Sample records for augmin subunit msd1

  1. Characterization of the Arabidopsis Augmin Complex Uncovers Its Critical Function in the Assembly of the Acentrosomal Spindle and Phragmoplast Microtubule Arrays[W

    PubMed Central

    Hotta, Takashi; Kong, Zhaosheng; Ho, Chin-Min Kimmy; Zeng, Cui Jing Tracy; Horio, Tetsuya; Fong, Sophia; Vuong, Trang; Lee, Yuh-Ru Julie; Liu, Bo

    2012-01-01

    Plant cells assemble the bipolar spindle and phragmoplast microtubule (MT) arrays in the absence of the centrosome structure. Our recent findings in Arabidopsis thaliana indicated that AUGMIN subunit3 (AUG3), a homolog of animal dim γ-tubulin 3, plays a critical role in γ-tubulin–dependent MT nucleation and amplification during mitosis. Here, we report the isolation of the entire plant augmin complex that contains eight subunits. Among them, AUG1 to AUG6 share low sequence similarity with their animal counterparts, but AUG7 and AUG8 share homology only with proteins of plant origin. Genetic analyses indicate that the AUG1, AUG2, AUG4, and AUG5 genes are essential, as stable mutations in these genes could only be transmitted to heterozygous plants. The sterile aug7-1 homozygous mutant in which AUG7 expression is significantly reduced exhibited pleiotropic phenotypes of seriously retarded vegetative and reproductive growth. The aug7-1 mutation caused delocalization of γ-tubulin in the mitotic spindle and phragmoplast. Consequently, spindles were abnormally elongated, and their poles failed to converge, as MTs were splayed to discrete positions rendering deformed arrays. In addition, the mutant phragmoplasts often had disorganized MT bundles with uneven edges. We conclude that assembly of MT arrays during plant mitosis depends on the augmin complex, which includes two plant-specific subunits. PMID:22505726

  2. Meiosis-Specific Stable Binding of Augmin to Acentrosomal Spindle Poles Promotes Biased Microtubule Assembly in Oocytes

    PubMed Central

    Colombié, Nathalie; Głuszek, A. Agata; Meireles, Ana M.; Ohkura, Hiroyuki

    2013-01-01

    In the oocytes of many animals including humans, the meiotic spindle assembles without centrosomes. It is still unclear how multiple pathways contribute to spindle microtubule assembly, and whether they are regulated differently in mitosis and meiosis. Augmin is a γ-tubulin recruiting complex which “amplifies” spindle microtubules by generating new microtubules along existing ones in mitosis. Here we show that in Drosophila melanogaster oocytes Augmin is dispensable for chromatin-driven assembly of bulk spindle microtubules, but is required for full microtubule assembly near the poles. The level of Augmin accumulated at spindle poles is well correlated with the degree of chromosome congression. Fluorescence recovery after photobleaching shows that Augmin stably associates with the polar regions of the spindle in oocytes, unlike in mitotic cells where it transiently and uniformly associates with the metaphase spindle. This stable association is enhanced by γ-tubulin and the kinesin-14 Ncd. Therefore, we suggest that meiosis-specific regulation of Augmin compensates for the lack of centrosomes in oocytes by actively biasing sites of microtubule generation within the spindle. PMID:23785300

  3. Intra-spindle Microtubule Assembly Regulates Clustering of Microtubule-Organizing Centers during Early Mouse Development.

    PubMed

    Watanabe, Sadanori; Shioi, Go; Furuta, Yasuhide; Goshima, Gohta

    2016-04-05

    Errors during cell division in oocytes and early embryos are linked to birth defects in mammals. Bipolar spindle assembly in early mouse embryos is unique in that three or more acentriolar microtubule-organizing centers (MTOCs) are initially formed and are then clustered into two spindle poles. Using a knockout mouse and live imaging of spindles in embryos, we demonstrate that MTOC clustering during the blastocyst stage requires augmin, a critical complex for MT-dependent MT nucleation within the spindle. Functional analyses in cultured cells with artificially increased numbers of centrosomes indicate that the lack of intra-spindle MT nucleation, but not loss of augmin per se or overall reduction of spindle MTs, is the cause of clustering failure. These data suggest that onset of mitosis with three or more MTOCs is turned into a typical bipolar division through augmin-dependent intra-spindle MT assembly. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. The fluctuating ribosome: thermal molecular dynamics characterized by neutron scattering

    NASA Astrophysics Data System (ADS)

    Zaccai, Giuseppe; Natali, Francesca; Peters, Judith; Řihová, Martina; Zimmerman, Ella; Ollivier, J.; Combet, J.; Maurel, Marie-Christine; Bashan, Anat; Yonath, Ada

    2016-11-01

    Conformational changes associated with ribosome function have been identified by X-ray crystallography and cryo-electron microscopy. These methods, however, inform poorly on timescales. Neutron scattering is well adapted for direct measurements of thermal molecular dynamics, the ‘lubricant’ for the conformational fluctuations required for biological activity. The method was applied to compare water dynamics and conformational fluctuations in the 30 S and 50 S ribosomal subunits from Haloarcula marismortui, under high salt, stable conditions. Similar free and hydration water diffusion parameters are found for both subunits. With respect to the 50 S subunit, the 30 S is characterized by a softer force constant and larger mean square displacements (MSD), which would facilitate conformational adjustments required for messenger and transfer RNA binding. It has been shown previously that systems from mesophiles and extremophiles are adapted to have similar MSD under their respective physiological conditions. This suggests that the results presented are not specific to halophiles in high salt but a general property of ribosome dynamics under corresponding, active conditions. The current study opens new perspectives for neutron scattering characterization of component functional molecular dynamics within the ribosome.

  5. Branching microtubule nucleation in Xenopus egg extracts mediated by augmin and TPX2

    PubMed Central

    Petry, Sabine; Groen, Aaron C.; Ishihara, Keisuke; Mitchison, Timothy J.; Vale, Ronald D.

    2013-01-01

    Summary The microtubules that comprise mitotic spindles in animal cells are nucleated at centrosomes and by spindle assembly factors that are activated in the vicinity of chromatin. Indirect evidence also has suggested that microtubules might be nucleated from pre-existing microtubules throughout the spindle, but this process has not been observed directly. Here, we demonstrate microtubule nucleation from the sides of existing microtubules in meiotic Xenopus egg extracts. Daughter microtubules grow at a low branch angle and with the same polarity as mother filaments. Branching microtubule nucleation requires gamma-tubulin and augmin and is stimulated by GTP-bound Ran and its effector TPX2, factors previously implicated in chromatin-stimulated nucleation. Because of the rapid amplification of microtubule numbers and the preservation of microtubule polarity, microtubule-dependent microtubule nucleation is well suited for spindle assembly and maintenance. PMID:23415226

  6. Cooperative unfolding of distinctive mechanoreceptor domains transduces force into signals

    PubMed Central

    Ju, Lining; Chen, Yunfeng; Xue, Lingzhou; Du, Xiaoping; Zhu, Cheng

    2016-01-01

    How cells sense their mechanical environment and transduce forces into biochemical signals is a crucial yet unresolved question in mechanobiology. Platelets use receptor glycoprotein Ib (GPIb), specifically its α subunit (GPIbα), to signal as they tether and translocate on von Willebrand factor (VWF) of injured arterial surfaces against blood flow. Force elicits catch bonds to slow VWF–GPIbα dissociation and unfolds the GPIbα leucine-rich repeat domain (LRRD) and juxtamembrane mechanosensitive domain (MSD). How these mechanical processes trigger biochemical signals remains unknown. Here we analyze these extracellular events and the resulting intracellular Ca2+ on a single platelet in real time, revealing that LRRD unfolding intensifies Ca2+ signal whereas MSD unfolding affects the type of Ca2+ signal. Therefore, LRRD and MSD are analog and digital force transducers, respectively. The >30 nm macroglycopeptide separating the two domains transmits force on the VWF–GPIbα bond (whose lifetime is prolonged by LRRD unfolding) to the MSD to enhance its unfolding, resulting in unfolding cooperativity at an optimal force. These elements may provide design principles for a generic mechanosensory protein machine. DOI: http://dx.doi.org/10.7554/eLife.15447.001 PMID:27434669

  7. 78 FR 24745 - Agency Information Collection Activities: Announcement of Board Approval Under Delegated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-26

    ... Securities Dealer. Agency form number: FR MSD-4; FR MSD-5. OMB control number: 7100-0100; 7100-0101... are municipal securities dealers. Estimated annual reporting hours: FR MSD-4, 20 hours; FR MSD-5, 13 hours. Estimated average hours per response: FR MSD-4, 1 hour; FR MSD-5, 0.25 hours. Number of...

  8. 75 FR 19973 - Agency Information Collection Activities: Announcement of Board Approval Under Delegated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-16

    ... Municipal Securities Dealer. Agency form number: FR MSD-4 and FR MSD-5. OMB control number: 7100-0100 and... activities as municipal securities dealers. Estimated annual reporting hours: FR MSD-4, 48 hours; and FR MSD-5, 36 hours. Estimated average hours per response: FR MSD-4, 1 hour; and FR MSD- 5, 0.25 hours...

  9. Msd1/SSX2IP-dependent microtubule anchorage ensures spindle orientation and primary cilia formation

    PubMed Central

    Hori, Akiko; Ikebe, Chiho; Tada, Masazumi; Toda, Takashi

    2014-01-01

    Anchoring microtubules to the centrosome is critical for cell geometry and polarity, yet the molecular mechanism remains unknown. Here we show that the conserved human Msd1/SSX2IP is required for microtubule anchoring. hMsd1/SSX2IP is delivered to the centrosome in a centriolar satellite-dependent manner and binds the microtubule-nucleator γ-tubulin complex. hMsd1/SSX2IP depletion leads to disorganised interphase microtubules and misoriented mitotic spindles with reduced length and intensity. Furthermore, hMsd1/SSX2IP is essential for ciliogenesis, and during zebrafish embryogenesis, knockdown of its orthologue results in ciliary defects and disturbs left-right asymmetry. We propose that the Msd1 family comprises conserved microtubule-anchoring proteins. PMID:24397932

  10. The Msd1–Wdr8–Pkl1 complex anchors microtubule minus ends to fission yeast spindle pole bodies

    PubMed Central

    Yukawa, Masashi; Ikebe, Chiho

    2015-01-01

    The minus ends of spindle microtubules are anchored to a microtubule-organizing center. The conserved Msd1/SSX2IP proteins are localized to the spindle pole body (SPB) and the centrosome in fission yeast and humans, respectively, and play a critical role in microtubule anchoring. In this paper, we show that fission yeast Msd1 forms a ternary complex with another conserved protein, Wdr8, and the minus end–directed Pkl1/kinesin-14. Individual deletion mutants displayed the identical spindle-protrusion phenotypes. Msd1 and Wdr8 were delivered by Pkl1 to mitotic SPBs, where Pkl1 was tethered through Msd1–Wdr8. The spindle-anchoring defect imposed by msd1/wdr8/pkl1 deletions was suppressed by a mutation of the plus end–directed Cut7/kinesin-5, which was shown to be mutual. Intriguingly, Pkl1 motor activity was not required for its anchoring role once targeted to the SPB. Therefore, spindle anchoring through Msd1–Wdr8–Pkl1 is crucial for balancing the Cut7/kinesin-5–mediated outward force at the SPB. Our analysis provides mechanistic insight into the spatiotemporal regulation of two opposing kinesins to ensure mitotic spindle bipolarity. PMID:25987607

  11. Association between pain catastrophising and musculoskeletal disorders is modified by past injuries in Malaysian military recruits.

    PubMed

    Mohd Din, F H; Rampal, Sanjay; Muslan, M A; Hoe, Victor C W

    2016-07-01

    Pain catastrophising is defined as exaggerated negative thoughts, which can occur during an actual or anticipated painful experience, such as musculoskeletal injuries (MSI) or disorders (MSD). The aims of this study are to examine the association between pain catastrophising and MSI and MSD in Malaysian Army male recruits, and evaluate the effects of past injury. A cohort of 611 male Malaysian Army recruits were recruited and followed up at 3 and 6 months. Pain catastrophising, MSD, sociodemographic and work factors were measured using a self-administered questionnaire, and MSI incidence was retrieved from the medical records. Multivariable fixed effects regression was used to model the cumulative incidence of MSD and MSI. Approximately 12% of the recruits were diagnosed with incident MSI and 80% reported incident MSD. Higher pain catastrophising at baseline was associated with higher 6 month MSD risk (adjusted OR (aOR) 1.6 per 1 SD increase of Pain Catastrophising Scale (PCS) scores; 95% CI 1.2 to 2.0), and longitudinally associated with MSD incidence (aOR 1.2, 95% CI 1.1 to 1.4). Pain catastrophising was not associated with MSI incidence (aOR 1.0, 95% CI 0.8 to 1.3). The association between pain catastrophising and self-reported MSD was stronger among recruits with self-reported past injury (p for interaction <0.001). Pain catastrophising was able to predict symptomatic MSD, and not physician-diagnosed MSI, and these findings are directly related to individual health beliefs. Pain catastrophising has a greater influence on how military recruits perceived their musculoskeletal conditions during training, and efforts to reduce pain catastrophising may be beneficial. 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/

  12. Effects of modified Sanhuang decoction () enema on serum tumor necrosis factor-α and colonic mucosa interleukin-1β, interleukin-6 levels in ulcerative colitis rats.

    PubMed

    Wang, Shuai; Zhou, Tao; Zhai, Jun-Peng; Wang, Li-Hua; Chen, Jing

    2014-11-01

    To investigate the effects of Modified Sanhuang Decoction (, MSD) enema on the serum tumor necrosis factor alpha (TNF-α) and colonic mucosa interleukin-1β (IL-1β), interleukin-6 (IL-6) levels in experimental ulcerative colitis (UC) rats. Forty-five male Wistar rats were randomly divided into 4 groups: normal group (n=12), model group (n=11), salazosulfapyridine (SASP) group (n=11) and MSD group (n=11). The UC model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Rats in the normal group and model group were clystered with 0.9% normal saline, while in the SASP group and MSD group were clystered with SASP and MSD enema, respectively. After drug administration (10 mL/kg body weight, for 7 days), colonic gross changes and colonic mucosa histology were observed, serum TNF-α and colonic mucosa IL-1β, IL-6 levels were tested by enzyme linked immunosorbent assay and radioimmunoassay, respectively. As compared with the normal group, the experimental UC rats, the colonic mucosal damage index scores (CMDIs), histopathological scores (HS) and the serum TNF-α and colonic mucosa IL-1β, IL-6 levels significantly increased (P<0.05 or P<0.01). In the MSD and SASP groups, the ulcer area significantly reduced, and edema disappeared. The CMDIs, HS, the serum TNF-α and colonic mucosa IL-1β, IL-6 levels in the MSD and SASP groups significantly decreased (P<0.05 or P<0.01) compared with the model group. The CMDIs in the MSD group were lower than that in the SASP group (P<0.05), but there were no significant differences in HS, serum TNF-α or colonic mucosa IL-1β, IL-6 levels between the MSD and SASP groups. MSD enema can improve colonic mucosa impairment and decrease serum TNF-α and colonic mucosa IL-1β, IL-6 levels in experimental UC.

  13. The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation

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

    Hori, Akiko; Morand, Agathe; Ikebe, Chiho

    2015-12-04

    The centrosome plays a pivotal role in a wide range of cellular processes and its dysfunction is causally linked to many human diseases including cancer and developmental and neurological disorders. This organelle contains more than one hundred components, and yet many of them remain uncharacterised. Here we identified a novel centrosome protein Wdr8, based upon the structural conservation of the fission yeast counterpart. We showed that Wdr8 constitutively localises to the centrosome and super resolution microscopy uncovered that this protein is enriched at the proximal end of the mother centriole. Furthermore, we identified hMsd1/SSX2IP, a conserved spindle anchoring protein, asmore » one of Wdr8 interactors by mass spectrometry. Wdr8 formed a complex and partially colocalised with hMsd1/SSX2IP. Intriguingly, knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. Indeed, Wdr8 depletion resulted in the reduced recruitment of hMsd1/SSX2IP to the mitotic centrosome, though the converse is not true. Together, we propose that the conserved Wdr8-hMsd1/SSX2IP complex plays a critical role in controlling proper spindle length and orientation. - Highlights: • Human Wdr8 is a centrosomal protein enriched in the proximal end of the centriole. • Wdr8 and hMsd1/SSX2IP form a complex conserved in fungi. • Depletion of Wdr8 results in shorter, tilted spindle microtubules. • Depletion phenotypes of Wdr8 are very similar to those of hMsd1/SSX2IP knockdown.« less

  14. Does age matter in predicting musculoskeletal disorder risk? An analysis of workplace predictors over 4 years.

    PubMed

    Oakman, Jodi; Neupane, Subas; Nygård, Clas-Håkan

    2016-10-01

    Musculoskeletal disorders (MSDs) are a major workplace issue. With increasing pressure to extend working lives, predictors of MSD risk across all age groups require accurate identification to inform risk reduction strategies. In 2005 and 2009, a survey was conducted in a Finnish food processing company (N = 734). Data on workplace physical and psychosocial hazards, work ability, job satisfaction and lifestyle-related variables were collected, and MSD risk was measured through assessment of work-related strain in four body areas. Predictors of MSD risk across three age groups (20-35, 36-49, 50+) were assessed with linear regression analysis. Physical hazards and MSD risk were related differently for each age group. The relationship between psychosocial hazards and MSD risk was less clear. For younger workers, physical hazards were not associated with MSD risk. In contrast, for those aged 36-49, repetitive movements (B = 1.76, p < 0.001) and awkward postures (B = 1.30, p = 0.02) were associated with increased MSD risk. For older workers, environmental hazards were positively associated with MSD risk (B = 0.37, p = 0.04). Predictors of MSD risk changed differently for each age group during 4 years of follow-up. For younger workers, change in environment and repetitive movements, for middle age team support and for older workers change in awkward posture were significant predictors of MSD risk. These results support the need for workplace-specific hazard surveillance data. This will ensure that all contributing factors to MSD risk can be accurately identified and controlled independent of age.

  15. Construction of small plasmid vectors for use in genetic improvement of the extremely acidophilic Acidithiobacillus caldus.

    PubMed

    Meng, Jianzhou; Wang, Huiyan; Liu, Xiangmei; Lin, Jianqun; Pang, Xin; Lin, Jianqiang

    2013-10-01

    The genetic improvement of biomining bacteria including Acidithiobacillus caldus could facilitate the bioleaching process of sulfur-containing minerals. However, the available vectors for use in A. caldus are very scanty and limited to relatively large broad-host-range IncQ plasmids. In this study, a set of small, mobilizable plasmid vectors (pBBR1MCS-6, pMSD1 and pMSD2) were constructed based on plasmid pBBR1MCS-2, which does not belong to the IncQ, IncW, or IncP groups. The function of the tac promoter on 5.8-kb pMSD2 was determined by inserting a kanamycin-resistant reporter gene. The resulting recombinant pMSD2-Km was successfully transferred by conjugation into A. caldus MTH-04 with transfer frequency of 1.38±0.64×10(-5). The stability and plasmid copy number of pMSD2-Km in A. caldus MTH-04 were 75±2.7% and 5-6 copies per cell, respectively. By inserting an arsABC operon into pMSD2, an arsenic-resistant recombinant pMSD2-As was constructed and transferred into A. caldus MTH-04 by conjugation. The arsenic tolerance of A. caldus MTH-04 containing pMSD2-As was obviously increased up to 45mM of NaAsO2. These vectors could be applied in genetic improvement of A. caldus as well as other bioleaching bacteria. Copyright © 2013 Elsevier GmbH. All rights reserved.

  16. 17 CFR 249.1100 - Form MSD, application for registration as a municipal securities dealer pursuant to rule 15Ba2-1...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form MSD, application for... of Municipal Securities Dealers § 249.1100 Form MSD, application for registration as a municipal... Exchange Act of 1934 (the “Act”), or to amend such application. Note: Copies of Form MSD have been filed...

  17. 12 CFR 10.2 - Filing requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....2 Filing requirements. (a) A national bank shall use Form MSD-4 (Uniform Application for Municipal... § 10.1(b). A national bank receiving a completed MSD-4 form from a person identified in § 10.1(b) must... securities principal or a municipal securities representative. (b) A national bank must submit Form MSD-5...

  18. Expert ratings of job demand and job control as predictors of injury and musculoskeletal disorder risk in a manufacturing cohort

    PubMed Central

    Cantley, Linda F; Tessier-Sherman, Baylah; Slade, Martin D; Galusha, Deron; Cullen, Mark R

    2016-01-01

    Objective To examine associations between workplace injury and musculoskeletal disorder (MSD) risk and expert ratings of job-level psychosocial demand and job control, adjusting for job-level physical demand. Methods Among a cohort of 9260 aluminium manufacturing workers in jobs for which expert ratings of job-level physical and psychological demand and control were obtained during the 2 years following rating obtainment, multivariate mixed effects models were used to estimate relative risk (RR) of minor injury and minor MSD, serious injury and MSD, minor MSD only and serious MSD only by tertile of demand and control, adjusting for physical demand as well as other recognised risk factors. Results Compared with workers in jobs rated as having low psychological demand, workers in jobs with high psychological demand had 49% greater risk of serious injury and serious MSD requiring medical treatment, work restrictions or lost work time (RR=1.49; 95% CI 1.10 to 2.01). Workers in jobs rated as having low control displayed increased risk for minor injury and minor MSD (RR=1.45; 95% CI 1.12 to 1.87) compared with those in jobs rated as having high control. Conclusions Using expert ratings of job-level exposures, this study provides evidence that psychological job demand and job control contribute independently to injury and MSD risk in a blue-collar manufacturing cohort, and emphasises the importance of monitoring psychosocial workplace exposures in addition to physical workplace exposures to promote worker health and safety. PMID:26163544

  19. 78 FR 36605 - Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ..., Washington, DC 20549-0213. Extension: Rule 15Ba2-1 and Form MSD. SEC File No. 270-0088, OMB Control No. 3235... existing collection of information provided for in Rule 15Ba2-1 (17 CFR 240.15Ba2-1) and Form MSD (17 CFR... registration with the Commission by a bank municipal securities dealer must be filed on Form MSD. The...

  20. 75 FR 35853 - Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-23

    ..., Washington, DC 20549-0213. Extension: Rule 15Ba2-1 and Form MSD; SEC File No. 270-0088; OMB Control No. 3235... collection of information provided for in Rule 15Ba2-1 (17 CFR 240.15Ba2-1) and Form MSD (17 CFR 249.1100... bank municipal securities dealer must be filed on Form MSD. The Commission uses the information...

  1. Correctors of the Major Cystic Fibrosis Mutant Interact through Membrane-Spanning Domains.

    PubMed

    Laselva, Onofrio; Molinski, Steven; Casavola, Valeria; Bear, Christine E

    2018-06-01

    The most common cystic fibrosis causing mutation is deletion of phenylalanine at position 508 (F508del), a mutation that leads to protein misassembly with defective processing. Small molecule corrector compounds: VX-809 or Corr-4a (C4) partially restores processing of the major mutant. These two prototypical corrector compounds cause an additive effect on F508del/cystic fibrosis transmembrane conductance regulator (CFTR) processing, and hence were proposed to act through distinct mechanisms: VX-809 stabilizing the first membrane-spanning domain (MSD) 1, and C4 acting on the second half of the molecule [consisting of MSD2 and/or nucleotide binding domain (NBD) 2]. We confirmed the effect of VX-809 in enhancing the stability of MSD1 and showed that it also allosterically modulates MSD2 when coexpressed with MSD1. We showed for the first time that C4 stabilizes the second half of the CFTR protein through its action on MSD2. Given the allosteric effect of VX-809 on MSD2, we were prompted to test the hypothesis that the two correctors interact in the full-length mutant protein. We did see evidence supporting their interaction in the full-length F508del-CFTR protein bearing secondary mutations targeting domain:domain interfaces. Disruption of the MSD1:F508del-NBD1 interaction (R170G) prevented correction by both compounds, pointing to the importance of this interface in processing. On the other hand, stabilization of the MSD2:F508del-NBD1 interface (by introducing R1070W) led to a synergistic effect of the compound combination on the total abundance of both the immature and mature forms of the protein. Together, these findings suggest that the two correctors interact in stabilizing the complex of MSDs in F508del-CFTR. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  2. VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1

    PubMed Central

    Ren, Hong Yu; Grove, Diane E.; De La Rosa, Oxana; Houck, Scott A.; Sopha, Pattarawut; Van Goor, Fredrick; Hoffman, Beth J.; Cyr, Douglas M.

    2013-01-01

    Cystic fibrosis (CF) is a fatal genetic disorder associated with defective hydration of lung airways due to the loss of chloride transport through the CF transmembrane conductance regulator protein (CFTR). CFTR contains two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory domain, and its channel assembly requires multiple interdomain contacts. The most common CF-causing mutation, F508del, occurs in NBD1 and results in misfolding and premature degradation of F508del-CFTR. VX-809 is an investigational CFTR corrector that partially restores CFTR function in people who are homozygous for F508del-CFTR. To identify the folding defect(s) in F508del-CFTR that must be repaired to treat CF, we explored the mechanism of VX-809 action. VX-809 stabilized an N-terminal domain in CFTR that contains only MSD1 and efficaciously restored function to CFTR forms that have missense mutations in MSD1. The action of VX-809 on MSD1 appears to suppress folding defects in F508del-CFTR by enhancing interactions among the NBD1, MSD1, and MSD2 domains. The ability of VX-809 to correct F508del-CFTR is enhanced when combined with mutations that improve F508del-NBD1 interaction with MSD2. These data suggest that the use of VX-809 in combination with an additional CFTR corrector that suppresses folding defects downstream of MSD1 may further enhance CFTR function in people with F508del-CFTR. PMID:23924900

  3. VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1.

    PubMed

    Ren, Hong Yu; Grove, Diane E; De La Rosa, Oxana; Houck, Scott A; Sopha, Pattarawut; Van Goor, Fredrick; Hoffman, Beth J; Cyr, Douglas M

    2013-10-01

    Cystic fibrosis (CF) is a fatal genetic disorder associated with defective hydration of lung airways due to the loss of chloride transport through the CF transmembrane conductance regulator protein (CFTR). CFTR contains two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory domain, and its channel assembly requires multiple interdomain contacts. The most common CF-causing mutation, F508del, occurs in NBD1 and results in misfolding and premature degradation of F508del-CFTR. VX-809 is an investigational CFTR corrector that partially restores CFTR function in people who are homozygous for F508del-CFTR. To identify the folding defect(s) in F508del-CFTR that must be repaired to treat CF, we explored the mechanism of VX-809 action. VX-809 stabilized an N-terminal domain in CFTR that contains only MSD1 and efficaciously restored function to CFTR forms that have missense mutations in MSD1. The action of VX-809 on MSD1 appears to suppress folding defects in F508del-CFTR by enhancing interactions among the NBD1, MSD1, and MSD2 domains. The ability of VX-809 to correct F508del-CFTR is enhanced when combined with mutations that improve F508del-NBD1 interaction with MSD2. These data suggest that the use of VX-809 in combination with an additional CFTR corrector that suppresses folding defects downstream of MSD1 may further enhance CFTR function in people with F508del-CFTR.

  4. Biomarkers of systemic inflammation in farmers with musculoskeletal disorders; a plasma proteomic study.

    PubMed

    Ghafouri, Bijar; Carlsson, Anders; Holmberg, Sara; Thelin, Anders; Tagesson, Christer

    2016-05-10

    Farmers have an increased risk for musculoskeletal disorders (MSD) such as osteoarthritis of the hip, low back pain, and neck and upper limb complaints. The underlying mechanisms are not fully understood. Work-related exposures and inflammatory responses might be involved. Our objective was to identify plasma proteins that differentiated farmers with MSD from rural referents. Plasma samples from 13 farmers with MSD and rural referents were included in the investigation. Gel based proteomics was used for protein analysis and proteins that differed significantly between the groups were identified by mass spectrometry. In total, 15 proteins differed significantly between the groups. The levels of leucine-rich alpha-2-glycoprotein, haptoglobin, complement factor B, serotransferrin, one isoform of kininogen, one isoform of alpha-1-antitrypsin, and two isoforms of hemopexin were higher in farmers with MSD than in referents. On the other hand, the levels of alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, vitamin D- binding protein, apolipoprotein A1, antithrombin, one isoform of kininogen, and one isoform of alpha-1-antitrypsin were lower in farmers than in referents. Many of the identified proteins are known to be involved in inflammation. Farmers with MSD had altered plasma levels of protein biomarkers compared to the referents, indicating that farmers with MSD may be subject to a more systemic inflammation. It is possible that the identified differences of proteins may give clues to the biochemical changes occurring during the development and progression of MSD in farmers, and that one or several of these protein biomarkers might eventually be used to identify and prevent work-related MSD.

  5. Association of TNF-α polymorphism rs1800629 with multisomatoform disorder in a group of German patients and healthy controls: an explorative study.

    PubMed

    Harms, Katharina C; Kapitza, Karl P; Pahl, Lisa; Tran, Anh-Thu; Volkmann, Lilly; Buers, Dennis; Karst, Matthias; Stuhrmann, Manfred; Bernateck, Michael

    2013-02-01

    The etiology of multisomatoform disorder (MSD) is still largely unknown, but genetic factors seem to have an influence on pathogenesis. Pain is a major symptom of MSD and polymorphisms of different proinflammatory cytokines have been found associated with pain in former studies. Therefore, we presumed that cytokine polymorphisms could also be associated with MSD. Groups of 148 MSD patients with pain as the leading clinical symptom and 149 age and gender matched healthy controls participated in this study. Nine cytokine polymorphisms were genotyped and statistically analyzed for associations with MSD. Allelic and genotypic associations were found for rs16944 (interleukin 1β), rs1800629 (tumor necrosis factor) and rs909253 (lymphotoxin α). After correcting for multiple testing, the association of rs1800629 with MSD remained significant. The rare A-allele was correlated with MSD (p=0.007). Since the common G-allele of rs1800629 (TNFα) occurs much more often in the control group than in the MSD group it is assumed to be protective. Being carrier of the A-allele seems to be a risk factor for MSD. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Expert ratings of job demand and job control as predictors of injury and musculoskeletal disorder risk in a manufacturing cohort.

    PubMed

    Cantley, Linda F; Tessier-Sherman, Baylah; Slade, Martin D; Galusha, Deron; Cullen, Mark R

    2016-04-01

    To examine associations between workplace injury and musculoskeletal disorder (MSD) risk and expert ratings of job-level psychosocial demand and job control, adjusting for job-level physical demand. Among a cohort of 9260 aluminium manufacturing workers in jobs for which expert ratings of job-level physical and psychological demand and control were obtained during the 2 years following rating obtainment, multivariate mixed effects models were used to estimate relative risk (RR) of minor injury and minor MSD, serious injury and MSD, minor MSD only and serious MSD only by tertile of demand and control, adjusting for physical demand as well as other recognised risk factors. Compared with workers in jobs rated as having low psychological demand, workers in jobs with high psychological demand had 49% greater risk of serious injury and serious MSD requiring medical treatment, work restrictions or lost work time (RR=1.49; 95% CI 1.10 to 2.01). Workers in jobs rated as having low control displayed increased risk for minor injury and minor MSD (RR=1.45; 95% CI 1.12 to 1.87) compared with those in jobs rated as having high control. Using expert ratings of job-level exposures, this study provides evidence that psychological job demand and job control contribute independently to injury and MSD risk in a blue-collar manufacturing cohort, and emphasises the importance of monitoring psychosocial workplace exposures in addition to physical workplace exposures to promote worker health and safety. 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/

  7. The neuroprotective effect of modified "Shengyu" decoction is mediated through an anti-inflammatory mechanism in the rat after traumatic brain injury.

    PubMed

    Zhao, Guang-Wei; Wang, Yong; Li, Yong-Cai; Jiang, Zheng-Lin; Sun, Li; Xi, Xin; He, Peng; Wang, Guo-Hua; Xu, Shi-Hui; Ma, Dong-Ming; Ke, Kai-Fu

    2014-01-01

    "Shengyu" decoction, a traditional Chinese medicine, has been used to treat diseases with deficit in "qi" and "blood" induced frequently by profound loss of blood or by long sores with heavy pus, in which a potential anti-inflammatory effect is implied. The modified "Shengyu" decoction (MSD) used in the present study was designed on the basis of the "Shengyu" decoction, additional four herbs were added in. Many ingredients in these herbs have been demonstrated to be anti-inflammatory and thus MSD may be used for the treatment of traumatic brain injury (TBI). To evaluate the neuroprotective effect and the underlying mechanisms of MSD on the rat brain after TBI. TBI was induced in the right cerebral cortex of male adult rats using Feeney's weight-drop method. The rats were administered a gavage of MSD (0.5, 1.0 or 2.0 ml/200 g) 6h after TBI. The neurological functions, brain water content, contusion volume, and neuron loss were determined. The levels of TNF-α, IL-1β, IL-6, and IL-10 and the number of GFAP- and Iba1-positive cells in the brain ipsilateral to TBI were also measured. Moreover, the influence of MSD on these variables was observed at the same time. The neurological deficits, brain water content, and neuron loss were significantly reduced after 1.0 or 2.0 ml/200 g of MSD treatment but not after 0.5 ml/200 g. In addition, treatment with MSD (1.0 ml/200 g) significantly increased the level of IL-10 and reduced the level of TNF-α and IL-1β and the number of GFAP- and Iba1-positive cells after TBI. However, the contusion volume of brain tissue and the expression of IL-6 were not significantly changed. MSD may be a potential therapeutic for the treatment of TBI because MSD alleviated secondary brain injury induced by TBI. In addition, MSD inhibited the inflammatory response through reducing the expression of inflammatory cytokines and the activation of microglial cells and astrocytes in the brain tissue of rats after TBI. Therefore, a potential anti-inflammatory mechanism of the "Shengyu" decoction was confirmed, which may be one of the main reasons of "Shengyu" decoction used to treat diseases with obvious inflammatory responses. © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Haploidentical and Matched Sibling Donor Hematopoietic Cell Transplantation for Patients with HLA-Homozygous Haplotypes.

    PubMed

    Kanda, Junya; Ikegame, Kazuhiro; Fuji, Shigeo; Kurokawa, Mineo; Kanamori, Heiwa; Fukuda, Takahiro; Ohashi, Kazuteru; Ishikawa, Jun; Ogawa, Hiroyasu; Inoue, Masami; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu

    2016-11-01

    More than 1% of the Japanese population has HLA-homozygous haplotypes. For patients with such haplotypes, HLA-haploidentical family members who have no HLA mismatch in the graft-versus-host direction are readily available donor candidates for hematopoietic cell transplantation (HCT). In this study, the outcomes of patients with homozygous HLA-A, -B, and -DRB1 antigens who received HCT without T cell depletion from a haploidentical related donor with mismatches in the host-versus-graft direction only (hetero-to-homo, n = 78) or from an HLA-matched sibling donor (MSD) (MSD-homo, n = 153) were compared with those in patients with heterozygous haplotypes who received HCT from an MSD (MSD-hetero, n = 7242). Transplant outcomes in the hetero-to-homo group were similar to those in the MSD-hetero group regarding neutrophil engraftment, grades III to IV acute graft-versus-host disease (aGVHD), nonrelapse mortality (NRM), relapse, and overall survival. On the other hand, the incidences of severe aGVHD and NRM in the MSD-homo group were significantly lower than those in the MSD-hetero group (grades III to IV aGVHD: aHR .50, P = .034; NRM: aHR .48, P = .004). In conclusion, patients with HLA-homozygous haplotypes achieved lower GVHD and NRM rates for MSD transplantation than those with HLA-heterozygous haplotypes. When an MSD or an appropriate alternative donor is not available for patients with HLA-homozygous haplotypes who need immediate transplantation, transplantation from a haploidentical donor without T cell depletion is a viable option, given the comparable transplant outcomes for hetero-to-homo HCT and MSD-hetero HCT. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Comparison of measured and estimated maximum skin doses during CT fluoroscopy lung biopsies.

    PubMed

    Zanca, F; Jacobs, A; Crijns, W; De Wever, W

    2014-07-01

    To measure patient-specific maximum skin dose (MSD) associated with CT fluoroscopy (CTF) lung biopsies and to compare measured MSD with the MSD estimated from phantom measurements, as well as with the CTDIvol of patient examinations. Data from 50 patients with lung lesions who underwent a CT fluoroscopy-guided biopsy were collected. The CT protocol consisted of a low-kilovoltage (80 kV) protocol used in combination with an algorithm for dose reduction to the radiology staff during the interventional procedure, HandCare (HC). MSD was assessed during each intervention using EBT2 gafchromic films positioned on patient skin. Lesion size, position, total fluoroscopy time, and patient-effective diameter were registered for each patient. Dose rates were also estimated at the surface of a normal-size anthropomorphic thorax phantom using a 10 cm pencil ionization chamber placed at every 30°, for a full rotation, with and without HC. Measured MSD was compared with MSD values estimated from the phantom measurements and with the cumulative CTDIvol of the procedure. The median measured MSD was 141 mGy (range 38-410 mGy) while the median cumulative CTDIvol was 72 mGy (range 24-262 mGy). The ratio between the MSD estimated from phantom measurements and the measured MSD was 0.87 (range 0.12-4.1) on average. In 72% of cases the estimated MSD underestimated the measured MSD, while in 28% of the cases it overestimated it. The same trend was observed for the ratio of cumulative CTDIvol and measured MSD. No trend was observed as a function of patient size. On average, estimated MSD from dose rate measurements on phantom as well as from CTDIvol of patient examinations underestimates the measured value of MSD. This can be attributed to deviations of the patient's body habitus from the standard phantom size and to patient positioning in the gantry during the procedure.

  10. The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation

    PubMed Central

    Hori, Akiko; Morand, Agathe; Ikebe, Chiho; Frith, David; Snijders, Ambrosius P.; Toda, Takashi

    2015-01-01

    The centrosome plays a pivotal role in a wide range of cellular processes and its dysfunction is causally linked to many human diseases including cancer and developmental and neurological disorders. This organelle contains more than one hundred components, and yet many of them remain uncharacterised. Here we identified a novel centrosome protein Wdr8, based upon the structural conservation of the fission yeast counterpart. We showed that Wdr8 constitutively localises to the centrosome and super resolution microscopy uncovered that this protein is enriched at the proximal end of the mother centriole. Furthermore, we identified hMsd1/SSX2IP, a conserved spindle anchoring protein, as one of Wdr8 interactors by mass spectrometry. Wdr8 formed a complex and partially colocalised with hMsd1/SSX2IP. Intriguingly, knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. Indeed, Wdr8 depletion resulted in the reduced recruitment of hMsd1/SSX2IP to the mitotic centrosome, though the converse is not true. Together, we propose that the conserved Wdr8-hMsd1/SSX2IP complex plays a critical role in controlling proper spindle length and orientation. PMID:26545777

  11. Neural, Hormonal, and Cognitive Correlates of Metabolic Dysfunction and Emotional Reactivity.

    PubMed

    Wolf, Tovah; Tsenkova, Vera; Ryff, Carol D; Davidson, Richard J; Willette, Auriel A

    2018-06-01

    Prediabetes and type 2 diabetes (i.e., hyperglycemia) are characterized by insulin resistance. These problems with energy metabolism may exacerbate emotional reactivity to negatively valenced stimuli and related phenomena such as predisposition toward negative affect, as well as cognitive deficits. Higher emotional reactivity is seen with hyperglycemia and insulin resistance. However, it is largely unknown how metabolic dysfunction correlates with related neural, hormonal, and cognitive outcomes. Among 331 adults from the Midlife in the United States study, eye-blink response (EBR) we cross sectionally examined to gauge reactivity to negative, positive, or neutrally valenced pictures from international affect picture system stimuli proximal to an acoustic startle probe. Increased EBR to negative stimuli was considered an index of stress reactivity. Frontal alpha asymmetry, a biomarker of negative affect predisposition, was determined using resting electroencephalography. Baseline urinary cortisol output was collected. Cognitive performance was gauged using the Brief Test of Adult Cognition by telephone. Fasting glucose and insulin characterized hyperglycemia or the homeostatic model assessment of insulin resistance. Higher homeostatic model assessment of insulin resistance corresponded to an increased startle response, measured by EBR magnitude, for negative versus positive stimuli (R = 0.218, F(1,457) = 5.48, p = .020, euglycemia: M(SD) = .092(.776), hyperglycemia: M(SD) = .120(.881)). Participants with hyperglycemia versus euglycemia showed greater right frontal alpha asymmetry (F(1,307) = 6.62, p = .011, euglycemia: M(SD) = .018(.167), hyperglycemia: M(SD) = -.029(.160)), and worse Brief Test of Adult Cognition by telephone arithmetic performance (F(1,284) = 4.25, p = .040, euglycemia: M(SD) = 2.390(1.526), hyperglycemia: M(SD) = 1.920(1.462)). Baseline urinary cortisol (log10 μg/12 hours) was also dysregulated in individuals with hyperglycemia (F(1,324) = 5.09, p = .025, euglycemia: M(SD) = 1.052 ± .332, hyperglycemia: M(SD) = .961 (.362)). These results suggest that dysmetabolism is associated with increased emotional reactivity, predisposition toward negative affect, and specific cognitive deficits.

  12. Prevalence of musculoskeletal disorders among school teachers from urban and rural areas in Chuquisaca, Bolivia: a cross-sectional study.

    PubMed

    Solis-Soto, María Teresa; Schön, Anabel; Solis-Soto, Angel; Parra, Manuel; Radon, Katja

    2017-10-27

    Musculoskeletal disorders (MSD) are important health problems in working populations. The study aimed to determine the prevalence of MSD among school teachers from urban and rural areas in Chuquisaca, Bolivia. A cross-sectional study was conducted in 60 randomly selected schools. In total, 1062 teachers were invited to participate (response 58%). The Spanish version of the Standardized Nordic questionnaire was used assessing the 12-months and 7-days prevalence of MSD as well as the 12-months prevalence of work limiting pain. Prevalence were calculated for the different parts of the body; as summary measures, MSD in any part of the body and in ≥3 parts of the body were assessed. Crude and adjusted odds ratios with 95% confidence intervals were calculated using logistic regression models adjusting for age, sex, teaching level and school type. Prevalence of MSD in any part of the body was 86% during the last 12 months, 63% during the last 7 days and 15% for work limiting pain. MSD was most common in the neck (12-months prevalence 47%) and least common in the wrist/hands (26%). In the adjusted model, teachers working in rural areas presented significantly higher odds than teachers from urban schools for work-limiting pain during the last 12-months considering any part of the body (aOR 2.2; 95% CI 1.1-4.1), and for ≥3 parts of the body (aOR 3.7; 95% CI 1.3-10.6). The prevalence of MSD is high in School teachers, even more in teachers working in rural areas. It is needed to identify risk factors for MSD in teachers in order to propose appropriate strategies to control and reduce it.

  13. An approach to the optical MSD adder

    NASA Astrophysics Data System (ADS)

    Takahashi, Hideya; Matsushita, Kenji; Shimizu, Eiji

    1990-07-01

    The intrinsic parallelism of optical elements for computation is presently taken fuller advantage of than heretofore possible through an optical implementation of the modified signed digit (MSD) number system, which yields carry-free addition and subtraction. In the present optical implementation of the MSD system, optical phase data are used to preclude negative value representation. Attention is given to an MSD adder array for addition operations on two n-digit trinary numbers; the output is composed of n + 1 trinary digits.

  14. Effects of Mentoring Speed Dating as an Innovative Matching Tool in Undergraduate Medical Education: A Mixed Methods Study.

    PubMed

    Guse, Jennifer; Schweigert, Eva; Kulms, Gerhild; Heinen, Ines; Martens, Claudia; Guse, Andreas H

    2016-01-01

    Choosing the right mentor is crucial for effective mentorship. Yet, many medical students have difficulties finding a suitable mentor. Thus we developed mentoring speed dating (MSD) as a promising matching tool to connect students and faculty mentors successfully. The purpose of this study was to explore mentees' and mentors' experience with MSD and investigate the impact of MSD on the perceived mentorship quality and continuance of the mentoring relationship. The authors completed a mixed methods study at the University Medical Center Hamburg-Eppendorf, Germany, between June 2011 and March 2014. They conducted four focus groups with mentees and mentors who participated in a mentoring speed dating event and analyzed transcripts using conventional content analysis with inductive categorizing. In addition, three mentoring cohorts (two matched via MSD, one matched via conventional online profiles) were surveyed on mentorship satisfaction and the 1-year continuance of their mentorship was monitored. Fifteen mentees and fifteen mentors participated in the focus groups. The authors identified several themes such as short and long term benefits of MSD and fulfillment of expectations. Benefits included finding out about the personal connection, matching expectations, providing an efficient overview of candidates. The survey was completed by 93 students (n = 29 without MSD; n = 64 with MSD). Independent t-tests and multivariate analysis of variance were used to analyze the impact of MSD on student's mentorship satisfaction. There were significant differences in responses to the items "Commitment of mentor" (p = .019) and "Constructive feedback" (p = .038) among the students who attended MSD and the students without MSD. After one year far more mentoring relationships existed among those mentees who participated in MSD in comparison to the "no MSD group". MSD is a valuable matching tool with beneficial effects on the mentorship quality. It enhances essential factors in the mentoring relationship such as commitment and satisfaction.

  15. Effects of Mentoring Speed Dating as an Innovative Matching Tool in Undergraduate Medical Education: A Mixed Methods Study

    PubMed Central

    Guse, Jennifer; Schweigert, Eva; Kulms, Gerhild; Heinen, Ines; Martens, Claudia; Guse, Andreas H.

    2016-01-01

    Objectives Choosing the right mentor is crucial for effective mentorship. Yet, many medical students have difficulties finding a suitable mentor. Thus we developed mentoring speed dating (MSD) as a promising matching tool to connect students and faculty mentors successfully. The purpose of this study was to explore mentees’ and mentors’ experience with MSD and investigate the impact of MSD on the perceived mentorship quality and continuance of the mentoring relationship. Methods The authors completed a mixed methods study at the University Medical Center Hamburg-Eppendorf, Germany, between June 2011 and March 2014. They conducted four focus groups with mentees and mentors who participated in a mentoring speed dating event and analyzed transcripts using conventional content analysis with inductive categorizing. In addition, three mentoring cohorts (two matched via MSD, one matched via conventional online profiles) were surveyed on mentorship satisfaction and the 1-year continuance of their mentorship was monitored. Fifteen mentees and fifteen mentors participated in the focus groups. The authors identified several themes such as short and long term benefits of MSD and fulfillment of expectations. Benefits included finding out about the personal connection, matching expectations, providing an efficient overview of candidates. The survey was completed by 93 students (n = 29 without MSD; n = 64 with MSD). Independent t-tests and multivariate analysis of variance were used to analyze the impact of MSD on student’s mentorship satisfaction. Results There were significant differences in responses to the items “Commitment of mentor” (p = .019) and “Constructive feedback” (p = .038) among the students who attended MSD and the students without MSD. After one year far more mentoring relationships existed among those mentees who participated in MSD in comparison to the “no MSD group”. Conclusion MSD is a valuable matching tool with beneficial effects on the mentorship quality. It enhances essential factors in the mentoring relationship such as commitment and satisfaction. PMID:26859845

  16. Musculoskeletal disorders and stress among footwear industry workers.

    PubMed

    de Almeida, Larissa Brentini; Vieira, Edgar Ramos; Zaia, José Eduardo; de Oliveira Santos, Branca Maria; Lourenço, Américo Riccardi Vaccari; Quemelo, Paulo Roberto Veiga

    2017-01-01

    Manufacturing footwear requires intense manual labor and high repetitions with low variability in function that may lead to musculoskeletal disorders (MSD) symptoms and psychological stress. To evaluate a potential association between musculoskeletal disorders (MSD) and perceived stress among footwear industry workers. The Nordic General Questionnaire (NGQ) and the Perceived Stress Scale (PSS-10) were completed by 357 footwear industry workers. The association between MSD and perceived stress was evaluated using the Chi-Square test and Odds Ratios along with their 95% Confidence Interval (95% CI) were calculated. The twelve-month prevalence of MSD symptoms among the respondents was 66% (n = 236) and the symptoms were significantly associated with perceived stress (p = 0.002, OR: 10, 95% CI: 1.7 to 60.6). The seven-day prevalence of MSD symptoms was 33% and the symptoms were also significantly associated with perceived stress (p = 0.001, OR: 2.7, 95% CI:0.8 to 9.3). The association between perceived stress and MSD symptoms indicates a strong association between MSD symptoms and perceived stress levels. Considering that these problems are important determinants of worker's health, a combined approach to reduce both stress and MSD symptoms is necessary for prevention and health promotion in the footwear industry.

  17. Phenotypic dysregulation of microglial activation in young offspring rats with maternal sleep deprivation-induced cognitive impairment

    PubMed Central

    Zhao, Qiuying; Xie, Xiaofang; Fan, Yonghua; Zhang, Jinqiang; Jiang, Wei; Wu, Xiaohui; Yan, Shuo; Chen, Yubo; Peng, Cheng; You, Zili

    2015-01-01

    Despite the potential adverse effects of maternal sleep deprivation (MSD) on physiological and behavioral aspects of offspring, the mechanisms remain poorly understood. The present study was intended to investigate the roles of microglia on neurodevelopment and cognition in young offspring rats with prenatal sleep deprivation. Pregnant Wistar rats received 72 h sleep deprivation in the last trimester of gestation, and their prepuberty male offspring were given the intraperitoneal injection with or without minocycline. The results showed the number of Iba1+ microglia increased, that of hippocampal neurogenesis decreased, and the hippocampus-dependent spatial learning and memory were impaired in MSD offspring. The classical microglial activation markers (M1 phenotype) IL-1β, IL-6, TNF-α, CD68 and iNOS were increased, while the alternative microglial activation markers (M2 phenotype) Arg1, Ym1, IL-4, IL-10 and CD206 were reduced in hippocampus of MSD offspring. After minocycline administration, the MSD offspring showed improvement in MWM behaviors and increase in BrdU+/DCX+ cells. Minocycline reduced Iba1+ cells, suppressed the production of pro-inflammatory molecules, and reversed the reduction of M2 microglial markers in the MSD prepuberty offspring. These results indicate that dysregulation in microglial pro- and anti-inflammatory activation is involved in MSD-induced inhibition of neurogenesis and impairment of spatial learning and memory. PMID:25830666

  18. Residues in the membrane-spanning domain core modulate conformation and fusogenicity of the HIV-1 envelope glycoprotein

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

    Shang Liang; Hunter, Eric, E-mail: eric.hunter2@emory.ed

    2010-09-01

    The membrane-spanning domain (MSD) of human immunodeficiency virus type I (HIV-1) envelope glycoprotein (Env) is critical for its biological activity. Initial studies have defined an almost invariant 'core' structure in the MSD and demonstrated that it is crucial for anchoring Env in the membrane and virus entry. We show here that amino acid substitutions in the MSD 'core' do not influence specific virus-cell attachment, nor CD4 receptor and CXCR4 coreceptor recognition by Env. However, substitutions within the MSD 'core' delayed the kinetics and reduced the efficiency of cell-cell fusion mediated by Env. Although we observed no evidence that membrane fusionmore » mediated by the MSD core mutants was arrested at a hemifusion stage, impaired Env fusogenicity was correlated with minor conformational changes in the V2, C1, and C5 regions in gp120 and the immunodominant loop in gp41. These changes could delay initiation of the conformational changes required in the fusion process.« less

  19. Interleukin-18 and CD30 serum levels in patients with moderate-severe depression.

    PubMed Central

    Merendino, Rosaria Alba; Di Rosa, Antonio Enrico; Di Pasquale, Giuseppe; Minciullo, Paola Lucia; Mangraviti, Carmela; Costantino, Antonella; Ruello, Antonella; Gangemi, Sebastiano

    2002-01-01

    Interleukin-18 (IL-18), a pro-inflammatory cytokine that plays an important role in the T-cell-helper type 1 response, is a new member of the family of cytokines produced in the brain. CD30 is a marker of T-cell-helper type 2 lymphocytes. We evaluated IL-18 and CD30 serum levels in 10 patients affected by moderate-severe depression (MSD). We demonstrated for the first time that serum IL-18 levels of MSD patients were significantly higher than those of healthy donors. On the contrary, no significant difference was found between serum CD30 levels of MSD patients compared with those of healthy donors. These data strengthen the hypothesis that MSD disease is associated with an inflammatory response, mainly T-cell-helper type 1, and suggest an important role for IL-18 in the pathophysiology of MSD. PMID:12396479

  20. HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA.

    PubMed

    He, Tian-Sheng; Chen, Tian; Wang, Dan-Dan; Xu, Liang-Guo

    2018-06-15

    Mitochondrial anti‑viral signaling protein (VISA), additionally termed MAVS, IPS‑1 and Cardif, is located at the outer membrane of mitochondria and is an essential adaptor in the Rig‑like receptor (RLRs) signaling pathway. Upon viral infection, activated RLRs interact with VISA on mitochondria, forming a RLR‑VISA platform, leading to the recruitment of different TRAF family members, including TRAF3, TRAF2 and TRAF6. This results in the phosphorylation and nuclear translocation of interferon regulatory factors 3 and 7 (IRF3/IRF7) by TANK binding kinase 1 (TBK1) and/or IKKε, as well as activation of NF‑κB, to induce type I interferons (IFNs) and pro‑inflammatory cytokines. It remains to be elucidated how VISA functions as a scaffold for protein complex assembly in mitochondria to regulate RLR‑VISA antiviral signaling. In the present study, it was demonstrated that HAUS augmin like complex subunit 8 (HAUS8) augments the RLR‑VISA‑dependent antiviral signaling pathway by targeting the VISA complex. Co‑immunoprecipitation verified that HAUS8 was associated with VISA and the VISA signaling complex components retinoic acid‑inducible gene I (RIG‑I) and TBK1 when the RLR‑VISA signaling pathway was activated. The data demonstrated that overexpression of HAUS8 significantly promoted the activity of the transcription factors NF‑κB, IRF3 and the IFN‑β promoter induced by Sendai virus‑mediated RLR‑VISA signaling. HAUS8 increased the polyubiquitination of VISA, RIG‑I and TBK1. Knockdown of HAUS8 inhibited the activation of the transcription factors IRF‑3, NF‑κB and the IFN‑β promoter triggered by Sendai virus. Collectively, these results demonstrated that HAUS8 may function as a positive regulator of RLR‑VISA dependent antiviral signaling by targeting the VISA complex, providing a novel regulatory mechanism of antiviral responses.

  1. Low back pain and widespread pain predict sickness absence among industrial workers

    PubMed Central

    Morken, Tone; Riise, Trond; Moen, Bente; Hauge, Signe HV; Holien, Solrun; Langedrag, Anne; Pedersen, Svein; Saue, Inger Lise L; Seljebø, Guri M; Thoppil, Varughese

    2003-01-01

    Background The prevalence of musculoskeletal disorders (MSD) in the aluminium industry is high, and there is a considerable work-related fraction. More knowledge about the predictors of sickness absence from MSD in this industry will be valuable in determining strategies for prevention. The aim of this study was to analyse the relative impact of body parts, psychosocial and individual factors as predictors for short- and long-term sickness absence from MSD among industrial workers. Methods A follow-up study was conducted among all the workers at eight aluminium plants in Norway. A questionnaire was completed by 5654 workers at baseline in 1998. A total of 3320 of these participated in the follow-up study in 2000. Cox regression analysis was applied to investigate the relative impact of MSD in various parts of the body and of psychosocial and individual factors reported in 1998 on short-term and long-term sickness absence from MSD reported in 2000. Results MSD accounted for 45% of all working days lost the year prior to follow-up in 2000. Blue-collar workers had significantly higher risk than white-collar workers for both short- and long-term sickness absence from MSD (long-term sickness absence: RR = 3.04, 95% CI 2.08–4.45). Widespread and low back pain in 1998 significantly predicted both short- and long-term sickness absence in 2000. In addition, shoulder pain predicted long-term sickness absence. Low social support predicted short-term sickness absence (RR = 1.28, 95% CI 1.11–1.49). Conclusions Reducing sickness absence from MSD among industrial workers requires focusing on the working conditions of blue-collar workers and risk factors for low back pain and widespread pain. Increasing social support in the work environment may have effects in reducing short-term sickness absence from MSD. PMID:12956891

  2. Mortality with musculoskeletal disorders as underlying cause in Sweden 1997-2013: a time trend aggregate level study.

    PubMed

    Kiadaliri, Aliasghar A; Englund, Martin

    2016-04-14

    The aim was to assess time trend of mortality with musculoskeletal disorders (MSD) as underlying cause of death in Sweden from 1997 to 2013. We obtained data on MSD as underlying cause of death across age and sex groups from the National Board of Health and Welfare's Cause of Death Register. Age-standardized mortality rates per million population for all MSD, its six major subgroups, and all other ICD-10 (International Classification of Disease) chapters were calculated. We computed the average annual percent change (AAPC) in the mortality rates across age/sex groups using joinpoint regression analysis by fitting a regression line to the natural logarithm of the age-standardized mortality rates and calendar year as a predictor. There were a total of 7 976 deaths (0.5% of all causes deaths) with MSD as the underlying cause of death (32.5% of these deaths caused by rheumatoid arthritis [RA]). The overall age-standardized mortality rates (95% CI) were 16.0 (15.4 to 16.7) and 24.9 (24.1 to 25.7) per million among men and women, respectively (women/men rate ratio 1.55; 95%CI 1.47 to 1.63). On average, mortality rate declined by 2.3% per year and only circulatory system mortality had a more favourable decline than mortality with MSD as underlying cause. Among MSD the highest decline was observed in RA (3.7% per year) during study period. Across age groups, while there were generally stable or declining trends, spondylopathies and osteoporosis mortality among people ≥ 75 years increased by 2 and 1.5% per year, respectively. In overall, mortality with MSD as underlying cause has declined in Sweden over last two decades, with the highest decline for RA. However, there are variations across MSD subgroups which warrants further investigations.

  3. Berkeley Lab - Materials Sciences Division

    Science.gov Websites

    ? Click Here! Resources for MSD Safety MSD Safety MSD's Integrated Safety Management Plan [PDF] Safety culture and policies at MSD MSD0010: Integrated Safety Management: Principles and Case Studies Calendar for MSD classes on Integrated Safety Management MSD0015 Handout - Waste Briefing Document [PDF] Waste

  4. 75 FR 53987 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-02

    ..., Washington, DC 20549-0213. Extension: Rule 15Ba2-1 and Form MSD; SEC File No. 270-0088; OMB Control No. 3235... by a bank municipal securities dealer must be filed on Form MSD (17 CFR 249.1100). The Commission uses the information contained in Form MSD to determine whether bank municipal securities dealers meet...

  5. Common mental and musculoskeletal disorders as predictors of disability retirement among Finns.

    PubMed

    Kaila-Kangas, Leena; Haukka, Eija; Miranda, Helena; Kivekäs, Teija; Ahola, Kirsi; Luukkonen, Ritva; Shiri, Rahman; Kääriä, Sanna; Heliövaara, Markku; Leino-Arjas, Päivi

    2014-08-01

    The contribution of common mental disorders (CMD) co-occurring with chronic musculoskeletal disorders (MSD) to disability retirement is not known. A nationally representative sample (the Health 2000 survey) comprised 3943 occupationally active Finns aged 30-63. MSD and other chronic disorders were assessed by a physician in a standardized clinical examination, and CMD using the Composite International Diagnostic Interview. Disability pension data for 2000-2011 was retrieved from national pension records. Cox regression was used with censoring for death and pension other than that for disability. Covariate information was based on an interview. The baseline prevalence of CMD was 9.4% and of MSD 31.1%. CMD co-occurred with MSD in 3.3% of participants. The risks inflicted by CMD and MSD were additive. Thirty-eight per cent of the co-morbid subjects, 18% of those with CMD and 19% of those with MSD retired prematurely during the average follow-up of 8.6 years. Compared with those with neither type of disorder, the hazard ratio (HR) for disability pension was 2.4 (95% CI 1.7-2.7) for CMD only, 2.2 (1.8-2.7) for MSD only, and 4.1 (2.9-5.7) for the occurrence of both, allowing for age, gender, other chronic disorders, working conditions, and socio-economic and lifestyle factors. No synergistic or antagonistic interactive effects were observed. The determinants were measured only once and we had no information on incident disorders during the follow-up. It is important to identify subjects with both mental and musculoskeletal complaints in order to efficiently support their work ability. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Mapping Global Potential Risk of Mango Sudden Decline Disease Caused by Ceratocystis fimbriata.

    PubMed

    Galdino, Tarcísio Visintin da Silva; Kumar, Sunil; Oliveira, Leonardo S S; Alfenas, Acelino C; Neven, Lisa G; Al-Sadi, Abdullah M; Picanço, Marcelo C

    2016-01-01

    The Mango Sudden Decline (MSD), also referred to as Mango Wilt, is an important disease of mango in Brazil, Oman and Pakistan. This fungus is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Stebbing), by infected plant material, and the infested soils where it is able to survive for long periods. The best way to avoid losses due to MSD is to prevent its establishment in mango production areas. Our objectives in this study were to: (1) predict the global potential distribution of MSD, (2) identify the mango growing areas that are under potential risk of MSD establishment, and (3) identify climatic factors associated with MSD distribution. Occurrence records were collected from Brazil, Oman and Pakistan where the disease is currently known to occur in mango. We used the correlative maximum entropy based model (MaxEnt) algorithm to assess the global potential distribution of MSD. The MaxEnt model predicted suitable areas in countries where the disease does not already occur in mango, but where mango is grown. Among these areas are the largest mango producers in the world including India, China, Thailand, Indonesia, and Mexico. The mean annual temperature, precipitation of coldest quarter, precipitation seasonality, and precipitation of driest month variables contributed most to the potential distribution of MSD disease. The mango bark beetle vector is known to occur beyond the locations where MSD currently exists and where the model predicted suitable areas, thus showing a high likelihood for disease establishment in areas predicted by our model. Our study is the first to map the potential risk of MSD establishment on a global scale. This information can be used in designing strategies to prevent introduction and establishment of MSD disease, and in preparation of efficient pest risk assessments and monitoring programs.

  7. Mapping Global Potential Risk of Mango Sudden Decline Disease Caused by Ceratocystis fimbriata

    PubMed Central

    Oliveira, Leonardo S. S.; Alfenas, Acelino C.; Neven, Lisa G.; Al-Sadi, Abdullah M.

    2016-01-01

    The Mango Sudden Decline (MSD), also referred to as Mango Wilt, is an important disease of mango in Brazil, Oman and Pakistan. This fungus is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Stebbing), by infected plant material, and the infested soils where it is able to survive for long periods. The best way to avoid losses due to MSD is to prevent its establishment in mango production areas. Our objectives in this study were to: (1) predict the global potential distribution of MSD, (2) identify the mango growing areas that are under potential risk of MSD establishment, and (3) identify climatic factors associated with MSD distribution. Occurrence records were collected from Brazil, Oman and Pakistan where the disease is currently known to occur in mango. We used the correlative maximum entropy based model (MaxEnt) algorithm to assess the global potential distribution of MSD. The MaxEnt model predicted suitable areas in countries where the disease does not already occur in mango, but where mango is grown. Among these areas are the largest mango producers in the world including India, China, Thailand, Indonesia, and Mexico. The mean annual temperature, precipitation of coldest quarter, precipitation seasonality, and precipitation of driest month variables contributed most to the potential distribution of MSD disease. The mango bark beetle vector is known to occur beyond the locations where MSD currently exists and where the model predicted suitable areas, thus showing a high likelihood for disease establishment in areas predicted by our model. Our study is the first to map the potential risk of MSD establishment on a global scale. This information can be used in designing strategies to prevent introduction and establishment of MSD disease, and in preparation of efficient pest risk assessments and monitoring programs. PMID:27415625

  8. Longitudinal relationship of work hours, mandatory overtime, and on-call to musculoskeletal problems in nurses.

    PubMed

    Trinkoff, Alison M; Le, Rong; Geiger-Brown, Jeanne; Lipscomb, Jane; Lang, Gary

    2006-11-01

    Nurses are at very high risk for work-related musculoskeletal injury/disorders (MSD) with low back pain/injury being the most frequently occurring MSD. Nurses are also likely to work extended schedules (long hours, on-call, mandatory overtime, working on days off). The purpose of this study was to examine the relationship of extended work schedules in nurses to MSD. Using a longitudinal, three wave survey of 2,617 registered nurses, Wave 1 work schedule data were related to neck, shoulder, and back (MSD) cases occurring in Waves 2 or 3. Schedule characteristics increasing MSD risk included 13+ hour/days, off-shifts, weekend work, work during time off (while sick, on days off, without breaks), and overtime/on-call. These increases in risk were not explained by psychological demands, but were largely explained by physical demands. Adverse schedules are significantly related to nurse MSD. Healthier schedules, less overtime, and reducing work on days off would minimize risk and recovery time. Copyright (c) 2006 Wiley-Liss, Inc.

  9. Anomalous diffusion of a probe in a bath of active granular chains

    NASA Astrophysics Data System (ADS)

    Jerez, Michael Jade Y.; Confesor, Mark Nolan P.; Carpio-Bernido, M. Victoria; Bernido, Christopher C.

    2017-08-01

    We investigate the dynamics of a passive probe particle in a bath of active granular chains (AGC). The bath and the probe are enclosed in an experimental compartment with a sinusoidal boundary to prevent AGC congestion along the boundary while connected to an electrodynamic shaker. Single AGC trajectory analysis reveals a persistent type of motion compared to a purely Brownian motion as seen in its mean squared displacement (MSD). It was found that at small concentration, Φ ≤ 0.44, the MSD exhibits two dynamical regimes characterized by two different scaling exponents. For small time scales, the dynamics is superdiffusive (1.32-1.63) with the MSD scaling exponent increasing monotonically with increasing AGC concentration. On the other hand, at long time, we recover the Brownian dynamics regime, MSD = DΔt, where the mobility D ∝ Φ. We quantify the probe dynamics at short time scale by modeling it as a fractional Brownian motion. The analytical form of the MSD agrees with experimental results.

  10. Evaporation Rates of Chemical Warfare Agents Using 5-CM Wind Tunnels I. CASARM Sulfur Mustard (HD) from Glass

    DTIC Science & Technology

    2008-10-01

    Blank CONTENTS 1. INTRODUCTION 9 2. EXPERIMENTAL PROCEDURES 9 2.1 Wind Tunnel 9 2.2 Agent 10 2.3 Gas Chromatography /Mass Spectrometry Detection 10...protective equipment. 2.3 Gas Chromatography /Mass Spectrometry Detection (GC/MSD) The GC/MSD analysis of the thermal desorption tubes was performed on a...coupled to thermal desorption tubes that were analyzed using gas chromatography /mass spectrometry detection (GC/MSD). Differences between the tunnels

  11. Effects of Modified Simiao Decoction on IL-1 β and TNF α Secretion in Monocytic THP-1 Cells with Monosodium Urate Crystals-Induced Inflammation.

    PubMed

    Liu, Ya-Fei; Tu, Sheng-Hao; Chen, Zhe; Wang, Yu; Hu, Yong-Hong; Dong, Hui

    2014-01-01

    Simiao pill, a Chinese herbal formula containing four herbs, has been used in the treatment of gouty arthritis for many years. The aim of this study was to explore the effects of modified Simiao decoction (MSD) on IL-1 β and TNF α secretion in monocytic THP-1 cells with monosodium urate (MSU) crystals-induced inflammation. The MSU crystals-induced inflammation model in THP-1 cells was successfully established by the stimulation of phorbol 12-myristate 13-acetate (PMA) and MSU crystals. Then, the MSD-derived serum or control serum extracted from rat was administered to different treatment groups. The morphology of MSU crystals and THP-1 cells was observed. IL-1 β and TNF α protein expression in supernatant of THP-1 cells were determined by ELISA. Our data demonstrated that MSU crystals induced time-dependent increase of IL-1 β and TNF α . Moreover, MSD significantly decreased IL-1 β release in THP-1 cells with MSU crystals-induced inflammation. These results suggest that MSD is promising in the treatment of MSU crystals-induced inflammation in THP-1 cells. MSD may act as an anti-IL-1 agent in treating gout. The underlying mechanism may be related to NALP3 inflammasome which needs to be validated in future studies.

  12. Effects of Modified Simiao Decoction on IL-1β and TNFα Secretion in Monocytic THP-1 Cells with Monosodium Urate Crystals-Induced Inflammation

    PubMed Central

    Liu, Ya-Fei; Tu, Sheng-Hao; Chen, Zhe; Wang, Yu; Hu, Yong-Hong; Dong, Hui

    2014-01-01

    Simiao pill, a Chinese herbal formula containing four herbs, has been used in the treatment of gouty arthritis for many years. The aim of this study was to explore the effects of modified Simiao decoction (MSD) on IL-1β and TNFα secretion in monocytic THP-1 cells with monosodium urate (MSU) crystals-induced inflammation. The MSU crystals-induced inflammation model in THP-1 cells was successfully established by the stimulation of phorbol 12-myristate 13-acetate (PMA) and MSU crystals. Then, the MSD-derived serum or control serum extracted from rat was administered to different treatment groups. The morphology of MSU crystals and THP-1 cells was observed. IL-1β and TNFα protein expression in supernatant of THP-1 cells were determined by ELISA. Our data demonstrated that MSU crystals induced time-dependent increase of IL-1β and TNFα. Moreover, MSD significantly decreased IL-1β release in THP-1 cells with MSU crystals-induced inflammation. These results suggest that MSD is promising in the treatment of MSU crystals-induced inflammation in THP-1 cells. MSD may act as an anti-IL-1 agent in treating gout. The underlying mechanism may be related to NALP3 inflammasome which needs to be validated in future studies. PMID:24999366

  13. Radiological analysis of minimal safe distance and optimal screw angle to avoid facet violation in open-door laminoplasty using precontoured plate.

    PubMed

    Min, Woo-Kie; Seo, Il; Na, Sang-Bong; Choi, Young-Seo; Choi, Ji-Yeon

    2017-01-01

    This study aimed to present radiologic analysis of minimal safe distance (MSD) and optimal screw angle (OSA) that enables to fix screws in a lateral mass safely without facet joint violation in open-door laminoplasty using a plate. A retrospective analysis was made of 22 patients (male: 17; female: 5), average age 62 years. Seventy-nine lateral mass screws were fixed among a total of 158 screws. MSD that doesn't allow 5-mm screws to violate a facet joint was measured for C3-C7 and a comparative analysis was performed. If the MSD is not secured, the OSA to be given to the cephalad direction is calculated to avoid violation of the facet joint. The screws violating inferior facet joints accounted for 34.1% of the screws fixed in inferior lateral mass. Joint surface to distal mini-screw distances were 3.18 ± 1.46 mm and 4.75 ± 1.71 mm in groups of facet joint violation and non-facet violation (FV), respectively ( p = 0.001). When 5-mm screws were inserted into a lateral mass, MSD was 4.39 ± 0.83 mm. The average MSD of C3, C4, and C5 was 4.05 ± 0.78 mm, 4.10 ± 0.70 mm, and 4.26 ± 0.74 mm, respectively. There was no significant differences among levels ( p > 0.05). The average MSD of C6 and C7 was 4.92 ± 0.81 mm and 4.80 ± 0.96 mm, respectively, showing significant differences from those of C3, C4, and C5 ( p < 0.05). If 6 mm of the MSD isn't secured, OSA showed in the cephalad direction of 11.5° for 5 mm and 22° for 4 mm approximately. We suggest that mini-screw on lateral mass can be fixed safely without FV, if they are fixed at MSD of 6 mm from a joint surface. Facet joint violation doesn't occur if an OSA is given in the cephalad direction in case of not enough MSD for mini-screws.

  14. Prevalence and Risk Factors Associated with Musculoskeletal Discomfort in Spay and Neuter Veterinarians.

    PubMed

    White, Sara C

    2013-02-04

    A cross-sectional study to investigate musculoskeletal discomfort (MSD) surveyed 219 veterinarians who currently or previously perform spays and neuters at least 4 hours per week. Participants were asked about the presence and severity of hand and body MSD during the previous month, whether MSD interfered with work or daily activities, whether they attributed their MSD to their spay/neuter work, and whether MSD had ever necessitated absence from work. The period prevalence of MSD was 99.1%, with 76.7% experiencing hand or wrist pain and 98.2% experiencing body pain. Hand discomfort was most commonly reported in the right thumb and/or thumb base (49.8%) and the right wrist (37.9%). Body discomfort was most commonly reported in the lower back (76.7%), shoulders (72.6%), and neck (71.7%). Increasing career length, increasing weekly hours in surgery and decreasing job satisfaction were the work-related factors with the greatest relative contribution accounting for variation in hand pain severity and total pain. Although 94.4% of respondents felt that posture during surgery is important, only 30.6% had received any instruction in posture and positioning for surgery. Future interventions should aim to optimize surgical efficiency, surgeon work schedules, and working environment. Analysis and intervention studies are required to determine further causes of MSD in these veterinarians and develop interventions to prevent MSD.

  15. Sexual dysfunction among Chinese married men aged 30-60 years: a population-based study in Hong Kong.

    PubMed

    Zhang, Huiping; Yip, Andrew W C; Fan, Susan; Yip, Paul S F

    2013-02-01

    To estimate the prevalence of, and risk factors associated with, sexual dysfunction among Hong Kong Chinese married men aged 30-60 years. The present study was a part of the Ninth Knowledge, Attitude, and Practice survey conducted in 2007 by the Family Planning Association of Hong Kong. The data set consisted of 728 face-to-face interviews with Hong Kong Chinese married men aged 30-60 years living in the community. The classification of sexual dysfunction in the "Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition" was used to measure male sexual dysfunction (MSD). Regarding MSD prevalence, approximately 15% of men reported ≥ 1 form of MSD, with a lack of sexual interest, erectile dysfunction, and premature ejaculation present in 11.1%, 4.3%, and 4.7%, respectively. Multivariate analysis showed that age (odds ratio 2.39), employment status (odds ratio 3.62), having a wife who sought medical help for sexual problems (odds ratio 4.47), liberal attitudes toward female sexual initiation (odds ratio 2.07), and marital dissatisfaction (odds ratio 2.35) were all statistically significant risk factors for MSD and its specific components among the sample. However, having traditional attitudes toward female sexual refusal was a protective factor for MSD (odds ratio 0.51) and lack of sexual interest (odds ratio 0.51). The prevalence of MSD was low among young and middle-age married men in Hong Kong. Factors contributing to the risk of MSD spanned the domains of socioeconomic status, attitudes toward sex, and relationship factors. These findings suggest future directions for public health policies and the delivery of services that address the prevention and treatment of MSD. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Matched sibling versus matched unrelated allogeneic hematopoietic stem cell transplantation in children with severe acquired aplastic anemia: experience of the polish pediatric group for hematopoietic stem cell transplantation.

    PubMed

    Szpecht, Dawid; Gorczyńska, Ewa; Kałwak, Krzysztof; Owoc-Lempach, Joanna; Choma, Marta; Styczyński, Jan; Goździk, Jolanta; Dłużniewska, Agnieszka; Wysocki, Mariusz; Kowalczyk, Jerzy R; Chybicka, Alicja; Pieczonka, Anna; Wachowiak, Jacek

    2012-06-01

    In the study, 48 children with severe acquired aplastic anemia (SAA) transplanted from matched sibling donor (MSD) between 1991 and 2009, and 38 children with SAA transplanted from matched unrelated donor (MUD) between 2000 and 2009 were evaluated. Engraftment was achieved in 45 (93.75 %) patients after MSD-hematopoietic stem cell transplantation (HSCT) and in 33 (86.8 %) after MUD-HSCT. Transplant-related mortality rate after MSD-HSCT was 8 %, while 37 % after MUD-HSCT. After MSD-HSCT 44 (91.7 %) patients are alive for 1-216 months (median: 85 months), while after MUD-HSCT 24 (63.2 %) patients for 1-84 months (median: 16 months). The 5-year probability of event-free survival after MSD-HSCT and MUD-HSCT was 87 and 53 %, respectively, while 5 years of overall survival was 91 and 64 %, respectively. It was concluded that MSD-HSCT as the first line treatment for children with SAA is a safe therapeutic approach with a low rate of treatment failures and excellent outcome. Results of MUD-HSCT in pediatric patients with SAA who failed to respond to immunosuppressive therapy are still inferior than those of MSD-HSCT. Treatment failures of MUD-HSCT are mainly related to infectious complications and graft failure. It seems, however, that HLA-matching of unrelated donors at allelic level along with early MUD-HSCT after FCA (FLUDA, low-dose cyclophosphamide, and anti-thymocyte globulin) conditioning, perhaps using lower Thymoglobulin dose could enable further improvement of long-term results in children with SAA who lack MSD.

  17. Effectiveness of participatory training for prevention of musculoskeletal disorders: a randomized controlled trial.

    PubMed

    Yu, Wenzhou; Yu, Ignatius T S; Wang, Xiaorong; Li, Zhimin; Wan, Sabrina; Qiu, Hong; Lin, Hui; Xie, Shaohua; Sun, Trevor

    2013-05-01

    Health and safety training program has been applied to prevent work-related musculoskeletal disorders (MSDs) in workplace. We evaluated the effectiveness of participatory training and didactic training programs on MSD prevention among frontline workers in Shenzhen, China. The authors randomly assigned 918 workers from intervention factories to receive participatory training (intervention group), and 907 workers from intervention factories and 1,654 workers from control factories to receive didactic training (control_1 group, control_2 group, respectively) from June 1, 2008 to November 30, 2009. Participants were asked to report experience of ache, pain or discomfort in 10 body parts at baseline and 1 year after training. Data were analyzed to compare the MSD prevalence 1 year before and 1 year after training in different groups from 2009 to 2010. The follow-up rate was 61 % (2,120/3,479) at 1 year after training. In the year after training, there were no statistically significant changes in the proportion of workers who reported MSD in any body part. MSD prevalence rates in the intervention group reduced from 16.8 to 9.9 % for lower extremities (χ(2) = 13.102, p < 0.001) and from 12.9 to 8.3 % (χ(2) = 9.433, p = 0.002) for wrist and finger at 1 year after training. However, the rates did not change significantly for upper back, lower back, neck, shoulder and elbow in the intervention group and for all 10 body parts in two control groups. Overall, the training programs did not seem to prevent the occurrence of MSD among frontline workers. However, participatory training might be effective to reduce MSD in the lower extremities and wrist and finger.

  18. Characterization of single-file diffusion in one-dimensional dusty plasma

    NASA Astrophysics Data System (ADS)

    Theisen, W. L.; Sheridan, T. E.

    2010-11-01

    Single-file diffusion occurs in one-dimensional systems when particles cannot pass each other and the mean-squared displacement (msd) of these particles increases with time t. Diffusive processes that follow Ficks law predict that the msd increases as t, however, single-file diffusion is sub-Fickean meaning that the msd is predicted to increase as t^1/2. One-dimensional dusty plasma rings have been created under strongly coupled, over-damped conditions. Particle position data from these rings will be analyzed to determine the scaling of the msd with time. Results will be compared with predictions of single-file diffusion theory.

  19. Relationship between fumonisin contamination of feed and mystery swine disease. A case-control study.

    PubMed

    Bane, D P; Neumann, E J; Hall, W F; Harlin, K S; Slife, R L

    1992-02-01

    Fumonisin is a recently identified mycotoxin that has been shown to be the cause of pulmonary edema disease in swine and leukoencephalomalacia in horses. Mystery Swine Disease (MSD), is an economically devastating disease complex of unknown etiology that has been reported to have occurred in several swine producing states since 1988. To determine the relationship between MSD and fumonisin, a case-control study was carried out in Illinois in mid-1990. Feed samples collected from 12 case and 9 control farms were analyzed for fumonisin. Sera from swine on all farms was screened for titers against encephalomyocarditis (EMC) virus and concentrations of alpha-1 acid glycoprotein (an acute phase reactive protein). Fumonisin concentrations greater than or equal to 20 ppm were found on 1 control farm (1/9) and 8 case farms (8/12). Titers against EMC virus (greater than or equal to 1:16) were found on 5 control farms (5/9) and on 6 case farms (6/12). Farms with greater than or equal to 20 ppm fumonisin in the feed were at significantly increased risk (OR = 11.2, Fisher's exact test p = 0.037) for MSD. Furthermore, the pi2 test for trend was (p = 0.017), meaning that as the level of fumonisin in the feed increased, the risk of MSD also increased. The presence of EMC virus titers in the sow herd was not a significant risk for MSD (OR = 1.25, Fisher's exact test p = 0.75). Alpha-1 acid glycoprotein concentrations obtained from a 2-week old nursing pigs differed significantly (p = 0.0005) between MSD case and control herds.

  20. 75 FR 5320 - Proposed Agency Information Collection Activities; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-02

    ..., identified by FR 4004, FR MSD-4, FR MSD-5, FR G-FIN, or FR G-FINW, by any of the following methods: Agency... form number: FR MSD-4 and FR MSD-5. OMB control number: 7100-0100 and 7100-0101. Frequency: On occasion... dealers. Estimated annual reporting hours: FR MSD-4, 48 hours; and FR MSD-5, 36 hours. Estimated average...

  1. Work-life conflict and musculoskeletal disorders: a cross-sectional study of an unexplored association

    PubMed Central

    2011-01-01

    Background The health consequences of work-family or rather work-life conflict (WLC) have been studied by numerous researchers. The work-related causes of musculoskeletal disorders (MSD) are also well explored. And stress (at work) has been found to be a consequence of WLC as well as a cause of MSD. But very little is known about a potential association between WLC and MSD and the possible mediating role of stress in this relationship. Methods Survey data collected in 2007 among the workforces of four large companies in Switzerland were used for this study. The study population covered 6091 employees. As the exposure variable and hypothesized risk factor for MSD, WLC was measured by using a 10-item scale based on an established 18-item scale on work-family conflict. The outcome variables used as indicators of MSD were (low) back pain and neck/shoulder pain. Stress as the assumed intervening variable was assessed by a validated single-item measure of general stress perception. Correlation coefficients (r), standardized regression coefficients (β) and multiple adjusted odds ratios (OR) were calculated as measures of association. Results WLC was found to be quite strongly associated with MSD (β = .21). This association turned out to be substantially confounded by physical strain at work, workload and job autonomy and was considerably reduced but far from being completely eliminated after adjusting for general stress as another identified risk factor of MSD and a proven strong correlate of WLC (r = .44). A significant and relevant association still remained (β = .10) after having controlled for all considered covariates. This association could be fully attributed to only one direction of WLC, namely the work-to-life conflict. In subsequent analyses, a clear gradient between this WLC direction and both types of MSD was found, and proved to be consistent for both men and women. Employees who were most exposed to such work-to-life conflict were also most at risk and showed a fivefold higher prevalence rate (19%-42%) and also an up to sixfold increased relative risk (OR = 3.8-6.3) of suffering greatly from these types of MSD compared with the least exposed reference group showing very low WLC in this direction. Including stress in the regression models again reduced the strength of the association significantly (OR = 1.9-4.1), giving an indication for a possible indirect effect of WLC on MSD mediated by stress. Conclusion Future research and workplace interventions for the prevention of MSD need to consider WLC as an important stressor, and the MSD risk factor identified in this study. PMID:21410950

  2. Work-life conflict and musculoskeletal disorders: a cross-sectional study of an unexplored association.

    PubMed

    Hämmig, Oliver; Knecht, Michaela; Läubli, Thomas; Bauer, Georg F

    2011-03-16

    The health consequences of work-family or rather work-life conflict (WLC) have been studied by numerous researchers. The work-related causes of musculoskeletal disorders (MSD) are also well explored. And stress (at work) has been found to be a consequence of WLC as well as a cause of MSD. But very little is known about a potential association between WLC and MSD and the possible mediating role of stress in this relationship. Survey data collected in 2007 among the workforces of four large companies in Switzerland were used for this study. The study population covered 6091 employees. As the exposure variable and hypothesized risk factor for MSD, WLC was measured by using a 10-item scale based on an established 18-item scale on work-family conflict. The outcome variables used as indicators of MSD were (low) back pain and neck/shoulder pain. Stress as the assumed intervening variable was assessed by a validated single-item measure of general stress perception. Correlation coefficients (r), standardized regression coefficients (β) and multiple adjusted odds ratios (OR) were calculated as measures of association. WLC was found to be quite strongly associated with MSD (β=.21). This association turned out to be substantially confounded by physical strain at work, workload and job autonomy and was considerably reduced but far from being completely eliminated after adjusting for general stress as another identified risk factor of MSD and a proven strong correlate of WLC (r=.44). A significant and relevant association still remained (β=.10) after having controlled for all considered covariates. This association could be fully attributed to only one direction of WLC, namely the work-to-life conflict. In subsequent analyses, a clear gradient between this WLC direction and both types of MSD was found, and proved to be consistent for both men and women. Employees who were most exposed to such work-to-life conflict were also most at risk and showed a fivefold higher prevalence rate (19%-42%) and also an up to sixfold increased relative risk (OR = 3.8-6.3) of suffering greatly from these types of MSD compared with the least exposed reference group showing very low WLC in this direction. Including stress in the regression models again reduced the strength of the association significantly (OR=1.9-4.1), giving an indication for a possible indirect effect of WLC on MSD mediated by stress. Future research and workplace interventions for the prevention of MSD need to consider WLC as an important stressor, and the MSD risk factor identified in this study. © 2011 Hämmig et al; licensee BioMed Central Ltd.

  3. Musculoskeletal disorders and skin disease among workers in a Japanese CD manufacturing plant.

    PubMed

    Smith, Derek Richard; Takeda, Yasuhisa; Mizutani, Takashi; Yamagata, Zentaro

    2002-12-01

    We investigated the prevalence of musculoskeletal disorders (MSD) and skin disease within a Japanese compact disk (CD) manufacturing plant. For this study, a stratified cross-section of workers completed self-reported questionnaires distributed over a 6-month time period. Low back pain (LBP) was the most commonly reported category (affecting 20.1%), followed by MSD of the shoulder (15.4%), neck (10.1%) and head (5.4%). Dermatitis was the most frequent skin disease (affecting 8.1%), followed by eczema (3.4%), acne (3.4%) and xerosis (2.7%). The odds of suffering neck MSD was 10.8 times higher among staff who sat in a chair all day (95% CI 1.8-112.8, P < 0.05). Standing all day was also a risk factor for this condition (OR 8.2, 95% CI 1.2-81.7, P < 0.05). Female gender increased the risk of shoulder MSD 4.3 fold (95% CI 1.4-13.7, P < 0.05), as did alcohol consumption (OR 3.3, 95% CI 1.1-11.9, P < 0.05). The odds of suffering any skin disease were significantly enhanced by working longer than 12 months in one's current job (OR 10.7, 95% CI 1.5-7.3, P < 0.05) and having a history of atopic disease (OR 7.2, 95% CI 2.6-21.4, P < 0.001). Overall, the staff within our study reported generally lower levels of MSD and skin disease than in previous investigations of other workplaces.

  4. Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study.

    PubMed

    Conan, Anne; O'Reilly, Ciara E; Ogola, Eric; Ochieng, J Benjamin; Blackstock, Anna J; Omore, Richard; Ochieng, Linus; Moke, Fenny; Parsons, Michele B; Xiao, Lihua; Roellig, Dawn; Farag, Tamer H; Nataro, James P; Kotloff, Karen L; Levine, Myron M; Mintz, Eric D; Breiman, Robert F; Cleaveland, Sarah; Knobel, Darryn L

    2017-08-01

    Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children's homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08-0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02-0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0-1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5-37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2-12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents.

  5. Accuracy of a disability instrument to identify workers likely to develop upper extremity musculoskeletal disorders.

    PubMed

    Stover, Bert; Silverstein, Barbara; Wickizer, Thomas; Martin, Diane P; Kaufman, Joel

    2007-06-01

    Work related upper extremity musculoskeletal disorders (MSD) result in substantial disability, and expense. Identifying workers or jobs with high risk can trigger intervention before workers are injured or the condition worsens. We investigated a disability instrument, the QuickDASH, as a workplace screening tool to identify workers at high risk of developing upper extremity MSDs. Subjects included workers reporting recurring upper extremity MSD symptoms in the past 7 days (n = 559). The QuickDASH was reasonably accurate at baseline with sensitivity of 73% for MSD diagnosis, and 96% for symptom severity. Specificity was 56% for diagnosis, and 53% for symptom severity. At 1-year follow-up sensitivity and specificity for MSD diagnosis was 72% and 54%, respectively, as predicted by the baseline QuickDASH score. For symptom severity, sensitivity and specificity were 86% and 52%. An a priori target sensitivity of 70% and specificity of 50% was met by symptom severity, work pace and quality, and MSD diagnosis. The QuickDASH may be useful for identifying jobs or workers with increased risk for upper extremity MSDs. It may provide an efficient health surveillance screening tool useful for targeting early workplace intervention for prevention of upper extremity MSD problems.

  6. Preliminary investigation of single-file diffusion in complex plasma rings

    NASA Astrophysics Data System (ADS)

    Theisen, W. L.; Sheridan, T. E.

    2010-04-01

    Particles in one-dimensional (1D) systems cannot pass each other. However, it is still possible to define a diffusion process where the mean-squared displacement (msd) of an ensemble of particles in a 1D chain increases with time t. This process is called single-file diffusion. In contrast to diffusive processes that follow Fick's law, msdt, single-file diffusion is sub-Fickean and the msd is predicted to increase as t^1/2. We have recently created 1D dusty (complex) plasma rings in the DONUT (Dusty ONU experimenT) apparatus. Particle position data from these rings will be analyzed to determine the scaling of the msd with time and results will be compared with predictions of single-file diffusion theory.

  7. Work disability benefits due to musculoskeletal disorders among Brazilian private sector workers.

    PubMed

    Vieira, E R; Albuquerque-Oliveira, P R; Barbosa-Branco, A

    2011-05-14

    To evaluate the prevalence and characteristics of disability benefits due to musculoskeletal disorders (MSD) granted to Brazilian private sector workers. This was a population-based epidemiological study of MSD-related benefits among registered private sector workers (n=32 959 329). The prevalence (benefits/10 000 workers/year) of work disability benefits was calculated by gender, age, state, Human Development Index (HDI), economic activity, MSD type and work-relatedness. The prevalence of MSD-related benefits in Brazil among registered private sector workers in 2008 was 93.6/10 000 workers. The prevalence increased with age, and was higher for women (112.2) than for men (88.1), although the former had shorter benefit duration. The gender-adjusted prevalence by state varied from 16.6 to 90.3 for non-work-related, and from 7.8 to 59.6 for work-related benefits. The Brazilian states with a high-very high HDI had the highest prevalence. The top four most common types of MSD-related benefits were due to back pain, intervertebral disc disorders, sinovitis/tenosynovitis and shoulder disorders. MSD is a frequent cause of work disability in Brazil. There were differences in prevalence among economic activities and between states grouped by HDI. This study demonstrates that further evaluation of the contributing factors associated with MSD-related disability benefits is required. Factors that should be considered include production processes, political organisation, socioeconomic and educational characteristics, the compensation and recording systems, and employee-employer power relationships. These factors may play an important role in the prevalence of MSD-related disability benefits, especially in countries with large socioeconomic iniquities such as Brazil.

  8. Poor safety climate, long work hours, and musculoskeletal discomfort among Latino horse farm workers.

    PubMed

    Swanberg, Jennifer; Clouser, Jessica Miller; Gan, Wenqi; Flunker, John C; Westneat, Susan; Browning, Steven R

    2017-09-03

    This study investigated the prevalence of self-reported musculoskeletal discomfort (MSD) and work-related factors associated with elevated MSD among Latino thoroughbred farm workers. Participants (N = 225) were recruited using a community-based purposive sampling approach to participate in in-person interviews. Of these workers, 85% experienced MSD. MSD was divided into tertiles; the upper tertile was defined as elevated. Multivariable Poisson regression revealed associations between any elevated MSD and longer tenure on horse farms, longer work hours, and poor safety climate. Elevated neck/back MSD was associated with longer tenure, longer work hours, and poor safety climate. Elevated upper extremity MSD was associated with age and poor safety climate. Elevated lower extremity MSD was associated with longer tenure, longer work hours, and being female. Musculoskeletal discomfort is common among these workers. Improving safety climate and minimizing long work hours is recommended.

  9. Sanitation and Hygiene-Specific Risk Factors for Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study, 2007-2011: Case-Control Study.

    PubMed

    Baker, Kelly K; O'Reilly, Ciara E; Levine, Myron M; Kotloff, Karen L; Nataro, James P; Ayers, Tracy L; Farag, Tamer H; Nasrin, Dilruba; Blackwelder, William C; Wu, Yukun; Alonso, Pedro L; Breiman, Robert F; Omore, Richard; Faruque, Abu S G; Das, Sumon Kumar; Ahmed, Shahnawaz; Saha, Debasish; Sow, Samba O; Sur, Dipika; Zaidi, Anita K M; Quadri, Fahreen; Mintz, Eric D

    2016-05-01

    Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged <5 y old experiencing MSD and for 12,390 asymptomatic age, gender, and neighborhood-matched controls. An MSD case was defined as a child with a diarrheal illness <7 d duration comprising ≥3 loose stools in 24 h and ≥1 of the following: sunken eyes, skin tenting, dysentery, intravenous (IV) rehydration, or hospitalization. Site-specific conditional logistic regression models were used to explore the association between sanitation and hygiene exposures and MSD. Most households at six sites (>93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1-2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India. This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved.

  10. Sub-Fickean Diffusion in a One-Dimensional Plasma Ring

    NASA Astrophysics Data System (ADS)

    Theisen, W. L.

    2013-12-01

    A one-dimensional dusty plasma ring is formed in a strongly-coupled complex plasma. The dust particles in the ring can be characterized as a one-dimensional system where the particles cannot pass each other. The particles perform random walks due to thermal motions. This single-file self diffusion is characterized by the mean-squared displacement (msd) of the individual particles which increases with time t. Diffusive processes that follow Ficks law predict that the msd increases as t, however, single-file diffusion is sub-Fickean meaning that the msd is predicted to increase as t^(1/2). Particle position data from the dusty plasma ring is analyzed to determine the scaling of the msd with time. Results are compared with predictions of single-file diffusion theory.

  11. Physician practicing preferences for conventional or homeopathic medicines in elderly subjects with musculoskeletal disorders in the EPI3-MSD cohort

    PubMed Central

    Danno, Karine; Joubert, Clementine; Duru, Gerard; Vetel, Jean-Marie

    2014-01-01

    Background Musculoskeletal pain is common in elderly persons. Analgesic use is high in the elderly and may involve unacceptable risk in individuals with chronic pain. Our aim was to compare the socio-demographic characteristics of elderly subjects with musculoskeletal disorders (MSD) and to assess medication use and clinical evolution of musculoskeletal pain according to physician prescribing preference: homeopathy (Ho) group, conventional medicine (CM) group, or mixed prescription (MX) group. Methods The EPI3 study was a 1 year observational survey carried out among general practitioners in France between March 2007 and July 2008. This sub-analysis was carried out on elderly subjects aged ≥70 years from the original EPI3 cohort. Socio-demographic data were collected at inclusion using a self-administered patient questionnaire and medical data were recorded for each patient. Quality of life was measured using the Short Form-12 questionnaire. Patients completed a structured telephone interview on their functional status (evaluated with the QuickDash questionnaire, EIFEL scale or Lequesne index) within 72 hours of inclusion. This telephone interview was repeated at 1, 3, and 12 months. Drug exposure was also assessed during these interviews. Results 146 patients (mean age ± standard deviation: 75.8±4.8 years) were analyzed (80.1% female, 74.7% MSD of the spine or lower limbs, 64.4% chronic MSD). Patients in the CM and MX groups were 3.7 times or 2.5 times more likely (odds ratio [OR] =3.71, 95% confidence interval [CI]: 1.12–12.30; OR =2.52, 95% CI: 1.05–6.05; respectively) to have used non-steroidal anti-inflammatory drugs (NSAIDs) than those in the Ho group. In contrast, analgesic use was comparable in the three groups (OR =1.06 [CM versus Ho], 95% CI: 0.09–12.11; OR =0.34 [MX versus Ho], 95% CI: 0.07–1.57). Overall functional score evolution was similar in the three groups over time (P=0.16). Conclusion NSAID use was significantly higher in elderly MSD patients consulting a conventional practice general practitioner. In contrast, analgesic use and MSD evolution were similar in the three groups. Consulting a homeopathic physician for MSD management does not appear to represent a loss of therapeutic opportunity, and decreases the use of NSAIDs. PMID:25298739

  12. Physician practicing preferences for conventional or homeopathic medicines in elderly subjects with musculoskeletal disorders in the EPI3-MSD cohort.

    PubMed

    Danno, Karine; Joubert, Clementine; Duru, Gerard; Vetel, Jean-Marie

    2014-01-01

    Musculoskeletal pain is common in elderly persons. Analgesic use is high in the elderly and may involve unacceptable risk in individuals with chronic pain. Our aim was to compare the socio-demographic characteristics of elderly subjects with musculoskeletal disorders (MSD) and to assess medication use and clinical evolution of musculoskeletal pain according to physician prescribing preference: homeopathy (Ho) group, conventional medicine (CM) group, or mixed prescription (MX) group. The EPI3 study was a 1 year observational survey carried out among general practitioners in France between March 2007 and July 2008. This sub-analysis was carried out on elderly subjects aged ≥70 years from the original EPI3 cohort. Socio-demographic data were collected at inclusion using a self-administered patient questionnaire and medical data were recorded for each patient. Quality of life was measured using the Short Form-12 questionnaire. Patients completed a structured telephone interview on their functional status (evaluated with the QuickDash questionnaire, EIFEL scale or Lequesne index) within 72 hours of inclusion. This telephone interview was repeated at 1, 3, and 12 months. Drug exposure was also assessed during these interviews. 146 patients (mean age ± standard deviation: 75.8±4.8 years) were analyzed (80.1% female, 74.7% MSD of the spine or lower limbs, 64.4% chronic MSD). Patients in the CM and MX groups were 3.7 times or 2.5 times more likely (odds ratio [OR] =3.71, 95% confidence interval [CI]: 1.12-12.30; OR =2.52, 95% CI: 1.05-6.05; respectively) to have used non-steroidal anti-inflammatory drugs (NSAIDs) than those in the Ho group. In contrast, analgesic use was comparable in the three groups (OR =1.06 [CM versus Ho], 95% CI: 0.09-12.11; OR =0.34 [MX versus Ho], 95% CI: 0.07-1.57). Overall functional score evolution was similar in the three groups over time (P=0.16). NSAID use was significantly higher in elderly MSD patients consulting a conventional practice general practitioner. In contrast, analgesic use and MSD evolution were similar in the three groups. Consulting a homeopathic physician for MSD management does not appear to represent a loss of therapeutic opportunity, and decreases the use of NSAIDs.

  13. E-MSD: an integrated data resource for bioinformatics.

    PubMed

    Golovin, A; Oldfield, T J; Tate, J G; Velankar, S; Barton, G J; Boutselakis, H; Dimitropoulos, D; Fillon, J; Hussain, A; Ionides, J M C; John, M; Keller, P A; Krissinel, E; McNeil, P; Naim, A; Newman, R; Pajon, A; Pineda, J; Rachedi, A; Copeland, J; Sitnov, A; Sobhany, S; Suarez-Uruena, A; Swaminathan, G J; Tagari, M; Tromm, S; Vranken, W; Henrick, K

    2004-01-01

    The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the Protein Data Bank (PDB) and to work towards the integration of various bioinformatics data resources. We have implemented a simple form-based interface that allows users to query the MSD directly. The MSD 'atlas pages' show all of the information in the MSD for a particular PDB entry. The group has designed new search interfaces aimed at specific areas of interest, such as the environment of ligands and the secondary structures of proteins. We have also implemented a novel search interface that begins to integrate separate MSD search services in a single graphical tool. We have worked closely with collaborators to build a new visualization tool that can present both structure and sequence data in a unified interface, and this data viewer is now used throughout the MSD services for the visualization and presentation of search results. Examples showcasing the functionality and power of these tools are available from tutorial webpages (http://www. ebi.ac.uk/msd-srv/docs/roadshow_tutorial/).

  14. E-MSD: an integrated data resource for bioinformatics

    PubMed Central

    Golovin, A.; Oldfield, T. J.; Tate, J. G.; Velankar, S.; Barton, G. J.; Boutselakis, H.; Dimitropoulos, D.; Fillon, J.; Hussain, A.; Ionides, J. M. C.; John, M.; Keller, P. A.; Krissinel, E.; McNeil, P.; Naim, A.; Newman, R.; Pajon, A.; Pineda, J.; Rachedi, A.; Copeland, J.; Sitnov, A.; Sobhany, S.; Suarez-Uruena, A.; Swaminathan, G. J.; Tagari, M.; Tromm, S.; Vranken, W.; Henrick, K.

    2004-01-01

    The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the Protein Data Bank (PDB) and to work towards the integration of various bioinformatics data resources. We have implemented a simple form-based interface that allows users to query the MSD directly. The MSD ‘atlas pages’ show all of the information in the MSD for a particular PDB entry. The group has designed new search interfaces aimed at specific areas of interest, such as the environment of ligands and the secondary structures of proteins. We have also implemented a novel search interface that begins to integrate separate MSD search services in a single graphical tool. We have worked closely with collaborators to build a new visualization tool that can present both structure and sequence data in a unified interface, and this data viewer is now used throughout the MSD services for the visualization and presentation of search results. Examples showcasing the functionality and power of these tools are available from tutorial webpages (http://www.ebi.ac.uk/msd-srv/docs/roadshow_tutorial/). PMID:14681397

  15. Musculoskeletal disorders among nursing staff: a comparison of five hospitals in Uganda

    PubMed Central

    Munabi, Ian Guyton; Buwembo, William; Kitara, David Lagoro; Ochieng, Joseph; Nabirye, Rose Chalo; Mwaka, Erisa Sabakaki

    2014-01-01

    Introduction Low and middle income countries have severe nursing staff shortages which is associated with risk of poor quality of patient care and increased patient exposure to adverse events. This is accompanied with increased risk of musculoskeletal disorders to the nursing staff. This paper sets out to identify and compare factors associated with musculoskeletal disorders among nursing staff in 5 different hospitals in Uganda. Methods This was a cross sectional study on nurses from 5 different hospitals in Uganda. The study used a 12 month recall of reported Musculoskeletal disorders (MSD) among nurses. Ethical approval was obtained. Logistic regression analysis and ANOVA were used. The level of significance was set at 0.05 for all statistical tests. Results There were 755 respondents of whom 433 (58.4%) were nurses. The prevalence of MSD at anybody site was 80.8%. There were significant differences in reported MSD among nursing staff across different hospital settings which were worse in the public hospitals as compared to the private and private not for profit hospitals (p <0.001). Age (adjusted OR 1.03, 95% CI 1.01-1.06), self reported poor general health status (adj OR 4.5, 95% CI 2.8-7.24) and stress as suggested by waking up tired in the morning (adj OR 3.4, 95% CI 2.17-5.32) were significant associated factors for MSD in this population. Conclusiom Reported MSD among nursing staff across 5 different hospitals is worse in public as compared to private hospitals. Age, self reported poor general health status and stress were important factors for MSD in this population. PMID:25018829

  16. Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study

    PubMed Central

    Conan, Anne; O’Reilly, Ciara E.; Ogola, Eric; Ochieng, J. Benjamin; Blackstock, Anna J.; Omore, Richard; Ochieng, Linus; Moke, Fenny; Parsons, Michele B.; Xiao, Lihua; Roellig, Dawn; Farag, Tamer H.; Nataro, James P.; Kotloff, Karen L.; Levine, Myron M.; Mintz, Eric D.; Breiman, Robert F.; Cleaveland, Sarah

    2017-01-01

    Background Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. Methodology/Principal findings We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children’s homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08–0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02–0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0–1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5–37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2–12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. Conclusions and significance Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents. PMID:28783751

  17. Musculoskeletal disorder risk factors among nursing professionals in low resource settings: a cross-sectional study in Uganda.

    PubMed

    Munabi, Ian G; Buwembo, William; Kitara, David L; Ochieng, Joseph; Mwaka, Erisa S

    2014-02-24

    Musculoskeletal disorders (MSD) constitute one of the main occupational hazards among health care workers. However, few epidemiological studies on work related MSD among nursing professionals have been carried out in Africa. The purpose of this study was to assess the work related musculoskeletal disorders and associated risk factors among nursing professionals in Uganda. This was a cross-sectional study of MSD among 880 nursing professionals from five selected hospitals in Uganda. Data was collected using a questionnaire adapted from the Dutch Musculoskeletal and Nordic Musculoskeletal questionnaires. Descriptive (mean, standard deviation and percentages) and inferential (Chi square test and logistic regression analysis) statistics were used to analyse data. Alpha level was set at p < 0.05. A total of 741 completed questionnaires were analysed (response rate 85.4%). The average age of the respondents was 35.4 (SD 10.7) years and a majority were female (85.7%). The average working hours per week was 43.7 (SD 18.9 hours). The 12-month period-prevalence of MSD at anybody site was 80.8%. The most common site of MSD was the lower back (61.9%). Significant risk factors for reported MSD included often working in a slightly bent posture (adjOR 2.25, 95% CI 1.20-4.26), often working in a slightly twisted posture for long (adjOR 1.97, 95% CI 1.03-3.77), mental exhaustion (adjOR 2.05, 95% CI 1.17-3.5), being absent from the work station for more than 6 months due to illness or an accident (adjO|R, 4.35, 95% CI 1.44-13.08) and feeling rested after a break (adjOR 2.09, 95% CI 1.16-3.76). Musculoskeletal disorders affect more than 80% of nursing professionals in Uganda with the most commonly, affected site being the lower back. Significant risk factors for MSD include; being absent from the work station for more than 6 months due to illness or an accident, working in awkward postures, pushing/pulling of heavy loads and mental exhaustion. There is a need for greater advocacy, better working conditions and adoption of strategies to reduce occupational injuries.

  18. The Prevalence of Musculoskeletal Disorder and Association with Productivity Loss: A Preliminary Study among Labour Intensive Manual Harvesting Activities in Oil Palm Plantation

    PubMed Central

    NG, Yee Guan; TAMRIN, Shamsul Bahri Mohd; YIK, Wai Mun; YUSOFF, Irwan Syah Mohd; MORI, Ippei

    2013-01-01

    Production agriculture such as harvesting in oil palm plantation has been frequently associated with MSD and significant loss of productivities. This study tends to evaluate from the viewpoint of health, the association between self-reported prevalence of musculoskeletal disorders and productivities; the impact of musculoskeletal disorders on productivity. A cross-sectional study was conducted among 143 harvesters in oil palm plantation. A general questionnaire was used to collect socio-demographic background data while Nordic Musculoskeletal Questionnaire was used to determine the prevalence of MSD. Expressed in 4 different indicators; daily harvesting quantity, efficiency score, sick leave and presenteeism, the productivity data were analysed for association. There is significant association between reported acute prevalence of MSD (within 7 d) and productivity loss in terms of presenteeism (χ2=5.088; p<0.05) as well as quantity of daily harvest (χ2=7.406; p<0.01). Logistic regression adjusted for age, BMI and smoking indicate that harvesters with MSD (past seven days) were more likely to be engaged in presenteeism (OR=2.87 95% CI=1.34, 6.14) and had lower daily productivity (OR=2.09 95% CI=1.02, 4.29) compared to harvesters without MSD (past 7 d). This study reveals that oil palm harvesters suffering acute MSD (for the past week) were likely to be still present to work and produce half lesser than their healthy counterparts. Thus, further study with comprehensive surveillance strategy is essential in order to determine the urgency or need of appropriate intervention. PMID:24292878

  19. The prevalence of musculoskeletal disorder and association with productivity loss: a preliminary study among labour intensive manual harvesting activities in oil palm plantation.

    PubMed

    Ng, Yee Guan; Tamrin, Shamsul Bahri Mohd; Yik, Wai Mun; Yusoff, Irwan Syah Mohd; Mori, Ippei

    2014-01-01

    Production agriculture such as harvesting in oil palm plantation has been frequently associated with MSD and significant loss of productivities. This study tends to evaluate from the viewpoint of health, the association between self-reported prevalence of musculoskeletal disorders and productivities; the impact of musculoskeletal disorders on productivity. A cross-sectional study was conducted among 143 harvesters in oil palm plantation. A general questionnaire was used to collect socio-demographic background data while Nordic Musculoskeletal Questionnaire was used to determine the prevalence of MSD. Expressed in 4 different indicators; daily harvesting quantity, efficiency score, sick leave and presenteeism, the productivity data were analysed for association. There is significant association between reported acute prevalence of MSD (within 7 d) and productivity loss in terms of presenteeism (χ(2)=5.088; p<0.05) as well as quantity of daily harvest (χ(2)=7.406; p<0.01). Logistic regression adjusted for age, BMI and smoking indicate that harvesters with MSD (past seven days) were more likely to be engaged in presenteeism (OR=2.87 95% CI=1.34, 6.14) and had lower daily productivity (OR=2.09 95% CI=1.02, 4.29) compared to harvesters without MSD (past 7 d). This study reveals that oil palm harvesters suffering acute MSD (for the past week) were likely to be still present to work and produce half lesser than their healthy counterparts. Thus, further study with comprehensive surveillance strategy is essential in order to determine the urgency or need of appropriate intervention.

  20. Haploidentical Transplantation Without In Vitro T-Cell Depletion Results in Outcomes Equivalent to Those of Contemporaneous Matched Sibling and Unrelated Donor Transplantation for Acute Leukemia.

    PubMed

    Yu, Sijian; Fan, Qian; Sun, Jing; Fan, Zhiping; Zhang, Yu; Jiang, Qianli; Huang, Fen; Xuan, Li; Dai, Min; Zhou, Hongsheng; Liu, Hui; Liu, Qi-Fa

    2016-03-01

    The aim of the study is to determine whether HLA-haploidentical-related donor (HRD) transplant can achieve equivalent outcomes and have stronger GVL compared to HLA-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants. A total of 355 consecutive patients with acute leukemia undergoing allogeneic transplant at our single institute between March 2008 and March 2014 were enrolled in this retrospective investigation. Of the 355 patients, 96 cases received HRD, 153 MSD, and 106 MUD transplants. HRD transplant was associated with higher incidences of grade II to IV aGVHD (40.6%) compared with MSD (23.5%, P = 0.002) and MUD transplants (34.0%, P = 0.049), whereas incidences of grade III to IV aGVHD (11.4%, 7.8%, 10.5%, respectively; P = 0.590) and cGVHD (29.5%, 24.0%, 29.5%, respectively; P = 0.538) did not differ among 3 groups. Five-year relapse rates were 19.2%, 26.8%, and 23.0% in 3 groups, respectively (P = 0.419). However, of 206 high-risk patients, the relapse rate in HRD transplant was lower than in MSD transplant (23.8% vs 41.9%, P = 0.026). Multivariate analysis showed that HRD had beneficial impact on relapse (for MSD: P = 0.006). Five-year transplant-related mortality was lower in MSD transplant compared with those in HRD (17.3% vs 26.4%, P = 0.041) and MUD transplants (17.3% vs 24.1%, P = 0.037). Five-year overall survival were 60.4%, 64.6%, and 61.0%, respectively, in HRD, MSD, and MUD groups (P = 0.371); 5-year disease-free survival were 59.6%, 58.8%, and 54.9%, respectively (P = 0.423). Our results suggest that HRD transplant results in outcomes equivalent to MSD and MUD transplants. HRD might carry a superior GVL effect compared to MSD for high-risk patients.

  1. Improvement in the neural stem cell proliferation in rats treated with modified "Shengyu" decoction may contribute to the neurorestoration.

    PubMed

    Chen, Miao-Miao; Zhao, Guang-Wei; He, Peng; Jiang, Zheng-Lin; Xi, Xin; Xu, Shi-Hui; Ma, Dong-Ming; Wang, Yong; Li, Yong-Cai; Wang, Guo-Hua

    2015-05-13

    "Shengyu" decoction, a traditional Chinese medicine, has been used to treat diseases with deficit in "qi" and "blood". The modified "Shengyu" decoction (MSD) used in the present study was designed to treat traumatic brain injury (TBI) on the basis of the "Shengyu" decoction, in which additional four herbs were added. Many ingredients in these herbs have been demonstrated to be effective for the treatment of brain injury. The present study was performed to evaluate the neurorestorative effect and the underlying mechanisms of MSD on the rat brain after a TBI. TBI was induced in the right cerebral cortex of adult rats using Feeney's weight-drop method. Intragastrical administration of MSD (1.0 ml/200 g) was begun 6h after TBI. The neurological functions and neuronal loss in the cortex and hippocampus were determined. The levels of nerve growth-related factors GDNF, NGF, NCAM, TN-C, and Nogo-A and the number of GFAP(+)/GDNF(+), BrdU(+)/nestin(+), BrdU(+)/NeuN(+) immunoreactive cells in the brain ipsilateral to TBI were also measured. Moreover, the influences of MSD on these variables were observed at the same time. We found that treatment with MSD in TBI rats ameliorated the neurological functions and alleviated neuronal loss. MSD treatment elevated the expression of GDNF, NGF, NCAM, and TN-C, and inhibited the expression of Nogo-A. Moreover, MSD treatment increased the number of GFAP(+)/GDNF(+), BrdU(+)/nestin(+), and BrdU(+)/NeuN(+) immunoreactive cells in the cortex and hippocampus. The present results suggest that MSD treatment in TBI rats could improve the proliferation of neural stem/progenitor cells and differentiation into neurons, which may facilitate neural regeneration and tissue repair and thus contribute to the recovery of neurological functions. These effects of modified "Shengyu" decoction may provide a foundation for the use of MSD as a prescription of medicinal herbs in the traditional medicine to treat brain injuries in order to improve the neurorestoration. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. 17 CFR 240.15Ba2-1 - Application for registration of municipal securities dealers which are banks or separately...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Board), shall be filed with the Commission on Form MSD (§ 249.950 of this chapter), in accordance with... inaccurate for any reason, applicant shall promptly file an amendment on Form MSD (§ 249.950 of this chapter...

  3. Molecular and structural characteristics of multidrug resistance-associated protein 7 in Chinese liver fluke Clonorchis sinensis.

    PubMed

    Dai, Fuhong; Yoo, Won Gi; Lee, Ji-Yun; Lu, Yanyan; Pak, Jhang Ho; Sohn, Woon-Mok; Hong, Sung-Jong

    2017-03-01

    Multidrug resistance-associated protein 7 (MRP7, ABCC10) is a C subfamily member of the ATP-binding cassette (ABC) superfamily. MRP7 is a lipophilic anion transporter that pumps endogenous and xenobiotic substrates from the cytoplasm to the extracellular milieu. Here, we cloned and characterized CsMRP7 as a novel ABC transporter from the Chinese liver fluke, Clonorchis sinensis. Full-length cDNA of CsMRP7 was 5174 nt, encoded 1636 amino acids (aa), and harbored a 147-bp 5'-untranslated region (5'-UTR) and 116-bp 3'-UTR. Phylogenetic analysis confirmed that CsMRP7 was closer to the ABCC subfamily than the ABCB subfamily. Tertiary structures of the N-terminal region (1-322 aa) and core region (323-1621 aa) of CsMRP7 were generated by homology modeling using glucagon receptor (PDB ID: 5ee7_A) and P-glycoprotein (PDB ID: 4f4c_A) as templates, respectively. CsMRP7 nucleotide-binding domain 2 (NBD2) was conserved more than NBD1, which was the sites of ATP binding and hydrolysis. Like typical long MRPs, CsMRP7 has an additional membrane-spanning domain 0 (MSD0) and cytoplasmic loop, along with a common structural fold consisting of MSD1-NBD1-MSD2-NBD2 as a single polypeptide assembly. MSD0, MSD1, and MSD2 consisted of TM1-7, TM8-13, and TM14-19, respectively. The CsMRP7 transcript was more abundant in the metacercariae than in the adult worms. Truncated NBD1 (39 kDa) and NBD2 (44 kDa) were produced in bacteria and mouse immune sera were raised. CsMRP7 was localized in the apical side of the intestinal epithelium, sperm in the testes and seminal receptacle, receptacle membrane, and mesenchymal tissue around intestine in the adult worm. These results provide molecular information and insights into structural and functional characteristics of CsMRP7 and homologs of flukes.

  4. Underreporting of musculoskeletal disorders in 10 regions in France in 2009.

    PubMed

    Rivière, Stéphanie; Penven, Emmanuelle; Cadéac-Birman, Hélène; Roquelaure, Yves; Valenty, Madeleine

    2014-10-01

    Underreporting of occupational diseases (OD) has been quantified, in particular in the United States, but little information is available in other countries. The aim of this study was to evaluate underreporting of musculoskeletal disorders (MSD) in France in 2009. We calculated an indicator that approximated the underreporting rate of MSD in 10 regions of France. Two databases were used: data on OD compensated by insurance funding and data from the surveillance program for uncompensated work-related diseases. Analyses were performed for carpal tunnel syndrome (CTS) and elbow, shoulder, and lumbar spine MSD. The underreporting rate was estimated at 59% (range 52-64%) for CTS, 73% (range 67-79%) for elbow MSD, 69% (range 63-74%) for shoulder MSD, and 63% (range 50-76%) for lumbar spine MSD. This study revealed that MSD are substantially underreported in France, as in the United States, despite the differences in workers' compensation systems. © 2014 Wiley Periodicals, Inc.

  5. E-MSD: an integrated data resource for bioinformatics.

    PubMed

    Velankar, S; McNeil, P; Mittard-Runte, V; Suarez, A; Barrell, D; Apweiler, R; Henrick, K

    2005-01-01

    The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the worldwide Protein Data Bank (wwPDB) and to work towards the integration of various bioinformatics data resources. One of the major obstacles to the improved integration of structural databases such as MSD and sequence databases like UniProt is the absence of up to date and well-maintained mapping between corresponding entries. We have worked closely with the UniProt group at the EBI to clean up the taxonomy and sequence cross-reference information in the MSD and UniProt databases. This information is vital for the reliable integration of the sequence family databases such as Pfam and Interpro with the structure-oriented databases of SCOP and CATH. This information has been made available to the eFamily group (http://www.efamily.org.uk/) and now forms the basis of the regular interchange of information between the member databases (MSD, UniProt, Pfam, Interpro, SCOP and CATH). This exchange of annotation information has enriched the structural information in the MSD database with annotation from wider sequence-oriented resources. This work was carried out under the 'Structure Integration with Function, Taxonomy and Sequences (SIFTS)' initiative (http://www.ebi.ac.uk/msd-srv/docs/sifts) in the MSD group.

  6. Prevalence and Risk Factors Associated with Musculoskeletal Discomfort in Spay and Neuter Veterinarians

    PubMed Central

    White, Sara C.

    2013-01-01

    Simple Summary This study examined musculoskeletal pain and discomfort in spay and neuter veterinarians using an internet-based questionnaire. Hand pain was most common in the right thumb and wrist, and body pain was most common in the lower back, shoulders, and neck. Several work-related risk factors for discomfort were discovered, including long career in spay and neuter, increasing weekly hours in surgery, and decreasing job satisfaction. Although most respondents felt posture during surgery was important, few spay and neuter veterinarians have received any instruction in posture or ergonomics in surgery. Abstract A cross-sectional study to investigate musculoskeletal discomfort (MSD) surveyed 219 veterinarians who currently or previously perform spays and neuters at least 4 hours per week. Participants were asked about the presence and severity of hand and body MSD during the previous month, whether MSD interfered with work or daily activities, whether they attributed their MSD to their spay/neuter work, and whether MSD had ever necessitated absence from work. The period prevalence of MSD was 99.1%, with 76.7% experiencing hand or wrist pain and 98.2% experiencing body pain. Hand discomfort was most commonly reported in the right thumb and/or thumb base (49.8%) and the right wrist (37.9%). Body discomfort was most commonly reported in the lower back (76.7%), shoulders (72.6%), and neck (71.7%). Increasing career length, increasing weekly hours in surgery and decreasing job satisfaction were the work-related factors with the greatest relative contribution accounting for variation in hand pain severity and total pain. Although 94.4% of respondents felt that posture during surgery is important, only 30.6% had received any instruction in posture and positioning for surgery. Future interventions should aim to optimize surgical efficiency, surgeon work schedules, and working environment. Analysis and intervention studies are required to determine further causes of MSD in these veterinarians and develop interventions to prevent MSD. PMID:26487311

  7. Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis.

    PubMed

    Ghosh, Nilanjan; Karmali, Reem; Rocha, Vanderson; Ahn, Kwang Woo; DiGilio, Alyssa; Hari, Parameswaran N; Bachanova, Veronika; Bacher, Ulrike; Dahi, Parastoo; de Lima, Marcos; D'Souza, Anita; Fenske, Timothy S; Ganguly, Siddhartha; Kharfan-Dabaja, Mohamed A; Prestidge, Tim D; Savani, Bipin N; Smith, Sonali M; Sureda, Anna M; Waller, Edmund K; Jaglowski, Samantha; Herrera, Alex F; Armand, Philippe; Salit, Rachel B; Wagner-Johnston, Nina D; Fuchs, Ephraim; Bolaños-Meade, Javier; Hamadani, Mehdi

    2016-09-10

    Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD. © 2016 by American Society of Clinical Oncology.

  8. Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis

    PubMed Central

    Ghosh, Nilanjan; Karmali, Reem; Rocha, Vanderson; Ahn, Kwang Woo; DiGilio, Alyssa; Hari, Parameswaran N.; Bachanova, Veronika; Bacher, Ulrike; Dahi, Parastoo; de Lima, Marcos; D’Souza, Anita; Fenske, Timothy S.; Ganguly, Siddhartha; Kharfan-Dabaja, Mohamed A.; Prestidge, Tim D.; Savani, Bipin N.; Smith, Sonali M.; Sureda, Anna M.; Waller, Edmund K.; Jaglowski, Samantha; Herrera, Alex F.; Armand, Philippe; Salit, Rachel B.; Wagner-Johnston, Nina D.; Fuchs, Ephraim; Bolaños-Meade, Javier

    2016-01-01

    Purpose Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor–based GVHD prophylaxis. Results Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD. PMID:27269951

  9. Job Hazard Analyses for Musculoskeletal Disorder Risk Factors in Pressing Operations of Dry-cleaning Establishments.

    PubMed

    Park, Jung-Keun

    2016-12-01

    Job hazard analyses were conducted to assess exposure to musculoskeletal disorder (MSD) risk factors in seven workers of three dry-cleaning establishments. In accordance with the Washington State Ergonomics Rule, the analyses were performed in two separate steps: (1) observation and checklist approaches were made to identify a "caution zone job" in the seven workers' pressing operations across the three shops; and (2) detailed posture and motion analyses were undertaken to determine a "MSD hazard" in one worker's operation using a video technique. One "caution zone job" was identified and it was the pressing operation job in which five physical risk factors were found in the pressing operations. The detailed analyses confirmed that one "MSD hazard", i.e., awkward posture in shoulders, was prevalent in the pressing operations of the three dry-cleaning facilities. It would be desirable to reduce MSD risk factors including awkward shoulder posture in the dry-cleaning industry.

  10. A descriptive study of U.S. OSHA penalties and inspection frequency for musculoskeletal disorders in the workplace.

    PubMed

    Courtney, T K; Clancy, E A

    1998-08-01

    Information on the frequency and cost of OSHA enforcement penalties for musculoskeletal disorders (MSD) in the literature is limited. Such information would be of value to organizations in estimating the likelihood and financial impact of enforcement activity in their operations. This descriptive study utilized data from federal Occupational Safety and Health Administration (OSHA) inspections to examine the distribution of penalty costs arising from inspections with MSD-related citations from January 1985 to June 1994 and to estimate the probability of OSHA inspection in general and OSHA citation for MSD hazards from October 1985 to September 1993. The mean and median values of proposed penalties were $47,707 and $3600 respectively. A substantial influence of 1991 changes to the penalty structure was noted with decreasing mean and increasing median penalty values. Penalty values increased with establishment size and were higher for unplanned than for planned inspections. The probability of a federal OSHA inspection for any establishment ranged from 1:50 in 1986 to 1:100 in 1993 whereas the estimated probability of an inspection with MSD-related citations ranged from 1:167,000 in 1996 to as much as 1:38,000 during the peak of enforcement activity in 1990. The probability of an inspection with MSD citations for the largest establishments during the period was more than 1000 times greater than that for the smallest. The results of this study may be utilized by organizations seeking to demonstrate the advantages of reducing musculoskeletal morbidity in the workplace.

  11. Transport Properties of Ibuprofen Encapsulated in Cyclodextrin Nanosponge Hydrogels: A Proton HR-MAS NMR Spectroscopy Study.

    PubMed

    Ferro, Monica; Castiglione, Franca; Punta, Carlo; Melone, Lucio; Panzeri, Walter; Rossi, Barbara; Trotta, Francesco; Mele, Andrea

    2016-08-15

    The chemical cross-linking of β-cyclodextrin (β-CD) with ethylenediaminetetraacetic dianhydride (EDTA) led to branched polymers referred to as cyclodextrin nanosponges (CDNSEDTA). Two different preparations are described with 1:4 and 1:8 CD-EDTA molar ratios. The corresponding cross-linked polymers were contacted with 0.27 M aqueous solution of ibuprofen sodium salt (IP) leading to homogeneous, colorless, drug loaded hydrogels. The systems were characterized by high resolution magic angle spinning (HR-MAS) NMR spectroscopy. Pulsed field gradient spin echo (PGSE) NMR spectroscopy was used to determine the mean square displacement (MSD) of IP inside the polymeric gel at different observation times td. The data were further processed in order to study the time dependence of MSD: MSD = f(td). The proposed methodology is useful to characterize the different diffusion regimes that, in principle, the solute may experience inside the hydrogel, namely normal or anomalous diffusion. The full protocols including the polymer preparation and purification, the obtainment of drug-loaded hydrogels, the NMR sample preparation, the measurement of MSD by HR-MAS NMR spectroscopy and the final data processing to achieve the time dependence of MSD are here reported and discussed. The presented experiments represent a paradigmatic case and the data are discussed in terms of innovative approach to the characterization of the transport properties of an encapsulated guest within a polymeric host of potential application for drug delivery.

  12. Back and neck pain disability and upper limb symptoms of home healthcare workers: A case-control study from Northern Italy.

    PubMed

    Riccò, Matteo; Pezzetti, Federica; Signorelli, Carlo

    2017-03-30

    Work-related musculoskeletal disorders (MSD) are quite frequent in healthcare workers (HCWs), but data about MSD in home-based healthcare workers (HHWs) are lacking. In this study we describe the prevalence of MSD among Italian HHWs. A case-control study was carried out among 300 random-selected female HCWs, the sample comprising 100 HHWs, 100 HCWs with a low exposure to patient handling (MAPO - Movimentazione e Assistenza Pazienti Ospedalizzati - Movement and Assistance of Hospital Patients index 0-5) and 100 HCWs with high exposure to patient handling (MAPO index ≥ 5.01). As a negative control group, 200 visual display unit workers were also randomly selected. Musculoskeletal disorder cases were collected using a standardized case definition. A multivariate logistic regression analysis was performed comparing the MSD prevalence in the 4 groups. The overall prevalence of MSD was 17% in the reference group and 28.3% for HCWs. HHWs and HCWs with MAPO index ≥ 5.01 had similar prevalence of neck pain (9% and 11%, respectively), whereas lumbosacral pain prevalence was higher in the HHWs group (31%), with similar results in residential HCWs groups (21% in MAPO index 0-5 group and 25% in MAPO index ≥ 5.01 group). HCWs of group MAPO index ≥ 5.01 and HHWs showed the higher prevalence of upper limb complaints, with a prevalence of 20% and 10%, respectively. In multivariate regression analysis, prevalence of MSD complaints was quite similar in HHWs (adjusted odds ratio (ORadj) = 2.335, 95% confidence interval (CI): 1.318-4.138) and in HCWs of the group MAPO ≥ 5.01 (ORadj = 2.729, 95% CI: 1.552-4.797). The prevalence of MSD in the examined HCWs was relatively high, with HHWs appearing as a particularly high-risk group for lumbosacral back pain. In higher exposed HCWs, upper-limb symptoms were particularly frequent, probably reflecting the different tasks required to manage residential and homebased patients. In conclusion, this study reaffirms the high prevalence of MSD in HHWs, seemly similar to high-risk residential groups. Int J Occup Med Environ Health 2017;30(2):291-304. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  13. The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS).

    PubMed

    Sow, Samba O; Muhsen, Khitam; Nasrin, Dilruba; Blackwelder, William C; Wu, Yukun; Farag, Tamer H; Panchalingam, Sandra; Sur, Dipika; Zaidi, Anita K M; Faruque, Abu S G; Saha, Debasish; Adegbola, Richard; Alonso, Pedro L; Breiman, Robert F; Bassat, Quique; Tamboura, Boubou; Sanogo, Doh; Onwuchekwa, Uma; Manna, Byomkesh; Ramamurthy, Thandavarayan; Kanungo, Suman; Ahmed, Shahnawaz; Qureshi, Shahida; Quadri, Farheen; Hossain, Anowar; Das, Sumon K; Antonio, Martin; Hossain, M Jahangir; Mandomando, Inacio; Nhampossa, Tacilta; Acácio, Sozinho; Omore, Richard; Oundo, Joseph O; Ochieng, John B; Mintz, Eric D; O'Reilly, Ciara E; Berkeley, Lynette Y; Livio, Sofie; Tennant, Sharon M; Sommerfelt, Halvor; Nataro, James P; Ziv-Baran, Tomer; Robins-Browne, Roy M; Mishcherkin, Vladimir; Zhang, Jixian; Liu, Jie; Houpt, Eric R; Kotloff, Karen L; Levine, Myron M

    2016-05-01

    The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27-4.67) and 3.18 (95% CI, 1.85-4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73-2.08) and 1.36 (95% CI, 0.66-2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33-5.01) and 4.88 (95% CI, 0.82-8.92) in infants and 4.04 (95% CI, 0.56-7.51) and 4.71 (95% CI, 0.24-9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies.

  14. The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS)

    PubMed Central

    Nasrin, Dilruba; Blackwelder, William C.; Wu, Yukun; Farag, Tamer H.; Panchalingam, Sandra; Sur, Dipika; Zaidi, Anita K. M.; Faruque, Abu S. G.; Saha, Debasish; Adegbola, Richard; Alonso, Pedro L.; Breiman, Robert F.; Bassat, Quique; Tamboura, Boubou; Sanogo, Doh; Onwuchekwa, Uma; Manna, Byomkesh; Ramamurthy, Thandavarayan; Kanungo, Suman; Ahmed, Shahnawaz; Qureshi, Shahida; Quadri, Farheen; Hossain, Anowar; Das, Sumon K.; Antonio, Martin; Hossain, M. Jahangir; Mandomando, Inacio; Nhampossa, Tacilta; Acácio, Sozinho; Omore, Richard; Oundo, Joseph O.; Ochieng, John B.; Mintz, Eric D.; O’Reilly, Ciara E.; Berkeley, Lynette Y.; Livio, Sofie; Tennant, Sharon M.; Sommerfelt, Halvor; Nataro, James P.; Ziv-Baran, Tomer; Robins-Browne, Roy M.; Mishcherkin, Vladimir; Zhang, Jixian; Liu, Jie; Houpt, Eric R.; Kotloff, Karen L.; Levine, Myron M.

    2016-01-01

    Background The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. Methods Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. Findings Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27–4.67) and 3.18 (95% CI, 1.85–4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73–2.08) and 1.36 (95% CI, 0.66–2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33–5.01) and 4.88 (95% CI, 0.82–8.92) in infants and 4.04 (95% CI, 0.56–7.51) and 4.71 (95% CI, 0.24–9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. Conclusions The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies. PMID:27219054

  15. A research framework for the development and implementation of interventions preventing work-related musculoskeletal disorders.

    PubMed

    van der Beek, Allard J; Dennerlein, Jack T; Huysmans, Maaike A; Mathiassen, Svend Erik; Burdorf, Alex; van Mechelen, Willem; van Dieën, Jaap H; Frings-Dresen, Monique Hw; Holtermann, Andreas; Janwantanakul, Prawit; van der Molen, Henk F; Rempel, David; Straker, Leon; Walker-Bone, Karen; Coenen, Pieter

    2017-11-01

    Objectives Work-related musculoskeletal disorders (MSD) are highly prevalent and put a large burden on (working) society. Primary prevention of work-related MSD focuses often on physical risk factors (such as manual lifting and awkward postures) but has not been too successful in reducing the MSD burden. This may partly be caused by insufficient knowledge of etiological mechanisms and/or a lack of adequately feasible interventions (theory failure and program failure, respectively), possibly due to limited integration of research disciplines. A research framework could link research disciplines thereby strengthening the development and implementation of preventive interventions. Our objective was to define and describe such a framework for multi-disciplinary research on work-related MSD prevention. Methods We described a framework for MSD prevention research, partly based on frameworks from other research fields (ie, sports injury prevention and public health). Results The framework is composed of a repeated sequence of six steps comprising the assessment of (i) incidence and severity of MSD, (ii) risk factors for MSD, and (iii) underlying mechanisms; and the (iv) development, (v) evaluation, and (vi) implementation of preventive intervention(s). Conclusions In the present framework for optimal work-related MSD prevention, research disciplines are linked. This framework can thereby help to improve theories and strengthen the development and implementation of prevention strategies for work-related MSD.

  16. E-MSD: an integrated data resource for bioinformatics

    PubMed Central

    Velankar, S.; McNeil, P.; Mittard-Runte, V.; Suarez, A.; Barrell, D.; Apweiler, R.; Henrick, K.

    2005-01-01

    The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the worldwide Protein Data Bank (wwPDB) and to work towards the integration of various bioinformatics data resources. One of the major obstacles to the improved integration of structural databases such as MSD and sequence databases like UniProt is the absence of up to date and well-maintained mapping between corresponding entries. We have worked closely with the UniProt group at the EBI to clean up the taxonomy and sequence cross-reference information in the MSD and UniProt databases. This information is vital for the reliable integration of the sequence family databases such as Pfam and Interpro with the structure-oriented databases of SCOP and CATH. This information has been made available to the eFamily group (http://www.efamily.org.uk/) and now forms the basis of the regular interchange of information between the member databases (MSD, UniProt, Pfam, Interpro, SCOP and CATH). This exchange of annotation information has enriched the structural information in the MSD database with annotation from wider sequence-oriented resources. This work was carried out under the ‘Structure Integration with Function, Taxonomy and Sequences (SIFTS)’ initiative (http://www.ebi.ac.uk/msd-srv/docs/sifts) in the MSD group. PMID:15608192

  17. Benefits from Funding the MSD Engineering List: A Fiscal Year 1999 Case Study

    DTIC Science & Technology

    2004-03-01

    BENEFITS FROM FUNDING THE MSD ENGINEERING LIST: A FISCAL YEAR 1999 CASE STUDY THESIS...States Government. AFIT/GLM/ENS/04-03 BENEFITS FROM FUNDING THE MSD ENGINEERING LIST: A FISCAL YEAR 1999 CASE STUDY...ENS/04-03 BENEFITS FROM FUNDING THE MSD ENGINEERING LIST: A FISCAL YEAR 1999 CASE STUDY David L. Gehrich, BS Captain, USAF

  18. Tracer particles in two-dimensional elastic networks diffuse logarithmically slow

    NASA Astrophysics Data System (ADS)

    Lizana, Ludvig; Ambjörnsson, Tobias; Lomholt, Michael A.

    2017-01-01

    Several experiments on tagged molecules or particles in living systems suggest that they move anomalously slow—their mean squared displacement (MSD) increase slower than linearly with time. Leading models aimed at understanding these experiments predict that the MSD grows as a power law with a growth exponent that is smaller than unity. However, in some experiments the growth is so slow (fitted exponent  ˜0.1-0.2) that they hint towards other mechanisms at play. In this paper, we theoretically demonstrate how in-plane collective modes excited by thermal fluctuations in a two dimensional membrane lead to logarithmic time dependence for the the tracer particle’s MSD.

  19. Gestational sac and embryonic growth are not useful as criteria to define miscarriage: a multicenter observational study.

    PubMed

    Abdallah, Y; Daemen, A; Guha, S; Syed, S; Naji, O; Pexsters, A; Kirk, E; Stalder, C; Gould, D; Ahmed, S; Bottomley, C; Timmerman, D; Bourne, T

    2011-11-01

    We studied changes in mean gestational sac diameter (MSD) and embryonic crown-rump length (CRL) in intrauterine pregnancies of uncertain viability (IPUVs). We aimed to establish cut-off values for MSD and CRL growth that could be definitively associated with either viability or miscarriage, and to establish the relationship between growth in MSD and appearance of embryonic structures in the gestational sac. One thousand and sixty consecutive IPUVs were recruited prospectively from four London University hospitals: 462 with no yolk sac or embryo, 419 with a yolk sac but no embryo, and 179 with an embryo but no heartbeat visible. IPUV was defined as an empty gestational sac with or without a yolk sac but no embryo seen with MSD < 20 or < 30 mm (depending on center) or an embryo with no heartbeat and CRL < 6 mm or < 8 mm (depending on center). Scans were repeated 7-14 days later. The endpoint was viability at first-trimester screening ultrasonography between 11 and 14 weeks. Change in MSD and CRL between the first and second scans of each pregnancy was compared with respect to viability and appearance of embryonic structures using the two-sample t-test. The study included 359 pregnancies in which a gestational sac with or without embryo was identified at the follow-up scan 7-14 days later. Of these, 192 were viable and 167 non-viable at the 11-14-week scan. MSD growth was significantly higher in viable than non-viable pregnancies (mean 1.003 vs. 0.503 mm/day; P < 0.001, 95% CI of difference 0.403-0.596). A difference in CRL growth was found between the two groups (mean 0.673 vs. 0.148 mm/day; P < 0.001, 95% CI of difference 0.345-0.703). MSD growth of 0.6 mm/day was associated with a specificity for diagnosing miscarriage of 90.1%, a sensitivity of 61.7% and 19 false-positive test results. A cut-off of CRL growth rate of 0.2 mm/day gave a sensitivity of 76.3% and there were no false-positive test results for miscarriage. On repeat scan the failure of either a yolk sac or embryo to be visualized was always associated with miscarriage. There is an overlap in MSD growth rates between viable and non-viable IPUV. No cut-off exists for MSD growth below which a viable pregnancy could be safely excluded. A cut-off value for CRL growth of 0.2 mm/day was always associated with miscarriage. These data suggest that criteria to diagnose miscarriage based on growth in MSD and CRL are potentially unsafe. However, finding an empty gestational sac on two scans more than 7 days apart is highly likely to indicate miscarriage, irrespective of growth. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  20. Assembly and misassembly of cystic fibrosis transmembrane conductance regulator: folding defects caused by deletion of F508 occur before and after the calnexin-dependent association of membrane spanning domain (MSD) 1 and MSD2.

    PubMed

    Rosser, Meredith F N; Grove, Diane E; Chen, Liling; Cyr, Douglas M

    2008-11-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is a polytopic membrane protein that functions as a Cl(-) channel and consists of two membrane spanning domains (MSDs), two cytosolic nucleotide binding domains (NBDs), and a cytosolic regulatory domain. Cytosolic 70-kDa heat shock protein (Hsp70), and endoplasmic reticulum-localized calnexin are chaperones that facilitate CFTR biogenesis. Hsp70 functions in both the cotranslational folding and posttranslational degradation of CFTR. Yet, the mechanism for calnexin action in folding and quality control of CFTR is not clear. Investigation of this question revealed that calnexin is not essential for CFTR or CFTRDeltaF508 degradation. We identified a dependence on calnexin for proper assembly of CFTR's membrane spanning domains. Interestingly, efficient folding of NBD2 was also found to be dependent upon calnexin binding to CFTR. Furthermore, we identified folding defects caused by deletion of F508 that occurred before and after the calnexin-dependent association of MSD1 and MSD2. Early folding defects are evident upon translation of the NBD1 and R-domain and are sensed by the RMA-1 ubiquitin ligase complex.

  1. A systematic review of musculoskeletal disorders among school teachers

    PubMed Central

    2011-01-01

    Background Musculoskeletal disorders (MSD) represent one of the most common and most expensive occupational health problems in both developed and developing countries. School teachers represent an occupational group among which there appears to be a high prevalence of MSD. Given that causes of MSD have been described as multi-factorial and prevalence rates vary between body sites and location of study, the objective of this systematic review was to investigate the prevalence and risk factors for MSD among teaching staff. Methods The study involved an extensive search of MEDLINE and EMBASE databases in 2011. All studies which reported on the prevalence and/or risk factors for MSD in the teaching profession were initially selected for inclusion. Reference lists of articles identified in the original search were then examined for additional publications. Of the 80 articles initially located, a final group of 33 met the inclusion criteria and were examined in detail. Results This review suggests that the prevalence of self-reported MSD among school teachers ranges between 39% and 95%. The most prevalent body sites appear to be the back, neck and upper limbs. Nursery school teachers appear to be more likely to report suffering from low back pain. Factors such as gender, age, length of employment and awkward posture have been associated with higher MSD prevalence rates. Conclusion Overall, this study suggests that school teachers are at a high risk of MSD. Further research, preferably longitudinal, is required to more thoroughly investigate the issue of MSD among teachers, with a greater emphasis on the possible wider use of ergonomic principles. This would represent a major step forward in the prevention of MSD among teachers, especially if easy to implement control measures could be recommended. PMID:22087739

  2. The symmetric MSD encoder for one-step adder of ternary optical computer

    NASA Astrophysics Data System (ADS)

    Kai, Song; LiPing, Yan

    2016-08-01

    The symmetric Modified Signed-Digit (MSD) encoding is important for achieving the one-step MSD adder of Ternary Optical Computer (TOC). The paper described the symmetric MSD encoding algorithm in detail, and developed its truth table which has nine rows and nine columns. According to the truth table, the state table was developed, and the optical-path structure and circuit-implementation scheme of the symmetric MSD encoder (SME) for one-step adder of TOC were proposed. Finally, a series of experiments were designed and performed. The observed results of the experiments showed that the scheme to implement SME was correct, feasible and efficient.

  3. Current DOT research on the effect of multiple site damage on structural integrity

    NASA Technical Reports Server (NTRS)

    Tong, P.; Arin, Kemal; Jeong, David Y.; Greif, R.; Brewer, John C.; Bobo, Stephan N.; Sampath, Sam N.

    1992-01-01

    Multiple site damage (MSD) is a type of cracking that may be found in aging airplanes and which may adversely affect their continuing airworthiness. The Volpe National Transportation Systems Center has supported the Federal Aviation Administration Technical Center on structural integrity research for the past two and half years. The work has focused on understanding the behavior of MSD, detection of MSD during airframe inspection, and the avoidance of MSD in future designs. These three elements of the MSD problem are addressed and a summary of the completed work, the current status, and requirements for future research is provided.

  4. [A comparative study of unrelated donor and matched-sibling donor allogeneic hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia].

    PubMed

    Zhou, J; Fu, Y W; Liang, L J; Wang, Q; Han, L J; Zu, Y L; Zhang, Yanli; Zhu, X H; Yu, F K; Fang, B J; Wei, X D; Song, Y P

    2016-12-01

    Objective: To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT) for children and adolescents with severe aplastic anemia (SAA). Methods: Clinical data of 34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015. According to the source of donor, the patients were divided into matched sibling donor allo-HSCT group (MSD group) and unrelated donor group (URD group). The clinical outcome of SAA children and adolescents receiving URD allo-HSCT was assessed, and patients in MSD allo-HSCT group were enrolled as control at the same period. Results: The rate of hematopoietic reconstitution, the time of neutrophil and platelet engraftment, incidence of chimerism and graft rejection between two groups were not statistically different.The incidence of acute graft-versus-host disease (GVHD) in URD group was significantly higher than that in MSD group [42.9%(6/14) vs 10.5%(2/19), P =0.047]. The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD in URD were higher than those in MSD group [21.4%(3/14) vs 5.3%(1/19), P =0.288; 35.7%(5/14) vs 5.3%(1/19), P =0.062, respectively], yet without significant difference between two groups. Other transplant-related complications including pulmonary complications, hemorrhagic cystitis, incidence of EBV and CMV reactivation and venous occlusive disease were comparable with two regimens. Estimated 5-years overall survival (OS) rate and disease free survival (DFS) rate were not statistically significant between URD group and MSD group [(84.4±6.6)% vs (89.4±7.1)%, (82.5±5.4)% vs (82.1±4.3)%; P =0.766, P =0.884, respectively]. Conclusions: By multivariate analysis, the outcome of URD allo-HSCT in SAA children and adolescent is similar to MSD allo-HSCT. It could be an alternative option as the first-line treatment for SAA children and adolescents without HLA matched sibling donors.

  5. Efficacy of a Combined Intracerebral and Systemic Gene Delivery Approach for the Treatment of a Severe Lysosomal Storage Disorder

    PubMed Central

    Spampanato, Carmine; De Leonibus, Elvira; Dama, Paola; Gargiulo, Annagiusi; Fraldi, Alessandro; Sorrentino, Nicolina Cristina; Russo, Fabio; Nusco, Edoardo; Auricchio, Alberto; Surace, Enrico M; Ballabio, Andrea

    2011-01-01

    Multiple sulfatase deficiency (MSD), a severe autosomal recessive disease is caused by mutations in the sulfatase modifying factor 1 gene (Sumf1). We have previously shown that in the Sumf1 knockout mouse model (Sumf1−/−) sulfatase activities are completely absent and, similarly to MSD patients, this mouse model displays growth retardation and early mortality. The severity of the phenotype makes MSD unsuitable to be treated by enzyme replacement or bone marrow transplantation, hence the importance of testing the efficacy of novel treatment strategies. Here we show that recombinant adeno-associated virus serotype 9 (rAAV9) vector injected into the cerebral ventricles of neonatal mice resulted in efficient and widespread transduction of the brain parenchyma. In addition, we compared a combined, intracerebral ventricles and systemic, administration of an rAAV9 vector encoding SUMF1 gene to the single administrations—either directly in brain, or systemic alone —in MSD mice. The combined treatment resulted in the global activation of sulfatases, near-complete clearance of glycosaminoglycans (GAGs) and decrease of inflammation in both the central nervous system (CNS) and visceral organs. Furthermore, behavioral abilities were improved by the combined treatment. These results underscore that the “combined” mode of rAAV9 vector administration is an efficient option for the treatment of severe whole-body disorders. PMID:21326216

  6. Measurement error of mean sac diameter and crown-rump length among pregnant women at Mulago hospital, Uganda.

    PubMed

    Ali, Sam; Byanyima, Rosemary Kusaba; Ononge, Sam; Ictho, Jerry; Nyamwiza, Jean; Loro, Emmanuel Lako Ernesto; Mukisa, John; Musewa, Angella; Nalutaaya, Annet; Ssenyonga, Ronald; Kawooya, Ismael; Temper, Benjamin; Katamba, Achilles; Kalyango, Joan; Karamagi, Charles

    2018-05-04

    Ultrasonography is essential in the prenatal diagnosis and care for the pregnant mothers. However, the measurements obtained often contain a small percentage of unavoidable error that may have serious clinical implications if substantial. We therefore evaluated the level of intra and inter-observer error in measuring mean sac diameter (MSD) and crown-rump length (CRL) in women between 6 and 10 weeks' gestation at Mulago hospital. This was a cross-sectional study conducted from January to March 2016. We enrolled 56 women with an intrauterine single viable embryo. The women were scanned using a transvaginal (TVS) technique by two observers who were blinded of each other's measurements. Each observer measured the CRL twice and the MSD once for each woman. Intra-class correlation coefficients (ICCs), 95% limits of agreement (LOA) and technical error of measurement (TEM) were used for analysis. Intra-observer ICCs for CRL measurements were 0.995 and 0.993 while inter-observer ICCs were 0.988 for CRL and 0.955 for MSD measurements. Intra-observer 95% LOA for CRL were ± 2.04 mm and ± 1.66 mm. Inter-observer LOA were ± 2.35 mm for CRL and ± 4.87 mm for MSD. The intra-observer relative TEM for CRL were 4.62% and 3.70% whereas inter-observer relative TEM were 5.88% and 5.93% for CRL and MSD respectively. Intra- and inter-observer error of CRL and MSD measurements among pregnant women at Mulago hospital were acceptable. This implies that at Mulago hospital, the error in pregnancy dating is within acceptable margins of ±3 days in first trimester, and the CRL and MSD cut offs of ≥7 mm and ≥ 25 mm respectively are fit for diagnosis of miscarriage on TVS. These findings should be extrapolated to the whole country with caution. Sonographers can achieve acceptable and comparable diagnostic accuracy levels of MSD and CLR measurements with proper training and adherence to practice guidelines.

  7. Service user and family member perspectives on services for mental health, substance use/addiction, and violence: a qualitative study of their goals, experiences and recommendations.

    PubMed

    Haskell, Rebecca; Graham, Kathryn; Bernards, Sharon; Flynn, Andrea; Wells, Samantha

    2016-01-01

    Mental health and substance use disorders (MSD) are significant public health concerns that often co-occur with violence. To improve services that address MSD and violence [MSD(V)], it is critical to understand the perspectives of those most affected, people who have sought help for MSD(V) (i.e., "service users"), especially those with co-occurring issues, as well as their family members. We conducted structured interviews with 73 service users and 41 family members of service users in two Ontario communities (one urban, one rural) regarding their goals related to help-seeking, positive and negative experiences, and recommendations for improving systems of care. Overall, participants expressed a need for services that: (1) are respectful, nonjudgmental, and supportive, help service users to feel more 'normal' and include education to reduce stigma; (2) are accessible, varied and publicly funded, thereby meeting individual needs and addressing equity concerns at a systems level; and (3) are coordinated, holistic and inclusive of family members who often support service users. The findings provide a rich understanding of how service users and their families perceive services for MSD(V) issues and identify key ways to better meet their needs.

  8. 36 CFR 3.13 - What conditions apply to the use of Marine Sanitation Devices (MSD)?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false What conditions apply to the use of Marine Sanitation Devices (MSD)? 3.13 Section 3.13 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR BOATING AND WATER USE ACTIVITIES § 3.13 What conditions apply...

  9. 36 CFR 3.13 - What conditions apply to the use of Marine Sanitation Devices (MSD)?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false What conditions apply to the use of Marine Sanitation Devices (MSD)? 3.13 Section 3.13 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR BOATING AND WATER USE ACTIVITIES § 3.13 What conditions apply...

  10. [Musculoskeletal disorders and temporary disability. Characteristics and duration. Catalonia, 2007-2010].

    PubMed

    Manent Bistué, Ignasi; Ramada Rodilla, José Mª; Serra Pujadas, Consol

    Musculoskeletal disorders (MSD) are the leading cause of sickness absence (SA) in Spain and the second in Catalonia. A greater knowledge of this field could allow the refocusing of social protection policies and interventions to reduce their frequency and duration. The objective of the study was to describe the characteristics and duration of SA due to MSD in Catalonia between 2007 and 2010. The study population included all incident SA episodes due to MSD during the period 2007-2010, registered in the Institut Català d'AvaluacionsMèdiques (ICAM) database.We selected the 10 most frequentMSD (824.646 episodes) and extracted 607.732 (74%) SA episodes. We calculated the median duration of SA and analyzed the differences with Mann-Whitney U or Kruskal-Wallis tests, and studied the differences with a post-hoc test. We also conducted a survival analysis using Kaplan-Meier curves. The most frequent MSD were low back pain and neck pain. Median duration was greater for gonarthrosis and calcific tendonitis of the shoulder. The median duration of SA episodes was greater when pain was due to an organic disorder, in women (Z=51770950,5; p<0,001), increased with age (K=17335,72; p<0,001), and was longer in self-employed workers (Z=20965263,1; p<0.001) and in those working in agriculture and livestock (K=736,822; p<0,001). This study shows that the median duration of SA caused by MSD is influenced by the diagnosis, sex, age, type of work and type of social protection. Copyright belongs to the Societat Catalana de Salut Laboral.

  11. Looking for new biomarkers of skin wound vitality with a cytokine-based multiplex assay: preliminary study.

    PubMed

    Peyron, Pierre-Antoine; Baccino, Éric; Nagot, Nicolas; Lehmann, Sylvain; Delaby, Constance

    2017-02-01

    Determination of skin wound vitality is an important issue in forensic practice. No reliable biomarker currently exists. Quantification of inflammatory cytokines in injured skin with MSD ® technology is an innovative and promising approach. This preliminary study aims to develop a protocol for the preparation and the analysis of skin samples. Samples from ante mortem wounds, post mortem wounds, and intact skin ("control samples") were taken from corpses at the autopsy. After an optimization of the pre-analytical protocol had been performed in terms of skin homogeneisation and proteic extraction, the concentration of TNF-α was measured in each sample with the MSD ® approach. Then five other cytokines of interest (IL-1β, IL-6, IL-10, IL-12p70 and IFN-γ) were simultaneously quantified with a MSD ® multiplex assay. The optimal pre-analytical conditions consist in a proteic extraction from a 6 mm diameter skin sample, in a PBS buffer with triton 0,05%. Our results show the linearity and the reproductibility of the TNF-α quantification with MSD ® , and an inter- and intra-individual variability of the concentrations of proteins. The MSD ® multiplex assay is likely to detect differential skin concentrations for each cytokine of interest. This preliminary study was used to develop and optimize the pre-analytical and analytical conditions of the MSD ® method using injured and healthy skin samples, for the purpose of looking for and identifying the cytokine, or the set of cytokines, that may be biomarkers of skin wound vitality.

  12. Berkeley Lab - Materials Sciences Division

    Science.gov Websites

    MSD Support Human Resources Facilities & Space Planning Procurement and Property Proposals & ; Finance Templates Travel One-Stop Acknowledging MSD Support Human Resources Facilities & Space Operations For information regarding Human Resources, procedures for acknowledging MSD support, division

  13. Estimating the returns to United Kingdom publicly funded musculoskeletal disease research in terms of net value of improved health outcomes.

    PubMed

    Glover, Matthew; Montague, Erin; Pollitt, Alexandra; Guthrie, Susan; Hanney, Stephen; Buxton, Martin; Grant, Jonathan

    2018-01-10

    Building on an approach applied to cardiovascular and cancer research, we estimated the economic returns from United Kingdom public- and charitable-funded musculoskeletal disease (MSD) research that arise from the net value of the improved health outcomes in the United Kingdom. To calculate the economic returns from MSD-related research in the United Kingdom, we estimated (1) the public and charitable expenditure on MSD-related research in the United Kingdom between 1970 and 2013; (2) the net monetary benefit (NMB), derived from the health benefit in quality adjusted life years (QALYs) valued in monetary terms (using a base-case value of a QALY of £25,000) minus the cost of delivering that benefit, for a prioritised list of interventions from 1994 to 2013; (3) the proportion of NMB attributable to United Kingdom research; and (4) the elapsed time between research funding and health gain. The data collected from these four key elements were used to estimate the internal rate of return (IRR) from MSD-related research investments on health benefits. We analysed the uncertainties in the IRR estimate using a one-way sensitivity analysis. Expressed in 2013 prices, total expenditure on MSD-related research from 1970 to 2013 was £3.5 billion, and for the period used to estimate the rate of return, 1978-1997, was £1.4 billion. Over the period 1994-2013 the key interventions analysed produced 871,000 QALYs with a NMB of £16 billion, allowing for the net NHS costs resulting from them and valuing a QALY at £25,000. The proportion of benefit attributable to United Kingdom research was 30% and the elapsed time between funding and impact of MSD treatments was 16 years. Our best estimate of the IRR from MSD-related research was 7%, which is similar to the 9% for CVD and 10% for cancer research. Our estimate of the IRR from the net health gain to public and charitable funding of MSD-related research in the United Kingdom is substantial, and justifies the research investments made between 1978 and 1997. We also demonstrated the applicability of the approach previously used in assessing the returns from cardiovascular and cancer research. Inevitably, with a study of this kind, there are a number of important assumptions and caveats that we highlight, and these can inform future research.

  14. The role of HIV infection in the etiology and epidemiology of diarrheal disease among children aged 0-59 months in Manhiça district, Rural Mozambique.

    PubMed

    Acácio, Sozinho; Nhampossa, Tacilta; Quintó, Llorenç; Vubil, Delfino; Sacoor, Charfudin; Kotloff, Karen; Farag, Tamer; Dilruba, Nasrin; Macete, Eusebio; Levine, Myron M; Alonso, Pedro; Mandomando, Inácio; Bassat, Quique

    2018-05-28

    Diarrhea is an important health problem among HIV-infected patients. This study evaluates the role of HIV on the epidemiology, etiology and severity of diarrheal disease among children. The Global Enteric Multicenter Study enrolled children with moderate-to-severe (MSD) and less severe (LSD) diarrhea between December 2007 and November 2012. One to three controls for MSD cases and one per LSD case were enrolled and matched by age, sex and neighborhood. All children were tested for HIV. Clinical, anthropometric data and stools were collected. A follow-up was performed at 60 days. 214 MSD cases and 418 controls, together with 349 LSD cases and 214 controls were tested. HIV prevalence among MSD cases was 25% (4% for matched controls) and 6% among LSD cases (6% among matched controls). HIV-infected children were more likely to have MSD (OR=5.6, p< 0.0001). Mortality rates were higher among HIV-infected children compared with uninfected (34 vs. 5 per 1000 children-weeks at risk; p=0.0039). Cryptosporidium, Giardia, EAEC (aatA only) were more prevalent among HIV-infected MSD-cases than uninfected ones. HIV is an important risk factor for MSD. The high mortality rate implies that children with MSD should be screened for HIV and managed accordingly. Copyright © 2018. Published by Elsevier Ltd.

  15. Conceptualization of the Sexual Response Models in Men: Are there Differences Between Sexually Functional and Dysfunctional Men?

    PubMed

    Connaughton, Catherine; McCabe, Marita; Karantzas, Gery

    2016-03-01

    Research to validate models of sexual response empirically in men with and without sexual dysfunction (MSD), as currently defined, is limited. To explore the extent to which the traditional linear or the Basson circular model best represents male sexual response for men with MSD and sexually functional men. In total, 573 men completed an online questionnaire to assess sexual function and aspects of the models of sexual response. In total, 42.2% of men (242) were sexually functional, and 57.8% (331) had at least one MSD. Models were built and tested using bootstrapping and structural equation modeling. Fit of models for men with and without MSD. The linear model and the initial circular model were a poor fit for men with and without MSD. A modified version of the circular model demonstrated adequate fit for the two groups and showed important interactions between psychological factors and sexual response for men with and without MSD. Male sexual response was not represented by the linear model for men with or without MSD, excluding possible healthy responsive desire. The circular model provided a better fit for the two groups of men but demonstrated that the relations between psychological factors and phases of sexual response were different for men with and without MSD as currently defined. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  16. Centriolar satellite– and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly

    PubMed Central

    Hori, Akiko; Peddie, Christopher J.; Collinson, Lucy M.; Toda, Takashi

    2015-01-01

    Centriolar satellites are numerous electron-dense granules dispersed around the centrosome. Mutations in their components are linked to various human diseases, but their molecular roles remain elusive. In particular, the significance of spatial communication between centriolar satellites and the centrosome is unknown. hMsd1/SSX2IP localizes to both the centrosome and centriolar satellites and is required for tethering microtubules to the centrosome. Here we show that hMsd1/SSX2IP-mediated microtubule anchoring is essential for proper centriole assembly and duplication. On hMsd1/SSX2IP knockdown, the centriolar satellites become stuck at the microtubule minus end near the centrosome. Intriguingly, these satellites contain many proteins that normally localize to the centrosome. Of importance, microtubule structures, albeit not being anchored properly, are still required for the emergence of abnormal satellites, as complete microtubule depolymerization results in the disappearance of these aggregates from the vicinity of the centrosome. We highlighted, using superresolution and electron microscopy, that under these conditions, centriole structures are faulty. Remarkably, these cells are insensitive to Plk4 overproduction–induced ectopic centriole formation, yet they accelerate centrosome reduplication upon hydroxyurea arrest. Finally, the appearance of satellite aggregates is cancer cell specific. Together our findings provide novel insights into the mechanism of centriole assembly and microtubule anchoring. PMID:25833712

  17. Quantitative PCR for detection of Shigella improves ascertainment of Shigella burden in children with moderate-to-severe diarrhea in low-income countries.

    PubMed

    Lindsay, Brianna; Ochieng, John B; Ikumapayi, Usman N; Toure, Aliou; Ahmed, Dilruba; Li, Shan; Panchalingam, Sandra; Levine, Myron M; Kotloff, Karen; Rasko, David A; Morris, Carolyn R; Juma, Jane; Fields, Barry S; Dione, Michel; Malle, Dramane; Becker, Stephen M; Houpt, Eric R; Nataro, James P; Sommerfelt, Halvor; Pop, Mihai; Oundo, Joe; Antonio, Martin; Hossain, Anowar; Tamboura, Boubou; Stine, O Colin

    2013-06-01

    Estimates of the prevalence of Shigella spp. are limited by the suboptimal sensitivity of current diagnostic and surveillance methods. We used a quantitative PCR (qPCR) assay to detect Shigella in the stool samples of 3,533 children aged <59 months from the Gambia, Mali, Kenya, and Bangladesh, with or without moderate-to-severe diarrhea (MSD). We compared the results from conventional culture to those from qPCR for the Shigella ipaH gene. Using MSD as the reference standard, we determined the optimal cutpoint to be 2.9 × 10(4) ipaH copies per 100 ng of stool DNA for set 1 (n = 877). One hundred fifty-eight (18%) specimens yielded >2.9 × 10(4) ipaH copies. Ninety (10%) specimens were positive by traditional culture for Shigella. Individuals with ≥ 2.9 × 10(4) ipaH copies have 5.6-times-higher odds of having diarrhea than those with <2.9 × 10(4) ipaH copies (95% confidence interval, 3.7 to 8.5; P < 0.0001). Nearly identical results were found using an independent set of samples. qPCR detected 155 additional MSD cases with high copy numbers of ipaH, a 90% increase from the 172 cases detected by culture in both samples. Among a subset (n = 2,874) comprising MSD cases and their age-, gender-, and location-matched controls, the fraction of MSD cases that were attributable to Shigella infection increased from 9.6% (n = 129) for culture to 17.6% (n = 262) for qPCR when employing our cutpoint. We suggest that qPCR with a cutpoint of approximately 1.4 × 10(4) ipaH copies be the new reference standard for the detection and diagnosis of shigellosis in children in low-income countries. The acceptance of this new standard would substantially increase the fraction of MSD cases that are attributable to Shigella.

  18. Pain-related musculoskeletal disorders, psychological comorbidity, and the relationship with physical and mental well-being in Gulf War veterans.

    PubMed

    Kelsall, Helen Louise; McKenzie, Dean Philip; Forbes, Andrew Benjamin; Roberts, Minainyo Helen; Urquhart, Donna Michelle; Sim, Malcolm Ross

    2014-04-01

    Occupational activities such as lifting loads, working in constrained spaces, and training increase the risk of pain-related musculoskeletal disorders (MSDs) in military veterans. Few studies have investigated MSD and psychological disorder in veterans, and previous studies had limitations. This cross-sectional study compared pain-related MSD and psychological comorbidity and well-being between 1381 male Australian 1990-1991 Gulf War veterans (veterans) and a military comparison group (n=1377, of whom 39.6% were serving and 32.7% had previously deployed). At a medical assessment, 2000-2002, reported doctor-diagnosed arthritis or rheumatism, back or neck problems, joint problems, and soft tissue disorders were rated by medical practitioners as nonmedical, unlikely, possible, or probable diagnoses. Only probable MSDs were analysed. Psychological disorders in the past 12 months were measured using the Composite International Diagnostic Interview. The Short-Form Health Survey (SF-12) assessed 4-week physical and mental well-being. Almost one-quarter of veterans (24.5%) and the comparison group (22.4%) reported an MSD. Having any or specific MSD was associated with depression and posttraumatic stress disorder (PTSD), but not alcohol disorders. Physical and mental well-being was poorer in those with an MSD compared to those without, in both study groups (eg, veterans with any MSD, difference in SF-12 physical component summary scale medians = -10.49: 95% confidence interval -12.40, -8.57), and in those with MSD and psychological comorbidity compared with MSD alone. Comorbidity of any MSD and psychological disorder was more common in veterans, but MSDs were associated with depression, PTSD, and poorer well-being in both groups. Psychological comorbidity needs consideration in MSD management. Longitudinal studies are needed to assess directionality and causality. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  19. Evaluation of monoclonal antibody-based sandwich direct ELISA (MSD-ELISA) for antigen detection of foot-and-mouth disease virus using clinical samples.

    PubMed

    Morioka, Kazuki; Fukai, Katsuhiko; Sakamoto, Kenichi; Yoshida, Kazuo; Kanno, Toru

    2014-01-01

    A monoclonal antibody-based sandwich direct ELISA (MSD-ELISA) method was previously developed for foot-and-mouth disease (FMD) viral antigen detection. Here we evaluated the sensitivity and specificity of two FMD viral antigen detection MSD-ELISAs and compared them with conventional indirect sandwich (IS)-ELISA. The MSD-ELISAs were able to detect the antigen in saliva samples of experimentally-infected pigs for a longer term compared to the IS-ELISA. We also used 178 RT-PCR-positive field samples from cattle and pigs affected by the 2010 type-O FMD outbreak in Japan, and we found that the sensitivities of both MSD-ELISAs were about 7 times higher than that of the IS-ELISA against each sample (P<0.01). In terms of the FMD-positive farm detection rate, the sensitivities of the MSD-ELISAs were about 6 times higher than that of the IS-ELISA against each farm (P<0.01). Although it is necessary to conduct further validation study using the other virus strains, MSD-ELISAs could be appropriate as a method to replace IS-ELISA for FMD antigen detection.

  20. Physiotherapy in Primary Care Triage - the effects on utilization of medical services at primary health care clinics by patients and sub-groups of patients with musculoskeletal disorders: a case-control study.

    PubMed

    Bornhöft, Lena; Larsson, Maria E H; Thorn, Jörgen

    2015-01-01

    Primary Care Triage is a patient sorting system used in some primary health care clinics (PHCCs) in Sweden where patients with musculoskeletal disorders (MSD) are triaged directly to physiotherapists. The purpose of this study was to investigate whether sorting/triaging patients seeking a PHCC for MSD directly to physiotherapists affects their utilization of medical services at the clinic for the MSD and to determine whether the effects of the triaging system vary for different sub-groups of patients. A retrospective case-control study design was used at two PHCCs. At the intervention clinic, 656 patients with MSD were initially triaged to physiotherapists. At the control clinic, 1673 patients were initially assessed by general practitioners (GPs). The main outcome measures were the number of patients continuing to visit GPs after the initial assessment, the number of patients receiving referrals to specialists/external examinations, doctors' notes for sick-leave or prescriptions for analgesics during one year, all for the original MSD. Significantly fewer patients triaged to physiotherapists required multiple GP visits for the MSD or received MSD-related referrals to specialists/external examinations, sick-leave recommendations or prescriptions during the following year compared to the GP-assessed group. This applies to all sub-groups except for the group with lower extremity disorders, which did not reach significance for either multiple GP visits or sick-leave recommendations. The reduced utilization of medical services by patients with MSD who were triaged to physiotherapists at a PHCC is likely due to altered management of MSD with initial assessment by physiotherapists.

  1. Wavepacket dynamics in one-dimensional system with long-range correlated disorder

    NASA Astrophysics Data System (ADS)

    Yamada, Hiroaki S.

    2018-03-01

    We numerically investigate dynamical property in the one-dimensional tight-binding model with long-range correlated disorder having power spectrum 1 /fα (α: spectrum exponent) generated by Fourier filtering method. For relatively small α <αc (=2) time-dependence of mean square displacement (MSD) of the initially localized wavepacket shows ballistic spread and localizes as time elapses. It is shown that α-dependence of the dynamical localization length determined by the MSD exhibits a simple scaling law in the localization regime for the relatively weak disorder strength W. Furthermore, scaled MSD by the dynamical localization length almost obeys an universal function from the ballistic to the localization regime in the various combinations of the parameters α and W.

  2. Determination of patulin in fruit juices using HPLC-DAD and GC-MSD techniques.

    PubMed

    Moukas, Athanasios; Panagiotopoulou, Vasiliki; Markaki, Panagiota

    2008-08-15

    A high performance liquid chromatography with a diode-array detector (HPLC-DAD) and a gas chromatography with a mass spectrometer (GC-MSD) are described for the determination of patulin (PAT) in apple juice. The limits of detection (DL) and quantification (QL) for the HPLC-DAD and GC-MSD method were found to be (DL=0.23μgkg(-1) QL=1.2μgkg(-1)) and (DL=5.8μgkg(-1) and QL=13.8μgkg(-1)), respectively. The recovery factors for HPLC-DAD and GC-MSD were found to be 99.5% (RSD%=0.73) and 41% (RSD%=10.03), respectively. The HPLC-DAD method was used to determine the occurrence of PAT in 90 samples of fruit juices. Results revealed the presence of PAT in 100% of the samples examined. The mean values of PAT in concentrated fruit juices and in the commercial fruit juices collected from the Greek market were found to be 10.54μg PAT kg(-1) and 5.57μg PAT kg(-1) juice, respectively. The most contaminated samples were four concentrated juices ranging from 18.10μg PAT kg(-1) to 36.8μg PAT kg(-1) juice. The daily exposure to patulin for the consumers of all ages in Greece, is ranging from 0.008μg PAT kg(-1) bw to 0.1μg PAT kg(-1) bw if the daily intake of fruit juices is from 0.1 to 0.5kg. With the exception to the most contaminated sample, the daily exposure due to the samples examined, is below the provisional maximum tolerable daily intake for PAT (0.4μg PAT kg(-1) bw). Copyright © 2008 Elsevier Ltd. All rights reserved.

  3. Fast processing of digital imaging and communications in medicine (DICOM) metadata using multiseries DICOM format.

    PubMed

    Ismail, Mahmoud; Philbin, James

    2015-04-01

    The digital imaging and communications in medicine (DICOM) information model combines pixel data and its metadata in a single object. There are user scenarios that only need metadata manipulation, such as deidentification and study migration. Most picture archiving and communication system use a database to store and update the metadata rather than updating the raw DICOM files themselves. The multiseries DICOM (MSD) format separates metadata from pixel data and eliminates duplicate attributes. This work promotes storing DICOM studies in MSD format to reduce the metadata processing time. A set of experiments are performed that update the metadata of a set of DICOM studies for deidentification and migration. The studies are stored in both the traditional single frame DICOM (SFD) format and the MSD format. The results show that it is faster to update studies' metadata in MSD format than in SFD format because the bulk data is separated in MSD and is not retrieved from the storage system. In addition, it is space efficient to store the deidentified studies in MSD format as it shares the same bulk data object with the original study. In summary, separation of metadata from pixel data using the MSD format provides fast metadata access and speeds up applications that process only the metadata.

  4. Fast processing of digital imaging and communications in medicine (DICOM) metadata using multiseries DICOM format

    PubMed Central

    Ismail, Mahmoud; Philbin, James

    2015-01-01

    Abstract. The digital imaging and communications in medicine (DICOM) information model combines pixel data and its metadata in a single object. There are user scenarios that only need metadata manipulation, such as deidentification and study migration. Most picture archiving and communication system use a database to store and update the metadata rather than updating the raw DICOM files themselves. The multiseries DICOM (MSD) format separates metadata from pixel data and eliminates duplicate attributes. This work promotes storing DICOM studies in MSD format to reduce the metadata processing time. A set of experiments are performed that update the metadata of a set of DICOM studies for deidentification and migration. The studies are stored in both the traditional single frame DICOM (SFD) format and the MSD format. The results show that it is faster to update studies’ metadata in MSD format than in SFD format because the bulk data is separated in MSD and is not retrieved from the storage system. In addition, it is space efficient to store the deidentified studies in MSD format as it shares the same bulk data object with the original study. In summary, separation of metadata from pixel data using the MSD format provides fast metadata access and speeds up applications that process only the metadata. PMID:26158117

  5. A novel tamponade agent for management of post partum hemorrhage: adaptation of the Xstat mini-sponge applicator for obstetric use.

    PubMed

    Rodriguez, Maria I; Jensen, Jeffrey T; Gregory, Kenton; Bullard, Mary; Longo, Paul; Heidel, Jerry; Edelman, Alison

    2017-06-13

    Although uterine tamponade is an effective treatment for postpartum hemorrhage (PPH), current methods have key limitations in their use, particularly in low resource settings. The XStat™ Mini Sponge Dressing (MSD) is approved for the management of non-compressible wounds in the battlefield/trauma setting. The MSD applies highly compressed medical sponges capable of stopping high-flow arterial bleeding within seconds. The objective of our study was to adopt the MSD for use in managing PPH. We performed desktop testing using a uterine model with pressure sensors to compare key design elements of the obstetrical prototype MSD (fundal pressure achieved, reduction in fluid loss, time to deploy, and time to remove) with alternativetechniques (uterine packing, balloon tamponade). To evaluate safety, we delivered the fetus of pregnant ewes by cesarean section and used the prototype to deliver the MSD into one uterine horn, and closed the hysterotomy. We followed the clinical recovery of animals (n = 3) over 24 h, and then removed the reproductive tract for histologic evaluation. To evaluate late effects, we surgically removed the MSDs after 24 h, and followed the clinical recovery of animals (n = 6) for an additional seven days before tissue removal. The obstetrical prototype has a long tapered delivery system designed to be deployed during vaginal examination, and administers three times the volume of the approved MSD trauma bandage. The MSD are deployed within a mesh bag to facilitate removal by vaginaltraction. On desktop testing, the MSD resulted in the highest average fundal pressure (113 mmHg), followed by the MSD bag device (85.8 mmHg), gauze packing (15.5 mmHg), and the uterine balloon (8.2 mmHg). The MSD bag test group achieved the largest fluid flow reduction of -74%, followed by gauze packing (-55%), MSD (-35%), and uterine balloon (-19%). Animal testing demonstrated good uterine fill with no evidence of adverse clinical recovery, uterine trauma or infection at 24 h, or up to 7 days following device removal. We adapted a highly effective trauma dressing and applicator for use in the treatment of severe PPH. Preliminary desktop and animal testing provide a basis for initial clinical trials in women.

  6. A prospective registration study to determine feasibility of hematopoietic SCT in adults with acute leukemia: planning, expectations and reality.

    PubMed

    Labopin, M; Gorin, N-C; Polge, E; Socié, G; Gurman, G; Gluckman, E; Jindra, P; Poiré, X; Schäfer-Eckart, K; Ruutu, T; Milone, G; Arcese, W; Mohty, M; Rocha, V

    2014-03-01

    For adults with acute leukemia, it is important to know whether the therapeutic schemes initially planned were actually implemented. The European Group for Blood and Marrow transplantation Acute Leukemia Working Party prospectively followed 695 consecutive patients who were registered at the time of HLA typing. Of 304 patients with an available matched sibling donor (MSD), SCT was planned in 264, chemotherapy in 33 and autografting in 7. For the rest, an unrelated donor (UD) search was initiated in 198. Among these, 117 were transplanted, 114 received chemotherapy and 77 underwent autografting. Probabilities of receiving a planned treatment were 60 and 65% at 1 and 2 years, respectively. Patients scheduled to receive MSD SCT had an 82% probability, whereas those scheduled to undergo UD SCT had a 57% probability, of receiving their transplant at 1 year. The only factor associated with a lower probability of MSD SCT in first remission was delayed HLA typing (HR=0.82; P=0.03). One year after enrollment, 40% of patients did not follow their initial treatment plan. Because OS was 50% only at 3 years and only 57% of the patients without a MSD underwent SCT, this suggests room for improvement in outcomes for adults with acute leukemia.

  7. Work–Life Imbalance and Musculoskeletal Disorders among South Korean Workers

    PubMed Central

    Kim, Young-Mee

    2017-01-01

    Employed workers often have family responsibilities such as childcare or homemaking. This dual burden may increase work-related health problems, particularly if there are conflicts between work and family responsibilities. This study assessed whether difficulty in work–life balance is associated with musculoskeletal disorders (MSD) among Korean employees. Data from the population-based Korean Working Conditions Survey of 2011, including 28,640 male and 21,392 female workers, were used. Men and women were analyzed separately to investigate gender differences. MSD were defined as pain in the back, neck, shoulder, or extremities during the past year. Self-assessed difficulty in work–life balance was defined as a work–life conflict (WLC). Adjustments for physical factors, as well as other occupational and socio-demographic variables, were made using multiple logistic regression analysis. Interaction terms including WLCs and key covariates were also incorporated. WLC was significantly associated with increased frequency of MSD in both men (OR: 1.49) and women (OR: 1.50). There were significant interaction effects between WLC and some key covariates (job stress for men and job stress, work hours, physical demand, and frequent overtime work for women). We suggest that having the flexibility to coordinate work and family life is important to prevent MSD among employees. PMID:29104228

  8. Work-Life Imbalance and Musculoskeletal Disorders among South Korean Workers.

    PubMed

    Kim, Young-Mee; Cho, Sung-Il

    2017-11-01

    Employed workers often have family responsibilities such as childcare or homemaking. This dual burden may increase work-related health problems, particularly if there are conflicts between work and family responsibilities. This study assessed whether difficulty in work-life balance is associated with musculoskeletal disorders (MSD) among Korean employees. Data from the population-based Korean Working Conditions Survey of 2011, including 28,640 male and 21,392 female workers, were used. Men and women were analyzed separately to investigate gender differences. MSD were defined as pain in the back, neck, shoulder, or extremities during the past year. Self-assessed difficulty in work-life balance was defined as a work-life conflict (WLC). Adjustments for physical factors, as well as other occupational and socio-demographic variables, were made using multiple logistic regression analysis. Interaction terms including WLCs and key covariates were also incorporated. WLC was significantly associated with increased frequency of MSD in both men (OR: 1.49) and women (OR: 1.50). There were significant interaction effects between WLC and some key covariates (job stress for men and job stress, work hours, physical demand, and frequent overtime work for women). We suggest that having the flexibility to coordinate work and family life is important to prevent MSD among employees.

  9. Fatigue analysis of multiple site damage at a row of holes in a wide panel

    NASA Technical Reports Server (NTRS)

    Buhler, Kimberley; Grandt, Alten F., Jr.; Moukawsher, E. J.

    1994-01-01

    This paper is concerned with predicting the fatigue life of unstiffened panels which contain multiple site damage (MSD). The initial damage consists of through-the-thickness cracks emanating from a row of holes in the center of a finite width panel. A fracture mechanics analysis has been developed to predict the growth, interaction, and coalescence of the various cracks which propagate in the panel. A strain-life analysis incorporating Neuber's rule for notches, and Miner's rule for cumulative damage, is also employed to predict crack initiation for holes without initial cracking. This analysis is compared with the results of a series of fatigue tests on 2024-T3 aluminum panels, and is shown to do an excellent job of predicting the influence of MSD on the fatigue life of nine inch wide specimens. Having established confidence in the ability to analyze the influence of MSD on fatigue life, a parametric study is conducted to examine the influence of various MSD scenarios in an unstiffened panel. The numerical study considered 135 cases in all, with the parametric variables being the applied cyclic stress level, the lead crack geometry, and the number and location of MSD cracks. The numerical analysis provides details for the manner in which lead cracks and MSD cracks grow and coalesce leading to final failure. The results indicate that MSD located adjacent to lead cracks is the most damaging configuration, while for cases without lead cracks, MSD clusters which are not separated by uncracked holes are most damaging.

  10. Canaries in the Coal Mine: Perceptions of Threat and Media System Dependency Relations.

    ERIC Educational Resources Information Center

    Loges, William E.

    1994-01-01

    Investigates whether the intensity and scope of media system dependency (MSD) relations are positively related to perceptions of threats in the environment. Finds that higher perceptions of threat are associated with more intense MSD relations; threat perceptions are strong predictors of the intensity of MSD relations when demographic variables…

  11. 18 CFR 1304.101 - Nonnavigable houseboats.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... follows with a properly installed and operating Marine Sanitation Device (MSD) or Sewage Holding Tank and... or Type II MSD. (2) Nonnavigable houseboats moored in: “No Discharge Lakes” must be equipped with... equipped with a Type I or Type II MSD, it must be secured to prevent discharge into the lake. (d) Approved...

  12. Cultural meanings of musculoskeletal diseases in Chile's Mapuche Population.

    PubMed

    Alarcon, Ana M; Vidal, Aldo; Castro, Marcela

    2013-10-01

    Eight out of 10 Mapuche indigenous women have a musculoskeletal disorder (MSD) and do not seek early medical aid. To study both the cultural meanings and implications of MSD from the Mapuche worldview. Ethnographic study carried out from 2008 to 2011 on indigenous reserves in southern Chile. Sixty-four Mapuches participated in comprehensive interviews, which were transcribed and analyzed by the research team. Five cultural domains: (a) foro kutran/bone disease is the general denomination of MSD; (b) Re-Rume Kutran/progressive and incurable course, refers to the course of the disease; (c) Kalül fücha mawiza/body is an old tree, describes internal manifestations such as worn bones, dry body, weak blood, and spiritual weakness; (d) witrür tripai foro/deformation is the external manifestation of MSD; and (e) Reñma ka lof kutran/family and community suffering refers to the impact of MSD. The explanation of MSD is consistent with the integrated body-nature-spirit worldview of the Mapuche. To provide cultural nursing health care so that patients receive prompt diagnosis and care.

  13. Impact of physician preferences for homeopathic or conventional medicines on patients with musculoskeletal disorders: results from the EPI3-MSD cohort.

    PubMed

    Rossignol, Michel; Begaud, Bernard; Engel, Pierre; Avouac, Bernard; Lert, France; Rouillon, Frederic; Bénichou, Jacques; Massol, Jacques; Duru, Gerard; Magnier, Anne-Marie; Guillemot, Didier; Grimaldi-Bensouda, Lamiae; Abenhaim, Lucien

    2012-10-01

    The objective of this study was to assess the effect of physician practicing preferences (PPP) in primary care for homeopathy (Ho), CAM (Complementary and alternative medicines) with conventional medicine (Mx) or exclusively conventional medicine (CM) on patients with musculoskeletal disorders (MSDs), with reference to clinical progression, drug consumption, side effects and loss of therapeutic opportunity. The EPI3-MSD study was a nationwide observational cohort of a representative sample of general practitioners (GP) and their patients in France. Recruitment of GP was stratified by PPP, which was self-declared. Diagnoses and comorbidities were recorded by GP at inclusion. Patients completed a standardized telephone interview at inclusion, one, three and twelve months, including MSD-functional scales and medication consumption. 1153 MSD patients were included in the three PPP groups. Patients did not differ between groups except for chronicity of MSDs (>12 weeks), which was higher in the Ho group (62.1%) than in the CM (48.6%) and Mx groups (50.3%). The twelve-month development of specific functional scores was identical across the three groups after controlling for baseline score (p > 0.05). After adjusting for propensity scores, NSAID use over 12 months was almost half in the Ho group (OR, 0.54; 95%CI, 0.38-0.78) as compared to the CM group; no difference was found in the Mx group (OR, 0.81; 95% CI: 0.59-1.15). MSD patients seen by homeopathic physicians showed a similar clinical progression when less exposed to NSAID in comparison to patients seen in CM practice, with fewer NSAID-related adverse events and no loss of therapeutic opportunity. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Stability and change of body mass index as a predictor of disability pension.

    PubMed

    Ropponen, Annina; Silventoinen, Karri; Koskenvuo, Markku; Svedberg, Pia; Kaprio, Jaakko

    2016-06-01

    To investigate whether stability or change in body mass index (BMI) predict disability pension (DP) due to musculoskeletal diagnosis (MSD) when controlling for familial confounding. Our study cohort consisted of 17,169 Finnish twins born before 1958. Data on BMI and multiple covariates from questionnaires in 1975 and 1981 were included and DPs were collected from the national pension registers until the end of 2004. Cox proportional hazards regression models with Hazard Ratios (HR) and 95% Confidence Intervals (CI) were used for statistical analyses. General DP was granted to 2853 individuals and DP due to MSD to 1143 individuals during the 23-year follow-up. A one-unit increase in BMI in both 1975 (HR 1.08, 95% CI 1.05, 1.10) and 1981 (HR 1.06, 95% CI 1.04, 1.07), as well as the stability of and change in BMI from 1975 to 1981 were all associated with an increased risk of DP. These associations held in the analyses controlling for multiple covariates (age, sex, socioeconomic status, education, marital status, leisure-time physical activity, and musculoskeletal pain), and mainly also familial confounding, that is, genetics and shared environment. HR for stable obesity was 2.28 (95% CI 1.69, 3.08) for DP due to MSD, and 1.91 (95% CI 1.56, 2.34) for general DP in the fully adjusted models. CONCLUSIONS BMI IS AN EARLY PREDICTOR OF GENERAL DP AND ALSO OF DP DUE TO MSD OWING TO THE INDEPENDENCY OF VARIOUS COVARIATES AND POTENTIALLY ALSO FAMILIAL CONFOUNDING, BMI MAY POSSIBLY HAVE A DIRECT EFFECT ON THE RISK OF DP. © 2016 the Nordic Societies of Public Health.

  15. An implementation evaluation of a qualitative culture assessment tool.

    PubMed

    Tappin, D C; Bentley, T A; Ashby, L E

    2015-03-01

    Safety culture has been identified as a critical element of healthy and safe workplaces and as such warrants the attention of ergonomists involved in occupational health and safety (OHS). This study sought to evaluate a tool for assessing organisational safety culture as it impacts a common OHS problem: musculoskeletal disorders (MSD). The level of advancement across nine cultural aspects was assessed in two implementation site organisations. These organisations, in residential healthcare and timber processing, enabled evaluation of the tool in contrasting settings, with reported MSD rates also high in both sectors. Interviews were conducted with 39 managers and workers across the two organisations. Interview responses and company documentation were compared by two researchers to the descriptor items for each MSD culture aspect. An assignment of the level of advancement, using a five stage framework, was made for each aspect. The tool was readily adapted to each implementation site context and provided sufficient evidence to assess their levels of advancement. Assessments for most MSD culture aspects were in the mid to upper levels of advancement, although the levels differed within each organisation, indicating that different aspects of MSD culture, as with safety culture, develop at a different pace within organisations. Areas for MSD culture improvement were identified for each organisation. Reflections are made on the use and merits of the tool by ergonomists for addressing MSD risk. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  16. Cost Effectiveness Study of Wastewater Management Systems for Selected U.S. Coast Guard Vessels. Volume V. Characteristics and Cost Estimates of Selected Marine Sanitary Devices

    DTIC Science & Technology

    1977-02-01

    emissions to meet Applicable standards for () disposal Of oJ~l-cOntAminated residues At sAG (A) MSD) suhsystem tias no potential for prr’ducing ail...odoriferous compounds are oxidized to mainly carbon dioxide and water vapor. The vapor treatment section (VTS) consists mainly of 1-1/2 inch piping...materials in black water stream. 61 Ability of MSD secondary emissions to moot applicable standards for tile discharge of air pollutants (a) No

  17. Predictors of musculoskeletal discomfort: A cross-cultural comparison between Malaysian and Australian office workers.

    PubMed

    Maakip, Ismail; Keegel, Tessa; Oakman, Jodi

    2017-04-01

    Prevalence and predictors associated with musculoskeletal disorders (MSDs) vary considerably between countries. It is plausible that socio-cultural contexts may contribute to these differences. We conducted a cross-sectional survey with 1184 Malaysian and Australian office workers with the aim to examine predictors associated with MSD discomfort. The 6-month period prevalence of self-reported MSD discomfort for Malaysian office workers was 92.8% and 71.2% among Australian workers. In Malaysia, a model regressing level of musculoskeletal discomfort against possible risk factors was significant overall (F [6, 370] = 17.35; p < 0.001) and explained 22% (r = 0.46) of its variance. MSD discomfort was significantly associated with predictors that included gender (β = 14), physical (β = 0.38) and psychosocial hazards (β = -0.10), and work-life balance (β = -0.13). In Australia, the regression model is also significant (F [6, 539] = 16.47; p < 0.001) with the model explaining 15.5% (r = 0.39) of the variance in MSD discomfort. Predictors such as gender (β = 0.14), physical (β = 24) and psychosocial hazards (β = -0.17), were associated with MSD discomfort in Australian office workers. Predictors associated with MSD discomfort were similar, but their relative importance differed. Work-life balance was significantly associated with increased MSD discomfort for the Malaysian population only. Design and implementation of MSD risk management needs to take into account the work practices and culture of the target population. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  18. The Effect of Multiple Sulfatase Deficiency (MSD) on Dental Development: Can We Use the Teeth as an Early Diagnostic Tool?

    PubMed

    Zilberman, Uri; Bibi, Haim

    2016-01-01

    Multiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of metabolism due to reduced catalytic activity of the different sulfatase. Affected individuals show neurologic deterioration with mental retardation, skeletal anomalies, organomegaly, and skin changes as in X-linked ichthyosis. The only organ that was not examined in MSD patients is the dentition. To evaluate the effect of the metabolic error on dental development in a patient with the intermediate severe late-infantile form of MSD (S155P). Histological and chemical study were performed on three deciduous and five permanent teeth from MSD patient and pair-matched normal patients. Tooth germ size and enamel thickness were reduced in both deciduous and permanent MSD teeth, and the scalloping feature of the DEJ was missing in MSD teeth causing enamel to break off from the dentin. The mineral components in the enamel and dentin were different. The metabolic error insults the teeth in the stage of organogenesis in both the deciduous and permanent dentition. The end result is teeth with very sharp cusp tips, thin hypomineralized enamel, and exposed dentin due to the break off of enamel. These findings are different from all other types of MPS syndromes.Clinically the phenotype of intermediate severe late-infantile form of MSD appeared during the third year of life. In children of parents that are carriers, we can diagnose the disease as early as birth using X-ray radiograph of the anterior upper region or as early as 6-8 months when the first deciduous tooth erupt and consider very early treatment to ameliorate the symptoms.

  19. Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles.

    PubMed

    Aiba, Toshiki; Saito, Toshiyuki; Hayashi, Akiko; Sato, Shinji; Yunokawa, Harunobu; Maruyama, Toru; Fujibuchi, Wataru; Kurita, Hisaka; Tohyama, Chiharu; Ohsako, Seiichiroh

    2017-03-09

    It has been pointed out that environmental factors or chemicals can cause diseases that are developmental in origin. To detect abnormal epigenetic alterations in DNA methylation, convenient and cost-effective methods are required for such research, in which multiple samples are processed simultaneously. We here present methylated site display (MSD), a unique technique for the preparation of DNA libraries. By combining it with amplified fragment length polymorphism (AFLP) analysis, we developed a new method, MSD-AFLP. Methylated site display libraries consist of only DNAs derived from DNA fragments that are CpG methylated at the 5' end in the original genomic DNA sample. To test the effectiveness of this method, CpG methylation levels in liver, kidney, and hippocampal tissues of mice were compared to examine if MSD-AFLP can detect subtle differences in the levels of tissue-specific differentially methylated CpGs. As a result, many CpG sites suspected to be tissue-specific differentially methylated were detected. Nucleotide sequences adjacent to these methyl-CpG sites were identified and we determined the methylation level by methylation-sensitive restriction endonuclease (MSRE)-PCR analysis to confirm the accuracy of AFLP analysis. The differences of the methylation level among tissues were almost identical among these methods. By MSD-AFLP analysis, we detected many CpGs showing less than 5% statistically significant tissue-specific difference and less than 10% degree of variability. Additionally, MSD-AFLP analysis could be used to identify CpG methylation sites in other organisms including humans. MSD-AFLP analysis can potentially be used to measure slight changes in CpG methylation level. Regarding the remarkable precision, sensitivity, and throughput of MSD-AFLP analysis studies, this method will be advantageous in a variety of epigenetics-based research.

  20. The integration between Business Model Canvas and Manufacturing System Design

    NASA Astrophysics Data System (ADS)

    Prasetyawan, Y.; Maulida, N.; Lutvitasari, M. R.

    2018-04-01

    Business Model Canvas (BMC) is an increasingly popular business design tool especially for a start-up business and new business player. In general, BMC seeks a balance between effective working patterns with suppliers, good relation with customers and ability to understand and manage internal resources. This balance will expedite the implementation of Manufacturing System Design (MSD). The existing use of BMC and MSD is frequently applied separately at various business levels. BMC business plan is primarily to have engagement with customers and explore potential revenue to increase profits, while MSD primarily aims to meet production targets with available resources. The purpose of this research is to provide a roadmap to align BMC and MSD. A series of simple mathematical (modified) and integration models are created to connect BMC and MSD. Several results in various industries (new, developed and mature) are presented and used as examples of implementation.

  1. Prevention of MSD within OHSMS/IMS: a systematic review of risk assessment strategies.

    PubMed

    Yazdani, Amin; Wells, Richard

    2012-01-01

    The purpose of this systematic review was to identify and summarize the research evidence on prevention of Musculoskeletal Disorders (MSD) within Occupational Health and Safety Management Systems (OHSMS) and Integrated Management Systems (IMS). Databases in business, management, engineering and health and safety were systematically searched and relevant publications were synthesized. The number of papers that could address the research questions was small. However, the review revealed that many of the techniques to address MSD hazards require substantial background knowledge and training. This may limit employees' involvement in the technical aspects of the risk assessment process. Also these techniques did not usually fit into techniques used by companies to address other risk factors within their management systems. This could result in MSD prevention becoming a separate issue that cannot be managed with company-wide tools. In addition, this review also suggested that there is a research gap concerning the MSD prevention within companies' management systems.

  2. Influence of age, body weight and body condition score before mating start date on the pubertal rate of maiden Holstein-Friesian heifers and implications for subsequent cow performance and profitability.

    PubMed

    Archbold, H; Shalloo, L; Kennedy, E; Pierce, K M; Buckley, F

    2012-07-01

    The aim of this study was to assess the influence of age, body weight (BW) and body condition score (BCS) of maiden Holstein-Friesian heifers before mating start date (MSD) on the rate of puberty, subsequent production and longevity and their implications with regard to farm profitability. Data were available on 871 Holstein-Friesian heifers from 48 herds. BW was recorded electronically and BCS was recorded by a single operator on a scale of 1 to 5. Heifer age was calculated as the number of days from birth to the day of visit. All of the independent variables of interest were grouped into three or four categories. Three age categories (thirtiles), four BW categories (quartiles) and four BCS categories (≤ 2.75, 3.00, 3.25 and ≥ 3.50) were formed. Heifers with an identifiable corpus lutuem (CL) in the presence or absence of large follicles and peri-ovulatory signs and with a plasma progesterone (P4) concentration ≥ 1 ng/ml were classified as pubertal. In addition, heifers without an identifiable CL in the presence or absence of large follicles and peri-ovulatory signs but with a P4 concentration ≥ 1 ng/ml were also classified as pubertal. Age, BW and BCS at MSD were all found to be significantly associated with pubertal rate (P < 0.05). Age was shown to have no practical implications on subsequent cow performance. BW at MSD was favourably associated with subsequent calving date (P < 0.05), subsequent cow BW (P < 0.001) and potential (305 days) milk fat plus protein yield (P < 0.001). BCS at MSD was found to be favourably associated with milk fat plus protein yield potential (P < 0.05) and BCS (P < 0.001) during lactation. The economic analysis undertaken indicated that larger, well-grown heifers will be more profitable because of superior production potential, all else being equal. However, because of the finding of poorer reproductive efficiency in heifers grown to more than 343 kg at MSD, heifers at ∼330 kg at MSD are deemed optimal. This will correspond to mature cow BW of ∼550 kg.

  3. Mitochondrial fluctuations as a measure of active biomechanical properties of mammalian cells

    NASA Astrophysics Data System (ADS)

    Xu, Wenlong; Alizadeh, Elaheh; Castle, Jordan; Prasad, Ashok

    A single-cell assay of mechanical properties would give significant insights into cellular processes. Force spectrum microscopy is one such technique, which involves both active and passive particle tracking microrheology on the same cells. Since active microrheology requires expensive instruments, it is of great interest to develop simpler alternatives. Here we study an alternative using endogenous mitochondrial fluctuations, rather than fluorescent beads, in particle tracking microrheology. Mitochondria of the C3H-10T1/2 cell line are labeled and tracked using confocal microscopy, their mean square displacement (MSD) measured, and mechanical parameters calculated. Active fluctuations are distinguished from passive fluctuations by treatment with ATP synthesis inhibitors. We find that the MSD of mitochondria resembles that of particles in viscoelastic media. However, comparisons of MSD between controls and cells disrupted in the actin or microtubule network showed surprisingly small effects, while ATP-depleted cells showed significantly decreased MSD, and characteristics of thermally driven fluctuations. Both active and ATP-depleted parameters showed heterogeneity among cells and between cell lines. This method is potentially very useful due to its simplicity. We gratefully acknowledge support from NSF CAREER Grant PHY-1151454 awarded to Ashok Prasad.

  4. Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study.

    PubMed

    Ruggeri, Annalisa; Battipaglia, Giorgia; Labopin, Myriam; Ehninger, Gerhard; Beelen, Dietrich; Tischer, Johanna; Ganser, Arnold; Schwerdtfeger, Rainer; Glass, Bertram; Finke, Jurgen; Michallet, Mauricette; Stelljes, Matthias; Jindra, Pavel; Arnold, Renate; Kröger, Nicolaus; Mohty, Mohamad; Nagler, Arnon

    2016-09-17

    Allogeneic stem cell transplantation is the only curative option for patients with acute myeloid leukemia (AML) experiencing relapse. Either matched sibling donor (MSD) or unrelated donor (UD) is indicated. We analyzed 1554 adults with AML transplanted from MSD (n = 961) or UD (n = 593, HLA-matched 10/10, n = 481; 9/10, n = 112). Compared to MSD, UD recipients were older (49 vs 52 years, p = 0.001), transplanted more recently (2009 vs 2006, p = 0.001), and with a longer interval to transplant (10 vs 9 months, p = 0.001). Conditioning regimen was more frequently myeloablative for patients transplanted with a MSD (61 vs 46 %, p = 0.001). Median follow-up was 28 (range 3-157) months. Cumulative incidence (CI) of neutrophil engraftment (p = 0.07), grades II-IV acute GVHD (p = 0.11), chronic GVHD (p = 0.9), and non-relapse mortality (NRM, p = 0.24) was not different according to the type of donor. At 2 years, CI of relapse (relapse incidence (RI)) was 57 vs 49 % (p = 0.001). Leukemia-free survival (LFS) at 2 years was 21 vs 26 % (p = 0.001), and overall survival (OS) was 26 vs 33 % (p = 0.004) for MSD vs UD, respectively. Chronic GVHD as time-dependent variable was associated with lower RI (HR 0.78, p = 0.05), higher NRM (HR 1.71, p = 0.001), and higher OS (HR 0.69, p = 0.001). According to HLA match, RI was 57 vs 50 vs 45 %, (p = 0.001) NRM was 23 vs 23 vs 29 % (p = 0.26), and LFS at 2 years was 21 vs 27 vs 25 % (p = 0.003) for MSD, 10/10, and 9/10 UD, respectively. In multivariate analysis adjusted for differences between the two groups, UD was associated with lower RI (HR 0.76, p = 0.001) and higher LFS (HR 0.83, p = 0.001) compared to MSD. Interval between diagnosis and transplant was the other factor associated with better outcomes (RI (HR 0.62, p < 0.001) and LFS (HR 0.67, p < 0.001)). Transplantation using UD was associated with better LFS and lower RI compared to MSD for high-risk patients with AML transplanted in first relapse.

  5. Toe thumb: a musculoskeletal disorder related to transesophageal echocardiography.

    PubMed

    Tewari, Prabhat; Raju, P S N; Neema, P K

    2014-01-01

    The musculoskeletal disorders (MSD) are common in healthcare providers and those who are doing sonography are also affected. There are reports of MSD in healthcare providers who do transthoracic echocardiography. Transesophageal echocardiography (TEE) is being regularly used in peri-operative setting. We describe MSD of hand in a cardiovascular and thoracic anesthesiologist who has been performing TEE scanning for 10% of his work-time in operating room and critical care area for the last 8 years. As the role of TEE is increasing and many doctors are doing it on a routine basis, the knowledge of association of MSD with TEE and measures to prevent it is important.

  6. E-MSD: improving data deposition and structure quality.

    PubMed

    Tagari, M; Tate, J; Swaminathan, G J; Newman, R; Naim, A; Vranken, W; Kapopoulou, A; Hussain, A; Fillon, J; Henrick, K; Velankar, S

    2006-01-01

    The Macromolecular Structure Database (MSD) (http://www.ebi.ac.uk/msd/) [H. Boutselakis, D. Dimitropoulos, J. Fillon, A. Golovin, K. Henrick, A. Hussain, J. Ionides, M. John, P. A. Keller, E. Krissinel et al. (2003) E-MSD: the European Bioinformatics Institute Macromolecular Structure Database. Nucleic Acids Res., 31, 458-462.] group is one of the three partners in the worldwide Protein DataBank (wwPDB), the consortium entrusted with the collation, maintenance and distribution of the global repository of macromolecular structure data [H. Berman, K. Henrick and H. Nakamura (2003) Announcing the worldwide Protein Data Bank. Nature Struct. Biol., 10, 980.]. Since its inception, the MSD group has worked with partners around the world to improve the quality of PDB data, through a clean up programme that addresses inconsistencies and inaccuracies in the legacy archive. The improvements in data quality in the legacy archive have been achieved largely through the creation of a unified data archive, in the form of a relational database that stores all of the data in the wwPDB. The three partners are working towards improving the tools and methods for the deposition of new data by the community at large. The implementation of the MSD database, together with the parallel development of improved tools and methodologies for data harvesting, validation and archival, has lead to significant improvements in the quality of data that enters the archive. Through this and related projects in the NMR and EM realms the MSD continues to improve the quality of publicly available structural data.

  7. The Effects of Modified Simiao Decoction in the Treatment of Gouty Arthritis: A Systematic Review and Meta-Analysis

    PubMed Central

    Huang, Ying; Wen, Cai-Yu-Zhu; Zhang, Jun-Jun; Xing, Guo-Lan; Chen, Zhe

    2017-01-01

    The modified Simiao decoctions (MSD) have been wildly applied in the treatment of gouty arthritis in China. However, the evidence needs to be evaluated by a systematic review and meta-analysis. After filtering, twenty-four randomised, controlled trials (RCTs) comparing the effects of MSD and anti-inflammation medications and/or urate-lowering therapies in patients with gouty arthritis were included. In comparison with anti-inflammation medications, urate-lowering therapies, or coadministration of anti-inflammation medications and urate-lowering therapies, MSD monotherapy significantly lowered serum uric acid (p < 0.00001, mean difference = −90.62, and 95% CI [−128.38, −52.86]; p < 0.00001, mean difference = −91.43, and 95% CI [−122.38, −60.49]; p = 0.02, mean difference = −40.30, and 95% CI [−74.24, −6.36], resp.). Compared with anti-inflammation medications and/or urate-lowering therapies, MSD monotherapy significantly decreased ESR (p < 0.00001; mean difference = −8.11; 95% CI [−12.53, −3.69]) and CRP (p = 0.03; mean difference = −3.21; 95% CI [−6.07, −0.36]). Additionally, the adverse effects (AEs) of MSD were fewer (p < 0.00001; OR = 0.08; 95% CI [0.05, 0.16]). MSD are effective in the treatment of gouty arthritis through anti-inflammation and lowering urate. However, the efficacy of MSD should be estimated with more RCTs. PMID:28373889

  8. Prevalence, diagnostics and management of musculoskeletal disorders in primary health care in Sweden – an investigation of 2000 randomly selected patient records

    PubMed Central

    Fahlström, Martin; Djupsjöbacka, Mats

    2016-01-01

    Abstract Rationale, aims and objectives The aims of this study is to investigate the prevalence of patients seeking care due to different musculoskeletal disorders (MSDs) at primary health care centres (PHCs), to chart different factors such as symptoms, diagnosis and actions prescribed for patients that visited the PHCs due to MSD and to make comparisons regarding differences due to gender, age and rural or urban PHC. Methods Patient records (2000) for patients in working age were randomly selected equally distributed on one rural and one urban PHC. A 3‐year period was reviewed retrospectively. For all patient records' background data, cause to the visit and diagnosis were registered. For visits due to MSD, type and location of symptoms and actions to resolve the patients problems were registered. Data was analysed using cross tabulation, multidimensional chi‐squared. Results The prevalence of MSD was high; almost 60% of all patients were seeking care due to MSD. Upper and lower limb problems were most common. Symptoms were most prevalent in the young and middle age groups. The patients got a variety of different diagnoses, and between 13 and 35% of the patients did not receive a MSD diagnose despite having MSD symptoms. There was a great variation in how the cases were handled. Conclusions The present study points out some weaknesses regarding diagnostics and management of MSD in primary care. PMID:27538347

  9. Prevalence, diagnostics and management of musculoskeletal disorders in primary health care in Sweden - an investigation of 2000 randomly selected patient records.

    PubMed

    Wiitavaara, Birgitta; Fahlström, Martin; Djupsjöbacka, Mats

    2017-04-01

    The aims of this study is to investigate the prevalence of patients seeking care due to different musculoskeletal disorders (MSDs) at primary health care centres (PHCs), to chart different factors such as symptoms, diagnosis and actions prescribed for patients that visited the PHCs due to MSD and to make comparisons regarding differences due to gender, age and rural or urban PHC. Patient records (2000) for patients in working age were randomly selected equally distributed on one rural and one urban PHC. A 3-year period was reviewed retrospectively. For all patient records' background data, cause to the visit and diagnosis were registered. For visits due to MSD, type and location of symptoms and actions to resolve the patients problems were registered. Data was analysed using cross tabulation, multidimensional chi-squared. The prevalence of MSD was high; almost 60% of all patients were seeking care due to MSD. Upper and lower limb problems were most common. Symptoms were most prevalent in the young and middle age groups. The patients got a variety of different diagnoses, and between 13 and 35% of the patients did not receive a MSD diagnose despite having MSD symptoms. There was a great variation in how the cases were handled. The present study points out some weaknesses regarding diagnostics and management of MSD in primary care. © 2016 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

  10. Meta Salud Diabetes study protocol: a cluster-randomised trial to reduce cardiovascular risk among a diabetic population of Mexico

    PubMed Central

    Cornejo Vucovich, Elsa; Ingram, Maia; Valenica, Celina; Castro Vasquez, Maria del Carmen; Gonzalez-Fagoaga, Eduardo; Geurnsey de Zapien, Jill

    2018-01-01

    Introduction Northern Mexico has among the highest rates of cardiovascular disease (CVD) and diabetes in the world. This research addresses core gaps in implementation science to develop, test and scale-up CVD risk-reduction interventions in diabetics through a national primary care health system. Methods and analysis The Meta Salud Diabetes (MSD) research project is a parallel two-arm cluster-randomised clinical behavioural trial based in 22 (n=22) health centres in Sonora, Mexico. MSD aims to evaluate the effectiveness of the MSD intervention for the secondary prevention of CVD risk factors among a diabetic population (n=320) compared with the study control of usual care. The MSD intervention consists of 2-hour class sessions delivered over a 13-week period providing educational information to encourage sustainable behavioural change to prevent disease complications including the adoption of physical activity. MSD is delivered within the context of Mexico’s national primary care health centre system by health professionals, including nurses, physicians and community health workers via existing social support groups for individuals diagnosed with chronic disease. Mixed models are used to estimate the effect of MSD by comparing cardiovascular risk, as measured by the Framingham Risk Score, between the trial arms. Secondary outcomes include hypertension, behavioural risk factors and psychosocial factors. Ethics and dissemination This work is supported by the National Institutes of Health, National Heart Lung and Blood Institute (1R01HL125996-01) and approved by the University of Arizona Research Institutional Review Board (Protocol 1508040144) and the Research Bioethics Committee at the University of Sonora. The first Internal Review Board approval date was 31 August 2015 with five subsequent approved amendments. This article refers to protocol V.0.2, dated 30 January 2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences and will be shared through meetings with health systems officials. Trial registration number NCT0280469; Pre-results. PMID:29530914

  11. Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

    PubMed

    Liang, X; Syed, A K; Russell, S R; Ware, J; Li, R

    2016-02-01

    ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance. © 2015 International Society on Thrombosis and Haemostasis.

  12. Cellular responses to the expression of unstable secretory proteins in the filamentous fungus Aspergillus oryzae.

    PubMed

    Yokota, Jun-Ichi; Shiro, Daisuke; Tanaka, Mizuki; Onozaki, Yasumichi; Mizutani, Osamu; Kakizono, Dararat; Ichinose, Sakurako; Shintani, Tomoko; Gomi, Katsuya; Shintani, Takahiro

    2017-03-01

    Filamentous fungi are often used as cell factories for recombinant protein production because of their ability to secrete large quantities of hydrolytic enzymes. However, even using strong transcriptional promoters, yields of nonfungal proteins are generally much lower than those of fungal proteins. Recent analyses revealed that expression of certain nonfungal secretory proteins induced the unfolded protein response (UPR), suggesting that they are recognized as proteins with folding defects in filamentous fungi. More recently, however, even highly expressed endogenous secretory proteins were found to evoke the UPR. These findings raise the question of whether the unfolded or misfolded state of proteins is selectively recognized by quality control mechanisms in filamentous fungi. In this study, a fungal secretory protein (1,2-α-D-mannosidase; MsdS) with a mutation that decreases its thermostability was expressed at different levels in Aspergillus oryzae. We found that, at moderate expression levels, wild-type MsdS was secreted to the medium, while the mutant was not. In the strain with a deletion for the hrdA gene, which is involved in the endoplasmic reticulum-associated degradation pathway, mutant MsdS had specifically increased levels in the intracellular fraction but was not secreted. When overexpressed, the mutant protein was secreted to the medium to a similar extent as the wild-type protein; however, the mutant underwent hyperglycosylation and induced the UPR. Deletion of α-amylase (the most abundant secretory protein in A. oryzae) alleviated the UPR induction by mutant MsdS overexpression. These findings suggest that misfolded MsdS and unfolded species of α-amylase might act synergistically for UPR induction.

  13. Comparison of Musculoskeletal Disorder Health Claims Between Construction Floor Layers and a General Working Population

    PubMed Central

    Dale, Ann Marie; Ryan, Daniel; Welch, Laura; Olsen, Margaret A.; Buchholz, Bryan; Evanoff, Bradley

    2014-01-01

    Objectives Compare rates of medical insurance claims for musculoskeletal disorders (MSD) between workers in a construction trade and a general worker population to determine if higher physical exposures in construction lead to higher rates of claims on personal medical insurance. Methods Health insurance claims between 2006 and 2010 from floor layers were frequency matched by age, gender, eligibility time, and geographic location to claims from insured workers in general industry obtained from MarketScan. We extracted MSD claims and dates of service from six regions of the body: neck, low back, knee, lower extremity, shoulder, and distal arm, and evaluated differences in claim rates. Results Fifty-one percent of floor layers (n=1,475) experienced musculoskeletal claims compared to 39% of MarketScan members (p<0.001). Claim rates were higher for floor layers across all body regions with nearly double the rate ratios for the knee and neck regions (RR: 2.10 and 2.07). The excess risk was greatest for the neck and low back regions; younger workers had disproportionately higher rates in the knee, neck, low back, and distal arm. A larger proportion of floor layers (22%) filed MSD claims in more than one body region compared to general workers (10%; p<0.001). Conclusions Floor layers have markedly higher rates of MSD claims compared to a general worker population, suggesting shifting of medical costs for work-related MSD to personal health insurance. The occurrence of disorders in multiple body regions and among the youngest workers highlights the need for improved work methods and tools for construction workers. PMID:25224720

  14. Evaluation of Seismic Performance and Effectiveness of Multiple Slim-Type Damper System for Seismic Response Control of Building Structures

    PubMed Central

    Kim, David; Sung, Eun Hee; Park, Kwan-Soon; Park, Jaegyun

    2014-01-01

    This paper presents the evaluation of seismic performance and cost-effectiveness of a multiple slim-type damper system developed for the vibration control of earthquake excited buildings. The multiple slim-type damper (MSD) that consists of several small slim-type dampers and linkage units can control damping capacity easily by changing the number of small dampers. To evaluate the performance of the MSD, dynamic loading tests are performed with three slim-type dampers manufactured at a real scale. Numerical simulations are also carried out by nonlinear time history analysis with a ten-story earthquake excited building structure. The seismic performance and cost-effectiveness of the MSD system are investigated according to the various installation configurations of the MSD system. From the results of numerical simulation and cost-effectiveness evaluation, it is shown that combinations of the MSD systems can effectively improve the seismic performance of earthquake excited building structures. PMID:25301387

  15. Multitask saliency detection model for synthetic aperture radar (SAR) image and its application in SAR and optical image fusion

    NASA Astrophysics Data System (ADS)

    Liu, Chunhui; Zhang, Duona; Zhao, Xintao

    2018-03-01

    Saliency detection in synthetic aperture radar (SAR) images is a difficult problem. This paper proposed a multitask saliency detection (MSD) model for the saliency detection task of SAR images. We extract four features of the SAR image, which include the intensity, orientation, uniqueness, and global contrast, as the input of the MSD model. The saliency map is generated by the multitask sparsity pursuit, which integrates the multiple features collaboratively. Detection of different scale features is also taken into consideration. Subjective and objective evaluation of the MSD model verifies its effectiveness. Based on the saliency maps obtained by the MSD model, we apply the saliency map of the SAR image to the SAR and color optical image fusion. The experimental results of real data show that the saliency map obtained by the MSD model helps to improve the fusion effect, and the salient areas in the SAR image can be highlighted in the fusion results.

  16. AGOR 28: SIO Shipyard Representative Bi-Weekly Progress Report

    DTIC Science & Technology

    2015-10-23

    constant tension operation. These items will be rechecked next week. 3 • Red Fox MSD – Tested and Commissioned by vendor...No operational issues, however both overboarding pumps had cracked housings. Vendor suspects factory defect and is replace with new. MSD ...593-001-3 MSD System Operational Test 10/6 422-001-3 Navigation Signal & Search Light Demonstration 10/9. 573-001-2 125% & 100 % Portable Crane 10/12

  17. Seeking Insights About Cycling Mood Disorders via Anonymized Search Logs

    PubMed Central

    White, Ryen W; Horvitz, Eric

    2014-01-01

    Background Mood disorders affect a significant portion of the general population. Cycling mood disorders are characterized by intermittent episodes (or events) of the disease. Objective Using anonymized Web search logs, we identify a population of people with significant interest in mood stabilizing drugs (MSD) and seek evidence of mood swings in this population. Methods We extracted queries to the Microsoft Bing search engine made by 20,046 Web searchers over six months, separately explored searcher demographics using data from a large external panel of users, and sought supporting information from people with mood disorders via a survey. We analyzed changes in information needs over time relative to searches on MSD. Results Queries for MSD focused on side effects and their relation to the disease. We found evidence of significant changes in search behavior and interests coinciding with days that MSD queries are made. These include large increases (>100%) in the access of nutrition information, commercial information, and adult materials. A survey of patients diagnosed with mood disorders provided evidence that repeated queries on MSD may come with exacerbations of mood disorder. A classifier predicting the occurrence of such queries one day before they are observed obtains strong performance (AUC=0.78). Conclusions Observed patterns in search behavior align with known behaviors and those highlighted by survey respondents. These observations suggest that searchers showing intensive interest in MSD may be patients who have been prescribed these drugs. Given behavioral dynamics, we surmise that the days on which MSD queries are made may coincide with commencement of mania or depression. Although we do not have data on mood changes and whether users have been diagnosed with bipolar illness, we see evidence of cycling in people who show interest in MSD and further show that we can predict impending shifts in behavior and interest. PMID:24568936

  18. Preliminary AMS Study in Cretaceous Igneous Rocks of Valle Chico Complex, Uruguay: Statistical Determination of Magnetic Susceptibility

    NASA Astrophysics Data System (ADS)

    Barcelona, H.; Mena, M.; Sanchez-Bettucci, L.

    2009-05-01

    The Valle Chico Complex, at southeast Uruguay, is related Paraná-Etendeka Province. The study involved basaltic lavas, quarz-syenites, and rhyolitic and trachytic dikes. Samples were taken from 18 sites and the AMS of 250 specimens was analyzed. The AMS is modeled by a second order tensor K and it graphical representation is a symmetric ellipsoid. The axes relations determine parameters which describe different properties like shape, lineation, and foliation, degree of anisotropy and bulk magnetic susceptibility. Under this perspective, one lava, dike, or igneous body can be considered a mosaic of magnetic susceptibility domains (MSD). The DSM is an area with specific degree of homogeneity in the distribution of parameters values and cinematic conditions. An average tensor would weigh only one MSD, but if the site is a mosaic, subsets of specimens with similar parameters can be created. Hypothesis tests can be used to establish parameter similarities. It would be suitable considered as a MSD the subsets with statistically significant differences in at least one of its means parameters, and therefore, be treated independently. Once defined the MSDs the tensor analysis continues. The basalt-andesitic lavas present MSD with an NNW magnetic foliation, dipping 10. The K1 are sub-horizontal, oriented E-W and reprsent the magmatic flow direction. The quartz-syenites show a variable magnetic fabric or prolate ellipsoids mayor axes dispose parallel to the flow direction (10 to the SSE). Deformed syenites show N300/11 magnetic foliation, consistent with the trend of fractures. The K1 is subvertical. The MSD defined in rhyolitic dikes have magnetic foliations consistent with the structural trend. The trachytic dikes show an important indetermination in the magnetic response. However, a 62/N90 magnetic lineation was defined. The MSDs obtained are consistent with the geological structures and contribute to the knowledge of the tectonic, magmatic and kinematic events.

  19. Process evaluation of knowledge transfer across industries: Leveraging Coca-Cola's supply chain expertise for medicine availability in Tanzania.

    PubMed

    Linnander, Erika; Yuan, Christina T; Ahmed, Shirin; Cherlin, Emily; Talbert-Slagle, Kristina; Curry, Leslie A

    2017-01-01

    Persistent gaps in the availability of essential medicines have slowed the achievement of global health targets. Despite the supply chain knowledge and expertise that ministries of health might glean from other industries, limited empirical research has examined the process of knowledge transfer from other industries into global public health. We examined a partnership designed to improve the availability of medical supplies in Tanzania by transferring knowledge from The Coca-Cola system to Tanzania's Medical Stores Department (MSD). We conducted a process evaluation including in-depth interviews with 70 participants between July 2011 and May 2014, corresponding to each phase of the partnership, with focus on challenges and strategies to address them, as well as benefits perceived by partners. Partners faced challenges in (1) identifying relevant knowledge to transfer, (2) translating operational solutions from Coca-Cola to MSD, and (3) maintaining momentum between project phases. Strategies to respond to these challenges emerged through real-time problem solving and included (1) leveraging the receptivity of MSD leadership, (2) engaging a boundary spanner to identify knowledge to transfer, (3) promoting local recognition of commonalities across industries, (4) engaging external technical experts to manage translation activities, (5) developing tools with visible benefits for MSD, (6) investing in local relationships, and (7) providing time and space for the partnership model to evolve. Benefits of the partnership perceived by MSD staff included enhanced collaboration and communication, more proactive orientations in managing operations, and greater attention to performance management. Benefits perceived by Coca-Cola staff included strengthened knowledge transfer capability and enhanced job satisfaction. Linking theoretical constructs with practical experiences from the field, we highlight the challenges, emergent strategies, and perceived benefits of a partnership across industry boundaries that may be useful to others seeking to promote the transfer of knowledge to improve global health.

  20. Process evaluation of knowledge transfer across industries: Leveraging Coca-Cola’s supply chain expertise for medicine availability in Tanzania

    PubMed Central

    Yuan, Christina T.; Ahmed, Shirin; Cherlin, Emily; Talbert-Slagle, Kristina; Curry, Leslie A.

    2017-01-01

    Persistent gaps in the availability of essential medicines have slowed the achievement of global health targets. Despite the supply chain knowledge and expertise that ministries of health might glean from other industries, limited empirical research has examined the process of knowledge transfer from other industries into global public health. We examined a partnership designed to improve the availability of medical supplies in Tanzania by transferring knowledge from The Coca-Cola system to Tanzania’s Medical Stores Department (MSD). We conducted a process evaluation including in-depth interviews with 70 participants between July 2011 and May 2014, corresponding to each phase of the partnership, with focus on challenges and strategies to address them, as well as benefits perceived by partners. Partners faced challenges in (1) identifying relevant knowledge to transfer, (2) translating operational solutions from Coca-Cola to MSD, and (3) maintaining momentum between project phases. Strategies to respond to these challenges emerged through real-time problem solving and included (1) leveraging the receptivity of MSD leadership, (2) engaging a boundary spanner to identify knowledge to transfer, (3) promoting local recognition of commonalities across industries, (4) engaging external technical experts to manage translation activities, (5) developing tools with visible benefits for MSD, (6) investing in local relationships, and (7) providing time and space for the partnership model to evolve. Benefits of the partnership perceived by MSD staff included enhanced collaboration and communication, more proactive orientations in managing operations, and greater attention to performance management. Benefits perceived by Coca-Cola staff included strengthened knowledge transfer capability and enhanced job satisfaction. Linking theoretical constructs with practical experiences from the field, we highlight the challenges, emergent strategies, and perceived benefits of a partnership across industry boundaries that may be useful to others seeking to promote the transfer of knowledge to improve global health. PMID:29121051

  1. Haploidentical transplantation compared with matched sibling and unrelated donor transplantation for adults with standard-risk acute lymphoblastic leukaemia in first complete remission.

    PubMed

    Han, Li-Jie; Wang, Yu; Fan, Zhi-Ping; Huang, Fen; Zhou, Jian; Fu, Yue-Wen; Qu, Hong; Xuan, Li; Xu, Na; Ye, Jie-Yu; Bian, Zhi-Lei; Song, Yong-Ping; Huang, Xiao-Jun; Liu, Qi-Fa

    2017-10-01

    We retrospectively investigated outcomes of haploidentical donor (HID) transplant for adults with standard-risk acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) compared with human leucocyte antigen (HLA)-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants. A total of 348 adult patients were enrolled, including 127 HID, 144 MSD and 77 MUD recipients. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 39·5%, 24·0% and 40·3% for HID, MSD and MUD, respectively (P = 0·020). However, there was no difference in grade III-IV aGVHD (11·4%, 7·7%, 13·5%, respectively, P = 0·468). The 5-year cumulative transplant-related mortality was 16·4%, 11·6% and 19·6% (P = 0·162), the 5-year relapse rate post-transplantation was 14·8%, 21·1% and 16·7% (P = 0·231), the 5-year overall survival was 70·1%, 73·7% and 69·8% (P = 0·525), and the 5-year disease-free survival was 68·7%, 67·3% and 63·7%, respectively (P = 0·606). Furthermore, the 3-year GVHD-free, relapse-free survival was not different (50·8%, 54·9% and 52·2%, respectively, P = 0·847). Our results indicate that the outcomes of HID transplants are equivalent to those of MSD and MUD, and that HID transplantation is a valid alternative for standard-risk adults with ALL in CR1 who lack matched donors. © 2017 John Wiley & Sons Ltd.

  2. Stability and change in health behaviours as predictors for disability pension: a prospective cohort study of Swedish twins

    PubMed Central

    2011-01-01

    Background Stability or changes of health behaviours have not been studied in association with incidence of disability pension (DP). The aims were to (1) investigate if stability or changes in health behaviours predict DP due to musculoskeletal diagnosis (MSD), (2) to evaluate if an association exists for DP in general, and (3) after taking familial confounding into account. Methods The study sample was 16,713 like-sexed twin individuals born in Sweden between 1935-1958 (6195 complete twin pairs) who had participated in two surveys 25 years apart, were alive, and not pensioned at the time of the latest survey. Cox proportional hazards analysis was used to assess the associations (hazard ratios (HR) with 95% confidence intervals (CI)) between stability and change in health behaviours (physical activity, tobacco and alcohol use, body mass index (BMI)), and number of pain locations collected at two time points 25 years apart and the incidence of DP until 2008. Results During the follow-up, 1843 (11%) individuals were granted DP with 747 of these due to MSD. A higher proportion of women were granted DP than men. Increase in BMI and stable use of tobacco products were predictors for DP due to MSD (HR 1.21-1.48) and DP in general (HR 1.10-1.41). The stability in the frequency of physical activity and increased frequency of physical activity were protective factors for DP due to MSD only when accounting for familial confounding. However, the number of pain locations (stability, increase, or decrease) was the strongest predictor for future DP due to MSD (HR 3.69, CI 2.99-4.56) and DP in general (HR 2.15, CI 1.92-2.42). In discordant pair analysis, the HRs for pain were lower, indicating potential familial confounding. Conclusions Health behaviours in adulthood, including an increase in pain locations were associated with the incidence of DP. The association between physical activity and DP was especially related to adulthood choices or habits, i.e., the individual decision about frequency of exercising. Thus, it is important to e.g. increase public awareness of the potential beneficial effects of exercise throughout life to avoid permanent exclusion from the labour market for medical reasons. PMID:21880151

  3. Stability and change in health behaviours as predictors for disability pension: a prospective cohort study of Swedish twins.

    PubMed

    Ropponen, Annina; Narusyte, Jurgita; Alexanderson, Kristina; Svedberg, Pia

    2011-08-31

    Stability or changes of health behaviours have not been studied in association with incidence of disability pension (DP). The aims were to (1) investigate if stability or changes in health behaviours predict DP due to musculoskeletal diagnosis (MSD), (2) to evaluate if an association exists for DP in general, and (3) after taking familial confounding into account. The study sample was 16,713 like-sexed twin individuals born in Sweden between 1935-1958 (6195 complete twin pairs) who had participated in two surveys 25 years apart, were alive, and not pensioned at the time of the latest survey. Cox proportional hazards analysis was used to assess the associations (hazard ratios (HR) with 95% confidence intervals (CI)) between stability and change in health behaviours (physical activity, tobacco and alcohol use, body mass index (BMI)), and number of pain locations collected at two time points 25 years apart and the incidence of DP until 2008. During the follow-up, 1843 (11%) individuals were granted DP with 747 of these due to MSD. A higher proportion of women were granted DP than men. Increase in BMI and stable use of tobacco products were predictors for DP due to MSD (HR 1.21-1.48) and DP in general (HR 1.10-1.41). The stability in the frequency of physical activity and increased frequency of physical activity were protective factors for DP due to MSD only when accounting for familial confounding. However, the number of pain locations (stability, increase, or decrease) was the strongest predictor for future DP due to MSD (HR 3.69, CI 2.99-4.56) and DP in general (HR 2.15, CI 1.92-2.42). In discordant pair analysis, the HRs for pain were lower, indicating potential familial confounding. Health behaviours in adulthood, including an increase in pain locations were associated with the incidence of DP. The association between physical activity and DP was especially related to adulthood choices or habits, i.e., the individual decision about frequency of exercising. Thus, it is important to e.g. increase public awareness of the potential beneficial effects of exercise throughout life to avoid permanent exclusion from the labour market for medical reasons.

  4. Design and implementation of the one-step MSD adder of optical computer.

    PubMed

    Song, Kai; Yan, Liping

    2012-03-01

    On the basis of the symmetric encoding algorithm for the modified signed-digit (MSD), a 7*7 truth table that can be realized with optical methods was developed. And based on the truth table, the optical path structures and circuit implementations of the one-step MSD adder of ternary optical computer (TOC) were designed. Experiments show that the scheme is correct, feasible, and efficient. © 2012 Optical Society of America

  5. Magnetic field line random walk in two-dimensional dynamical turbulence

    NASA Astrophysics Data System (ADS)

    Wang, J. F.; Qin, G.; Ma, Q. M.; Song, T.; Yuan, S. B.

    2017-08-01

    The field line random walk (FLRW) of magnetic turbulence is one of the important topics in plasma physics and astrophysics. In this article, by using the field line tracing method, the mean square displacement (MSD) of FLRW is calculated on all possible length scales for pure two-dimensional turbulence with the damping dynamical model. We demonstrate that in order to describe FLRW with the damping dynamical model, a new dimensionless quantity R is needed to be introduced. On different length scales, dimensionless MSD shows different relationships with the dimensionless quantity R. Although the temporal effect affects the MSD of FLRW and even changes regimes of FLRW, it does not affect the relationship between the dimensionless MSD and dimensionless quantity R on all possible length scales.

  6. Dynamic behaviors of water contained in calcium-silicate-hydrate gel at different temperatures studied by quasi-elastic neutron scattering spectroscopy

    NASA Astrophysics Data System (ADS)

    Yi, Zhou; Deng, Pei-Na; Zhang, Li-Li; Li, Hua

    2016-10-01

    The dynamic behaviors of water contained in calcium-silicate-hydrate (C-S-H) gel with different water content values from 10% to 30% (by weight), are studied by using an empirical diffusion model (EDM) to analyze the experimental data of quasi-elastic neutron scattering (QENS) spectra at measured temperatures ranging from 230 K to 280 K. In the study, the experimental QENS spectra with the whole Q-range are considered. Several important parameters including the bound/immobile water elastic coefficient A, the bound water index BWI, the Lorentzian with a half-width at half-maximum (HWHM) Γ 1(Q) and Γ 2(Q), the self-diffusion coefficients D t1 and D t2 of water molecules, the average residence times τ 01 and τ 02, and the proton mean squared displacement (MSD) are obtained. The results show that the QENS spectra can be fitted very well not only for small Q (≤ 1 Å-1) but also for large Q. The bound/immobile water fraction in a C-S-H gel sample can be shown by the fitted BWI. The distinction between bound/immobile and mobile water, which includes confined water and ultra-confined water, can be seen by the fitted MSD. All the MSD tend to be the smallest value below 0.25 Å2 (the MSD of bound/immobile water) as the Q increases to 1.9 Å-1, no matter what the temperature and water content are. Furthermore, by the abrupt changes of the fitted values of D t1, τ 01, and Γ 1(Q), a crossover temperature at 250 K, namely the liquid-to-crystal-like transition temperature, can be identified for confined water in large gel pores (LGPs) and/or small gel pores (SGPs) contained in the C-S-H gel sample with 30% water content.

  7. Aging underdamped scaled Brownian motion: Ensemble- and time-averaged particle displacements, nonergodicity, and the failure of the overdamping approximation.

    PubMed

    Safdari, Hadiseh; Cherstvy, Andrey G; Chechkin, Aleksei V; Bodrova, Anna; Metzler, Ralf

    2017-01-01

    We investigate both analytically and by computer simulations the ensemble- and time-averaged, nonergodic, and aging properties of massive particles diffusing in a medium with a time dependent diffusivity. We call this stochastic diffusion process the (aging) underdamped scaled Brownian motion (UDSBM). We demonstrate how the mean squared displacement (MSD) and the time-averaged MSD of UDSBM are affected by the inertial term in the Langevin equation, both at short, intermediate, and even long diffusion times. In particular, we quantify the ballistic regime for the MSD and the time-averaged MSD as well as the spread of individual time-averaged MSD trajectories. One of the main effects we observe is that, both for the MSD and the time-averaged MSD, for superdiffusive UDSBM the ballistic regime is much shorter than for ordinary Brownian motion. In contrast, for subdiffusive UDSBM, the ballistic region extends to much longer diffusion times. Therefore, particular care needs to be taken under what conditions the overdamped limit indeed provides a correct description, even in the long time limit. We also analyze to what extent ergodicity in the Boltzmann-Khinchin sense in this nonstationary system is broken, both for subdiffusive and superdiffusive UDSBM. Finally, the limiting case of ultraslow UDSBM is considered, with a mixed logarithmic and power-law dependence of the ensemble- and time-averaged MSDs of the particles. In the limit of strong aging, remarkably, the ordinary UDSBM and the ultraslow UDSBM behave similarly in the short time ballistic limit. The approaches developed here open ways for considering other stochastic processes under physically important conditions when a finite particle mass and aging in the system cannot be neglected.

  8. Aging underdamped scaled Brownian motion: Ensemble- and time-averaged particle displacements, nonergodicity, and the failure of the overdamping approximation

    NASA Astrophysics Data System (ADS)

    Safdari, Hadiseh; Cherstvy, Andrey G.; Chechkin, Aleksei V.; Bodrova, Anna; Metzler, Ralf

    2017-01-01

    We investigate both analytically and by computer simulations the ensemble- and time-averaged, nonergodic, and aging properties of massive particles diffusing in a medium with a time dependent diffusivity. We call this stochastic diffusion process the (aging) underdamped scaled Brownian motion (UDSBM). We demonstrate how the mean squared displacement (MSD) and the time-averaged MSD of UDSBM are affected by the inertial term in the Langevin equation, both at short, intermediate, and even long diffusion times. In particular, we quantify the ballistic regime for the MSD and the time-averaged MSD as well as the spread of individual time-averaged MSD trajectories. One of the main effects we observe is that, both for the MSD and the time-averaged MSD, for superdiffusive UDSBM the ballistic regime is much shorter than for ordinary Brownian motion. In contrast, for subdiffusive UDSBM, the ballistic region extends to much longer diffusion times. Therefore, particular care needs to be taken under what conditions the overdamped limit indeed provides a correct description, even in the long time limit. We also analyze to what extent ergodicity in the Boltzmann-Khinchin sense in this nonstationary system is broken, both for subdiffusive and superdiffusive UDSBM. Finally, the limiting case of ultraslow UDSBM is considered, with a mixed logarithmic and power-law dependence of the ensemble- and time-averaged MSDs of the particles. In the limit of strong aging, remarkably, the ordinary UDSBM and the ultraslow UDSBM behave similarly in the short time ballistic limit. The approaches developed here open ways for considering other stochastic processes under physically important conditions when a finite particle mass and aging in the system cannot be neglected.

  9. Depression and anxiety in multisomatoform disorder: prevalence and clinical predictors in primary care.

    PubMed

    Muller, Jacqueline E; Wentzel, Ignatius; Nel, Daniel G; Stein, Dan J

    2008-06-01

    Multisomatoform disorder (MSD) is characterised by > or = 3 medically inexplicable, troublesome physical symptoms, together with a > or = 2-year history of somatisation. The aim of this study was to evaluate the prevalence of depressive and anxiety disorders in a South African sample MSD, and to compare demographic and clinical outcomes in those patients with and without co-morbidity. Fifty-one adult outpatients with MSD were recruited from primary care clinics in the Cape Town metropolitan area. Participants were assessed for the presence of co-morbid depressive and anxiety disorders using the Mini Neuropsychiatric Interview-Plus (MINI-Plus). Outcomes included somatic symptom severity, disability, reported sick days and health care visits, pain experience, patient satisfaction with health services, and clinician-experienced difficulty. A current co-morbid depressive disorder was present in 29.4% (N = 15) of patients, and a current co-morbid anxiety disorder in 52.9% (N = 27). MSD patients with a co-morbid depressive disorder (current or lifetime) had significantly higher physical symptom counts, greater functional impairment, higher unemployment rates, more clinician-reported difficulties, and more dissatisfaction with health care services than those without the disorder. A larger number of co-morbid disorders was associated with greater overall disability. High rates of co-morbid depressive and anxiety disorders were present in a South African sample of primary care patients with MSD. Not all patients had co-morbidity, which is consistent with the view that MSD should be viewed as an independent disorder. However, co-morbid depressive disorders were associated with increased symptom severity and functional impairment, consistent with previous reports from developing countries, emphasising the importance of comorbidity in MSD.

  10. Validation of a multiplex electrochemiluminescent immunoassay platform in human and mouse samples

    PubMed Central

    Bastarache, J.A.; Koyama, T.; Wickersham, N.E; Ware, L.B.

    2014-01-01

    Despite the widespread use of multiplex immunoassays, there are very few scientific reports that test the accuracy and reliability of a platform prior to publication of experimental data. Our laboratory has previously demonstrated the need for new assay platform validation prior to use of biologic samples from large studies in order to optimize sample handling and assay performance. In this study, our goal was to test the accuracy and reproducibility of an electrochemiluminescent multiplex immunoassay platform (Meso Scale Discovery, MSD®) and compare this platform to validated, singleplex immunoassays (R&D Systems®) using actual study subject (human plasma and mouse bronchoalveolar lavage fluid (BALF) and plasma) samples. We found that the MSD platform performed well on intra- and inter-assay comparisons, spike and recovery and cross-platform comparisons. The mean intra-assay CV% and range for MSD was 3.49 (0.0-10.4) for IL-6 and 2.04 (0.1-7.9) for IL-8. The correlation between values for identical samples measured on both MSD and R&D was R=0.97 for both analytes. The mouse MSD assay had a broader range of CV% with means ranging from 9.5-28.5 depending on the analyte. The range of mean CV% was similar for single plex ELISAs at 4.3-23.7 depending on the analyte. Regardless of species or sample type, CV% was more variable at lower protein concentrations. In conclusion, we validated a multiplex electrochemiluminscent assay system and found that it has superior test characteristics in human plasma compared to mouse BALF and plasma. Both human and MSD assays compared favorably to well-validated singleplex ELISA's PMID:24768796

  11. Danish Observational Study of Eldercare work and musculoskeletal disorderS (DOSES): a prospective study at 20 nursing homes in Denmark

    PubMed Central

    Karstad, Kristina; Jørgensen, Anette F B; Greiner, Birgit A; Burdorf, Alex; Søgaard, Karen; Rugulies, Reiner; Holtermann, Andreas

    2018-01-01

    Purpose Musculoskeletal disorders (MSDs), sickness absence and premature retirement are highly prevalent among eldercare workers. We conducted a prospective observational workplace study with the main purpose to investigate longitudinal associations between physical and psychosocial working conditions and occurrence of MSD and its consequences (pain-related interference with daily work activities and sickness absence) among Danish eldercare workers. Participants At 20 Danish nursing homes, a total of 941 eldercare workers employed in day and evening shifts were invited to the study. Of those, 553 participated in the baseline measurements, and 441 completed the total period of 12 months follow-up. Findings to date Data were collected from September 2013 to January 2016. Physical and psychosocial working conditions were assessed with multiple methods (observations, accelerometer measurements and work schedules), and multiple levels of information (nursing home, ward, resident and eldercare worker) were incorporated in the data collection. MSD and the consequences hereof were assessed monthly during a 1-year follow-up. Study participants and non-participants were comparable on most of the 27 sociodemographic, health and working condition characteristics at baseline. The exceptions were higher neck–shoulder pain intensity, less sickness absence, more exposure to negative behaviour from residents and a higher percentage of working day shifts and fewer evening shifts among participants compared with non-participants. Future plans The first publications will report on the associations of physical and psychosocial working conditions with occurrence of MSD and its consequences. In addition, the cohort gives the opportunity to investigate the importance of organisational, management and team factors for distribution of physical work demands and development of MSD among the workers. This will provide important knowledge for future workplace interventions to reduce MSD and sickness absence. PMID:29490965

  12. Stone heterogeneity index on single-energy noncontrast computed tomography can be a positive predictor of urinary stone composition

    PubMed Central

    Lee, Jong Soo; Cho, Kang Su; Lee, Seung Hwan; Yoon, Young Eun; Kang, Dong Hyuk; Jeong, Won Sik; Jung, Hae Do; Kwon, Jong Kyou

    2018-01-01

    The aim of this study was to investigate the correlation between stone composition and single-energy noncontrast computed tomography (NCCT) parameters, including stone heterogeneity index (SHI) and mean stone density (MSD), in patients with urinary calculi. We retrospectively reviewed medical records of 255 patients who underwent operations or procedures for urinary stones or had spontaneous stone passage between December 2014 and October 2015. Among these, 214 patients with urinary calculi who underwent NCCT and stone composition analyses were included in the study. Maximal stone length (MSL), mean stone density (MSD), and stone heterogeneity index (SHI) were determined on pretreatment NCCT. The mean MSD (454.68±177.80 HU) and SHI (115.82±96.31 HU) of uric acid stones were lower than those of all other types. Based on post hoc tests, MSD was lower for uric acid stones than for the other types (vs. CaOx: P<0.001; vs. infection stones: P<0.001). SHI was lower for uric acid stones than for the other types (vs. CaOx: P<0.001; vs. infection stones: P<0.001) Receiver operating characteristic curves of uric acid stones for MSD and SHI demonstrated that SHI (cut-off value: 140.4 HU) was superior to MSD (cut-off value: 572.3 HU) in predicting uric acid stones (P<0.001). PMID:29649219

  13. Musculoskeletal disorders in shipyard industry: prevalence, health care use, and absenteeism.

    PubMed

    Alexopoulos, Evangelos C; Tanagra, Dimitra; Konstantinou, Eleni; Burdorf, Alex

    2006-11-24

    It is unclear whether the well-known risk factors for the occurrence of musculoskeletal disorders (MSD) also play an important role in the determining consequences of MSD in terms of sickness absence and health care use. A cross-sectional study was conducted among 853 shipyard employees. Data were collected by questionnaire on physical and psychosocial workload, need for recovery, perceived general health, occurrence of musculoskeletal complaints, and health care use during the past year. Retrospective data on absenteeism were also available from the company register. In total, 37%, 22%, and 15% of employees reported complaints of low back, shoulder/neck, and hand/wrist during the past 12 months, respectively. Among all employees with at least one MSD, 27% visited a physician at least once and 20% took at least one period of sick leave. Various individual and work-related factors were associated with the occurrence of MSD. Health care use and absenteeism were strongest influenced by chronicity of musculoskeletal complaints and comorbidity with other musculoskeletal complaints and, to a lesser extent, by work-related factors. In programmes aimed at preventing the unfavourable consequences of MSD in terms of sickness absence and health care use it is important to identify the (individual) factors that determine the development of chronicity of complaints. These factors may differ from the well-know risk factors for the occurrence of MSD that are targeted in primary prevention.

  14. Meta Salud Diabetes study protocol: a cluster-randomised trial to reduce cardiovascular risk among a diabetic population of Mexico.

    PubMed

    Sabo, Samantha; Denman Champion, Catalina; Bell, Melanie L; Cornejo Vucovich, Elsa; Ingram, Maia; Valenica, Celina; Castro Vasquez, Maria Del Carmen; Gonzalez-Fagoaga, Eduardo; Geurnsey de Zapien, Jill; Rosales, Cecilia B

    2018-03-12

    Northern Mexico has among the highest rates of cardiovascular disease (CVD) and diabetes in the world. This research addresses core gaps in implementation science to develop, test and scale-up CVD risk-reduction interventions in diabetics through a national primary care health system. The Meta Salud Diabetes (MSD) research project is a parallel two-arm cluster-randomised clinical behavioural trial based in 22 (n=22) health centres in Sonora, Mexico. MSD aims to evaluate the effectiveness of the MSD intervention for the secondary prevention of CVD risk factors among a diabetic population (n=320) compared with the study control of usual care. The MSD intervention consists of 2-hour class sessions delivered over a 13-week period providing educational information to encourage sustainable behavioural change to prevent disease complications including the adoption of physical activity. MSD is delivered within the context of Mexico's national primary care health centre system by health professionals, including nurses, physicians and community health workers via existing social support groups for individuals diagnosed with chronic disease. Mixed models are used to estimate the effect of MSD by comparing cardiovascular risk, as measured by the Framingham Risk Score, between the trial arms. Secondary outcomes include hypertension, behavioural risk factors and psychosocial factors. This work is supported by the National Institutes of Health, National Heart Lung and Blood Institute (1R01HL125996-01) and approved by the University of Arizona Research Institutional Review Board (Protocol 1508040144) and the Research Bioethics Committee at the University of Sonora. The first Internal Review Board approval date was 31 August 2015 with five subsequent approved amendments. This article refers to protocol V.0.2, dated 30 January 2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences and will be shared through meetings with health systems officials. NCT0280469; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Ureteral stenting can be a negative predictor for successful outcome following shock wave lithotripsy in patients with ureteral stones.

    PubMed

    Kang, Dong Hyuk; Cho, Kang Su; Ham, Won Sik; Chung, Doo Yong; Kwon, Jong Kyou; Choi, Young Deuk; Lee, Joo Yong

    2016-11-01

    To evaluate ureteral stenting as a negative predictive factor influencing ureteral stone clearance and to estimate the probability of one-session success in shock wave lithotripsy (SWL) patients with a ureteral stone. We retrospectively reviewed the medical records of 1,651 patients who underwent their first SWL. Among these patients, 680 had a ureteral stone measuring 4-20 mm and were thus eligible for our study. The 57 patients who underwent ureteral stenting during SWL were identified. Maximal stone length (MSL), mean stone density (MSD), skin-to-stone distance (SSD), and stone heterogeneity index (SHI) were determined by pre-SWL noncontrast computed tomography. After propensity score matching, 399 patients were extracted from the total patient cohort. There were no significant differences between stenting and stentless groups after matching, except for a higher one-session success rate in the stentless group (78.6% vs. 49.1%, p=0.026). In multivariate analysis, shorter MSL, lower MSD, higher SHI, and absence of a stent were positive predictors for one-session success in patients who underwent SWL. Using cutoff values of MSL and MSD obtained from receiver operator curve analysis, in patients with a lower MSD (≤784 HU), the success rate was lower in those with a stent (61.1%) than in those without (83.5%) (p=0.001). However, in patients with a higher MSL (>10 mm), the success rate was lower in those with a stent (23.6%) than in those without (52.2%) (p=0.002). Ureteral stenting during SWL was a negative predictor of one-session success in patients with a ureteral stone.

  16. Calculating the number of shock waves, expulsion time, and optimum stone parameters based on noncontrast computerized tomography characteristics.

    PubMed

    Foda, Khaled; Abdeldaeim, Hussein; Youssif, Mohamed; Assem, Akram

    2013-11-01

    To define the parameters that accompanied a successful extracorporeal shock wave lithotripsy (ESWL), namely the number of shock waves (SWs), expulsion time (ET), mean stone density (MSD), and the skin-to-stone distance (SSD). A total of 368 patients diagnosed with renal calculi using noncontrast computerized tomography had their MSD, diameter, and SSD recorded. All patients were treated using a Siemens lithotripter. ESWL success meant a stone-free status or presence of residual fragments <3 mm, ET was the time in days for the successful clearance of stone fragments. Correlation was performed between the stone characteristics, number of SWs, and ET. Two multiple regression analysis models defined the number of SWs and ET. Two receiver operating characteristic curves plotted the best MSD cutoff value and optimum SSD for a successful ESWL. Three hundred one patients were ESWL successes. A significant positive correlation was elicited between number of SWs and stone diameter, density and SSD; between ET and stone diameter and density. Multiple regressions concluded 2 equations: Number of SWs = 265.108 + 5.103 x1 + 22.39 x2 + 10.931 x3 ET (days) = -10.85 + 0.031 x1 + 2.11 x2 x1 = stone density (Hounsfield unit [HUs]), x2 = stone diameter (mm), and x3 = SSD (mm). Receiver operating characteristic curves demonstrated a cutoff value of ≤ 934 HUs with 94.4% sensitivity and 66.7% specificity and P = .0211. The SSD curve showed that a distance ≤ 99 mm was 85.7% sensitive, 87.5% specific, P <.0001. Stone disintegration is not recommended if MSD is >934 HUs and SSD >99 mm. The required number of SWs and the expected ET can be anticipated. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. HLA-Matched Sibling versus Unrelated versus Haploidentical Related Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients Aged Over 60 Years with Acute Myeloid Leukemia: A Single-Center Donor Comparison.

    PubMed

    Devillier, Raynier; Legrand, Faezeh; Rey, Jérôme; Castagna, Luca; Fürst, Sabine; Granata, Angela; Charbonnier, Aude; Harbi, Samia; d'Incan, Evelyne; Pagliardini, Thomas; Faucher, Catherine; Lemarie, Claude; Saillard, Colombe; Calmels, Boris; Mohty, Bilal; Maisano, Valerio; Weiller, Pierre-Jean; Chabannon, Christian; Vey, Norbert; Blaise, Didier

    2018-02-12

    Haploidentical related donor (HRD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) was developed as a valid option for the treatment of acute myeloid leukemia (AML) in the absence of a matched donor. However, many investigators are reluctant to consider the use of this alternative in elderly patients, anticipating high morbidity. Here, we report a single-center comparison of HRD versus matched sibling donor (MSD) and unrelated donor (UD) allo-HSCT for patients with AML aged ≥60 years. Ninety-four patients (MSD: n = 31; UD: n = 30; HRD: n = 33) were analyzed. The median age was 65 (range, 60 to 73) years. We observed a higher cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) after UD allo-HSCT (MSD versus UD versus HRD: 3% versus 33% versus 6%, respectively; P = .006). Two-year cumulative incidence of moderate or severe chronic GVHD was 17%, 27%, and 16% in the MSD, UD, and HRD groups, respectively (P = .487). No difference was observed in the 2-year cumulative incidence of relapse or nonrelapse mortality (NRM) (relapse: MSD versus UD versus HRD: 32% versus 25% versus 25%, respectively; P = .411; NRM: MSD versus UD versus HRD: 19% versus 27% versus 24%, respectively; P = .709). At 2 years, progression-free survival, overall survival, and GVHD- and relapse-free survival were 48%, 50%, and 39%, respectively, in the MSD group; 48%, 51%, and 23%, respectively, in the UD group; and 50%, 52%, and 32%, respectively, in the HRD group, without statistically significant differences between the groups. We conclude that HRD allo-HSCT is highly feasible and no less efficient than MSD or UD allo-HSCT in patients with AML aged ≥60 years. Thus, the absence of a HLA-identical donor should not limit the consideration of allo-HSCT for the treatment of AML. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Is neuroplasticity in the central nervous system the missing link to our understanding of chronic musculoskeletal disorders?

    PubMed

    Pelletier, René; Higgins, Johanne; Bourbonnais, Daniel

    2015-02-12

    Musculoskeletal rehabilitative care and research have traditionally been guided by a structural pathology paradigm and directed their resources towards the structural, functional, and biological abnormalities located locally within the musculoskeletal system to understand and treat Musculoskeletal Disorders (MSD). However the structural pathology model does not adequately explain many of the clinical and experimental findings in subjects with chronic MSD and, more importantly, treatment guided by this paradigm fails to effectively treat many of these conditions. Increasing evidence reveals structural and functional changes within the Central Nervous System (CNS) of people with chronic MSD that appear to play a prominent role in the pathophysiology of these disorders. These neuroplastic changes are reflective of adaptive neurophysiological processes occurring as the result of altered afferent stimuli including nociceptive and neuropathic transmission to spinal, subcortical and cortical areas with MSD that are initially beneficial but may persist in a chronic state, may be part and parcel in the pathophysiology of the condition and the development and maintenance of chronic signs and symptoms. Neuroplastic changes within different areas of the CNS may help to explain the transition from acute to chronic conditions, sensory-motor findings, perceptual disturbances, why some individuals continue to experience pain when no structural cause can be discerned, and why some fail to respond to conservative interventions in subjects with chronic MSD. We argue that a change in paradigm is necessary that integrates CNS changes associated with chronic MSD and that these findings are highly relevant for the design and implementation of rehabilitative interventions for this population. Recent findings suggest that a change in model and approach is required in the rehabilitation of chronic MSD that integrate the findings of neuroplastic changes across the CNS and are targeted by rehabilitative interventions. Effects of current interventions may be mediated through peripheral and central changes but may not specifically address all underlying neuroplastic changes in the CNS potentially associated with chronic MSD. Novel approaches to address these neuroplastic changes show promise and require further investigation to improve efficacy of currents approaches.

  19. Prevalence of work-related musculoskeletal injuries among South Indian hand screen-printing workers.

    PubMed

    Shankar, S; Naveen Kumar, R; Mohankumar, P; Jayaraman, Srinivasan

    2017-01-01

    Hand screen-printing (HSP) plays a predominant role in textile industries in developing countries. Workers from HSP industry were mostly affected by musculoskeletal injury due to monotonous, and prolonged work nature and poor workplace environment. The present study aims to investigate the prevalence of work-related musculoskeletal disorder (MSD) symptoms and risk factors associated among the HSP industry workers. Cochran's sample size for categorical data was used to select 385 HSP workers of 1000 samples from various provinces of Tamil Nadu, INDIA. Modified Nordic based questionnaire was used to assess the musculoskeletal injuries and risk factors among HSP workers. The statistical analysis revealed that 62.5% workers are prone to MSD symptoms with lower back (75.1%), shoulder (66.2%), knees (58.7%), and ankle/feet (55.6%). Age, experience, marital status, stress in the job were the risk factors which significantly (p < 0.05) associated with the reported MSDs. Further, this study result infers that the subjects with higher age and experience are exposed higher levels of MSD prevalence of 85.5% and 92.0% respectively in past 12 months than other groups. Among the different work categories in HSP task, the workers reported with the maximum discomfort during printing work (63.1%) with Odds ratio as 10.38 and 95% CI is 6.18-17.4. than the material handling and drying task. Study results infer that HSP workers are prone to lower back and shoulder pain followed by knees and ankle feet regions. Socio-demographic factors, awkward posture and repetitive movements contribute to cause MSD among hand screen-printing workers.

  20. Musculoskeletal symptoms as related to ergonomic factors in Iranian hand-woven carpet industry and general guidelines for workstation design.

    PubMed

    Choobineh, Alireza; Lahmi, Mohammadali; Shahnavaz, Houshang; Jazani, Reza Khani; Hosseini, Mostafa

    2004-01-01

    Carpet weaving is a high risk occupation for developing musculoskeletal disorders (MSDs). The objectives of the present study, which was carried out in the Iranian hand-woven carpet industry, were determination of the prevalence of MSD symptoms, identification of major factors associated with MSD symptoms and development of guidelines for workstation design. 1,439 randomly selected weavers participated in this study. A questionnaire was used to collect data on MSD symptoms. The results revealed that the prevalence rates for symptoms in different body regions were high as compared to the general Iranian population (for neck, back and large joints, p <.0001). The results of multivariate analyses showed that major ergonomic factors associated with musculoskeletal symptoms were loom type, working posture, daily working time and seat type. Based on the results, some general guidelines for designing weaving workstations were developed. A prototype test showed that the new workstation was acceptable for subject tests and that it improved working posture.

  1. Measuring a diffusion coefficient by single-particle tracking: statistical analysis of experimental mean squared displacement curves.

    PubMed

    Ernst, Dominique; Köhler, Jürgen

    2013-01-21

    We provide experimental results on the accuracy of diffusion coefficients obtained by a mean squared displacement (MSD) analysis of single-particle trajectories. We have recorded very long trajectories comprising more than 1.5 × 10(5) data points and decomposed these long trajectories into shorter segments providing us with ensembles of trajectories of variable lengths. This enabled a statistical analysis of the resulting MSD curves as a function of the lengths of the segments. We find that the relative error of the diffusion coefficient can be minimized by taking an optimum number of points into account for fitting the MSD curves, and that this optimum does not depend on the segment length. Yet, the magnitude of the relative error for the diffusion coefficient does, and achieving an accuracy in the order of 10% requires the recording of trajectories with about 1000 data points. Finally, we compare our results with theoretical predictions and find very good qualitative and quantitative agreement between experiment and theory.

  2. Berkeley Lab - Materials Sciences Division

    Science.gov Websites

    Berkeley Lab Berkeley Lab A-Z Index Phone Book Jobs Search DOE Search MSD Go MSD - Materials Investigators Division Staff Facilities and Centers Staff Jobs Safety Personnel Resources Committees In Case of

  3. Prevention of musculoskeletal disorders within management systems: A scoping review of practices, approaches, and techniques.

    PubMed

    Yazdani, Amin; Neumann, W Patrick; Imbeau, Daniel; Bigelow, Philip; Pagell, Mark; Wells, Richard

    2015-11-01

    The purpose of this study was to identify and summarize the current research evidence on approaches to preventing musculoskeletal disorders (MSD) within Occupational Health and Safety Management Systems (OHSMS). Databases in business, engineering, and health and safety were searched and 718 potentially relevant publications were identified and examined for their relevance. Twenty-one papers met the selection criteria and were subjected to thematic analysis. There was very little literature describing the integration of MSD risk assessment and prevention into management systems. This lack of information may isolate MSD prevention, leading to difficulties in preventing these disorders at an organizational level. The findings of this review argue for further research to integrate MSD prevention into management systems and to evaluate the effectiveness of the approach. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  4. Examining the interaction of force and repetition on musculoskeletal disorder risk: a systematic literature review.

    PubMed

    Gallagher, Sean; Heberger, John R

    2013-02-01

    Our aims were (a) to perform a systematic literature review of epidemiological studies that examined the interaction of force and repetition with respect to musculoskeletal disorder (MSD) risk, (b) to assess the relationship of force and repetition in fatigue failure studies of musculoskeletal tissues, and (c) to synthesize these findings. Many epidemiological studies have examined the effects of force and repetition on MSD risk; however, relatively few have examined the interaction between these risk factors. In a literature search, we identified 12 studies that allowed evaluation of a force-repetition interaction with respect to MSD risk. Identified studies were subjected to a methodological quality assessment and critical review. We evaluated laboratory studies of fatigue failure to examine tissue failure responses to force and repetition. Of the 12 epidemiological studies that tested a Force x Repetition interaction, 10 reported evidence of interaction. Based on these results, the suggestion is made that force and repetition may be interdependent in terms of their influence on MSD risk. Fatigue failure studies of musculoskeletal tissues show a pattern of failure that mirrors the MSD risk observed in epidemiological studies. Evidence suggests that there may be interdependence between force and repetition with respect to MSD risk. Repetition seems to result in modest increases in risk for low-force tasks but rapid increases in risk for high-force tasks. This interaction may be representative of a fatigue failure process in affected tissues.

  5. A probabilistic fatigue analysis of multiple site damage

    NASA Technical Reports Server (NTRS)

    Rohrbaugh, S. M.; Ruff, D.; Hillberry, B. M.; Mccabe, G.; Grandt, A. F., Jr.

    1994-01-01

    The variability in initial crack size and fatigue crack growth is incorporated in a probabilistic model that is used to predict the fatigue lives for unstiffened aluminum alloy panels containing multiple site damage (MSD). The uncertainty of the damage in the MSD panel is represented by a distribution of fatigue crack lengths that are analytically derived from equivalent initial flaw sizes. The variability in fatigue crack growth rate is characterized by stochastic descriptions of crack growth parameters for a modified Paris crack growth law. A Monte-Carlo simulation explicitly describes the MSD panel by randomly selecting values from the stochastic variables and then grows the MSD cracks with a deterministic fatigue model until the panel fails. Different simulations investigate the influences of the fatigue variability on the distributions of remaining fatigue lives. Six cases that consider fixed and variable conditions of initial crack size and fatigue crack growth rate are examined. The crack size distribution exhibited a dominant effect on the remaining fatigue life distribution, and the variable crack growth rate exhibited a lesser effect on the distribution. In addition, the probabilistic model predicted that only a small percentage of the life remains after a lead crack develops in the MSD panel.

  6. Computational comparison of quantum-mechanical models for multistep direct reactions

    NASA Astrophysics Data System (ADS)

    Koning, A. J.; Akkermans, J. M.

    1993-02-01

    We have carried out a computational comparison of all existing quantum-mechanical models for multistep direct (MSD) reactions. The various MSD models, including the so-called Feshbach-Kerman-Koonin, Tamura-Udagawa-Lenske and Nishioka-Yoshida-Weidenmüller models, have been implemented in a single computer system. All model calculations thus use the same set of parameters and the same numerical techniques; only one adjustable parameter is employed. The computational results have been compared with experimental energy spectra and angular distributions for several nuclear reactions, namely, 90Zr(p,p') at 80 MeV, 209Bi(p,p') at 62 MeV, and 93Nb(n,n') at 25.7 MeV. In addition, the results have been compared with the Kalbach systematics and with semiclassical exciton model calculations. All quantum MSD models provide a good fit to the experimental data. In addition, they reproduce the systematics very well and are clearly better than semiclassical model calculations. We furthermore show that the calculated predictions do not differ very strongly between the various quantum MSD models, leading to the conclusion that the simplest MSD model (the Feshbach-Kerman-Koonin model) is adequate for the analysis of experimental data.

  7. Self-Reported Musculoskeletal Disorders of the Distal Upper Extremities and the Neck in German Veterinarians: A Cross-Sectional Study

    PubMed Central

    Kozak, Agnessa; Schedlbauer, Grita; Peters, Claudia; Nienhaus, Albert

    2014-01-01

    Background Veterinary work is a physically demanding profession and entails the risk of injuries and diseases of the musculoskeletal system, particularly in the upper body. The prevalence of musculoskeletal disorders (MSD), the consequences and work-related accidents in German veterinarians were investigated. Work-related and individual factors associated with MSD of upper extremities and the neck were analyzed. Methods In 2011, a self-reporting Standardized Nordic Questionnaire was mailed to registered veterinarians in seven federal medical associations in Germany. A total of 3174 (38.4%) veterinarians responded. Logistic regression analysis was used to determine the association between risk factors and MSD-related impairment of daily activities. Results MSD in the neck (66.6%) and shoulder (60.5%) were more prevalent than in the hand (34.5%) or elbow (24.5%). Normal activities were affected in 28.7% (neck), 29.5% (shoulder), 19.4% (hand) and 14% (elbow) of the respondents. MSD in the upper body occurred significantly more often in large animal practitioners. Accidents that resulted in MSD were most frequently reported in the hand/wrist (14.3%) or in the shoulder (10.8%). The majority of all accidents in the distal upper extremities were caused by animals than by other factors (19% vs. 9.2%). For each area of the body, a specific set of individual and work-related factors contributed significantly to severe MSD: Older age, gender, previous injuries, BMI, practice type, veterinary procedures such as dentistry, rectal procedures and obstetric procedures as well as high demands and personal burnout. Conclusion From the perspective of occupational health and safety, it seems to be necessary to improve accident prevention and to optimize the ergonomics of specific tasks. Our data suggest the need for target group-specific preventive measures that also focus on the psychological factors at work. PMID:24586718

  8. The Prevalence of and Risk Factors Associated with Musculoskeletal Disorders among Sonographers in Central China: A Cross-Sectional Study

    PubMed Central

    Feng, Qingmin; Liu, Shenglin; Yang, Lei; Xie, Mingxing

    2016-01-01

    Objective Studies from industrialized countries show that musculoskeletal disorders (MSD) occur commonly in sonographers. However, little is known about sonographers in China, where the awareness of ergonomics and MSD, workload, and available equipment/facilities may differ. We aimed to investigate the prevalence of MSD and associated risk factors in sonographers in central China. Methods A cross-sectional survey was conducted with 381 sonographers from 14 randomly selected tertiary hospitals in Hubei province, central China. Musculoskeletal symptoms (using the Nordic Questionnaire) and risk factors (mostly derived from the Health Benefit Trust survey instrument and the Dutch Musculoskeletal Questionnaire) were recorded. Multivariate logistic regression was used to quantify associations between risk factors and MSD. Results The 12-month period prevalence of MSD was 98.3%, being highest in the neck (93.5%) and shoulder (92.2%), followed by the lower back (83.2%), wrist/hand, upper back, and elbow. Factors contributing to neck pain were psychological fatigue, shoulder abduction and trunk bend-and-twist posture. Height-adjustable tables and chairs were protective factors. Shoulder pain was associated with female sex, health status, mental stress, shoulder abduction, and trunk bend-and-twist posture. Height-adjustable chairs and the awareness of adjusting the workstation before scanning were protective factors. Elbow pain was associated with health status and height-adjustable tables. Wrist/hand pain was associated with female sex, bending the wrist, and working with obese patients. Upper back pain was associated with shoulder abduction, height-adjustable chairs, and device location. Lower back pain was associated with the number of scans performed per day, awkward postures, bending the trunk, twisting or bending the neck forward, and using a footrest. Conclusions This study suggests a high prevalence of MSD in sonographers in central China. Hence, it is necessary to improve the awareness of MSD by training, and the ergonomics of their current work environment by addressing physical workload, and psychological and equipment/facility-related factors. PMID:27695095

  9. [Analysis of the factors influencing the internal reporting of nosocomial infections. A review of 108 notifications].

    PubMed

    Penel, N; Fournier, C; Roussel-Delvallez, M; Deberles, M-F; Buisset, E; Cazin, J-L; Leclercq, B

    2003-11-29

    Since July 26, 2001, the external reporting to the regional office of health and social affairs (Direction départementale des affaires sanitaires et sociales--Ddass) and the coordination centre (Comité de lutte contre les infections nosocomiales--Cclin) for the fight against nosocomial infections (NI) is mandatory. However, the modalities of internal reporting to the Clin are unknown. We performed a retrospective analysis of 108 cases of NI reported over 23 months in 4 medical-surgical departments (MSD) with 14 to 35 NI reported/MSD. The distribution of the bacteria responsible was compared with that of the local epidemiological state (chi2 test). A correlation analysis was performed between the number of NI reported in each MSD and the structural characteristics and activity index of these MSD (Spearmann's correlation test). The NI were predominantly infections related to a catheter (43), lower respiratory tract (25) and infection of the site of surgery (19). Ninety were documented biologically, among which 10 implied multi-resistant bacteria. Ninety-four NI were associated with the prescription of an antibiotic. Compared with the local epidemiological state, the NI reported generally implied multi-resistant bacteria (p=0.009). The other microbiological data had little implication. In each of the MSD, the number of cases reported was independent of: the global activity, the number of interventions, the mean duration of hospitalisation, the number of beds, the number of clinicians, the number of new patients managed and the chemotherapy outpatient activity. Conversely, there was a strong correlation between the global consumption of antibiotics (r=0.78), and the number of the Clin members in each MSD DMC (r=0.82). In each MSD, the internal reporting of NI relies on the discovery of multi-resistant bacteria, but above all on the implication of those involved in the fight against nosocomial infections.

  10. Modified-Signed-Digit Optical Computing Using Fan-Out

    NASA Technical Reports Server (NTRS)

    Liu, Hua-Kuang; Zhou, Shaomin; Yeh, Pochi

    1996-01-01

    Experimental optical computing system containing optical fan-out elements implements modified signed-digit (MSD) arithmetic and logic. In comparison with previous optical implementations of MSD arithmetic, this one characterized by larger throughput, greater flexibility, and simpler optics.

  11. Dissolution comparisons using a Multivariate Statistical Distance (MSD) test and a comparison of various approaches for calculating the measurements of dissolution profile comparison.

    PubMed

    Cardot, J-M; Roudier, B; Schütz, H

    2017-07-01

    The f 2 test is generally used for comparing dissolution profiles. In cases of high variability, the f 2 test is not applicable, and the Multivariate Statistical Distance (MSD) test is frequently proposed as an alternative by the FDA and EMA. The guidelines provide only general recommendations. MSD tests can be performed either on raw data with or without time as a variable or on parameters of models. In addition, data can be limited-as in the case of the f 2 test-to dissolutions of up to 85% or to all available data. In the context of the present paper, the recommended calculation included all raw dissolution data up to the first point greater than 85% as a variable-without the various times as parameters. The proposed MSD overcomes several drawbacks found in other methods.

  12. Differential Modulation of Rhythmic Brain Activity in Healthy Adults by a T-Type Calcium Channel Blocker: An MEG Study

    PubMed Central

    Walton, Kerry D.; Maillet, Emeline L.; Garcia, John; Cardozo, Timothy; Galatzer-Levy, Isaac; Llinás, Rodolfo R.

    2017-01-01

    1-octanol is a therapeutic candidate for disorders involving the abnormal activation of the T-type calcium current since it blocks this current specifically. Such disorders include essential tremor and a group of neurological and psychiatric disorders resulting from thalamocortical dysrhythmia (TCD). For example, clinically, the observable phenotype in essential tremor is the tremor itself. The differential diagnostic of TCD is not based only on clinical signs and symptoms. Rather, TCD incorporates an electromagnetic biomarker, the presence of abnormal thalamocortical low frequency brain oscillations. The effect of 1-octanol on brain activity has not been tested. As a preliminary step to such a TCD study, we examined the short-term effects of a single dose of 1-octanol on resting brain activity in 32 healthy adults using magnetoencephalograpy. Visual inspection of baseline power spectra revealed that the subjects fell into those with strong low frequency activity (set 2, n = 11) and those without such activity, but dominated by an alpha peak (set 1, n = 22). Cross-validated linear discriminant analysis, using mean spectral density (MSD) in nine frequency bands as predictors, found overall that 82.5% of the subjects were classified as determined by visual inspection. The effect of 1-octanol on the MSD in narrow frequency bands differed between the two subject groups. In set 1 subjects the MSD increased in the 4.5-6.5Hz and 6.5–8.5 Hz bands. This was consistent with a widening of the alpha peak toward lower frequencies. In the set two subjects the MSD decrease in the 2.5–4.5 Hz and 4.5–6.5 Hz bands. This decreased power is consistent with the blocking effect of 1-octanol on T-type calcium channels. The subjects reported no adverse effects of the 1-octanol. Since stronger low frequency activity is characteristic of patients with TCD, 1-octanol and other T-type calcium channel blockers are good candidates for treatment of this group of disorders following a placebo-controlled study. PMID:28217089

  13. Differential Modulation of Rhythmic Brain Activity in Healthy Adults by a T-Type Calcium Channel Blocker: An MEG Study.

    PubMed

    Walton, Kerry D; Maillet, Emeline L; Garcia, John; Cardozo, Timothy; Galatzer-Levy, Isaac; Llinás, Rodolfo R

    2017-01-01

    1-octanol is a therapeutic candidate for disorders involving the abnormal activation of the T-type calcium current since it blocks this current specifically. Such disorders include essential tremor and a group of neurological and psychiatric disorders resulting from thalamocortical dysrhythmia (TCD). For example, clinically, the observable phenotype in essential tremor is the tremor itself. The differential diagnostic of TCD is not based only on clinical signs and symptoms. Rather, TCD incorporates an electromagnetic biomarker, the presence of abnormal thalamocortical low frequency brain oscillations. The effect of 1-octanol on brain activity has not been tested. As a preliminary step to such a TCD study, we examined the short-term effects of a single dose of 1-octanol on resting brain activity in 32 healthy adults using magnetoencephalograpy. Visual inspection of baseline power spectra revealed that the subjects fell into those with strong low frequency activity (set 2, n = 11) and those without such activity, but dominated by an alpha peak (set 1, n = 22). Cross-validated linear discriminant analysis, using mean spectral density (MSD) in nine frequency bands as predictors, found overall that 82.5% of the subjects were classified as determined by visual inspection. The effect of 1-octanol on the MSD in narrow frequency bands differed between the two subject groups. In set 1 subjects the MSD increased in the 4.5-6.5Hz and 6.5-8.5 Hz bands. This was consistent with a widening of the alpha peak toward lower frequencies. In the set two subjects the MSD decrease in the 2.5-4.5 Hz and 4.5-6.5 Hz bands. This decreased power is consistent with the blocking effect of 1-octanol on T-type calcium channels. The subjects reported no adverse effects of the 1-octanol. Since stronger low frequency activity is characteristic of patients with TCD, 1-octanol and other T-type calcium channel blockers are good candidates for treatment of this group of disorders following a placebo-controlled study.

  14. Investigation on musculoskeletal discomfort and ergonomics risk factors among production team members at an automotive component assembly plant

    NASA Astrophysics Data System (ADS)

    Aziz, Fazilah Abdul; Ghazalli, Zakri; Zuki Mohamed, Nik Mohd; Isfar, Amri

    2017-10-01

    Musculoskeletal discomfort (MSD) is very common condition in automotive industry. MSD is affecting the worker’s health, well-being and lower down the productivity. Therefore, the main objective of this study was to identify the prevalence of MSD and ergonomics risk factors among the production team members at a selected automotive component manufacturer in Malaysia. MSD data were collected by conducting structure interview with all participants by referring to the Cornell Musculoskeletal Disorder Questionnaire (CMDQ). Those production team members who achieved a total discomfort score for all body regions more than 100 was selected for job task assessment. The physical exposure risk factors of work related musculoskeletal disorders (WMSD) has evaluated by using Quick Exposure Check (QEC) techniques. The results of the study identified the severe MSD associated with production assembly team members. It is expected that the prevalence of MSD for those production assembly team members was lower back (75.4%), upper back (63.2%), right shoulder (61.4%), and right wrist (60%). The QEC analysis discovered that about 70% of job tasks had very high risks for neck posture and 60% had high risks for the back (in moving condition) and shoulder/arm postures. There were 80% of respondents have produced a high score for exposure risk to vibration. As a conclusion, the main implication of the current study is that special attention should be paid to the physical and psychosocial aspects in production team members with musculoskeletal discomfort to improve their safety, health, and well-being, maintain work ability and productivity.

  15. Identifying the most successful dose (MSD) in dose-finding studies in cancer.

    PubMed

    Zohar, Sarah; O'Quigley, John

    2006-01-01

    For a dose finding study in cancer, the most successful dose (MSD), among a group of available doses, is that dose at which the overall success rate is the highest. This rate is the product of the rate of seeing non-toxicities together with the rate of tumor response. A successful dose finding trial in this context is one where we manage to identify the MSD in an efficient manner. In practice we may also need to consider algorithms for identifying the MSD which can incorporate certain restrictions, the most common restriction maintaining the estimated toxicity rate alone below some maximum rate. In this case the MSD may correspond to a different level than that for the unconstrained MSD and, in providing a final recommendation, it is important to underline that it is subject to the given constraint. We work with the approach described in O'Quigley et al. [Biometrics 2001; 57(4):1018-1029]. The focus of that work was dose finding in HIV where both information on toxicity and efficacy were almost immediately available. Recent cancer studies are beginning to fall under this same heading where, as before, toxicity can be quickly evaluated and, in addition, we can rely on biological markers or other measures of tumor response. Mindful of the particular context of cancer, our purpose here is to consider the methodology developed by O'Quigley et al. and its practical implementation. We also carry out a study on the doubly under-parameterized model, developed by O'Quigley et al. but not

  16. Is complementary and alternative medicine effective in job satisfaction among dentists with musculoskeletal disorders? A cross sectional study.

    PubMed

    Gupta, Devanand; Bhaskar, Dara John; Gupta, Rajendra Kumar; Jain, Ankita; Yadav, Priyanka; Dalai, Deepak Ranjan; Singh, Rajeshwar; Singh, Nisha; Chaudhary, Varunjeet; Singh, Ankit; Yadav, Ankit; Karim, Bushra

    2014-01-01

    Musculoskeletal disorders have serious impact on the profession of dentistry. There is common occurrence of pain due to incorrect posture in dental professionals. Complementary and alternative medicine (CAM) therapies may cast a new light on preventing and intercepting musculoskeletal disorders (MSD). An epidemiological study was conducted in an effort to contribute to the prevention of musculoskeletal disorders in dentistry. The purpose of this study was to determine the prevalence of MSD at dentists using CAM as a treatment and preventive modality for MSD and to compare job/career satisfaction between dentists who use CAM and conventional therapy (CT). Dentists registered in Uttrakhand state, India, under the Dental Council of India and registered members of the Indian Dental Association, Uttrakhand branch (N = 1496) were surveyed. Statistical analysis was conducted using SPSS 17. A response rate of 84% (N = 1257) was obtained, revealing that 90% (N = 1131) had the problem of MSD. Seventy three percentage (N = 826) of dentists with MSD reported the use of CAM and CT. Complementary and alternative medicine users reported greater overall health (72.7% vs. 51%, p < 0.001), job satisfaction (61.2% vs. 35%, p < 0.001) and work efficiency compared to CT users. Complementary and alternative medicine therapies may improve quality of life, reduce work interruption and enhance job satisfaction for dentists who suffers from MSD. Through the course of their studies, dentists should be equipped with knowledge on ergonomics and CAM therapies, such as yoga and others, to help them prevent musculoskeletal disorders more effectively.

  17. Berkeley Lab - Materials Sciences Division

    Science.gov Websites

    MSD Support Human Resources Facilities & Space Planning Procurement and Property Proposals & ; Finance Templates Travel One-Stop Acknowledging MSD Support Human Resources Facilities & Space Planning Procurement and Property Proposals & Finance Templates Travel Human Resources General

  18. Comparison of three gas chromatography methods for the determination of slip agents in polyethylene films.

    PubMed

    Garrido-López, Alvaro; Esquiu, Vanesa; Tena, María Teresa

    2007-05-25

    Polymers require the use of some slip agents, such as oleamide and erucamide, in order to reduce their friction coefficient and to make films easier to handle. In this communication, three analytical methods consisting in pressurized liquid extraction (PLE) and gas chromatography (GC) are used to determine oleamide and erucamide in polyethylene films. The sample was extracted with pure isopropanol (two times) at 105 degrees C for 16 min. Then, the liquid extract containing oleamide and erucamide was analyzed by GC and three different detection systems: flame ionization detector (FID), thermoionic selective detector (TSD) and ion-trap mass spectrometry detector (MSD). Oleamide and erucamide were separated using a 30 m x 0.25 mm (I.D.) 5% phenyl-95% dimethyl-polysiloxane capillary column in 12 min. The chromatographic methods were characterized and compared in terms of repeatability, linearity and sensitivity. The GC-FID and GC-TSD methods were linear up to about 60 microg ml(-1), whereas the linear range for the GC-MSD method was shorter, from 20.5 to 42 microg ml(-1). LODs identified with GC-MSD were two times higher than those identified with the other two methods. Repeatability values (expressed as relative standard deviation) of less than 2.5% were found for FID and TSD but they were above 10% for MSD. Finally, each method was applied to determine the content of erucamide and oleamide in several polyethylene films and the results obtained were compared with those obtained from the nitrogen content measured by pyrolysis and gas-phase chemiluminescence. No significant differences were observed between the results of the methods.

  19. Integration of GC-MSD and ER-Calux® assay into a single protocol for determining steroid estrogens in environmental samples.

    PubMed

    Avberšek, Miha; Žegura, Bojana; Filipič, Metka; Heath, Ester

    2011-11-01

    There are many published studies that use either chemical or biological methods to investigate steroid estrogens in the aquatic environment, but rarer are those that combine both. In this study, gas chromatography with mass selective detection (GC-MSD) and the ER-Calux(®) estrogenicity assay were integrated into a single protocol for simultaneous determination of natural (estrone--E1, 17β-estradiol--E2, estriol--E3) and synthetic (17α-ethinylestradiol--EE2) steroid estrogens concentrations and the total estrogenic potential of environmental samples. For integration purposes, several solvents were investigated and the commonly used dimethyl sulphoxide (DMSO) in the ER-Calux(®) assay was replaced by ethyl acetate, which is more compatible with gas chromatography and enables the same sample to be analysed by both GC-MSD and the ER-Calux(®) assay. The integrated protocol was initially tested using a standard mixture of estrogens. The results for pure standards showed that the estrogenicity calculated on the basis of GC-MSD and the ER-Calux(®) assay exhibited good correlation (r(2)=0.96; α=0.94). The result remained the same when spiked waste water extracts were tested (r(2)=0.92, α=1.02). When applied to real waste water influent and effluent samples the results proved (r(2)=0.93; α=0.99) the applicability of the protocol. The main advantages of this newly developed protocol are simple sample handling for both methods, and reduced material consumption and labour. In addition, it can be applied as either a complete or sequential analysis where the ER-Calux(®) assay is used as a pre-screening method prior to the chemical analysis. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. U1snRNP-mediated suppression of polyadenylation in conjunction with the RNA structure controls poly (A) site selection in foamy viruses

    PubMed Central

    2013-01-01

    Background During reverse transcription, retroviruses duplicate the long terminal repeats (LTRs). These identical LTRs carry both promoter regions and functional polyadenylation sites. To express full-length transcripts, retroviruses have to suppress polyadenylation in the 5′LTR and activate polyadenylation in the 3′LTR. Foamy viruses have a unique LTR structure with respect to the location of the major splice donor (MSD), which is located upstream of the polyadenylation signal. Results Here, we describe the mechanisms of foamy viruses regulating polyadenylation. We show that binding of the U1 small nuclear ribonucleoprotein (U1snRNP) to the MSD suppresses polyadenylation at the 5′LTR. In contrast, polyadenylation at the 3′LTR is achieved by adoption of a different RNA structure at the MSD region, which blocks U1snRNP binding and furthers RNA cleavage and subsequent polyadenylation. Conclusion Recently, it was shown that U1snRNP is able to suppress the usage of intronic cryptic polyadenylation sites in the cellular genome. Foamy viruses take advantage of this surveillance mechanism to suppress premature polyadenylation at the 5’end of their RNA. At the 3’end, Foamy viruses use a secondary structure to presumably block access of U1snRNP and thereby activate polyadenylation at the end of the genome. Our data reveal a contribution of U1snRNP to cellular polyadenylation site selection and to the regulation of gene expression. PMID:23718736

  1. 78 FR 41803 - Notice of Lodging of Proposed Amendment to Consent Decree Under the Clean Water Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-11

    ... original 2012 consent decree, the Metropolitan St. Louis Sewer District (``MSD'') agreed to undertake... specific combined sewer overflow control measures. MSD still is in the process of complying with the 2012...

  2. Modified signed-digit trinary addition using synthetic wavelet filter

    NASA Astrophysics Data System (ADS)

    Iftekharuddin, K. M.; Razzaque, M. A.

    2000-09-01

    The modified signed-digit (MSD) number system has been a topic of interest as it allows for parallel carry-free addition of two numbers for digital optical computing. In this paper, harmonic wavelet joint transform (HWJT)-based correlation technique is introduced for optical implementation of MSD trinary adder implementation. The realization of the carry-propagation-free addition of MSD trinary numerals is demonstrated using synthetic HWJT correlator model. It is also shown that the proposed synthetic wavelet filter-based correlator shows high performance in logic processing. Simulation results are presented to validate the performance of the proposed technique.

  3. Fracture analysis of stiffened panels under biaxial loading with widespread cracking

    NASA Technical Reports Server (NTRS)

    Newman, J. C., Jr.; Dawicke, D. S.

    1995-01-01

    An elastic-plastic finite-element analysis with a critical crack-tip-opening angle (CTOA) fracture criterion was used to model stable crack growth and fracture of 2024-T3 aluminum alloy (bare and clad) panels for several thicknesses. The panels had either single or multiple-site damage (MSD) cracks subjected to uniaxial or biaxial loading. Analyses were also conducted on cracked stiffened panels with single or MSD cracks. The critical CTOA value for each thickness was determined by matching the failure load on a middle-crack tension specimen. Comparisons were made between the critical angles determined from the finite-element analyses and those measured with photographic methods. Predicted load-against-crack extension and failure loads for panels under biaxial loading, panels with MSD cracks, and panels with various number of stiffeners were compared with test data, whenever possible. The predicted results agreed well with the test data even for large-scale plastic deformations. The analyses were also able to predict stable tearing behavior of a large lead crack in the presence of MSD cracks. The analyses were then used to study the influence of stiffeners on residual strength in the presence of widespread fatigue cracking. Small MSD cracks were found to greatly reduce the residual strength for large lead cracks even for stiffened panels.

  4. Fracture analysis of stiffened panels under biaxial loading with widespread cracking

    NASA Technical Reports Server (NTRS)

    Newman, J. C., Jr.

    1995-01-01

    An elastic-plastic finite-element analysis with a critical crack-tip opening angle (CTOA) fracture criterion was used to model stable crack growth and fracture of 2024-T3 aluminum alloy (bare and clad) panels for several thicknesses. The panels had either single or multiple-site damage (MSD) cracks subjected to uniaxial or biaxial loading. Analyses were also conducted on cracked stiffened panels with single or MSD cracks. The critical CTOA value for each thickness was determined by matching the failure load on a middle-crack tension specimen. Comparisons were made between the critical angles determined from the finite-element analyses and those measured with photographic methods. Predicted load-against-crack extension and failure loads for panels under biaxial loading, panels with MSD cracks, and panels with various numbers of stiffeners were compared with test data whenever possible. The predicted results agreed well with the test data even for large-scale plastic deformations. The analyses were also able to predict stable tearing behavior of a large lead crack in the presence of MSD cracks. The analyses were then used to study the influence of stiffeners on residual strength in the presence of widespread fatigue cracking. Small MSD cracks were found to greatly reduce the residual strength for large lead cracks even for stiffened panels.

  5. A laboratory study of multiple site damage in fuselage lap splices

    DOT National Transportation Integrated Search

    1993-12-01

    This report details an experimental study that was conducted to explore the causes of : fuselage lap splice multiple site damage (MSD), which has been observed in several : aging aircraft. MSD was partially responsible for the 1988 Aloha Airlines acc...

  6. Mortality Surveillance for Infectious Diseases in the U.S. Department of Defense (1998-2013).

    PubMed

    Potter, Robert N; Tremaine, Ladd A; Gaydos, Joel C

    2017-03-01

    The Mortality Surveillance Division (MSD) of the U.S. Armed Forces Medical Examiner System was established in 1998 to improve surveillance for all military deaths although emphasizing deaths from infectious diseases. Establishment of the MSD was part of the 1997 Department of Defense initiative to improve surveillance and response for emerging infectious diseases. Before 1998, mortality surveillance was limited to compiling information from death certificates, a system that provided limited useful information and lacked the timeliness needed to take meaningful action to address emerging infectious disease threats. The MSD was tasked to quickly identify all infectious disease deaths and the infecting agents. The system developed by the MSD staff identified deaths in near real-time and immediately notified military Public Health authorities of situations that warranted an investigation. Autopsy, medical, and investigative reports were collected. Testing specimens for agent identification was encouraged. The data and information collected were archived in the MSD-developed Medical Mortality Registry (MMR), a database that included all active duty Service Member deaths and contained manner and cause of death with medical, demographic, circumstantial, and diagnostic information. The MMR was the only comprehensive, autopsy-based source for mortality information on active duty military deaths. During 1998-2013, 217 (1.3%) infectious disease deaths were identified among 16,192 noncombat deaths. Of the 217 deaths, 29.5% were classified as respiratory, 18.0% cardiac, 15.2% blood borne, 12.9% nervous system, and 12.4% sepsis. A pathogen was identified for 64.5%. Agents of military interest identified included Neisseria meningitidis, influenza viruses, adenoviruses, and malaria. Neisseria meningitidis was identified in 10 fatal cases; grouping of the agent was done for eight cases. Four were group B, two were C, and two were Y. All eight had been immunized with a quadrivalent meningococcal vaccine. The most commonly detected respiratory agent was influenza virus (nine deaths), three of which were the 2009 pandemic H1N1 influenza virus. Adenoviruses were identified as the infectious agents in a total of nine deaths. Two deaths resulted from Plasmodium falciparum malaria infections acquired in Africa during military deployments. An important but unexplained finding was that Black Service Members made up only16.3% of all military personnel but accounted for 28.6% of all infectious disease deaths. The time lag between death and notification of the MSD at the start of this surveillance program was 24 to 48 hours. The lag at the end of the reported surveillance period was 8 to 24 hours. The MSD surveillance system identified an agent in 140 of 217 (64.5%) uniformed deaths. In a similar program by the Centers for Disease Control and Prevention, in 122 cases with specimens, an agent could be identified in 34 (28%). MMR data and information provided strong support for re-establishing the military recruit adenovirus vaccination program, which ceased in 1999 and was finally re-established in 2011. MMR data and information also assisted in monitoring the military meningococcal vaccine program, helped to describe the virulence of circulating influenza viruses, and identified areas where deadly malaria infections were not being prevented. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

  7. Evaluation of self-reported work ability and usefulness of interventions among sick-listed patients.

    PubMed

    Wåhlin, Charlotte; Ekberg, Kerstin; Persson, Jan; Bernfort, Lars; Öberg, Birgitta

    2013-03-01

    To describe the types of intervention offered, to investigate the relationship between the type of intervention given, patient-reported usefulness of interventions and the effect on self-reported work ability in a cohort of sick-listed patients with musculoskeletal disorders (MSD) or mental disorders (MD). A prospective cohort study was performed including 810 newly sick-listed patients (MSD 62 % and MD 38 %). The baseline questionnaire included sociodemographic characteristics and measures of work ability. The 3-month follow-up questionnaire included measures of work ability, type of intervention received, and judgment of usefulness. Twenty-five percent received medical intervention modalities (MI) only, 45 % received a combination of medical and rehabilitative intervention modalities (CRI) and 31 % received work-related interventions combined with medical or rehabilitative intervention modalities (WI). Behavioural treatments were more common for patients with MD compared with MSD and exercise therapy were more common for patients with MSD. The most prevalent workplace interventions were adjustment of work tasks or the work environment. Among patients with MD, WI was found to be useful and improved work ability significantly more compared with only MI or CRI. For patients with MSD, no significant differences in improved work ability were found between interventions. Patients with MD who received a combination of work-related and clinical interventions reported best usefulness and best improvement in work ability. There was no difference in improvements in work ability between rehabilitation methods in the MSD group. There seems to be a gap between scientific evidence and praxis behaviour in the rehabilitation process. Unimodal rehabilitation was widely applied in the early rehabilitation process, a multimodal treatment approach was rare and only one-third received work-related interventions. It remains a challenge to understand who needs what type of intervention.

  8. Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure.

    PubMed

    Smith, Sonali M; Godfrey, James; Ahn, Kwang Woo; DiGilio, Alyssa; Ahmed, Sairah; Agrawal, Vaibhav; Bachanova, Veronika; Bacher, Ulrike; Bashey, Asad; Bolaños-Meade, Javier; Cairo, Mitchell; Chen, Andy; Chhabra, Saurabh; Copelan, Edward; Dahi, Parastoo B; Aljurf, Mahmoud; Farooq, Umar; Ganguly, Siddhartha; Hertzberg, Mark; Holmberg, Leona; Inwards, David; Kanate, Abraham S; Karmali, Reem; Kenkre, Vaishalee P; Kharfan-Dabaja, Mohamed A; Klein, Andreas; Lazarus, Hillard M; Mei, Matthew; Mussetti, Alberto; Nishihori, Taiga; Ramakrishnan Geethakumari, Praveen; Saad, Ayman; Savani, Bipin N; Schouten, Harry C; Shah, Nirav; Urbano-Ispizua, Alvaro; Vij, Ravi; Vose, Julie; Sureda, Anna; Hamadani, Mehdi

    2018-06-15

    Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated. This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM). Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P < .0001). The 5-year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto-HCT (58%; P < .0001). Patients with high-risk FL, as defined by ETF, undergoing auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has lower relapse rates than auto-HCT but similar OS. Cancer 2018;124:2541-51. © 2018 American Cancer Society. © 2018 American Cancer Society.

  9. Working mothers and early childhood outcomes: lessons from the Canadian National Longitudinal Study on Children and Youth.

    PubMed

    Sherlock, R L; Synnes, A R; Koehoorn, M

    2008-04-01

    More mothers are choosing to return to work during the first 2 years of their child's life with an uncertain impact on early developmental outcomes. To determine the association between duration of maternity leave and motor and social development of toddlers. Population-based, retrospective cohort study. The Canadian National Longitudinal Survey on Children and Youth (NLSCY) Cycle 3 provides data on the characteristics and life experience of Canadian children. For sampled households, the person most knowledgeable about the child completed a survey on demographics, parent characteristics and family environment. The analysis was limited to 6664 families with children up to 2 years. Logistic regression was used to assess the association between duration of maternity leave and impaired performance (<-1 SD below the mean) on the Motor and Social Development (MSD) scale adjusted for multiple covariates including maternal age, gender, breastfeeding and socioeconomic status. One month of maternity leave increased the odds of impaired performance on the MSD by 3% (OR 1.03, 95% CI 1.02, 1.04). This was also seen with categorized maternity leave duration. Being male (OR 1.53, 95% CI 1.35, 1.74) and having a younger mother (OR 1.48, 95% CI 0.98, 2.23) increased the risk of impaired performance on the MSD while being of higher SES reduced the risk (OR 0.96, 95% CI 0.93, 1.00). There is an association between duration of maternity leave and impaired performance in motor and social development in children up to 2 years.

  10. Influence of obesity and physical workload on disability benefits among construction workers followed up for 37 years.

    PubMed

    Robroek, Suzan J W; Järvholm, Bengt; van der Beek, Allard J; Proper, Karin I; Wahlström, Jens; Burdorf, Alex

    2017-09-01

    The objectives of this study are to investigate the relation between obesity and labour force exit via diagnosis-specific disability benefits, and whether physical workload modifies this association. A longitudinal analysis was performed among 3 28 743 Swedish construction workers in the age of 15-65 years. Body weight and height were measured at a health examination and enriched with register information on disability benefits up to 37 years later. Diagnoses of disability benefits were categorised into cardiovascular diseases (CVDs), musculoskeletal diseases (MSDs), mental disorders and others. A job exposure matrix, based on self-reported lifting of heavy loads and working in bent forward or twisted position, was applied as a measure of physical workload. Cox proportional hazards regression analyses were performed, and the relative excess risk due to interaction (RERI) between obesity and physical workload was calculated. Obese construction workers were at increased risk of receiving disability benefits (HR 1.70, 95% CI 1.65 to 2.76), mainly through CVD (HR 2.30) and MSD (HR 1.71). Construction workers with a high physical workload were also more likely to receive a disability benefit (HR 2.28, 95% CI 2.21 to 2.34), particularly via MSD (HR 3.02). Obesity in combination with a higher physical workload increased the risk of disability benefits (RERI 0.28) more than the sum of the risks of obesity and higher physical workload, particularly for MSD (RERI 0.44). Obesity and a high physical workload are risk factors for disability benefit. Furthermore, these factors are synergistic risk factors for labour force exit via disability benefit through MSD. Comprehensive programmes that target health promotion to prevent obesity and ergonomic interventions to reduce physical workload are important to facilitate sustained employment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Alessandra Lanzara

    Science.gov Websites

    Berkeley Lab Berkeley Lab A-Z Index Phone Book Jobs Search DOE Search MSD Go MSD - Materials Investigators Division Staff Facilities and Centers Staff Jobs Safety Personnel Resources Committees In Case of ; Finance Templates Travel One-Stop Investigators Division Staff Facilities and Centers Staff Jobs

  12. ENHANCING TEST SENSITIVITY IN TOXICITY TESTING BY USING A STATISTICAL PERFORMANCE STANDARD

    EPA Science Inventory

    Previous reports have shown that within-test sensitivity can vary markedly among laboratories. Experts have advocated an empirical approach to controlling test variability based on the MSD, control means, and other test acceptability criteria. (The MSD represents the smallest dif...

  13. 36 CFR 3.13 - What conditions apply to the use of Marine Sanitation Devices (MSD)?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the door to the space enclosing the toilets with a padlock or door handle key lock. (c) The... fresh water that is equipped with toilet facilities and/or a MSD that is capable of discharge, must lock...

  14. 36 CFR 3.13 - What conditions apply to the use of Marine Sanitation Devices (MSD)?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the door to the space enclosing the toilets with a padlock or door handle key lock. (c) The... fresh water that is equipped with toilet facilities and/or a MSD that is capable of discharge, must lock...

  15. 36 CFR 3.13 - What conditions apply to the use of Marine Sanitation Devices (MSD)?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the door to the space enclosing the toilets with a padlock or door handle key lock. (c) The... fresh water that is equipped with toilet facilities and/or a MSD that is capable of discharge, must lock...

  16. Atomic mean-square displacement of a solid: A Green's-function approach

    NASA Astrophysics Data System (ADS)

    Shukla, R. C.; Hübschle, Hermann

    1989-07-01

    We have presented a Green's-function method of calculating the atomic mean-square displacement (MSD) of a solid. The method effectively sums a class of all anharmonic contributions to the MSD. From the point of view of perturbation theory (PT) our expression for MSD includes the lowest-order (λ2) PT contributions (cubic and quartic) with correct numerical coefficients. The numerical results obtained by this method in the high-temperature limit for a fcc nearest-neighbor Lennard-Jones-solid model are in excellent agreement with the Monte Carlo (MC) method for the same model over the entire temperature range of the solid. Highly accurate results for the order-λ2 PT contributions to MSD are obtained by eliminating the uncertainty in the convergence of the cubic contributions in the earlier work of Heiser, Shukla, and Cowly and they are now in much better agreement with the MC results but still inferior to the Green's-function method at the highest temperature.

  17. Return-to-work for multiple jobholders with a work-related musculoskeletal disorder: A population-based, matched cohort in British Columbia.

    PubMed

    Maas, Esther T; Koehoorn, Mieke; McLeod, Christopher B

    2018-01-01

    Multiple jobholders (MJHs) have a higher risk of injury compared to single jobholders (SJHs), but it is unknown if return-to-work (RTW) after a work injury is affected by multiple jobholding. This study examined the association between multiple versus single jobholding and time to RTW for workers with a work-related musculoskeletal disorder (MSD). We used administrative workers' compensation data to identify injured workers with an accepted MSD lost-time claim between 2010-2014 in British Columbia, Canada (n = 125,639 SJHs and 9,029 MJHs). The outcome was days until RTW during twelve months after the first day of time-loss. The MJH and SJH cohorts were balanced using coarsened exact matching that yielded a final matched cohort of 8,389 MJHs and 8,389 SJHs. The outcome was estimated with Cox regression, using piecewise models, and the hazard ratios were stratified by type of MSD, a serious injury indicator, gender, weekly workdays preceding MSD, and wage categories. MJHs were less likely to RTW compared to SJHs within the first six months after the first time-loss day, with greater and longer lasting effects for males, workers with a serious injury, and a higher wage. No difference between MJHs and SJHs was found for workers who had a six- or seven-day work week preceding MSD, for workers with dislocations, and for workers who were still off work after six months. Overall, MJHs with a workweek of maximum five days are disadvantaged compared to SJHs in terms of RTW following a work-related MSD within the first six months after the first time-loss day. This difference might be caused by more precarious job contracts for MJHs that challenges RTW because of lack of support for modified work, higher workload, and reduced likelihood that MJHs file a workers' compensation claim. Despite adjusting for type of MSD, severity of injury and occupation, the differences persisted for the vast majority of the study sample.

  18. Return-to-work for multiple jobholders with a work-related musculoskeletal disorder: A population-based, matched cohort in British Columbia

    PubMed Central

    Koehoorn, Mieke; McLeod, Christopher B.

    2018-01-01

    Introduction Multiple jobholders (MJHs) have a higher risk of injury compared to single jobholders (SJHs), but it is unknown if return-to-work (RTW) after a work injury is affected by multiple jobholding. This study examined the association between multiple versus single jobholding and time to RTW for workers with a work-related musculoskeletal disorder (MSD). Methods We used administrative workers’ compensation data to identify injured workers with an accepted MSD lost-time claim between 2010–2014 in British Columbia, Canada (n = 125,639 SJHs and 9,029 MJHs). The outcome was days until RTW during twelve months after the first day of time-loss. The MJH and SJH cohorts were balanced using coarsened exact matching that yielded a final matched cohort of 8,389 MJHs and 8,389 SJHs. The outcome was estimated with Cox regression, using piecewise models, and the hazard ratios were stratified by type of MSD, a serious injury indicator, gender, weekly workdays preceding MSD, and wage categories. Results MJHs were less likely to RTW compared to SJHs within the first six months after the first time-loss day, with greater and longer lasting effects for males, workers with a serious injury, and a higher wage. No difference between MJHs and SJHs was found for workers who had a six- or seven-day work week preceding MSD, for workers with dislocations, and for workers who were still off work after six months. Conclusions Overall, MJHs with a workweek of maximum five days are disadvantaged compared to SJHs in terms of RTW following a work-related MSD within the first six months after the first time-loss day. This difference might be caused by more precarious job contracts for MJHs that challenges RTW because of lack of support for modified work, higher workload, and reduced likelihood that MJHs file a workers’ compensation claim. Despite adjusting for type of MSD, severity of injury and occupation, the differences persisted for the vast majority of the study sample. PMID:29614128

  19. Overview of a multi-stakeholder dialogue around Shared Services for Health: the Digital Health Opportunity in Bangladesh.

    PubMed

    Ashraf, Sania; Moore, Carolyn; Gupta, Vaibhav; Chowdhury, Anir; Azad, Abul K; Singh, Neelu; Hagan, David; Labrique, Alain B

    2015-12-09

    National level policymaking and implementation includes multiple stakeholders with varied interests and priorities. Multi-stakeholder dialogues (MSDs) can facilitate consensus building through collective identification of challenges, recognition of shared goals and interests, and creation of solution pathways. This can shape joint planning and implementation for long-term efficiency in health and other sectors. Scaling up the effective use of information and communication technologies (ICTs) requires cohesive strategic planning towards a shared goal. In Bangladesh, the government and partners convened an MSD in March 2015 to increase stakeholder engagement in policymaking and implementation of a national ICT or electronic or mobile health (eHealth or mHealth) strategy, which seeks to incorporate ICTs into the national health system, aligning with the Digital Bangladesh Vision 2021. Relevant stakeholders were identified and key priorities and challenges were mapped through key informant interviews. An MSD was conducted with key stakeholders in Dhaka, Bangladesh. The MSD included presentations, group option generation, agreement and prioritization of barriers to scaling up ICTs. The MSD approach to building consensus on key priorities highlights the value of dialogue and collaboration with relevant stakeholders to encourage country ownership of nationwide efforts such as ICT scale-up. This MSD showed the dynamic context in which stakeholders operate, including those from academia, donors and foundations, healthcare professionals, associations, multilateral organizations, non-governmental organizations, partner countries and the private sector. Through this MSD, participants improved understanding of each other's contributions and interests, identified existing relationships, and agreed on policy and implementation gaps that needed to be filled. Collaboration among stakeholders in ICT efforts and research can promote a cohesive approach to scaling up, as well as improve policymaking by integrating interests and feedback of different key cross sectoral actors. MSDs can align stakeholders to identify challenges and solution pathways, and lead to coordinated action and accountability for resources and results. In addition, the MSD template and approach has been useful to guide ICT scale up in Bangladesh and could be replicated in other contexts to facilitate multi-constituency, multi-sector collaboration.

  20. Detecting uniaxial single domain grains with a modified IRM technique

    NASA Astrophysics Data System (ADS)

    Mitra, R.; Tauxe, L.; Gee, J. S.

    2011-12-01

    Mid-ocean ridge basalt (MORB) specimens have often been found to have high ratios of saturation remanence to saturation magnetization (Mrs/Ms). This has been attributed either to dominant cubic anisotropy or to insufficient saturating field leading to overestimation of Mrs/Ms of a dominantly uniaxial single domain (USD) assemblage. To resolve this debate, we develop an independent technique to detect USD assemblages. The experimental protocol involves subjecting the specimen to bidirectional impulse fields at each step. The experiment is similar to the conventional isothermal remanent magnetization (IRM) acquisition experiment but the field is applied twice, in antiparallel directions. We define a new parameter, IRAT, as the ratio of the remanences at each field step and show it to have characteristic behaviour for the two assemblages; IRAT ˜1 at all field steps for USD and <1 with a strong field dependence for multi-axial single domain (MSD) grains. We verified the theoretical predictions experimentally with representative USD and MSD specimens. Experiments with MORBs gave low IRATs for specimens having high Mrs/Ms. This argues for a dominant MSD assemblage in the MORBs, possibly cubic in nature. Although undersaturation of the samples can indeed be a contributing factor to the exceptionally high Mrs/Ms, this study shows that the nature of the assemblage cannot be dominantly USD.

  1. Case Study: Installation and Monitoring of Green Infrastructure Stormwater Controls in Louisville, Kentucky

    EPA Science Inventory

    In 2005, the Louisville and Jefferson County Metropolitan Sewer District (MSD) entered into a Consent Decree with the U.S. Environmental Protection Agency (EPA), Kentucky Department for Environmental Protection, and the U.S. Department of Justice. In 2009, MSD submitted the Inte...

  2. Berkeley Lab - Materials Sciences Division

    Science.gov Websites

    Synthesis Condensed Matter and Materials Physics Scattering and Instrumentation Science Centers Center for Berkeley Lab Berkeley Lab A-Z Index Phone Book Jobs Search DOE Search MSD Go MSD - Materials Sciences Division About Organization Contact Research Core Programs Materials Discovery, Design and

  3. Comparable Outcomes after HLA-Matched Sibling and Alternative Donor Hematopoietic Cell Transplantation for Children with Fanconi Anemia and Severe Aplastic Anemia.

    PubMed

    Ebens, Christen L; DeFor, Todd E; Tryon, Rebecca; Wagner, John E; MacMillan, Margaret L

    2018-04-01

    Fanconi anemia (FA)-associated severe aplastic anemia (SAA) requires allogeneic hematopoietic cell transplantation (HCT) for cure. With the evolution of conditioning regimens over time, outcomes of alternative donor HCT (AD-HCT) have improved dramatically. We compared outcomes of HLA-matched sibling donor HCT (MSD-HCT; n = 17) and AD-HCT (n = 57) performed for FA-associated SAA at a single institution between 2001 and 2016. Overall survival at 5 years was 94% for MSD-HCT versus 86% for AD-HCT, neutrophil engraftment was 100% versus 95%, platelet recovery was 100% versus 89%, grade II-IV acute graft-versus-host disease (GVHD) was 6% versus 12%, grade III-IV acute GVHD was 6% versus 4%, and chronic GVHD was 0 versus 7%, with no statistically significant differences by type of transplant. The use of UCB was associated with decreased rates of neutrophil recovery in AD-HCT and platelet recovery in both MSD-HCT and AD-HCT. A trend toward a higher serious infection density before day +100 post-HCT was observed in AD-HCT compared with MSD-HCT (P = .02). These data demonstrate that AD-HCT should be considered at the same time as MSD-HCT for patients with FA-associated SAA. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  4. Is there a stronger graft-versus-leukemia effect using HLA-haploidentical donors compared with HLA-identical siblings?

    PubMed

    Ringdén, O; Labopin, M; Ciceri, F; Velardi, A; Bacigalupo, A; Arcese, W; Ghavamzadeh, A; Hamladji, R M; Schmid, C; Nagler, A; Mohty, M

    2016-02-01

    Haploidentical hematopoietic stem cell transplants (HSCTs) are increasingly used, but it is unknown whether they have a stronger graft-versus-leukemia (GVL) effect. We analyzed 10 679 acute leukemia patients who underwent HSCT from an HLA-matched sibling donor (MSD, n=9815) or a haploidentical donor (⩾2 HLA-antigen disparity, n=864) between 2007 and 2012, reported to the European Group for Blood and Marrow Transplantation. In a Cox regression model, acute and chronic graft-versus-host disease (GVHD) was added as time-dependent variables. There was no difference in probability of relapse between recipients of haploidentical and MSD grafts. Factors of importance for relapse after T-cell-replete grafts included remission status at HSCT, Karnofsky score ⩽80, acute GVHD of grade II or higher and chronic GVHD (P<10(-5)). Patients with post-transplant cyclophosphamide (n=194) had similar outcome as other T-cell-replete haploidentical transplants (n=369). Non-relapse mortality was significantly higher in the haploidentical group compared with that in MSD patients (P<10(-5)). Leukemia-free survival was superior in the MSD patients receiving T-cell-replete (P<10(-5)) or T-cell-depleted grafts (P=0.0006). The risk of relapse was the same in acute leukemia patients who received haploidentical donor grafts as in those given MSD transplants, suggesting a similar GVL effect.

  5. Studying the association between musculoskeletal disorders, quality of life and mental health. A primary care pilot study in rural Crete, Greece

    PubMed Central

    2009-01-01

    Background The burden of musculoskeletal disorders (MSD) on the general health and well-being of the population has been documented in various studies. The objective of this study was to explore the association between MSD and the quality of life and mental health of patients and to discuss issues concerning care seeking patterns in rural Greece. Methods Patients registered at one rural Primary Care Centre (PCC) in Crete were invited to complete the Nordic Musculoskeletal Questionnaire (NMQ) for the analysis of musculoskeletal symptoms, together with validated instruments for measuring health related quality of life (SF-36) and mental distress (GHQ-28). Results The prevalence rate of MSD was found to be 71.2%, with low back and knee pain being the most common symptoms. Most conditions significantly impaired the quality of life, especially the physical dimensions of SF-36. Depression was strongly correlated to most MSD (p < 0.001). Multiple logistic analyses revealed that patients who consulted the PCC due to MSD were likely to have more mental distress or impaired physical functioning compared to those who did not. Conclusion Musculoskeletal disorders were common in patients attending the rural PCC of this study and were associated with a poor quality of life and mental distress that affected their consultation behaviour. PMID:19930570

  6. Evaluation of the multi-seeded (msd) mutant of sorghum for ethanol production

    USDA-ARS?s Scientific Manuscript database

    Grain sorghum [Sorghum bicolor (L.) Moench], a cost effective crop in semiarid regions, is an underestimated supplement to corn in starch based ethanol production. Twenty three multi-seeded (msd) mutant sorghums and one wild type sorghum BTx623 were evaluated for ethanol production and effect of che...

  7. Characterization of a multi-seeded (msd) mutant of sorghum that displays significant enhancement in seed number

    USDA-ARS?s Scientific Manuscript database

    Sorghum (Sorghum bicolor L. Moench) cultivars and germplasm display branched inflorescence or panicle, characterized by spikelets composed of a single sessile, fertile floret that develop into viable seed and one or two adjacent sterile pedicellate florets (Monoseeded [MSD] trait). Based on total nu...

  8. Case Study: Installation and Monitoring of Green Infrastructure Stormwater Controls in Louisville, Kentucky (Abstract)

    EPA Science Inventory

    In 2005, the Louisville and Jefferson County Metropolitan Sewer District (MSD) entered into a Consent Decree with the U.S. Environmental Protection Agency (EPA), Kentucky Dept. of Environmental Protection, and the U.S. Department of Justice. In 2009, the MSD submitted the Integr...

  9. Case Study: Installation and Monitoring of Green Infrastructure Stormwater Controls in Louisville, Kentucky - slides

    EPA Science Inventory

    In 2005, the Louisville and Jefferson County Metropolitan Sewer District (MSD) entered into a Consent Decree with the U.S. Environmental Protection Agency (EPA), Kentucky Department for Environmental Protection, and the U.S. Department of Justice. MSD committed to monitor the pe...

  10. 18 CFR 1304.401 - Marine sanitation devices.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 2 2012-04-01 2012-04-01 false Marine sanitation... Miscellaneous § 1304.401 Marine sanitation devices. No person operating a commercial boat dock permitted under... equipped with a marine sanitation device (MSD) unless such MSD is in compliance with all applicable...

  11. 18 CFR 1304.401 - Marine sanitation devices.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Marine sanitation... Miscellaneous § 1304.401 Marine sanitation devices. No person operating a commercial boat dock permitted under... equipped with a marine sanitation device (MSD) unless such MSD is in compliance with all applicable...

  12. 18 CFR 1304.401 - Marine sanitation devices.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 2 2013-04-01 2012-04-01 true Marine sanitation... Miscellaneous § 1304.401 Marine sanitation devices. No person operating a commercial boat dock permitted under... equipped with a marine sanitation device (MSD) unless such MSD is in compliance with all applicable...

  13. 18 CFR 1304.401 - Marine sanitation devices.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 2 2014-04-01 2014-04-01 false Marine sanitation... Miscellaneous § 1304.401 Marine sanitation devices. No person operating a commercial boat dock permitted under... equipped with a marine sanitation device (MSD) unless such MSD is in compliance with all applicable...

  14. 18 CFR 1304.401 - Marine sanitation devices.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Marine sanitation... Miscellaneous § 1304.401 Marine sanitation devices. No person operating a commercial boat dock permitted under... equipped with a marine sanitation device (MSD) unless such MSD is in compliance with all applicable...

  15. Berkeley Lab - Materials Sciences Division

    Science.gov Websites

    Computational Study of Excited-State Phenomena in Energy Materials Center for X-ray Optics MSD Facilities Ion Excited-State Phenomena in Energy Materials Center for X-ray Optics MSD Facilities Ion Beam Analysis Behavior of Lithium Metal across a Rigid Block Copolymer Electrolyte Membrane. Journal of the

  16. Matched signal detection on graphs: Theory and application to brain imaging data classification.

    PubMed

    Hu, Chenhui; Sepulcre, Jorge; Johnson, Keith A; Fakhri, Georges E; Lu, Yue M; Li, Quanzheng

    2016-01-15

    Motivated by recent progress in signal processing on graphs, we have developed a matched signal detection (MSD) theory for signals with intrinsic structures described by weighted graphs. First, we regard graph Laplacian eigenvalues as frequencies of graph-signals and assume that the signal is in a subspace spanned by the first few graph Laplacian eigenvectors associated with lower eigenvalues. The conventional matched subspace detector can be applied to this case. Furthermore, we study signals that may not merely live in a subspace. Concretely, we consider signals with bounded variation on graphs and more general signals that are randomly drawn from a prior distribution. For bounded variation signals, the test is a weighted energy detector. For the random signals, the test statistic is the difference of signal variations on associated graphs, if a degenerate Gaussian distribution specified by the graph Laplacian is adopted. We evaluate the effectiveness of the MSD on graphs both with simulated and real data sets. Specifically, we apply MSD to the brain imaging data classification problem of Alzheimer's disease (AD) based on two independent data sets: 1) positron emission tomography data with Pittsburgh compound-B tracer of 30 AD and 40 normal control (NC) subjects, and 2) resting-state functional magnetic resonance imaging (R-fMRI) data of 30 early mild cognitive impairment and 20 NC subjects. Our results demonstrate that the MSD approach is able to outperform the traditional methods and help detect AD at an early stage, probably due to the success of exploiting the manifold structure of the data. Copyright © 2015. Published by Elsevier Inc.

  17. [Hematopoietic Reconstitution and Prognosis of HLA Matched and Haploidentical Hematopoietic Stem Cell Transplantation Using Modified FC/ATG Conditioning for Treatment of Severe Aplastic Anemia].

    PubMed

    Wang, Li; Wu, Ya-Mei; Cao, Yong-Bin; Li, Xiao-Hong; Xu, Li-Xin; Wang, Hai-Tao; Gao, Ya-Hui; Wu, Xiao-Xiong

    2016-12-01

    To analyse the feasibility and compare differences between hematopoietic reconstitution and prognosis of patients with severe aplastic anemia(SAA) after matched sibling donor (MSD) or haploidentical family donor (HFD) hematopoietic stem cell transplantation (HSCT) using the modified FC/ATG conditioning. The clinical data of 56 patients with SAA who received HSCT in First Affiliated Hospital of Chinese PLA General Hospital from January 2011 to June 2016 were analyzed retrospectively. The hematopoietic reconstitution, graft verus host disease (GVHD), transplantation related toxicity (TRT) and prognosis after transplantation were compared. Furthermore, the modifed conditioning FC/ATG included low-dose cyclophosphamide (total dose 100 mg/kg), infustion of third-party donor-derived mesenchymal stem cells. All 56 patients with MSD-HSCT or HFD-HSCT achieved hematopoietic reconstitution. Among them, not only the recovery of neutrophils and platelets, but also the incidences of III-IV aGVHD, extensive cGVHD and TRT were not significantly different (the P value were 0.58, 0.61, 0.73, 0.73 and 0.67, respectively). After following-up for 32(2-66) months, 48 patients alive well, the 1-year overall survival rates were 86% in HFD-HSCT group and 89% in MSD-HSCT group, respectively (P=0.58). After HSCT using the modifed FC/ATG conditioning, patients with SAA achieved stable engraftment, low toxicity, mild GVHD and excellent outcomes. Furthermore, the HFD-HSCT achieved comparable outcomes to MSD-HSCT and may be served as an alternate therapy for patients with SAA.

  18. Health-related effects of early part-time sick leave due to musculoskeletal disorders: a randomized controlled trial.

    PubMed

    Shiri, Rahman; Kausto, Johanna; Martimo, Kari-Pekka; Kaila-Kangas, Leena; Takala, Esa-Pekka; Viikari-Juntura, Eira

    2013-01-01

    Previously we reported that early part-time sick leave enhances return to work (RTW) among employees with musculoskeletal disorders (MSD). This paper assesses the health-related effects of this intervention. Patients aged 18-60 years who were unable to perform their regular work due to MSD were randomized to part- or full-time sick leave groups. In the former, workload was reduced by halving working time. Using validated questionnaires, we assessed pain intensity and interference with work and sleep, region-specific disability due to MSD, self-rated general health, health-related quality of life (measured via EuroQol), productivity loss, depression, and sleep disturbance at baseline, 1, 3, 8, 12, and 52 weeks. We analyzed the repeated measures data (171-356 observations) with the generalized estimating equation approach. The intervention (part-time sick leave) and control (full-time sick leave) groups did not differ with regard to pain intensity, pain interference with work and sleep, region-specific disability, productivity loss, depression, or sleep disturbance. The intervention group reported better self-rated general health (adjusted P=0.07) and health-related quality of life (adjusted P=0.02) than the control group. In subgroup analyses, the intervention was more effective among the patients whose current problem began occurring <6 weeks before baseline and those with ≤30% productivity loss at baseline. Our findings showed that part-time sick leave did not exacerbate pain-related symptoms and functional disability, but improved self-rated general health and health-related quality of life in the early stage of work disability due to MSD.

  19. Anomalous Diffusion of Particles Dispersed in Xanthan Solutions Subjected to Shear Flow

    NASA Astrophysics Data System (ADS)

    Takikawa, Yoshinori; Yasuta, Muneharu; Fujii, Shuji; Orihara, Hiroshi; Tanaka, Yoshimi; Nishinari, Katsuyoshi

    2018-05-01

    Xanthan gum exhibits viscoelastic and shear-thinning properties. We investigate the Brownian motion of particles dispersed in xanthan gum solutions that are subjected to simple shear flow. The mean square displacements (MSDs) are obtained in both the flow and vorticity directions. In the absence of shear flow, subdiffusion is observed, MSD ∝ tα with α < 1, where t is time. In the presence of shear flow, however, the exponent α becomes larger together with the MSD itself in both the flow and vorticity directions. We show that the diffusion is enhanced by Taylor dispersion in the flow direction, whereas in the vorticity direction it is enhanced by nonthermal self-diffusion.

  20. Epidemiology, Seasonality and Factors Associated with Rotavirus Infection among Children with Moderate-to-Severe Diarrhea in Rural Western Kenya, 2008–2012: The Global Enteric Multicenter Study (GEMS)

    PubMed Central

    Omore, Richard; Tate, Jacqueline E.; O’Reilly, Ciara E.; Ayers, Tracy; Williamson, John; Moke, Feny; Schilling, Katie A.; Awuor, Alex O.; Jaron, Peter; Ochieng, John B.; Oundo, Joseph; Parashar, Umesh D.; Parsons, Michele B.; Bopp, Cheryl C.; Nasrin, Dilruba; Farag, Tamer H.; Kotloff, Karen L.; Nataro, James P.; Panchalingam, Sandra; Levine, Myron M.; Laserson, Kayla F.; Nuorti, J. Pekka; Mintz, Eric D.; Breiman, Robert F.

    2016-01-01

    Objective To evaluate factors associated with rotavirus diarrhea and to describe severity of illness among children <5 years old with non-dysenteric, moderate-to-severe diarrhea (MSD) in rural western Kenya. Methods We analyzed data from children <5 years old with non-dysenteric MSD enrolled as cases in the Global Enteric Multicenter Study (GEMS) in Kenya. A non-dysenteric MSD case was defined as a child with ≥3 loose stools in 24 hrs. and one or more of the following: sunken eyes, skin tenting, intravenous rehydration, or hospitalization, who sought care at a sentinel health center within 7 days of illness onset. Rotavirus antigens in stool samples were detected by ELISA. Demographic and clinical information was collected at enrollment and during a single follow-up home visit at approximately 60 days. We analyzed diarrhea severity using a GEMS 17 point numerical scoring system adapted from the Vesikari score. We used logistic regression to evaluate factors associated with rotavirus infection. Results From January 31, 2008 to September 30, 2012, among 1,637 (92%) non-dysenteric MSD cases, rotavirus was detected in stools of 245 (15.0%). Rotavirus-positive compared with negative cases were: younger (median age, 8 vs. 13 months; p<0.0001), had more severe illness (median severity score, 9 vs 8; p<0.0001) and had to be hospitalized more frequently (37/245 [15.1%] vs. 134/1,392 [9.6%]), p <0.013). Independent factors associated with rotavirus infection included age 0–11 months old (aOR = 5.29, 95% CI 3.14–8.89) and presenting with vomiting ≥3 times/24hrs (aOR = 2.58, 95% CI [1.91–3.48]). Rotavirus was detected more commonly in warm and dry months than in the cool and rainy months (142/691 [20%] vs 70/673 [10%]) p<0.0001). Conclusions Diarrhea caused by rotavirus is associated with severe symptoms leading to hospitalization. Consistent with other settings, infants had the greatest burden of disease. PMID:27494517

  1. Chromosomal instability in women with primary ovarian insufficiency.

    PubMed

    Katari, Sunita; Aarabi, Mahmoud; Kintigh, Angela; Mann, Susan; Yatsenko, Svetlana A; Sanfilippo, Joseph S; Zeleznik, Anthony J; Rajkovic, Aleksandar

    2018-02-07

    What is the prevalence of somatic chromosomal instability among women with idiopathic primary ovarian insufficiency (POI)? A subset of women with idiopathic POI may have functional impairment in DNA repair leading to chromosomal instability in their soma. The formation and repair of DNA double-strand breaks during meiotic recombination are fundamental processes of gametogenesis. Oocytes with compromised DNA integrity are susceptible to apoptosis which could trigger premature ovarian aging and accelerated wastage of the human follicle reserve. Genomewide association studies, as well as whole exome sequencing, have implicated multiple genes involved in DNA damage repair. However, the prevalence of defective DNA damage repair in the soma of women with POI is unknown. In total, 46 women with POI and 15 family members were evaluated for excessive mitomycin-C (MMC)-induced chromosome breakage. Healthy fertile females (n = 20) and two lymphoblastoid cell lines served as negative and as positive controls, respectively. We performed a pilot functional study utilizing MMC to assess chromosomal instability in the peripheral blood of participants. A high-resolution array comparative genomic hybridization (aCGH) was performed on 16 POI patients to identify copy number variations (CNVs) for a set of 341 targeted genes implicated in DNA repair. Array CGH revealed three POI patients (3/16, 18.8%) with pathogenic CNVs. Excessive chromosomal breakage suggestive of a constitutional deficiency in DNA repair was detected in one POI patient with the 16p12.3 duplication. In two patients with negative chromosome breakage analysis, aCGH detected a Xq28 deletion comprising the Centrin EF-hand Protein 2 (CETN2) and HAUS Augmin Like Complex Subunit 7 (HAUS7) genes essential for meiotic DNA repair, and a duplication in the 3p22.2 region comprising a part of the ATPase domain of the MutL Homolog 1 (MLH1) gene. Peripheral lymphocytes, used as a surrogate tissue to quantify induced chromosome damage, may not be representative of all the affected tissues. Another limitation pertains to the MMC assay which detects homologous repair pathway defects and does not test deficiencies in other DNA repair pathways. Our results provide evidence for functional impairment of DNA repair in idiopathic POI, which may predispose the patients to other DNA repair-related conditions such as accelerated aging and/or cancer susceptibility. Funding was provided by the National Institute of Child Health and Human Development. There were no competing interests to declare. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  2. Potential of multiseeded mutant (msd) to boost sorghum grain yield

    USDA-ARS?s Scientific Manuscript database

    Seed number per plant is an important determinant of the grain yield in cereal and other crops. We have isolated a class of multiseeded (msd) sorghum (Sorghum bicolor L. Moench) mutants that are capable of producing three times the seed number and twice the seed weight per panicle as compared with t...

  3. Classification of Professional Values Based on Motivational Content: An Exploratory Study on Italian Adolescents

    ERIC Educational Resources Information Center

    Pallini, Susanna; Bove, Giuseppe; Laghi, Fiorenzo

    2011-01-01

    This study applies a multidimensional scaling (MSD) technique to investigate the structural validity of the Work Values Inventory for Adolescents with a sample of Italian students. The MSD results indicated the presence of two underlying orthogonal dimensions: individuality versus sociality and conservation versus exploration. Implications for…

  4. Mainstream Teachers' Experiences of Communicating with Students with Multiple and Severe Disabilities

    ERIC Educational Resources Information Center

    De Bortoli, Tania; Balandin, Susan; Foreman, Phil; Arthur-Kelly, Michael; Mathisen, Bernice

    2012-01-01

    The aim of this study was to explore regular teachers' perceptions and experiences of supports and obstacles to communicative interactions for students with multiple and severe disabilities (MSD). Five teachers of students with MSD participated in two in-depth interviews. Interview transcripts were analysed using content analysis. Transcripts were…

  5. Hand, Foot, and Mouth Disease Preliminarily Diagnosed as Hypochondriasis.

    ERIC Educational Resources Information Center

    Davidson, Michael Jay; And Others

    1990-01-01

    A case in which a dental student with hand, foot, and mouth disease was told he had "medical student disease" (MSD), or hypochondriasis, is related; literature pertaining to the occurrence and treatment of MSD is reviewed, and the importance of care in approaches to both students and patients are discussed. (MSE)

  6. Berkeley Lab - Materials Sciences Division

    Science.gov Websites

    Synthesis Condensed Matter and Materials Physics Scattering and Instrumentation Science Centers Center for materials and phenomena at multiple time and length scales. Through our core programs and research centers Berkeley Lab Berkeley Lab A-Z Index Phone Book Jobs Search DOE Search MSD Go MSD - Materials

  7. The application of an industry level participatory ergonomics approach in developing MSD interventions.

    PubMed

    Tappin, D C; Vitalis, A; Bentley, T A

    2016-01-01

    Participatory ergonomics projects are traditionally applied within one organisation. In this study, a participative approach was applied across the New Zealand meat processing industry, involving multiple organisations and geographical regions. The purpose was to develop interventions to reduce musculoskeletal disorder (MSD) risk. This paper considers the value of an industry level participatory ergonomics approach in achieving this. The main rationale for a participative approach included the need for industry credibility, and to generate MSD interventions that address industry level MSD risk factors. An industry key stakeholder group became the primary vehicle for formal participation. The study resulted in an intervention plan that included the wider work system and industry practices. These interventions were championed across the industry by the key stakeholder group and have extended beyond the life of the study. While this approach helped to meet the study aim, the existence of an industry-supported key stakeholder group and a mandate for the initiative are important prerequisites for success. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  8. On decoding of multi-level MPSK modulation codes

    NASA Technical Reports Server (NTRS)

    Lin, Shu; Gupta, Alok Kumar

    1990-01-01

    The decoding problem of multi-level block modulation codes is investigated. The hardware design of soft-decision Viterbi decoder for some short length 8-PSK block modulation codes is presented. An effective way to reduce the hardware complexity of the decoder by reducing the branch metric and path metric, using a non-uniform floating-point to integer mapping scheme, is proposed and discussed. The simulation results of the design are presented. The multi-stage decoding (MSD) of multi-level modulation codes is also investigated. The cases of soft-decision and hard-decision MSD are considered and their performance are evaluated for several codes of different lengths and different minimum squared Euclidean distances. It is shown that the soft-decision MSD reduces the decoding complexity drastically and it is suboptimum. The hard-decision MSD further simplifies the decoding while still maintaining a reasonable coding gain over the uncoded system, if the component codes are chosen properly. Finally, some basic 3-level 8-PSK modulation codes using BCH codes as component codes are constructed and their coding gains are found for hard decision multistage decoding.

  9. Prevalence and predictors for musculoskeletal discomfort in Malaysian office workers: Investigating explanatory factors for a developing country.

    PubMed

    Maakip, Ismail; Keegel, Tessa; Oakman, Jodi

    2016-03-01

    Musculoskeletal disorders (MSDs) are a major occupational health issue for workers in developed and developing countries, including Malaysia. Most research related to MSDs has been undertaken in developed countries; given the different regulatory and cultural practices it is plausible that contributions of hazard and risk factors may be different. A population of Malaysian public service office workers were surveyed (N = 417, 65.5% response rate) to determine prevalence and associated predictors of MSD discomfort. The 6-month period prevalence of MSD discomfort was 92.8% (95%CI = 90.2-95.2%). Akaike's Information Criterion (AIC) analyses was used to compare a range of models and determine a model of best fit. Contributions associated with MSD discomfort in the final model consisted of physical demands (61%), workload (14%), gender (13%), work-home balance (9%) and psychosocial factors (3%). Factors associated with MSD discomfort were similar in developed and developing countries but the relative contribution of factors was different, providing insight into future development of risk management strategies. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  10. Inflammation reduces physiological tissue tolerance in the development of work-related musculoskeletal disorders.

    PubMed

    Barr, Ann E; Barbe, Mary F

    2004-02-01

    Work-related musculoskeletal disorders (MSDs) cause substantial worker discomfort, disability and loss of productivity. Due to the difficulty in analyzing the tissues of patients in the early stages of work-related MSD, there is controversy concerning the pathomechanisms of the development of these disorders. The pathophysiology of work-related MSD can be studied more easily in animal models. The purpose of this review is to relate theories of the development of tissue injury due to repeated motion to findings of recent investigations in animals that address the role of the inflammatory response in propagating tissue injury and contributing to chronic or recurring tissue injury. These tissue effects are related to behavioral indicators of discomfort and movement dysfunction with the aim of clarifying key time points for specific intervention approaches. The results from animal models of MSD are discussed in the light of findings in patients, whose tissues are examined at a much later phase of MSD development. Finally, a conceptual model of the potentially negative impact of inflammation on tissue tolerance is proposed along with suggestions for future research directions.

  11. Quality of Piped and Stored Water in Households with Children Under Five Years of Age Enrolled in the Mali Site of the Global Enteric Multi-Center Study (GEMS)

    PubMed Central

    Baker, Kelly K.; Sow, Samba O.; Kotloff, Karen L.; Nataro, James P.; Farag, Tamer H.; Tamboura, Boubou; Doumbia, Mama; Sanogo, Doh; Diarra, Drissa; O'Reilly, Ciara E.; Mintz, Eric; Panchalingam, Sandra; Wu, Yukun; Blackwelder, William C.; Levine, Myron M.

    2013-01-01

    Water, sanitation, and hygiene information was collected during a matched case-control study of moderate and severe diarrhea (MSD) among 4,096 children < 5 years of age in Bamako, Mali. Primary use of piped water (conditional odds ratio [cOR] = 0.45; 0.34–0.62), continuous water access (cOR = 0.30; 0.20–0.43), fetching water daily (cOR = 0.77; 0.63–0.96), and breastfeeding (cOR = 0.65; 0.49–0.88) significantly reduced the likelihood of MSD. Fetching water in > 30 minutes (cOR = 2.56; 1.55–4.23) was associated with MSD. Piped tap water and courier-delivered water contained high (> 2 mg/L) concentrations of free residual chlorine and no detectable Escherichia coli. However, many households stored water overnight, resulting in inadequate free residual chlorine (< 0.2 mg/L) for preventing microbial contamination. Coliforms and E. coli were detected in 48% and 8% of stored household water samples, respectively. Although most of Bamako's population enjoys access to an improved water source, water quality is often compromised during household storage. PMID:23836570

  12. Residual Strength Analyses of Riveted Lap-Splice Joints

    NASA Technical Reports Server (NTRS)

    Seshadri, B. R.; Newman, J. C., Jr.

    2000-01-01

    The objective of this paper was to analyze the crack-linkup behavior in riveted-stiffened lap-splice joint panels with small multiple-site damage (MSD) cracks at several adjacent rivet holes. Analyses are based on the STAGS (STructural Analysis of General Shells) code with the critical crack-tip-opening angle (CTOA) fracture criterion. To account for high constraint around a crack front, the "plane strain core" option in STAGS was used. The importance of modeling rivet flexibility with fastener elements that accurately model load transfer across the joint is discussed. Fastener holes are not modeled but rivet connectivity is accounted for by attaching rivets to the sheet on one side of the cracks that simulated both the rivet diameter and MSD cracks. Residual strength analyses made on 2024-T3 alloy (1.6-mm thick) riveted-lap-splice joints with a lead crack and various size MSD cracks were compared with test data from Boeing Airplane Company. Analyses were conducted for both restrained and unrestrained buckling conditions. Comparison of results from these analyses and results from lap-splice-joint test panels, which were partially restrained against buckling indicate that the test results were bounded by the failure loads predicted by the analyses with restrained and unrestrained conditions.

  13. Transvaginal ultrasound in threatened abortions with empty gestational sacs.

    PubMed

    Tongsong, T; Wanapirak, C; Srisomboon, J; Sirichotiyakul, S; Polsrisuthikul, T; Pongsatha, S

    1994-09-01

    To determine whether transvaginal ultrasound criteria alone can distinguish viable from non-viable gestational sacs at a single examination. A prospective descriptive study was undertaken and analysis performed on 211 pregnancies complicated by threatened abortion and empty gestation sacs diagnosed by transvaginal ultrasound. The main outcome measure was the final diagnosis of viable or non-viable gestation on subsequent transvaginal sonography. The study shows that a single transvaginal ultrasound examination is useful in differentiating viable from non-viable gestation sacs. The mean sac diameter (MSD) was found to be the most useful criterion for determining non-viability. An MSD of > or = 17 mm that lacked an embryo and an MSD of > or = 13 mm without visible yolk sac were reliable predictors of non-viable gestation sacs at a single examination with 100% specificity and 100% positive predictive value. An MSD > or = 13 mm without visible yolk sac was the most sensitive criterion. Using MSD criteria, 73% of non-viable gestations could be reliably identified without any false-positive diagnoses. Deformed shape, low position and thin decidual reaction are strong indicators of non-viable gestations but are not 100% accurate. There is still a significant proportion of empty sacs, where no accurate distinction between viable and non-viable can be made according to one criterion at a single examination and in these cases serial examinations should be carried out before any active management is advocated. In most cases, transvaginal sonographic criteria alone can distinguish viable from non-viable empty gestational sacs at a single examination.

  14. Comparative study of in vitro ocular surface cytotoxicity of a fixed combination of 0.5% timolol/1% dorzolamide eyedrop and its components with 0.005% benzalkonium chloride.

    PubMed

    Ayaki, Masahiko; Iwasawa, Atsuo; Niwano, Yoshimi

    2012-01-01

    We evaluated the cytotoxicity of antiglaucoma ophthalmic solutions preserved with the same concentration of benzalkonium chloride (BAK) in four cultured corneal and conjunctival cell lines. The viability of cell cultures was determined following the exposure of cells to timolol maleate, dorzolamide, and their fixed combination, Kosoputo(®) (MSD, a Japanese formulation of Cosopt(®) (Merck)), and two commercially available eyedrop solutions, 0.5% Timpotol(®) (containing 0.5% timolol maleate, MSD) and 1% Trusopt(®) (containing 1% dorzolamide, MSD) for varying exposure times and at various dilutions using the MTT and neutral red assays. All the three commercially available eyedrop solutions tested in this study were preserved with 0.005% BAK. The toxicity of each solution was compared using the % cell viability score (CVS) . Cell viability was also subjected to statistical analysis using ANOVA, Dunnett's multiple comparison tests and a chi-square test. %CVS50/%CVS40/80s for the tested solutions were 53/-13 for 0.5% Timoptol(®), 100/88 for preservative-free 0.5% timolol maleate, 50/ -10 for 1% Trusopt(®), 72/100 for preservative-free 1% dorzolamide, and 44/-17 for Kosoputo(®). The results of statistical analysis were consistent to them. In conclusion, Kosoputo(®) had greater cytotoxicity than each component; however, in actual use it may have the advantages of reduced toxicity (side effect) due to reduced instillation frequency, and better patient adherence to the treatment regimen as well as a comparable pressure reduction effect.

  15. Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency.

    PubMed

    Dvorak, Christopher C; Hassan, Amel; Slatter, Mary A; Hönig, Manfred; Lankester, Arjan C; Buckley, Rebecca H; Pulsipher, Michael A; Davis, Jeffrey H; Güngör, Tayfun; Gabriel, Melissa; Bleesing, Jacob H; Bunin, Nancy; Sedlacek, Petr; Connelly, James A; Crawford, David F; Notarangelo, Luigi D; Pai, Sung-Yun; Hassid, Jake; Veys, Paul; Gennery, Andrew R; Cowan, Morton J

    2014-10-01

    Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy. We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs. We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66). Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P < .01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P < .01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P < .001). Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Neural correlates of cued recall in young and older adults: an event-related potential study.

    PubMed

    Angel, Lucie; Fay, Séverine; Bouazzaoui, Badiâa; Granjon, Lionel; Isingrini, Michel

    2009-01-07

    This experiment investigated age differences in electrophysiological correlates of retrieval success in a word-stem cued recall task. Young adults (M+/-SD: 21.4 years+/-1.9) performed this memory task more accurately than older participants (M+/-SD: 65.1 years+/-3.3). Robust event-related brain potential (ERP) old/new effects were identified in both age groups. The main age differences were observed in latency and lateralization of ERP effects. Young adults exhibited a parietal effect that became focused over left parietal electrodes, whereas no asymmetry was observed in older adults. Moreover, ERP effects were more delayed in the older group. Overall, these findings provide some evidence of the reduction of processing speed during aging and suggest that young and older adults may recruit distinct cerebral patterns during episodic cued recall.

  17. Homology of aspartyl- and lysyl-tRNA synthetases.

    PubMed Central

    Gampel, A; Tzagoloff, A

    1989-01-01

    The yeast nuclear gene MSD1 coding for mitochondrial aspartyl-tRNA synthetase has been cloned and sequenced. The identity of the gene is confirmed by the following evidence. (i) The primary structure of the protein derived from the gene sequence is similar to that of the yeast cytoplasmic aspartyl-tRNA synthetase. (ii) In situ disruption of MSD1 in a respiratory-competent haploid strain of yeast induces a pleiotropic phenotype consistent with a lesion in mitochondrial protein synthesis. (iii) Mitochondria from a mutant with a disrupted chromosomal copy of MSD1 are unable to acylate mitochondrial aspartyl-tRNA. The primary structures of the cytoplasmic and mitochondrial aspartyl-tRNA synthetases are similar to the yeast cytoplasmic lysyl-tRNA synthetase, suggesting that the two types of synthetases may have a common evolutionary origin. Searches of the current protein banks also have revealed a high degree of sequence similarity of the lysyl-tRNA synthetase to the product of the Escherichia coli herC gene and to the partial sequence of a protein encoded by an unidentified reading frame located adjacent to the E. coli frdA gene. Based on the sequence similarities and the map positions of the herC and frdA loci, we propose herC to be the structural gene of the constitutively expressed lysyl-tRNA synthetase of E. coli and the unidentified reading frame to be the structural gene of the heat-inducible lysyl-tRNA synthetase. Images PMID:2668951

  18. Automatic falx cerebri and tentorium cerebelli segmentation from magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Glaister, Jeffrey; Carass, Aaron; Pham, Dzung L.; Butman, John A.; Prince, Jerry L.

    2017-03-01

    The falx cerebri and tentorium cerebelli are dural structures found in the brain. Due to the roles both structures play in constraining brain motion, the falx and tentorium must be identified and included in finite element models of the head to accurately predict brain dynamics during injury events. To date there has been very little research work on automatically segmenting these two structures, which is understandable given that their 1) thin structure challenges the resolution limits of in vivo 3D imaging, and 2) contrast with respect to surrounding tissue is low in standard magnetic resonance imaging. An automatic segmentation algorithm to find the falx and tentorium which uses the results of a multi-atlas segmentation and cortical reconstruction algorithm is proposed. Gray matter labels are used to find the location of the falx and tentorium. The proposed algorithm is applied to five datasets with manual delineations. 3D visualizations of the final results are provided, and Hausdorff distance (HD) and mean surface distance (MSD) is calculated to quantify the accuracy of the proposed method. For the falx, the mean HD is 43.84 voxels and the mean MSD is 2.78 voxels, with the largest errors occurring at the frontal inferior falx boundary. For the tentorium, the mean HD is 14.50 voxels and mean MSD is 1.38 voxels.

  19. Automatic falx cerebri and tentorium cerebelli segmentation from Magnetic Resonance Images.

    PubMed

    Glaister, Jeffrey; Carass, Aaron; Pham, Dzung L; Butman, John A; Prince, Jerry L

    2017-02-01

    The falx cerebri and tentorium cerebelli are dural structures found in the brain. Due to the roles both structures play in constraining brain motion, the falx and tentorium must be identified and included in finite element models of the head to accurately predict brain dynamics during injury events. To date there has been very little research work on automatically segmenting these two structures, which is understandable given that their 1) thin structure challenges the resolution limits of in vivo 3D imaging, and 2) contrast with respect to surrounding tissue is low in standard magnetic resonance imaging. An automatic segmentation algorithm to find the falx and tentorium which uses the results of a multi-atlas segmentation and cortical reconstruction algorithm is proposed. Gray matter labels are used to find the location of the falx and tentorium. The proposed algorithm is applied to five datasets with manual delineations. 3D visualizations of the final results are provided, and Hausdorff distance (HD) and mean surface distance (MSD) is calculated to quantify the accuracy of the proposed method. For the falx, the mean HD is 43.84 voxels and the mean MSD is 2.78 voxels, with the largest errors occurring at the frontal inferior falx boundary. For the tentorium, the mean HD is 14.50 voxels and mean MSD is 1.38 voxels.

  20. MODEL SCHOOL DIVISION--A REPORT OF THE BOARD OF EDUCATION, JUNE, 1967.

    ERIC Educational Resources Information Center

    HANSEN, CARL F.; NICKENS, NORMAN W.

    DESCRIBED IN THIS REPORT IS THE MODEL SCHOOL DIVISION (MSD) WHICH SERVES THE INNER-CITY PUBLIC SCHOOLS OF WASHINGTON, D.C. FUNCTIONING AS A SEMI-AUTONOMOUS UNIT WITHIN THE SCHOOL SYSTEM, MSD HAS AS ITS BASIC OBJECTIVES IMPROVING EDUCATIONAL QUALITY, SERVING THE SPECIAL EDUCATIONAL NEEDS OF THE COMMUNITY, STIMULATING SCHOOL-COMMUNITY INVOLVEMENT,…

  1. An Evaluation of a Summer Reading Institute, 1968.

    ERIC Educational Resources Information Center

    Rosenfeld, Michael

    This document describes part of the evaluation of a six-week reading institute for 69 K-3 teachers from the Raymond School, Model School Division (MSD), Washington, D.C. and thereby provides an evaluation model for schools to use in their own inservice training programs. Two evaluation instruments developed by an MSD innovation team in cooperation…

  2. 76 FR 78253 - New York State Prohibition of Discharges of Vessel Sewage; Final Affirmative Determination

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-16

    ... holding tank, to a municipal wastewater treatment plant or to an on-site septic system. With 37 pumpouts... and install holding tanks for effluent. Such retrofitting is complicated due to the extremely limited... Sanitation Device (MSD) can be converted to a Type III MSD, commonly called a holding tank, which can be...

  3. Virtual Reality and Cellular Phones as a Complementary Intervention for Veterans with PTSD and Substance Use Disorders

    DTIC Science & Technology

    2011-10-01

    substance use disorders (SUDs). The novel intervention uses virtual reality as a cue exposure platform to extinguish cravings to drug-related cues...Pretreatment Posttreament Outcome Variable M(SD) M(SD) PTSD Symptoms, past month (CAPS) 82.4 (18.7) 42.9 (33.5) Nicotine (Fagerstrom) 8.00 (3.46

  4. A fracture criterion for widespread cracking in thin-sheet aluminum alloys

    NASA Technical Reports Server (NTRS)

    Newman, J. C., Jr.; Dawicke, D. S.; Sutton, M. A.; Bigelow, C. A.

    1993-01-01

    An elastic-plastic finite-element analysis was used with a critical crack-tip-opening angle (CTOA) fracture criterion to model stable crack growth in thin-sheet 2024-T3 aluminum alloy panels with single and multiple-site damage (MSD) cracks. Comparisons were made between critical angles determined from the analyses and those measured with photographic methods. Calculated load against crack extension and load against crack-tip displacement on single crack specimens agreed well with test data even for large-scale plastic deformations. The analyses were also able to predict the stable tearing behavior of large lead cracks in the presence of stably tearing MSD cracks. Small MSD cracks significantly reduced the residual strength for large lead cracks.

  5. The Global Enteric Multicenter Study (GEMS) of Diarrheal Disease in Infants and Young Children in Developing Countries: Epidemiologic and Clinical Methods of the Case/Control Study

    PubMed Central

    Kotloff, Karen L.; Blackwelder, William C.; Nasrin, Dilruba; Nataro, James P.; Farag, Tamer H.; van Eijk, Annemieke; Adegbola, Richard A.; Alonso, Pedro L.; Breiman, Robert F.; Golam Faruque, Abu Syed; Saha, Debasish; Sow, Samba O.; Sur, Dipika; Zaidi, Anita K. M.; Biswas, Kousick; Panchalingam, Sandra; Clemens, John D.; Cohen, Dani; Glass, Roger I.; Mintz, Eric D.; Sommerfelt, Halvor; Levine, Myron M.

    2012-01-01

    Background. Diarrhea is a leading cause of illness and death among children aged <5 years in developing countries. This paper describes the clinical and epidemiological methods used to conduct the Global Enteric Multicenter Study (GEMS), a 3-year, prospective, age-stratified, case/control study to estimate the population-based burden, microbiologic etiology, and adverse clinical consequences of acute moderate-to-severe diarrhea (MSD) among a censused population of children aged 0–59 months seeking care at health centers in sub-Saharan Africa and South Asia. Methods. GEMS was conducted at 7 field sites, each serving a population whose demography and healthcare utilization practices for childhood diarrhea were documented. We aimed to enroll 220 MSD cases per year from selected health centers serving each site in each of 3 age strata (0–11, 12–23, and 24–59 months), along with 1–3 matched community controls. Cases and controls supplied clinical, epidemiologic, and anthropometric data at enrollment and again approximately 60 days later, and provided enrollment stool specimens for identification and characterization of potential diarrheal pathogens. Verbal autopsy was performed if a child died. Analytic strategies will calculate the fraction of MSD attributable to each pathogen and the incidence, financial costs, nutritional consequences, and case fatality overall and by pathogen. Conclusions. When completed, GEMS will provide estimates of the incidence, etiology, and outcomes of MSD among infants and young children in sub-Saharan Africa and South Asia. This information can guide development and implementation of public health interventions to diminish morbidity and mortality from diarrheal diseases. PMID:23169936

  6. A population of wheat multiple synthetic derivatives: an effective platform to explore, harness and utilize genetic diversity of Aegilops tauschii for wheat improvement.

    PubMed

    Gorafi, Yasir Serag Alnor; Kim, June-Sik; Elbashir, Awad Ahmed Elawad; Tsujimoto, Hisashi

    2018-04-28

    The multiple synthetic derivatives platform described in this study will provide an opportunity for effective utilization of Aegilops tauschii traits and genes for wheat breeding. Introducing genes from wild relatives is the best option to increase genetic diversity and discover new alleles necessary for wheat improvement. A population harboring genomic fragments from the diploid wheat progenitor Aegilops tauschii Coss. in the background of bread wheat (Triticum aestivum L.) was developed by crossing and backcrossing 43 synthetic wheat lines with the common wheat cultivar Norin 61. We named this population multiple synthetic derivatives (MSD). To validate the suitability of this population for wheat breeding and genetic studies, we randomly selected 400 MSD lines and genotyped them by using Diversity Array Technology sequencing markers. We scored black glume as a qualitative trait and heading time in two environments in Sudan as a quantitative trait. Our results showed high genetic diversity and less recombination which is expected from the nature of the population. Genome-wide association (GWA) analysis showed one QTL at the short arm of chromosome 1D different from those alleles reported previously indicating that black glume in the MSD population is controlled by new allele at the same locus. For heading time, from the two environments, GWA analysis revealed three QTLs on the short arms of chromosomes 2A, 2B and 2D and two on the long arms of chromosomes 5A and 5D. Using the MSD population, which represents the diversity of 43 Ae. tauschii accessions representing most of its natural habitat, QTLs or genes and desired phenotypes (such as drought, heat and salinity tolerance) could be identified and selected for utilization in wheat breeding.

  7. Statistics of actin-propelled trajectories in noisy environments

    NASA Astrophysics Data System (ADS)

    Wen, Fu-Lai; Chen, Hsuan-Yi; Leung, Kwan-tai

    2016-06-01

    Actin polymerization is ubiquitously utilized to power the locomotion of eukaryotic cells and pathogenic bacteria in living systems. Inevitably, actin polymerization and depolymerization proceed in a fluctuating environment that renders the locomotion stochastic. Previously, we have introduced a deterministic model that manages to reproduce actin-propelled trajectories in experiments, but not to address fluctuations around them. To remedy this, here we supplement the deterministic model with noise terms. It enables us to compute the effects of fluctuating actin density and forces on the trajectories. Specifically, the mean-squared displacement (MSD) of the trajectories is computed and found to show a super-ballistic scaling with an exponent 3 in the early stage, followed by a crossover to a normal, diffusive scaling of exponent 1 in the late stage. For open-end trajectories such as straights and S-shaped curves, the time of crossover matches the decay time of orientational order of the velocities along trajectories, suggesting that it is the spreading of velocities that leads to the crossover. We show that the super-ballistic scaling of MSD arises from the initial, linearly increasing correlation of velocities, before time translational symmetry is established. When the spreading of velocities reaches a steady state in the long-time limit, short-range correlation then yields a diffusive scaling in MSD. In contrast, close-loop trajectories like circles exhibit localized periodic motion, which inhibits spreading. The initial super-ballistic scaling of MSD arises from velocity correlation that both linearly increases and oscillates in time. Finally, we find that the above statistical features of the trajectories transcend the nature of noises, be it additive or multiplicative, and generalize to other self-propelled systems that are not necessarily actin based.

  8. The ergonomics body posture on repetitive and heavy lifting activities of workers in aerospace manufacturing warehouse

    NASA Astrophysics Data System (ADS)

    Kamat, S. R.; Zula, N. E. N. Md; Rayme, N. S.; Shamsuddin, S.; Husain, K.

    2017-06-01

    Warehouse is an important entity in manufacturing organizations. It usually involves working activities that relate ergonomics risk factors including repetitive and heavy lifting activities. Aerospace manufacturing workers are prone of having musculoskeletal disorder (MSD) problems because of the manual handling activities. From the questionnaires is states that the workers may have experience discomforts experience during manual handling work. Thus, the objectives of this study are; to investigate the body posture and analyze the level of discomfort for body posture of the workers while performing the repetitive and heavy lifting activities that cause MSD problems and to suggest proper body posture and alternatives to reduce the MSD related problems. Methodology of this study involves interviews, questionnaires distribution, anthropometry measurements, RULA (Right Upper Limb Assessment) assessment sheet and CATIA V5 RULA analysis, NIOSH lifting index (LI) and recommended weight limit (RWL). Ten workers are selected for pilot study and as for anthropometry measurement all workers in the warehouse department were involved. From the first pilot study, the RULA assessment score in CATIA V5 shows the highest score which is 7 for all postures and results after improvement of working posture is very low hence, detecting weight of the material handling is not in recommendation. To reduce the risk of MSD through the improvisation of working posture, the weight limit is also calculated in order to have a RWL for each worker. Therefore, proposing a guideline for the aerospace workers involved with repetitive movement and excessive lifting will help in reducing the risk of getting MSD.

  9. The contribution of major diagnostic causes to socioeconomic differences in disability retirement.

    PubMed

    Polvinen, Anu; Laaksonen, Mikko; Gould, Raija; Lahelma, Eero; Martikainen, Pekka

    2014-07-01

    The aim of this study was twofold: to investigate socioeconomic differences in disability retirement (DR) due to major diseases and find out which diseases contribute most to the overall socioeconomic differences in DR. The data were longitudinal register-based (10% sample of Finns) from Statistics Finland. These data included 258 428 participants aged 35-64 years during the follow-up. The participants were employed or unemployed before the follow-up period 1997-2010. Of all participants, 14 303 men and 13 188 women ended up in DR during the follow-up. Socioeconomic status was categorized into upper- and lower-class non-manual employees, manual workers, and self-employed persons. Cox models were used to estimate hazard ratios for DR due to different diseases. Compared to upper-class non-manual employees, DR was especially high for manual workers whose retirement diagnoses included psychoactive substance use, musculoskeletal diseases (MSD), or cardiovascular diseases. Socioeconomic differences in DR were stronger for younger age groups and men versus women. For females and males, the largest part of the excess DR among manual workers compared to upper-class non-manual employees was due to MSD. In the age group 54-64 years, the contribution of MSD to the total excess was >50% among male manual workers and 75% among female manual workers. Excess DR due to mental disorders concerned only 35-54-year-old manual workers (among 23% men and 26% women). The contribution of MSD to the total excess DR among lower socioeconomic groups was large. Prevention of MSD among manual workers would likely reduce socioeconomic differences in DR.

  10. Developing a Satellite Educational Program for Deaf and Hard of Hearing Students Residing in a Rural Setting.

    ERIC Educational Resources Information Center

    Witt, Sheree; Howell, Ruth

    The Allegany County School System and the Maryland School for the Deaf (MSD) have collaborated to develop a satellite program that brings MSD educational services to hard-of-hearing and deaf elementary students in rural western Maryland. In the past 5 years, the number of hearing-impaired preschoolers in Allegany and Garrett Counties increased…

  11. Five Essential Features of Quality Educational Programs for Students with Moderate and Severe Intellectual Disability: A Guide for Administrators

    ERIC Educational Resources Information Center

    Pennington, Robert; Courtade, Ginevra; Jones Ault, Melinda; Delano, Monica

    2016-01-01

    Despite encouraging changes in the expectations of programming for persons with moderate to severe intellectual disability (MSD), data suggest that programs for these individuals are still lacking in several critical areas. Building administrators play a key role in promoting high quality programs for students with MSD within local schools but may…

  12. Examination of postures and frequency of musculoskeletal disorders among manual workers in Calcutta, India.

    PubMed

    Sarkar, Krishnendu; Dev, Samrat; Das, Tamal; Chakrabarty, Sabarni; Gangopadhyay, Somnath

    2016-04-01

    Manual material handling (MMH) activities require workers to adopt various awkward postures leading to the development of musculoskeletal disorders (MSD). To investigate the postures adopted during heavy load handling and the frequency of MSDs among MMH workers in Calcutta, India. We conducted a cross-sectional study with 100 MMH workers. MSD frequency was assessed via the Standardized Nordic Questionnaire. The Ovako Working Posture Assessment System (OWAS) was used to analyze working posture. We used logistic regression to predict MSD risk factors. Ninety five percent of workers reported a MSD in at least one body part in the past 12 months. According to OWAS results, 83% of the analysed work postures require immediate corrective measures for worker safety. The most harmful posture was carrying a heavy load overhead. Carrying more than 120 kg increased the odds of low back and neck pain by 4.527 and 4.555, respectively. This sample had a high frequency of reported MSDs, likely attributed to physiologically strenuous occupational activities repeated on average of 30-40 times daily. Ergonomic interventions, such as the use of handcarts, and occupational training are urgently needed.

  13. Interannual Variability of the Bimodal Distribution of Summertime Rainfall Over Central America and Tropical Storm Activity in the Far-Eastern Pacific

    NASA Technical Reports Server (NTRS)

    Curtis, Scott; Starr, David OC. (Technical Monitor)

    2002-01-01

    The summer climate of southern Mexico and Central America is characterized by a mid summer drought (MSD), where rainfall is reduced by 40% in July as compared to June and September. A mid-summer reduction in the climatological number of eastern Pacific tropical cyclones has also been noted. Little is understood about the climatology and interannual variability of these minima. The present study uses a novel approach to quantify the bimodal distribution of summertime rainfall for the globe and finds that this feature of the annual cycle is most extreme over Pan America and adjacent oceans. One dominant interannual signal in this region occurs the summer before a strong winter El Nino/Southern Oscillation ENSO. Before El Nino events the region is dry, the MSD is strong and centered over the ocean, and the mid-summer minimum in tropical cyclone frequency is most pronounced. This is significantly different from Neutral cases (non-El Nino and non-La Nina) when the MSD is weak and positioned over the land bridge. The MSD is highly variable for La Nina years, and there is not an obvious mid-summer minimum in the number of tropical cyclones.

  14. Musculoskeletal disorder risk as a function of vehicle rotation angle during assembly tasks.

    PubMed

    Ferguson, Sue A; Marras, Williams S; Gary Allread, W; Knapik, Gregory G; Vandlen, Kimberly A; Splittstoesser, Riley E; Yang, Gang

    2011-07-01

    Musculoskeletal disorders (MSD) are costly and common problem in automotive manufacturing. The research goal was to quantify MSD exposure as a function of vehicle rotation angle and region during assembly tasks. The study was conducted at the Center for Occupational Health in Automotive Manufacturing (COHAM) Laboratory. Twelve subjects participated in the study. The vehicle was divided into seven regions, (3 interior, 2 underbody and 2 engine regions) representative of work areas during assembly. Three vehicle rotation angles were examined for each region. The standard horizontal assembly condition (0° rotation) was the reference frame. Exposure was assessed on the spine loads and posture, shoulder posture and muscle activity, neck posture and muscle activity as well as wrist posture. In all regions, rotating the vehicle reduced musculoskeletal exposure. In five of the seven regions 45° of vehicle rotation represented the position that reduced MSD exposure most. Two of the seven regions indicated 90° of vehicle rotation had the greatest impact for reducing MSD exposure. This study demonstrated that vehicle rotation shows promise for reducing exposure to risk factors for MDS during automobile assembly tasks. Copyright © 2010 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  15. Novel algorithm and MATLAB-based program for automated power law analysis of single particle, time-dependent mean-square displacement

    NASA Astrophysics Data System (ADS)

    Umansky, Moti; Weihs, Daphne

    2012-08-01

    In many physical and biophysical studies, single-particle tracking is utilized to reveal interactions, diffusion coefficients, active modes of driving motion, dynamic local structure, micromechanics, and microrheology. The basic analysis applied to those data is to determine the time-dependent mean-square displacement (MSD) of particle trajectories and perform time- and ensemble-averaging of similar motions. The motion of particles typically exhibits time-dependent power-law scaling, and only trajectories with qualitatively and quantitatively comparable MSD should be ensembled. Ensemble averaging trajectories that arise from different mechanisms, e.g., actively driven and diffusive, is incorrect and can result inaccurate correlations between structure, mechanics, and activity. We have developed an algorithm to automatically and accurately determine power-law scaling of experimentally measured single-particle MSD. Trajectories can then categorized and grouped according to user defined cutoffs of time, amplitudes, scaling exponent values, or combinations. Power-law fits are then provided for each trajectory alongside categorized groups of trajectories, histograms of power laws, and the ensemble-averaged MSD of each group. The codes are designed to be easily incorporated into existing user codes. We expect that this algorithm and program will be invaluable to anyone performing single-particle tracking, be it in physical or biophysical systems. Catalogue identifier: AEMD_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEMD_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 25 892 No. of bytes in distributed program, including test data, etc.: 5 572 780 Distribution format: tar.gz Programming language: MATLAB (MathWorks Inc.) version 7.11 (2010b) or higher, program should also be backwards compatible. Symbolic Math Toolboxes (5.5) is required. The Curve Fitting Toolbox (3.0) is recommended. Computer: Tested on Windows only, yet should work on any computer running MATLAB. In Windows 7, should be used as administrator, if the user is not the administrator the program may not be able to save outputs and temporary outputs to all locations. Operating system: Any supporting MATLAB (MathWorks Inc.) v7.11 / 2010b or higher. Supplementary material: Sample output files (approx. 30 MBytes) are available. Classification: 12 External routines: Several MATLAB subfunctions (m-files), freely available on the web, were used as part of and included in, this code: count, NaN suite, parseArgs, roundsd, subaxis, wcov, wmean, and the executable pdfTK.exe. Nature of problem: In many physical and biophysical areas employing single-particle tracking, having the time-dependent power-laws governing the time-averaged meansquare displacement (MSD) of a single particle is crucial. Those power laws determine the mode-of-motion and hint at the underlying mechanisms driving motion. Accurate determination of the power laws that describe each trajectory will allow categorization into groups for further analysis of single trajectories or ensemble analysis, e.g. ensemble and time-averaged MSD. Solution method: The algorithm in the provided program automatically analyzes and fits time-dependent power laws to single particle trajectories, then group particles according to user defined cutoffs. It accepts time-dependent trajectories of several particles, each trajectory is run through the program, its time-averaged MSD is calculated, and power laws are determined in regions where the MSD is linear on a log-log scale. Our algorithm searches for high-curvature points in experimental data, here time-dependent MSD. Those serve as anchor points for determining the ranges of the power-law fits. Power-law scaling is then accurately determined and error estimations of the parameters and quality of fit are provided. After all single trajectory time-averaged MSDs are fit, we obtain cutoffs from the user to categorize and segment the power laws into groups; cutoff are either in exponents of the power laws, time of appearance of the fits, or both together. The trajectories are sorted according to the cutoffs and the time- and ensemble-averaged MSD of each group is provided, with histograms of the distributions of the exponents in each group. The program then allows the user to generate new trajectory files with trajectories segmented according to the determined groups, for any further required analysis. Additional comments: README file giving the names and a brief description of all the files that make-up the package and clear instructions on the installation and execution of the program is included in the distribution package. Running time: On an i5 Windows 7 machine with 4 GB RAM the automated parts of the run (excluding data loading and user input) take less than 45 minutes to analyze and save all stages for an 844 trajectory file, including optional PDF save. Trajectory length did not affect run time (tested up to 3600 frames/trajectory), which was on average 3.2±0.4 seconds per trajectory.

  16. Aging ballistic Lévy walks

    NASA Astrophysics Data System (ADS)

    Magdziarz, Marcin; Zorawik, Tomasz

    2017-02-01

    Aging can be observed for numerous physical systems. In such systems statistical properties [like probability distribution, mean square displacement (MSD), first-passage time] depend on a time span ta between the initialization and the beginning of observations. In this paper we study aging properties of ballistic Lévy walks and two closely related jump models: wait-first and jump-first. We calculate explicitly their probability distributions and MSDs. It turns out that despite similarities these models react very differently to the delay ta. Aging weakly affects the shape of probability density function and MSD of standard Lévy walks. For the jump models the shape of the probability density function is changed drastically. Moreover for the wait-first jump model we observe a different behavior of MSD when ta≪t and ta≫t .

  17. [Between mind and body. Psychologicall methods for patients with musculoskeletal pain].

    PubMed

    Jabłońska-Brzozowska, Judyta

    According to the currently prevailing trends in medicine in restoring the psychosomatic unity of human, it is important to ask the question about the function and role of psychology in the rehabilitation of patients with chronic musculoskeletal disorder, MSD. In this article authors present the theoretical basis of psychical and body rehabilitation of patients with MSD. In the first part of this article, problem of the prevalence of MSD in population, its biological, psychological and social components and its impact on the economy of the country, have been discussed. Secondly, there was a focus on the mental representation of the body and its role as a psychophysical integrating unit. The following sections discuss therapeutic methods, like cognitive-behavioral therapy and chosen body work methods as complex rehabilitation of patients with musculoskeletal pain.

  18. Transoral Incisionless Fundoplication Effective in Eliminating GERD Symptoms in Partial Responders to Proton Pump Inhibitor Therapy at 6 Months

    PubMed Central

    Barnes, William E.; Simoni, Gilbert; Shughoury, Ahmad B.; Mavrelis, Peter G.; Raza, Mamoon; Heise, Jeffrey A.; Turgeon, Daniel G.; Fox, Mark A.

    2015-01-01

    Background. Incomplete control of troublesome regurgitation and extraesophageal manifestations of chronic gastroesophageal reflux disease (GERD) is a known limitation of proton pump inhibitor (PPI) therapy. This multicenter randomized study compared the efficacy of transoral incisionless fundoplication (TIF) against PPIs in controlling these symptoms in patients with small hiatal hernias. Methods. Between June and August 2012, 63 patients were randomized at 7 US community hospitals. Patients in the PPI group were placed on maximum standard dose (MSD). Patients in the TIF group underwent esophagogastric fundoplication using the EsophyX2 device. Primary outcome was elimination of daily troublesome regurgitation or extraesophageal symptoms. Secondary outcomes were normalization of esophageal acid exposure (EAE), PPI usage and healing of esophagitis. Results. Of 63 randomized patients (40 TIF and 23 PPI), 3 were lost to follow-up leaving 39 TIF and 21 PPI patients for analysis. At 6-month follow-up, troublesome regurgitation was eliminated in 97% of TIF patients versus 50% of PPI patients, relative risk (RR) = 1.9, 95% confidence interval (CI) = 1.2-3.11 (P = .006). Globally, 62% of TIF patients experienced elimination of regurgitation and extraesophageal symptoms versus 5% of PPI patients, RR = 12.9, 95% CI = 1.9-88.9 (P = .009). EAE was normalized in 54% of TIF patients (off PPIs) versus 52% of PPI patients (on MSD), RR = 1.0, 95% CI = 0.6-1.7 (P = .914). Ninety percent of TIF patients were off PPIs. Conclusion. At 6-month follow-up, TIF was more effective than MSD PPI therapy in eliminating troublesome regurgitation and extraesophageal symptoms of GERD. PMID:24756976

  19. Treatment of chromium contaminated plating shop rinsewater streams by reverse osmosis

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

    Walker, J.F.; Brown, C.H. Jr.; Wilson, J.H.

    1988-01-01

    Wastewater is discharged to the local sanitary sewer, which is regulated by a Metropolitan Sewer District (MSD). The MSD has established discharge limits and reports have indicated that the major source of wastewater and primary area of concern is the discharge from the industrial plating shop within the plant complex. This plating shop generates /approximately/1100 m/sup 3/ (300,000 gal) of wastewater per day. Because construction of a new plating shop is currently planned, a complete renovation of the existing plating shop is not economically feasible. The sponsor demonstrated the use of innovative wastewater treatment technologies that will minimize the amountmore » of wastewater generated from the plating processes and maintain compliance with MSD discharge limits until the new plating shop is constructed. The problems at the facility have been analyzed and a treatment system utilizing reverse osmosis (RO), with volume reduction of the RO concentrate by evaporation, has been recommended. The utilization of RO meets the specification for the demonstration of innovative technology. This paper discusses the problem analysis at the plant as well as the results of a pilot scale RO test program currently being conducted. The installation of the full scale unit is dependent on the successful completion of the RO pilot tests. 1 ref., 6 figs., 3 tabs.« less

  20. Transmembrane protein CD93 diffuses by a continuous time random walk.

    NASA Astrophysics Data System (ADS)

    Goiko, Maria; de Bruyn, John; Heit, Bryan

    Molecular motion within the cell membrane is a poorly-defined process. In this study, we characterized the diffusion of the transmembrane protein CD93. By careful analysis of the dependence of the ensemble-averaged mean squared displacement (EA-MSD, r2) on time t and the ensemble-averaged, time-averaged MSD (EA-TAMSD, δ2) on lag time τ and total measurement time T, we showed that the motion of CD93 is well-described by a continuous-time random walk (CTRW). CD93 tracks were acquired using single particle tracking. The tracks were classified as confined or free, and the behavior of the MSD analyzed. EA-MSDs of both populations grew non-linearly with t, indicative of anomalous diffusion. Their EA-TAMSDs were found to depend on both τ and T, indicating non-ergodicity. Free molecules had r2 tα and δ2 (τ /T 1 - α) , with α 0 . 5 , consistent with a CTRW. Mean maximal excursion analysis supported this result. Confined CD93 had r2 t0 and δ2 (τ / T) α , with α 0 . 3 , consistent with a confined CTRW. CTRWs are described by a series of random jumps interspersed with power-law distributed waiting times, and may arise due to the interactions of CD93 with the endocytic machinery. NSERC.

  1. The role of Kenya in the trans-African spread of maize streak virus strain A.

    PubMed

    Pande, Daniel; Madzokere, Eugene; Hartnady, Penelope; Kraberger, Simona; Hadfield, James; Rosario, Karyna; Jäschke, Anja; Monjane, Adérito L; Owor, Betty E; Dida, Mathews M; Shepherd, Dionne N; Martin, Darren P; Varsani, Arvind; Harkins, Gordon W

    2017-03-15

    Maize streak virus (MSV), the causal agent of maize streak disease (MSD), is the most important viral pathogen of Africa's staple food crop, maize. Previous phylogeographic analyses have revealed that the most widely-distributed and common MSV variant, MSV-A 1 , has been repeatedly traversing Africa over the past fifty years with long-range movements departing from either the Lake Victoria region of East Africa, or the region around the convergence of Zimbabwe, South Africa and Mozambique in southern Africa. Despite Kenya being the second most important maize producing country in East Africa, little is known about the Kenyan MSV population and its contribution to the ongoing diversification and trans-continental dissemination of MSV-A 1 . We therefore undertook a sampling survey in this country between 2008 and 2011, collecting MSD prevalence data in 119 farmers' fields, symptom severity data for 170 maize plants and complete MSV genome sequence data for 159 MSV isolates. We then used phylogenetic and phylogeographic analyses to show that whereas the Kenyan MSV population is likely primarily derived from the MSV population in neighbouring Uganda, it displays considerably more geographical structure than the Ugandan population. Further, this geographical structure likely confounds apparent associations between virus genotypes and both symptom severity and MSD prevalence in Kenya. Finally, we find that Kenya is probably a sink rather than a source of MSV diversification and movement, and therefore, unlike Uganda, Kenya probably does not play a major role in the trans-continental dissemination of MSV-A 1 . Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The Relationship between Mean Square Differences and Standard Error of Measurement: Comment on Barchard (2012)

    ERIC Educational Resources Information Center

    Pan, Tianshu; Yin, Yue

    2012-01-01

    In the discussion of mean square difference (MSD) and standard error of measurement (SEM), Barchard (2012) concluded that the MSD between 2 sets of test scores is greater than 2(SEM)[superscript 2] and SEM underestimates the score difference between 2 tests when the 2 tests are not parallel. This conclusion has limitations for 2 reasons. First,…

  3. Berkeley Lab - Materials Sciences Division

    Science.gov Websites

    Berkeley Lab Berkeley Lab A-Z Index Phone Book Jobs Search DOE Search MSD Go MSD - Materials Investigators Ager, Joel W » Alivisatos, A Paul » Altman, Ehud » Analytis, James » Anderson, Christopher  , Naomi » Gullikson, Eric M » Harris, Stephen J » Hasan, M. Zahid » Hellman, Frances » Helms, Brett A

  4. SLAC Phone Directory: Search Form

    Science.gov Websites

    Facilities LCLS Hard X-Ray LCLS IT & Networking LCLS IT Photon Systems LCLS Instrumentation Dev LCLS Delivery Dept LCLS Science Research & DevDiv LCLS Soft X-Ray LCLS Technical Support LCLS User Beam Line Ops Sup SSRL MSD Hard X-rays SSRL MSD Soft X-rays SSRL MSDBeam Line Elec SSRL MSDBeam Line

  5. St. Francis Rain Garden Water Quality Sampling Interim Data Report; Total Nitrogen, Total Phosphorus, Sediments or Solids, and E. Coli for the period April to June, 2014

    EPA Science Inventory

    This interim data reported is being provided per request to the Metropolitan Sewer District (MSD) to provide summary statistics on a limited set of water quality parameters as measured at the St. Francis Rain Garden site in the Lick Run Valley as it pertains to MSD's Project Grou...

  6. Development of the chronic obstructive pulmonary disease morning symptom diary (COPD-MSD).

    PubMed

    Globe, Gary; Currie, Brooke; Leidy, Nancy Kline; Jones, Paul; Mannino, David; Martinez, Fernando; Klekotka, Paul; O'Quinn, Sean; Karlsson, Niklas; Wiklund, Ingela

    2016-07-16

    The morning tends to be the most difficult time of day for many patients with chronic obstructive pulmonary disease (COPD) when symptoms can limit one's ability to perform even simple activities. Morning symptoms have been linked to higher levels of work absenteeism, thereby increasing the already substantial economic burden associated with COPD. A validated patient-reported outcome (PRO) instrument designed to capture morning symptoms will allow for a more comprehensive approach to the evaluation of treatment benefit in COPD clinical trials. A qualitative interview study was conducted among a sample of symptomatic adults with COPD. Concept elicitation interviews (n = 35) were conducted to identify COPD morning symptoms, followed by cognitive interviews (n = 21) to ensure patient comprehension of the items, instructions and response options of the draft COPD Morning Symptom Diary (COPD-MSD). All interview transcript data were coded using ATLAS.ti software for content analysis. Mean age of the concept elicitation and cognitive interview sample was 65.0 years (±7.5) and 62.3 years (±8.3), respectively. The study sample represented the full range of COPD severity (Global Initiative for Chronic Lung Disease [GOLD] classifications I-IV) and included a mix of racial backgrounds, employment status and educational achievement. During the concept elicitation interviews, the three most frequently reported morning symptoms were shortness of breath (n = 35/35; 100 %), phlegm/mucus (n = 31/35; 88.6 %), and cough (n = 30/35; 85.7 %). A group of clinical and instrument development experts convened to review the concept elicitation data and develop the initial 32-item draft COPD-MSD. Cognitive interviews indicated subjects found the draft COPD-MSD to be comprehensive, clear, and easy to understand. The COPD-MSD underwent minor editorial revisions and streamlining based on cognitive interviews and input from the experts to yield the final 19-item daily diary. This study supports the content validity of the new COPD-MSD and positions the diary for quantitative psychometric testing.

  7. Observed soil temperature trends associated with climate change in the Tibetan Plateau, 1960-2014

    NASA Astrophysics Data System (ADS)

    Fang, Xuewei; Luo, Siqiong; Lyu, Shihua

    2018-01-01

    Soil temperature, an important indicator of climate change, has rarely explored due to scarce observations, especially in the Tibetan Plateau (TP) area. In this study, changes observed in five meteorological variables obtained from the TP between 1960 and 2014 were investigated using two non-parametric methods, the modified Mann-Kendall test and Sen's slope estimator method. Analysis of annual series from 1960 to 2014 has shown that surface (0 cm), shallow (5-20 cm), deep (40-320 cm) soil temperatures (ST), mean air temperature (AT), and precipitation (P) increased with rates of 0.47 °C/decade, 0.36 °C/decade, 0.36 °C/decade, 0.35 °C/decade, and 7.36 mm/decade, respectively, while maximum frozen soil depth (MFD) as well as snow cover depth (MSD) decreased with rates of 5.58 and 0.07 cm/decade. Trends were significant at 99 or 95% confidence level for the variables, with the exception of P and MSD. More impressive rate of the ST at each level than the AT indicates the clear response of soil to climate warming on a regional scale. Monthly changes observed in surface ST in the past decades were consistent with those of AT, indicating a central place of AT in the soil warming. In addition, with the exception of MFD, regional scale increasing trend of P as well as the decreasing MSD also shed light on the mechanisms driving soil trends. Significant negative-dominated correlation coefficients (α = 0.05) between ST and MSD indicate the decreasing MSD trends in TP were attributable to increasing ST, especially in surface layer. Owing to the frozen ground, the relationship between ST and P is complicated in the area. Higher P also induced higher ST, while the inhibition of freeze and thaw process on the ST in summer. With the increasing AT, P accompanied with the decreasing MFD, MSD should be the major factors induced the conspicuous soil warming of the TP in the past decades.

  8. Relationship of Musculoskeletal Disorder Pain to Patterns of Clinical Care in California Dental Hygienists.

    PubMed

    Humann, Pamela; Rowe, Dorothy J

    2015-10-01

    To relate self-reported levels of musculoskeletal disorder (MSD) pain and patterns of clinical care among members of the California Dental Hygienists' Association (CDHA), using a web-based survey. The 24-item survey consisted of questions on patterns of clinical care, health habits, experience with MSD pain and demographic information. Recruitment information, including survey link and consent form, was emailed to the CDHA for distribution to its members. Descriptive analysis and cross tabulations were conducted using the online software program Qualtrics™. A Chi-square test determined statistical significant differences between the responses of the no/mild pain and moderate/severe pain groups. The response rate was 19% (500/2,700). Ninety-six percent of all respondents reported some level of MSD pain, causing nearly 25% of the respondents to miss work. Respondents, who reported moderate/severe pain, treated more patients per day (p=0.007) and on average treated greater numbers of moderate to heavy calculus patients (p=0.017) than those respondents reporting no/mild pain. Forty percent of the respondents in the moderate/severe group treated more than 8 patients per day. A higher percentage of respondents (p=0.000) in the moderate/severe pain group than in the no/mild group reported using proper posture less than 50% of treatment time. Using proper posture more than 50% of treatment time was more frequent in respondents who had practiced more than (p=0.012), compared with less than, 5 years. Workload and ergonomics are related to MSD pain. Educational programs need to emphasize the importance of these factors in the development and reduction of MSD pain. Copyright © 2015 The American Dental Hygienists’ Association.

  9. Health care seeking for Childhood Diarrhea in Developing Countries: Evidence from Seven Sites in Africa and Asia

    PubMed Central

    Nasrin, Dilruba; Wu, Yukun; Blackwelder, William C.; Farag, Tamer H.; Saha, Debasish; Sow, Samba O.; Alonso, Pedro L.; Breiman, Robert F.; Sur, Dipika; Faruque, Abu S. G.; Zaidi, Anita K. M.; Biswas, Kousick; Van Eijk, Anna Maria; Walker, Damian G.; Levine, Myron M.; Kotloff, Karen L.

    2013-01-01

    We performed serial Health Care Utilization and Attitudes Surveys (HUASs) among caretakers of children ages 0–59 months randomly selected from demographically defined populations participating in the Global Enteric Multicenter Study (GEMS), a case-control study of moderate-to-severe diarrhea (MSD) in seven developing countries. The surveys aimed to estimate the proportion of children with MSD who would present to sentinel health centers (SHCs) where GEMS case recruitment would occur and provide a basis for adjusting disease incidence rates to include cases not seen at the SHCs. The proportion of children at each site reported to have had an incident episode of MSD during the 7 days preceding the survey ranged from 0.7% to 4.4% for infants (0–11 months of age), from 0.4% to 4.7% for toddlers (12–23 months of age), and from 0.3% to 2.4% for preschoolers (24–59 months of age). The proportion of MSD episodes at each site taken to an SHC within 7 days of diarrhea onset was 15–56%, 17–64%, and 7–33% in the three age strata, respectively. High cost of care and insufficient knowledge about danger signs were associated with lack of any care-seeking outside the home. Most children were not offered recommended fluids and continuing feeds at home. We have shown the utility of serial HUASs as a tool for optimizing operational and methodological issues related to the performance of a large case-control study and deriving population-based incidence rates of MSD. Moreover, the surveys suggest key targets for educational interventions that might improve the outcome of diarrheal diseases in low-resource settings. PMID:23629939

  10. Main clinical, therapeutic and technical factors related to patient's maximum skin dose in interventional cardiology procedures

    PubMed Central

    Journy, N; Sinno-Tellier, S; Maccia, C; Le Tertre, A; Pirard, P; Pagès, P; Eilstein, D; Donadieu, J; Bar, O

    2012-01-01

    Objective The study aimed to characterise the factors related to the X-ray dose delivered to the patient's skin during interventional cardiology procedures. Methods We studied 177 coronary angiographies (CAs) and/or percutaneous transluminal coronary angioplasties (PTCAs) carried out in a French clinic on the same radiography table. The clinical and therapeutic characteristics, and the technical parameters of the procedures, were collected. The dose area product (DAP) and the maximum skin dose (MSD) were measured by an ionisation chamber (Diamentor; Philips, Amsterdam, The Netherlands) and radiosensitive film (Gafchromic; International Specialty Products Advanced Materials Group, Wayne, NJ). Multivariate analyses were used to assess the effects of the factors of interest on dose. Results The mean MSD and DAP were respectively 389 mGy and 65 Gy cm−2 for CAs, and 916 mGy and 69 Gy cm−2 for PTCAs. For 8% of the procedures, the MSD exceeded 2 Gy. Although a linear relationship between the MSD and the DAP was observed for CAs (r=0.93), a simple extrapolation of such a model to PTCAs would lead to an inadequate assessment of the risk, especially for the highest dose values. For PTCAs, the body mass index, the therapeutic complexity, the fluoroscopy time and the number of cine frames were independent explanatory factors of the MSD, whoever the practitioner was. Moreover, the effect of technical factors such as collimation, cinematography settings and X-ray tube orientations on the DAP was shown. Conclusion Optimising the technical options for interventional procedures and training staff on radiation protection might notably reduce the dose and ultimately avoid patient skin lesions. PMID:22457404

  11. Climate Change and the Central American Mid-summer Drought - The Importance of Changing Precipitation Patterns for Food and Water Security

    NASA Astrophysics Data System (ADS)

    Maurer, E. P.; Stewart, I. T.; Sundstrom, W.; Bacon, C. M.

    2016-12-01

    In addition to periodic long-term drought, much of Central America experiences a rainy season with two peaks separated by a dry period of weeks to over a month in duration, termed the mid-summer drought (MSD). Food and water security for smallholder farmers in the region hinge on accommodating this phenomenon, anticipating its arrival and estimating its duration. Model output from 1980 through the late 21st century projects changes in precipitation amount, variability, and timing, with potential to affect regional food production. Using surveys of farmer experiences in conjunction with gridded daily precipitation for a historic period on multiple scales, and with projections through the 21st century, we characterize the MSD across much of Central America using four measures: onset date, duration, intensity, and minimum, and test for significant changes. Our findings indicate that the most significant changes are for the duration, which, by the end of the century, is projected to increase by an average of over a week, and the MSD minimum precipitation, which is projected to decline by an average of over 26%, with statistically significant changes for most of Nicaragua, Honduras, El Salvador, and Guatemala (assuming a higher emissions pathway through the 21st century). These changes toward a longer and drier MSD have important implications for food and water security for vulnerable communities through the region. We find that for the four metrics the changes in interannual variability are small compared to historical variability, and are generally statistically insignificant. New farmer survey results are compared to findings from our climate analysis for the historic period, are used to interpret what MSD characteristics are of greatest interest locally, and are used for the development of adaptation strategies.

  12. Comparison of musculoskeletal disorder health claims between construction floor layers and a general working population.

    PubMed

    Dale, Ann Marie; Ryan, Daniel; Welch, Laura; Olsen, Margaret A; Buchholz, Bryan; Evanoff, Bradley

    2015-01-01

    Compare rates of medical insurance claims for musculoskeletal disorders (MSD) between workers in a construction trade and a general worker population to determine if higher physical exposures in construction lead to higher rates of claims on personal medical insurance. Health insurance claims between 2006 and 2010 from floor layers were frequency matched by age, gender, eligibility time and geographic location to claims from insured workers in general industry obtained from MarketScan. We extracted MSD claims and dates of service from six regions of the body: neck, low back, knee, lower extremity, shoulder and distal arm, and evaluated differences in claim rates. Fifty-one per cent of floor layers (n=1475) experienced musculoskeletal claims compared with 39% of MarketScan members (p<0.001). Claim rates were higher for floor layers across all body regions with nearly double the rate ratios for the knee and neck regions (RR 2.10 and 2.07). The excess risk was greatest for the neck and low back regions; younger workers had disproportionately higher rates in the knee, neck, low back and distal arm. A larger proportion of floor layers (22%) filed MSD claims in more than one body region compared with general workers (10%; p<0.001). Floor layers have markedly higher rates of MSD claims compared with a general worker population, suggesting a shifting of medical costs for work-related MSD to personal health insurance. The occurrence of disorders in multiple body regions and among the youngest workers highlights the need for improved work methods and tools for construction workers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Inter-rater reliability of direct observations of the physical and psychosocial working conditions in eldercare: An evaluation in the DOSES project.

    PubMed

    Karstad, Kristina; Rugulies, Reiner; Skotte, Jørgen; Munch, Pernille Kold; Greiner, Birgit A; Burdorf, Alex; Søgaard, Karen; Holtermann, Andreas

    2018-05-01

    The aim of the study was to develop and evaluate the reliability of the "Danish observational study of eldercare work and musculoskeletal disorders" (DOSES) observation instrument to assess physical and psychosocial risk factors for musculoskeletal disorders (MSD) in eldercare work. During 1.5 years, sixteen raters conducted 117 inter-rater observations from 11 nursing homes. Reliability was evaluated using percent agreement and Gwet's AC1 coefficient. Of the 18 examined items, inter-rater reliability was excellent for 7 items (AC1>0.75) fair to good for 7 items (AC1 0.40-0.75) and poor for 2 items (AC1 0-0.40). For 2 items there was no agreement between the raters (AC1 <0). The reliability did not differ between the first and second half of the data collection period and the inter-rater observations were representative regarding occurrence of events in eldercare work. The instrument is appropriate for assessing physical and psychosocial risk factors for MSD among eldercare workers. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Manganese Deficiency in Chlamydomonas Results in Loss of Photosystem II and MnSOD Function, Sensitivity to Peroxides, and Secondary Phosphorus and Iron Deficiency1[W][OA

    PubMed Central

    Allen, Michael D.; Kropat, Janette; Tottey, Stephen; Del Campo, José A.; Merchant, Sabeeha S.

    2007-01-01

    For photoheterotrophic growth, a Chlamydomonas reinhardtii cell requires at least 1.7 × 107 manganese ions in the medium. At lower manganese ion concentrations (typically <0.5 μm), cells divide more slowly, accumulate less chlorophyll, and the culture reaches stationary phase at lower cell density. Below 0.1 μm supplemental manganese ion in the medium, the cells are photosynthetically defective. This is accompanied by decreased abundance of D1, which binds the Mn4Ca cluster, and release of the OEE proteins from the membrane. Assay of Mn superoxide dismutase (MnSOD) indicates loss of activity of two isozymes in proportion to the Mn deficiency. The expression of MSD3 through MSD5, encoding various isoforms of the MnSODs, is up-regulated severalfold in Mn-deficient cells, but neither expression nor activity of the plastid Fe-containing superoxide dismutase is changed, which contrasts with the dramatically increased MSD3 expression and plastid MnSOD activity in Fe-deficient cells. Mn-deficient cells are selectively sensitive to peroxide but not methyl viologen or Rose Bengal, and GPXs, APX, and MSRA2 genes (encoding glutathione peroxidase, ascorbate peroxidase, and methionine sulfoxide reductase 2) are slightly up-regulated. Elemental analysis indicates that the Mn, Fe, and P contents of cells in the Mn-deficient cultures were reduced in proportion to the deficiency. A natural resistance-associated macrophage protein homolog and one of five metal tolerance proteins were induced in Mn-deficient cells but not in Fe-deficient cells, suggesting that the corresponding gene products may be components of a Mn2+-selective assimilation pathway. PMID:17085511

  15. Similar outcomes of allogeneic hematopoietic cell transplantation from unrelated donor and umbilical cord blood vs. sibling donor for pediatric acute myeloid leukemia: Multicenter experience in China.

    PubMed

    Tang, Xiangfeng; Chen, Jing; Fang, Jianpei; Sun, Xin; Qin, Mao Quan; Li, Junhui; Zhu, Yiping; Luan, Zuo

    2015-06-01

    In a multicenter study, we have conducted a retrospective study on 73 pediatric AML patients who were primary refractory or in greater than CR1 and investigated MSD (or MMSD) (n = 20), URD (n = 23), and UCB (n = 30) HCT between January 1998 and October 2009. The median day to neutrophil engraftment was similar in all groups. The median day to platelet engraftment was longer in the UCB group. The number of HLA mismatch was higher in the UCB group (p = 0.034); however, the cumulative incidence of grade III-IV aGVHD was not different among all groups (p = 0.125); furthermore, cGVHD was lower in the UCB group (p = 0.078). The risk of relapse did not differ among all groups (RR = 1.28, p = 0.125), but the patients of MSD (or MMSD) grafts had a trend of higher risk recurrence. Sixty-two patients survived with a median follow-up of 58.2 months. Five-yr LFS was 73.1%, 59.8%, and 59.6% for URD, UCB, and MSD (or MMDS), respectively (p = 0.426). Five-yr LFS in CR1 was 68.9%, with a significantly better result compared to 41.7% in CR2 (p = 0.025). Our comparisons suggest that pediatric AML patients receiving UCB had a higher early TRM, a lower cGVHD rate, and a similar long-term survival. The outcome of URD and UCB is comparable to that of a suitable sibling for pediatric AML. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Ultrasound imaging diagnostics: healthcare risks for urologists.

    PubMed

    Martino, Tilde; Massaro, Tommaso; Martino, Paolo; Martino, Pasquale

    2010-12-01

    The objectives of this study are: 1) assessing if Ultrasound (US) used during US scans can represent a risk for the healthcare of urologists; 2) verifying the frequency of Carpal Tunnel Syndrome (CTS) symptoms and musculoskeletal disorders (MSD), trying to assess the possible correlation with job load and US scanning procedures; 3) assessing the role of individual factors like age, gender and physical activity in determining such disorders. A group of 35 voluntary urologists carrying out ultrasound scans were selected: 13 were working for the 1 degrees Teaching Hospital Urology, 11 for the 2 degrees Teaching Hospital Urology, 2 for the Hospitalization Urology of the Policlinico of Bari and 9 for Urology of Public Corporation Di Venere of Bari. A questionnaire, divided in two parts, was administered to the sample: the first aimed at collecting demographic data and at describing the operators' workload and the second focused on the possible presence of CTS and MSD symptoms. 32 urologists over 35 performed more than 5 scans per week and more than 5 scans per day. On average the specialists were carrying out this activity since 18 years wheras for post-graduate students, this time was about 4 years. Twenty-six subjects (74%) showed no symptoms, 8 subjects (23%) showed from 1 to 4 symptoms which can be associated to the presence of CTS; only one subject presents more than 5 symptoms. As regards MSD, 6 urologists (17%) did not present disorders, 24 subjects (69%) showed from 1 to 4 symptoms and 5 subjects (14%) presented more than 5 symptoms. The use of US scan examination is completely safe both for the healthcare of the patients and the operator. For what concerns healthcare risks, it is highly recommended to adopt a correct posture when performing the examination and to use the provided chair.

  17. Allowing for MSD prevention during facilities planning for a public service: an a posteriori analysis of 10 library design projects.

    PubMed

    Bellemare, Marie; Trudel, Louis; Ledoux, Elise; Montreuil, Sylvie; Marier, Micheline; Laberge, Marie; Vincent, Patrick

    2006-01-01

    Research was conducted to identify an ergonomics-based intervention model designed to factor in musculoskeletal disorder (MSD) prevention when library projects are being designed. The first stage of the research involved an a posteriori analysis of 10 recent redesign projects. The purpose of the analysis was to document perceptions about the attention given to MSD prevention measures over the course of a project on the part of 2 categories of employees: librarians responsible for such projects and personnel working in the libraries before and after changes. Subjects were interviewed in focus groups. Outcomes of the analysis can guide our ergonomic assessment of current situations and contribute to a better understanding of the way inclusion or improvement of prevention measures can support the workplace design process.

  18. Observed Changes in the Alertness and Communicative Involvement of Students with Multiple and Severe Disability Following In-Class Mentor Modelling for Staff in Segregated and General Education Classrooms

    ERIC Educational Resources Information Center

    Foreman, P.; Arthur-Kelly, M.; Bennett, D.; Neilands, J.; Colyvas, K.

    2014-01-01

    Background: The improvement of engagement and involvement in communicative and socially centred exchanges for individuals with multiple and severe disability (MSD) presents complex and urgent challenges to educators. This paper reports the findings of an intervention study designed to enhance the interactive skills of students with MSD using an…

  19. Automatic Data Processing Equipment (ADPE) acquisition plan for the medical sciences

    NASA Technical Reports Server (NTRS)

    1979-01-01

    An effective mechanism for meeting the SLSD/MSD data handling/processing requirements for Shuttle is discussed. The ability to meet these requirements depends upon the availability of a general purpose high speed digital computer system. This system is expected to implement those data base management and processing functions required across all SLSD/MSD programs during training, laboratory operations/analysis, simulations, mission operations, and post mission analysis/reporting.

  20. The National Shipbuilding Research Program: Producibility Cost Reductions through Alternative Materials and Processes

    DTIC Science & Technology

    1999-03-01

    steel; -60F - 250 F; nonflammable acrylic mod- ified methyl - methacrylate Hernon MI React 761; Act 63 two component unprimed steel/primed/ painted trowel... MSD ) of the University of Michigan Transportation Institute (UMTRI), the Shipyards Division of Avondale Industries, and Damilic Corporation, to...classification society requirements. This research was conducted by the research team of the Marine Systems Division ( MSD ) of the University of Michigan

  1. Evaluation of Multiple Immunoassay Technology Platforms to Select the Anti-Drug Antibody Assay Exhibiting the Most Appropriate Drug and Target Tolerance

    PubMed Central

    Collet-Brose, Justine

    2016-01-01

    The aim of this study was, at the assay development stage and thus with an appropriate degree of rigor, to select the most appropriate technology platform and sample pretreatment procedure for a clinical ADA assay. Thus, ELISA, MSD, Gyrolab, and AlphaLISA immunoassay platforms were evaluated in association with target depletion and acid dissociation sample pretreatment steps. An acid dissociation step successfully improved the drug tolerance for all 4 technology platforms and the required drug tolerance was achieved with the Gyrolab and MSD platforms. The target tolerance was shown to be better for the ELISA format, where an acid dissociation treatment step alone was sufficient to achieve the desired target tolerance. However, inclusion of a target depletion step in conjunction with the acid treatment raised the target tolerance to the desired level for all of the technologies. A higher sensitivity was observed for the MSD and Gyrolab assays and the ELISA, MSD, and Gyrolab all displayed acceptable interdonor variability. This study highlights the usefulness of evaluating the performance of different assay platforms at an early stage in the assay development process to aid in the selection of the best fit-for-purpose technology platform and sample pretreatment steps. PMID:27243038

  2. Multistate approaches in computational protein design

    PubMed Central

    Davey, James A; Chica, Roberto A

    2012-01-01

    Computational protein design (CPD) is a useful tool for protein engineers. It has been successfully applied towards the creation of proteins with increased thermostability, improved binding affinity, novel enzymatic activity, and altered ligand specificity. Traditionally, CPD calculations search and rank sequences using a single fixed protein backbone template in an approach referred to as single-state design (SSD). While SSD has enjoyed considerable success, certain design objectives require the explicit consideration of multiple conformational and/or chemical states. Cases where a “multistate” approach may be advantageous over the SSD approach include designing conformational changes into proteins, using native ensembles to mimic backbone flexibility, and designing ligand or oligomeric association specificities. These design objectives can be efficiently tackled using multistate design (MSD), an emerging methodology in CPD that considers any number of protein conformational or chemical states as inputs instead of a single protein backbone template, as in SSD. In this review article, recent examples of the successful design of a desired property into proteins using MSD are described. These studies employing MSD are divided into two categories—those that utilized multiple conformational states, and those that utilized multiple chemical states. In addition, the scoring of competing states during negative design is discussed as a current challenge for MSD. PMID:22811394

  3. A non-local structural derivative model for characterization of ultraslow diffusion in dense colloids

    NASA Astrophysics Data System (ADS)

    Liang, Yingjie; Chen, Wen

    2018-03-01

    Ultraslow diffusion has been observed in numerous complicated systems. Its mean squared displacement (MSD) is not a power law function of time, but instead a logarithmic function, and in some cases grows even more slowly than the logarithmic rate. The distributed-order fractional diffusion equation model simply does not work for the general ultraslow diffusion. Recent study has used the local structural derivative to describe ultraslow diffusion dynamics by using the inverse Mittag-Leffler function as the structural function, in which the MSD is a function of inverse Mittag-Leffler function. In this study, a new stretched logarithmic diffusion law and its underlying non-local structural derivative diffusion model are proposed to characterize the ultraslow diffusion in aging dense colloidal glass at both the short and long waiting times. It is observed that the aging dynamics of dense colloids is a class of the stretched logarithmic ultraslow diffusion processes. Compared with the power, the logarithmic, and the inverse Mittag-Leffler diffusion laws, the stretched logarithmic diffusion law has better precision in fitting the MSD of the colloidal particles at high densities. The corresponding non-local structural derivative diffusion equation manifests clear physical mechanism, and its structural function is equivalent to the first-order derivative of the MSD.

  4. Full-Scale Testing and Analysis of Curved Aircraft Fuselage Panels.

    DOT National Transportation Integrated Search

    1993-12-01

    The report presents data on (1) residual strength of aircraft panels containing Multiple-Site Damage (MSD) in lap splices, and (2) fatigue strength of panels subjected to cyclic pressure loading. The testing was conducted using the dedicated Aging Ai...

  5. Search for HRV-parameters that detect a sympathetic shift in heart failure patients on β-blocker treatment.

    PubMed

    Zhang, Yanru; de Peuter, Olav R; Kamphuisen, Pieter W; Karemaker, John M

    2013-01-01

    A sympathetic shift in heart rate variability (HRV) from high to lower frequencies may be an early signal of deterioration in a monitored patient. Most chronic heart failure (CHF) patients receive β-blockers. This tends to obscure HRV observation by increasing the fast variations. We tested which HRV parameters would still detect the change into a sympathetic state. β-blocker (Carvedilol®) treated CHF patients underwent a protocol of 10 min supine rest, followed by 10 min active standing. CHF patients (NYHA Class II-IV) n = 15, 10m/5f, mean age 58.4 years (47-72); healthy controls n = 29, 18m/11f, mean age 62.9 years (49-78). Interbeat intervals (IBI) were extracted from the finger blood pressure wave (Nexfin®). Both linear and non-linear HRV analyses were applied that (1) might be able to differentiate patients from healthy controls under resting conditions and (2) detect the change into a sympathetic state in the present short recordings. Linear: mean-IBI, SD-IBI, root mean square of successive differences (rMSSD), pIBI-50 (the proportion of intervals that differs by more than 50 ms from the previous), LF, HF, and LF/HF ratio. Non-linear: Sample entropy (SampEn), Multiscale entropy (MSE), and derived: Multiscale variance (MSV) and Multiscale rMSSD (MSD). In the supine resting situation patients differed from controls by having higher HF and, consequently, lower LF/HF. In addition their longer range (τ = 6-10) MSE was lower as well. The sympathetic shift was, in controls, detected by mean-IBI, rMSSD, pIBI-50, and LF/HF, all going down; in CHF by mean-IBI, rMSSD, pIBI-50, and MSD (τ = 6-10) going down. MSD6-10 introduced here works as a band-pass filter favoring frequencies from 0.02 to 0.1 Hz. In β-blocker treated CHF patients, traditional time domain analysis (mean-IBI, rMSSD, pIBI-50) and MSD6-10 provide the most useful information to detect a condition change.

  6. Relationship between productivity, quality and musculoskeletal disorder risk among deboning workers in a Chilean salmon industry.

    PubMed

    Ilardi, Juan S

    2012-01-01

    The purpose of this ergonomic investigation is to establish a relationship between quality, productivity and risk of musculoskeletal disorder (MSD) in manual bone-removal process in the salmon fish industry. The method consists in a follow up study of 14 workers in a lane that processes salmon steak. Time between each steak (work cycle), quality of the steak's meat through inspection of deepness and length of the gapping generated by the manual bone-removal process and risk for musculoskeletal disorders through OCRA method were considered for this study. IMC and musculoskeletal Nordic Questionnaire of Kourinka were applied to the workers evaluated. Fourteen women worker's completed the evaluation, age 37.67 ± 8.1, with 65.27 ± 34.41 months of experience, with an IMC of 27.18 ± 3.87 (1.52 ± 0.057 meters of height) at the time of the evaluation. Time for deboning per steak averaged 38 ± 14 seconds with 68.33 ± 14.79 steaks per hour per worker. In quality terms, 74% of the steaks were qualified as "premium steaks" and 26% as "grade or industrial" (lower category and cheapest price). OCRA index for the right hand average 13.79 ± 4.59 and 3.59 ± 0.41 for the left hand. From Nordic questionnaire 80% of the workers manifested musculoskeletal symptoms in the right hand/wrist, followed up by shoulder with 60% of the workers and arm/elbow with over 50%. There was no statistically significant relationship between productivity and quality of the steak after manual bone removal process and between quality and MSD risk. However, there was a statistically significant relationship between productivity and MSD risk (p<0.05). Discussion around the results allows to see complementary results that did have strong correlation between MSD risk and the presence of lower grade salmon steaks and between areas that present musculoskeletal symptoms (MSS) and the intensity of the MSS (p<0.05). The results showed that further research is needed to validate these relationships, due to the increasing demands of health-care services from this productive sector, considering its importance for this region.

  7. Mechanism-based corrector combination restores ΔF508-CFTR folding and function

    PubMed Central

    Okiyoneda, Tsukasa; Veit, Guido; Dekkers, Johanna F.; Bagdany, Miklos; Soya, Naoto; Xu, Haijin; Roldan, Ariel; Verkman, Alan S.; Kurth, Mark; Simon, Agnes; Hegedus, Tamas; Beekman, Jeffrey M.; Lukacs, Gergely L.

    2013-01-01

    The most common cystic fibrosis (CF) mutation, ΔF508 in the nucleotide binding domain-1 (NBD1), impairs CFTR coupled-domain folding, plasma membrane (PM) expression, function and stability. VX-809, a promising investigational corrector of ΔF508-CFTR misprocessing, has limited clinical benefit and incompletely understood mechanism, hampering drug development. Based on the effect of second site suppressor mutations, robust ΔF508-CFTR correction likely requires stabilization of NBD1 and the membrane spanning domains (MSDs)-NBD1 interface, both established primary conformational defects. Here, we elucidated the molecular targets of available correctors; class-I stabilizes the NBD1-MSD1/2 interface, class-II targets NBD2, and only chemical chaperones, surrogates of class-III correctors, stabilize the human ΔF508-NBD1. While VX-809 can correct missense mutations primarily destabilizing the NBD1-MSD1/2 interface, functional PM expression of ΔF508-CFTR also requires compounds that counteract the NBD1 and NBD2 stability defects in CF bronchial epithelial cells and intestinal organoids. Thus, structure-guided corrector combination represents an effective approach for CF therapy. PMID:23666117

  8. Variable-order fractional MSD function to describe the evolution of protein lateral diffusion ability in cell membranes

    NASA Astrophysics Data System (ADS)

    Yin, Deshun; Qu, Pengfei

    2018-02-01

    Protein lateral diffusion is considered anomalous in the plasma membrane. And this diffusion is related to membrane microstructure. In order to better describe the property of protein lateral diffusion and find out the inner relationship between protein lateral diffusion and membrane microstructure, this article applies variable-order fractional mean square displacement (f-MSD) function for characterizing the anomalous diffusion. It is found that the variable order can reflect the evolution of diffusion ability. The results of numerical simulation demonstrate variable-order f-MSD function can predict the tendency of anomalous diffusion during the process of confined diffusion. It is also noted that protein lateral diffusion ability during the processes of confined and hop diffusion can be split into three parts. In addition, the comparative analyses reveal that the variable order is related to the confinement-domain size and microstructure of compartment boundary too.

  9. Molecular dynamics simulations of aggregation of copper nanoparticles with different heating rates

    NASA Astrophysics Data System (ADS)

    Li, Qibin; Wang, Meng; Liang, Yunpei; Lin, Liyang; Fu, Tao; Wei, Peitang; Peng, Tiefeng

    2017-06-01

    Molecular dynamics simulations were employed to investigate the heating rates' effect on aggregation of two copper nanoparticles. The aggregation can be distinguished into three distinct regimes by the contacting and melting of nanoparticles. The nanoparticles contacting at a lower temperature during the sintering with lower heating rate, meanwhile, some temporary stacking fault exists at the contacting neck. The aggregation properties of the system, i.e. neck diameter, shrinkage ratio, potential energy, mean square displacement (MSD) and relative gyration radius, experience drastic changes due to the free surface annihilation. After the nanoparticles coalesced for a stable period, the shrinkage ratio, MSD, relative gyration radius and neck diameter of the system are dramatically changed during the melting process. It is shown that the shrinkage ratio and MSD have relative larger increasing ratio for a lower heating rate. While the evolution of the relative gyration radius and neck diameter is only sensitive to the temperature.

  10. Musculoskeletal disorder costs and medical claim filing in the US retail trade sector.

    PubMed

    Bhattacharya, Anasua; Leigh, J Paul

    2011-01-01

    The average costs of Musculoskeletal Disorder (MSD) and odds ratios for filing medical claims related to MSD were examined. The medical claims were identified by ICD 9 codes for four US Census regions within retail trade. Large private firms' medical claims data from Thomson Reuters Inc. MarketScan databases for the years 2003 through 2006 were used. Average costs were highest for claims related to lumbar region (ICD 9 Code: 724.02) and number of claims were largest for low back syndrome (ICD 9 Code: 724.2). Whereas the odds of filing an MSD claim did not vary greatly over time, average costs declined over time. The odds of filing claims rose with age and were higher for females and southerners than men and non-southerners. Total estimated national medical costs for MSDs within retail trade were $389 million (2007 USD).

  11. Demonstration of an optoelectronic interconnect architecture for a parallel modified signed-digit adder and subtracter

    NASA Astrophysics Data System (ADS)

    Sun, Degui; Wang, Na-Xin; He, Li-Ming; Weng, Zhao-Heng; Wang, Daheng; Chen, Ray T.

    1996-06-01

    A space-position-logic-encoding scheme is proposed and demonstrated. This encoding scheme not only makes the best use of the convenience of binary logic operation, but is also suitable for the trinary property of modified signed- digit (MSD) numbers. Based on the space-position-logic-encoding scheme, a fully parallel modified signed-digit adder and subtractor is built using optoelectronic switch technologies in conjunction with fiber-multistage 3D optoelectronic interconnects. Thus an effective combination of a parallel algorithm and a parallel architecture is implemented. In addition, the performance of the optoelectronic switches used in this system is experimentally studied and verified. Both the 3-bit experimental model and the experimental results of a parallel addition and a parallel subtraction are provided and discussed. Finally, the speed ratio between the MSD adder and binary adders is discussed and the advantage of the MSD in operating speed is demonstrated.

  12. Kinetics of proton migration in liquid water.

    PubMed

    Chen, Hanning; Voth, Gregory A; Agmon, Noam

    2010-01-14

    We have utilized multistate empirical valence bond (MS-EVB3) simulations of protonated liquid water to calculate the relative mean-square displacement (MSD) and the history-independent time correlation function, c(t), of the hydrated proton center of excess charge (CEC) with respect to the water molecule on which it has initially resided. The MSD is nonlinear for the first 15 ps, suggesting that the relative diffusion coefficient increases from a small value, D(0), at short separations to its larger bulk value, D(infinity), at large separations. With the ensuing distance-dependent diffusion coefficient, D(r), the time dependence of both the MSD and c(t) agrees quantitatively with the solution of a diffusion equation for reversible geminate recombination. This suggests that the relative motion of the CEC is not independent from the nearby water molecules, in agreement with theoretical and experimental observations that large water clusters participate in the mechanism of proton mobility.

  13. Posturedontics: How does dentistry fit you?

    PubMed

    Jodalli, Praveen S; Kurana, Suchi; Shameema; Ragher, Mallikarjuna; Khed, Jaishree; Prabhu, Vishnu

    2015-08-01

    Dentists are at high risk for musculoskeletal disorders (MSD's) due to their work. MSD's is an umbrella term for number of injuries affecting different parts of the body, including joints, muscles, tendons, nerves that can arise from sudden exertion or making the same motions repeatedly. These injuries can develop over time and can lead to long-term disability. Dental professional often develop musculoskeletal problems due to bad working habits, uncomfortable physical posture causing unnecessary musculoskeletal loading, discomfort and fatigue. Ergonomic principles when it is applied, it will help to reduce stress and eliminate many potential injuries and disorders associated with the overuse of muscles, bad posture, and repeated tasks. This can be accomplished by using a proper dental chair, lighting and the selection of ergonomically-friendly equipment to fit the dental professionals physical capabilities and limitations. This review addresses about the basics of ergonomics, positioning, viewing, handling, and prevention of MSD's.

  14. Posturedontics: How does dentistry fit you?

    PubMed Central

    Jodalli, Praveen S.; Kurana, Suchi; Shameema; Ragher, Mallikarjuna; Khed, Jaishree; Prabhu, Vishnu

    2015-01-01

    Dentists are at high risk for musculoskeletal disorders (MSD's) due to their work. MSD's is an umbrella term for number of injuries affecting different parts of the body, including joints, muscles, tendons, nerves that can arise from sudden exertion or making the same motions repeatedly. These injuries can develop over time and can lead to long-term disability. Dental professional often develop musculoskeletal problems due to bad working habits, uncomfortable physical posture causing unnecessary musculoskeletal loading, discomfort and fatigue. Ergonomic principles when it is applied, it will help to reduce stress and eliminate many potential injuries and disorders associated with the overuse of muscles, bad posture, and repeated tasks. This can be accomplished by using a proper dental chair, lighting and the selection of ergonomically-friendly equipment to fit the dental professionals physical capabilities and limitations. This review addresses about the basics of ergonomics, positioning, viewing, handling, and prevention of MSD's. PMID:26538885

  15. Priority effects among young‐of‐the‐year fish: reduced growth of bluegill sunfish (Lepomis macrochirus) caused by yellow perch (Perca flavescens)?

    USGS Publications Warehouse

    Kaemingk, Mark A.; Jolley, Jeff C.; Willis, David W.; Chipps, Steven R.

    2012-01-01

    1. When available, Daphnia spp. are often preferred by age-0 yellow perch and bluegill sunfish because of energetic profitability. We hypothesised that predation by age-0 yellow perch could lead to a midsummer decline (MSD) of Daphnia spp. and that priority effects may favour yellow perch because they hatch before bluegill, allowing them to capitalise on Daphnia spp. prior to bluegill emergence.2. Data were collected from 2004 to 2010 in Pelican Lake, Nebraska, U.S.A. The lake experienced a prolonged MSD in all but 1 year (2005), generally occurring within the first 2 weeks of June except in 2008 and 2010 when it occurred at the end of June. MSD timing is not solely related to seasonal patterns of age-0 yellow perch consumption. Nevertheless, when Daphnia spp. biomass was low during 2004 and 2006–2010 (<4 mg wet weight L−1), predation by age-0 yellow perch seems to have suppressed Daphnia spp. biomass (i.e. <1.0 mg wet weight L−1). The exception was 2005 when age-0 yellow perch were absent.3. Growth of age-0 bluegill was significantly faster in 2005, when Daphnia spp. were available in greater densities (>4 mg wet weight L−1) compared with the other years (<0.2 mg wet weight L−1).4. We conclude that age-0 yellow perch are capable of reducing Daphnia biomass prior to the arrival of age-0 bluegill, ultimately slowing bluegill growth. Thus, priority effects favour age-0 yellow perch when competing with age-0 bluegill for Daphnia. However, these effects may be minimised if there is a shorter time between hatching of the two species, higher Daphnia spp. densities or lower age-0 yellow perch densities.

  16. GPS receiver CODE bias estimation: A comparison of two methods

    NASA Astrophysics Data System (ADS)

    McCaffrey, Anthony M.; Jayachandran, P. T.; Themens, D. R.; Langley, R. B.

    2017-04-01

    The Global Positioning System (GPS) is a valuable tool in the measurement and monitoring of ionospheric total electron content (TEC). To obtain accurate GPS-derived TEC, satellite and receiver hardware biases, known as differential code biases (DCBs), must be estimated and removed. The Center for Orbit Determination in Europe (CODE) provides monthly averages of receiver DCBs for a significant number of stations in the International Global Navigation Satellite Systems Service (IGS) network. A comparison of the monthly receiver DCBs provided by CODE with DCBs estimated using the minimization of standard deviations (MSD) method on both daily and monthly time intervals, is presented. Calibrated TEC obtained using CODE-derived DCBs, is accurate to within 0.74 TEC units (TECU) in differenced slant TEC (sTEC), while calibrated sTEC using MSD-derived DCBs results in an accuracy of 1.48 TECU.

  17. A 24 h investigation of the hydrogeochemistry of baseflow and stormwater in an urban area impacted by mining: Butte, Montana

    USGS Publications Warehouse

    Gammons, Christopher H.; Shope, Christopher L.; Duaime, Terence E.

    2005-01-01

    Changes in water quality during a storm event were continuously monitored over a 24 h period at a single location along an urban stormwater drain in Butte, Montana. The Butte Metro Storm Drain (MSD) collects groundwater baseflow and stormwater draining Butte Hill, a densely populated site that has been severely impacted by 130 years of mining, milling, and smelting of copper-rich, polymetallic mineral deposits. On the afternoon of 26 June 2002, a heavy thunderstorm caused streamflow in the MSD to increase 100-fold, from 0·2 ft3 s−1 to more than 20 ft3 s−1. Hourly discharge and water quality data were collected before, during, and following the storm. The most significant finding was that the calculated loads (grams per hour) of both dissolved and particulate copper passing down the MSD increased more than 100-fold in the first hour following the storm, and remained elevated over baseline conditions for the remainder of the study period. Other metals, such as zinc, cadmium, and manganese, showed a decrease in load from pre-storm to post-storm conditions. In addition to the large flush of copper, loads of soluble phosphorus increased during the storm, whereas dissolved oxygen dropped to low levels (<2 mg l−1). These results show that infrequent storm events in Butte have the potential to generate large volumes of runoff that exceed Montana water quality standards for acute exposure of aquatic life to copper, as well as depressed levels of dissolved oxygen. This study has important implications to ongoing reclamation activities in the upper Clark Fork Superfund site, particularly with respect to management of storm flow, and may be applicable to other watersheds impacted by mining activities.

  18. Manganese deficiency in Chlamydomonas results in loss of photosystem II and MnSOD function, sensitivity to peroxides, and secondary phosphorus and iron deficiency.

    PubMed

    Allen, Michael D; Kropat, Janette; Tottey, Stephen; Del Campo, José A; Merchant, Sabeeha S

    2007-01-01

    For photoheterotrophic growth, a Chlamydomonas reinhardtii cell requires at least 1.7 x 10(7) manganese ions in the medium. At lower manganese ion concentrations (typically <0.5 microm), cells divide more slowly, accumulate less chlorophyll, and the culture reaches stationary phase at lower cell density. Below 0.1 microm supplemental manganese ion in the medium, the cells are photosynthetically defective. This is accompanied by decreased abundance of D1, which binds the Mn(4)Ca cluster, and release of the OEE proteins from the membrane. Assay of Mn superoxide dismutase (MnSOD) indicates loss of activity of two isozymes in proportion to the Mn deficiency. The expression of MSD3 through MSD5, encoding various isoforms of the MnSODs, is up-regulated severalfold in Mn-deficient cells, but neither expression nor activity of the plastid Fe-containing superoxide dismutase is changed, which contrasts with the dramatically increased MSD3 expression and plastid MnSOD activity in Fe-deficient cells. Mn-deficient cells are selectively sensitive to peroxide but not methyl viologen or Rose Bengal, and GPXs, APX, and MSRA2 genes (encoding glutathione peroxidase, ascorbate peroxidase, and methionine sulfoxide reductase 2) are slightly up-regulated. Elemental analysis indicates that the Mn, Fe, and P contents of cells in the Mn-deficient cultures were reduced in proportion to the deficiency. A natural resistance-associated macrophage protein homolog and one of five metal tolerance proteins were induced in Mn-deficient cells but not in Fe-deficient cells, suggesting that the corresponding gene products may be components of a Mn(2+)-selective assimilation pathway.

  19. Autosomal Linkage Scan for Loci Predisposing to Comorbid Dependence on Multiple Substances

    PubMed Central

    Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R.; Farrer, Lindsay A.; Elston, Robert C.; Gelernter, Joel

    2014-01-01

    Multiple substance dependence (MSD) trait comorbidity is common, and MSD patients are often severely affected clinically. While shared genetic risks have been documented, so far there has been no published report using the linkage scan approach to survey risk loci for MSD as a phenotype. A total of 1,758 individuals in 739 families [384 African American (AA) and 355 European American (EA) families] ascertained via affected sib-pairs with cocaine or opioid or alcohol dependence were genotyped using an array-based linkage panel of single-nucleotide polymorphism markers. Fuzzy clustering analysis was conducted on individuals with alcohol, cannabis, cocaine, opioid, and nicotine dependence for AAs and EAs separately, and linkage scans were conducted for the output membership coefficients using Merlin-regression. In EAs, we observed an autosome-wide significant linkage signal on chromosome 4 (peak lod = 3.31 at 68.3 cM; empirical autosome-wide P = 0.038), and a suggestive linkage signal on chromosome 21 (peak lod = 2.37 at 19.4 cM). In AAs, four suggestive linkage peaks were observed: two peaks on chromosome 10 (lod = 2.66 at 96.7 cM and lod = 3.02 at 147.6 cM] and the other two on chromosomes 3 (lod = 2.81 at 145.5 cM) and 9 (lod = 1.93 at 146.8 cM). Three particularly promising candidate genes, GABRA4, GABRB1, and CLOCK, are located within or very close to the autosome-wide significant linkage region for EAs on chromosome 4. This is the first linkage evidence supporting existence of genetic loci influencing risk for several comorbid disorders simultaneously in two major US populations. PMID:22354695

  20. Reduced dose cyclophosphamide, fludarabine and antithymocyte globulin for sibling and unrelated transplant of children with severe and very severe aplastic anemia.

    PubMed

    Chung, Nack-Gyun; Lee, Jae Wook; Jang, Pil-Sang; Jeong, Dae-Chul; Cho, Bin; Kim, Hack-Ki

    2013-06-01

    We evaluated the results of a novel conditioning regimen of reduced dose cyclophosphamide (Cy, 25 mg/kg for four days), fludarabine (Flu, 30 mg/m(2) for four days), and rabbit ATG (2.5 mg/kg for three days) for allogeneic transplant of children with SAA, implemented since January 2009. Overall, 23 patients were treated with this regimen (16 male, seven female), including 10 diagnosed with VSAA. Donors included eight-MSD and 15 UD (five-matched UD, and 10 mismatched UD). All patients showed neutrophil and platelet engraftment. Cumulative incidence of acute (grade 2 or above) and chronic GVHD was 26.1% and 8.7%, respectively. Estimated two-yr FFS and OS for the entire cohort was 90.3 ± 6.5%. Rates of TRM and graft failure were 5.3% and 4.3%, respectively. No difference in OS was found according to disease severity (SAA vs. VSAA, p = 0.184), or according to donor type (MSD vs. UD, p = 0.699). Excellent outcomes of patients with VSAA underscore the efficacy of allogeneic transplant as a means of expediting hematopoietic recovery. Improved survival of UD transplant reaffirms its role as a valid therapeutic alternative in the absence of MSD. © 2013 John Wiley & Sons A/S.

  1. Comparison of Eight Equations That Predict Percent Body Fat Using Skinfolds in American Youth

    PubMed Central

    Roberts, Amy; Cai, Jianwen; Berge, Jerica M.; Stevens, June

    2016-01-01

    Abstract Background: Skinfolds are often used in equations to predict percent body fat (PBF) in youth. Although there are numerous such equations published, there is limited information to help researchers determine which equation to use for their sample. Methods: Using data from the 1999–2006 National Health and Nutrition Examination Surveys (NHANES), we compared eight published equations for prediction of PBF. These published equations all included triceps and/or subscapular skinfold measurements. We examined the PBF equations in a nationally representative sample of American youth that was matched by age, sex, and race/ethnicity to the original equation development population and a full sample of 8- to 18-year-olds. We compared the equation-predicted PBF to the dual-emission X-ray absorptiometry (DXA)-measured PBF. The adjusted R2, root mean square error (RMSE), and mean signed difference (MSD) were compared. The MSDs were used to examine accuracy and differential bias by age, sex, and race/ethnicity. Results: When applied to the full range of 8- 18-year-old youth, the R2 values ranged from 0.495 to 0.738. The MSD between predicted and DXA-measured PBF indicated high average accuracy (MSD between −1.0 and 1.0) for only three equations (Bray subscapular equation and Dezenberg equations [with and without race/ethnicity]). The majority of the equations showed differential bias by sex, race/ethnicity, weight status, or age. Conclusions: These findings indicate that investigators should use caution in the selection of an equation to predict PBF in youth given that results may vary systematically in important subgroups. PMID:27045618

  2. Comparison of Eight Equations That Predict Percent Body Fat Using Skinfolds in American Youth.

    PubMed

    Truesdale, Kimberly P; Roberts, Amy; Cai, Jianwen; Berge, Jerica M; Stevens, June

    2016-08-01

    Skinfolds are often used in equations to predict percent body fat (PBF) in youth. Although there are numerous such equations published, there is limited information to help researchers determine which equation to use for their sample. Using data from the 1999-2006 National Health and Nutrition Examination Surveys (NHANES), we compared eight published equations for prediction of PBF. These published equations all included triceps and/or subscapular skinfold measurements. We examined the PBF equations in a nationally representative sample of American youth that was matched by age, sex, and race/ethnicity to the original equation development population and a full sample of 8- to 18-year-olds. We compared the equation-predicted PBF to the dual-emission X-ray absorptiometry (DXA)-measured PBF. The adjusted R(2), root mean square error (RMSE), and mean signed difference (MSD) were compared. The MSDs were used to examine accuracy and differential bias by age, sex, and race/ethnicity. When applied to the full range of 8- 18-year-old youth, the R(2) values ranged from 0.495 to 0.738. The MSD between predicted and DXA-measured PBF indicated high average accuracy (MSD between -1.0 and 1.0) for only three equations (Bray subscapular equation and Dezenberg equations [with and without race/ethnicity]). The majority of the equations showed differential bias by sex, race/ethnicity, weight status, or age. These findings indicate that investigators should use caution in the selection of an equation to predict PBF in youth given that results may vary systematically in important subgroups.

  3. The role of transients in the Mid Summer Drought over the Tropical Americas

    NASA Astrophysics Data System (ADS)

    Herrera, E.; Magaña Rueda, V.; Caetano, E.

    2013-05-01

    The Mid Summer Drought (MSD) has raised the interested of those interested in regional climate dynamics since it appears to be a unique characteristic of the tropical Americas climate. The MSD corresponds to a relative minimum in summer precipitation between July and August in the Mesoamerican region. Several theories have been posed to explain its origin including the annual cycle march of the ITCZ, a teleconnection from the Asian monsoon region, or an air sea interaction process that relates the warm pools over the eastern Pacific and the Caribbean Sea. However, none of them has addressed the various characteristics of the MSD described by Magaña et al (1999) and Magaña and Caetano (2005). In the present paper, the role of the transient mean flow interaction over the Caribbean Sea is explored. The Caribbean Low Level Jet (CLLJ) and the transients interact in such a way that the CLLJ reaches maximum intensity when the MSD occurs. This is a period of minimum Perturbation Kinetic Energy in the region, suggesting that a CLLJ stronger than approximately 15 m/s tends to inhibit the amplification of eddies. Transients are crucial dynamic elements to produce precipitation over the Mexico and Central American region. Over the eastern Pacific warm pool, tropical convection and sea surface temperature are related by a sort of Clausius Clapeyron exponential equation. However, there are two branches for the relationship, one for the first maximum in tropical convection during June, and a second one during September, with a relative minimum corresponding to the MSD in July - August. The most interesting aspect of such patterns is that while the June exponential curves occurs at SST larger than 28°C, the curve corresponding to September takes place at lower SSTs, suggesting that transient activity in this period is necessary to enhance tropical convective activity during the latter part of the summer rains in the region. This is exactly the period when PKE increases over the Intra Americas Seas and the eastern tropical Pacific. A more comprehensive qualitative model is proposed to connect the various dynamical elements in the region that result in the MSD. This new model presents a more complicated picture of the regional climate dynamics than various theories have proposed.

  4. 75 FR 35852 - Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-23

    ... SECURITIES AND EXCHANGE COMMISSION Proposed Collection; Comment Request Upon Written Request, Copies Available From: Securities and Exchange Commission, Office of Investor Education and Advocacy, Washington, DC 20549-0213. Extension: Rule 15Bc3-1 and Form MSD; SEC File No. 270-93; OMB Control No. 3235...

  5. Two-step digit-set-restricted modified signed-digit addition-subtraction algorithm and its optoelectronic implementation.

    PubMed

    Qian, F; Li, G; Ruan, H; Jing, H; Liu, L

    1999-09-10

    A novel, to our knowledge, two-step digit-set-restricted modified signed-digit (MSD) addition-subtraction algorithm is proposed. With the introduction of the reference digits, the operand words are mapped into an intermediate carry word with all digits restricted to the set {1, 0} and an intermediate sum word with all digits restricted to the set {0, 1}, which can be summed to form the final result without carry generation. The operation can be performed in parallel by use of binary logic. An optical system that utilizes an electron-trapping device is suggested for accomplishing the required binary logic operations. By programming of the illumination of data arrays, any complex logic operations of multiple variables can be realized without additional temporal latency of the intermediate results. This technique has a high space-bandwidth product and signal-to-noise ratio. The main structure can be stacked to construct a compact optoelectronic MSD adder-subtracter.

  6. Fatigue damage assessment of high-usage in-service aircraft fuselage structure

    NASA Astrophysics Data System (ADS)

    Mosinyi, Bao Rasebolai

    As the commercial and military aircraft fleets continue to age, there is a growing concern that multiple-site damage (MSD) can compromise structural integrity. Multiple site damage is the simultaneous occurrence of many small cracks at independent structural locations, and is the natural result of fatigue, corrosion, fretting and other possible damage mechanisms. These MSD cracks may linkup and form a fatigue lead crack of critical length. The presence of MSD also reduces the structure's ability to withstand longer cracks. The objective of the current study is to assess, both experimentally and analytically, MSD formation and growth in the lap joint of curved panels removed from a retired aircraft. A Boeing 727-232 airplane owned and operated by Delta Air Lines, and retired at its design service goal, was selected for the study. Two panels removed from the left-hand side of the fuselage crown, near stringer 4L, were subjected to extended fatigue testing using the Full-Scale Aircraft Structural Test Evaluation and Research (FASTER) facility located at the Federal Aviation Administration (FAA) William J. Hughes Technical Center. The state of MSD was continuously assessed using several nondestructive inspection (NDI) methods. Damage to the load attachment points of the first panel resulted in termination of the fatigue test at 43,500 fatigue cycles, before cracks had developed in the lap joint. The fatigue test for the second panel was initially conducted under simulated in-service loading conditions for 120,000 cycles, and no cracks were detected in the skin of the panel test section. Artificial damage was then introduced into the panel at selected rivets in the critical (lower) rivet row, and the fatigue loads were increased. Visually detectable crack growth from the artificial notches was first seen after 133,000 cycles. The resulting lead crack grew along the lower rivet row, eventually forming an 11.8" long unstable crack after 141,771 cycles, at which point the test was terminated. Posttest fractograpic examinations of the crack surfaces were conducted, revealing the presence of subsurface MSD at the critical rivet row of the lap joint. Special attention was also given to the stringer clips that attach the fuselage frames to the stringers, since they also experienced cracking during the fatigue tests. The performance of the different conventional and emerging NDI methods was also assessed, and some of the emerging NDI methods were quite effective in detecting and measuring the length of subsurface cracks. Delta Air Lines conducted a separate destructive investigation on the state of damage along the right-hand side of the fuselage, near stringer 4R. A comparison of these two studies showed that the lap joint on the left hand-side of the aircraft, along stringer 4L, had better fatigue life than the one on the opposite side, along stringer 4R. The cause of the difference in fatigue life was investigated by close examination of the rivet installation qualities, and was found to be a result of better rivet installation along the lap joint at stringer 4L. Finite element models for both the skin and substructures of the panels were developed and geometrically nonlinear finite element analyses were conducted to verify the loading conditions and to determine near-field parameters governing MSD initiation and growth. Fatigue crack growth predictions based on the NASGRO equation were in good agreement with the experimental crack growth data for through-the-thickness cracks. For subsurface cracks, simulation of crack growth was found to correlate better with fractography data when an empirical crack growth model was used. The results of the study contribute to the understanding of the initiation and growth of MSD in the inner skin layer of a lap joint, and provide valuable data for the evaluation and validation of analytical methodologies to predict MSD initiation and growth and a better understanding on the effect of manufacturing quality on damage accumulation along the lap joint.

  7. In Conversation with Jim Schuck: Nano-optics

    ScienceCinema

    Jim Schuck and Alice Egan

    2017-12-09

    Sponsored by Berkeley Lab's Materials Sciences Division (MSD), "In Conversation with" is a next generation science seminar series. Host Alice Egan is the assistant to MSD Director Miquel Salmeron. Alice conducts a fun and informative interview, touching on the lives and work of the guest. The first In Conversation With took place July 9 with Jim Schuck, a staff scientist in the Molecular Foundry's Imaging and Manipulation Facility as our first guest. He discussed the world of Nano-optics.

  8. In Conversation with Jim Schuck: Nano-optics

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

    Jim Schuck and Alice Egan

    Sponsored by Berkeley Lab's Materials Sciences Division (MSD), "In Conversation with" is a next generation science seminar series. Host Alice Egan is the assistant to MSD Director Miquel Salmeron. Alice conducts a fun and informative interview, touching on the lives and work of the guest. The first In Conversation With took place July 9 with Jim Schuck, a staff scientist in the Molecular Foundry's Imaging and Manipulation Facility as our first guest. He discussed the world of Nano-optics.

  9. Communication: Distinguishing between short-time non-Fickian diffusion and long-time Fickian diffusion for a random walk on a crowded lattice

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

    Ellery, Adam J.; Simpson, Matthew J.; Baker, Ruth E.

    2016-05-07

    The motion of cells and molecules through biological environments is often hindered by the presence of other cells and molecules. A common approach to modeling this kind of hindered transport is to examine the mean squared displacement (MSD) of a motile tracer particle in a lattice-based stochastic random walk in which some lattice sites are occupied by obstacles. Unfortunately, stochastic models can be computationally expensive to analyze because we must average over a large ensemble of identically prepared realizations to obtain meaningful results. To overcome this limitation we describe an exact method for analyzing a lattice-based model of the motionmore » of an agent moving through a crowded environment. Using our approach we calculate the exact MSD of the motile agent. Our analysis confirms the existence of a transition period where, at first, the MSD does not follow a power law with time. However, after a sufficiently long period of time, the MSD increases in proportion to time. This latter phase corresponds to Fickian diffusion with a reduced diffusivity owing to the presence of the obstacles. Our main result is to provide a mathematically motivated, reproducible, and objective estimate of the amount of time required for the transport to become Fickian. Our new method to calculate this crossover time does not rely on stochastic simulations.« less

  10. Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons.

    PubMed

    Ali, Yousuf O; Bradley, Gillian; Lu, Hui-Chen

    2017-03-07

    Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer's, Huntington's, Parkinson's diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons.

  11. Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons

    PubMed Central

    Ali, Yousuf O.; Bradley, Gillian; Lu, Hui-Chen

    2017-01-01

    Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer’s, Huntington’s, Parkinson’s diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons. PMID:28266613

  12. Anti-inflammatory activity of cannabinoid receptor 2 ligands in primary hPDL fibroblasts.

    PubMed

    Abidi, Ammaar H; Presley, Chaela S; Dabbous, Mustafa; Tipton, David A; Mustafa, Suni M; Moore, Bob M

    2018-03-01

    Approximately 65 million adults in the US have periodontitis, causing tooth loss and decreased quality of life. Cannabinoids modulate immune responses, and endocannabinoids are prevalent during oral cavity inflammation. Targets for intervention in periodontal inflammation are cannabinoid type 1 and 2 receptors (CB1R, CB2R), particularly CB2R because its levels increase during inflammation. We previously demonstrated that SMM-189 (CB2R inverse agonist) decreased pro-inflammatory cytokine production in primary microglial cells. The hypothesis of this study was that cannabinoids anandamide (AEA), HU-308 (CB2R selective agonist), and SMM-189 decrease pro-inflammatory IL-6 and MCP-1 production by primary human periodontal ligament fibroblasts (hPDLFs) stimulated with P. gingivalis LPS, TNF-α, or IL-1β. Cytotoxic effects of cannabinoid compounds (10 -4 -10 -6.5  M), LPS (1-1000 ng/ml), TNFα (10 ng/ml) and IL-1β (1 ng/ml) were assessed by measuring effects on cellular dehydrogenase activity. IL-6 and MCP-1 production were measured using Mesoscale Discovery (MSD) Human Pro-Inflammatory IL-6 and MSD Human Chemokine MCP-1 kits and analyzed using MSD Sector 2400 machine. EC 50 values for AEA, SMM-189, and HU-308 were 16 μM, 13 μM, and 7.3 μM respectively. LPS (1 μg/ml), TNF-α (10 ng/ml), and IL-1β (1 ng/ml) increased IL-6 and MCP-1 production, which were inhibited by AEA, SMM-189, and HU-308. AEA alone significantly increased IL-6, but not MCP-1 levels, but the other cannabinoids alone had no effect. The effective inhibition of LPS, TNF-α, IL-1β stimulated IL-6 and MCP-1 production by CB2R ligands in hPDLFs suggests that targeting the endocannabinoid system may lead to development of novel drugs for periodontal therapy, aiding strategies to improve oral health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. SU-E-J-129: Atlas Development for Cardiac Automatic Contouring Using Multi-Atlas Segmentation

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

    Zhou, R; Yang, J; Pan, T

    Purpose: To develop a set of atlases for automatic contouring of cardiac structures to determine heart radiation dose and the associated toxicity. Methods: Six thoracic cancer patients with both contrast and non-contrast CT images were acquired for this study. Eight radiation oncologists manually and independently delineated cardiac contours on the non-contrast CT by referring to the fused contrast CT and following the RTOG 1106 atlas contouring guideline. Fifteen regions of interest (ROIs) were delineated, including heart, four chambers, four coronary arteries, pulmonary artery and vein, inferior and superior vena cava, and ascending and descending aorta. Individual expert contours were fusedmore » using the simultaneous truth and performance level estimation (STAPLE) algorithm for each ROI and each patient. The fused contours became atlases for an in-house multi-atlas segmentation. Using leave-one-out test, we generated auto-segmented contours for each ROI and each patient. The auto-segmented contours were compared with the fused contours using the Dice similarity coefficient (DSC) and the mean surface distance (MSD). Results: Inter-observer variability was not obvious for heart, chambers, and aorta but was large for other structures that were not clearly distinguishable on CT image. The average DSC between individual expert contours and the fused contours were less than 50% for coronary arteries and pulmonary vein, and the average MSD were greater than 4.0 mm. The largest MSD of expert contours deviating from the fused contours was 2.5 cm. The mean DSC and MSD of auto-segmented contours were within one standard deviation of expert contouring variability except the right coronary artery. The coronary arteries, vena cava, and pulmonary vein had DSC<70% and MSD>3.0 mm. Conclusion: A set of cardiac atlases was created for cardiac automatic contouring, the accuracy of which was comparable to the variability in expert contouring. However, substantial modification may need for auto-segmented contours of indistinguishable small structures.« less

  14. Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT.

    PubMed

    Dufour, Carlo; Veys, Paul; Carraro, Elisa; Bhatnagar, Neha; Pillon, Marta; Wynn, Rob; Gibson, Brenda; Vora, Ajay J; Steward, Colin G; Ewins, Anna M; Hough, Rachael E; de la Fuente, Josu; Velangi, Mark; Amrolia, Persis J; Skinner, Roderick; Bacigalupo, Andrea; Risitano, Antonio M; Socie, Gerard; Peffault de Latour, Regis; Passweg, Jakob; Rovo, Alicia; Tichelli, André; Schrezenmeier, Hubert; Hochsmann, Britta; Bader, Peter; van Biezen, Anja; Aljurf, Mahmoud D; Kulasekararaj, Austin; Marsh, Judith C; Samarasinghe, Sujith

    2015-11-01

    We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 ± 4% compared to 91 ± 3% in the MSD controls (P = 0·30) and 94 ± 3% in the IST controls (P = 0·68) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (P = 0·02).The 2-year event-free survival in the upfront cohort was 92 ± 5% compared to 87 ± 4% in MSD controls (P = 0·37), 40 ± 7% in IST controls (P = 0·0001) and 74 ± 9% in the unrelated donor HSCT post-IST failure controls (n = 24) (P = 0·02). Outcomes for upfront-unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first-line therapy in selected paediatric patients who lack a MSD. © 2015 John Wiley & Sons Ltd.

  15. An improved size exclusion-HPLC method for molecular size distribution analysis of immunoglobulin G using sodium perchlorate in the eluent.

    PubMed

    Wang, Hsiaoling; Levi, Mark S; Del Grosso, Alfred V; McCormick, William M; Bhattacharyya, Lokesh

    2017-05-10

    Size exclusion (SE) high performance liquid chromatography (HPLC) is widely used for the molecular size distribution (MSD) analyses of various therapeutic proteins. We report development and validation of a SE-HPLC method for MSD analyses of immunoglobulin G (IgG) in products using a TSKgel SuperSW3000 column and eluting it with 0.4M NaClO 4 , a chaotropic salt, in 40mM phosphate buffer, pH 6.8. The chromatograms show distinct peaks of aggregates, tetramer, and two dimers, as well as the monomer and fragment peaks. In addition, the method offers about half the run time (12min), better peak resolution, improved peak shape and more stable base-line compared to HPLC methods reported in the literature, including that in the European Pharmacopeia (EP). A comparison of MSD analysis results between our method and the EP method shows interactions between the protein and the stationary phase and partial adsorption of aggregates and tetramer on the stationary phase, when the latter method is used. Thus, the EP method shows lower percent of aggregates and tetramer than are actually present in the products. In view of the fact that aggregates have been attributed to playing a critical role in adverse reactions due to IgG products, our observation raises a major concern regarding the actual aggregate content in these products since the EP method is widely used for MSD analyses of IgG products. Our method eliminates (or substantially reduces) the interactions between the proteins and stationary phase as well as the adsorption of proteins onto the column. Our results also show that NaClO 4 in the eluent is more effective in overcoming the protein/column interactions compared to Arg-HCl, another chaotropic salt. NaClO 4 is shown not to affect the molecular size and relative distribution of different molecular forms of IgG. The method validated as per ICH Q2(R1) guideline using IgG products, shows good specificity, accuracy, precision and a linear concentration dependence of peak areas for different molecular forms. In summary, our method gives more reliable results than the SE-HPLC methods for MSD analyses of IgG reported in the literature, including the EP, particularly for aggregates and tetramer. The results are interpreted in terms of ionic (polar) and hydrophobic interactions between the stationary phase and the IgG protein. Published by Elsevier B.V.

  16. The effect of multimorbidity on sickness absence by specific diagnoses.

    PubMed

    Ubalde-Lopez, M; Delclos, G L; Benavides, F G; Calvo-Bonacho, E; Gimeno, D

    2017-03-01

    As the world's population ages, the prevalence of multiple chronic and non-chronic health-related conditions is increasing. Research on multimorbidity, the co-occurrence of two or more health-related conditions, has mainly involved patient and older populations. Its effect in working populations, presumably younger and healthier, is not well known but could conceivably affect sickness absence (SA) and ability to return to work. To examine the effect of multimorbidity on the incidence and duration of SA episodes by frequent diagnostic groups. A prospective study (in 2006-2008) of workers in Spain. Information on health-related conditions was gathered with a standardized questionnaire and used to construct a sex-specific multidimensional multimorbidity score (MDMS). In order to estimate the effect of MDMS on incidence and duration of SA episodes due to cardiovascular diseases (CVD), musculoskeletal disorders (MSD) and mental health disorders (MHD), we fitted Cox models adjusted by age, occupational social class and number of prior SA episodes for both sexes. The study population was 372370. Men with high MDMS showed a trend towards higher incidence risk for SA due to CVD and MSD [adjusted hazard ratio (aHR) = 2.03; 95% confidence interval (CI) 1.48-2.78 and aHR = 1.20; 95% CI 1.01-1.43, respectively]. Women showed a similar trend for MSD, but MHD had the strongest association (aHR = 4.78; 95% CI 1.97-11.62) for high MDMS. In both sexes, the effect of MDMS was strongest among those without a prior SA. No consistent associations with SA duration were observed. Multimorbidity increased the risk of incident musculoskeletal, mental and cardiovascular SA episodes but not their duration. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  17. Toxic Substances Registry System. Index of Material Safety Data Sheets

    NASA Technical Reports Server (NTRS)

    1994-01-01

    The October 1994 revision of the KSC Toxic Substances Registry System (TSRS) Material Safety Data Sheets (MSD's) is presented. The listed MSD's which were submitted to the TSRS are maintained by the Base Operations Contractors of the Biomedical Operations and Research Office of KSC. The purpose of the index is to provide a means of accessing information on the hazards associated with the toxic and otherwise hazardous chemicals stored and used at KSC. Indices are provided for manufacturers, trademarks, and stock numbers.

  18. Non-equilibrium Numerical Analysis of Microwave-supported Detonation Threshold Propagating through Diatomic Gas

    NASA Astrophysics Data System (ADS)

    Shiraishi, Hiroyuki

    2015-09-01

    Microwave-supported Detonation (MSD), one type of Microwave-supported Plasma (MSP), is considered as one of the most important phenomena because it can generate high pressure and high temperature for beam-powered space propulsion systems. In this study, I numerically simulate MSD waves propagating through a diatomic gas. In order to evaluate the threshold of beam intensity, I use the physical-fluid dynamics scheme, which has been developed for simulating unsteady and non-equilibrium LSD waves propagating through a hydrogen gas.

  19. The Effect of a Third Generation Hemostatic Dressing in a Subclavian Artery and Vein Transection Porcine Model

    DTIC Science & Technology

    2014-04-01

    The MSD is comprised of a syringe applicator filled with compressed chitosan coated sponges which are delivered into the wound at the site of the...transmitted effectively to the deep subclavian vessels to stop hemorrhage. As a result of their non-compressible nature and paucity of effective field...followed by three minutes of compression to the packed dressing. The mini- sponge dressing (MSD) is a novel product that utilizes compressed, chitosan

  20. Improved computational treatment of transonic flow about swept wings

    NASA Technical Reports Server (NTRS)

    Ballhaus, W. F.; Bailey, F. R.; Frick, J.

    1976-01-01

    Relaxation solutions to classical three-dimensional small-disturbance (CSD) theory for transonic flow about lifting swept wings are reported. For such wings, the CSD theory was found to be a poor approximation to the full potential equation in regions of the flow field that are essentially two-dimensional in a plane normal to the sweep direction. The effect of this deficiency on the capture of embedded shock waves in terms of (1) the conditions under which shock waves can exist and (2) the relations they must satisfy when they do exist is emphasized. A modified small-disturbance (MSD) equation, derived by retaining two previously neglected terms, was proposed and shown to be a consistent approximation to the full potential equation over a wider range of sweep angles. The effect of these extra terms is demonstrated by comparing CSD, MSD, and experimental wing surface pressures.

  1. Performance of fuselage pressure structure

    NASA Technical Reports Server (NTRS)

    Maclin, James R.

    1992-01-01

    There are currently more than 1,000 Boeing airplanes around the world over 20 years old. That number is expected to double by the year 1995. With these statistics comes the reality that structural airworthiness will be in the forefront of aviation issues well into the next century. The results of previous and recent test programs Boeing has implemented to study the structural performance of older airplanes relative to pressurized fuselage sections are described. Included in testing were flat panels with multiple site damage (MSD), a full-scale 737 and 2 747s as well as panels representing a 737 and 777, and a generic aircraft in large pressure-test fixtures. Because damage is a normal part of aging, focus is on the degree to which structural integrity is maintained after failure or partial failure of any structural element, including multiple site damage (MSD), and multiple element damage (MED).

  2. 1- and 2-particle Microrheology of Hyaluronic Acid

    NASA Astrophysics Data System (ADS)

    Sagan, Austin; Kearns, Sarah; Ross, David; Das, Moumita; Thurston, George; Franklin, Scott

    2015-03-01

    Hyaluronic acid (also called HA or Hyaluronan) is a high molecular weight polysaccaride ubiquitous in the extracellular matrix of soft tissue such as cartilage, skin, the eye's vitreous gel and synovial fluid. It has been shown to play an important role in mechanotransduction, cell migration and proliferation, and in tissue morphodynamics. We present a confocal microrheology study of hyaluronic acid of varying concentrations. The mean squared displacement (MSD) of sub-micron colloidal tracer particles is tracked in two dimensions and shows a transition from diffusive motion at low concentrations to small-time trapping by the protein network as the concentration increases. Correlations between particle motion can be used to determine an effective mean-squared displacement which deviates from the single-particle MSD as the fluid becomes less homogeneous. The real and effective mean-squared displacements are used to probe the local and space-averaged frequency dependent rheological properties of the fluid as the concentration changes.

  3. Prefoldin Subunits Are Protected from Ubiquitin-Proteasome System-mediated Degradation by Forming Complex with Other Constituent Subunits*

    PubMed Central

    Miyazawa, Makoto; Tashiro, Erika; Kitaura, Hirotake; Maita, Hiroshi; Suto, Hiroo; Iguchi-Ariga, Sanae M. M.; Ariga, Hiroyoshi

    2011-01-01

    The molecular chaperone prefoldin (PFD) is a complex comprised of six different subunits, PFD1-PFD6, and delivers newly synthesized unfolded proteins to cytosolic chaperonin TRiC/CCT to facilitate the folding of proteins. PFD subunits also have functions different from the function of the PFD complex. We previously identified MM-1α/PFD5 as a novel c-Myc-binding protein and found that MM-1α suppresses transformation activity of c-Myc. However, it remains unclear how cells regulate protein levels of individual subunits and what mechanisms alter the ratio of their activities between subunits and their complex. In this study, we found that knockdown of one subunit decreased protein levels of other subunits and that transfection of five subunits other than MM-1α into cells increased the level of endogenous MM-1α. We also found that treatment of cells with MG132, a proteasome inhibitor, increased the level of transfected/overexpressed MM-1α but not that of endogenous MM-1α, indicating that overexpressed MM-1α, but not endogenous MM-1α, was degraded by the ubiquitin proteasome system (UPS). Experiments using other PFD subunits showed that the UPS degraded a monomer of PFD subunits, though extents of degradation varied among subunits. Furthermore, the level of one subunit was increased after co-transfection with the respective subunit, indicating that there are specific combinations between subunits to be stabilized. These results suggest mutual regulation of protein levels among PFD subunits and show how individual subunits form the PFD complex without degradation. PMID:21478150

  4. 78 FR 52586 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-23

    ... SECURITIES AND EXCHANGE COMMISSION Submission for OMB Review; Comment Request Upon Written Request, Copies Available From: Securities and Exchange Commission, Office of Investor Education and Advocacy, Washington, DC 20549-0213. Extension: Rule 15Ba2-1 and Form MSD, SEC File No. 270-0088, OMB Control No. 3235...

  5. Musculoskeletal disorders and associated healthcare costs among family members of injured workers.

    PubMed

    Asfaw, Abay; Pana-Cryan, Regina; Bushnell, Tim; Sauter, Steven

    2015-11-01

    Research has infrequently looked beyond the injured worker when gauging the burden of occupational injury. We explored the relationship between occupational injury and musculoskeletal disorders (MSDs) among family members of injured workers. We used 2005 and 2006 Truven Health Analytics databases, which contain information on workers' compensation and family healthcare claims. We used descriptive analyses, and negative binomial and two-part models. Family members of severely injured workers had a 15% increase in the total number of MSD outpatient claims and a 34% increase in the mean cost of MSD claims compared to family members of non-severely injured workers within 3 months after injury. Extrapolating cost results to the national level implies that severe occupational injury would be associated with between $29 and $33 million additional cost of family member outpatient MSD claims. Occupational injury can impose a formerly unrecognized health burden on family members of injured workers. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  6. Langevin dynamics for ramified structures

    NASA Astrophysics Data System (ADS)

    Méndez, Vicenç; Iomin, Alexander; Horsthemke, Werner; Campos, Daniel

    2017-06-01

    We propose a generalized Langevin formalism to describe transport in combs and similar ramified structures. Our approach consists of a Langevin equation without drift for the motion along the backbone. The motion along the secondary branches may be described either by a Langevin equation or by other types of random processes. The mean square displacement (MSD) along the backbone characterizes the transport through the ramified structure. We derive a general analytical expression for this observable in terms of the probability distribution function of the motion along the secondary branches. We apply our result to various types of motion along the secondary branches of finite or infinite length, such as subdiffusion, superdiffusion, and Langevin dynamics with colored Gaussian noise and with non-Gaussian white noise. Monte Carlo simulations show excellent agreement with the analytical results. The MSD for the case of Gaussian noise is shown to be independent of the noise color. We conclude by generalizing our analytical expression for the MSD to the case where each secondary branch is n dimensional.

  7. A comment on the position dependent diffusion coefficient representation of structural heterogeneity

    NASA Astrophysics Data System (ADS)

    Wolfson, Molly; Liepold, Christopher; Lin, Binhua; Rice, Stuart A.

    2018-05-01

    Experimental studies of the variation of the mean square displacement (MSD) of a particle in a confined colloid suspension that exhibits density variations on the scale length of the particle diameter are not in agreement with the prediction that the spatial variation in MSD should mimic the spatial variation in density. The predicted behavior is derived from the expectation that the MSD of a particle depends on the system density and the assumption that the force acting on a particle is a point function of position. The experimental data are obtained from studies of the MSDs of particles in narrow ribbon channels and between narrowly spaced parallel plates and from new data, reported herein, of the radial and azimuthal MSDs of a colloid particle in a dense colloid suspension confined to a small circular cavity. In each of these geometries, a dense colloid suspension exhibits pronounced density oscillations with spacing of a particle diameter. We remove the discrepancy between prediction and experiment using the Fisher-Methfessel interpretation of how local equilibrium in an inhomogeneous system is maintained to argue that the force acting on a particle is delocalized over a volume with radius equal to a particle diameter. Our interpretation has relevance to the relationship between the scale of inhomogeneity and the utility of translation of the particle MSD into a position dependent diffusion coefficient and to the use of a spatially dependent diffusion coefficient to describe mass transport in a heterogeneous system.

  8. Effect of systematic ergonomic hazard identification and control implementation on musculoskeletal disorder and injury risk.

    PubMed

    Cantley, Linda F; Taiwo, Oyebode A; Galusha, Deron; Barbour, Russell; Slade, Martin D; Tessier-Sherman, Baylah; Cullen, Mark R

    2014-01-01

    This study aimed to examine the effect of an ergonomic hazard control (HC) initiative, undertaken as part of a company ergonomics standard, on worker injury risk. Using the company's ergonomic hazards database to identify jobs with and without ergonomic HC implementation and linking to individual job and injury histories, injury risk among person-jobs with HC implementation (the HC group) was compared to those without HC (NoHC group) using random coefficient models. Further analysis of the HC group was conducted to determine the effect of additional ergonomic hazards controlled on injury risk. Among 123 jobs at 17 plant locations, 347 ergonomic hazards were quantitatively identified during the study period. HC were implemented for 204 quantified ergonomic hazards in 84 jobs, impacting 10 385 persons (12 967 person-jobs). No HC were implemented for quantified ergonomic hazards in the remaining 39 jobs affecting 4155 persons (5046 person-jobs). Adjusting for age, sex, plant origin, and year to control for any temporal trend in injury risk, the relative risk (RR) for musculoskeletal disorder (MSD) was 0.85 and the RR for any injury or MSD was 0.92 in the HC compared to NoHC group. Among the HC group, each ergonomic hazard controlled was associated with risk reduction for MSD and acute injury outcomes (RR 0.93). Systematic ergonomic HC through participatory ergonomics, as part of a mandatory company ergonomics standard, is associated with MSD and injury risk reduction among workers in jobs with HC implemented.

  9. Association Between Shigella Infection and Diarrhea Varies Based on Location and Age of Children.

    PubMed

    Lindsay, Brianna; Saha, Debasish; Sanogo, Doh; Das, Sumon Kumar; Omore, Richard; Farag, Tamer H; Nasrin, Dilruba; Li, Shan; Panchalingam, Sandra; Levine, Myron M; Kotloff, Karen; Nataro, James P; Magder, Laurence; Hungerford, Laura; Faruque, A S G; Oundo, Joseph; Hossain, M Anowar; Adeyemi, Mitchell; Stine, Oscar Colin

    2015-11-01

    Molecular identification of the invasion plasmid antigen-H (ipaH) gene has been established as a useful detection mechanism for Shigella spp. The Global Enteric Multicenter Study (GEMS) identified the etiology and burden of moderate-to-severe diarrhea (MSD) in sub-Saharan Africa and south Asia using a case-control study and traditional culture techniques. Here, we used quantitative polymerase chain reaction (qPCR) to identify Shigella spp. in 2,611 stool specimens from GEMS and compared these results to those using culture. Demographic and nutritional characteristics were assessed as possible risk factors. The qPCR identified more cases of shigellosis than culture; however, the distribution of demographic characteristics was similar by both methods. In regression models adjusting for Shigella quantity, age, and site, children who were exclusively breast-fed had significantly lower odds of MSD compared with children who were not breast-fed (odds ratio [OR] = 0.47, 95% confidence interval (CI) = 0.28-0.81). The association between Shigella quantity and MSD increased with age, with a peak in children of 24-35 months of age (OR = 8.2, 95% CI = 4.3-15.7) and the relationship between Shigella quantity and disease was greatest in Bangladesh (OR = 13.2, 95% CI = 7.3-23.8). This study found that qPCR identified more cases of Shigella and age, site, and breast-feeding status were significant risk factors for MSD. © The American Society of Tropical Medicine and Hygiene.

  10. Paleoecological reconstruction of hominin-bearing middle Pliocene localities at Woranso-Mille, Ethiopia.

    PubMed

    Curran, Sabrina C; Haile-Selassie, Yohannes

    2016-07-01

    Woranso-Mille is a paleoanthropological site in Ethiopia sampling an important and under-represented time period in human evolution (3.8-3.6 million years ago). Specimens of cf. Australopithecus anamensis, Australopithecus afarensis, and the recently named Australopithecus deyiremeda have been recovered from this site. Using multiple habitat proxies, this study provides a paleoecological reconstruction of two fossiliferous collection areas from Woranso-Mille, Aralee Issie (ARI) and Mesgid Dora (MSD). Previous reconstructions based on faunal assemblages have pointed, due to the presence of aepycerotins, alcelaphins, and proboscideans, to the existence of open habitats as well as more closed ones, based on the occurrence of cercopithecids, giraffids, and traglephins. Results from community structure analysis (proportions of locomotor and dietary adaptations) at ARI and MSD indicated a predominance of open habitats, such as shrublands. Mesowear analysis revealed that ungulates of all dietary types (grazers, leaf and fruit browsers, and mixed feeders) were present in nearly equal proportions. Ecomorphological analyses using linear measurements of the astragalus and phalanges indicated that bovids utilizing locomotor behaviors associated with all habitat types were present, though the intermediate-cover habitat bovids were best represented in the sample (Heavy cover at ARI and Light cover at MSD). Together, these results suggest that the ARI and MSD localities were heterogeneous habitats (mosaics), likely with densely vegetated areas along a paleo-river and more open regions (woodlands, grasslands) available away from the river. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. How compatible are participatory ergonomics programs with occupational health and safety management systems?

    PubMed

    Yazdani, Amin; Neumann, W Patrick; Imbeau, Daniel; Bigelow, Philip; Pagell, Mark; Theberge, Nancy; Hilbrecht, Margo; Wells, Richard

    2015-03-01

    Musculoskeletal disorders (MSD) are a major cause of pain, disability, and costs. Prevention of MSD at work is frequently described in terms of implementing an ergonomics program, often a participatory ergonomics (PE) program. Most other workplace injury prevention activities take place under the umbrella of a formal or informal occupational health and safety management system (OHSMS). This study assesses the similarities and differences between OHSMS and PE as such knowledge could help improve MSD prevention activities. Methods Using the internationally recognized Occupational Health and Safety Assessment Series (OHSAS 18001), 21 OHSMS elements were extracted. In order to define PE operationally, we identified the 20 most frequently cited papers on PE and extracted content relevant to each of the OHSAS 18001 elements. The PE literature provided a substantial amount of detail on five elements: (i) hazard identification, risk assessment and determining controls; (ii) resources, roles, responsibility, accountability, and authority; (iii) competence, training and awareness; (iv) participation and consultation; and (v) performance measurement and monitoring. However, of the 21 OHSAS elements, the PE literature was silent on 8 and provided few details on 8 others. The PE literature did not speak to many elements described in OHSMS and even when it did, the language used was often different. This may negatively affect the effectiveness and sustainability of PE initiatives within organizations. It is expected that paying attention to the approaches and language used in management system frameworks could make prevention of MSD activities more effective and sustainable.

  12. Properties of human brain sodium channel α-subunits expressed in HEK293 cells and their modulation by carbamazepine, phenytoin and lamotrigine

    PubMed Central

    Qiao, Xin; Sun, Guangchun; Clare, Jeffrey J; Werkman, Taco R; Wadman, Wytse J

    2014-01-01

    Background and purpose Voltage-activated Na+ channels contain one distinct α-subunit. In the brain NaV1.1, NaV1.2, NaV1.3 and NaV1.6 are the four most abundantly expressed α-subunits. The antiepileptic drugs (AEDs) carbamazepine, phenytoin and lamotrigine have voltage-gated Na+ channels as their primary therapeutic targets. This study provides a systematic comparison of the biophysical properties of these four α-subunits and characterizes their interaction with carbamazepine, phenytoin and lamotrigine. Experimental approach Na+ currents were recorded in voltage-clamp mode in HEK293 cells stably expressing one of the four α-subunits. Key results NaV1.2 and NaV1.3 subunits have a relatively slow recovery from inactivation, compared with the other subunits and NaV1.1 subunits generate the largest window current. Lamotrigine evokes a larger maximal shift of the steady-state inactivation relationship than carbamazepine or phenytoin. Carbamazepine shows the highest binding rate to the α-subunits. Lamotrigine binding to NaV1.1 subunits is faster than to the other α-subunits. Lamotrigine unbinding from the α-subunits is slower than that of carbamazepine and phenytoin. Conclusions and implications The four Na+ channel α-subunits show subtle differences in their biophysical properties, which, in combination with their (sub)cellular expression patterns in the brain, could contribute to differences in neuronal excitability. We also observed differences in the parameters that characterize AED binding to the Na+ channel subunits. Particularly, lamotrigine binding to the four α-subunits suggests a subunit-specific response. Such differences will have consequences for the clinical efficacy of AEDs. Knowledge of the biophysical and binding parameters could be employed to optimize therapeutic strategies and drug development. PMID:24283699

  13. Content and concurrent validity of the motivation for change questionnaire.

    PubMed

    Grahn, Birgitta; Gard, Gunvor

    2008-03-01

    Musculoskeletal disorders (MSD) are nowadays seen within a biopsychosocial framework, including salutogenic factors, motivation factors, and coping ability. Such a framework recognizes the importance of motivational factors in health promotion and in rehabilitation. The Motivation for Change Questionnaire (MCQ) has been developed to measure the strength of individuals' motivation for change in life, MCQ part 1, and work situation, MCQ part 2. The purpose of the study was to test the content and concurrent validity of the MCQ on patients with prolonged musculoskeletal disorders referred to interdisciplinary rehabilitation as a basis for use in medical and occupational rehabilitation. Content validity was studied among an expert group of 20 rehabilitation professionals at a rehabilitation centre, and with 10 individuals suffering from prolonged MSD in the south of Sweden. The experts evaluated the clinical relevance of each question in MCQ. Concurrent validity was studied on 58 patients with prolonged MSD at an interdisciplinary rehabilitation centre in the south of Sweden. They answered MCQ, QPS Nordic questionnaire, KASAM and the Action theory questionnaire. Spearman's rank correlation coefficient was used in the analyses. The MCQ covered and measured areas of relevance according to content validity. No floor effects in any of the subscales of MCQ part 1 were seen. In MCQ part 2, floor effects were seen in two sub indexes. As for concurrent validity subscales of MCQ correlated significantly with QPS Nordic questionnaire and KASAM. Findings so far indicate the instrument to be valid for use within the present patient group. The questionnaire can be used to identify patient's motivating factors for change in life and work, as a basis for motivational work within rehabilitation.

  14. Assembly of the stator in Escherichia coli ATP synthase. Complexation of alpha subunit with other F1 subunits is prerequisite for delta subunit binding to the N-terminal region of alpha

    PubMed Central

    Senior, Alan E.; Muharemagi, Alma; Wilke-Mounts, Susan

    2008-01-01

    Alpha subunit of Escherichia coli ATP synthase was expressed with a C-terminal 6-His tag and purified. Pure alpha was monomeric, competent in nucleotide binding, and had normal N-terminal sequence. In F1-subunit dissociation/reassociation experiments it supported full reconstitution of ATPase, and reassociated complexes were able to bind to F1-depleted membranes with restoration of ATP-driven proton pumping. Therefore interaction between the stator delta subunit and the N-terminal residue 1-22 region of alpha occurred normally when pure alpha was complexed with other F1 subunits. On the other hand, three different types of experiment showed that no interaction occurred between pure delta and isolated alpha subunit. Unlike in F1, the N-terminal region of isolated alpha was not susceptible to trypsin cleavage. Therefore, during assembly of ATP synthase, complexation of alpha subunit with other F1 subunits is prerequisite for delta subunit binding to the N-terminal region of alpha. We suggest that the N-terminal 1-22 residues of alpha are sequestered in isolated alpha until released by binding of beta to alpha subunit. This prevents 1/1 delta/alpha complexes from forming, and provides a satisfactory explanation of the stoichiometry of one delta per three alpha seen in the F1 sector of ATP synthase, assuming that steric hindrance prevents binding of more than one delta to the alpha3/beta3 hexagon. The cytoplasmic fragment of the b subunit (bsol) did not bind to isolated alpha. It might also be that complexation of alpha with beta subunits is prerequisite for direct binding of stator b subunit to the F1-sector. PMID:17176112

  15. ARC - A source of multisensor satellite data for polar science

    NASA Technical Reports Server (NTRS)

    Van Woert, Michael L.; Whritner, Robert H.; Waliser, Duane E.; Bromwich, David H.; Comiso, J. C.

    1992-01-01

    The NSF's Antarctic Research Center (ARC) has been established to furnish real-time polar-orbiting satellite data in support of Antarctic field studies, as well as to maintain a multisensor satellite data (MSD) archive for retrospective data analysis. An account is presently given of the ways in which the complementary nature of an MSD set can deepen understanding of Antarctic physical processes. An active microwave SAR with 30-m resolution and a radar altimeter will be added to the ARC resources later in this decade, as will the Earth Observing System.

  16. Outcomes of Allogeneic Hematopoietic Cell Transplantation in Children and Young Adults with Chronic Myeloid Leukemia: A CIBMTR Cohort Analysis.

    PubMed

    Chaudhury, Sonali; Sparapani, Rodney; Hu, Zhen-Huan; Nishihori, Taiga; Abdel-Azim, Hisham; Malone, Adriana; Olsson, Richard; Hamadani, Mehdi; Daly, Andrew; Bacher, Ulrike; Wirk, Baldeep M; Kamble, Rammurti T; Gale, Robert P; Wood, William A; Hale, Gregory; Wiernik, Peter H; Hashmi, Shahrukh K; Marks, David; Ustun, Celalettin; Munker, Reinhold; Savani, Bipin N; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Kalaycio, Matt; Maziarz, Richard; Hijiya, Nobuko; Saber, Wael

    2016-06-01

    Chronic myeloid leukemia (CML) in children and young adults is uncommon. Young patients have long life expectancies and low morbidity with hematopoietic cell transplantation (HCT). Prolonged tyrosine kinase inhibitor (TKI) use may cause significant morbidity. In addition, indication for HCT in patients in the first chronic phase is not established. We hence retrospectively evaluated outcomes in 449 CML patients with early disease receiving myeloablative HCT reported to the CIBMTR. We analyzed various factors affecting outcome, specifically the effect of age and pre-HCT TKI in pediatric patients (age < 18 years, n = 177) and young adults (age 18 to 29 years, n = 272) with the goal of identifying prognostic factors. Post-HCT probability rates of 5-year overall survival (OS) and leukemia-free survival (LFS) were 75% and 59%, respectively. Rates of OS and LFS were 76% and 57% in <18-year and 74% and 60% in 18- to 29-year group, respectively, by univariate analysis (P = .1 and = .6). Five-year rates of OS for HLA matched sibling donor (MSD) and bone marrow (BM) stem cell source were 83% and 80%, respectively. In multivariate analysis there was no effect of age (<18 versus 18 to 29) or pre-HCT TKI therapy on OS, LFS, transplant related mortality, or relapse. Favorable factors for OS were MSD (P < .001) and recent HCT (2003 to 2010; P = .04). LFS was superior with MSD (P < .001), BM as graft source (P = .001), and performance scores > 90 (P = .03) compared with unrelated or mismatched peripheral blood stem cells donors and recipients with lower performance scores. Older age was associated with increased incidence of chronic graft-versus-host disease (P = .0002). In the current era, HCT outcomes are similar in young patients and children with early CML, and best outcomes are achieved with BM grafts and MSD. Copyright © 2016 The American Society for Blood and Marrow Transplantation. All rights reserved.

  17. Na+, K+-ATPase β1 subunit associates with α1 subunit modulating a "higher-NKA-in-hyposmotic media" response in gills of euryhaline milkfish, Chanos chanos.

    PubMed

    Hu, Yau-Chung; Chu, Keng-Fu; Yang, Wen-Kai; Lee, Tsung-Han

    2017-10-01

    The euryhaline milkfish (Chanos chanos) is a popular aquaculture species that can be cultured in fresh water, brackish water, or seawater in Southeast Asia. In gills of the milkfish, Na + , K + -ATPase (i.e., NKA; sodium pump) responds to salinity challenges including changes in mRNA abundance, protein amount, and activity. The functional pump is composed of a heterodimeric protein complex composed of α- and β-subunits. Among the NKA genes, α1-β1 isozyme comprises the major form of NKA subunits in mammalian osmoregulatory organs; however, most studies on fish gills have focused on the α1 subunit and did not verify the α1-β1 isozyme. Based on the sequenced milkfish transcriptome, an NKA β1 subunit gene was identified that had the highest amino acid homology to β233, a NKA β1 subunit paralog originally identified in the eel. Despite this high level of homology to β233, phylogenetic analysis and the fact that only a single NKA β1 subunit gene exists in the milkfish suggest that the milkfish gene should be referred to as the NKA β1 subunit gene. The results of accurate domain prediction of the β1 subunit, co-localization of α1 and β1 subunits in epithelial ionocytes, and co-immunoprecipitation of α1 and β1 subunits, indicated the formation of a α1-β1 complex in milkfish gills. Moreover, when transferred to hyposmotic media (fresh water) from seawater, parallel increases in branchial mRNA and protein expression of NKA α1 and β1 subunits suggested their roles in hypo-osmoregulation of euryhaline milkfish. This study molecularly characterized the NKA β1 subunit and provided the first evidence for an NKA α1-β1 association in gill ionocytes of euryhaline teleosts.

  18. Subunits of the Snf1 kinase heterotrimer show interdependence for association and activity.

    PubMed

    Elbing, Karin; Rubenstein, Eric M; McCartney, Rhonda R; Schmidt, Martin C

    2006-09-08

    The Snf1 kinase and its mammalian orthologue, the AMP-activated protein kinase (AMPK), function as heterotrimers composed of a catalytic alpha-subunit and two non-catalytic subunits, beta and gamma. The beta-subunit is thought to hold the complex together and control subcellular localization whereas the gamma-subunit plays a regulatory role by binding to and blocking the function of an auto-inhibitory domain (AID) present in the alpha-subunit. In addition, catalytic activity requires phosphorylation by a distinct upstream kinase. In yeast, any one of three Snf1-activating kinases, Sak1, Tos3, or Elm1, can fulfill this role. We have previously shown that Sak1 is the only Snf1-activating kinase that forms a stable complex with Snf1. Here we show that the formation of the Sak1.Snf1 complex requires the beta- and gamma-subunits in vivo. However, formation of the Sak1.Snf1 complex is not necessary for glucose-regulated phosphorylation of the Snf1 activation loop. Snf1 kinase purified from cells lacking the beta-subunits do not contain any gamma-subunit, indicating that the Snf1 kinase does not form a stable alphagamma dimer in vivo. In vitro kinase assays using purified full-length and truncated Snf1 proteins demonstrate that the kinase domain, which lacks the AID, is significantly more active than the full-length Snf1 protein. Addition of purified beta- and gamma-subunits could stimulate the kinase activity of the full-length alpha-subunit but only when all three subunits were present, suggesting an interdependence of all three subunits for assembly of a functional complex.

  19. A Comparison between Mathematics Textbook Content and a Statewide Mathematics Proficiency Test.

    ERIC Educational Resources Information Center

    Chandler, Donald G.; Brosnan, Patricia A.

    1995-01-01

    Percentages of mathematics content for 7 text series, grades 1-8, were compared with percentages on the Ohio Ninth Grade Proficiency Test. Ratios of text:test percentages were arithmetic (63:30), measurement (10:25), geometry (12:15), data analysis (11:15), and algebra (4:15). Implications are discussed. (MSD)

  20. 17 CFR 400.4 - Information concerning associated persons of financial institutions that are government...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... completed and current Form U-4 (promulgated by a self-regulatory organization) or Form MSD-4 (as required... regulatory agency for such financial institution, a statement correcting such information. (c) For the... shall: (1) Promptly obtain and, within 10 days thereafter, file with the appropriate regulatory agency...

  1. The Shaped Charge Concept. Part 2. The History of Shaped Charges

    DTIC Science & Technology

    1990-09-01

    research of Evans. Ubbel•ode. LAmurd-Jones, Devonihire, and An&ew. 1hW U.K. Mufied cadmium liners (which probably produce molten jets) msd steel liners...34 Mathematical Jet Theory of Lined Hollow Charges." BRL Report No. 370, U.S. Army Ballistic Research Laboratory. Aberdeen Proving Ground, MD, 18 June

  2. A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer.

    PubMed

    Groenewoud, E R; Cohlen, B J; Al-Oraiby, A; Brinkhuis, E A; Broekmans, F J M; de Bruin, J P; van den Dool, G; Fleisher, K; Friederich, J; Goddijn, M; Hoek, A; Hoozemans, D A; Kaaijk, E M; Koks, C A M; Laven, J S E; van der Linden, P J Q; Manger, A P; Slappendel, E; Spinder, T; Kollen, B J; Macklon, N S

    2016-07-01

    Are live birth rates (LBRs) after artificial cycle frozen-thawed embryo transfer (AC-FET) non-inferior to LBRs after modified natural cycle frozen-thawed embryo transfer (mNC-FET)? AC-FET is non-inferior to mNC-FET with regard to LBRs, clinical and ongoing pregnancy rates (OPRs) but AC-FET does result in higher cancellation rates. Pooling prior retrospective studies of AC-FET and mNC-FET results in comparable pregnancy and LBRs. However, these results have not yet been confirmed by a prospective randomized trial. In this non-inferiority prospective randomized controlled trial (acronym 'ANTARCTICA' trial), conducted from February 2009 to April 2014, 1032 patients were included of which 959 were available for analysis. The primary outcome of the study was live birth. Secondary outcomes were clinical and ongoing pregnancy, cycle cancellation and endometrium thickness. A cost-efficiency analysis was performed. This study was conducted in both secondary and tertiary fertility centres in the Netherlands. Patients included in this study had to be 18-40 years old, had to have a regular menstruation cycle between 26 and 35 days and frozen-thawed embryos to be transferred had to derive from one of the first three IVF or IVF-ICSI treatment cycles. Patients with a uterine anomaly, a contraindication for one of the prescribed medications in this study or patients undergoing a donor gamete procedure were excluded from participation. Patients were randomized based on a 1:1 allocation to either one cycle of mNC-FET or AC-FET. All embryos were cryopreserved using a slow-freeze technique. LBR after mNC-FET was 11.5% (57/495) versus 8.8% in AC-FET (41/464) resulting in an absolute difference in LBR of -0.027 in favour of mNC-FET (95% confidence interval (CI) -0.065-0.012; P = 0.171). Clinical pregnancy occurred in 94/495 (19.0%) patients in mNC-FET versus 75/464 (16.0%) patients in AC-FET (odds ratio (OR) 0.8, 95% CI 0.6-1.1, P = 0.25). 57/495 (11.5%) mNC-FET resulted in ongoing pregnancy versus 45/464 (9.6%) AC-FET (OR 0.7, 95% CI 0.5-1.1, P = 0.15). χ(2) test confirmed the lack of superiority. Significantly more cycles were cancelled in AC-FET (124/464 versus 101/495, OR 1.4, 95% CI 1.1-1.9, P = 0.02). The costs of each of the endometrial preparation methods were comparable (€617.50 per cycle in NC-FET versus €625.73 per cycle in AC-FET, P = 0.54). The minimum of 1150 patients required for adequate statistical power was not achieved. Moreover, LBRs were lower than anticipated in the sample size calculation. LBRs after AC-FET were not inferior to those achieved by mNC-FET. No significant differences in clinical and OPR were observed. The costs of both treatment approaches were comparable. An educational grant was received during the conduct of this study. Merck Sharpe Dohme had no influence on the design, execution and analyses of this study. E.R.G. received an education grant by Merck Sharpe Dohme (MSD) during the conduct of the present study. B.J.C. reports grants from MSD during the conduct of the study. A.H. reports grants from MSD and Ferring BV the Netherlands and personal fees from MSD. Grants from ZonMW, the Dutch Organization for Health Research and Development. J.S.E.L. reports grants from Ferring, MSD, Organon, Merck Serono and Schering-Plough during the conduct of the study. F.J.M.B. receives monetary compensation as member of the external advisory board for Merck Serono, consultancy work for Gedeon Richter, educational activities for Ferring BV, research cooperation with Ansh Labs and a strategic cooperation with Roche on automated anti Mullerian hormone assay development. N.S.M. reports receiving monetary compensations for external advisory and speaking work for Ferring BV, MSD, Anecova and Merck Serono during the conduct of the study. All reported competing interests are outside the submitted work. No other relationships or activities that could appear to have influenced the submitted work. Netherlands trial register, number NTR 1586. 13 January 2009. 20 April 2009. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer

    PubMed Central

    Groenewoud, E.R.; Cohlen, B.J.; Al-Oraiby, A.; Brinkhuis, E.A.; Broekmans, F.J.M.; de Bruin, J.P.; van den Dool, G.; Fleisher, K.; Friederich, J.; Goddijn, M.; Hoek, A.; Hoozemans, D.A.; Kaaijk, E.M.; Koks, C.A.M.; Laven, J.S.E.; van der Linden, P.J.Q.; Manger, A.P.; Slappendel, E.; Spinder, T.; Kollen, B.J.; Macklon, N.S.

    2016-01-01

    Abstract STUDY QUESTION Are live birth rates (LBRs) after artificial cycle frozen-thawed embryo transfer (AC-FET) non-inferior to LBRs after modified natural cycle frozen-thawed embryo transfer (mNC-FET)? SUMMARY ANSWER AC-FET is non-inferior to mNC-FET with regard to LBRs, clinical and ongoing pregnancy rates (OPRs) but AC-FET does result in higher cancellation rates. WHAT IS ALREADY KNOWN Pooling prior retrospective studies of AC-FET and mNC-FET results in comparable pregnancy and LBRs. However, these results have not yet been confirmed by a prospective randomized trial. STUDY DESIGN, SIZE AND DURATION In this non-inferiority prospective randomized controlled trial (acronym ‘ANTARCTICA’ trial), conducted from February 2009 to April 2014, 1032 patients were included of which 959 were available for analysis. The primary outcome of the study was live birth. Secondary outcomes were clinical and ongoing pregnancy, cycle cancellation and endometrium thickness. A cost-efficiency analysis was performed. PARTICIPANT/MATERIALS, SETTING, METHODS This study was conducted in both secondary and tertiary fertility centres in the Netherlands. Patients included in this study had to be 18–40 years old, had to have a regular menstruation cycle between 26 and 35 days and frozen-thawed embryos to be transferred had to derive from one of the first three IVF or IVF–ICSI treatment cycles. Patients with a uterine anomaly, a contraindication for one of the prescribed medications in this study or patients undergoing a donor gamete procedure were excluded from participation. Patients were randomized based on a 1:1 allocation to either one cycle of mNC-FET or AC-FET. All embryos were cryopreserved using a slow-freeze technique. MAIN RESULTS AND THE ROLE OF CHANCE LBR after mNC-FET was 11.5% (57/495) versus 8.8% in AC-FET (41/464) resulting in an absolute difference in LBR of −0.027 in favour of mNC-FET (95% confidence interval (CI) −0.065–0.012; P = 0.171). Clinical pregnancy occurred in 94/495 (19.0%) patients in mNC-FET versus 75/464 (16.0%) patients in AC-FET (odds ratio (OR) 0.8, 95% CI 0.6–1.1, P = 0.25). 57/495 (11.5%) mNC-FET resulted in ongoing pregnancy versus 45/464 (9.6%) AC-FET (OR 0.7, 95% CI 0.5–1.1, P = 0.15). χ2 test confirmed the lack of superiority. Significantly more cycles were cancelled in AC-FET (124/464 versus 101/495, OR 1.4, 95% CI 1.1–1.9, P = 0.02). The costs of each of the endometrial preparation methods were comparable (€617.50 per cycle in NC-FET versus €625.73 per cycle in AC-FET, P = 0.54). LIMITATIONS, REASONS FOR CAUTION The minimum of 1150 patients required for adequate statistical power was not achieved. Moreover, LBRs were lower than anticipated in the sample size calculation. WIDER IMPLICATIONS OF THE FINDINGS LBRs after AC-FET were not inferior to those achieved by mNC-FET. No significant differences in clinical and OPR were observed. The costs of both treatment approaches were comparable. STUDY FUNDING/COMPETING INTEREST(S) An educational grant was received during the conduct of this study. Merck Sharpe Dohme had no influence on the design, execution and analyses of this study. E.R.G. received an education grant by Merck Sharpe Dohme (MSD) during the conduct of the present study. B.J.C. reports grants from MSD during the conduct of the study. A.H. reports grants from MSD and Ferring BV the Netherlands and personal fees from MSD. Grants from ZonMW, the Dutch Organization for Health Research and Development. J.S.E.L. reports grants from Ferring, MSD, Organon, Merck Serono and Schering-Plough during the conduct of the study. F.J.M.B. receives monetary compensation as member of the external advisory board for Merck Serono, consultancy work for Gedeon Richter, educational activities for Ferring BV, research cooperation with Ansh Labs and a strategic cooperation with Roche on automated anti Mullerian hormone assay development. N.S.M. reports receiving monetary compensations for external advisory and speaking work for Ferring BV, MSD, Anecova and Merck Serono during the conduct of the study. All reported competing interests are outside the submitted work. No other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER Netherlands trial register, number NTR 1586. TRIAL REGISTRATION DATE 13 January 2009. FIRST PATIENT INCLUDED 20 April 2009. PMID:27179265

  4. The first transmembrane domain (TM1) of β2-subunit binds to the transmembrane domain S1 of α-subunit in BK potassium channels

    PubMed Central

    Morera, Francisco J.; Alioua, Abderrahmane; Kundu, Pallob; Salazar, Marcelo; Gonzalez, Carlos; Martinez, Agustin D.; Stefani, Enrico; Toro, Ligia; Latorre, Ramon

    2012-01-01

    The BK channel is one of the most broadly expressed ion channels in mammals. In many tissues, the BK channel pore-forming α-subunit is associated to an auxiliary β-subunit that modulates the voltage- and Ca2+-dependent activation of the channel. Structural components present in β-subunits that are important for the physical association with the α-subunit are yet unknown. Here, we show through co-immunoprecipitation that the intracellular C-terminus, the second transmembrane domain (TM2) and the extracellular loop of the β2-subunit are dispensable for association with the α-subunit pointing transmembrane domain 1 (TM1) as responsible for the interaction. Indeed, the TOXCAT assay for transmembrane protein–protein interactions demonstrated for the first time that TM1 of the β2-subunit physically binds to the transmembrane S1 domain of the α-subunit. PMID:22710124

  5. Housefly Population Density Correlates with Shigellosis among Children in Mirzapur, Bangladesh: A Time Series Analysis

    PubMed Central

    Farag, Tamer H.; Faruque, Abu S.; Wu, Yukun; Das, Sumon K.; Hossain, Anowar; Ahmed, Shahnawaz; Ahmed, Dilruba; Nasrin, Dilruba; Kotloff, Karen L.; Panchilangam, Sandra; Nataro, James P.; Cohen, Dani; Blackwelder, William C.; Levine, Myron M.

    2013-01-01

    Background Shigella infections are a public health problem in developing and transitional countries because of high transmissibility, severity of clinical disease, widespread antibiotic resistance and lack of a licensed vaccine. Whereas Shigellae are known to be transmitted primarily by direct fecal-oral contact and less commonly by contaminated food and water, the role of the housefly Musca domestica as a mechanical vector of transmission is less appreciated. We sought to assess the contribution of houseflies to Shigella-associated moderate-to-severe diarrhea (MSD) among children less than five years old in Mirzapur, Bangladesh, a site where shigellosis is hyperendemic, and to model the potential impact of a housefly control intervention. Methods Stool samples from 843 children presenting to Kumudini Hospital during 2009–2010 with new episodes of MSD (diarrhea accompanied by dehydration, dysentery or hospitalization) were analyzed. Housefly density was measured twice weekly in six randomly selected sentinel households. Poisson time series regression was performed and autoregression-adjusted attributable fractions (AFs) were calculated using the Bruzzi method, with standard errors via jackknife procedure. Findings Dramatic springtime peaks in housefly density in 2009 and 2010 were followed one to two months later by peaks of Shigella-associated MSD among toddlers and pre-school children. Poisson time series regression showed that housefly density was associated with Shigella cases at three lags (six weeks) (Incidence Rate Ratio = 1.39 [95% CI: 1.23 to 1.58] for each log increase in fly count), an association that was not confounded by ambient air temperature. Autocorrelation-adjusted AF calculations showed that a housefly control intervention could have prevented approximately 37% of the Shigella cases over the study period. Interpretation Houseflies may play an important role in the seasonal transmission of Shigella in some developing country ecologies. Interventions to control houseflies should be evaluated as possible additions to the public health arsenal to diminish Shigella (and perhaps other causes of) diarrheal infection. PMID:23818998

  6. Housefly population density correlates with shigellosis among children in Mirzapur, Bangladesh: a time series analysis.

    PubMed

    Farag, Tamer H; Faruque, Abu S; Wu, Yukun; Das, Sumon K; Hossain, Anowar; Ahmed, Shahnawaz; Ahmed, Dilruba; Nasrin, Dilruba; Kotloff, Karen L; Panchilangam, Sandra; Nataro, James P; Cohen, Dani; Blackwelder, William C; Levine, Myron M

    2013-01-01

    Shigella infections are a public health problem in developing and transitional countries because of high transmissibility, severity of clinical disease, widespread antibiotic resistance and lack of a licensed vaccine. Whereas Shigellae are known to be transmitted primarily by direct fecal-oral contact and less commonly by contaminated food and water, the role of the housefly Musca domestica as a mechanical vector of transmission is less appreciated. We sought to assess the contribution of houseflies to Shigella-associated moderate-to-severe diarrhea (MSD) among children less than five years old in Mirzapur, Bangladesh, a site where shigellosis is hyperendemic, and to model the potential impact of a housefly control intervention. Stool samples from 843 children presenting to Kumudini Hospital during 2009-2010 with new episodes of MSD (diarrhea accompanied by dehydration, dysentery or hospitalization) were analyzed. Housefly density was measured twice weekly in six randomly selected sentinel households. Poisson time series regression was performed and autoregression-adjusted attributable fractions (AFs) were calculated using the Bruzzi method, with standard errors via jackknife procedure. Dramatic springtime peaks in housefly density in 2009 and 2010 were followed one to two months later by peaks of Shigella-associated MSD among toddlers and pre-school children. Poisson time series regression showed that housefly density was associated with Shigella cases at three lags (six weeks) (Incidence Rate Ratio = 1.39 [95% CI: 1.23 to 1.58] for each log increase in fly count), an association that was not confounded by ambient air temperature. Autocorrelation-adjusted AF calculations showed that a housefly control intervention could have prevented approximately 37% of the Shigella cases over the study period. Houseflies may play an important role in the seasonal transmission of Shigella in some developing country ecologies. Interventions to control houseflies should be evaluated as possible additions to the public health arsenal to diminish Shigella (and perhaps other causes of) diarrheal infection.

  7. Immunogenicity of a low-dose diphtheria, tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria, tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study.

    PubMed

    John, T; Voysey, M; Yu, L M; McCarthy, N; Baudin, M; Richard, P; Fiquet, A; Kitchin, N; Pollard, A J

    2015-08-26

    This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap-IPV, Repevax(®); Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis(®); Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap-IPV, Tetravac(®); Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection. All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap-IPV, Tdap+OPV and DTap-IPV, respectively, had protective antitoxin levels greater than 0.1IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV. Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Perceptions, attitudes and experiences of family caregivers of patients with musculoskeletal diseases: a qualitative approach.

    PubMed

    Alfaro, Noelia; Lázaro, Pablo; Gabriele, Giovanna; Garcia-Vicuña, Rosario; Jover, Juan Ángel; Sevilla, Jordi

    2013-01-01

    To determine the perceptions, attitudes and experiences among family caregivers of patients with musculoskeletal diseases (MSD). Descriptive, exploratory, qualitative study. Two discussion groups were organized with family caregivers of MSD patients, representing the caregiver profile: gender (men/women) and age (31-45 years/46-65 years); and patient profiles: MSD type (rheumatoid arthritis/ankylosing spondylitis), work status (yes or no for the variables housewife, at least 3 episodes of sick leave, patients who abandoned their work, and patients with permanent work disability). A content analysis based on the Grounded Theory was done to detect and explore emerging categories. The emerging dimensions were: alterations in daily life activities, need for caregiver support, physical and psychological impact on the caregiver, characteristics of the patient, and several aspects of care. Relevant experiences mentioned were: the diagnosis of a MSD changes the patient and their family members' life affecting work, financial, social, psychological and physical spheres, making it necessary help for basic activities of daily living. Early age at onset or severe MSDs require dedication and effort on the part of caregivers which increases with time. This leads to a great emotional overload on the caregivers, which may be modulated by the support they receive when providing care. The primary consequences for caregivers are loss of purchasing power, work problems, social isolation and emotional stress. Programs for effective at-home support need to be developed with streamlined administrative processes to quickly classify the level of disability and provide official assistance. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  9. Effect of systematic ergonomic hazard identification and control implementation on musculoskeletal disorder and injury risk

    PubMed Central

    Cantley, Linda F; Taiwo, Oyebode A; Galusha, Deron; Barbour, Russell; Slade, Martin D; Tessier-Sherman, Baylah; Cullen, Mark R

    2014-01-01

    Objectives This study aimed to examine the effect of an ergonomic hazard control (HC) initiative, undertaken as part of a company ergonomics standard, on worker injury risk. Methods Using the company's ergonomic hazards database to identify jobs with and without ergonomic HC implementation and linking to individual job and injury histories, injury risk among person-jobs with HC implementation (the HC group) was compared to those without HC (NoHC group) using random coefficient models. Further analysis of the HC group was conducted to determine the effect of additional ergonomic hazards controlled on injury risk. Results Among 123jobs at 17 plant locations, 347 ergonomic hazards were quantitatively identified during the study period. HC were implemented for 204 quantified ergonomic hazards in 84 jobs, impacting 10 385 persons (12 967 person-jobs). No HC were implemented for quantified ergonomic hazards in the remaining 39 jobs affecting 4155 persons (5046 person-jobs). Adjusting for age, sex, plant origin, and year to control for any temporal trend in injury risk, the relative risk (RR) for musculoskeletal disorder (MSD) was 0.85 and the RR for any injury or MSD was 0.92 in the HC compared to NoHC group. Among the HC group, each ergonomic hazard controlled was associated with risk reduction for MSD and acute injury outcomes (RR 0.93). Conclusion Systematic ergonomic HC through participatory ergonomics, as part of a mandatory company ergonomics standard, is associated with MSD and injury risk reduction among workers in jobs with HC implemented. PMID:24142048

  10. Workstyle and Musculoskeletal Discomfort (MSD): Exploring the Influence of Work Culture in Malaysia.

    PubMed

    Maakip, Ismail; Keegel, Tessa; Oakman, Jodi

    2015-12-01

    Workstyle can be defined as an individual pattern of cognitions, behaviours and physiological reactivity that can occur while performing job tasks. Workstyle has been associated with the development of musculoskeletal disorders (MSDs) amongst office workers in developed countries. However, little is known about the contribution of workstyle on MSDs in developing countries such as Malaysia. The objective of this cross-sectional study was to examine the relationship between workstyle and musculoskeletal discomfort in a sample of office workers in Malaysia. Office workers (N = 417; response rate 65.5 %) from four organisations completed a survey measuring physical and psychosocial hazards, job satisfaction, work-life balance, workstyle, and MSD discomfort levels. Hierarchical regression analyses were undertaken to examine predictors associated with self-reported musculoskeletal discomfort, and more specifically the relationship between workstyle and MSD discomfort. Musculoskeletal discomfort was significantly associated with working through pain, mental health, physical demands, gender and work-life balance (R (2) = 50.2, adjusted R (2) = 0.48; F (13, 324) = 25.09, p = 0.001). Working through pain is the strongest risk factor associated with MSD discomfort (ß = 0.49, p = 0.001) compared to other potential risk factors. Working through pain is influenced by work, social culture and religious beliefs. Workplace MSDs interventions that focus on the impact of physical and psychosocial hazards with emphasis on addressing adverse workstyles should take into account aspects related to work and social culture of the target population. Changes are recommended at both employee and management levels such as better communications and understanding concerning workplace problems with regards to minimizing MSDs at work.

  11. Role of Occupational Stress and Burnout in Prevalence of Musculoskeletal Disorders Among Embassy Personnel of Foreign Countries in Iran

    PubMed Central

    Aghilinejad, Mashaallah; Sadeghi, Zargham; Abdullah, Amer; Sarebanha, Shima; Bahrami-Ahmadi, Amir

    2014-01-01

    Background: Occupation is one of the major parts of our daily lives that might cause a great amount of stress. Stress and job burnout are linked together. The association between musculoskeletal disorders (MSD) and burnout syndrome as a psychosocial factor was investigated previously. Objectives: The aim of this study was to identify the role of occupational stress and burnout in musculoskeletal complaint among diplomatic employees of different embassies in Iran. Materials and Methods: In a cross-sectional study, we assessed 200 employees of the foreign countries embassies in Iran. The participants were selected randomly from all the embassy personnel. Study questionnaires were delivered to the participants and finally 161 questionnaires were returned to the researchers (response rate: 80.5%). An assessment of burnout and MSD were made using the Maslach Burnout Inventory (MBI) and Nordic questionnaires. The work place stress was measured by the work place stress questionnaire. Results: Mean occupational stress was significantly higher among embassy personnel with MSD than among the personnel without this syndrome during the preceding week (17.18 ± 3.42 and 16.06 ± 2.19, respectively; P = 0.02) and the preceding year (17.17 ± 3.11 and 16.74 ± 3.03, respectively; P < 0.01) to the study. Only smoking and occupational stress were identified as independent predictors of MSD among embassy personnel. Conclusions: It seems that association between musculoskeletal complaints and burnout syndrome was more complex than being attributed to only occupation stress. Further studies are recommended to determine other related factors to this association. PMID:25031868

  12. Role of occupational stress and burnout in prevalence of musculoskeletal disorders among embassy personnel of foreign countries in iran.

    PubMed

    Aghilinejad, Mashaallah; Sadeghi, Zargham; Abdullah, Amer; Sarebanha, Shima; Bahrami-Ahmadi, Amir

    2014-05-01

    Occupation is one of the major parts of our daily lives that might cause a great amount of stress. Stress and job burnout are linked together. The association between musculoskeletal disorders (MSD) and burnout syndrome as a psychosocial factor was investigated previously. The aim of this study was to identify the role of occupational stress and burnout in musculoskeletal complaint among diplomatic employees of different embassies in Iran. In a cross-sectional study, we assessed 200 employees of the foreign countries embassies in Iran. The participants were selected randomly from all the embassy personnel. Study questionnaires were delivered to the participants and finally 161 questionnaires were returned to the researchers (response rate: 80.5%). An assessment of burnout and MSD were made using the Maslach Burnout Inventory (MBI) and Nordic questionnaires. The work place stress was measured by the work place stress questionnaire. Mean occupational stress was significantly higher among embassy personnel with MSD than among the personnel without this syndrome during the preceding week (17.18 ± 3.42 and 16.06 ± 2.19, respectively; P = 0.02) and the preceding year (17.17 ± 3.11 and 16.74 ± 3.03, respectively; P < 0.01) to the study. Only smoking and occupational stress were identified as independent predictors of MSD among embassy personnel. It seems that association between musculoskeletal complaints and burnout syndrome was more complex than being attributed to only occupation stress. Further studies are recommended to determine other related factors to this association.

  13. Chromosomal locus tracking with proper accounting of static and dynamic errors

    PubMed Central

    Backlund, Mikael P.; Joyner, Ryan; Moerner, W. E.

    2015-01-01

    The mean-squared displacement (MSD) and velocity autocorrelation (VAC) of tracked single particles or molecules are ubiquitous metrics for extracting parameters that describe the object’s motion, but they are both corrupted by experimental errors that hinder the quantitative extraction of underlying parameters. For the simple case of pure Brownian motion, the effects of localization error due to photon statistics (“static error”) and motion blur due to finite exposure time (“dynamic error”) on the MSD and VAC are already routinely treated. However, particles moving through complex environments such as cells, nuclei, or polymers often exhibit anomalous diffusion, for which the effects of these errors are less often sufficiently treated. We present data from tracked chromosomal loci in yeast that demonstrate the necessity of properly accounting for both static and dynamic error in the context of an anomalous diffusion that is consistent with a fractional Brownian motion (FBM). We compare these data to analytical forms of the expected values of the MSD and VAC for a general FBM in the presence of these errors. PMID:26172745

  14. Genetic variation in heat tolerance-related traits in a population of wheat multiple synthetic derivatives

    PubMed Central

    Elbashir, Awad A. E.; Gorafi, Yasir S. A.; Tahir, Izzat S. A.; Elhashimi, Ashraf. M. A.; Abdalla, Modather G. A.; Tsujimoto, Hisashi

    2017-01-01

    In wheat (Triticum aestivum L.) high temperature (≥30°C) during grain filling leads to considerable reduction in grain yield. We studied 400 multiple synthetic derivatives (MSD) lines to examine the genetic variability of heat stress–adaptive traits and to identify new sources of heat tolerance to be used in wheat breeding programs. The experiment was arranged in an augmented randomized complete block design in four environments in Sudan. A wide range of genetic variability was found in most of the traits in all environments. For all traits examined, we found MSD lines that showed better performance than their parent ‘Norin 61’ and two adapted Sudanese cultivars. Using the heat tolerance efficiency, we identified 13 highly heat-tolerant lines and several lines with intermediate heat tolerance and good yield potential. We also identified lines with alleles that can be used to increase wheat yield potential. Our study revealed that the use of the MSD population is an efficient way to explore the genetic variation in Ae. tauschii for wheat breeding and improvement. PMID:29398942

  15. Isolating long-wavelength fluctuation from structural relaxation in two-dimensional glass: cage-relative displacement

    NASA Astrophysics Data System (ADS)

    Shiba, Hayato; Keim, Peter; Kawasaki, Takeshi

    2018-03-01

    It has recently been revealed that long-wavelength fluctuation exists in two-dimensional (2D) glassy systems, having the same origin as that given by the Mermin-Wagner theorem for 2D crystalline solids. In this paper, we discuss how to characterise quantitatively the long-wavelength fluctuation in a molecular dynamics simulation of a lightly supercooled liquid. We employ the cage-relative mean-square displacement (MSD), defined on relative displacement to its cage, to quantitatively separate the long-wavelength fluctuation from the original MSD. For increasing system size the amplitude of acoustic long wavelength fluctuations not only increases but shifts to later times causing a crossover with structural relaxation of caging particles. We further analyse the dynamic correlation length using the cage-relative quantities. It grows as the structural relaxation becomes slower with decreasing temperature, uncovering an overestimation by the four-point correlation function due to the long-wavelength fluctuation. These findings motivate the usage of cage-relative MSD as a starting point for analysis of 2D glassy dynamics.

  16. Design and implementation of the modified signed digit multiplication routine on a ternary optical computer.

    PubMed

    Xu, Qun; Wang, Xianchao; Xu, Chao

    2017-06-01

    Multiplication with traditional electronic computers is faced with a low calculating accuracy and a long computation time delay. To overcome these problems, the modified signed digit (MSD) multiplication routine is established based on the MSD system and the carry-free adder. Also, its parallel algorithm and optimization techniques are studied in detail. With the help of a ternary optical computer's characteristics, the structured data processor is designed especially for the multiplication routine. Several ternary optical operators are constructed to perform M transformations and summations in parallel, which has accelerated the iterative process of multiplication. In particular, the routine allocates data bits of the ternary optical processor based on digits of multiplication input, so the accuracy of the calculation results can always satisfy the users. Finally, the routine is verified by simulation experiments, and the results are in full compliance with the expectations. Compared with an electronic computer, the MSD multiplication routine is not only good at dealing with large-value data and high-precision arithmetic, but also maintains lower power consumption and fewer calculating delays.

  17. Deciphering the function of the CNGB1b subunit in olfactory CNG channels.

    PubMed

    Nache, Vasilica; Wongsamitkul, Nisa; Kusch, Jana; Zimmer, Thomas; Schwede, Frank; Benndorf, Klaus

    2016-07-11

    Olfactory cyclic nucleotide-gated (CNG) ion channels are key players in the signal transduction cascade of olfactory sensory neurons. The second messengers cAMP and cGMP directly activate these channels, generating a depolarizing receptor potential. Olfactory CNG channels are composed of two CNGA2 subunits and two modulatory subunits, CNGA4, and CNGB1b. So far the exact role of the modulatory subunits for channel activation is not fully understood. By measuring ligand binding and channel activation simultaneously, we show that in functional heterotetrameric channels not only the CNGA2 subunits and the CNGA4 subunit but also the CNGB1b subunit binds cyclic nucleotides and, moreover, also alone translates this signal to open the pore. In addition, we show that the CNGB1b subunit is the most sensitive subunit in a heterotetrameric channel to cyclic nucleotides and that it accelerates deactivation to a similar extent as does the CNGA4 subunit. In conclusion, the CNGB1b subunit participates in ligand-gated activation of olfactory CNG channels and, particularly, contributes to rapid termination of odorant signal in an olfactory sensory neuron.

  18. Differential plasma membrane targeting of voltage-dependent calcium channel subunits expressed in a polarized epithelial cell line

    PubMed Central

    Brice, Nicola L; Dolphin, Annette C

    1999-01-01

    Voltage-dependent calcium channels (VDCCs) show a highly non-uniform distribution in many cell types, including neurons and other polarized secretory cells. We have examined whether this can be mimicked in a polarized epithelial cell line (Madin-Darby canine kidney), which has been used extensively to study the targeting of proteins. We expressed the VDCC α1A, α1B or α1C subunits either alone or in combination with accessory subunits α2-δ and the different β subunits, and examined their localization immunocytochemically. An α1 subunit was only targeted to the plasma membrane if co-expressed with the accessory subunits. The combination α1C/α2-δ and all β subunits was always localized predominantly to the basolateral membrane. It has been suggested that this is equivalent to somatodendritic targeting in neurons. In contrast, the α1B subunit was expressed at the apical membrane with all the accessory subunit combinations, by 24 h after microinjection. This membrane destination shows some parallels with axonal targeting in neurons. The α1A subunit was consistently observed at the apical membrane in the combinations α1A/α2-δ/β1b or β4. In contrast, when co-expressed with α2-δ/β2a, α1A was clearly targeted to the basolateral membrane. In conclusion, the VDCC α1 subunit appears to be the primary determinant for targeting the VDCC complex, but the β subunit can modify this destination, particularly for α1A. PMID:10066897

  19. GABAA receptors: Various stoichiometrics of subunit arrangement in α1β3 and α1β3ε receptors.

    PubMed

    Has, Ahmad Tarmizi Che; Chebib, Mary

    2018-05-15

    GABAA receptors (GABAARs) are members of the Cys-loop ligand-gated ion channel (LGIC) superfamily, which includes nicotinic acetylcholine, glycine, and serotonin (5HT3) receptors [1,2,3,4]. LGICs typically mediate fast synaptic transmission via the movement of ions through channels gated by neurotransmitters, such as acetylcholine for nicotinic receptors and GABA for GABAARs [5]. The term Cys-loop receptors originates from the presence of a conserved disulphide bond (or bridge) which holds together two cysteine amino acids of the loop that forms from the structure of polypeptides in the extracellular domain of the receptor's subunit [6]. GABAARs are pentameric transmembrane protein complexes consisting of five subunits from a variety of polypeptide subunits [7,8]. All of these subunits are pseudo-symmetrically organized in the plane of the membrane, with a Cl--selective channel in the middle of the complex. To date, nineteen GABAAR subunits have been identified and categorized into eight classes, α1-6, β1-3, γ1-3, δ, ε, θ, π and ρ1-3, but their variety is further broadened by the existence of several splice forms for certain subunits (e.g., α6, β2 and γ2) [9,10,11,12]. The subunits within each class have an amino acid sequence homology of 70% or more, whereas those with a sequence homology of 30% or less are grouped into different classes [13,14]. A subunit consists of four transmembrane domains (TM1-TM4), each forming an α-helix; a large extracellular N-terminal domain that incorporates part of the orthosteric agonist/antagonist binding site; a large intracellular loop between the TM3 and TM4; a small intracellular loop between TM1 and TM2; a small extracellular loop between TM2 and TM3; and a C-terminal extracellular domain [15,16]. Each subunit is arranged in such a way as to create principal and complementary interfaces with the other subunits, and in a position such that the TM2 of each subunit forms the wall of the channel pore [17,18,19]. The major subunit combination found in the brain comprises α1, β2 and γ2 subunits with the stoichiometry 2α1:2β2:1γ2 [18,20]. For the GABAA α1β2γ2 receptors, the subunits form a specific arrangement in which α1 and β2 subunits alternate with each other and are connected by a γ2 subunit (Figure A) [16,20,21]. For minor subtypes, different α and β subunits have been detected to co-exist as proven by the existence of GABAARs containing α1α2, α1α3, α1α5, α2α3, α3α5, α4α1, α4α2 and α4α3 in the central nervous system [22,23]. Meanwhile, the same pattern has been detected with β and γ subunits, at least the co-occurrence of β in the same GABAAR as well as γ2 with γ3, indicating that these subunits have the capacity to co-exist with each other [24,25,26]. Since different subunits can actually occur in one receptor, GABAARs are considered to exist in a multi-subunit arrangement, leading to ambiguity in the determination of a receptor's stoichiometry. In this review, we first briefly discuss the different subunit arrangements of α1 and β3 subunits in the binary α1β3 receptors. Then we review the GABAA ε-containing receptors predominantly in terms of the ability of ε subunit to present in different position in the ternary α1β3ε receptors, which introduce distinct populations of receptor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Is mobility in the labor market a solution to sustainable return to work for some sick listed persons?

    PubMed

    Ekberg, Kerstin; Wåhlin, Charlotte; Persson, Jan; Bernfort, Lars; Öberg, Birgitta

    2011-09-01

    The study aims to identify characteristics associated with long-term expectations of professional stability or mobility among recently sick-listed workers, and to study whether expectations of professional mobility and turnover intentions were associated with duration of sick leave. A cross-sectional study was performed on baseline measures in a prospective cohort study of patients who were granted sick leave due to musculoskeletal (MSD) or mental (MD) disorders. A total of 1,375 individuals fulfilled the inclusion criteria. A baseline questionnaire was sent by mail within 3 weeks of their first day of certified medical sickness; 962 individuals responded (70%). The main diagnosis was MSD in 595 (62%) individuals and MD in 367 (38%). Expectations of ability to remain in the present profession in 2 years was associated with better health and health-related resources, younger age, higher education, and better effort-reward balance. Effort-reward imbalance, MD, high burnout scores, and better educational and occupational position were associated with turnover intentions. Low expectations of ability to remain in the present profession defined two vulnerable groups with regard to RTW, those with no turnover intentions were older, had lower personal resources, more often had MSD, and slower RTW rate. Those with turnover intentions had a clear effort-reward imbalance and high burnout scores. The results of this explorative study underline the importance of differentiating RTW-interventions based on knowledge about the sick-listed person's resources in relation to the labor market and the work place, and their expectations of future employment and employability.

  1. Critical Conditions for Liquid Chromatography of Statistical Copolymers: Functionality Type and Composition Distribution Characterization by UP-LCCC/ESI-MS.

    PubMed

    Epping, Ruben; Panne, Ulrich; Falkenhagen, Jana

    2017-02-07

    Statistical ethylene oxide (EO) and propylene oxide (PO) copolymers of different monomer compositions and different average molar masses additionally containing two kinds of end groups (FTD) were investigated by ultra high pressure liquid chromatography under critical conditions (UP-LCCC) combined with electrospray ionization time-of flight mass spectrometry (ESI-TOF-MS). Theoretical predictions of the existence of a critical adsorption point (CPA) for statistical copolymers with a given chemical and sequence distribution1 could be studied and confirmed. A fundamentally new approach to determine these critical conditions in a copolymer, alongside the inevitable chemical composition distribution (CCD), with mass spectrometric detection, is described. The shift of the critical eluent composition with the monomer composition of the polymers was determined. Due to the broad molar mass distribution (MMD) and the presumed existence of different end group functionalities as well as monomer sequence distribution (MSD), gradient separation only by CCD was not possible. Therefore, isocratic separation conditions at the CPA of definite CCD fractions were developed. Although the various present distributions partly superimposed the separation process, the goal of separation by end group functionality was still achieved on the basis of the additional dimension of ESI-TOF-MS. The existence of HO-H besides the desired allylO-H end group functionalities was confirmed and their amount estimated. Furthermore, indications for a MSD were found by UPLC/MS/MS measurements. This approach offers for the first time the possibility to obtain a fingerprint of a broad distributed statistical copolymer including MMD, FTD, CCD, and MSD.

  2. Improving the accuracy of protein stability predictions with multistate design using a variety of backbone ensembles.

    PubMed

    Davey, James A; Chica, Roberto A

    2014-05-01

    Multistate computational protein design (MSD) with backbone ensembles approximating conformational flexibility can predict higher quality sequences than single-state design with a single fixed backbone. However, it is currently unclear what characteristics of backbone ensembles are required for the accurate prediction of protein sequence stability. In this study, we aimed to improve the accuracy of protein stability predictions made with MSD by using a variety of backbone ensembles to recapitulate the experimentally measured stability of 85 Streptococcal protein G domain β1 sequences. Ensembles tested here include an NMR ensemble as well as those generated by molecular dynamics (MD) simulations, by Backrub motions, and by PertMin, a new method that we developed involving the perturbation of atomic coordinates followed by energy minimization. MSD with the PertMin ensembles resulted in the most accurate predictions by providing the highest number of stable sequences in the top 25, and by correctly binning sequences as stable or unstable with the highest success rate (≈90%) and the lowest number of false positives. The performance of PertMin ensembles is due to the fact that their members closely resemble the input crystal structure and have low potential energy. Conversely, the NMR ensemble as well as those generated by MD simulations at 500 or 1000 K reduced prediction accuracy due to their low structural similarity to the crystal structure. The ensembles tested herein thus represent on- or off-target models of the native protein fold and could be used in future studies to design for desired properties other than stability. Copyright © 2013 Wiley Periodicals, Inc.

  3. Rotation of Subunits During Catalysis by Escherichia coli F_1-ATPase

    NASA Astrophysics Data System (ADS)

    Duncan, Thomas M.; Bulygin, Vladimir V.; Zhou, Yuantai; Hutcheon, Marcus L.; Cross, Richard L.

    1995-11-01

    During oxidative and photo-phosphorylation, F_0F_1-ATP synthases couple the movement of protons down an electrochemical gradient to the synthesis of ATP. One proposed mechanistic feature that has remained speculative is that this coupling process requires the rotation of subunits within F_0F_1. Guided by a recent, high-resolution structure for bovine F_1 [Abrahams, J. P., Leslie, A. G., Lutter, R. & Walker, J. E. (1994) Nature (London) 370, 621-628], we have developed a critical test for rotation of the central γ subunit relative to the three catalytic β subunits in soluble F_1 from Escherichia coli. In the bovine F_1 structure, a specific point of contact between the γ subunit and one of the three catalytic β subunits includes positioning of the homolog of E. coli γ-subunit C87 (γC87) close to the β-subunit 380DELSEED386 sequence. A βD380C mutation allowed us to induce formation of a specific disulfide bond between β and γC87 in soluble E. coli F_1. Formation of the crosslink inactivated βD380C-F_1, and reduction restored full activity. Using a dissociation/reassembly approach with crosslinked βD380C-F_1, we incorporated radiolabeled β subunits into the two noncrosslinked β-subunit positions of F_1. After reduction of the initial nonradio-active β-γ crosslink, only exposure to conditions for catalytic turnover results in similar reactivities of unlabeled and radiolabeled β subunits with γC87 upon reoxidation. The results demonstrate that γ subunit rotates relative to the β subunits during catalysis.

  4. Analysis and prediction of Multiple-Site Damage (MSD) fatigue crack growth

    NASA Technical Reports Server (NTRS)

    Dawicke, D. S.; Newman, J. C., Jr.

    1992-01-01

    A technique was developed to calculate the stress intensity factor for multiple interacting cracks. The analysis was verified through comparison with accepted methods of calculating stress intensity factors. The technique was incorporated into a fatigue crack growth prediction model and used to predict the fatigue crack growth life for multiple-site damage (MSD). The analysis was verified through comparison with experiments conducted on uniaxially loaded flat panels with multiple cracks. Configuration with nearly equal and unequal crack distribution were examined. The fatigue crack growth predictions agreed within 20 percent of the experimental lives for all crack configurations considered.

  5. Identification of TNT Transformation Products in Soil

    DTIC Science & Technology

    1992-06-01

    Unannounced 0 Just i•icatio BYDlstrtbton, --.- Availabilit ? CodoeS Dist Special moI QUA=~lI3E1 3 ii CONTENTS Preface...extracted. Soil-to-solvent ratios varied from 1:2 to (Jenkins et al. 1989) and water (Jenkins et al. 1986, 1:5 (mass [g]:volume [mL]); the smallest...cultures, composting systems and MassSelectiveDetector (MSD) throughaHewlett- water , little research has been conducted to define Packard 5890 Series

  6. Rapid and Stereoselective Conversion of a "trans"-Cinnamic Acid to a beta-Bromostyrene

    ERIC Educational Resources Information Center

    Evans, Thomas A.

    2006-01-01

    The stereoselective synthesis of an aryl vinyl bromide is accomplished in a rapid microscale reaction of "trans"-4-methoxycinnamic acid with N-bromosuccinimide in dichloromethane. The product is purified by dry column vacuum chromatography and its stereochemistry is determined by [superscript 1]H NMR. TLC, GC and GC-MSD can also be used. This…

  7. Teaching Core Content with Real-Life Applications to Secondary Students with Moderate and Severe Disabilities

    ERIC Educational Resources Information Center

    Collins, Belva C.; Karl, Jennifer; Riggs, Leah; Galloway, Carey C.; Hager, Karen D.

    2010-01-01

    Many students identified as having moderate and severe disabilities (MSD) benefit from a curriculum that includes instruction on the functional skills that they will need to successfully transition to adulthood. In particular, this includes students with cognitive disabilities who are most likely to qualify in the 1% who are eligible for the…

  8. Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.

    PubMed

    Rettig, J; Heinemann, S H; Wunder, F; Lorra, C; Parcej, D N; Dolly, J O; Pongs, O

    1994-05-26

    Structural and functional diversity of voltage-gated Kv1-type potassium channels in rat brain is enhanced by the association of two different types of subunits, the membrane-bound, poreforming alpha-subunits and a peripheral beta-subunit. We have cloned a beta-subunit (Kv beta 1) that is specifically expressed in the rat nervous system. Association of Kv beta 1 with alpha-subunits confers rapid A-type inactivation on non-inactivating Kv1 channels (delayed rectifiers) in expression systems in vitro. This effect is mediated by an inactivating ball domain in the Kv beta 1 amino terminus.

  9. Structural and molecular characterization of the prefoldin beta subunit from Thermococcus strain KS-1.

    PubMed

    Kida, Hiroshi; Sugano, Yuri; Iizuka, Ryo; Fujihashi, Masahiro; Yohda, Masafumi; Miki, Kunio

    2008-11-14

    Prefoldin (PFD) is a heterohexameric molecular chaperone that is found in eukaryotic cytosol and archaea. PFD is composed of alpha and beta subunits and forms a "jellyfish-like" structure. PFD binds and stabilizes nascent polypeptide chains and transfers them to group II chaperonins for completion of their folding. Recently, the whole genome of Thermococcus kodakaraensis KOD1 was reported and shown to contain the genes of two alpha and two beta subunits of PFD. The genome of Thermococcus strain KS-1 also possesses two sets of alpha (alpha1 and alpha2) and beta subunits (beta1 and beta2) of PFD (TsPFD). However, the functions and roles of each of these PFD subunits have not been investigated in detail. Here, we report the crystal structure of the TsPFD beta1 subunit at 1.9 A resolution and its functional analysis. TsPFD beta1 subunits form a tetramer with four coiled-coil tentacles resembling the jellyfish-like structure of heterohexameric PFD. The beta hairpin linkers of beta1 subunits assemble to form a beta barrel "body" around a central fourfold axis. Size-exclusion chromatography and multi-angle light-scattering analyses show that the beta1 subunits form a tetramer at pH 8.0 and a dimer of tetramers at pH 6.8. The tetrameric beta1 subunits can protect against aggregation of relatively small proteins, insulin or lysozyme. The structural and biochemical analyses imply that PFD beta1 subunits act as molecular chaperones in living cells of some archaea.

  10. Immunochemical analysis of Micrococcus lysodeikticus (luteus) F1-ATPase and its subunits.

    PubMed

    Urban, C; Salton, M R

    1983-08-31

    The F1-ATPase from Micrococcus lysodeikticus has been purified to 95% protein homogeneity in this laboratory and as all other bacterial F1S, possesses five distinct subunits with molecular weights ranging from 60 000 to 10 000 (Huberman, M. and Salton, M.R.J. (1979) Biochim. Biophys. Acta 547, 230-240). In this communication, we demonstrate the immunochemical reactivities of antibodies to native and SDS-dissociated subunits with the native and dissociated F1-ATPase and show that: (1) the antibodies generated to the native or SDS-dissociated subunits react with the native molecule; (2) all of the subunits comprising the F1 are antigenically unique as determined by crossed immunoelectrophoresis and the Ouchterlony double-diffusion techniques; (3) antibodies to the SDS-denatured individual delta- and epsilon-subunits can be used to destabilize the interaction of these specific subunits with the rest of the native F1; and (4) all subunit antibodies as well as anti-native F1 were found to inhibit ATPase activity to varying degrees, the strongest inhibition being seen with antibodies to the total F1 and anti-alpha- and anti-beta-subunit antibodies. The interaction of specific subunit antibodies may provide a new and novel way to study further and characterize the catalytic portions of F1-ATPases and in general may offer an additional method for the examination of multimeric proteins.

  11. Mediterranean-style diet reduces metabolic syndrome components in obese children and adolescents with obesity

    PubMed Central

    2014-01-01

    Background The beneficial effects of the Mediterranean diet have been amply proven in adults with cardiovascular risk factors. The effects of this diet have not been extensively assessed in pediatric populations with obesity, insulin resistance (IR) and metabolic syndrome (MetS). The aim of this study was to assess the efficacy of the Mediterranean style diet (MSD) to decrease cardiovascular risk factors in children and adolescents with obesity. Methods Participants were randomly assigned to a MSD rich in polyunsaturated fatty acids, fiber, flavonoids and antioxidants (60% of energy from carbohydrate, 25% from fat, and 15% from protein, (n = 24); or a standard diet (55% of carbohydrate, 30% from fat and 15% from protein, (n = 25), the caloric ingest was individualized. At baseline and 16-week of intervention, the glucose, triglycerides (TG), total cholesterol (TC), HDL-C, LDL-C were measured as well as the body composition and anthropometric data. The diet compliance was determined by the 24-hour recalls. Paired Student’s t and Macnemar’s test were used to compare effects in biochemical, body composition, anthropometric, and dietary variables. Results The MSD group had a significantly decrease in BMI, lean mass, fat mass, glucose, TC, TG, HDL-C and LDL-C. (p < 0.05); the diet compliance increased consumption of omega 9 fatty acids, zinc, vitamin E, selenium, and decreased consumption of saturated fatty acids (p < 0.05). The standard diet group decrease in glucose levels and frequency of glucose >100 mg/dL (p < 0.05). Conclusion The MSD improves the BMI, glucose and lipid profile in children and adolescents with obesity and any MetS component. PMID:24997634

  12. A promising biotechnical approach to pest management of Diabrotica virgifera virgifera in Illinois maize fields under kairomonal shielding with the new MSD technique.

    PubMed

    Hummel, H E; Shaw, J T; Hein, D F

    2005-01-01

    Environmentally compatible and sustainable plant protection requires novel approaches to pest management characterized by minimal emphasis on toxicants. Classical toxicants traditionally dominated economic entomology for half a century. But worldwide problems with environmental pollution and with increasing resistance levels in all major pesticide classes and in many key insect species including Diabrotica virgifera virgifera (D.v.v.) strongly advocate a rethinking and a change in management paradigms used. Soft, minimally invasive, biological, biotechnical and cultural approaches should replace hard pesticides which are in favor up to now. Fortunately, pheromones, kairomones, plant attractants, better traps, new plant varieties and cultural methods like crop rotation, in short more sophisticated methods are now available as pressure for finding and exploring novel strategies increases. Facing this situation, a new biotechnical approach of population reduction of D.v.v., called "MSD" technique, is introduced. MSD is characterized as an approach combining mass trapping, shielding and deflecting of adult insects along an invisible odor barrier of synthetic kairomone which diminishes the flux of insects across a high capacity trap line baited with kairomone, thus reducing both the population fluctuation and number and its reproductive success within the shielded area. In the case of D.v.v. in Zea mays fields, effects realized by the MSD technique have been measured simultaneously by a number of independent criteria during the summers of 2003 and 2004 at 2 different locations in Illinois maize fields of up to one half hectare size. Results observed are statistically significant and cannot be explained by mass trapping alone. There is also an additional shielding and deflection, in short "diversion" effect whose basic sensory and behavioral mechanisms call for future exploration.

  13. Mediterranean-style diet reduces metabolic syndrome components in obese children and adolescents with obesity.

    PubMed

    Velázquez-López, Lubia; Santiago-Díaz, Gerardo; Nava-Hernández, Julia; Muñoz-Torres, Abril V; Medina-Bravo, Patricia; Torres-Tamayo, Margarita

    2014-07-05

    The beneficial effects of the Mediterranean diet have been amply proven in adults with cardiovascular risk factors. The effects of this diet have not been extensively assessed in pediatric populations with obesity, insulin resistance (IR) and metabolic syndrome (MetS). The aim of this study was to assess the efficacy of the Mediterranean style diet (MSD) to decrease cardiovascular risk factors in children and adolescents with obesity. Participants were randomly assigned to a MSD rich in polyunsaturated fatty acids, fiber, flavonoids and antioxidants (60% of energy from carbohydrate, 25% from fat, and 15% from protein, (n = 24); or a standard diet (55% of carbohydrate, 30% from fat and 15% from protein, (n = 25), the caloric ingest was individualized. At baseline and 16-week of intervention, the glucose, triglycerides (TG), total cholesterol (TC), HDL-C, LDL-C were measured as well as the body composition and anthropometric data. The diet compliance was determined by the 24-hour recalls.Paired Student's t and Macnemar's test were used to compare effects in biochemical, body composition, anthropometric, and dietary variables. The MSD group had a significantly decrease in BMI, lean mass, fat mass, glucose, TC, TG, HDL-C and LDL-C. (p < 0.05); the diet compliance increased consumption of omega 9 fatty acids, zinc, vitamin E, selenium, and decreased consumption of saturated fatty acids (p < 0.05). The standard diet group decrease in glucose levels and frequency of glucose >100 mg/dL (p < 0.05). The MSD improves the BMI, glucose and lipid profile in children and adolescents with obesity and any MetS component.

  14. Diffusing-wave spectroscopy in an inhomogeneous object: Local viscoelastic spectra from ultrasound-assisted measurement of correlation decay arising from the ultrasound focal volume

    NASA Astrophysics Data System (ADS)

    Chandran, R. Sriram; Sarkar, Saikat; Kanhirodan, Rajan; Roy, Debasish; Vasu, Ram Mohan

    2014-07-01

    We demonstrate diffusing-wave spectroscopy (DWS) in a localized region of a viscoelastically inhomogeneous object by measurement of the intensity autocorrelation [g2(τ)] that captures only the decay introduced by the temperature-induced Brownian motion in the region. The region is roughly specified by the focal volume of an ultrasound transducer which introduces region specific mechanical vibration owing to insonification. Essential characteristics of the localized non-Markovian dynamics are contained in the decay of the modulation depth [M(τ)], introduced by the ultrasound forcing in the focal volume selected, on g2(τ). The modulation depth M (τi) at any delay time τi can be measured by short-time Fourier transform of g2(τ) and measurement of the magnitude of the spectrum at the ultrasound drive frequency. By following the established theoretical framework of DWS, we are able to connect the decay in M (τ) to the mean-squared displacement (MSD) of scattering centers and the MSD to G*(ω), the complex viscoelastic spectrum. A two-region composite polyvinyl alcohol phantom with different viscoelastic properties is selected for demonstrating local DWS-based recovery of G*(ω) corresponding to these regions from the measured region specific M (τi)vsτi. The ultrasound-assisted measurement of MSD is verified by simulating, using a generalized Langevin equation (GLE), the dynamics of the particles in the region selected as well as by the usual DWS experiment without the ultrasound. It is shown that whereas the MSD obtained by solving the GLE without the ultrasound forcing agreed with its experimental counterpart covering small and large values of τ, the match was good only in the initial transients in regard to experimental measurements with ultrasound.

  15. Structure of a thermophilic F1-ATPase inhibited by an ε-subunit: deeper insight into the ε-inhibition mechanism.

    PubMed

    Shirakihara, Yasuo; Shiratori, Aya; Tanikawa, Hiromi; Nakasako, Masayoshi; Yoshida, Masasuke; Suzuki, Toshiharu

    2015-08-01

    F1-ATPase (F1) is the catalytic sector in F(o)F1-ATP synthase that is responsible for ATP production in living cells. In catalysis, its three catalytic β-subunits undergo nucleotide occupancy-dependent and concerted open-close conformational changes that are accompanied by rotation of the γ-subunit. Bacterial and chloroplast F1 are inhibited by their own ε-subunit. In the ε-inhibited Escherichia coli F1 structure, the ε-subunit stabilizes the overall conformation (half-closed, closed, open) of the β-subunits by inserting its C-terminal helix into the α3β3 cavity. The structure of ε-inhibited thermophilic F1 is similar to that of E. coli F1, showing a similar conformation of the ε-subunit, but the thermophilic ε-subunit stabilizes another unique overall conformation (open, closed, open) of the β-subunits. The ε-C-terminal helix 2 and hook are conserved between the two structures in interactions with target residues and in their positions. Rest of the ε-C-terminal domains are in quite different conformations and positions, and have different modes of interaction with targets. This region is thought to serve ε-inhibition differently. For inhibition, the ε-subunit contacts the second catches of some of the β- and α-subunits, the N- and C-terminal helices, and some of the Rossmann fold segments. Those contacts, as a whole, lead to positioning of those β- and α- second catches in ε-inhibition-specific positions, and prevent rotation of the γ-subunit. Some of the structural features are observed even in IF1 inhibition in mitochondrial F1. © 2015 FEBS.

  16. Large conductance Ca(2+)-activated K(+) channel (BKCa) activating properties of a series of novel N-arylbenzamides: Channel subunit dependent effects.

    PubMed

    Kirby, R W; Martelli, A; Calderone, V; McKay, N G; Lawson, K

    2013-07-15

    Large conductance calcium activated potassium channels (BKCa) are fundamental in the control of cellular excitability. Thus, compounds that activate BKCa channels could provide potential therapies in the treatment of pathologies of the cardiovascular and central nervous system. A series of novel N-arylbenzamide compounds, and the reference compound NS1619, were evaluated for BKCa channel opener properties in Human Embryonic Kidney (HEK293) cells expressing the human BKCa channel α-subunit alone or α+β1-subunit complex. Channel activity was determined using a non-radioactive Rb(+) efflux assay to construct concentration effect curves for each compound. All N-arylbenzamide compounds and NS1619 evoked significant (p <0.05) concentration related increases in Rb(+) efflux both in cells expressing α-subunit alone or α+β1-subunits. Co-expression of the β1-subunit modified the Rb(+) efflux responses, relative to that obtained in cells expressing the α-subunit alone, for most of the N-arylbenzamide compounds, in contrast to NS1619. The EC40 values of NS1619, BKMe1 and BKOEt1 were not significantly affected by the co-expression of the BKCa channel α+β1-subunits. In contrast, 5 other N-arylbenzamides (BKPr2, BKPr3, BKPr4, BKH1 and BKVV) showed a significant (p <0.05) 2- to 10-fold increase in EC40 values when tested on the BKCa α+β1-subunit expressing cells compared to BKCa α-subunit expressing cells. Further, the Emax values for BKPr4, BKVV and BKH1 were lower in the BKCa channel α+β1-subunit expressing cells. In conclusion, the N-arylbenzamides studied, like NS1619, were able to activate BKCa channels formed of the α-subunit only. The co-expression of the β1-subunit, however, modified the ability of certain compounds to active the channel leading to differentiated pharmacodynamic profiles. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Structural Determinants for Functional Coupling Between the β and α Subunits in the Ca2+-activated K+ (BK) Channel

    PubMed Central

    Orio, Patricio; Torres, Yolima; Rojas, Patricio; Carvacho, Ingrid; Garcia, Maria L.; Toro, Ligia; Valverde, Miguel A.; Latorre, Ramon

    2006-01-01

    High conductance, calcium- and voltage-activated potassium (BK, MaxiK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (β) subunits. The most remarkable effects of β1 and β2 subunits are an increase of the calcium sensitivity and the slow down of channel kinetics. However, the detailed characteristics of channels formed by α and β1 or β2 are dissimilar, the most remarkable difference being a reduction of the voltage sensitivity in the presence of β1 but not β2. Here we reveal the molecular regions in these β subunits that determine their differential functional coupling with the pore-forming α-subunit. We made chimeric constructs between β1 and β2 subunits, and BK channels formed by α and chimeric β subunits were expressed in Xenopus laevis oocytes. The electrophysiological characteristics of the resulting channels were determined using the patch clamp technique. Chimeric exchange of the different regions of the β1 and β2 subunits demonstrates that the NH3 and COOH termini are the most relevant regions in defining the behavior of either subunit. This strongly suggests that the intracellular domains are crucial for the fine tuning of the effects of these β subunits. Moreover, the intracellular domains of β1 are responsible for the reduction of the BK channel voltage dependence. This agrees with previous studies that suggested the intracellular regions of the α-subunit to be the target of the modulation by the β1-subunit. PMID:16446507

  18. Corifollitropin alfa followed by highly purified HMG versus recombinant FSH in young poor ovarian responders: a multicentre randomized controlled clinical trial.

    PubMed

    Drakopoulos, Panagiotis; Vuong, Thi Ngoc Lan; Ho, Ngoc Anh Vu; Vaiarelli, Alberto; Ho, Manh Tuong; Blockeel, Christophe; Camus, Michel; Lam, Anh Tuan; van de Vijver, Arne; Humaidan, Peter; Tournaye, Herman; Polyzos, Nikolaos P

    2017-11-01

    Does administration of corifollitropin alfa followed by highly purified (hp) HMG result in higher ongoing pregnancy rates compared with daily recombinant FSH (rFSH) in young poor responders? Corifollitropin alfa followed by hp-HMG does not increase ongoing pregnancy rates compared with rFSH in young poor responders, although more supernumerary cryopreserved embryos were obtained with corifollitropin alfa and hp-HMG. Poor ovarian response remains one of the main therapeutic challenges in women undergoing ovarian stimulation, given that very low live birth rates of 6% have been reported in this particular group of infertile patients. Nevertheless, concerns have been raised that a degree of heterogeneity remains, as the prognostic effect of individual factors is still unclear, particularly for the young poor responder group. The rationale for conducting the current randomized trial was based on the results of a previous pilot study demonstrating promising results with the administration of hp-HMG following corifollitropin alpha in women younger than 40 years of age, fulfilling the 'Bologna' criteria. A multicenter, phase III, superiority, randomized trial was conducted using a parallel two-arm design. The study included 152 patients younger than 40 years old and fulfilling the 'Bologna' criteria for poor ovarian response, from one tertiary referral centre in Europe and one tertiary referral centre in Asia. Enrolment was performed from March 2013 to May 2016. Eligible patients were randomized to either administration of 150 μg corifollitropin alfa followed by 300 IU hp-HMG (Group A) or to 300 IU of daily recombinant FSH (Group B) in a fixed GnRH antagonist protocol. The randomization sequence was created using a computer generated randomization list stratified by centre, using 1:1 allocation. The primary outcome was ongoing pregnancy rate (defined as the presence of an intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 9-10 weeks of gestation). Secondary outcomes included embryo cryopreservation rates, clinical and biochemical pregnancy rates and number of oocytes retrieved. Overall, 152 poor ovarian responders defined by the 'Bologna' criteria were included in the study. Using an intention-to treat analysis, the ongoing pregnancy rates did not differ significantly between Group A 11/77 (14.3%) and Group B 11/70 (15.7%), absolute difference: -0.4 (-11.5 to 10.8), OR = 0.9 (0.4-2.4). Biochemical and clinical pregnancy rates, live birth rates and the number of oocytes retrieved were also comparable between the two groups. Nevertheless, more patients in the corifollitropin alfa group had cryopreserved embryos compared to the rFSH group [22 (28.6%) versus 10 (14.3%), OR = 2.4 (1.01-5.5)]. Incidentally, Asian patients had significantly lower cancellation rates compared to European poor responders [2/64 (3.1%) versus 17/83 (20.4%), OR = 0.12 (0.03-0.5)]. This discrepancy could be explained by the fact that Asian women were better prognosis patients than European patients, with significantly lower FSH [9.8 (5.3) versus 11.5 (5.4), P = 0.017] and significantly higher AMH [1.1 (0.9) versus 0.4 (0.3), P-value <0.001] levels. Ongoing pregnancy rates close to 14% for both treatment groups differ significantly from the hypothesized primary outcome rates used in the power calculation. Therefore, our randomized trial might have been underpowered to detect smaller differences. The use of multiple secondary outcomes and multiple comparisons could have increased a Type 1 error. Finally, although the chance of selection biases remains low given the nature of the infertile population, the open-label design could have been a limitation. Poor ovarian response represents a challenge and although a specific protocol may have increased the number of cryopreserved embryos, no difference was observed in ongoing pregnancy rates. Our study, being one of the largest RCTs in 'Bologna' criteria poor responders, highlights that baseline characteristics may play a crucial role in clinical prognosis of this population. Given that ovarian stimulation using novel protocols does not seem to significantly increase pregnancy rates even in young women, we suggest that future clinical research should focus on increasing the number of recruitable follicles and on oocyte quality rather than evaluating different stimulation protocols. No external funding was used for this study. P.D., N.L.V., N.A.V.H., A.V., M.T.H., M.C., A.T.L. and A.V.V. have no conflict of interest to report. C.B. has received unrestricted research grants from MSD and Ferring as well as honoraria for lectures from Abbott, MSD, Merck and Ferring. P.H has received unrestricted research grants from MSD, Merck and Ferring as well as honoraria for lectures from Merck, MSD and IBSA. H.T. has received unrestricted research grants from MSD, Merck, Ferring, Cook, Roche Diagnostics, Besins International and Goodlife as well as consultation fees for research project in female infertility from Merck Finox, Abbott and ObsEva. N.P.P. has received unrestricted research grants from MSD, Ferring, Roche Diagnostics and Besins International as well as honoraria for lectures from MSD, Merck and Ferring. The EUDRACT number of the trial was 2013-000583-29 and the study was registered at clinicaltrials.gov (NCT01816321). 19 February 2013. 28 February 2013. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  19. Subunit rotation of ATP synthase embedded in membranes: a or β subunit rotation relative to the c subunit ring

    PubMed Central

    Nishio, Kazuaki; Iwamoto-Kihara, Atsuko; Yamamoto, Akitsugu; Wada, Yoh; Futai, Masamitsu

    2002-01-01

    ATP synthase FoF1 (α3β3γδɛab2c10–14) couples an electrochemical proton gradient and a chemical reaction through the rotation of its subunit assembly. In this study, we engineered FoF1 to examine the rotation of the catalytic F1 β or membrane sector Fo a subunit when the Fo c subunit ring was immobilized; a biotin-tag was introduced onto the β or a subunit, and a His-tag onto the c subunit ring. Membrane fragments were obtained from Escherichia coli cells carrying the recombinant plasmid for the engineered FoF1 and were immobilized on a glass surface. An actin filament connected to the β or a subunit rotated counterclockwise on the addition of ATP, and generated essentially the same torque as one connected to the c ring of FoF1 immobilized through a His-tag linked to the α or β subunit. These results established that the γɛc10–14 and α3β3δab2 complexes are mechanical units of the membrane-embedded enzyme involved in rotational catalysis. PMID:12357031

  20. The morphological and chemical characteristics of striatal neurons immunoreactive for the alpha1-subunit of the GABA(A) receptor in the rat.

    PubMed

    Waldvogel, H J; Kubota, Y; Trevallyan, S C; Kawaguchi, Y; Fritschy, J M; Mohler, H; Faull, R L

    1997-10-01

    The distribution, morphology and chemical characteristics of neurons immunoreactive for the alpha1-subunit of the GABA(A) receptor in the striatum of the basal ganglia in the rat brain were investigated at the light, confocal and electron microscope levels using single, double and triple immunohistochemical labelling techniques. The results showed that alpha1-subunit immunoreactive neurons were sparsely distributed throughout the rat striatum. Double and triple labelling results showed that all the alpha1-subunit-immunoreactive neurons were positive for glutamate decarboxylase and immunoreactive for the beta2,3 and gamma2 subunits of the GABA(A) receptor. Three types of alpha1-subunit-immunoreactive neurons were identified in the striatum on the basis of cellular morphology and chemical characteristics. The most numerous alpha1-subunit-immunoreactive neurons were medium-sized, aspiny neurons with a widely branching dendritic tree. They were parvalbumin-negative and were located mainly in the dorsolateral regions of the striatum. Electron microscopy showed that these neurons had an indented nuclear membrane, typical of striatal interneurons, and were surrounded by small numbers of axon terminals which established alpha1-subunit-immunoreactive synaptic contacts with the soma and dendrites. These cells were classified as type 1 alpha1-subunit-immunoreactive neurons and comprised 75% of the total population of alpha1-subunit-immunoreactive neurons in the striatum. The remaining alpha1-subunit-immunoreactive neurons comprised of a heterogeneous population of large-sized neurons localized in the ventral and medial regions of the striatum. The most numerous large-sized cells were parvalbumin-negative, had two to three relatively short branching dendrites and were designated type 2 alpha1-subunit-immunoreactive neurons. Electron microscopy showed that the type 2 neurons were characterized by a highly convoluted nuclear membrane and were sparsely covered with small axon terminals. The type 2 neurons comprised 20% of the total population of alpha1-subunit-immunoreactive neurons. The remaining large-sized alpha1-immunoreactive cells were designated type 3 cells; they were positive for parvalbumin and were distinguished by long branching dendrites extending dorsally for 600-800 microm into the striatum. These neurons comprised 5% of the total population of alpha1-subunit-immunoreactive neurons and were surrounded by enkephalin-immunoreactive terminals. Electron microscopy showed that the alpha1-subunit type 3 neurons had an indented nuclear membrane and were densely covered with small axon terminals which established alpha1-subunit-immunoreactive symmetrical synaptic contacts with the soma and dendrites. These results provide a detailed characterization of the distribution, morphology and chemical characteristics of the alpha1-subunit-immunoreactive neurons in the rat striatum and suggest that the type 1 and type 2 neurons comprise of separate populations of striatal interneurons while the type 3 neurons may represent the large striatonigral projection neurons described by Bolam et al. [Bolam J. P., Somogyi P., Totterdell S. and Smith A. D. (1981) Neuroscience 6, 2141-2157.].

  1. Depressive and manic-hypomanic spectrum psychopathology in patients with anorexia nervosa.

    PubMed

    Wildes, Jennifer E; Marcus, Marsha D; Gaskill, Jill A; Ringham, Rebecca

    2007-01-01

    We used a dimensional measure of mood psychopathology to document lifetime depressive and manic-hypomanic spectrum symptoms in 50 patients with anorexia nervosa (AN). Participants provided demographic information and completed the Self-Report Questionnaire for Mood Spectrum, a 161-item instrument that documents lifetime symptoms, traits, and behaviors characteristic of threshold and subthreshold mood episodes. Analyses focused on the association of depressive and manic-hypomanic component scores with indicators of clinical severity in AN. Lifetime severity of depressive (M[SD] = 39.1[13.9]) and manic-hypomanic (M[SD] = 23.8[12.1]) spectrum symptoms exceeded the established thresholds for clinical significance on these scales (ie, score > or =22). There was a positive correlation between the number of manic-hypomanic items endorsed and the number of depressive items endorsed. After controlling for lifetime history of mood disorder, severity of depressive and manic-hypomanic spectrum symptomatology also was associated with a history of self-induced vomiting and suicidality in patients with AN. These data provide initial evidence for the clinical significance of depressive and manic-hypomanic spectrum symptoms in patients with AN. Future work is needed to determine how mood spectrum psychopathology might impact the course and treatment of AN.

  2. The use of atlas registration and graph cuts for prostate segmentation in magnetic resonance images

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

    Korsager, Anne Sofie, E-mail: asko@hst.aau.dk; Østergaard, Lasse Riis; Fortunati, Valerio

    2015-04-15

    Purpose: An automatic method for 3D prostate segmentation in magnetic resonance (MR) images is presented for planning image-guided radiotherapy treatment of prostate cancer. Methods: A spatial prior based on intersubject atlas registration is combined with organ-specific intensity information in a graph cut segmentation framework. The segmentation is tested on 67 axial T{sub 2}-weighted MR images in a leave-one-out cross validation experiment and compared with both manual reference segmentations and with multiatlas-based segmentations using majority voting atlas fusion. The impact of atlas selection is investigated in both the traditional atlas-based segmentation and the new graph cut method that combines atlas andmore » intensity information in order to improve the segmentation accuracy. Best results were achieved using the method that combines intensity information, shape information, and atlas selection in the graph cut framework. Results: A mean Dice similarity coefficient (DSC) of 0.88 and a mean surface distance (MSD) of 1.45 mm with respect to the manual delineation were achieved. Conclusions: This approaches the interobserver DSC of 0.90 and interobserver MSD 0f 1.15 mm and is comparable to other studies performing prostate segmentation in MR.« less

  3. State transition of a non-Ohmic damping system in a corrugated plane.

    PubMed

    Lü, Kun; Bao, Jing-Dong

    2007-12-01

    Anomalous transport of a particle subjected to non-Ohmic damping of the power delta in a tilted periodic potential is investigated via Monte Carlo simulation of the generalized Langevin equation. It is found that the system exhibits two relative motion modes: the locked state and the running state. In an environment of sub-Ohmic damping (0=2D_(eff)(delta){t(delta_eff} . Our result shows that the effective power index delta_(eff) can be enhanced and is a nonmonotonic function of the temperature and the driving force. The mixture of the two motion modes also leads to a breakdown of the hysteresis loop of the mobility.

  4. Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans

    PubMed Central

    Lange, Karen I.; Heinrichs, Jeffrey; Cheung, Karen; Srayko, Martin

    2013-01-01

    Summary Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B′, B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo. PMID:23336080

  5. Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans.

    PubMed

    Lange, Karen I; Heinrichs, Jeffrey; Cheung, Karen; Srayko, Martin

    2013-01-15

    Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B', B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo.

  6. Conopeptide Vt3.1 preferentially inhibits BK potassium channels containing β4 subunits via electrostatic interactions.

    PubMed

    Li, Min; Chang, Shan; Yang, Longjin; Shi, Jingyi; McFarland, Kelli; Yang, Xiao; Moller, Alyssa; Wang, Chunguang; Zou, Xiaoqin; Chi, Chengwu; Cui, Jianmin

    2014-02-21

    BK channel β subunits (β1-β4) modulate the function of channels formed by slo1 subunits to produce tissue-specific phenotypes. The molecular mechanism of how the homologous β subunits differentially alter BK channel functions and the role of different BK channel functions in various physiologic processes remain unclear. By studying channels expressed in Xenopus laevis oocytes, we show a novel disulfide-cross-linked dimer conopeptide, Vt3.1 that preferentially inhibits BK channels containing the β4 subunit, which is most abundantly expressed in brain and important for neuronal functions. Vt3.1 inhibits the currents by a maximum of 71%, shifts the G-V relation by 45 mV approximately half-saturation concentrations, and alters both open and closed time of single channel activities, indicating that the toxin alters voltage dependence of the channel. Vt3.1 contains basic residues and inhibits voltage-dependent activation by electrostatic interactions with acidic residues in the extracellular loops of the slo1 and β4 subunits. These results suggest a large interaction surface between the slo1 subunit of BK channels and the β4 subunit, providing structural insight into the molecular interactions between slo1 and β4 subunits. The results also suggest that Vt3.1 is an excellent tool for studying β subunit modulation of BK channels and for understanding the physiological roles of BK channels in neurophysiology.

  7. Characterization of photosystem 1 chlorophyll a/b-binding apoprotein accumulation in developing soybean using type-specific antibodies

    NASA Technical Reports Server (NTRS)

    Henry, R. L.; Armbrust, T.; Gallegos, G.; Guikema, J. A.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    The structure and supramolecular assembly of the soybean photosystem 1 (PS 1) chlorophyll a/b-binding antenna (LHC 1) was examined. We identified the subunit composition of LHC 1 in soybean and followed the accumulation of individual subunits during light-induced assembly. We observed four LHC 1 subunits, at 23, 22, 21 and 20.5 kDa, obtained partial sequence information by amino-terminal sequence analysis, and classified the 20.5, 22, and 21 kDa subunits as being encoded by type I, II, and IV chlorophyll a/b binding protein genes, respectively. Antisera against LHC 1 subunits were used to follow the accumulation of individual subunits during the light-initiated transition from etioplast to chloroplast. Several points are noteworthy. First, monospecific antibody against the 22 kDa subunit decorated a 25 kDa peptide in etiolated tissue, which declined during maturation. This decline correlated with the light-induced appearance of mature 22 kDa peptide, suggesting a precursor/product relationship. Second, the same antibody identified a 22 kDa protein in mature corn, but not a larger band in etiolated corn, suggesting that LHC 1 accumulation is regulated differently between species before the onset of chlorophyll biosynthesis. Third, the mature 22 kDa subunit appeared somewhat later than the other LHC 1 peptides during greening, implying that this subunit is less intimately associated with the PS1 core than are the subunits appearing earlier in development.

  8. Comparable results of autologous and allogeneic haematopoietic stem cell transplantation for adults with Philadelphia-positive acute lymphoblastic leukaemia in first complete molecular remission: An analysis by the Acute Leukemia Working Party of the EBMT.

    PubMed

    Giebel, Sebastian; Labopin, Myriam; Potter, Michael; Poiré, Xavier; Sengeloev, Henrik; Socié, Gerard; Huynh, Anne; Afanasyev, Boris V; Schanz, Urs; Ringden, Olle; Kalhs, Peter; Beelen, Dietrich W; Campos, Antonio M; Masszi, Tamás; Canaani, Jonathan; Mohty, Mohamad; Nagler, Arnon

    2018-06-01

    Allogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction containing tyrosine kinase inhibitors (TKIs). We retrospectively compared results of myeloablative alloHSCT from either matched sibling donor (MSD) or unrelated donor (URD) with autologous (auto) HSCT for adults with Ph+ ALL in molecular remission, treated between 2007 and 2014. In univariate analysis, the incidence of relapse at 2 years was 47% after autoHSCT, 28% after MSD-HSCT and 19% after URD-HSCT (P = 0.0002). Respective rates of non-relapse mortality were 2%, 18%, and 22% (P = 0.001). The probabilities of leukaemia-free survival were 52%, 55% and 60% (P = 0.69), while overall survival rates were 70%, 70% and 69% (P = 0.58), respectively. In multivariate analysis, there was a trend towards increased risk of overall mortality after MSD-HSCT (hazard ratio [HR], 1.5, P = 0.12) and URD-HSCT (HR, 1.6, P = 0.08) when referred to autoHSCT. The use of total body irradiation (TBI)-based regimens was associated with reduced risk of relapse (HR, 0.65, P = 0.02) and overall mortality (HR, 0.67, P = 0.01). In the era of TKIs, outcomes of myeloablative autoHSCT and alloHSCT for patients with Ph+ ALL in first molecular remission are comparable. Therefore, autoHSCT appears to be an attractive treatment option potentially allowing for circumvention of alloHSCT sequelae. Irrespective of the type of donor, TBI-based regimens should be considered the preferable type of conditioning for Ph+ ALL. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. The Growth of Multi-Site Fatigue Damage in Fuselage Lap Joints

    NASA Technical Reports Server (NTRS)

    Piascik, Robert S.; Willard, Scott A.

    1999-01-01

    Destructive examinations were performed to document the progression of multi-site damage (MSD) in three lap joint panels that were removed from a full scale fuselage test article that was tested to 60,000 full pressurization cycles. Similar fatigue crack growth characteristics were observed for small cracks (50 microns to 10 mm) emanating from counter bore rivets, straight shank rivets, and 100 deg counter sink rivets. Good correlation of the fatigue crack growth data base obtained in this study and FASTRAN Code predictions show that the growth of MSD in the fuselage lap joint structure can be predicted by fracture mechanics based methods.

  10. Thermodynamic properties of semiconductor compounds studied based on Debye-Waller factors

    NASA Astrophysics Data System (ADS)

    Van Hung, Nguyen; Toan, Nguyen Cong; Ba Duc, Nguyen; Vuong, Dinh Quoc

    2015-08-01

    Thermodynamic properties of semiconductor compounds have been studied based on Debye-Waller factors (DWFs) described by the mean square displacement (MSD) which has close relation with the mean square relative displacement (MSRD). Their analytical expressions have been derived based on the statistical moment method (SMM) and the empirical many-body Stillinger-Weber potentials. Numerical results for the MSDs of GaAs, GaP, InP, InSb, which have zinc-blende structure, are found to be in reasonable agreement with experiment and other theories. This paper shows that an elements value for MSD is dependent on the binary semiconductor compound within which it resides.

  11. Automatic segmentation and classification of gestational sac based on mean sac diameter using medical ultrasound image

    NASA Astrophysics Data System (ADS)

    Khazendar, Shan; Farren, Jessica; Al-Assam, Hisham; Sayasneh, Ahmed; Du, Hongbo; Bourne, Tom; Jassim, Sabah A.

    2014-05-01

    Ultrasound is an effective multipurpose imaging modality that has been widely used for monitoring and diagnosing early pregnancy events. Technology developments coupled with wide public acceptance has made ultrasound an ideal tool for better understanding and diagnosing of early pregnancy. The first measurable signs of an early pregnancy are the geometric characteristics of the Gestational Sac (GS). Currently, the size of the GS is manually estimated from ultrasound images. The manual measurement involves multiple subjective decisions, in which dimensions are taken in three planes to establish what is known as Mean Sac Diameter (MSD). The manual measurement results in inter- and intra-observer variations, which may lead to difficulties in diagnosis. This paper proposes a fully automated diagnosis solution to accurately identify miscarriage cases in the first trimester of pregnancy based on automatic quantification of the MSD. Our study shows a strong positive correlation between the manual and the automatic MSD estimations. Our experimental results based on a dataset of 68 ultrasound images illustrate the effectiveness of the proposed scheme in identifying early miscarriage cases with classification accuracies comparable with those of domain experts using K nearest neighbor classifier on automatically estimated MSDs.

  12. Distributional behavior of diffusion coefficients obtained by single trajectories in annealed transit time model

    NASA Astrophysics Data System (ADS)

    Akimoto, Takuma; Yamamoto, Eiji

    2016-12-01

    Local diffusion coefficients in disordered systems such as spin glass systems and living cells are highly heterogeneous and may change over time. Such a time-dependent and spatially heterogeneous environment results in irreproducibility of single-particle-tracking measurements. Irreproducibility of time-averaged observables has been theoretically studied in the context of weak ergodicity breaking in stochastic processes. Here, we provide rigorous descriptions of equilibrium and non-equilibrium diffusion processes for the annealed transit time model, which is a heterogeneous diffusion model in living cells. We give analytical solutions for the mean square displacement (MSD) and the relative standard deviation of the time-averaged MSD for equilibrium and non-equilibrium situations. We find that the time-averaged MSD grows linearly with time and that the time-averaged diffusion coefficients are intrinsically random (irreproducible) even in the long-time measurements in non-equilibrium situations. Furthermore, the distribution of the time-averaged diffusion coefficients converges to a universal distribution in the sense that it does not depend on initial conditions. Our findings pave the way for a theoretical understanding of distributional behavior of the time-averaged diffusion coefficients in disordered systems.

  13. V-T theory for the self-intermediate scattering function in a monatomic liquid

    NASA Astrophysics Data System (ADS)

    Wallace, Duane C.; Chisolm, Eric D.; De Lorenzi-Venneri, Giulia

    2017-02-01

    In V-T theory the atomic motion is harmonic vibrations in a liquid-specific potential energy valley, plus transits, which move the system rapidly among the multitude of such valleys. In its first application to the self intermediate scattering function (SISF), V-T theory produced an accurate account of molecular dynamics (MD) data at all wave numbers q and time t. Recently, analysis of the mean square displacement (MSD) resolved a crossover behavior that was not observed in the SISF study. Our purpose here is to apply the more accurate MSD calibration to the SISF, and assess the results. We derive and discuss the theoretical equations for vibrational and transit contributions to the SISF. The time evolution is divided into three successive intervals: the vibrational interval when the vibrational contribution alone accurately accounts for the MD data; the crossover when the vibrational contribution saturates and the transit contribution becomes resolved; and the diffusive interval when the transit contribution alone accurately accounts for the MD data. The resulting theoretical error is extremely small at all q and t. V-T theory is compared to mode-coupling theories for the MSD and SISF, and to recent developments in Brownian motion experiments and theory.

  14. Atomic motion from the mean square displacement in a monatomic liquid

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

    Wallace, Duane C.; De Lorenzi-Venneri, Giulia; Chisolm, Eric D.

    V-T theory is constructed in the many-body Hamiltonian formulation, and is being developed as a novel approach to liquid dynamics theory. In this theory the liquid atomic motion consists of two contributions, normal mode vibrations in a single representative potential energy valley, and transits, which carry the system across boundaries between valleys. The mean square displacement time correlation function (the MSD) is a direct measure of the atomic motion, and our goal is to determine if the V-T formalism can produce a physically sensible account of this motion. We employ molecular dynamics (MD) data for a system representing liquid Na,more » and find the motion evolves in three successive time intervals: on the first 'vibrational' interval, the vibrational motion alone gives a highly accurate account of the MD data; on the second 'crossover' interval, the vibrational MSD saturates to a constant while the transit motion builds up from zero; on the third 'random walk' interval, the transit motion produces a purely diffusive random walk of the vibrational equilibrium positions. Furthermore, this motional evolution agrees with, and adds refinement to, the MSD atomic motion as described by current liquid dynamics theories.« less

  15. Atomic motion from the mean square displacement in a monatomic liquid

    DOE PAGES

    Wallace, Duane C.; De Lorenzi-Venneri, Giulia; Chisolm, Eric D.

    2016-04-08

    V-T theory is constructed in the many-body Hamiltonian formulation, and is being developed as a novel approach to liquid dynamics theory. In this theory the liquid atomic motion consists of two contributions, normal mode vibrations in a single representative potential energy valley, and transits, which carry the system across boundaries between valleys. The mean square displacement time correlation function (the MSD) is a direct measure of the atomic motion, and our goal is to determine if the V-T formalism can produce a physically sensible account of this motion. We employ molecular dynamics (MD) data for a system representing liquid Na,more » and find the motion evolves in three successive time intervals: on the first 'vibrational' interval, the vibrational motion alone gives a highly accurate account of the MD data; on the second 'crossover' interval, the vibrational MSD saturates to a constant while the transit motion builds up from zero; on the third 'random walk' interval, the transit motion produces a purely diffusive random walk of the vibrational equilibrium positions. Furthermore, this motional evolution agrees with, and adds refinement to, the MSD atomic motion as described by current liquid dynamics theories.« less

  16. A multiple maximum scatter difference discriminant criterion for facial feature extraction.

    PubMed

    Song, Fengxi; Zhang, David; Mei, Dayong; Guo, Zhongwei

    2007-12-01

    Maximum scatter difference (MSD) discriminant criterion was a recently presented binary discriminant criterion for pattern classification that utilizes the generalized scatter difference rather than the generalized Rayleigh quotient as a class separability measure, thereby avoiding the singularity problem when addressing small-sample-size problems. MSD classifiers based on this criterion have been quite effective on face-recognition tasks, but as they are binary classifiers, they are not as efficient on large-scale classification tasks. To address the problem, this paper generalizes the classification-oriented binary criterion to its multiple counterpart--multiple MSD (MMSD) discriminant criterion for facial feature extraction. The MMSD feature-extraction method, which is based on this novel discriminant criterion, is a new subspace-based feature-extraction method. Unlike most other subspace-based feature-extraction methods, the MMSD computes its discriminant vectors from both the range of the between-class scatter matrix and the null space of the within-class scatter matrix. The MMSD is theoretically elegant and easy to calculate. Extensive experimental studies conducted on the benchmark database, FERET, show that the MMSD out-performs state-of-the-art facial feature-extraction methods such as null space method, direct linear discriminant analysis (LDA), eigenface, Fisherface, and complete LDA.

  17. Pain, fatigue, function and participation among long-term manual wheelchair users partnered with a mobility service dog.

    PubMed

    Vincent, Claude; Gagnon, Dany H; Dumont, Frédéric

    2017-11-20

    To assess the effects of a mobility service dog (MSD) on pain, fatigue, wheelchair-related functional tasks, participation and satisfaction among manual wheelchair users over a nine-month period. A longitudinal study with repeated assessment times before and three, six and nine months after intervention was achieved. Intervention consisted in partnering each participant with a MSD. The setting is a well-established provincial service dog training school and participants homes. A convenience sample of 24 long-term manual wheelchair users with a spinal cord injury was involved. Outcome measures were: Wheelchair User's Shoulder Pain Index (WUSPI), Rate of Perceived Exertion (RPE), vitality scale from the SF-36, grip strength, Wheelchair Skills Test (WST), Canadian Occupational Performance Measure (COPM), Reintegration to Normal Living Index (RNLI), Life Space Assessment, Psychosocial Impact of Assistive Devices Scale (PIADS) and Quebec User Evaluation of Satisfaction with assistive Technology (QUEST 2.0). Shoulder and wrist pain as well as fatigue decreased significantly over time with the use of a MSD as evidenced by scores from WUSPI, RPE and SF-36 (feeling less worn out). Manual wheelchair propulsion skills (steep slopes, soft surfaces and thresholds) improved significantly over time as confirmed by the WST. Participation increased significantly over time as revealed by the COPM (for five occupations) and the RNLI (for five items). Satisfaction with the MSD was high over time (QUEST: nine items) and with a high positive psychosocial impact (PIADS: 10 items). MSD represents a valuable mobility assistive technology option for manual wheelchair users. IMPLICATIONS FOR REHABILITATION   For manual wheelchair users partenered with mobility service dog  • Shoulder pain and fatigue significantly decreased and continued to decrease between the third and sixth month and the ninth month.   • Performance with propelling the wheelchair up steep slopes increased from 41 to 88% and on soft surfaces increased from 53 to 100% after 3 months, respectively.   • Occupational performance satisfaction was significantly increased for mobility in relation with the transfers, navigating in a natural environment and picking up objects.   • High satisfaction towards psychosocial competency, psychosocial adequacy and self-esteem were reported at months three, six and nine.

  18. Molecular dynamics simulation of imidazolium-based ionic liquids. I. Dynamics and diffusion coefficient.

    PubMed

    Kowsari, M H; Alavi, Saman; Ashrafizaadeh, Mahmud; Najafi, Bijan

    2008-12-14

    Molecular dynamics simulations are used to study the dynamics and transport properties of 12 room-temperature ionic liquids of the 1-alkyl-3-methylimidazolium [amim](+) (alkyl = methyl, ethyl, propyl, and butyl) family with PF(6)(-), NO(3)(-), and Cl(-) counterions. The explicit atom transferable force field of Canongia Lopes et al. [J. Phys. Chem. B 108, 2038 (2004)] is used in the simulations. In this first part, the dynamics of the ionic liquids are characterized by studying the mean-square displacement (MSD) and the velocity autocorrelation function (VACF) for the centers of mass of the ions at 400 K. Trajectory averaging was employed to evaluate the diffusion coefficients at two temperatures from the linear slope of MSD(t) functions in the range of 150-300 ps and from the integration of the VACF(t) functions at 400 K. Detailed comparisons are made between the diffusion results from the MSD and VACF methods. The diffusion coefficients from the integration of the VACFs are closer to experimental values than the diffusion coefficients calculated from the slope of MSDs. Both methods can show good agreement with experiment in predicting relative trends in the diffusion coefficients and determining the role of the cation and anion structures on the dynamical behavior of this family of ionic liquids. The MSD and self-diffusion of relatively heavier imidazolium cations are larger than those of the lighter anions from the Einstein results, except for the case of [bmim][Cl]. The cationic transference number generally decreases with temperature, in good agreement with experiments. For the same anion, the cationic transference numbers decrease with increasing length of the alkyl chain, and for the same cation, the trends in the cationic transference numbers are [NO(3)](-) < [Cl](-) < [PF(6)](-). The trends in the diffusion coefficient in the series of cations with identical anions are [emim](+) > [pmim](+) > [bmim](+) and those for anions with identical cations are [NO(3)](-) > [PF(6)](-) > [Cl](-). The [dmim](+) has a relatively low diffusion coefficient due to its symmetric structure and good packing in the liquid phase. The major factor for determining the magnitude of the self-diffusion is the geometric shape of the anion of the ionic liquid. Other important factors are the ion size and the charge delocalization in the anion.

  19. The NMDA receptor NR2A subunit regulates proliferation of MKN45 human gastric cancer cells

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

    Watanabe, Kanako; Department of Anesthesiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501; Kanno, Takeshi

    2008-03-07

    The present study investigated proliferation of MKN28 and MKN45 human gastric cancer cells regulated by the N-methyl-D-aspartate (NMDA) receptor subunit. The NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5) inhibited proliferation of MKN45 cells, but not MKN28 cells. Of the NMDA subunits such as NR1, NR2 (2A, 2B, 2C, and 2D), and NR3 (3A and 3B), all the NMDA subunit mRNAs except for the NR2B subunit mRNA were expressed in both MKN28 and MKN45 cells. MKN45 cells were characterized by higher expression of the NR2A subunit mRNA and lower expression of the NR1 subunit mRNA, but MKN28 otherwise by higher expression ofmore » the NR1 subunit mRNA and lower expression of the NR2A subunit mRNA. MKN45 cell proliferation was also inhibited by silencing the NR2A subunit-targeted gene. For MKN45 cells, AP5 or knocking-down the NR2A subunit increased the proportion of cells in the G{sub 1} phase of cell cycling and decreased the proportion in the S/G{sub 2} phase. The results of the present study, thus, suggest that blockage of NMDA receptors including the NR2A subunit suppresses MKN45 cell proliferation due to cell cycle arrest at the G{sub 1} phase; in other words, the NR2A subunit promotes MKN45 cell proliferation by accelerating cell cycling.« less

  20. Predictors of diarrheal mortality and patterns of caregiver health seeking behavior in in Karachi, Pakistan

    PubMed Central

    Qamar, Farah Naz; Zaman, Umber; Quadri, Farheen; Khan, Asia; Shaikh, Babar Tasneem; Azam, Iqbal; Nasrin, Dilruba; Kotloff, Karen; Levine, Myron; Brown, Nick; Zaidi, Anita K M

    2016-01-01

    Background Pakistan is unfortunately among the five countries that contributed to the most deaths due to diarrhea and pneumonia in 2010. To explore factors associated with diarrheal deaths we assessed care–seeking behavior and other predictors of diarrhea–related mortality in children in selected low–income peri–urban communities of Karachi, Pakistan. Methods A mixed methods study (qualitative and quantitative) using matched case–control design and focus group discussions with parents of children with moderate to severe diarrhea (MSD) was undertaken. Cases were children  <5 years of age who died within 60 days of developing an episode of MSD. Controls were age–matched children who survived after 60 days of an episode of MSD. Demographic, clinical, and care–related behavioral predictors of mortality were assessed. Conditional logistic regression was performed, matched adjusted odds ratios (mOR) are reported. Results Parents of 77 cases and 154 controls were interviewed. Cases were less likely to receive appropriate care compared to controls (mOR = 0.2, 95% confidence interval (CI) 0.05–0.91). Refusal for hospital admission (OR = 8.9, 95% CI 2.6–30.8), and delays in reaching the health facility (OR = 3.6, 95% CI 1.0–12.9) were significant independent predictors of mortality. We found strong beliefs in traditional and spiritual healing in the population; use of both modern and traditional/spiritual treatments concurrently was common. Conclusion Appropriate care seeking behavior predicts survival in children with diarrhea in Pakistan. There is a complex belief system relating to traditional and standard therapies. Health education for appropriate health care seeking should be implemented in order to achieve a substantial decline in diarrheal disease mortality in Pakistan. PMID:27606059

  1. Statistical analysis of quiet stance sway in 2-D

    PubMed Central

    DiZio, Paul; Lackner, James R.

    2014-01-01

    Subjects exposed to a rotating environment that perturbs their postural sway show adaptive changes in their voluntary spatially directed postural motion to restore accurate movement paths but do not exhibit any obvious learning during passive stance. We have found, however, that a variable known to characterize the degree of stochasticity in quiet stance can also reveal subtle learning phenomena in passive stance. We extended Chow and Collins (Phys Rev E 52(1):909–912, 1995) one-dimensional pinned-polymer model (PPM) to two dimensions (2-D) and then evaluated the model’s ability to make analytical predictions for 2-D quiet stance. To test the model, we tracked center of mass and centers of foot pressures, and compared and contrasted stance sway for the anterior–posterior versus medio-lateral directions before, during, and after exposure to rotation at 10 rpm. Sway of the body during rotation generated Coriolis forces that acted perpendicular to the direction of sway. We found significant adaptive changes for three characteristic features of the mean square displacement (MSD) function: the exponent of the power law defined at short time scales, the proportionality constant of the power law, and the saturation plateau value defined at longer time scales. The exponent of the power law of MSD at a short time scale lies within the bounds predicted by the 2-D PPM. The change in MSD during exposure to rotation also had a power-law exponent in the range predicted by the theoretical model. We discuss the Coriolis force paradigm for studying postural and movement control and the applicability of the PPM model in 2-D for studying postural adaptation. PMID:24477760

  2. Impact of Colic Pain as a Significant Factor for Predicting the Stone Free Rate of One-Session Shock Wave Lithotripsy for Treating Ureter Stones: A Bayesian Logistic Regression Model Analysis

    PubMed Central

    Chung, Doo Yong; Cho, Kang Su; Lee, Dae Hun; Han, Jang Hee; Kang, Dong Hyuk; Jung, Hae Do; Kown, Jong Kyou; Ham, Won Sik; Choi, Young Deuk; Lee, Joo Yong

    2015-01-01

    Purpose This study was conducted to evaluate colic pain as a prognostic pretreatment factor that can influence ureter stone clearance and to estimate the probability of stone-free status in shock wave lithotripsy (SWL) patients with a ureter stone. Materials and Methods We retrospectively reviewed the medical records of 1,418 patients who underwent their first SWL between 2005 and 2013. Among these patients, 551 had a ureter stone measuring 4–20 mm and were thus eligible for our analyses. The colic pain as the chief complaint was defined as either subjective flank pain during history taking and physical examination. Propensity-scores for established for colic pain was calculated for each patient using multivariate logistic regression based upon the following covariates: age, maximal stone length (MSL), and mean stone density (MSD). Each factor was evaluated as predictor for stone-free status by Bayesian and non-Bayesian logistic regression model. Results After propensity-score matching, 217 patients were extracted in each group from the total patient cohort. There were no statistical differences in variables used in propensity- score matching. One-session success and stone-free rate were also higher in the painful group (73.7% and 71.0%, respectively) than in the painless group (63.6% and 60.4%, respectively). In multivariate non-Bayesian and Bayesian logistic regression models, a painful stone, shorter MSL, and lower MSD were significant factors for one-session stone-free status in patients who underwent SWL. Conclusions Colic pain in patients with ureter calculi was one of the significant predicting factors including MSL and MSD for one-session stone-free status of SWL. PMID:25902059

  3. Development and validation of panoptic Meso scale discovery assay to quantify total systemic interleukin-6

    PubMed Central

    Chaturvedi, Shalini; Siegel, Derick; Wagner, Carrie L; Park, Jaehong; van de Velde, Helgi; Vermeulen, Jessica; Fung, Man-Cheong; Reddy, Manjula; Hall, Brett; Sasser, Kate

    2015-01-01

    Aim Interleukin-6 (IL-6), a multifunctional cytokine, exists in several forms ranging from a low molecular weight (MW 20–30 kDa) non-complexed form to high MW (200–450 kDa), complexes. Accurate baseline IL-6 assessment is pivotal to understand clinical responses to IL-6-targeted treatments. Existing assays measure only the low MW, non-complexed IL-6 form. The present work aimed to develop a validated assay to measure accurately total IL-6 (complexed and non-complexed) in serum or plasma as matrix in a high throughput and easily standardized format for clinical testing. Methods Commercial capture and detection antibodies were screened against humanized IL-6 and evaluated in an enzyme-linked immunosorbent assay format. The best antibody combinations were screened to identify an antibody pair that gave minimum background and maximum recovery of IL-6 in the presence of 100% serum matrix. A plate-based total IL-6 assay was developed and transferred to the Meso Scale Discovery (MSD) platform for large scale clinical testing. Results The top-performing antibody pair from 36 capture and four detection candidates was validated on the MSD platform. The lower limit of quantification in human serum samples (n = 6) was 9.77 pg l–1, recovery ranged from 93.13–113.27%, the overall pooled coefficients of variation were 20.12% (inter-assay) and 8.67% (intra-assay). High MW forms of IL-6, in size fractionated serum samples from myelodysplastic syndrome and rheumatoid arthritis patients, were detected by the assay but not by a commercial kit. Conclusion This novel panoptic (sees all forms) IL-6 MSD assay that measures both high and low MW forms may have clinical utility. PMID:25847183

  4. Evaluation of Musculoskeletal Disorders in Dentists and Application of DMAIC Technique to Improve the Ergonomics at Dental Clinics and Meta-Analysis of Literature.

    PubMed

    Bedi, H S; Moon, Ninad Joshirao; Bhatia, Vineet; Sidhu, Gagandeep Kaur; Khan, Nadia

    2015-06-01

    Musculoskeletal disorders (MSD) result in discomfort, pain and illness that can result in disruption or impairment of dental practice. A cross-sectional study consisting of 60 dentists was carried out to determine musculoskeletal work related pain in major cities of Northern India. The study was planned in two phases. In the first phase, the subjects were given questionnaire related to the musculoskeletal pain happened over the last twelve months. In the second phase of study, improvement was carried out by recommending the subjects to implement ergonomics at their workplace. After three months subjects were again approached and given questionnaire about the musculoskeletal disorders. DMAIC (define, measure, analyse, improve and control) methodology of six sigma strategy was used to access the MSDs. Chi-square test was used for the analysis and a p-value of less than or equal to 0.05 was considered statistically significant. The overall prevalence of musculoskeletal problems in the present study was found to be 68.3%. After three months only 23 respondents applied ergonomics at their work place, prevalence of pain was reduced in neck from 47.8% to 21.7% out of total 23 respondents, shoulder pain 39.1% to 17.3%, pain in elbows from 26% to 21.7%, as well as in other locomotor organs. The p-value was significant with p <0.05. MSD represents a major occupational health issue for dentists in India as well as worldwide and result revealed necessitates the need of workshops to create awareness of ergonomics as effective measures for reducing MSD among dentists.

  5. Evaluation of Musculoskeletal Disorders in Dentists and Application of DMAIC Technique to Improve the Ergonomics at Dental Clinics and Meta-Analysis of Literature

    PubMed Central

    Bedi, H.S.; Moon, Ninad Joshirao; Bhatia, Vineet; Khan, Nadia

    2015-01-01

    Introduction Musculoskeletal disorders (MSD) result in discomfort, pain and illness that can result in disruption or impairment of dental practice. Materials and Methods A cross-sectional study consisting of 60 dentists was carried out to determine musculoskeletal work related pain in major cities of Northern India. The study was planned in two phases. In the first phase, the subjects were given questionnaire related to the musculoskeletal pain happened over the last twelve months. In the second phase of study, improvement was carried out by recommending the subjects to implement ergonomics at their workplace. After three months subjects were again approached and given questionnaire about the musculoskeletal disorders. DMAIC (define, measure, analyse, improve and control) methodology of six sigma strategy was used to access the MSDs. Chi-square test was used for the analysis and a p-value of less than or equal to 0.05 was considered statistically significant. Results The overall prevalence of musculoskeletal problems in the present study was found to be 68.3%. After three months only 23 respondents applied ergonomics at their work place, prevalence of pain was reduced in neck from 47.8% to 21.7% out of total 23 respondents, shoulder pain 39.1% to 17.3%, pain in elbows from 26% to 21.7%, as well as in other locomotor organs. The p-value was significant with p <0.05. Conclusion MSD represents a major occupational health issue for dentists in India as well as worldwide and result revealed necessitates the need of workshops to create awareness of ergonomics as effective measures for reducing MSD among dentists. PMID:26266205

  6. Sequence and properties of HMW subunit 1Bx20 from pasta wheat (Triticum durum) which is associated with poor end use properties.

    PubMed

    Shewry, P R; Gilbert, S M; Savage, A W J; Tatham, A S; Wan, Y-F; Belton, P S; Wellner, N; D'Ovidio, R; Békés, F; Halford, N G

    2003-02-01

    The gene encoding high-molecular-weight (HMW) subunit 1Bx20 was isolated from durum wheat cv. Lira. It encodes a mature protein of 774 amino acid residues with an M(r) of 83,913. Comparison with the sequence of subunit 1Bx7 showed over 96% identity, the main difference being the substitution of two cysteine residues in the N-terminal domain of subunit 1Bx7 with tyrosine residues in 1Bx20. Comparison of the structures and stabilities of the two subunits purified from wheat using Fourier-transform infra-red and circular dichroism spectroscopy showed no significant differences. However, incorporation of subunit 1Bx7 into a base flour gave increased dough strength and stability measured by Mixograph analysis, while incorporation of subunit 1Bx20 resulted in small positive or negative effects on the parameters measured. It is concluded that the different effects of the two subunits could relate to the differences in their cysteine contents, thereby affecting the cross-linking and hence properties of the glutenin polymers.

  7. Numerical Analysis of Permittivity with Loss in Isotropic Binary Composites

    DTIC Science & Technology

    1992-06-01

    even) 8080 Sqvi = 1/4 of squate whose edges are: Lszi*Lszi 8090 Bilv = the number of nodes between bilayers z={l,2 3,4 5,6 8100 INTEGER Lyri,Swi,Ovri...610 1 COMmon Memory 620 COM /Info/ INTEGER Dsrc,Kond,Ptrn,Knj, Spcs ,Meth,Back,Sgj,Svr,Fln$[80J,Msd$[60],COMPL...Periodic or wrap around 780 ! Ptrn = Pixel fill pattern choice 790 ! Knj = permittivity conjugation, 0=none l=alternating 2=averaged 800 1 Spcs = number

  8. Decreased surface expression of the δ subunit of the GABAA receptor contributes to reduced tonic inhibition in dentate granule cells in a mouse model of fragile X syndrome.

    PubMed

    Zhang, Nianhui; Peng, Zechun; Tong, Xiaoping; Lindemeyer, A Kerstin; Cetina, Yliana; Huang, Christine S; Olsen, Richard W; Otis, Thomas S; Houser, Carolyn R

    2017-11-01

    While numerous changes in the GABA system have been identified in models of Fragile X Syndrome (FXS), alterations in subunits of the GABA A receptors (GABA A Rs) that mediate tonic inhibition are particularly intriguing. Considering the key role of tonic inhibition in controlling neuronal excitability, reduced tonic inhibition could contribute to FXS-associated disorders such as hyperactivity, hypersensitivity, and increased seizure susceptibility. The current study has focused on the expression and function of the δ subunit of the GABA A R, a major subunit involved in tonic inhibition, in granule cells of the dentate gyrus in the Fmr1 knockout (KO) mouse model of FXS. Electrophysiological studies of dentate granule cells revealed a marked, nearly four-fold, decrease in tonic inhibition in the Fmr1 KO mice, as well as reduced effects of two δ subunit-preferring pharmacological agents, THIP and DS2, supporting the suggestion that δ subunit-containing GABA A Rs are compromised in the Fmr1 KO mice. Immunohistochemistry demonstrated a small but statistically significant decrease in δ subunit labeling in the molecular layer of the dentate gyrus in Fmr1 KO mice compared to wildtype (WT) littermates. The discrepancy between the large deficits in GABA-mediated tonic inhibition in granule cells in the Fmr1 KO mice and only modest reductions in immunolabeling of the δ subunit led to studies of surface expression of the δ subunit. Cross-linking experiments followed by Western blot analysis demonstrated a small, non-significant decrease in total δ subunit protein in the hippocampus of Fmr1 KO mice, but a four-fold decrease in surface expression of the δ subunit in these mice. No significant changes were observed in total or surface expression of the α4 subunit protein, a major partner of the δ subunit in the forebrain. Postembedding immunogold labeling for the δ subunit demonstrated a large, three-fold, decrease in the number of symmetric synapses with immunolabeling at perisynaptic locations in Fmr1 KO mice. While α4 immunogold particles were also reduced at perisynaptic locations in the Fmr1 KO mice, the labeling was increased at synaptic sites. Together these findings suggest that, in the dentate gyrus, altered surface expression of the δ subunit, rather than a decrease in δ subunit expression alone, could be limiting δ subunit-mediated tonic inhibition in this model of FXS. Finding ways to increase surface expression of the δ subunit of the GABA A R could be a novel approach to treatment of hyperexcitability-related alterations in FXS. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Effects of fumonisin B1 and mycotoxin binders on growth performance, tibia characteristics, gut physiology, and stress indicators in broiler chickens raised in different stocking densities.

    PubMed

    Lee, S; Kim, D-H; Keum, M-C; Han, E; An, B-K; Chang, H-H; Choi, Y-H; Moon, B-H; Lee, K-W

    2018-03-01

    The present study was carried out to investigate the effects of stocking density, fumonisin B1 (FB), and mycotoxin binder (TB) on growth performance, bone quality, physiological stress indicators, and gut health in broiler chickens. Day-old Ross 308 male broiler chicks (n = 1,440/experiment) were randomly allocated to 72 floor pens in a 3 × 2 × 2 factorial arrangement, using 3 stocking densities (12.5 birds/m2 [HSD], 10 birds/m2 [MSD], or 7.5 birds/m2 [LSD]), 2 levels of purified FB (0 or 10 ppm), and 2 levels of TB (0 or 0.2%). Each treatment had 6 replicates (n = 6/treatment) and experiments lasted 34 days. All data were analyzed using 3-way ANOVA with stocking density level, FB, and TB as main factors. Body weight gain and feed intake were lower (P < 0.05) in broilers kept at HSD and MSD compared to LSD-housed counterparts. Birds fed an FB-contaminated diet exhibited a higher feed-to-gain ratio compared with those fed an FB-free diet (P < 0.05). None of the treatments affected intestinal morphology or ileal secretory immunoglobulin A levels. Stocking density affected tibia breaking strength (P < 0.05), which was lower in chickens housed at HSD compared with LSD-housed chickens. The heterophil/lymphocyte ratio (H/L ratio) was elevated (P < 0.05) in HSD and MSD groups compared with the LSD group. Serum nitric oxide (NO) levels were elevated (P < 0.05) in chickens fed the FB-contaminated diet compared with the control diet-fed counterparts. Significant interaction (P < 0.05) between FB and TB on serum NO levels was noted. In summary, increasing stocking density lowered growth performance and bone quality, but increased the H/L ratio. Dietary TB did not affect FB-induced increases in the feed-to-gain ratio. No interaction was observed between stocking density and FB for the measured variables.

  10. Design of Work Facilities for Reducing Musculoskeletal Disorders Risk in Paper Pallet Assembly Station

    NASA Astrophysics Data System (ADS)

    Mardi Safitri, Dian; Arfi Nabila, Zahra; Azmi, Nora

    2018-03-01

    Musculoskeletal Disorders (MSD) is one of the ergonomic risks due to manual activity, non-neutral posture and repetitive motion. The purpose of this study is to measure risk and implement ergonomic interventions to reduce the risk of MSD on the paper pallet assembly work station. Measurements to work posture are done by Ovako Working Posture Analysis (OWAS) methods and Rapid Entire Body Assessment (REBA) method, while the measurement of work repetitiveness was using Strain Index (SI) method. Assembly processes operators are identified has the highest risk level. OWAS score, Strain Index, and REBA values are 4, 20.25, and 11. Ergonomic improvements are needed to reduce that level of risk. Proposed improvements will be developed using the Quality Function Deployment (QFD) method applied with Axiomatic House of Quality (AHOQ) and Morphological Chart. As the result, risk level based on OWAS score & REBA score turn out from 4 & 11 to be 1 & 2. Biomechanics analysis of the operator also shows the decreasing values for L4-L5 moment, compression, joint shear, and joint moment strength.

  11. Inherent conformational flexibility of F1-ATPase α-subunit.

    PubMed

    Hahn-Herrera, Otto; Salcedo, Guillermo; Barril, Xavier; García-Hernández, Enrique

    2016-09-01

    The core of F1-ATPase consists of three catalytic (β) and three noncatalytic (α) subunits, forming a hexameric ring in alternating positions. A wealth of experimental and theoretical data has provided a detailed picture of the complex role played by catalytic subunits. Although major conformational changes have only been seen in β-subunits, it is clear that α-subunits have to respond to these changes in order to be able to transmit information during the rotary mechanism. However, the conformational behavior of α-subunits has not been explored in detail. Here, we have combined unbiased molecular dynamics (MD) simulations and calorimetrically measured thermodynamic signatures to investigate the conformational flexibility of isolated α-subunits, as a step toward deepening our understanding of its function inside the α3β3 ring. The simulations indicate that the open-to-closed conformational transition of the α-subunit is essentially barrierless, which is ideal to accompany and transmit the movement of the catalytic subunits. Calorimetric measurements of the recombinant α-subunit from Geobacillus kaustophilus indicate that the isolated subunit undergoes no significant conformational changes upon nucleotide binding. Simulations confirm that the nucleotide-free and nucleotide-bound subunits show average conformations similar to that observed in the F1 crystal structure, but they reveal an increased conformational flexibility of the isolated α-subunit upon MgATP binding, which might explain the evolutionary conserved capacity of α-subunits to recognize nucleotides with considerable strength. Furthermore, we elucidate the different dependencies that α- and β-subunits show on Mg(II) for recognizing ATP. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. NASA airframe structural integrity program

    NASA Technical Reports Server (NTRS)

    Harris, Charles E.

    1991-01-01

    NASA has initiated a research program with the long-term objective of supporting the aerospace industry in addressing issues related to the aging commercial transport fleet. The interdisciplinary program combines advanced fatigue crack growth prediction methodology with innovative nondestructive examination technology with the focus on multi-site damage (MSD) at riveted connections. A fracture mechanics evaluation of the concept of pressure proof testing the fuselage to screen for MSD has been completed. Also, a successful laboratory demonstration of the ability of the thermal flux method to detect disbonds at riveted lap splice joints has been conducted. All long-term program elements have been initiated and the plans for the methodology verification program are being coordinated with the airframe manufacturers.

  13. NASA airframe structural integrity program

    NASA Technical Reports Server (NTRS)

    Harris, Charles E.

    1990-01-01

    NASA initiated a research program with the long-term objective of supporting the aerospace industry in addressing issues related to the aging of the commercial transport fleet. The program combines advanced fatigue crack growth prediction methodology with innovative nondestructive examination technology with the focus on multi-stage damage (MSD) at rivited connections. A fracture mechanics evaluation of the concept of pressure proof testing the fuselage to screen for MSD was completed. A successful laboratory demonstration of the ability of the thermal flux method to detect disbonds at rivited lap splice joints was conducted. All long-term program elements were initiated, and the plans for the methodology verification program are being coordinated with the airframe manufacturers.

  14. Subunit stoichiometry of the CNG channel of rod photoreceptors.

    PubMed

    Weitz, Dietmar; Ficek, Nicole; Kremmer, Elisabeth; Bauer, Paul J; Kaupp, U Benjamin

    2002-12-05

    Cyclic nucleotide-gated (CNG) channels play a central role in the conversion of sensory stimuli into electrical signals. CNG channels form heterooligomeric complexes built of A and B subunits. Here, we study the subunit stoichiometry of the native rod CNG channel by chemical crosslinking. The apparent molecular weight (M(w)) of each crosslink product was determined by SDS-PAGE, and its composition was analyzed by Western blotting using antibodies specific for the A1 or B1 subunit. The number of crosslink products and their M(w) as well as the immunological identification of A1 and B1 subunits in the crosslink products led us to conclude that the native rod CNG channel is a tetramer composed of three A1 and one B1 subunit. This is an example of violation of symmetry in tetrameric channels.

  15. Down regulated expression of the beta1 subunit of the big-conductance Ca2+ sensitive K+ channel in sphincter of Oddi cells from rabbits fed with a high cholesterol diet.

    PubMed

    Du, Pang; Cui, Guang-Bin; Wang, Ya-Rong; Zhang, Xiao-Yong; Ma, Ke-Jun; Wei, Jing-Guo

    2006-12-01

    Hypercholesterolemia, which is closely related to gallbladder bile stasis, can cause sphincter of Oddi dysfunction (SOD) by increasing the tension of sphincter of Oddi (SO). Intracellular calcium ion concentration ([Ca(2+)](i)) could influence the tension of SO. The beta1 subunit of the big-conductance Ca(2+) sensitive K(+) channel (BK(Ca)) can enhance the sensitivity of the BK(Ca) channel to [Ca(2+)](i). Absence and decline of the BKCa channel subunit beta1 could lead to many diseases. However, the relationship between hypercholesterolemia and the expression of beta1 subunit is not well understood. In this study, we successfully expressed and purified the rabbit BK(Ca) beta1 subunit protein and prepared its polyclonal antibody. The specificity of the prepared antibody was determined by Western blotting. A SOD rabbit model induced by a high cholesterol diet was established and the expression of the beta1 subunit of SO was determined by immunohistochemical staining and western blotting. Compared with the controls, our results demonstrated that hypercholesterolemia could decrease the expression of the beta1 subunit in the SO cells from rabbits. This indicates that lower expression of BKCa channel beta1 subunit might induce SOD.

  16. A comparison of an ATPase from the archaebacterium Halobacterium saccharovorum with the F1 moiety from the Escherichia coli ATP Synthase

    NASA Technical Reports Server (NTRS)

    Stan-Lotter, Helga; Hochstein, Lawrence I.

    1989-01-01

    A purified ATPase associated with membranes from Halobacterium saccharovorum was compared with the F sub 1 moiety from the Escherichia coli ATP Synthase. The halobacterial enzyme was composed of two major (I and II) and two minor subunits (III and IV), whose molecular masses were 87 kDa, 60 kDa, 29 kDa, and 20 kDa, respectively. The isoelectric points of these subunits ranged from 4.1 to 4.8, which in the case of the subunits I and II was consistent with the presence of an excess of acidic amino acids (20 to 22 Mol percent). Peptide mapping of sodium dodecylsulfate-denatured subunits I and II showed no relationship between the primary structures of the individual halobacterial subunits or similarities to the subunits of the F sub 1 ATPase (EC 3.6.1.34) from E. coli. Trypsin inactivation of the halobacterial ATPase was accompanied by the partial degradation of the major subunits. This observation, taken in conjunction with molecular masses of the subunits and the native enzyme, was consistent with the previously proposed stoichiometry of 2:2:1:1. These results suggest that H. saccharovorum, and possibly, Halobacteria in general, possess an ATPase which is unlike the ubiquitous F sub o F sub 1 - ATP Synthase.

  17. Clinical validation of a point-of-care multiplexed in vitro immunoassay using monoclonal antibodies (the MSD influenza test) in four hospitals in Vietnam.

    PubMed

    van Doorn, H Rogier; Kinh, Nguyen van; Tuan, Ha Manh; Tuan, Tran Anh; Minh, Ngo Ngoc Quang; Bryant, Juliet E; Hang, Vu thi Ty; Uyen, Le thi Tham; Thinh, Le Quoc; Anh, Tran thi Ngoc; Lan, Nguyen Phu Huong; Trung, Nguyen Vu; Taylor, Walter; Merson, Laura; Wertheim, Heiman F L; Farrar, Jeremy; Wolbers, Marcel; Chau, Nguyen van Vinh; de Jong, Menno D

    2012-05-01

    Point-of-care (POC) diagnostic tests for influenza can considerably shorten the time to clinical decision making. An investigational POC test based on a multiplexed immunoassay was developed by Meso Scale Diagnostics, LLC (MSD), with the objective to make a more sensitive rapid test that can also subtype influenza A viruses (1977 H1, H3, and H5). Between February and November 2010, we conducted a prospective multicenter study at four hospitals in Vietnam and compared the performance of this test to that of the WHO/CDC real-time reverse transcriptase PCR (RT-PCR) on nasal and throat swab specimens from patients presenting with influenza-like illness. Five hundred sixty-three adults and children with a median age of 25 months were enrolled. Sensitivity and specificity of the test with combined results from nasal and throat swab samples were 74.0% (131/177) and 99.7% (351/352), respectively, compared to RT-PCR. The POC test was as sensitive for influenza virus B as for influenza virus A (74.4% [64/86] versus 73.6% [67/91]). The positivity rate was associated with lower cycle threshold values (a marker for higher viral loads), sample type (73.6% for nasal swab versus 52.4% for throat swab), and younger age. A total of 210 (18.7%) out of 1,126 MSD tests failed, and for 34 (6%) of patients, both test samples failed (these were excluded from the performance analysis). Subtyping could be assessed only for influenza virus A/H3N2, as 1977 H1N1 was not circulating at the time and no H5N1-infected patients were enrolled, and was successful only in 9/54 patients infected with H3 influenza virus who had a positive POC test result for influenza virus A. This novel POC test provided highly sensitive detection of influenza viruses A and B compared to the reported sensitivities of other rapid tests. However, 18.7% of tests failed for technical reasons and subtyping for H3 was poor. Drawbacks to the technology include the requirement for a dedicated reader instrument and the need for continual updating of subtyping antibodies within the test array.

  18. β-Subunits of the SnRK1 Complexes Share a Common Ancestral Function Together with Expression and Function Specificities; Physical Interaction with Nitrate Reductase Specifically Occurs via AKINβ1-Subunit1[C][OA

    PubMed Central

    Polge, Cécile; Jossier, Mathieu; Crozet, Pierre; Gissot, Lionel; Thomas, Martine

    2008-01-01

    The SNF1/AMPK/SnRK1 kinases are evolutionary conserved kinases involved in yeast, mammals, and plants in the control of energy balance. These heterotrimeric enzymes are composed of one α-type catalytic subunit and two γ- and β-type regulatory subunits. In yeast it has been proposed that the β-type subunits regulate both the localization of the kinase complexes within the cell and the interaction of the kinases with their targets. In this work, we demonstrate that the three β-type subunits of Arabidopsis (Arabidopsis thaliana; AKINβ1, AKINβ2, and AKINβ3) restore the growth phenotype of the yeast sip1Δsip2Δgal83Δ triple mutant, thus suggesting the conservation of an ancestral function. Expression analyses, using AKINβ promoter∷β-glucuronidase transgenic lines, reveal different and specific patterns of expression for each subunit according to organs, developmental stages, and environmental conditions. Finally, our results show that the β-type subunits are involved in the specificity of interaction of the kinase with the cytosolic nitrate reductase. Together with previous cell-free phosphorylation data, they strongly support the proposal that nitrate reductase is a real target of SnRK1 in the physiological context. Altogether our data suggest the conservation of ancestral basic function(s) together with specialized functions for each β-type subunit in plants. PMID:18768910

  19. V-T theory for the Self-Intermediate Scattering Function in a Monatomic Liquid

    DOE PAGES

    Wallace, Duane C.; Chisolm, Eric D.; De Lorenzi-Venneri, Giulia

    2016-12-12

    In V-T theory the atomic motion is harmonic vibrations in a liquid-specific potential energy valley, plus transits, which move the system rapidly among the multitude of such valleys. Here, in its first application to the self intermediate scattering function (SISF), V-T theory produced an accurate account of molecular dynamics (MD) data at all wave numbers q and time t. Recently, analysis of the mean square displacement (MSD) resolved a crossover behavior that was not observed in the SISF study. Our purpose here is to apply the more accurate MSD calibration to the SISF, and assess the results. We derive andmore » discuss the theoretical equations for vibrational and transit contributions to the SISF. The time evolution is divided into three successive intervals: the vibrational interval when the vibrational contribution alone accurately accounts for the MD data; the crossover when the vibrational contribution saturates and the transit contribution becomes resolved; and the diffusive interval when the transit contribution alone accurately accounts for the MD data. Finally, the resulting theoretical error is extremely small at all q and t. V-T theory is compared to mode-coupling theories for the MSD and SISF, and to recent developments in Brownian motion experiments and theory.« less

  20. Wheat multiple synthetic derivatives: a new source for heat stress tolerance adaptive traits

    PubMed Central

    Elbashir, Awad Ahmed Elawad; Gorafi, Yasir Serag Alnor; Tahir, Izzat Sidahmed Ali; Kim, June-Sik; Tsujimoto, Hisashi

    2017-01-01

    Heat stress is detrimental to wheat (Triticum aestivum L.) productivity. In this study, we aimed to select heat-tolerant plants from a multiple synthetic derivatives (MSD) population and evaluate their agronomic and physiological traits. We selected six tolerant plants from the population with the background of the cultivar ‘Norin 61’ (N61) and established six MNH (MSD population of N61 selected as heat stress-tolerant) lines. We grew these lines with N61 in the field and growth chamber. In the field, we used optimum and late sowings to ensure plant exposure to heat. In the growth chamber, in addition to N61, we used the heat-tolerant cultivars ‘Gelenson’ and ‘Bacanora’. We confirmed that MNH2 and MNH5 lines acquired heat tolerance. These lines had higher photosynthesis and stomata conductance and exhibited no reduction in grain yield and biomass under heat stress compared to N61. We noticed that N61 had relatively good adaptability to heat stress. Our results indicate that the MSD population includes the diversity of Aegilops tauschii and is a promising resource to uncover useful quantitative traits derived from this wild species. Selected lines could be useful for heat stress tolerance breeding. PMID:28744178

  1. Design of Protein Multi-specificity Using an Independent Sequence Search Reduces the Barrier to Low Energy Sequences

    PubMed Central

    Sevy, Alexander M.; Jacobs, Tim M.; Crowe, James E.; Meiler, Jens

    2015-01-01

    Computational protein design has found great success in engineering proteins for thermodynamic stability, binding specificity, or enzymatic activity in a ‘single state’ design (SSD) paradigm. Multi-specificity design (MSD), on the other hand, involves considering the stability of multiple protein states simultaneously. We have developed a novel MSD algorithm, which we refer to as REstrained CONvergence in multi-specificity design (RECON). The algorithm allows each state to adopt its own sequence throughout the design process rather than enforcing a single sequence on all states. Convergence to a single sequence is encouraged through an incrementally increasing convergence restraint for corresponding positions. Compared to MSD algorithms that enforce (constrain) an identical sequence on all states the energy landscape is simplified, which accelerates the search drastically. As a result, RECON can readily be used in simulations with a flexible protein backbone. We have benchmarked RECON on two design tasks. First, we designed antibodies derived from a common germline gene against their diverse targets to assess recovery of the germline, polyspecific sequence. Second, we design “promiscuous”, polyspecific proteins against all binding partners and measure recovery of the native sequence. We show that RECON is able to efficiently recover native-like, biologically relevant sequences in this diverse set of protein complexes. PMID:26147100

  2. The effects of physical and psychosocial factors and ergonomic conditions on the prevalence of musculoskeletal disorders among dentists in Malaysia.

    PubMed

    Taib, Mohd Firdaus Mohd; Bahn, Sangwoo; Yun, Myung Hwan; Taib, Mohd Syukri Mohd

    2017-01-01

    Musculoskeletal disorders (MSDs) have been recognized as one of the main occupational health problems for dentists. Many studies have suggested that dentists experience work-related pain or discomfort in the neck, shoulder, and back, as well as in other parts of the body. This study aimed to examine the relationship between specific physical and psychosocial factors and/or ergonomic conditions on MSD symptoms among dentists in Malaysia. A group of 85 dentists was asked to complete a questionnaire to determine whether their complaints were related to physical and psychosocial factors and/or ergonomic conditions in their practices. Among the nine reviewed body areas, the shoulders were most often affected by symptoms of MSDs (92.7%). Moreover, MSDs of the neck and upper back were most likely to prevent these practitioners from engaging in normal activities (32.9%). In general, no significant differences were found in the prevalence of MSD symptoms in relation to gender, age, body mass index, years in practice, number of patients, and frequency of breaks. Our results were consistent with those reported in other studies that focused on MSD problems among dentists in other countries. To reduce the prevalence of MSDs, more attention should be paid to instituting ergonomically sensible approaches in the dental practice setting.

  3. Statistical analysis of particle trajectories in living cells

    NASA Astrophysics Data System (ADS)

    Briane, Vincent; Kervrann, Charles; Vimond, Myriam

    2018-06-01

    Recent advances in molecular biology and fluorescence microscopy imaging have made possible the inference of the dynamics of molecules in living cells. Such inference allows us to understand and determine the organization and function of the cell. The trajectories of particles (e.g., biomolecules) in living cells, computed with the help of object tracking methods, can be modeled with diffusion processes. Three types of diffusion are considered: (i) free diffusion, (ii) subdiffusion, and (iii) superdiffusion. The mean-square displacement (MSD) is generally used to discriminate the three types of particle dynamics. We propose here a nonparametric three-decision test as an alternative to the MSD method. The rejection of the null hypothesis, i.e., free diffusion, is accompanied by claims of the direction of the alternative (subdiffusion or superdiffusion). We study the asymptotic behavior of the test statistic under the null hypothesis and under parametric alternatives which are currently considered in the biophysics literature. In addition, we adapt the multiple-testing procedure of Benjamini and Hochberg to fit with the three-decision-test setting, in order to apply the test procedure to a collection of independent trajectories. The performance of our procedure is much better than the MSD method as confirmed by Monte Carlo experiments. The method is demonstrated on real data sets corresponding to protein dynamics observed in fluorescence microscopy.

  4. Identification of critical residues of subunit H in its interaction with subunit E of the A-ATP synthase from Methanocaldococcus jannaschii.

    PubMed

    Gayen, Shovanlal; Balakrishna, Asha M; Biuković, Goran; Yulei, Wu; Hunke, Cornelia; Grüber, Gerhard

    2008-04-01

    The boomerang-like H subunit of A(1)A(0) ATP synthase forms one of the peripheral stalks connecting the A(1) and A(0) sections. Structural analyses of the N-terminal part (H1-47) of subunit H of the A(1)A(0) ATP synthase from Methanocaldococcus jannaschii have been performed by NMR spectroscopy. Our initial NMR structural calculations for H1-47 indicate that amino acid residues 7-44 fold into a single alpha-helical structure. Using the purified N- (E1-100) and C-terminal domains (E101-206) of subunit E, NMR titration experiments revealed that the N-terminal residues Met1-6, Lys10, Glu11, Ala15, Val20 and Glu24 of H1-47 interact specifically with the N-terminal domain E1-100 of subunit E. A more detailed picture regarding the residues of E1-100 involved in this association was obtained by titration studies using the N-terminal peptides E1-20, E21-40 and E41-60. These data indicate that the N-terminal tail E41-60 interacts with the N-terminal amino acids of H1-47, and this has been confirmed by fluorescence correlation spectroscopy results. Analysis of (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra of the central stalk subunit F in the presence and absence of E101-206 show no obvious interaction between the C-terminal domain of E and subunit F. The data presented provide, for the first time, structural insights into the interaction of subunits E and H, and their arrangement within A(1)A(0) ATP synthase.

  5. Inhibition of F1-ATPase Rotational Catalysis by the Carboxyl-terminal Domain of the ϵ Subunit*

    PubMed Central

    Nakanishi-Matsui, Mayumi; Sekiya, Mizuki; Yano, Shio; Futai, Masamitsu

    2014-01-01

    Escherichia coli ATP synthase (F0F1) couples catalysis and proton transport through subunit rotation. The ϵ subunit, an endogenous inhibitor, lowers F1-ATPase activity by decreasing the rotation speed and extending the duration of the inhibited state (Sekiya, M., Hosokawa, H., Nakanishi-Matsui, M., Al-Shawi, M. K., Nakamoto, R. K., and Futai, M. (2010) Single molecule behavior of inhibited and active states of Escherichia coli ATP synthase F1 rotation. J. Biol. Chem. 285, 42058–42067). In this study, we constructed a series of ϵ subunits truncated successively from the carboxyl-terminal domain (helix 1/loop 2/helix 2) and examined their effects on rotational catalysis (ATPase activity, average rotation rate, and duration of inhibited state). As expected, the ϵ subunit lacking helix 2 caused about ½-fold reduced inhibition, and that without loop 2/helix 2 or helix 1/loop 2/helix 2 showed a further reduced effect. Substitution of ϵSer108 in loop 2 and ϵTyr114 in helix 2, which possibly interact with the β and γ subunits, respectively, decreased the inhibitory effect. These results suggest that the carboxyl-terminal domain of the ϵ subunit plays a pivotal role in the inhibition of F1 rotation through interaction with other subunits. PMID:25228697

  6. Atomic force microscopy of ionotropic receptors bearing subunit-specific tags provides a method for determining receptor architecture

    NASA Astrophysics Data System (ADS)

    Neish, Calum S.; Martin, Ian L.; Davies, Martin; Henderson, Robert M.; Edwardson, J. Michael

    2003-08-01

    We have developed an atomic force microscopy (AFM)-based method for the determination of the subunit architecture of ionotropic receptors, and tested the method using the GABAA receptor as a model system. The most common form of the GABAA receptor probably consists of 2alpha1-, 2beta2- and 1gamma2-subunits. We show here that the arrangement of subunits around the central Cl- ion channel can be deduced by AFM of receptors tagged with subunit-specific antibodies. Transfection of cells with DNA encoding alpha1-, beta2- and gamma2-subunits resulted in the production of receptors containing all three subunits, as judged by both immunoblot analysis and the binding of [3H]-Ro15-1788, a specific radioligand for the GABAA receptor. A His6-tag on the alpha1-subunit was used to purify the receptor from membrane fractions of transfected cells. After incubation with anti-His6 immunoglobulin G, some receptors became tagged with either one or two antibody molecules. AFM analysis of complexes containing two bound antibodies showed that the most common angle between the two tags was 135°, close to the value of 144° expected if the two alpha-subunits are separated by a third subunit. This method is applicable to the complete elucidation of the subunit arrangement around the GABAA receptor rosette, and can also be applied to other ionotropic receptors.

  7. Comparison of Voltage Gated K+ Currents in Arterial Myocytes with Heterologously Expressed K v Subunits.

    PubMed

    Cox, Robert H; Fromme, Samantha

    2016-12-01

    We have shown that three components contribute to functional voltage gated K + (K v ) currents in rat small mesenteric artery myocytes: (1) Kv1.2 plus Kv1.5 with Kvβ1.2 subunits, (2) Kv2.1 probably associated with Kv9.3 subunits, and (3) Kv7.4 subunits. To confirm and address subunit stoichiometry of the first two, we have compared the biophysical properties of K v currents in small mesenteric artery myocytes with those of K v subunits heterologously expressed in HEK293 cells using whole cell voltage clamp methods. Selective inhibitors of Kv1 (correolide, COR) and Kv2 (stromatoxin, ScTx) channels were used to separate these K v current components. Conductance-voltage and steady state inactivation data along with time constants of activation, inactivation, and deactivation of native K v components were generally well represented by those of Kv1.2-1.5-β1.2 and Kv2.1-9.3 channels. The slope of the steady state inactivation-voltage curve (availability slope) proved to be the most sensitive measure of accessory subunit presence. The availability slope curves exhibited a single peak for both native K v components. Availability slope curves for Kv1.2-1.5-β1.2 and Kv2.1-9.3 channels expressed in human embryonic kidney cells also exhibited a single peak that shifted to more depolarized voltages with increasing accessory to α subunit transfection ratio. Availability slope curves for SxTc-insensitive currents were similar to those of Kv1.2-1.5 expressed with Kvβ1.2 at a 1:5 molar ratio while curves for COR-insensitive currents closely resembled those of Kv2.1 expressed with Kv9.3 at a 1:1 molar ratio. These results support the suggested K v subunit combinations in small mesenteric artery, and further suggest that Kv1 α and Kvβ1.2 but not Kv2.1 and Kv9.3 subunits are present in a saturated (4:4) stoichiometry.

  8. Metastatic Spine Tumor Surgery: A Comparative Study of Minimally Invasive Approach Using Percutaneous Pedicle Screws Fixation Versus Open Approach.

    PubMed

    Kumar, Naresh; Malhotra, Rishi; Maharajan, Karthikeyan; Zaw, Aye S; Wu, Pang Hung; Makandura, Milindu C; Po Liu, Gabriel Ka; Thambiah, Joseph; Wong, Hee-Kit

    2017-10-01

    Prospective cohort study. Minimally invasive spinal surgery (MISS) has been gaining recognition in patients with metastatic spine disease (MSD). The advantages are reduction in blood loss, hospital stay, and postoperative morbidity. Most of the studies were case series with very few comparing the outcomes of MISS to open approaches. To evaluate and compare the clinical and perioperative outcomes of MISS versus open approach in patients with symptomatic MSD, who underwent posterior spinal stabilization and/or decompression. Our study included 45 MSD patients; 27 managed by MISS and 18 by open approach. All patients had MSD presenting with symptoms of neurological deficit, spinal instability, or both. Preoperative, intraoperative, and postoperative data were collected for comparison of the 2 approaches. All patients were followed up until the end of study period (maximum up to 4 years from time of surgery) or till their demise. The clinical outcome measures were pain control, neurological and functional status, whereas perioperative outcomes were blood loss, operative time, length of hospital stay, and time taken to initiate radiotherapy/chemotherapy after index surgery. Majority of patients in both groups showed improvement in pain, neurological status, independent ambulation, and ECOG score in the postoperative period with no significant differences between the 2 groups. There was a significant reduction in intraoperative blood loss (621 mL less, P<0.001) in the MISS group. The average time to initiate radiotherapy after surgery was 13 days (range, 12-16 d) in MISS and 24 days (range, 16-40 d) in the open group. This difference was statistically significant (P<0.001). Operative time and duration of hospital stay were also favorable in the MISS group, although the differences were not significant. MISS is comparable with open approach demonstrating similar improvements in clinical outcomes, that is pain control, neurological and functional status. MISS approaches have also shown promising results due to lesser intraoperative blood loss and allowing earlier radiotherapy/chemotherapy.

  9. Automated toxicological screening reports of modified Agilent MSD Chemstation combined with Microsoft Visual Basic application programs.

    PubMed

    Choe, Sanggil; Kim, Suncheun; Choi, Hyeyoung; Choi, Hwakyoung; Chung, Heesun; Hwang, Bangyeon

    2010-06-15

    Agilent GC-MS MSD Chemstation offers automated library search report for toxicological screening using total ion chromatogram (TIC) and mass spectroscopy in normal mode. Numerous peaks appear in the chromatogram of biological specimen such as blood or urine and often large migrating peaks obscure small target peaks, in addition, any target peaks of low abundance regularly give wrong library search result or low matching score. As a result, retention time and mass spectrum of all the peaks in the chromatogram have to be checked to see if they are relevant. These repeated actions are very tedious and time-consuming to toxicologists. MSD Chemstation software operates using a number of macro files which give commands and instructions on how to work on and extract data from the chromatogram and spectroscopy. These macro files are developed by the own compiler of the software. All the original macro files can be modified and new macro files can be added to the original software by users. To get more accurate results with more convenient method and to save time for data analysis, we developed new macro files for reports generation and inserted new menus in the Enhanced Data Analysis program. Toxicological screening reports generated by these new macro files are in text mode or graphic mode and these reports can be generated with three different automated subtraction options. Text reports have Brief mode and Full mode and graphic reports have the option with or without mass spectrum mode. Matched mass spectrum and matching score for detected compounds are printed in reports by modified library searching modules. We have also developed an independent application program named DrugMan. This program manages drug groups, lists and parameters that are in use in MSD Chemstation. The incorporation of DrugMan with modified macro modules provides a powerful tool for toxicological screening and save a lot of valuable time on toxicological work. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Workers' experiences with compensated sick leave due to musculoskeletal disorder: a qualitative study.

    PubMed

    Choi, Min; Kim, Hyoung-Ryoul; Lee, Jinwoo; Lee, Hye-Eun; Byun, Junsu; Won, Jong Uk

    2014-01-01

    The most common occupational disease that is compensated by Industrial Accident Compensation Insurance (IACI) in Korea is musculoskeletal disease (MSD). Although complaints about the workers' compensation system have been raised by injured workers with MSD, studies that examine workers' experiences with the Korean system are rare. This paper is a qualitative study designed to examine injured workers' experiences with the workers' compensation system in Korea. The aim of this study is to explore the drawbacks of the workers' compensation system and to suggest ways to improve this system. All workers from an automobile parts factory in Anseong, GyeongGi province who were compensated for MSD by IACI from January 2003 to August 2013 were invited to participate. Among these 153 workers, 142 workers completed the study. Semi-structured open-ended interviews and questionnaires were administered by occupational physicians. The responses of 131 workers were analyzed after excluding 11 workers, 7 of whom provided incomplete answers and 4 of whom were compensated by accidental injury. Based on their age, disease, department of employment, and compensation time, 16 of these 131 workers were invited to participate in an individual in-depth interview. In-depth interviews were conducted by one of 3 occupational physicians until the interview contents were saturated. Injured workers with MSD reported that the workers' compensation system was intimidating. These workers suffered more emotional distress than physical illness due to the workers' compensation system. Injured workers reported that they were treated inadequately and remained isolated for most of the recuperation period. The compensation period was terminated without ample guidance or a plan for an appropriate rehabilitation process. Interventions to alleviate the negative experiences of injured workers, including quality control of the medical care institutions and provisions for mental and psychological care for injured workers, are needed to help injured workers return to work earlier and more healthy.

  11. VIP in construction: systematic development and evaluation of a multifaceted health programme aiming to improve physical activity levels and dietary patterns among construction workers

    PubMed Central

    2012-01-01

    Background The prevalence of both overweight and musculoskeletal disorders (MSD) in the construction industry is high. Many interventions in the occupational setting aim at the prevention and reduction of these health problems, but it is still unclear how these programmes should be designed. To determine the effectiveness of interventions on these health outcomes randomised controlled trials (RCTs) are needed. The aim of this study is to systematically develop a tailored intervention for prevention and reduction of overweight and MSD among construction workers and to describe the evaluation study regarding its (cost-)effectiveness. Methods/Design The Intervention Mapping (IM) protocol was applied to develop and implement a tailored programme aimed at the prevention and reduction of overweight and MSD. The (cost-) effectiveness of the intervention programme will be evaluated using an RCT. Furthermore, a process evaluation will be conducted. The research population will consist of blue collar workers of a large construction company in the Netherlands. Intervention The intervention programme will be aimed at improving (vigorous) physical activity levels and healthy dietary behaviour and will consist of tailored information, face-to-face and telephone counselling, training instruction (a fitness "card" to be used for exercises), and materials designed for the intervention (overview of the company health promoting facilities, waist circumference measuring tape, pedometer, BMI card, calorie guide, recipes, and knowledge test). Main study parameters/endpoints The intervention effect on body weight and waist circumference (primary outcome measures), as well as on lifestyle behaviour, MSD, fitness, CVD risk indicators, and work-related outcomes (i.e. productivity, sick leave) (secondary outcome measures) will be assessed. Discussion The development of the VIP in construction intervention led to a health programme tailored to the needs of construction workers. This programme, if proven effective, can be directly implemented. Trial registration Netherlands Trial Register (NTR): NTR2095 PMID:22289212

  12. Stimulation of the cardiac myocyte Na+-K+ pump due to reversal of its constitutive oxidative inhibition

    PubMed Central

    Chia, Karin K. M.; Liu, Chia-Chi; Hamilton, Elisha J.; Garcia, Alvaro; Fry, Natasha A.; Hannam, William; Figtree, Gemma A.

    2015-01-01

    Protein kinase C can activate NADPH oxidase and induce glutathionylation of the β1-Na+-K+ pump subunit, inhibiting activity of the catalytic α-subunit. To examine if signaling of nitric oxide-induced soluble guanylyl cyclase (sGC)/cGMP/protein kinase G can cause Na+-K+ pump stimulation by counteracting PKC/NADPH oxidase-dependent inhibition, cardiac myocytes were exposed to ANG II to activate NADPH oxidase and inhibit Na+-K+ pump current (Ip). Coexposure to 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1) to stimulate sGC prevented the decrease of Ip. Prevention of the decrease was abolished by inhibition of protein phosphatases (PP) 2A but not by inhibition of PP1, and it was reproduced by an activator of PP2A. Consistent with a reciprocal relationship between β1-Na+-K+ pump subunit glutathionylation and pump activity, YC-1 decreased ANG II-induced β1-subunit glutathionylation. The decrease induced by YC-1 was abolished by a PP2A inhibitor. YC-1 decreased phosphorylation of the cytosolic p47phox NADPH oxidase subunit and its coimmunoprecipitation with the membranous p22phox subunit, and it decreased O2·−-sensitive dihydroethidium fluorescence of myocytes. Addition of recombinant PP2A to myocyte lysate decreased phosphorylation of p47phox indicating the subunit could be a substrate for PP2A. The effects of YC-1 to decrease coimmunoprecipitation of p22phox and p47phox NADPH oxidase subunits and decrease β1-Na+-K+ pump subunit glutathionylation were reproduced by activation of nitric oxide-dependent receptor signaling. We conclude that sGC activation in cardiac myocytes causes a PP2A-dependent decrease in NADPH oxidase activity and a decrease in β1 pump subunit glutathionylation. This could account for pump stimulation with neurohormonal oxidative stress expected in vivo. PMID:26084308

  13. Treating inertia in passive microbead rheology.

    PubMed

    Indei, Tsutomu; Schieber, Jay D; Córdoba, Andrés; Pilyugina, Ekaterina

    2012-02-01

    The dynamic modulus G(*) of a viscoelastic medium is often measured by following the trajectory of a small bead subject to Brownian motion in a method called "passive microbead rheology." This equivalence between the positional autocorrelation function of the tracer bead and G(*) is assumed via the generalized Stokes-Einstein relation (GSER). However, inertia of both bead and medium are neglected in the GSER so that the analysis based on the GSER is not valid at high frequency where inertia is important. In this paper we show how to treat both contributions to inertia properly in one-bead passive microrheological analysis. A Maxwell fluid is studied as the simplest example of a viscoelastic fluid to resolve some apparent paradoxes of eliminating inertia. In the original GSER, the mean-square displacement (MSD) of the tracer bead does not satisfy the correct initial condition. If bead inertia is considered, the proper initial condition is realized, thereby indicating an importance of including inertia, but the MSD oscillates at a time regime smaller than the relaxation time of the fluid. This behavior is rather different from the original result of the GSER and what is observed. What is more, the discrepancy from the GSER result becomes worse with decreasing bead mass, and there is an anomalous gap between the MSD derived by naïvely taking the zero-mass limit in the equation of motion and the MSD for finite bead mass as indicated by McKinley et al. [J. Rheol. 53, 1487 (2009)]. In this paper we show what is necessary to take the zero-mass limit of the bead safely and correctly without causing either the inertial oscillation or the anomalous gap, while obtaining the proper initial condition. The presence of a very small purely viscous element can be used to eliminate bead inertia safely once included in the GSER. We also show that if the medium contains relaxation times outside the window where the single-mode Maxwell behavior is observed, the oscillation can be attenuated inside the window. This attenuation is realized even in the absence of a purely viscous element. Finally, fluid inertia also affects the bead autocorrelation through the Basset force and the fluid dragged around with the bead. We show that the Basset force plays the same role as the purely viscous element in high-frequency regime, and the oscillation of MSD is suppressed if fluid density and bead density are comparable. © 2012 American Physical Society

  14. Functional diversification of maize RNA polymerase IV and V subtypes via alternative catalytic subunits

    DOE PAGES

    Haag, Jeremy R.; Brower-Toland, Brent; Krieger, Elysia K.; ...

    2014-10-02

    Unlike nuclear multisubunit RNA polymerases I, II, and III, whose subunit compositions are conserved throughout eukaryotes, plant RNA polymerases IV and V are nonessential, Pol II-related enzymes whose subunit compositions are still evolving. Whereas Arabidopsis Pols IV and V differ from Pol II in four or five of their 12 subunits, respectively, and differ from one another in three subunits, proteomic analyses show that maize Pols IV and V differ from Pol II in six subunits but differ from each other only in their largest subunits. Use of alternative catalytic second subunits, which are nonredundant for development and paramutation, yieldsmore » at least two sub-types of Pol IV and three subtypes of Pol V in maize. Pol IV/Pol V associations with MOP1, RMR1, AGO121, Zm_DRD1/CHR127, SHH2a, and SHH2b extend parallels between paramutation in maize and the RNA-directed DNA methylation pathway in Arabidopsis.« less

  15. Functional diversification of maize RNA polymerase IV and V subtypes via alternative catalytic subunits

    PubMed Central

    Haag, Jeremy R.; Brower-Toland, Brent; Krieger, Elysia K.; Sidorenko, Lyudmila; Nicora, Carrie D.; Norbeck, Angela D.; Irsigler, Andre; LaRue, Huachun; Brzeski, Jan; McGinnis, Karen; Ivashuta, Sergey; Pasa-Tolic, Ljiljana; Chandler, Vicki L.; Pikaard, Craig S.

    2014-01-01

    Summary Unlike nuclear multisubunit RNA polymerases I, II and III, whose subunit compositions are conserved throughout eukaryotes, plant RNA Polymerases IV and V are non-essential, Pol II-related enzymes whose subunit compositions are still evolving. Whereas Arabidopsis Pols IV and V differ from Pol II in four or five of their twelve subunits, respectively, and differ from one another in three subunits, proteomic analyses show that maize Pols IV and V differ from Pol II in six subunits, but differ from each other only in their largest subunits. Use of alternative catalytic second-subunits, which are non-redundant for development and paramutation, yields at least two subtypes of Pol IV, and three subtypes of Pol V in maize. Pol IV/V associations with MOP1, RMR1, AGO121, Zm_DRD1/CHR127, SHH2a and SHH2b extend parallels between paramutation in maize and the RNA-directed DNA methylation pathway in Arabidopsis. PMID:25284785

  16. Collaborating To Serve Arizona Students & Families More Effectively: Phase 1 Report. Evaluation of Murphy School District-Department of Economic Security Collaborative Project.

    ERIC Educational Resources Information Center

    Izu, Jo Ann; Carreon, Tori

    This report presents the results of Phase I of an evaluation of the Murphy School District (MSD)-Department of Economic Security (DES) collaborative effort, one of the first interagency partnerships in the state of Arizona that attempts to address the needs of students and their families more effectively. The primary purposes of the evaluation are…

  17. Cost Effectiveness Study of Wastewater Management Systems for Selected U.S. Coast Guard Vessels. Volume 2. Effectiveness Assessment of Candidate Systems

    DTIC Science & Technology

    1977-03-01

    267 Input Layout for Each Card Type ...................... 269 Input Sequence .......................... 271 SAMPLE PROBLEM...13 3 Sample Data rormn Used for Documenting MSD Effectiveness Attribute Data ........................... 15 -1 Sample Form Used for Documenting WMS...from commodes, urinals and garbage grinder) and gray (galley and turbid, i.e., output from sinks, showers, laundry, deck, drains, etc.) wastewaters

  18. Occupational injury and illness recording and reporting requirements. Final rule.

    PubMed

    2001-10-12

    The Occupational Safety and Health Administration (OSHA) is delaying the effective date of three provisions of the Occupational Injury and Illness Recording and Reporting Requirements rule published January 19, 2001 (66 FR 5916-6135) and is establishing interim criteria for recording cases of work-related hearing loss. The provisions being delayed are sections 1904.10 (a) and (b), which specify recording criteria for cases involving occupational hearing loss, section 1904.12, which defines "musculoskeletal disorder (MSD)" and requires employers to check the MSD column on the OSHA Log if an employee experiences a work-related musculoskeletal disorder, and section 1904.29(b)(7)(vi), which states that MSDs are not considered privacy concern cases. The effective date of these provisions is delayed from January 1, 2002 until January 1, 2003. OSHA will continue to evaluate sections 1904.10 and 1904.12 over the next year. OSHA is also adding a new paragraph(c) to section 1904.10, establishing criteria for recording cases of work-related hearing loss during calendar year 2002. Section 1904.10(c) codifies the enforcement policy in effect since 1991, under which employers must record work related shifts in hearing of an average of 25 dB or more at 2000, 3000 and 4000 hertz in either ear.

  19. Risk factors and clinical features of text message injuries.

    PubMed

    Sharan, Deepak; Ajeesh, P S

    2012-01-01

    Use of mobile phone and sending text message is a very common in today's life. While sending a text message the users need to use their thumb and other palm muscles extensively. The thumb most of the time adducted on the key pad of the mobile and use high force to type the letters. Studies in literature showed that text messaging has an adverse effect on musculoskeletal system of hand. But the extensive study on the type of disorders set in among the users who extensively use mobile phone for texting. This study aims at to evaluate risk factor and clinical feature of the MSD due to hand held devices. Twenty seven subjects participated in this study. Predefined protocols were used to evaluate type of MSD occurred among the subjects. The study revealed that development of tendinitis in extensor pollicis longus, myofascial pain syndrome (70.37%) of adductor pollicis, 1st interossei and extensor digitorum communis . Other associated problems diagnosed were thoracic outlet syndrome (51.85%), fibromyalgia syndrome (25.93%), hypothyroidism (7.41%), wrist tendinitis (14.81%) and De Quervain's syndrome (7.41%). It has been observed that the pathology were tendinitis of extensor pollicis longus, myofascial pain syndrome of thenar muscles and 1st interossei, extensor digitorum communis.

  20. Multiplicative surrogate standard deviation: a group metric for the glycemic variability of individual hospitalized patients.

    PubMed

    Braithwaite, Susan S; Umpierrez, Guillermo E; Chase, J Geoffrey

    2013-09-01

    Group metrics are described to quantify blood glucose (BG) variability of hospitalized patients. The "multiplicative surrogate standard deviation" (MSSD) is the reverse-transformed group mean of the standard deviations (SDs) of the logarithmically transformed BG data set of each patient. The "geometric group mean" (GGM) is the reverse-transformed group mean of the means of the logarithmically transformed BG data set of each patient. Before reverse transformation is performed, the mean of means and mean of SDs each has its own SD, which becomes a multiplicative standard deviation (MSD) after reverse transformation. Statistical predictions and comparisons of parametric or nonparametric tests remain valid after reverse transformation. A subset of a previously published BG data set of 20 critically ill patients from the first 72 h of treatment under the SPRINT protocol was transformed logarithmically. After rank ordering according to the SD of the logarithmically transformed BG data of each patient, the cohort was divided into two equal groups, those having lower or higher variability. For the entire cohort, the GGM was 106 (÷/× 1.07) mg/dl, and MSSD was 1.24 (÷/× 1.07). For the subgroups having lower and higher variability, respectively, the GGM did not differ, 104 (÷/× 1.07) versus 109 (÷/× 1.07) mg/dl, but the MSSD differed, 1.17 (÷/× 1.03) versus 1.31 (÷/× 1.05), p = .00004. By using the MSSD with its MSD, groups can be characterized and compared according to glycemic variability of individual patient members. © 2013 Diabetes Technology Society.

  1. Enzymatic activities produced by mixed Saccharomyces and non-Saccharomyces cultures: relationship with wine volatile composition.

    PubMed

    Maturano, Yolanda Paola; Assof, Mariela; Fabani, María Paula; Nally, María Cristina; Jofré, Viviana; Rodríguez Assaf, Leticia Anahí; Toro, María Eugenia; Castellanos de Figueroa, Lucía Inés; Vazquez, Fabio

    2015-11-01

    During certain wine fermentation processes, yeasts, and mainly non-Saccharomyces strains, produce and secrete enzymes such as β-glucosidases, proteases, pectinases, xylanases and amylases. The effects of enzyme activity on the aromatic quality of wines during grape juice fermentation, using different co-inoculation strategies of non-Saccharomyces and Saccharomyces cerevisiae yeasts, were assessed in the current study. Three strains with appropriate enological performance and high enzymatic activities, BSc562 (S. cerevisiae), BDv566 (Debaryomyces vanrijiae) and BCs403 (Candida sake), were assayed in pure and mixed Saccharomyces/non-Saccharomyces cultures. β-Glucosidase, pectinase, protease, xylanase and amylase activities were quantified during fermentations. The aromatic profile of pure and mixed cultures was determined at the end of each fermentation. In mixed cultures, non-Saccharomyces species were detected until day 4-5 of the fermentation process, and highest populations were observed in MSD2 (10% S. cerevisiae/90% D. vanrijiae) and MSC1 (1% S. cerevisiae/99% C. sake). According to correlation and multivariate analysis, MSD2 presented the highest concentrations of terpenes and higher alcohols which were associated with pectinase, amylase and xylanase activities. On the other hand, MSC1 high levels of β-glucosidase, proteolytic and xylanolytic activities were correlated to esters and fatty acids. Our study contributes to a better understanding of the effect of enzymatic activities by yeasts on compound transformations that occur during wine fermentation.

  2. Immunohistochemical analyses of alpha1 and alpha3 Na+/K+-ATPase subunit expression in medulloblastomas.

    PubMed

    Suñol, Mariona; Cusi, Victoria; Cruz, Ofelia; Kiss, Robert; Lefranc, Florence

    2011-03-01

    The levels of expression of the α1 and α3 subunits of the Na(+)/K(+)-ATPase (the NaK sodium pump) in medulloblastomas are unclear. This study investigated the expression of the NaK subunits using immunohistochemical methods in 29 medulloblastomas including 23 classic, three large-cell/anaplastic and three nodular/desmoplastic medulloblastomas, as well as in three atypical teratoid/rhabdoid tumors (AT/RTs). There was overexpression of the α1 or α3 NaK subunits in more than half of the medulloblastomas and atypical AT/RTs, with about one-third of these tumours displaying overexpression of both subunits. These preliminary data suggest that targeting these subunits in AT/RTs and medulloblastomas that overexpress these proteins may lead to therapeutic benefit. These findings warrant confirmation in larger numbers of patients than those used in this study. Moreover, it should be determined whether inhibition of the α1/α3 NaK subunits can be integrated into the risk stratification schemes already in use for medulloblastoma patients.

  3. Prolonged exposure of chromaffin cells to nitric oxide down-regulates the activity of soluble guanylyl cyclase and corresponding mRNA and protein levels

    PubMed Central

    Ferrero, Rut; Torres, Magdalena

    2002-01-01

    Background Soluble guanylyl cyclase (sGC) is the main receptor for nitric oxide (NO) when the latter is produced at low concentrations. This enzyme exists mainly as a heterodimer consisting of one α and one β subunit and converts GTP to the second intracellular messenger cGMP. In turn, cGMP plays a key role in regulating several physiological processes in the nervous system. The aim of the present study was to explore the effects of a NO donor on sGC activity and its protein and subunit mRNA levels in a neural cell model. Results Continuous exposure of bovine adrenal chromaffin cells in culture to the nitric oxide donor, diethylenetriamine NONOate (DETA/NO), resulted in a lower capacity of the cells to synthesize cGMP in response to a subsequent NO stimulus. This effect was not prevented by an increase of intracellular reduced glutathione level. DETA/NO treatment decreased sGC subunit mRNA and β1 subunit protein levels. Both sGC activity and β1 subunit levels decreased more rapidly in chromaffin cells exposed to NO than in cells exposed to the protein synthesis inhibitor, cycloheximide, suggesting that NO decreases β1 subunit stability. The presence of cGMP-dependent protein kinase (PKG) inhibitors effectively prevented the DETA/NO-induced down regulation of sGC subunit mRNA and partially inhibited the reduction in β1 subunits. Conclusions These results suggest that activation of PKG mediates the drop in sGC subunit mRNA levels, and that NO down-regulates sGC activity by decreasing subunit mRNA levels through a cGMP-dependent mechanism, and by reducing β1 subunit stability. PMID:12350235

  4. Development and use of domain-specific antibodies in a characterization of the large subunits of soybean photosystem 1

    NASA Technical Reports Server (NTRS)

    Henry, R. L.; Takemoto, L. J.; Murphy, J.; Gallegos, G. L.; Guikema, J. A.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    The molecular architecture of the soybean photosystem 1 reaction center complex was examined using a combination of surface labeling and immunological methodology on isolated thylakoid membranes. Synthetic peptides (12 to 14 amino acids in length) were prepared which correspond to the N-terminal regions of the 83 and 82.4 kDa subunits of photosystem 1 (the PsaA and PsaB proteins, respectively). Similarly, a synthetic peptide was prepared corresponding to the C-terminal region of the PsaB subunit. These peptides were conjugated to a carrier protein, and were used for the production of polyclonal antibodies in rabbits. The resulting sera could distinguish between the PsaA and PsaB photosystem 1 subunits by Western blot analysis, and could identify appropriate size classes of cyanogen bromide cleavage fragments as predicted from the primary sequences of these two subunits. When soybean thylakoid membranes were surface-labeled with N-hydroxysuccinimidobiotin, several subunits of the complete photosystem 1 lipid/protein complex incorporated label. These included the light harvesting chlorophyll proteins of photosystem 1, and peptides thought to aid in the docking of ferredoxin to the complex during photosynthetic electron transport. However, the PsaA and PsaB subunits showed very little biotinylation. When these subunits were examined for the domains to which biotin did attach, most of the observed label was associated with the N-terminal domain of the PsaA subunit, as identified using a domain-specific polyclonal antisera.

  5. Berkeley Lab - Materials Sciences Division

    Science.gov Websites

    ; Finance Templates Travel One-Stop Acknowledging MSD Support Human Resources Facilities & Space Planning Procurement and Property Proposals & Finance Templates Travel Facilities & Space Planning

  6. Escherichia coli F1Fo-ATP synthase with a b/δ fusion protein allows analysis of the function of the individual b subunits.

    PubMed

    Gajadeera, Chathurada S; Weber, Joachim

    2013-09-13

    The "stator stalk" of F1Fo-ATP synthase is essential for rotational catalysis as it connects the nonrotating portions of the enzyme. In Escherichia coli, the stator stalk consists of two (identical) b subunits and the δ subunit. In mycobacteria, one of the b subunits and the δ subunit are replaced by a b/δ fusion protein; the remaining b subunit is of the shorter b' type. In the present study, it is shown that it is possible to generate a functional E. coli ATP synthase containing a b/δ fusion protein. This construct allowed the analysis of the roles of the individual b subunits. The full-length b subunit (which in this case is covalently linked to δ in the fusion protein) is responsible for connecting the stalk to the catalytic F1 subcomplex. It is not required for interaction with the membrane-embedded Fo subcomplex, as its transmembrane helix can be removed. Attachment to Fo is the function of the other b subunit which in turn has only a minor (if any at all) role in binding to δ. Also in E. coli the second b subunit can be shortened to a b' type.

  7. 256 fs, 2 nJ soliton pulse generation from MoS2 mode-locked fiber laser

    NASA Astrophysics Data System (ADS)

    Jiang, Zike; Chen, Hao; Li, Jiarong; Yin, Jinde; Wang, Jinzhang; Yan, Peiguang

    2017-12-01

    We demonstrate an Er-doped fiber laser (EDFL) mode-locked by a MoS2 saturable absorber (SA), delivering a 256 fs, 2 nJ soliton pulse at 1563.4 nm. The nonlinear property of the SA prepared by magnetron sputtering deposition (MSD) is measured with a modulation depth (MD) of ∼19.48% and a saturable intensity of 4.14 MW/cm2. To the best of our knowledge, the generated soliton pulse has the highest pulse energy of 2 nJ among the reported mode-locked EDFLs based on transition metal dichalcogenides (TMDs). Our results indicate that MSD-grown SAs could offer an exciting platform for high pulse energy and ultrashort pulse generation.

  8. Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?

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

    Chadha, Awalpreet S.; Liu, Guan; Chen, Hsiang-Chun

    2017-02-01

    Purpose: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gymore » (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. Results: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. Conclusion: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.« less

  9. A computational biomechanical analysis to assess the trade-off between chest deflection and spine translation in side impact.

    PubMed

    Pipkorn, Bengt; Subit, Damien; Donlon, John Paul; Sunnevång, Cecilia

    2014-01-01

    The objective of this study is to evaluate how the impact energy is apportioned between chest deflection and translation of the vehicle occupant for various side impact conditions. The Autoliv Total Human Model for Safety (modified THUMS v1.4) was subjected to localized lateral constant velocity impacts to the upper body. First, the impact tests performed on postmortem human subjects (PMHS) were replicated to evaluate THUMS biofidelity. In these tests, a 75-mm-tall flat probe impacted the thorax at 3 m/s at 3 levels (shoulder, upper chest, and mid-chest) and 3 angles (lateral, +15° posterolateral, and -15° anterolateral), for a stroke of 72 mm. Second, a parametric analysis was performed: the Autoliv THUMS response to a 250-mm impact was evaluated for varying impact levels (shoulder to mid-thorax by 50-mm increments), obliquity (0° [pure lateral] to +20° [posterior impacts] and to -20° [anterior impacts], by 5° steps), and impactor pitch (from 0 to 25° by 5° steps). A total of 139 simulations were run. The impactor force, chest deflection, spine displacement, and spine velocity were calculated for each simulation. The Autoliv THUMS biofidelity was found acceptable. Overall, the predictions from the model were in good agreement with the PMHS results. The worst ratings were observed for the anterolateral impacts. For the parametric analysis, maximum chest deflection (MCD) and maximum spine displacement (MSD) were found to consistently follow opposite trends with increasing obliquity. This trend was level dependent, with greater MCD (lower MSD) for the higher impact levels. However, the spine velocity for the 250-mm impactor stroke followed an independent trend that could not be linked to MCD or MSD. This suggests that the spine velocity, which can be used as a proxy for the thorax kinetic energy, needs to be included in the design parameters of countermeasures for side impact protection. The parametric analysis reveals a trade-off between the deformation of the chest (and therefore the risk of rib fracture) and the lateral translation of the spine: reducing the maximum chest deflection comes at the cost of increasing the occupant lateral displacement. The trade-off between MCD and MSD is location dependent, which suggests that an optimum point of loading on the chest for the action of a safety system can be found.

  10. Inhibition of F1-ATPase rotational catalysis by the carboxyl-terminal domain of the ϵ subunit.

    PubMed

    Nakanishi-Matsui, Mayumi; Sekiya, Mizuki; Yano, Shio; Futai, Masamitsu

    2014-10-31

    Escherichia coli ATP synthase (F0F1) couples catalysis and proton transport through subunit rotation. The ϵ subunit, an endogenous inhibitor, lowers F1-ATPase activity by decreasing the rotation speed and extending the duration of the inhibited state (Sekiya, M., Hosokawa, H., Nakanishi-Matsui, M., Al-Shawi, M. K., Nakamoto, R. K., and Futai, M. (2010) Single molecule behavior of inhibited and active states of Escherichia coli ATP synthase F1 rotation. J. Biol. Chem. 285, 42058-42067). In this study, we constructed a series of ϵ subunits truncated successively from the carboxyl-terminal domain (helix 1/loop 2/helix 2) and examined their effects on rotational catalysis (ATPase activity, average rotation rate, and duration of inhibited state). As expected, the ϵ subunit lacking helix 2 caused about ½-fold reduced inhibition, and that without loop 2/helix 2 or helix 1/loop 2/helix 2 showed a further reduced effect. Substitution of ϵSer(108) in loop 2 and ϵTyr(114) in helix 2, which possibly interact with the β and γ subunits, respectively, decreased the inhibitory effect. These results suggest that the carboxyl-terminal domain of the ϵ subunit plays a pivotal role in the inhibition of F1 rotation through interaction with other subunits. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Impact of Ancillary Subunits on Ventricular Repolarization

    PubMed Central

    Abbott, Geoffrey W.; Xu, Xianghua; Roepke, Torsten K.

    2007-01-01

    Voltage-gated potassium (Kv) channels generate the outward K+ ion currents that constitute the primary force in ventricular repolarization. Kv channels comprise tetramers of pore-forming α subunits and, in probably the majority of cases in vivo, ancillary or β subunits that help define the properties of the Kv current generated. Ancillary subunits can be broadly categorized as cytoplasmic or transmembrane, and can modify Kv channel trafficking, conductance, gating, ion selectivity, regulation and pharmacology. Because of their often profound effects on Kv channel function, studies of the molecular correlates of ventricular repolarization must take into account ancillary subunits as well as α subunits. Cytoplasmic ancillary subunits include the Kvβ subunits, which regulate a range of Kv channels and may link channel gating to redox potential; and the KChIPs, which appear most often associated with Kv4 subfamily channels that generate the ventricular Ito current. Transmembrane ancillary subunits include the MinK-related proteins (MiRPs) encoded by KCNE genes, which modulate members of most Kv α subunit subfamilies; and the putative 12-transmembrane domain KCR1 protein which modulates hERG. In some cases, such as the ventricular IKs channel complex, it is well-established that the KCNQ1 α subunit must co-assemble with the MinK (KCNE1) single transmembrane domain ancillary subunit for recapitulation of the characteristic, unusually slowly-activating IKs current. In other cases it is not so clear-cut, and in particular the roles of the other MinK-related proteins (MiRPs 1–4) in regulating cardiac Kv channels such as KCNQ1 and hERG in vivo are under debate. MiRP1 alters hERG function and pharmacology, and inherited MiRP1 mutations are associated with inherited and acquired arrhythmias, but controversy exists over the native role of MiRP1 in regulating hERG (and therefore ventricular IKr) in vivo. Some ancillary subunits may exhibit varied expression to shape spatial Kv current variation, e.g. KChIP2 and the epicardial-endocardial Ito current density gradient. Indeed, it is likely that most native ventricular Kv channels exhibit temporal and spatial heterogeneity of subunit composition, complicating both modeling of their functional impact on the ventricular action potential and design of specific current-targeted compounds. Here, we discuss current thinking and lines of experimentation aimed at resolving the complexities of the Kv channel complexes that repolarize the human ventricular myocardium. PMID:17993327

  12. Structure-function of proteins interacting with the α1 pore-forming subunit of high-voltage-activated calcium channels

    PubMed Central

    Neely, Alan; Hidalgo, Patricia

    2014-01-01

    Openings of high-voltage-activated (HVA) calcium channels lead to a transient increase in calcium concentration that in turn activate a plethora of cellular functions, including muscle contraction, secretion and gene transcription. To coordinate all these responses calcium channels form supramolecular assemblies containing effectors and regulatory proteins that couple calcium influx to the downstream signal cascades and to feedback elements. According to the original biochemical characterization of skeletal muscle Dihydropyridine receptors, HVA calcium channels are multi-subunit protein complexes consisting of a pore-forming subunit (α1) associated with four additional polypeptide chains β, α2, δ, and γ, often referred to as accessory subunits. Twenty-five years after the first purification of a high-voltage calcium channel, the concept of a flexible stoichiometry to expand the repertoire of mechanisms that regulate calcium channel influx has emerged. Several other proteins have been identified that associate directly with the α1-subunit, including calmodulin and multiple members of the small and large GTPase family. Some of these proteins only interact with a subset of α1-subunits and during specific stages of biogenesis. More strikingly, most of the α1-subunit interacting proteins, such as the β-subunit and small GTPases, regulate both gating and trafficking through a variety of mechanisms. Modulation of channel activity covers almost all biophysical properties of the channel. Likewise, regulation of the number of channels in the plasma membrane is performed by altering the release of the α1-subunit from the endoplasmic reticulum, by reducing its degradation or enhancing its recycling back to the cell surface. In this review, we discuss the structural basis, interplay and functional role of selected proteins that interact with the central pore-forming subunit of HVA calcium channels. PMID:24917826

  13. Kv channel subunits that contribute to voltage-gated K+ current in renal vascular smooth muscle.

    PubMed

    Fergus, Daniel J; Martens, Jeffrey R; England, Sarah K

    2003-03-01

    The rat renal arterial vasculature displays differences in K(+) channel current phenotypes along its length. Small arcuate to cortical radial arteries express a delayed rectifier phenotype, while the predominant Kv current in larger arcuate and interlobar arteries is composed of both transient and sustained components. We sought to determine whether Kvalpha subunits in the rat renal interlobar and arcuate arteries form heterotetramers, which may account for the unique currents, and whether modulatory Kvbeta subunits are present in renal vascular smooth muscle cells. RT-PCR indicated the presence of several different Kvalpha subunit isoform transcripts. Co-immunoprecipitation with immunoblotting and immunohistochemical evidence suggests that a portion of the K(+) current phenotype is a heteromultimer containing delayed-rectifier Kv1.2 and A-type Kv1.4 channel subunits. RT-PCR and immunoblot analyses also demonstrated the presence of both Kvbeta1.2 and Kvbeta1.3 in renal arteries. These results suggest that heteromultimeric formation of Kvalpha subunits and the presence of modulatory Kvbeta subunits are important factors in mediating Kv currents in the renal microvasculature and suggest a potentially critical role for these channel subunits in blood pressure regulation.

  14. Differential Roles of the Glycogen-Binding Domains of β Subunits in Regulation of the Snf1 Kinase Complex▿

    PubMed Central

    Mangat, Simmanjeet; Chandrashekarappa, Dakshayini; McCartney, Rhonda R.; Elbing, Karin; Schmidt, Martin C.

    2010-01-01

    Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic α subunit and regulatory β and γ subunits. In this study, the role of the β subunits in the regulation of Snf1 activity was examined. Yeasts express three isoforms of the AMP-activated protein kinase consisting of Snf1 (α), Snf4 (γ), and one of three alternative β subunits, either Sip1, Sip2, or Gal83. The Gal83 isoform of the Snf1 complex is the most abundant and was analyzed in the greatest detail. All three β subunits contain a conserved domain referred to as the glycogen-binding domain. The deletion of this domain from Gal83 results in a deregulation of the Snf1 kinase, as judged by a constitutive activity independent of glucose availability. In contrast, the deletion of this homologous domain from the Sip1 and Sip2 subunits had little effect on Snf1 kinase regulation. Therefore, the different Snf1 kinase isoforms are regulated through distinct mechanisms, which may contribute to their specialized roles in different stress response pathways. In addition, the β subunits are subjected to phosphorylation. The responsible kinases were identified as being Snf1 and casein kinase II. The significance of the phosphorylation is unclear since the deletion of the region containing the phosphorylation sites in Gal83 had little effect on the regulation of Snf1 in response to glucose limitation. PMID:19897735

  15. Differential roles of the glycogen-binding domains of beta subunits in regulation of the Snf1 kinase complex.

    PubMed

    Mangat, Simmanjeet; Chandrashekarappa, Dakshayini; McCartney, Rhonda R; Elbing, Karin; Schmidt, Martin C

    2010-01-01

    Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic alpha subunit and regulatory beta and gamma subunits. In this study, the role of the beta subunits in the regulation of Snf1 activity was examined. Yeasts express three isoforms of the AMP-activated protein kinase consisting of Snf1 (alpha), Snf4 (gamma), and one of three alternative beta subunits, either Sip1, Sip2, or Gal83. The Gal83 isoform of the Snf1 complex is the most abundant and was analyzed in the greatest detail. All three beta subunits contain a conserved domain referred to as the glycogen-binding domain. The deletion of this domain from Gal83 results in a deregulation of the Snf1 kinase, as judged by a constitutive activity independent of glucose availability. In contrast, the deletion of this homologous domain from the Sip1 and Sip2 subunits had little effect on Snf1 kinase regulation. Therefore, the different Snf1 kinase isoforms are regulated through distinct mechanisms, which may contribute to their specialized roles in different stress response pathways. In addition, the beta subunits are subjected to phosphorylation. The responsible kinases were identified as being Snf1 and casein kinase II. The significance of the phosphorylation is unclear since the deletion of the region containing the phosphorylation sites in Gal83 had little effect on the regulation of Snf1 in response to glucose limitation.

  16. 49 CFR 225.5 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... also does not include counseling. Musculoskeletal disorder (MSD) means a disorder of the muscles... illness resulting from a sexual assault; (3) Mental illnesses; (4) HIV infection, hepatitis, or...

  17. Nmd3p Is a Crm1p-Dependent Adapter Protein for Nuclear Export of the Large Ribosomal Subunit

    PubMed Central

    Ho, Jennifer Hei-Ngam; Kallstrom, George; Johnson, Arlen W.

    2000-01-01

    In eukaryotic cells, nuclear export of nascent ribosomal subunits through the nuclear pore complex depends on the small GTPase Ran. However, neither the nuclear export signals (NESs) for the ribosomal subunits nor the receptor proteins, which recognize the NESs and mediate export of the subunits, have been identified. We showed previously that Nmd3p is an essential protein from yeast that is required for a late step in biogenesis of the large (60S) ribosomal subunit. Here, we show that Nmd3p shuttles and that deletion of the NES from Nmd3p leads to nuclear accumulation of the mutant protein, inhibition of the 60S subunit biogenesis, and inhibition of the nuclear export of 60S subunits. Moreover, the 60S subunits that accumulate in the nucleus can be coimmunoprecipitated with the NES-deficient Nmd3p. 60S subunit biogenesis and export of truncated Nmd3p were restored by the addition of an exogenous NES. To identify the export receptor for Nmd3p we show that Nmd3p shuttling and 60S export is blocked by the Crm1p-specific inhibitor leptomycin B. These results identify Crm1p as the receptor for Nmd3p export. Thus, export of the 60S subunit is mediated by the adapter protein Nmd3p in a Crm1p-dependent pathway. PMID:11086007

  18. Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA.

    PubMed

    Hoshi, Toshinori; Tian, Yutao; Xu, Rong; Heinemann, Stefan H; Hou, Shangwei

    2013-03-19

    Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.

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

    Fu Guo; Institute of Neuroscience, Department of Neurobiology, Second Military Medical University, Shanghai 200433; Yang Huayan

    Macrophage differentiation antigen associated with complement three receptor function (Mac-1) belongs to {beta}{sub 2} subfamily of integrins that mediate important cell-cell and cell-extracellular matrix interactions. Biochemical studies have indicated that Mac-1 is a constitutive heterodimer in vitro. Here, we detected the heterodimerization of Mac-1 subunits in living cells by means of two fluorescence resonance energy transfer (FRET) techniques (fluorescence microscopy and fluorescence spectroscopy) and our results demonstrated that there is constitutive heterodimerization of the Mac-1 subunits and this constitutive heterodimerization of the Mac-1 subunits is cell-type independent. Through FRET imaging, we found that heterodimers of Mac-1 mainly localized in plasmamore » membrane, perinuclear, and Golgi area in living cells. Furthermore, through analysis of the estimated physical distances between cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP) fused to Mac-1 subunits, we suggested that the conformation of Mac-1 subunits is not affected by the fusion of CFP or YFP and inferred that Mac-1 subunits take different conformation when expressed in Chinese hamster ovary (CHO) and human embryonic kidney (HEK) 293T cells, respectively.« less

  20. Effect of Cavβ Subunits on Structural Organization of Cav1.2 Calcium Channels

    PubMed Central

    Duong, Son Q.; Thomas, Sam; Harry, Jo Beth; Patel, Chirag; Lao, Qi Zong; Soldatov, Nikolai M.

    2009-01-01

    Background Voltage-gated Cav1.2 calcium channels play a crucial role in Ca2+ signaling. The pore-forming α1C subunit is regulated by accessory Cavβ subunits, cytoplasmic proteins of various size encoded by four different genes (Cavβ1 - β4) and expressed in a tissue-specific manner. Methods and Results Here we investigated the effect of three major Cavβ types, β1b, β2d and β3, on the structure of Cav1.2 in the plasma membrane of live cells. Total internal reflection fluorescence microscopy showed that the tendency of Cav1.2 to form clusters depends on the type of the Cavβ subunit present. The highest density of Cav1.2 clusters in the plasma membrane and the smallest cluster size were observed with neuronal/cardiac β1b present. Cav1.2 channels containing β3, the predominant Cavβ subunit of vascular smooth muscle cells, were organized in a significantly smaller number of larger clusters. The inter- and intramolecular distances between α1C and Cavβ in the plasma membrane of live cells were measured by three-color FRET microscopy. The results confirm that the proximity of Cav1.2 channels in the plasma membrane depends on the Cavβ type. The presence of different Cavβ subunits does not result in significant differences in the intramolecular distance between the termini of α1C, but significantly affects the distance between the termini of neighbor α1C subunits, which varies from 67 Å with β1b to 79 Å with β3. Conclusions Thus, our results show that the structural organization of Cav1.2 channels in the plasma membrane depends on the type of Cavβ subunits present. PMID:19492014

  1. Heterodimerization with the β1 subunit directs the α2 subunit of nitric oxide-sensitive guanylyl cyclase to calcium-insensitive cell-cell contacts in HEK293 cells: Interaction with Lin7a.

    PubMed

    Hochheiser, Julia; Haase, Tobias; Busker, Mareike; Sömmer, Anne; Kreienkamp, Hans-Jürgen; Behrends, Sönke

    2016-12-15

    Nitric oxide-sensitive guanylyl cyclase is a heterodimeric enzyme consisting of an α and a β subunit. Two different α subunits (α 1 and α 2 ) give rise to two heterodimeric enzymes α 1 /β 1 and α 2 /β 1 . Both coexist in a wide range of tissues including blood vessels and the lung, but expression of the α 2 /β 1 form is generally much lower and approaches levels similar to the α 1 /β 1 form in the brain only. In the present paper, we show that the α 2 /β 1 form interacts with Lin7a in mouse brain synaptosomes based on co-precipitation analysis. In HEK293 cells, we found that the overexpressed α 2 /β 1 form, but not the α 1 /β 1 form is directed to calcium-insensitive cell-cell contacts. The isolated PDZ binding motif of an amino-terminally truncated α 2 subunit was sufficient for cell-cell contact localization. For the full length α 2 subunit with the PDZ binding motif this was only the case in the heterodimer configuration with the β 1 subunit, but not as isolated α 2 subunit. We conclude that the PDZ binding motif of the α 2 subunit is only accessible in the heterodimer conformation of the mature nitric oxide-sensitive enzyme. Interaction with Lin7a, a small scaffold protein important for synaptic function and cell polarity, can direct this complex to nectin based cell-cell contacts via MPP3 in HEK293 cells. We conclude that heterodimerization is a prerequisite for further protein-protein interactions that direct the α 2 /β 1 form to strategic sites of the cell membrane with adjacent neighbouring cells. Drugs increasing the nitric oxide-sensitivity of this specific form may be particularly effective. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Impact of lower challenge doses of enterotoxigenic Escherichia coli on clinical outcome, intestinal colonization and immune responses in adult volunteers.

    PubMed

    Chakraborty, Subhra; Harro, Clayton; DeNearing, Barbara; Brubaker, Jessica; Connor, Sean; Maier, Nicole; Dally, Len; Flores, Jorge; Bourgeois, A Louis; Walker, Richard; Sack, David A

    2018-04-01

    A reliable and effective human challenge model is needed to help down-select the most promising ETEC vaccines currently under development. Such a model would need to reliably induce diarrhea in a high proportion of volunteers using the lowest possible inoculum to maximize safety and sensitivity. Previously we validated a challenge model that utilized a dose of 2x107 CFU of ETEC strain H10407 (LT+, ST+, CFA/I+ and O78+) to induce attack rates for moderate to severe diarrhea (MSD) of ~60-70%. Here we detail efforts to further refine the model in an attempt to determine if a lower challenge dose of H10407 can be used. Thirty subjects were randomized 1:1 to receive an oral administration of H10407 at doses of 106 or 105 CFU in bicarbonate buffer. After challenge, subjects were monitored for signs and symptoms of enteric illness and stool samples were collected to detect shedding of the challenge strain. Systemic and mucosal immune responses were measured using serum, antibody in lymphocyte supernatant and fecal samples. The attack rate was 13.3% (2/15) and 26.7% (4/15) for MSD in the 105 and 106 groups, respectively. Four MSD cases met criteria for early antibiotic treatment. All subjects but one shed the challenge strain in fecal samples. The frequency and magnitude of anti-LT toxin, CFA/I and LPS O78 immune responses were antigen, dose, severity of diarrhea and shedding levels dependent. Notably, although of lower magnitude, there were considerable immune responses in the subjects with no diarrhea. This may indicate that immune responses to asymptomatic infections of ETEC in children in the endemic countries may contribute to protection. Based on this and our prior studies, we conclude that a dose of 2x107 H10407 remains the lowest practical dose for use in future volunteer studies evaluating candidate vaccines and other preventive or therapeutic ETEC interventions. ClinicalTrials.gov NCT00844493.

  3. Impact of lower challenge doses of enterotoxigenic Escherichia coli on clinical outcome, intestinal colonization and immune responses in adult volunteers

    PubMed Central

    DeNearing, Barbara; Brubaker, Jessica; Connor, Sean; Maier, Nicole; Dally, Len; Flores, Jorge; Bourgeois, A. Louis; Walker, Richard; Sack, David A.

    2018-01-01

    A reliable and effective human challenge model is needed to help down-select the most promising ETEC vaccines currently under development. Such a model would need to reliably induce diarrhea in a high proportion of volunteers using the lowest possible inoculum to maximize safety and sensitivity. Previously we validated a challenge model that utilized a dose of 2x107 CFU of ETEC strain H10407 (LT+, ST+, CFA/I+ and O78+) to induce attack rates for moderate to severe diarrhea (MSD) of ~60–70%. Here we detail efforts to further refine the model in an attempt to determine if a lower challenge dose of H10407 can be used. Thirty subjects were randomized 1:1 to receive an oral administration of H10407 at doses of 106 or 105 CFU in bicarbonate buffer. After challenge, subjects were monitored for signs and symptoms of enteric illness and stool samples were collected to detect shedding of the challenge strain. Systemic and mucosal immune responses were measured using serum, antibody in lymphocyte supernatant and fecal samples. The attack rate was 13.3% (2/15) and 26.7% (4/15) for MSD in the 105 and 106 groups, respectively. Four MSD cases met criteria for early antibiotic treatment. All subjects but one shed the challenge strain in fecal samples. The frequency and magnitude of anti-LT toxin, CFA/I and LPS O78 immune responses were antigen, dose, severity of diarrhea and shedding levels dependent. Notably, although of lower magnitude, there were considerable immune responses in the subjects with no diarrhea. This may indicate that immune responses to asymptomatic infections of ETEC in children in the endemic countries may contribute to protection. Based on this and our prior studies, we conclude that a dose of 2x107 H10407 remains the lowest practical dose for use in future volunteer studies evaluating candidate vaccines and other preventive or therapeutic ETEC interventions. Trial registration: ClinicalTrials.gov NCT00844493. PMID:29702652

  4. Treatment of clozapine-associated obesity and diabetes with exenatide (CODEX) in adults with schizophrenia: study protocol for a pilot randomised controlled trial.

    PubMed

    Mayfield, Karla; Siskind, Dan; Winckel, Karl; Hollingworth, Samantha; Kisely, Steve; Russell, Anthony W

    2015-06-01

    Clozapine causes significant metabolic disturbances including obesity and type 2 diabetes. Recent evidence that reduced glucagon-like-peptide-1 (GLP-1) may contribute to aetiology of clozapine-associated metabolic dysregulation suggests a potential therapeutic role for GLP-1 agonists. This open-label, pilot randomised controlled trial evaluates the effect of exenatide in clozapine-treated obese adults who have schizophrenia, with or without poorly controlled diabetes. Sixty out-patients will be randomised to once weekly extended release exenatide or treatment as usual for 24 weeks. To evaluate the feasibility of larger studies regarding methodology, acceptability, tolerability and estimate efficacy for glycaemic control or weight loss. Secondary outcomes are psychosis severity and metabolic parameters. This is the first trial investigating GLP-1 agonists for glycaemic control and weight loss in clozapine-treated patients with either diabetes or obesity. Clozapine-associated obesity and diabetes with exenatide (CODEX) will provide proof-of-concept empirical evidence addressing whether this novel treatment is practical and worthy of further investigation. A.W.R. has received speaker honoraria and travel grants from AstraZeneca, BoehringerIngelheim, Eli Lilly, MSD, Novo Nordisk and Sanofi and has participated on advisory panels for MSD and Novo Nordisk. © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

  5. Stone heterogeneity index as the standard deviation of Hounsfield units: A novel predictor for shock-wave lithotripsy outcomes in ureter calculi

    PubMed Central

    Lee, Joo Yong; Kim, Jae Heon; Kang, Dong Hyuk; Chung, Doo Yong; Lee, Dae Hun; Do Jung, Hae; Kwon, Jong Kyou; Cho, Kang Su

    2016-01-01

    We investigated whether stone heterogeneity index (SHI), which a proxy of such variations, was defined as the standard deviation of a Hounsfield unit (HU) on non-contrast computed tomography (NCCT), can be a novel predictor for shock-wave lithotripsy (SWL) outcomes in patients with ureteral stones. Medical records were obtained from the consecutive database of 1,519 patients who underwent the first session of SWL for urinary stones between 2005 and 2013. Ultimately, 604 patients with radiopaque ureteral stones were eligible for this study. Stone related variables including stone size, mean stone density (MSD), skin-to-stone distance, and SHI were obtained on NCCT. Patients were classified into the low and high SHI groups using mean SHI and compared. One-session success rate in the high SHI group was better than in the low SHI group (74.3% vs. 63.9%, P = 0.008). Multivariate logistic regression analyses revealed that smaller stone size (OR 0.889, 95% CI: 0.841–0.937, P < 0.001), lower MSD (OR 0.995, 95% CI: 0.994–0.996, P < 0.001), and higher SHI (OR 1.011, 95% CI: 1.008–1.014, P < 0.001) were independent predictors of one-session success. The radiologic heterogeneity of urinary stones or SHI was an independent predictor for SWL success in patients with ureteral calculi and a useful clinical parameter for stone fragility. PMID:27035621

  6. Stone heterogeneity index as the standard deviation of Hounsfield units: A novel predictor for shock-wave lithotripsy outcomes in ureter calculi.

    PubMed

    Lee, Joo Yong; Kim, Jae Heon; Kang, Dong Hyuk; Chung, Doo Yong; Lee, Dae Hun; Do Jung, Hae; Kwon, Jong Kyou; Cho, Kang Su

    2016-04-01

    We investigated whether stone heterogeneity index (SHI), which a proxy of such variations, was defined as the standard deviation of a Hounsfield unit (HU) on non-contrast computed tomography (NCCT), can be a novel predictor for shock-wave lithotripsy (SWL) outcomes in patients with ureteral stones. Medical records were obtained from the consecutive database of 1,519 patients who underwent the first session of SWL for urinary stones between 2005 and 2013. Ultimately, 604 patients with radiopaque ureteral stones were eligible for this study. Stone related variables including stone size, mean stone density (MSD), skin-to-stone distance, and SHI were obtained on NCCT. Patients were classified into the low and high SHI groups using mean SHI and compared. One-session success rate in the high SHI group was better than in the low SHI group (74.3% vs. 63.9%, P = 0.008). Multivariate logistic regression analyses revealed that smaller stone size (OR 0.889, 95% CI: 0.841-0.937, P < 0.001), lower MSD (OR 0.995, 95% CI: 0.994-0.996, P < 0.001), and higher SHI (OR 1.011, 95% CI: 1.008-1.014, P < 0.001) were independent predictors of one-session success. The radiologic heterogeneity of urinary stones or SHI was an independent predictor for SWL success in patients with ureteral calculi and a useful clinical parameter for stone fragility.

  7. Continuous Sputter Deposition Coating of Long Monofilaments

    DTIC Science & Technology

    2014-04-01

    sectional view of sample 1. Using SEM, the copper coated monofilament was observed to be smooth with little to no indications of flaking or cracked...monofilament. The magnetron sputter deposition (MSD) process was used to apply copper coatings on the order of 10–100 nanometers thick onto both nylon...of monofilaments. Though only copper coatings are discussed in this report, the system could also be used to apply a variety of sputtered metal or

  8. LINKING GABAA RECEPTOR SUBUNITS TO ALCOHOL-INDUCED CONDITIONED TASTE AVERSION AND RECOVERY FROM ACUTE ALCOHOL INTOXICATION

    PubMed Central

    Blednov, Y.A.; Benavidez, J.M.; Black, M.; Chandra, D.; Homanics, G.E.; Rudolph, U.; Harris, R.A.

    2012-01-01

    GABA type A receptors (GABAA-R) are important for ethanol actions and it is of interest to link individual subunits with specific ethanol behaviors. We studied null mutant mice for six different GABAA-R subunits (α1, α2, α3, α4, α5 and δ). Only mice lacking the α2 subunit showed reduction of conditioned taste aversion (CTA) to ethanol. These results are in agreement with data from knock-in mice with mutation of the ethanol-sensitive site in the α2-subunit (Blednov et al., 2011) and indicate this aversive property of ethanol is dependent on ethanol action on α2-containing GABAA-R. Deletion of the α2-subunit led to faster recovery whereas absence of the α3-subunit slowed recovery from ethanol-induced incoordination (rotarod). Deletion of the other four subunits did not affect this behavior. Similar changes in this behavior for the α2 and α3 null mutants were found for flurazepam motor-incoordination. However, no differences in recovery were found in motor-incoordinating effects of an α1-selective modulator (zolpidem) or an α4-selective agonist (gaboxadol). Therefore, recovery of rotarod incoordination is under control of two GABAA-R subunits: α2 and α3. For motor activity, α3 null mice demonstrated higher activation by ethanol (1 g/kg) whereas both α2 and α3 (-/-) knockout mice were less sensitive to ethanol-induced reduction of motor activity (1.5 g/kg). These studies demonstrate that the effects of ethanol at GABAergic synapses containing α2 subunit are important for specific behavioral effects of ethanol which may be relevant to the genetic linkage of the α2 subunit with human alcoholism. PMID:23147414

  9. Extracting quantitative measures from EAP: a small clinical study using BFOR.

    PubMed

    Hosseinbor, A Pasha; Chung, Moo K; Wu, Yu-Chien; Fleming, John O; Field, Aaron S; Alexander, Andrew L

    2012-01-01

    The ensemble average propagator (EAP) describes the 3D average diffusion process of water molecules, capturing both its radial and angular contents, and hence providing rich information about complex tissue microstructure properties. Bessel Fourier orientation reconstruction (BFOR) is one of several analytical, non-Cartesian EAP reconstruction schemes employing multiple shell acquisitions that have recently been proposed. Such modeling bases have not yet been fully exploited in the extraction of rotationally invariant q-space indices that describe the degree of diffusion anisotropy/restrictivity. Such quantitative measures include the zero-displacement probability (P(o)), mean squared displacement (MSD), q-space inverse variance (QIV), and generalized fractional anisotropy (GFA), and all are simply scalar features of the EAP. In this study, a general relationship between MSD and q-space diffusion signal is derived and an EAP-based definition of GFA is introduced. A significant part of the paper is dedicated to utilizing BFOR in a clinical dataset, comprised of 5 multiple sclerosis (MS) patients and 4 healthy controls, to estimate P(o), MSD, QIV, and GFA of corpus callosum, and specifically, to see if such indices can detect changes between normal appearing white matter (NAWM) and healthy white matter (WM). Although the sample size is small, this study is a proof of concept that can be extended to larger sample sizes in the future.

  10. A visual ergonomics intervention in mail sorting facilities: effects on eyes, muscles and productivity.

    PubMed

    Hemphälä, Hillevi; Eklund, Jörgen

    2012-01-01

    Visual requirements are high when sorting mail. The purpose of this visual ergonomics intervention study was to evaluate the visual environment in mail sorting facilities and to explore opportunities for improving the work situation by reducing visual strain, improving the visual work environment and reducing mail sorting time. Twenty-seven postmen/women participated in a pre-intervention study, which included questionnaires on their experiences of light, visual ergonomics, health, and musculoskeletal symptoms. Measurements of lighting conditions and productivity were also performed along with eye examinations of the postmen/women. The results from the pre-intervention study showed that the postmen/women who suffered from eyestrain had a higher prevalence of musculoskeletal disorders (MSD) and sorted slower, than those without eyestrain. Illuminance and illuminance uniformity improved as a result of the intervention. The two post-intervention follow-ups showed a higher prevalence of MSD among the postmen/women with eyestrain than among those without. The previous differences in sorting time for employees with and without eyestrain disappeared. After the intervention, the postmen/women felt better in general, experienced less work induced stress, and considered that the total general lighting had improved. The most pronounced decreases in eyestrain, MSD, and mail sorting time were seen among the younger participants of the group. Copyright © 2011 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  11. Local collective motion analysis for multi-probe dynamic imaging and microrheology

    NASA Astrophysics Data System (ADS)

    Khan, Manas; Mason, Thomas G.

    2016-08-01

    Dynamical artifacts, such as mechanical drift, advection, and hydrodynamic flow, can adversely affect multi-probe dynamic imaging and passive particle-tracking microrheology experiments. Alternatively, active driving by molecular motors can cause interesting non-Brownian motion of probes in local regions. Existing drift-correction techniques, which require large ensembles of probes or fast temporal sampling, are inadequate for handling complex spatio-temporal drifts and non-Brownian motion of localized domains containing relatively few probes. Here, we report an analytical method based on local collective motion (LCM) analysis of as few as two probes for detecting the presence of non-Brownian motion and for accurately eliminating it to reveal the underlying Brownian motion. By calculating an ensemble-average, time-dependent, LCM mean square displacement (MSD) of two or more localized probes and comparing this MSD to constituent single-probe MSDs, we can identify temporal regimes during which either thermal or athermal motion dominates. Single-probe motion, when referenced relative to the moving frame attached to the multi-probe LCM trajectory, provides a true Brownian MSD after scaling by an appropriate correction factor that depends on the number of probes used in LCM analysis. We show that LCM analysis can be used to correct many different dynamical artifacts, including spatially varying drifts, gradient flows, cell motion, time-dependent drift, and temporally varying oscillatory advection, thereby offering a significant improvement over existing approaches.

  12. Strange kinetics of bulk-mediated diffusion on lipid bilayers

    PubMed Central

    Campagnola, Grace; Nepal, Kanti; Peersen, Olve B.

    2016-01-01

    Diffusion at solid-liquid interfaces is crucial in many technological and biophysical processes. Although its behavior seems deceivingly simple, recent studies showing passive superdiffusive transport suggest diffusion on surfaces may hide rich complexities. In particular, bulk-mediated diffusion occurs when molecules are transiently released from the surface to perform three-dimensional excursions into the liquid bulk. This phenomenon bears the dichotomy where a molecule always return to the surface but the mean jump length is infinite. Such behavior is associated with a breakdown of the central limit theorem and weak ergodicity breaking. Here, we use single-particle tracking to study the statistics of bulk-mediated diffusion on a supported lipid bilayer. We find that the time-averaged mean square displacement (MSD) of individual trajectories, the archetypal measure in diffusion processes, does not converge to the ensemble MSD but it remains a random variable, even in the long observation-time limit. The distribution of time averages is shown to agree with a Lévy flight model. Our results also unravel intriguing anomalies in the statistics of displacements. The time averaged MSD is shown to depend on experimental time and investigations of fractional moments show a scaling 〈|r(t)|q〉 ∼ tqv(q) with non-linear exponents, i.e. v(q) ≠ const. This type of behavior is termed strong anomalous diffusion and is rare among experimental observations. PMID:27095275

  13. Widespread fatigue damage monitoring: Issues and concerns

    NASA Technical Reports Server (NTRS)

    Swift, T.

    1994-01-01

    This paper is intended to illustrate the considerable effect that small in-service undetectable multi-site-damage (MSD) can have on the residual strength capability of aging aircraft structures. In general, very few people in the industry believe that tiny cracks of undetectable size are a problem because they know that many aircraft have been able to survive much larger damage. In fact they have been certified for this large damage capability. However, this is not the issue. The real issue is the effect the tiny cracks, at multiple sites, have on the large damage capability which the industry has become accustomed to expect and which the aircraft have been certified to sustain. The concern is that this message does not appear to be fully understood by many people outside the fracture community. The prime purpose of this paper, therefore, has been to convey this message by describing in simple terms the net section yielding phenomenon in ductile materials which causes loss in lead crack residual strength in the presence of MSD. The explanation continues with a number of examples on complex stiffened structures, using the results of previous finite element analyses, which illustrate that the effect of MSD is extremely sensitive to structural configuration. It is hoped that those members of the aviation community who believe that tiny cracks are not a problem will read this paper very carefully.

  14. Recent advances in treatment of aplastic anemia

    PubMed Central

    Shin, Seung Hwan; Lee, Sung Eun

    2014-01-01

    Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA. PMID:25378968

  15. L-type Calcium Channel Blockers Enhance Trafficking and Function of Epilepsy-associated α1(D219N) Subunits of GABA(A) Receptors.

    PubMed

    Han, Dong-Yun; Guan, Bo-Jhih; Wang, Ya-Juan; Hatzoglou, Maria; Mu, Ting-Wei

    2015-09-18

    Gamma-aminobutyric acid type A (GABAA) receptors are the primary inhibitory ion channels in the mammalian central nervous system and play an essential role in regulating inhibition-excitation balance in neural circuits. The α1 subunit harboring the D219N mutation of GABAA receptors was reported to be retained in the endoplasmic reticulum (ER) and traffic inefficiently to the plasma membrane, leading to a loss of function of α1(D219N) subunits and thus idiopathic generalized epilepsy (IGE). We present the use of small molecule proteostasis regulators to enhance the forward trafficking of α1(D219N) subunits to restore their function. We showed that treatment with verapamil (4 μM, 24 h), an L-type calcium channel blocker, substantially increases the α1(D219N) subunit cell surface level in both HEK293 cells and neuronal SH-SY5Y cells and remarkably restores the GABA-induced maximal chloride current in HEK293 cells expressing α1(D219N)β2γ2 receptors to a level that is comparable to wild type receptors. Our drug mechanism study revealed that verapamil treatment promotes the ER to Golgi trafficking of the α1(D219N) subunits post-translationally. To achieve that, verapamil treatment enhances the interaction between the α1(D219N) subunit and β2 subunit and prevents the aggregation of the mutant protein by shifting the protein from the detergent-insoluble fractions to detergent-soluble fractions. By combining (35)S pulse-chase labeling and MG-132 inhibition experiments, we demonstrated that verapamil treatment does not inhibit the ER-associated degradation of the α1(D219N) subunit. In addition, its effect does not involve a dynamin-1 dependent endocytosis. To gain further mechanistic insight, we showed that verapamil increases the interaction between the mutant protein and calnexin and calreticulin, two major lectin chaperones in the ER. Moreover, calnexin binding promotes the forward trafficking of the mutant subunit. Taken together, our data indicate that verapamil treatment enhances the calnexin-assisted forward trafficking and subunit assembly, which leads to substantially enhanced functional surface expression of the mutant receptors. Since verapamil is an FDA-approved drug that crosses blood-brain barrier and has been used as an additional medication for some epilepsies, our findings suggest that verapamil holds great promise to be developed to ameliorate IGE resulting from α1(D219N) subunit trafficking deficiency.

  16. Berkeley Lab - Materials Sciences Division

    Science.gov Websites

    MSD Support Human Resources Facilities & Space Planning Procurement and Property Proposals & Planning Procurement and Property Proposals & Finance Templates Travel Procurement and Property This

  17. Berkeley Lab - Materials Sciences Division

    Science.gov Websites

    ; Finance Templates Travel One-Stop Acknowledging MSD Support Human Resources Facilities & Space Planning Procurement and Property Proposals & Finance Templates Travel Travel This page has been moved

  18. MUC1 and MUC4: Switching the Emphasis from Large to Small

    PubMed Central

    Carraway, Kermit L.

    2011-01-01

    Summation The MUC1 and MUC4 membrane mucins are each composed of a large alpha (α) and a small beta (β) subunit. The α subunits are fully exposed at the cell surface and contain variable numbers of repeated amino acid sequences that are heavily glycosylated. In contrast, the β subunits are much smaller and are anchored within the cell membrane, with their amino-terminal portions exposed at the cell surface and their carboxy-terminal tails facing the cytosol. Studies over the last several years are challenging the long-held belief that α subunits play the predominant role in cancer by conferring cellular properties that allow tumor cells to evade immune recognition and destruction. Indeed, the β subunits of MUC1 and MUC4 have emerged as oncogenes, as they engage signaling pathways responsible for tumor initiation and progression. Thus, a switch in the emphasis from the large α to the small β subunits offers attractive possibilities for successful clinical application. Such a focus shift is further supported by the absence of allelic polymorphism and variable glycosylation in the β subunit as well as by the presence of the β subunit in most MUC1 and MUC4 isoforms expressed by tumors. MUC1α, also known as CA15.3, is a Food and Drug Administration-approved serum biomarker for breast cancer, but its use is no longer recommended by the American Society of Clinical Oncology. However, comparison of β subunit expression in normal and malignant breast tissues may offer a novel approach to the exploitation of membrane mucins as biomarkers, as MUC1β-induced gene signatures with prognostic and predictive values in breast cancer have been reported. Preclinical studies with peptides that interfere with MUC1β oncogenic functions also look promising. PMID:21728842

  19. α2-containing GABAA receptors expressed in hippocampal region CA3 control fast network oscillations

    PubMed Central

    Heistek, Tim S; Ruiperez-Alonso, Marta; Timmerman, A Jaap; Brussaard, Arjen B; Mansvelder, Huibert D

    2013-01-01

    GABAA receptors are critically involved in hippocampal oscillations. GABAA receptor α1 and α2 subunits are differentially expressed throughout the hippocampal circuitry and thereby may have distinct contributions to oscillations. It is unknown which GABAA receptor α subunit controls hippocampal oscillations and where these receptors are expressed. To address these questions we used transgenic mice expressing GABAA receptor α1 and/or α2 subunits with point mutations (H101R) that render these receptors insensitive to allosteric modulation at the benzodiazepine binding site, and tested how increased or decreased function of α subunits affects hippocampal oscillations. Positive allosteric modulation by zolpidem prolonged decay kinetics of hippocampal GABAergic synaptic transmission and reduced the frequency of cholinergically induced oscillations. Allosteric modulation of GABAergic receptors in CA3 altered oscillation frequency in CA1, while modulation of GABA receptors in CA1 did not affect oscillations. In mice having a point mutation (H101R) at the GABAA receptor α2 subunit, zolpidem effects on cholinergically induced oscillations were strongly reduced compared to wild-type animals, while zolpidem modulation was still present in mice with the H101R mutation at the α1 subunit. Furthermore, genetic knockout of α2 subunits strongly reduced oscillations, whereas knockout of α1 subunits had no effect. Allosteric modulation of GABAergic receptors was strongly reduced in unitary connections between fast spiking interneurons and pyramidal neurons in CA3 of α2H101R mice, but not of α1H101R mice, suggesting that fast spiking interneuron to pyramidal neuron synapses in CA3 contain α2 subunits. These findings suggest that α2-containing GABAA receptors expressed in the CA3 region provide the inhibition that controls hippocampal rhythm during cholinergically induced oscillations. PMID:23109109

  20. SU-F-BRF-01: A GPU Framework for Developing Interactive High-Resolution Patient-Specific Biomechanical Models

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

    Neylon, J; Qi, S; Sheng, K

    2014-06-15

    Purpose: To develop a GPU-based framework that can generate highresolution and patient-specific biomechanical models from a given simulation CT and contoured structures, optimized to run at interactive speeds, for addressing adaptive radiotherapy objectives. Method: A Massspring-damping (MSD) model was generated from a given simulation CT. The model's mass elements were generated for every voxel of anatomy, and positioned in a deformation space in the GPU memory. MSD connections were established between neighboring mass elements in a dense distribution. Contoured internal structures allowed control over elastic material properties of different tissues. Once the model was initialized in GPU memory, skeletal anatomymore » was actuated using rigid-body transformations, while soft tissues were governed by elastic corrective forces and constraints, which included tensile forces, shear forces, and spring damping forces. The model was validated by applying a known load to a soft tissue block and comparing the observed deformation to ground truth calculations from established elastic mechanics. Results: Our analyses showed that both local and global load experiments yielded results with a correlation coefficient R{sup 2} > 0.98 compared to ground truth. Models were generated for several anatomical regions. Head and neck models accurately simulated posture changes by rotating the skeletal anatomy in three dimensions. Pelvic models were developed for realistic deformations for changes in bladder volume. Thoracic models demonstrated breast deformation due to gravity when changing treatment position from supine to prone. The GPU framework performed at greater than 30 iterations per second for over 1 million mass elements with up to 26 MSD connections each. Conclusions: Realistic simulations of site-specific, complex posture and physiological changes were simulated at interactive speeds using patient data. Incorporating such a model with live patient tracking would facilitate real time assessment of variations of the actual anatomy and delivered dose for adaptive intervention and re-planning.« less

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