associated genes. GIANT2 predicts tissue-specific interactions by integrating diverse functional genomics data from now over 61 400 experiments for 283 diverse tissues and cell-types. GIANT2 does not require any registration or installation and is freely available for use at http://giant-v2.princeton.edu.

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