Science.gov

Sample records for early phase response

  1. Regulatory parameters of the lung immune response during the early phase of experimental trichinellosis.

    PubMed

    Falduto, Guido H; Vila, Cecilia C; Saracino, María P; Gentilini, María V; Venturiello, Stella M

    2016-11-15

    Parasitic infection caused by Trichinella spiralis provokes an early stimulation of the mucosal immune system which causes an allergic inflammatory response in the lungs. The present work was intended to characterize the kinetics of emergence of regulatory parameters in Wistar rat lungs during this early inflammatory response, between days 0 and 13p.i. The presence of regulatory cells such as regulatory T cells (Tregs) and alternatively activated macrophages (AAM) was analyzed in lung cell suspensions. Moreover, a regulatory cytokine (TGF-β) was studied in lung tissue extracts. Considering that newborn larvae (NBL) travel along the pulmonary microvasculature, the ability of this parasite stage to modulate the activation of lung macrophages was evaluated. For this purpose, lung macrophages from non-infected or infected rats (day 6p.i.) were cultured with live or dead NBL. Arginase activity (characteristic of AAM) and nitric oxide (NO produced by iNOS, characteristic of classical activated macrophages) were measured after 48h. Our results revealed a significant increase in the percentage of Tregs on days 6 and 13p.i., arginase activity on day 13p.i. and TGF-β levels on days 6 and 13p.i. Lung macrophages from non-infected rats cultured with live NBL showed a significant increase in arginase activity and NO levels. Live and dead NBL induced a significant increase in arginase activity in lung macrophages from infected rats. Only live NBL significantly increased NO levels in these macrophages. The present work demonstrates for the first time, the emergence of regulatory parameters in the early lung immune response during T. spiralis infection. The immumodulatory properties exerted by NBL during its passage through this organ could be the cause of such regulation. Moreover, we have shown the ability of NBL to activate macrophages from the lung parenchyma by the classical and alternative pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials.

    PubMed

    George, Angela; Kristeleit, Rebecca; Rafii, Saeed; Michie, Caroline O; Bowen, Rebecca; Michalarea, Vasiliki; van Hagen, Tom; Wong, Mabel; Rallis, Grigorios; Molife, L Rhoda; Lopez, Juanita; Banerji, Udai; Banerjee, Susana N; Gore, Martin E; de Bono, Johann S; Kaye, Stan B; Yap, Timothy A

    2017-05-01

    Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010. A total of 200 AOC patients with progressive disease were allocated to ≥1 trial each, with a total of 281 allocations. Of these, 135 (68%) patients commenced ≥1 trial (mean 1.4 [1-8]), totaling 216 allocated trials; 65 (32%) patients did not start due to deterioration resulting from rapidly progressive disease (63 patients) or patient choice (2 patients). Response Evaluation Criteria in Solid Tumours (RECIST) complete/partial responses (CR/PR) were observed in 43 (20%) of those starting trials, including those on poly(ADP-ribose) polymerase (PARP) inhibitors (18/79 [23%]), antiangiogenics (9/65 [14%]) and chemotherapy combinations (14/43 [33%]). Factors associated with CR/PR included: fewer prior treatments, platinum-sensitive disease, CR/PR with prior therapy, (the United States-based) Eastern Cooperative Oncology Group (ECOG) performance status score, fewer metastatic sites, higher albumin and haemoglobin levels, lower white cell counts and baseline CA125 levels, germline BRCA1/2 mutations and better RMH Prognostic Score. Mean survival was 32° months for patients who achieved CR/PR. Treatments were generally well tolerated. Most patients with AOC (134/200 [67%]) received ≥1 subsequent line of therapy after phase I trials. Our data suggest that phase I trial referrals should be considered earlier in the AOC treatment pathway and before the onset of rapid disease progression particularly with the emergence of

  3. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    PubMed

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

  4. Considering baseline factors and early response rates to optimize therapy for chronic myeloid leukemia in chronic phase.

    PubMed

    Akard, Luke P; Bixby, Dale

    2016-05-01

    Multiple BCR-ABL tyrosine kinase inhibitors (TKIs) are available for the treatment of chronic myeloid leukemia in chronic phase (CML-CP), and several baseline and on-treatment predictive factors have been identified that can be used to help guide TKI selection for individual patients. In particular, early molecular response (EMR; BCR-ABL ≤10% on the International Scale at 3 months) has become an accepted benchmark for evaluating whether patients with CML-CP are responding optimally to frontline TKI therapy. Failure to achieve EMR is considered an inadequate initial response according to the National Comprehensive Cancer Network guidelines and a warning response according to the European LeukemiaNet recommendations. Here we review data supporting the importance of achieving EMR for improving patients' long-term outcomes and discuss key considerations for selecting a frontline TKI in light of these data. Because a higher proportion of patients achieve EMR with second-generation TKIs such as nilotinib and dasatinib than with imatinib, these TKIs may be preferable for many patients, particularly those with known negative prognostic factors at baseline. We also discuss other considerations for frontline TKI choice, including toxicities, cost-effectiveness, and the emerging goals of deep molecular response and treatment-free remission.

  5. Potential subjects' responses to an ethics questionnaire in a phase I study of deep brain stimulation in early Parkinson's disease.

    PubMed

    Finder, Stuart G; Bliton, Mark J; Gill, Chandler E; Davis, Thomas L; Konrad, Peter E; Charles, P David

    2012-01-01

    Central to ethically justified clinical trial design is the need for an informed consent process responsive to how potential subjects actually comprehend study participation, especially study goals, risks, and potential benefits. This will be particularly challenging when studying deep brain stimulation and whether it impedes symptom progression in Parkinson's disease, since potential subjects will be Parkinson's patients for whom deep brain stimulation will likely have therapeutic value in the future as their disease progresses. As part of an expanded informed consent process for a pilot Phase I study of deep brain stimulation in early stage Parkinson's disease, an ethics questionnaire composed of 13 open-ended questions was distributed to potential subjects. The questionnaire was designed to guide potential subjects in thinking about their potential participation. While the purpose of the study (safety and tolerability) was extensively presented during the informed consent process, in returned responses 70 percent focused on effectiveness and 91 percent included personal benefit as poten- tial benefit from enrolling. However, 91 percent also indicated helping other Parkinson's patients as motivation when considering whether or not to enroll. This combination of responses highlights two issues to which investigators need to pay close attention in future trial designs: (1) how, and in what ways, informed consent processes reinforce potential subjects' preconceived understandings of benefit, and (2) that potential subjects see themselves as part of a community of Parkinson's sufferers with responsibilities extending beyond self-interest. More importantly, it invites speculation that a different paradigm for informed consent may be needed.

  6. Role of phase instabilities in the early response of bulk fused silica during laser-induced breakdown

    NASA Astrophysics Data System (ADS)

    Demange, P.; Negres, R. A.; Raman, R. N.; Colvin, J. D.; Demos, S. G.

    2011-08-01

    We report on the experimental and hydrocode modeling investigation of the early material response to localized energy deposition via nanosecond laser pulses in bulk fused silica. A time-resolved microscope system was used to acquire transient images with adequate spatial and temporal resolution to resolve the material behavior from the onset of the process. These images revealed a high-pressure shock front propagating at twice the speed of sound at ambient conditions and bounding a region of modified material at delays up to one nanosecond. Hydrocode simulations matching the experimental conditions were also performed and indicated initial pressures of ˜40 GPa and temperatures of ˜1 eV at the absorption region. Both the simulations and the image data show a clear boundary between distinct material phases, a hot plasma and solid silica, with a suggestion that growth of perturbations at the Rayleigh-Taylor unstable interface between the two phases is the seed mechanism for the growth of cracks into the stressed solid.

  7. The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases

    PubMed Central

    Rhodes, Lesley E.; Gledhill, Karl; Masoodi, Mojgan; Haylett, Ann K.; Brownrigg, Margaret; Thody, Anthony J.; Tobin, Desmond J.; Nicolaou, Anna

    2009-01-01

    Sunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids, and their subsequent metabolism by cyclooxygenases (COXs) and lipoxygenases (LOXs) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course. We exposed skin of healthy humans (n=32) to UVB and, for 72 h, examined expression of proinflammatory and anti-inflammatory eicosanoids using LC/ESI-MS/MS, and examined immunohistochemical expression of COX-2, 12-LOX, 15-LOX, and leukocyte markers, while quantifying clinical erythema. We show that vasodilatory prostaglandins (PGs) PGE2, PGF2α, and PGE3 accompany the erythema in the first 24–48 h, associated with increased COX-2 expression at 24 h. Novel, potent leukocyte chemoattractants 11-, 12-, and 8-monohydroxy-eicosatetraenoic acid (HETE) are elevated from 4 to 72 h, in association with peak dermal neutrophil influx at 24 h, and increased dermal CD3+ lymphocytes and 12- and 15-LOX expression from 24 to 72 h. Anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72 h. Sunburn is characterized by overlapping sequential profiles of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution.—Rhodes, L. E., Gledhill, K., Masoodi, M., Haylett, A. K., Brownrigg, M., Thody, A. J., Tobin, D. J., Nicolaou, A. The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases. PMID:19584301

  8. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION)

    PubMed Central

    Jabbour, Elias; Saglio, Giuseppe; Steegmann, Juan Luis; Shah, Neil P.; Boqué, Concepción; Chuah, Charles; Pavlovsky, Carolina; Mayer, Jiří; Cortes, Jorge; Baccarani, Michele; Kim, Dong-Wook; Bradley-Garelik, M. Brigid; Mohamed, Hesham; Wildgust, Mark; Hochhaus, Andreas

    2014-01-01

    This analysis explores the impact of early cytogenetic and molecular responses on the outcomes of patients with chronic myeloid leukemia in chronic phase (CML-CP) in the phase 3 DASatinib versus Imatinib Study In treatment-Naive CML patients trial with a minimum follow-up of 3 years. Patients with newly diagnosed CML-CP were randomized to receive 100 mg dasatinib (n = 259) or 400 mg imatinib (n = 260) once daily. The retrospective landmark analysis included patients evaluable at the relevant time point (3, 6, or 12 months). Median time to complete cytogenetic response was 3 vs 6 months with dasatinib vs imatinib. At 3 and 6 months, the proportion of patients with BCR-ABL transcript levels ≤10% was higher in the dasatinib arm. Deeper responses at 3, 6, and 12 months were observed in a higher proportion of patients on dasatinib therapy and were associated with better 3-year progression-free survival and overall survival in both arms. First-line dasatinib resulted in faster and deeper responses compared with imatinib. The achievement of an early molecular response was predictive of improved progression-free survival and overall survival, supporting new milestones for optimal response in patients with early CML-CP treated with tyrosine kinase inhibitors. This study was registered at www.clinicaltrials.gov as NCT00481247. PMID:24311723

  9. Human Dose-Response Data for Francisella tularensis and a Dose- and Time-Dependent Mathematical Model of Early-Phase Fever Associated with Tularemia After Inhalation Exposure.

    PubMed

    McClellan, Gene; Coleman, Margaret; Crary, David; Thurman, Alec; Thran, Brandolyn

    2018-04-25

    Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis, strain Schu S4, which causes tularemia. The data set includes incidence of early-phase febrile illness following administration of well-characterized inhaled doses of F. tularensis. Supplemental data on human body temperature profiles over time available from de-identified case reports is also presented. A unified, logically consistent model of early-phase febrile illness is described as a lognormal dose-response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near-maximum body temperature. Inhaled dose-dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual-by-individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early-phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis. © 2018 Society for Risk Analysis.

  10. Early- and later-phases satellite cell responses and myonuclear content with resistance training in young men.

    PubMed

    Damas, Felipe; Libardi, Cleiton A; Ugrinowitsch, Carlos; Vechin, Felipe C; Lixandrão, Manoel E; Snijders, Tim; Nederveen, Joshua P; Bacurau, Aline V; Brum, Patricia; Tricoli, Valmor; Roschel, Hamilton; Parise, Gianni; Phillips, Stuart M

    2018-01-01

    Satellite cells (SC) are associated with skeletal muscle remodelling after muscle damage and/or extensive hypertrophy resulting from resistance training (RT). We recently reported that early increases in muscle protein synthesis (MPS) during RT appear to be directed toward muscle damage repair, but MPS contributes to hypertrophy with progressive muscle damage attenuation. However, modulations in acute-chronic SC content with RT during the initial (1st-wk: high damage), early (3rd-wk: attenuated damage), and later (10th-wk: no damage) stages is not well characterized. Ten young men (27 ± 1 y, 23.6 ± 1.0 kg·m-2) underwent 10-wks of RT and muscle biopsies (vastus-lateralis) were taken before (Pre) and post (48h) the 1st (T1), 5th (T2) and final (T3) RT sessions to evaluate fibre type specific SC content, cross-sectional area (fCSA) and myonuclear number by immunohistochemistry. We observed RT-induced hypertrophy after 10-wks of RT (fCSA increased ~16% in type II, P < 0.04; ~8% in type I [ns]). SC content increased 48h post-exercise at T1 (~69% in type I [P = 0.014]; ~42% in type II [ns]), and this increase was sustained throughout RT (pre T2: ~65%, ~92%; pre T3: ~30% [ns], ~87%, for the increase in type I and II, respectively, vs. pre T1 [P < 0.05]). Increased SC content was not coupled with changes in myonuclear number. SC have a more pronounced role in muscle repair during the initial phase of RT than muscle hypertrophy resulted from 10-wks RT in young men. Chronic elevated SC pool size with RT is important providing proper environment for future stresses or larger fCSA increases.

  11. Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C.

    PubMed

    Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan; Cho, Nam-Hyuk

    2017-01-01

    Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.

  12. Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C

    PubMed Central

    Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan

    2017-01-01

    Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients. PMID:28614389

  13. Inter-cohort cannibalism of early benthic phase blue king crabs (Paralithodes platypus): alternate foraging strategies in different habitats lead to different functional responses.

    PubMed

    Daly, Benjamin; Long, W Christopher

    2014-01-01

    Blue king crabs (Paralithodes platypus) are commercially and ecologically important in Alaska, USA, but population abundances have fluctuated over the past several decades likely resulting from a combination of environmental and biological factors, including recruitment variability. Cannibalism between cohorts may be a source of mortality limiting recruitment success in the wild, but the degree of inter-cohort cannibalism is unknown for early benthic phase blue king crabs. In laboratory experiments, we evaluated the effects of habitat type (sand and shell) on the predator functional response and foraging behavior of year-1 blue king crabs as predators of year-0 conspecifics and examined the effects of predator presence on crypsis of prey crabs. In sand, consumption rates increased with predator size and prey density until satiation, while predation rates in shell were low regardless of predator size or prey density. These differential predation rates yielded a type III functional response in sand but a type I functional response in shell habitat. Crypsis of prey crabs was generally high and did not change in the presence of predators. Predator foraging activity was reduced in shell and may be an adaptive behavior to balance foraging efficiency and susceptibility to larger predators. Our results demonstrate that early benthic phase blue king crabs are cannibalistic between cohorts in the laboratory and that shell material is extremely effective for reducing encounter rates with conspecific predators. The distribution and abundance of such habitat may be important for recruitment success in some populations. Future studies should compare benthic habitat and species assemblages in areas with variable abundances, such as the Pribilof Islands and Saint Matthew Island in the eastern Bering Sea, to better understand possible mechanisms for recruitment variability.

  14. Inter-Cohort Cannibalism of Early Benthic Phase Blue King Crabs (Paralithodes platypus): Alternate Foraging Strategies in Different Habitats Lead to Different Functional Responses

    PubMed Central

    Daly, Benjamin; Long, W. Christopher

    2014-01-01

    Blue king crabs (Paralithodes platypus) are commercially and ecologically important in Alaska, USA, but population abundances have fluctuated over the past several decades likely resulting from a combination of environmental and biological factors, including recruitment variability. Cannibalism between cohorts may be a source of mortality limiting recruitment success in the wild, but the degree of inter-cohort cannibalism is unknown for early benthic phase blue king crabs. In laboratory experiments, we evaluated the effects of habitat type (sand and shell) on the predator functional response and foraging behavior of year-1 blue king crabs as predators of year-0 conspecifics and examined the effects of predator presence on crypsis of prey crabs. In sand, consumption rates increased with predator size and prey density until satiation, while predation rates in shell were low regardless of predator size or prey density. These differential predation rates yielded a type III functional response in sand but a type I functional response in shell habitat. Crypsis of prey crabs was generally high and did not change in the presence of predators. Predator foraging activity was reduced in shell and may be an adaptive behavior to balance foraging efficiency and susceptibility to larger predators. Our results demonstrate that early benthic phase blue king crabs are cannibalistic between cohorts in the laboratory and that shell material is extremely effective for reducing encounter rates with conspecific predators. The distribution and abundance of such habitat may be important for recruitment success in some populations. Future studies should compare benthic habitat and species assemblages in areas with variable abundances, such as the Pribilof Islands and Saint Matthew Island in the eastern Bering Sea, to better understand possible mechanisms for recruitment variability. PMID:24558414

  15. Pharmacogenomics in early-phase clinical development

    PubMed Central

    Burt, Tal; Dhillon, Savita

    2015-01-01

    Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs. PMID:23837482

  16. Early non-response to certolizumab pegol in rheumatoid arthritis predicts treatment failure at one year. Data from a randomised phase III clinical trial.

    PubMed

    Berenbaum, Francis; Pham, Thao; Claudepierre, Pascal; de Chalus, Thibault; Joubert, Jean-Michel; Saadoun, Carine; Riou França, Lionel; Fautrel, Bruno

    2018-01-01

    To compare different early clinical criteria of non-response determined at three months as predictors of clinical failure at one year in patients with rheumatoid arthritis starting therapy with certolizumab pegol. Data were derived from a randomised Phase III clinical trial in patients with rheumatoid arthritis who failed to respond to methotrexate monotherapy. Patients included in this post-hoc analysis were treated with certolizumab pegol (400mg qd reduced to 200mg qd after one month) and with methotrexate. The study duration was twelve months. Response at three months was determined with the American College of Rheumatology-50, Disease Assessment Score-28 ESR, Health Assessment Questionnaire and the Clinical Disease Activity Index. The performance of these measures at predicting treatment failure at twelve months defined by the American College of Rheumatology-50 criteria was determined, using the positive predictive values as the principal evaluation criterion. Three hundred and eighty two patients were available for analysis and 225 completed the twelve-month follow-up. At Week 52, 149 (38.1%) patients met the American College of Rheumatology-50 response criterion. Positive predictive values ranged from 81% for a decrease in Health Assessment Questionnaire- Disability index score since baseline >0.22 to 95% for a decrease in Disease Assessment Score-28 score since baseline≥1.2. Sensitivity was≤70% in all cases. Performance of these measures was similar irrespective of the definition of treatment failure at 12months. Simple clinical measures of disease activity can predict future treatment failure reliably and are appropriate for implementing treat-to-target treatment strategies in everyday practice. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  17. Brain responses to food images during the early and late follicular phase of the menstrual cycle in healthy young women: relation to fasting and feeding1234

    PubMed Central

    Ziemke, Florencia; Magkos, Faidon; Barrios, Fernando A; Brinkoetter, Mary; Boyd, Ingrid; Rifkin-Graboi, Anne; Yannakoulia, Mary; Rojas, Rafael; Pascual-Leone, Alvaro; Mantzoros, Christos S

    2011-01-01

    Background: Food intake fluctuates throughout the menstrual cycle; it is greater during the early follicular and luteal phases than in the late follicular (periovulatory) phase. Ovarian steroids can influence brain areas that process food-related information, but the specific contribution of individual hormones and the importance of the prandial state remain unknown. Objective: The objective was to examine whether brain activation during food visualization is affected by changes in estradiol concentration in the fasted and fed conditions. Design: Nine eumenorrheic, lean young women [mean (±SD) age: 26.2 ± 3.2 y; body mass index (in kg/m2): 22.4 ± 1.2] completed 2 visits, one in the early (low estradiol) and one in the late (high estradiol) follicular phase of their menstrual cycle. At each visit, subjects underwent functional magnetic resonance imaging while they viewed food and nonfood images, before and after a standardized meal. Region-of-interest analysis was used to examine the effect of follicular phase and prandial state on brain activation (food > nonfood contrast) and its association with estradiol concentration. Results: Differences were identified in the inferior frontal and fusiform gyri. In these areas, visualization of food elicited greater activation in the fed state than during fasting but only in the late follicular phase, when estradiol concentration was high. The change in estradiol concentration across the follicular phase (late minus early) was inversely correlated with the change in fusiform gyrus activation in the fasted state but not in the fed state. Conclusion: Our findings suggest that estradiol may reduce food intake by decreasing sensitivity to food cues in the ventral visual pathway under conditions of energy deprivation. This trial was registered at clinicaltrials.gov as NCT00130117. PMID:21593494

  18. [Early mobilization. Competencies, responsibilities, milestones].

    PubMed

    Nydahl, P; Dewes, M; Dubb, R; Filipovic, S; Hermes, C; Jüttner, F; Kaltwasser, A; Klarmann, S; Klas, K; Mende, H; Rothaug, O; Schuchhardt, D

    2016-03-01

    Early mobilization is an evident, interprofessional concept to improve the outcome of intensive care patients. It reduces psychocognitive deficits and delirium and attenuates a general deconditioning, including atrophy of the respiratory pump and skeletal muscles. In this regard the interdisciplinary approach of early mobilization, taking into account different levels of mobilization, appears to be beneficial. The purpose of this study was to explore opinions on collaboration and tasks between different professional groups. During the 25th Bremen Conference on Intensive Medicine and Nursing on 20 February 2015, a questionnaire survey was carried out among the 120 participants of the German Early Mobilization Network meeting. In all, 102 questionnaires were analyzed. Most participants reported on the interdisciplinarity of the approach, but none of the tasks and responsibilities concerning early mobilization can be assigned to a single professional group. The practical implementation of mobilizing orally intubated patients may require two registered nurses as well as a physical therapist. Implementation in daily practice seems to be heterogeneous. There is no consensus regarding collaboration, competencies, and responsibilities with respect to early mobilization of intensive care patients. The approach to date has been characterized by a lack of interprofessional communication, which may lead to an inefficient use of the broad and varied base of knowledge and experienceof the different professions.

  19. Phase III Early Restoration Public Meetings | NOAA Gulf Spill Restoration

    Archive Home Phase III Early Restoration Public Meetings Phase III Early Restoration Public Meetings share Posted on December 6, 2013 | Assessment and Early Restoration Restoration Area Title: Phase III Early on the draft plan for the third phase of Early Restoration, which proposes more than $625 million in

  20. Effect of golden needle mushroom (Flammulina velutipes) stem waste on laying performance, calcium utilization, immune response and serum immunity at early phase of production.

    PubMed

    Mahfuz, Shad; Song, Hui; Liu, Zhongjun; Liu, Xinyu; Diao, Zipeng; Ren, Guihong; Guo, Zhixin; Cui, Yan

    2018-05-01

    This experiment was conducted to evaluate the effects of golden needle mushroom ( Flammulina velutipes ) stem waste (FVW), on organic eggs production, calcium utilization, antibody response, serum immunoglobulin, and serum cytokine concentration at early phase of production in laying hens. A total 210, 19 weeks old aged ISA Brown layers were randomly assigned into 5 equal treatment groups, with 7 replications of 6 hens each. Dietary treatment included a standard basal diet as control; antibiotic (0.05% flavomycin); 2% FVW; 4% FVW; and 6% FVW. The experimental duration was 10 weeks. There was no significant differences (p>0.05) on hen day egg production, egg weight, egg mass, feed intake, and feed conversion ratio (FCR) among experimental groups. Unmarketable eggs were significantly lower (p<0.05) both in 4% FVW and 6% FVW fed groups than control group. The calcium retention and calcium in egg shell deposition were significantly higher (p<0.05) in FVW inclusion groups than control and antibiotic groups. Antibody titers against Newcastle diseases were significantly higher (p<0.05) in 6% FVW fed group (except combined with 4% FVW at day 147) and infectious bronchitis were significantly higher (p< 0.05) in FVW fed groups (except 2% FVW and 4% FVW at day 161) than control and antibiotic groups. Serum immunoglobulin sIgA was significantly higher (p<0.05) in all levels of FVW and IgG was significantly higher (p<0.05) in 4% FVW than control and antibiotic groups. Serum cytokine concentration interleukin-2 (IL-2) was significantly higher (p<0.05) in 6% FVW; IL-6 and tumor necrotic factor-α were significantly higher (p<0.05) both in 4% FVW and 6% FVW than control and antibiotic groups; IL-4 was significantly higher (p<0.05) in antibiotic, 2% FVW and 4% FVW fed groups than control. F. velutipes mushroom waste can be used as a novel substitute for antibiotic for organic egg production and sound health status in laying hens.

  1. Phase V of Early Restoration | NOAA Gulf Spill Restoration

    Phase V Early Restoration Plan and Environmental Assessment. The project will acquire land along Florida million. Phase V Early Restoration Plan and Environmental Assessment (pdf, 10 MB) Draft Phase V Early Restoration Plan and Environmental Assessment (Executive Summary) (2 MB) Phase V Fact Sheet (pdf, 2 MB) Gulf

  2. Phase III of Early Restoration | NOAA Gulf Spill Restoration

    information about this phase of Early Restoration, including fact sheets on each project. The final Phase III 44 projects are documented in a final Record of Decision. Information about Phase III of Early Archive Home Phase III of Early Restoration Phase III of Early Restoration Beach habitat would be restored

  3. Induction of a pathological complete response by four courses of neoadjuvant chemotherapy for gastric cancer: early results of the randomized phase II COMPASS trial.

    PubMed

    Yoshikawa, Takaki; Tanabe, Kazuaki; Nishikawa, Kazuhiro; Ito, Yuichi; Matsui, Takanori; Kimura, Yutaka; Hirabayashi, Naoki; Mikata, Shoki; Iwahashi, Makoto; Fukushima, Ryoji; Takiguchi, Nobuhiro; Miyashiro, Isao; Morita, Satoshi; Miyashita, Yumi; Tsuburaya, Aakira; Sakamoto, Junichi

    2014-01-01

    The prognosis for stage 3 gastric cancer is not satisfactory, even with S-1 adjuvant chemotherapy. A randomized phase II trial was conducted to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. The primary endpoint was overall survival. We clarified the impact of these regimens on the secondary endpoints, including the clinical and pathological responses, chemotherapy-related toxicities, and surgical results. Patients received S-1 (80 mg/m(2) for 21 days with 1 week's rest)/cisplatin (60 mg/m(2) at day 8) or paclitaxel/cisplatin (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week's rest) as neoadjuvant chemotherapy. Eighty-three patients were assigned to arm A (two courses of SC, n = 21), arm B (four courses of SC, n = 20), arm C (two courses of PC, n = 21), and arm D (four courses of PC, n = 21). Pathological response rate was 43 % in arm A, 40 % in arm B, 29 % in arm C, and 38 % in arm D. Pathological complete response was only observed in arms B (10 %) and D (10 %). Most bone marrow toxicities, nausea, vomiting, alopecia, and fatigue were slightly higher but acceptable in arms B and D. Grade 3/4 surgical morbidities were not commonly observed in all four arms. Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen.

  4. Early detection and rapid response

    Westbrooks, Randy G.; Eplee, Robert E.; Simberloff, Daniel; Rejmánek, Marcel

    2011-01-01

    Prevention is the first line of defense against introduced invasive species - it is always preferable to prevent the introduction of new invaders into a region or country. However, it is not always possible to detect all alien hitchhikers imported in cargo, or to predict with any degree of certainty which introduced species will become invasive over time. Fortunately, the majority of introduced plants and animals don't become invasive. But, according to scientists at Cornell University, costs and losses due to species that do become invasive are now estimated to be over $137 billion/year in the United States. Early detection and rapid response (EDRR) is the second line of defense against introduced invasive species - EDRR is the preferred management strategy for preventing the establishment and spread of invasive species. Over the past 50 years, there has been a gradual shift away from large and medium scale federal/state single-agency-led weed eradication programs in the United States, to smaller interagency-led projects involving impacted and potential stakeholders. The importance of volunteer weed spotters in detecting and reporting suspected new invasive species has also been recognized in recent years.

  5. Phase IV of Early Restoration | NOAA Gulf Spill Restoration

    Trustees published the Final Phase IV Early Restoration Plan and Environmental Assessments. The plan habitats. Useful Links: Final Phase IV Early Restoration Plan and Environmental Assessments (pdf, 4.8 MB ) Final Phase IV Early Restoration Plan and Environmental Assessments Executive Summary (pdf, 729 KB

  6. Early caregiving and physiological stress responses.

    PubMed

    Luecken, Linda J; Lemery, Kathryn S

    2004-05-01

    Inadequate early caregiving has been associated with risks of stress-related psychological and physical illness over the life span. Dysregulated physiological stress responses may represent a mechanism linking early caregiving to health outcomes. This paper reviews evidence linking early caregiving to physiological responses that can increase vulnerability to stress-related illness. A number of high-risk family characteristics, including high conflict, divorce, abuse, and parental psychopathology, are considered in the development of stress vulnerability. Three theoretical pathways linking caregiving to physiological stress responses are outlined: genetic, psychosocial, and cognitive-affective. Exciting preliminary evidence suggests that early caregiving can impact long-term physiological stress responses. Directions for future research in this area are suggested.

  7. Phase III Early Restoration Meeting | NOAA Gulf Spill Restoration

    Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News Publications Press Releases Story programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

  8. Phase III Early Restoration Meeting - Pensacola, FL (rescheduled) | NOAA

    Restoration Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

  9. Poor early response to methotrexate portends inadequate long-term outcomes in patients with moderate-to-severe psoriasis: Evidence from 2 phase 3 clinical trials.

    PubMed

    Gordon, Kenneth B; Betts, Keith A; Sundaram, Murali; Signorovitch, James E; Li, Junlong; Xie, Meng; Wu, Eric Q; Okun, Martin M

    2017-12-01

    Most methotrexate-treated psoriasis patients do not achieve a long-term PASI75 (75% reduction from baseline Psoriasis Area and Severity Index score) response. Indications of nonresponse can be apparent after only 4 weeks of treatment. To develop a prediction rule to identify patients unlikely to respond adequately to methotrexate. Patient-level data from CHAMPION (NCT00235820, N = 110) was used to construct a prediction model for week 16 PASI75 by using patient baseline characteristics and week 4 PASI25. A prediction rule was determined on the basis of the sensitivity and specificity and validated in terms of week 16 PASI75 response in an independent validation sample from trial M10-255 (NCT00679731, N = 163). PASI25 achievement at week 4 (odds ratio = 8.917) was highly predictive of response with methotrexate at week 16. Patients with a predicted response probability <30% were recommended to discontinue methotrexate. The rates of week 16 PASI75 response were 65.8% and 21.1% (P < .001) for patients recommended to continue and discontinue methotrexate, respectively. The CHAMPION trial excluded patients previously treated with biologics, and the M10-255 trial had no restrictions. A prediction rule was developed and validated to identify patients unlikely to respond adequately to methotrexate. The rule indicates that 4 weeks of methotrexate might be sufficient to predict long-term response with limited safety risk. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  10. Tertiary disaster response phase 1.

    DOT National Transportation Integrated Search

    2007-01-01

    The events of 9/11 and Katrina focused national attention on issues surrounding disaster prevention and response, but as is evident the world continues to be inundated with catastrophic disasters whether man-made through war and terrorism or natural ...

  11. Inferring cardiac phase response curve in vivo

    NASA Astrophysics Data System (ADS)

    Pikovsky, Arkady; Kralemann, Bjoern; Fruehwirth, Matthias; Rosenblum, Michael; Kenner, Thomas; Schaefer, Jochen; Moser, Maximilian

    2014-03-01

    Characterizing properties of biological oscillators with phase response cirves (PRC) is one of main theoretical tools in neuroscience, cardio-respiratory physiology, and chronobiology. We present a technique that allows the extraction of the PRC from a non-invasive observation of a system consisting of two interacting oscillators, in this case heartbeat and respiration, in its natural environment and under free-running conditions. We use this method to obtain the phase coupling functions describing cardio-respiratory interactions and the phase response curve of 17 healthy humans. We show at which phase the cardiac beat is susceptible to respiratory drive and extract the respiratory-related component of heart rate variability. This non-invasive method of bivariate data analysis for the determination of phase response curves of coupled oscillators may find application in other biological and physical systems.

  12. Changes in intraocular pressure values measured with noncontact tonometer (NCT), ocular response analyzer (ORA) and corvis scheimpflug technology tonometer (CST) in the early phase after small incision lenticule extraction (SMILE).

    PubMed

    Shen, Yang; Su, Xiangjian; Liu, Xiu; Miao, Huamao; Fang, Xuejun; Zhou, Xingtao

    2016-11-18

    Corneal biomechanical properties are always compromised after corneal refractive surgeries thus leading to underestimated intraocular pressure (IOP) that complicates the management of IOP. We investigated the changes in postoperative baseline of IOP values measured with noncontact tonometer (NCT), ocular response analyzer (ORA) and corvis scheimpflug technology (CST) in the early phase after small incision lenticule extraction (SMILE). Twenty-two eyes (-6.76 ± 1.39D) of 22 moderate and high myopes, (28.36 ± 7.14 years, 12 male and 10 female) were involved in this prospective study. IOP values were measured using a non-contact tomometer (NCT-IOP), an ocular response analyzer (corneal-compensated IOP, IOPcc and Goldmann-correlated IOP, IOPg) and a Corvis scheimpflug technology tonometer (CST-IOP) preoperatively, at 20 min and 24 h, postoperatively. Repeated measures analysis of variance (RM-ANOVA), Pearson's correlation analysis and multiple linear regression models (stepwise) were performed. Cut-off P values were 0.05. Except for IOPcc, NCT-IOP, IOPg, and CST-IOP values significantly decreased after SMILE procedure (All P values <0.05). ΔCCT, as well as ΔMRSE and ΔKm, did not significantly correlated with ΔNCT-IOP, ΔIOPcc, ΔIOPg or ΔCST-IOP, (all P values >0.05). Multiple linear regression models (stepwise) showed that the practical post-operative IOP value was the main predictor of the theoretical post-operative NCT-IOP, IOPcc and IOPg values (all P values <0.001). The postoperative applanation time 1 (AT1) value (B = 8.079, t = 4.866, P < 0.001), preoperative central corneal thickness (CCT) value (B = 0.035, t = 2.732, P = 0.014) and postoperative peak distance (PD) value (B = 0.515, t = 2.176, P = 0.043) were the main predictors of the theoretical post-operative CST-IOP value. IOP values are underestimated when assessed after SMILE by using NCT-IOP, IOPg and CST-IOP. The practical postoperative IOPcc value

  13. A prospective phase II trial of response adapted whole brain radiotherapy after high dose methotrexate based chemotherapy in patients with newly diagnosed primary central nervous system lymphoma-analysis of acute toxicity profile and early clinical outcome.

    PubMed

    Adhikari, Narayan; Biswas, Ahitagni; Gogia, Ajay; Sahoo, Ranjit Kumar; Garg, Ajay; Nehra, Ashima; Sharma, Mehar Chand; Bhasker, Suman; Singh, Manmohan; Sreenivas, Vishnubhatla; Chawla, Rohan; Joshi, Garima; Kumar, Lalit; Chander, Subhash

    2018-04-09

    The treatment of primary CNS lymphoma (PCNSL) comprises high dose methotrexate (HDMTX) based chemotherapy followed by whole brain radiotherapy (WBRT), the major drawback of which is long term neurotoxicity. We intended to assess the feasibility of response adapted WBRT in PCNSL in the Indian setting. We screened 32 patients and enrolled 22 eligible patients with PCNSL from 2015 to 2017 in a prospective phase II trial. The patients underwent five 2-weekly cycles of induction chemotherapy with rituximab, methotrexate, vincristine, procarbazine. Patients with complete response(CR) to induction chemotherapy were given reduced dose WBRT 23.4 Gy/13 fractions/2.5 weeks while those with partial response (PR), stable or progressive disease (SD or PD) were given standard dose WBRT 45 Gy/25 fractions/5 weeks. Thereafter two cycles of consolidation chemotherapy with cytarabine were given. The primary endpoints of the study were assessment of response rate (RR) and progression free survival (PFS). The secondary endpoints of the study were assessment of overall survival (OS), toxicity profile of treatment and serial changes in quality of life and neuropsychological parameters. Out of 19 patients who completed HDMTX based chemotherapy, 10 (52.63%) patients achieved CR, 8 (42.11%) patients had PR and 1 patient had PD. After a median follow-up period of 11.25 months, the estimated median OS was 19 months. The actuarial rates of PFS and OS were respectively 94.1 and 68.2% at 1 year and 50.2 and 48.5% at 2 years. Three patients in reduced dose WBRT arm had recurrence and two of them died of progressive disease, whereas there was no recurrence or disease related death in standard dose WBRT arm. On univariate analysis of PFS, age ≤ 50 years and use of standard dose WBRT (45 Gy) led to significantly improved outcome (p value 0.03 and 0.02 respectively). In patients with PCNSL, reduced dose WBRT after CR to HDMTX based chemotherapy may lead to suboptimal clinical outcome due

  14. Chandra Catches Early Phase of Cosmic Assembly

    NASA Astrophysics Data System (ADS)

    2004-08-01

    A NASA Chandra X-ray Observatory image has revealed a complex of several intergalactic hot gas clouds in the process of merging. The superb Chandra spatial resolution made it possible to distinguish individual galaxies from the massive clouds of hot gas. One of the clouds, which that envelops hundreds of galaxies, has an extraordinarily low concentration of iron atoms, indicating that it is in the very early stages of cluster evolution. "We may be seeing hot intergalactic gas in a relatively pristine state before it has been polluted by gas from galaxies," said Q. Daniel Wang of the University of Massachusetts in Amherst, and lead author on an upcoming Astrophysical Journal article describing the study. "This discovery should provide valuable insight into how the most massive structures in the universe are assembled." 3-Panel Image of Abell 2125, Its Core & Galaxy C153 3-Panel Image of Abell 2125, Its Core & Galaxy C153 The complex, known as Abell 2125,is about 3 billion light years from Earth, and is seen at a time about 11 billion years after the Big Bang, when many galaxy clusters are believed to have formed. The Chandra Abell 2125 image shows several huge elongated clouds of multimillion degree gas coming together from different directions. These hot gas clouds, each of which contains hundreds of galaxies, appear to be in the process of merging to form a single massive galaxy cluster. Chandra, Hubble Space Telescope, and Very Large Array radio telescope data show that several galaxies in the Abell 2125 core cluster are being stripped of their gas as they fall through surrounding high-pressure hot gas. This stripping process has enriched the core cluster's gas in heavy elements such as iron. Abell 2125's Core & Galaxy C153 Abell 2125's Core & Galaxy C153 The gas in the pristine cloud, which is still several million light years away from the core cluster, is conspicuous for its lack of iron atoms. This anemic cloud must be in a very early evolutionary stage. The

  15. Mechanisms of the early phases of plant gravitropism

    NASA Technical Reports Server (NTRS)

    Kiss, J. Z.

    2000-01-01

    Gravitropism is directed growth of a plant or plant organ in response to gravity and can be divided into the following temporal sequence: perception, transduction, and response. This article is a review of the research on the early events of gravitropism (i.e., phenomena associated with the perception and transduction phases). The two major hypotheses for graviperception are the protoplast-pressure and starch-statolith models. While most researchers support the concept of statoliths, there are suggestions that plants have multiple mechanisms of perception. Evidence supports the hypothesis that the actin cytoskeleton is involved in graviperception/transduction, but the details of these mechanisms remain elusive. A number of recent developments, such as increased use of the molecular genetic approach, magnetophoresis, and laser ablation, have facilitated research in graviperception and have allowed for refinement of the current models. In addition, the entire continuum of acceleration forces from hypo- to hyper-gravity have been useful in studying perception mechanisms. Future interdisciplinary molecular approaches and the availability of sophisticated laboratories on the International Space Station should help to develop new insights into mechanisms of gravitropism in plants.

  16. Harmonic Phase Response of Nonlinear Radar Targets

    DTIC Science & Technology

    2015-10-01

    while allowing its harmonics to pass through. The weak harmonic responses are then amplified to allow for easier detection and measurement . 4...where the phase of the 2nd and 3rd harmonic of the received electromagnetic wave from nonlinear targets was measured and plotted against the frequency

  17. Fluctuation-driven electroweak phase transition. [in early universe

    NASA Technical Reports Server (NTRS)

    Gleiser, Marcelo; Kolb, Edward W.

    1992-01-01

    We examine the dynamics of the electroweak phase transition in the early Universe. For Higgs masses in the range 46 less than or = M sub H less than or = 150 GeV and top quark masses less than 200 GeV, regions of symmetric and asymmetric vacuum coexist to below the critical temperature, with thermal equilibrium between the two phases maintained by fluctuations of both phases. We propose that the transition to the asymmetric vacuum is completed by percolation of these subcritical fluctuations. Our results are relevant to scenarios of baryogenesis that invoke a weakly first-order phase transition at the electroweak scale.

  18. Concentration-Response Modeling of ECG Data From Early-Phase Clinical Studies as an Alternative Clinical and Regulatory Approach to Assessing QT Risk - Experience From the Development Program of Lemborexant.

    PubMed

    Murphy, Patricia J; Yasuda, Sanae; Nakai, Kenya; Yoshinaga, Takashi; Hall, Nancy; Zhou, Meijian; Aluri, Jagadeesh; Rege, Bhaskar; Moline, Margaret; Ferry, Jim; Darpo, Borje

    2017-01-01

    Lemborexant is a novel dual orexin receptor antagonist being developed to treat insomnia. Its potential to cause QT prolongation was evaluated using plasma concentration-response (CR) modeling applied to data from 2 multiple ascending-dose (MAD) studies. In the primary MAD study, placebo or lemborexant (2.5 to 75 mg) was administered for 14 consecutive nights. In another MAD study designed to "bridge" pharmacokinetic and safety data between Japanese and non-Japanese subjects (J-MAD), placebo or lemborexant (2.5, 10, or 25 mg) was administered for 14 consecutive nights. QT intervals were estimated using a high-precision measurement technique and evaluated using a linear mixed-effects CR model, for each study separately and for the pooled data set. When each study was analyzed separately, the slopes of the CR relationship were shallow and not statistically significant. In the pooled analysis, the slope of the CR relationship was -0.00002 milliseconds per ng/mL (90%CI, -0.01019 to 0.01014 milliseconds). The highest observed C max was 400 ng/mL, representing a margin 8-fold above exposures expected for the highest planned clinical dose. The model-predicted QTc effect at 400 ng/mL was 1.1 milliseconds (90%CI, -3.49 to 5.78 milliseconds). In neither the J-MAD study nor the pooled analysis was an effect of race identified. CR modeling of data from early-phase clinical studies, including plasma levels far exceeding those anticipated clinically, indicated that a QT effect >10 milliseconds could be excluded. Regulatory agreement with this methodology demonstrates the effectiveness of a CR modeling approach as an alternative to thorough QT studies. © 2016, The American College of Clinical Pharmacology.

  19. Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates

    PubMed Central

    Vohs, Jenifer L.; Hummer, Tom A.; Yung, Matthew G.; Francis, Michael M.; Lysaker, Paul H.; Breier, Alan

    2015-01-01

    Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis. PMID:26132568

  20. Phase III Early Restoration Meeting - Galveston, TX | NOAA Gulf Spill

    Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

  1. Volunteering for early phase gene transfer research in Parkinson disease.

    PubMed

    Kim, S Y H; Holloway, R G; Frank, S; Beck, C A; Zimmerman, C; Wilson, R; Kieburtz, K

    2006-04-11

    For early phase trials of novel interventions-such as gene transfer for Parkinson disease (PD)--whose focus is primarily on safety and tolerability, it is important that participants have a realistic understanding of the goals of such research. Recently, some have expressed concern that patients with PD may have unrealistic expectations. The authors examined why patients with PD might volunteer for invasive early phase research by interviewing 92 patients with PD and comparing those who would (n = 46) and those who would not (n = 46) participate in a hypothetical phase I gene-transfer study. The two groups' demographic, clinical, functional, and quality of life measures, as well as their understanding of the research protocol, were similar. The groups did not differ on their perception of potential for personal benefit nor on the level of likelihood of benefit they saw as a precondition for volunteering. However, those willing to participate tended to perceive lower probability of risk, were tolerant of greater probability of risk, and were more optimistic about the phase I study's potential benefits to society. They also appeared more decisive and action-oriented than the unwilling group. It is likely that the decision whether to participate in early phase PD gene transfer studies will depend mostly on patients' attitudes regarding risk, optimism about science, and an action orientation, rather than on their clinical, functional, or demographic characteristics.

  2. Beryllium and boron constraints on an early Galactic bright phase

    NASA Technical Reports Server (NTRS)

    Fields, Brian D.; Schramm, David N.; Truran, James W.

    1993-01-01

    The recent observations of Be and B in metal-deficient halo dwarfs are used to constrain a 'bright phase' of enhanced cosmic-ray flux in the early Galaxy. Assuming that this Be and B arises from cosmic-ray spallation in the early Galaxy, limits are placed on the intensity of the early (Population II) cosmic-ray flux relative to the present (Population I) flux. A simple estimate of bounds on the flux ratio is 1 - 40. This upper bound would restrict galaxies like our own from producing neutrino fluxes that would be detectable in any currently proposed detectors. It is found that the relative enhancement of the early flux varies inversely with the relative time of enhancement. It is noted that associated gamma-ray production via pp - pi sup 0 pp may be a significant contribution to the gamma-ray background above 100 MeV.

  3. Assessment of early response biomarkers in relation to long‐term survival in patients with HER2‐negative breast cancer receiving neoadjuvant chemotherapy plus bevacizumab: Results from the Phase II PROMIX trial

    PubMed Central

    Kimbung, Siker; Markholm, Ida; Bjöhle, Judith; Lekberg, Tobias; von Wachenfeldt, Anna; Azavedo, Edward; Saracco, Ariel; Hellström, Mats; Veerla, Srinivas; Paquet, Eric; Bendahl, Pär‐Ola; Fernö, Mårten; Bergh, Jonas; Loman, Niklas

    2017-01-01

    Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response‐guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One‐hundred‐and‐fifty patients with large, operable and locally advanced HER2‐negative breast cancer received epirubicin and docetaxel, with the addition of bevacizumab. Patients underwent tumor biopsies at baseline, after Cycle 2 and at the time of surgery. The primary end point, pCR, and its relation with the secondary endpoints event‐free survival (EFS), overall survival (OS) and gene expression profiles, are reported. The pCR rate was 13% (95% CI 8.6–20.2), with significantly more pCRs among triple‐negative [28% (95% CI 14.8–45.4)] than among hormone receptor positive (HR+) tumors [9% (95% CI 4.6–16.3); (OR = 3.9 [CI = 1.5–10.3])]. pCR rates were not associated with EFS or OS. PAM50 subtypes significantly changed after Cycle 2 (p = 0.03) and an index of absolute changes in PAM50 correlations between these time‐points was associated with EFS [HR = 0.62 (CI = 0.3–1.1)]. In univariable analyses, signatures for angiogenesis, proliferation, estrogen receptor signaling, invasion and metastasis, and immune response, measured after Cycle 2, were associated with pCR in HR+ tumors. Evaluation of changes in molecular subtypes and other signatures early in the course of neoadjuvant treatment may be predictive of pCR and EFS. These factors may help guide further treatment and should be considered when designing neoadjuvant trials. PMID:28940389

  4. Human Adolescent Phase Response Curves to Bright White Light.

    PubMed

    Crowley, Stephanie J; Eastman, Charmane I

    2017-08-01

    Older adolescents are particularly vulnerable to circadian misalignment and sleep restriction, primarily due to early school start times. Light can shift the circadian system and could help attenuate circadian misalignment; however, a phase response curve (PRC) to determine the optimal time for receiving light and avoiding light is not available for adolescents. We constructed light PRCs for late pubertal to postpubertal adolescents aged 14 to 17 years. Participants completed 2 counterbalanced 5-day laboratory sessions after 8 or 9 days of scheduled sleep at home. Each session included phase assessments to measure the dim light melatonin onset (DLMO) before and after 3 days of free-running through an ultradian light-dark (wake-sleep) cycle (2 h dim [~20 lux] light, 2 h dark). In one session, intermittent bright white light (~5000 lux; four 20-min exposures) was alternated with 10 min of dim room light once per day for 3 consecutive days. The time of light varied among participants to cover the 24-h day. For each individual, the phase shift to bright light was corrected for the free-run derived from the other laboratory session with no bright light. One PRC showed phase shifts in response to light start time relative to the DLMO and another relative to home sleep. Phase delay shifts occurred around the hours corresponding to home bedtime. Phase advances occurred during the hours surrounding wake time and later in the afternoon. The transition from delays to advances occurred at the midpoint of home sleep. The adolescent PRCs presented here provide a valuable tool to time bright light in adolescents.

  5. Dispositional Optimism and Therapeutic Expectations in Early Phase Oncology Trials

    PubMed Central

    Jansen, Lynn A.; Mahadevan, Daruka; Appelbaum, Paul S.; Klein, William MP; Weinstein, Neil D.; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P.

    2016-01-01

    Purpose Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early phase oncology trials. Optimism, however, is not a unitary construct – it can also be defined as a general disposition, or what is called dispositional optimism. We assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. We also assessed how dispositional optimism related to unrealistic optimism. Methods Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Results Dispositional optimism was significantly associated with higher expectations for personal therapeutic benefit (Spearman r=0.333, p<0.0001), but was not associated with the therapeutic misconception. (Spearman r=−0.075, p=0.329). Dispositional optimism was weakly associated with unrealistic optimism (Spearman r=0.215, p=0.005). In multivariate analysis, both dispositional optimism (p=0.02) and unrealistic optimism (p<0.0001) were independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (p=.0001), but not dispositional optimism, was independently associated with the therapeutic misconception. Conclusion High expectations for therapeutic benefit among patient-subjects in early phase oncology trials should not be assumed to result from misunderstanding of specific information about the trials. Our data reveal that these expectations are associated with either a dispositionally positive outlook on life or biased expectations about specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early phase oncology research. PMID:26882017

  6. Statistical controversies in clinical research: early-phase adaptive design for combination immunotherapies.

    PubMed

    Wages, N A; Slingluff, C L; Petroni, G R

    2017-04-01

    In recent years, investigators have asserted that the 3 + 3 design lacks flexibility, making its use in modern early-phase trial settings, such as combinations and/or biological agents, inefficient. More innovative approaches are required to address contemporary research questions, such as those posed in trials involving immunotherapies. We describe the implementation of an adaptive design for identifying an optimal treatment regimen, defined by low toxicity and high immune response, in an early-phase trial of a melanoma helper peptide vaccine plus novel adjuvant combinations. Operating characteristics demonstrate the ability of the method to effectively recommend optimal regimens in a high percentage of trials with reasonable sample sizes. The proposed design is a practical, early-phase, adaptive method for use with combined immunotherapy regimens. This design can be applied more broadly to early-phase combination studies, as it was used in an ongoing study of two small molecule inhibitors in relapsed/refractory mantle cell lymphoma. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Hepatic expression of the GH/JAK/STAT/IGF pathway, acute-phase response signalling and complement system are affected in mouse offspring by prenatal and early postnatal exposure to maternal high-protein diet.

    PubMed

    Vanselow, Jens; Kucia, Marzena; Langhammer, Martina; Koczan, Dirk; Rehfeldt, Charlotte; Metges, Cornelia C

    2011-12-01

    Effects of pre- and early postnatal exposure to maternal high-protein diets are not well understood. Transcription profiling was performed in male mouse offspring exposed to maternal high-protein diet during pregnancy and/or lactation to identify affected hepatic molecular pathways. Dams were fed isoenergetic diets with control (20% w/w) or high protein levels (40%). The hepatic expression profiles were evaluated by differential microarray analysis 3 days (d3) and 3 weeks (d21) after birth. Offspring from three different high-protein dietary groups, HP (d3, high-protein diet during pregnancy), HPHP (d21, high-protein diet during pregnancy and lactation) and CHP (d21, control diet during pregnancy and high-protein diet during lactation), were compared with age-matched offspring from dams fed control diet. Offspring body and liver mass of all high-protein groups were decreased. Prenatal high-protein diet affected hepatic expression of genes mapping to the acute response/complement system and the GH/JAK/STAT/IGF signalling pathways. Maternal exposure to high-protein diet during lactation affected hepatic gene expression of the same pathways but additionally affected genes mapping to protein, fatty acid, hexose and pyruvate metabolism. (1) Genes of the acute response/complement system and GH/JAK/STAT/IGF pathways were down-regulated in offspring of dams exposed to high-protein diets during pregnancy and/or lactation. (2) Genes related to nutrient and energy metabolism, however, were only affected when high-protein diet was administered during lactation. (3) Modulation of the GH/JAK/STAT/IGF pathway might be responsible for reduced body and liver masses by maternal high-protein diet.

  8. The Development of Attention and Response Inhibition in Early Childhood

    ERIC Educational Resources Information Center

    Bartgis, Jami; Thomas, David G.; Lefler, Elizabeth K.; Hartung, Cynthia M.

    2008-01-01

    The goal of this study was to examine the development of attention and response inhibition from ages 5 to 7. Forty children (20 5-year-olds and 20 7-year-olds) completed four counterbalanced phases of a continuous performance task. Phase 1 was designed to measure attention without distraction, Phase 2 was designed to measure attention with…

  9. Early disaster response in Haiti: the Israeli field hospital experience.

    PubMed

    Kreiss, Yitshak; Merin, Ofer; Peleg, Kobi; Levy, Gad; Vinker, Shlomo; Sagi, Ram; Abargel, Avi; Bartal, Carmi; Lin, Guy; Bar, Ariel; Bar-On, Elhanan; Schwaber, Mitchell J; Ash, Nachman

    2010-07-06

    The earthquake that struck Haiti in January 2010 caused an estimated 230,000 deaths and injured approximately 250,000 people. The Israel Defense Forces Medical Corps Field Hospital was fully operational on site only 89 hours after the earthquake struck and was capable of providing sophisticated medical care. During the 10 days the hospital was operational, its staff treated 1111 patients, hospitalized 737 patients, and performed 244 operations on 203 patients. The field hospital also served as a referral center for medical teams from other countries that were deployed in the surrounding areas. The key factor that enabled rapid response during the early phase of the disaster from a distance of 6000 miles was a well-prepared and trained medical unit maintained on continuous alert. The prompt deployment of advanced-capability field hospitals is essential in disaster relief, especially in countries with minimal medical infrastructure. The changing medical requirements of people in an earthquake zone dictate that field hospitals be designed to operate with maximum flexibility and versatility regarding triage, staff positioning, treatment priorities, and hospitalization policies. Early coordination with local administrative bodies is indispensable.

  10. Cytokine expression during early and late phase of acute Puumala hantavirus infection

    PubMed Central

    2011-01-01

    Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection

  11. Geoeffectiveness during the early phase of Solar Cycle 24

    NASA Astrophysics Data System (ADS)

    Pande, Bimal

    Geoeffectiveness during the early phase of Solar Cycle 24 \\underline{} Abstract\\underline{} It is very important and interesting to understand the solar eruptions because it produces the geoeffectiveness in our Earth environment. In the rise phase of the solar cycle, geoeffective events are less frequent, thus this provide us better opportunity to study these events including the detection of their source regions. Keeping this in mind, we have analysed the data of rise phase of current solar cycle 24 ( 2009-2012). During above time period, we have selected 59 geoeffective events having Disturbance Storm Time (Dst) index < -50 nT. Based on the Dst index, we divided the events into two categories i.e. moderate (< -50 nT > -100 nT ) and intense ( <-100 nT). To locate the solar source regions of geoeffective and SEPs associated events, we have used available images, movies and Solar Geophysical data (SGD) list: for example movies from SOHO/EIT, images and movies from the Solar Dynamic Observatory (SDO). In this study, we will discuss and compare the different properties of associated CMEs, flares and their relation with geoeffectiveness.

  12. De-Escalation Strategies in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer (BC): Final Analysis of the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early BC HER2- and Hormone Receptor-Positive Phase II Randomized Trial-Efficacy, Safety, and Predictive Markers for 12 Weeks of Neoadjuvant Trastuzumab Emtansine With or Without Endocrine Therapy (ET) Versus Trastuzumab Plus ET.

    PubMed

    Harbeck, Nadia; Gluz, Oleg; Christgen, Matthias; Kates, Ronald Ernest; Braun, Michael; Küemmel, Sherko; Schumacher, Claudia; Potenberg, Jochem; Kraemer, Stefan; Kleine-Tebbe, Anke; Augustin, Doris; Aktas, Bahriye; Forstbauer, Helmut; Tio, Joke; von Schumann, Raquel; Liedtke, Cornelia; Grischke, Eva-Maria; Schumacher, Johannes; Wuerstlein, Rachel; Kreipe, Hans Heinrich; Nitz, Ulrike Anneliese

    2017-09-10

    Purpose Human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or with the potent antibody-cytotoxic, anti-HER2 compound trastuzumab emtansine (T-DM1) with or without ET for this subgroup. The West German Study Group trial, ADAPT (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer) compares pathologic complete response (pCR) rates of T-DM1 versus trastuzumab with ET in early HER2-positive/HR-positive breast cancer. Patients and Methods In this prospective, neoadjuvant, phase II trial, 375 patients with early breast cancer with HER2-positive and HR-positive status (n = 463 screened) were randomly assigned to 12 weeks of T-DM1 with or without ET or to trastuzumab with ET. The primary end point was pCR (ypT0/is/ypN0). Early response was assessed in 3-week post-therapeutic core biopsies (proliferation decrease ≥ 30% Ki-67 or cellularity response). Secondary end points included safety and predictive impact of early response on pCR. Adjuvant therapy followed national standards. Results Baseline characteristics were well balanced among the arms. More than 90% of patients completed the therapy per protocol. pCR was observed in 41.0% of patients treated with T-DM1, 41.5% of patients treated with T-DM1 and ET, and 15.1% with trastuzumab and ET ( P < .001). Early responders (67% of patients with assessable response) achieved pCR in 35.7% compared with 19.8% in nonresponders (odds ratio, 2.2; 95% CI, 1.24 to 4.19). T-DM1 was associated with a significantly higher prevalence of grade 1 to 2 toxicities, especially thrombocytopenia, nausea, and elevation of liver enzymes. Overall toxicity was low; seventeen

  13. The Early Anthropogenic Hypothesis: Challenges and Responses

    NASA Astrophysics Data System (ADS)

    Ruddiman, William F.

    2007-12-01

    Ruddiman (2003) proposed that late Holocene anthropogenic intervention caused CH4 and CO2 increases that kept climate from cooling and that preindustrial pandemics caused CO2 decreases and a small cooling. Every aspect of this early anthropogenic hypothesis has been challenged: the timescale, the issue of stage 11 as a better analog, the ability of human activities to account for the gas anomalies, and the impact of the pandemics. This review finds that the late Holocene gas trends are anomalous in all ice timescales; greenhouse gases decreased during the closest stage 11 insolation analog; disproportionate biomass burning and rice irrigation can explain the methane anomaly; and pandemics explain half of the CO2 decrease since 1000 years ago. Only ˜25% of the CO2 anomaly can, however, be explained by carbon from early deforestation. The remainder must have come from climate system feedbacks, including a Holocene ocean that remained anomalously warm because of anthropogenic intervention.

  14. Early response to therapy and survival in multiple myeloma.

    PubMed

    Schaar, C G; Kluin-Nelemans, J C; le Cessie, S; Franck, P F H; te Marvelde, M C; Wijermans, P W

    2004-04-01

    Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan-prednisone therapy (MP: melphalan 0.25 mg/kg, prednisone 1.0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)-MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.

  15. Inside information: Financial conflicts of interest for research subjects in early phase clinical trials.

    PubMed

    Helft, Paul R; Ratain, Mark J; Epstein, Richard A; Siegler, Mark

    2004-05-05

    In recent years, several research subjects have told us that they had bought or intended to buy stock in the companies sponsoring the clinical trials in which they were enrolled. This situation has led us to ask what, if any, are physician-investigators' scientific, ethical, and legal responsibilities concerning research subjects who choose to buy stock in the companies sponsoring the clinical trials in which they are participating. Although the scope of this problem is unknown and is likely to be small, this commentary examines the scientific, ethical, and legal concerns raised by such activities on the part of research subjects enrolled in early phase clinical trials. In addition, this commentary also outlines the basis for our opinion that research subjects involved in an early phase clinical trial should avoid the financial conflicts of interest created by trading stock in the company sponsoring the clinical trial.

  16. Accumulation of unsaturated lipids in monocytes during early phase pyrogen tolerance.

    PubMed

    Szewczenko-Pawlikowski, M; Kozak, W

    2000-04-12

    This paper presents data that inspired a new explanation for the mechanism of early phase endotoxin tolerance. Rabbits injected intravenously with LPS from Salmonella abortus developed a two-phase fever (6 h) and monophasic hyperlipidemia of very low density lipoproteins (two consecutive days). If during these days rabbits were injected with the same dose of LPS at 24-h intervals, the second phase of fever disappeared, i.e. early phase pyrogenic tolerance was obtained. This was correlated with a decrease of lipoprotein hyperlipidemia (measured 1.5 h after LPS injection) and an accumulation of lipids rich in double bonds in monocytes (measured 3.5 h after LPS injection). Results showed that the degree of unsaturation of acyl chains (AC) in monocytes (AC/DB, DB=double bonds) is negatively correlated (r=-0.72) with fever response (fever index). The authors maintain that a gradual increase in monocyte membrane fluidity is an adaptation to repeated exposure of monocytes to lipid A and is responsible for the progressive desensitization of monocytes to endotoxin. It is suggested that disorders of this mechanism lead to an accumulation of abnormal quantities of saturated lipids and cholesterol within macrophages, which, as foam cells, are the starting point for atherosclerosis pathology.

  17. Gene expression profiles of Vibrio parahaemolyticus in the early stationary phase.

    PubMed

    Meng, L; Alter, T; Aho, T; Huehn, S

    2015-09-01

    Vibrio (V.) parahaemolyticus is an aquatic bacterium capable of causing foodborne gastroenteritis. In the environment or the food chain, V. parahaemolyticus cells are usually forced into the stationary phase, the common phase for bacterial survival in the environment. So far, little is known about whole genomic expression of V. parahaemolyticus in the early stationary phase compared with the exponential growth phase. We performed whole transcriptomic profiling of V. parahaemolyticus cells in both phases (exponential and early stationary phase). Our data showed in total that 172 genes were induced in early stationary phase, while 61 genes were repressed in early stationary phase compared with the exponential phase. Three functional categories showed stable gene expression in the early stationary phase. Eleven functional categories showed that up-regulation of genes was dominant over down-regulation in the early stationary phase. Although genes related to endogenous metabolism were repressed in the early stationary phase, massive regulation of gene expression occurred in the early stationary phase, indicating the expressed gene set of V. parahaemolyticus in the early stationary phase impacts environmental survival. Vibrio (V.) parahaemolyticus is one of the main bacterial causes of foodborne intestinal infections. This bacterium usually is forced into stationary phase in the environment, which includes, e.g. seafood. When bacteria are in stationary phase, physiological changes can lead to a resistance to many stresses, including physical and chemical challenges during food processing. To the best of our knowledge, highlighting the whole genome expression changes in the early stationary phase compared with exponential phase, as well as the investigation of physiological changes of V. parahaemolyticus such as the survival mechanism in the stationary phase has been the very first study in this field. © 2015 The Society for Applied Microbiology.

  18. Early Human Testing Initiative Phase 1 Regenerative Life Support Systems

    1995-08-08

    Early Human Testing (EHT) Initiative Phase 1 Regenerative Life Support Systems Laboratory (RLSSL). Nigel Packham activities in the Variable Pressure Growth Chamber which he lived inside for 15 days. A crowd of well-wishers outside the test chamber, at the console are John Lewis, Ed Mohr and Marybeth Edeen (15577). Packham exiting the chamber (15578-81). Packham is the focus of television cameras and reporters (15582-3). Don Henninger interviewed by reporters (15584). Packham is presented with a jacket after his stay in the chamber (15585). Packham inside the wheat growth chamber checking the condition of the plants (15586-7, 15597). Packham exercising on a recumbant bicycle (15588, 15592). Packham, through the window into the growth chamber, displays a handful of wheat plants to console monitor Dan Barta (15589-90). Group portrait of the team conducting the Early Human Testing Initiative Phase 1 Regenerative Life Support Systems test and include, front row, from left: Jeff Dominick and Don Overton and back row, from left, unidentified member, Marybeth Edeen, Nigel Packham, John Lewis, Ed Mohr, Dan Barta and Tim Monk (15591). Harry Halford prepares to send a package through the airlock to Packham (15593). Packham displays a handful of wheat plants (15594). Packham fixes himself a bowl of cereal (15595) and retrieves a carton of milk from the refrigerator (15596). Packham retrieves a package from the airlock (15598). Packham packs up trash in plastic bag (15599-600) and sends it back through the airlock (15601). Packham gets a cup of water (15602) and heats it in the microwave (15603).

  19. Early Campus Response to Disruptive Behavior

    ERIC Educational Resources Information Center

    Stump, Linda J.; Zdziarski, Eugene L.

    2008-01-01

    As major events define generations and tragedies define and refine protocol response to significant incidents, a sense of comfort and confidence is attained as the authors train individually and organizationally to respond to extreme events, and yet those who have experienced them know that no plan goes as it should. There are, however, steps or…

  20. Menarche: Responses of Early Adolescent Females.

    ERIC Educational Resources Information Center

    McGrory, Arlene

    1990-01-01

    Investigated responses of menarcheal age females to menarche. Results from 95 girls indicated that premenarcheal girls thought menses was more debilitating than did postmenarcheal girls. Subjects who had been menstruating longer considered menses natural event but denied its effects. Found no significant difference in overall self-esteem and…

  1. The acute phase response of cod (Gadus morhua L.): expression of immune response genes.

    PubMed

    Audunsdottir, Sigridur S; Magnadottir, Bergljot; Gisladottir, Berglind; Jonsson, Zophonias O; Bragason, Birkir Th

    2012-02-01

    An acute phase response (APR) was experimentally induced in Atlantic cod (Gadus morhua L.) by intramuscular injection of turpentine oil. The change in the expression of immune related genes was monitored in the anterior kidney and the spleen over a period of 7 days. The genes examined were two types of pentraxins, apolipoprotein A1 (ApoA-I), the complement component C3, interleukin-1β (IL-1β), transferrin, cathelicidin, and hepcidin. All genes were constitutively expressed in both organs and their expression amplified by the turpentine injection. A pattern of response was observed both with respect to the organ preference and to the timing of a maximum response. The increased gene expression of the pentraxins, ApoA-I and C3 was restricted to the anterior kidney, the gene expression of IL-1β, cathelicidin, and transferrin increased in both organs, while hepcidin gene expression was only significantly increased in the spleen. The pentraxins and ApoA-I appear to be early mediators of APR in cod, possibly stimulating C3 and IL-1β response, while the antimicrobial peptides may play a minor role. The increase in transferrin gene expression in both organs, and apparent indifference to cortisol release associated with the turpentine injection, suggests that this could be a typical acute phase protein in cod. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Exploring early public responses to geoengineering.

    PubMed

    Pidgeon, Nick; Corner, Adam; Parkhill, Karen; Spence, Alexa; Butler, Catherine; Poortinga, Wouter

    2012-09-13

    Proposals for geoengineering the Earth's climate are prime examples of emerging or 'upstream' technologies, because many aspects of their effectiveness, cost and risks are yet to be researched, and in many cases are highly uncertain. This paper contributes to the emerging debate about the social acceptability of geoengineering technologies by presenting preliminary evidence on public responses to geoengineering from two of the very first UK studies of public perceptions and responses. The discussion draws upon two datasets: qualitative data (from an interview study conducted in 42 households in 2009), and quantitative data (from a subsequent nationwide survey (n=1822) of British public opinion). Unsurprisingly, baseline awareness of geoengineering was extremely low in both cases. The data from the survey indicate that, when briefly explained to people, carbon dioxide removal approaches were preferred to solar radiation management, while significant positive correlations were also found between concern about climate change and support for different geoengineering approaches. We discuss some of the wider considerations that are likely to shape public perceptions of geoengineering as it enters the media and public sphere, and conclude that, aside from technical considerations, public perceptions are likely to prove a key element influencing the debate over questions of the acceptability of geoengineering proposals.

  3. Antigravity treadmill training during the early rehabilitation phase following unicompartmental knee arthroplasty: A case series.

    PubMed

    Huang, Chun-Hao; Schroeder, E Todd; Powers, Christopher

    2018-02-26

    Patients who have undergone unicompartmental knee arthroplasty (UKA) have been reported to exhibit altered gait 19-25 months post-surgery. The most common gait impairment in this population is inadequate knee flexion and a corresponding decrease in the knee extensor moment during loading response (i.e., quadriceps avoidance). The purpose of this case series was to determine whether incorporation of antigravity treadmill training into a standard physical therapy program can eliminate quadriceps avoidance gait during the early rehabilitation phase following UKA. Four females who underwent UKA were recruited for this study. Participants completed antigravity treadmill training three times per week for 12 weeks in addition to their standard physical therapy program. Instrumented gait analysis was performed at baseline (pre-intervention), week 6 (mid-intervention), and week 12 (post-intervention). We found that peak knee flexion and the peak knee extensor moment during the weight acceptance phase of gait increased to normal values following the 12-week intervention period (14.1 ± 6.5° to 20.6 ± 1.5° and 0.4 ± 0.3 to 0.7 ± 0.2 Nm/kg respectively). The findings of this case series suggest that a standard physical therapy program that incorporates early gait training using an antigravity treadmill may be beneficial in eliminating "quadriceps avoidance" during the early rehabilitation phase following UKA.

  4. Phase III Early Restoration Meeting - Corpus Christi, TX | NOAA Gulf Spill

    Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

  5. Phase III Early Restoration Meeting - Lake Charles, LA | NOAA Gulf Spill

    Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News early restoration planning for Phase III and future early restoration plans. Open House: 5:30pm Public

  6. Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

    PubMed Central

    Cullingford, Timothy E; Markou, Thomais; Fuller, Stephen J; Giraldo, Alejandro; Pikkarainen, Sampsa; Zoumpoulidou, Georgia; Alsafi, Ali; Ekere, Collins; Kemp, Timothy J; Dennis, Jayne L; Game, Laurence; Sugden, Peter H; Clerk, Angela

    2008-01-01

    Background Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in

  7. Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

    PubMed Central

    Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

    2014-01-01

    The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

  8. Blood gene expression profiling of an early acetaminophen response.

    PubMed

    Bushel, P R; Fannin, R D; Gerrish, K; Watkins, P B; Paules, R S

    2017-06-01

    Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.

  9. Blood Gene Expression Profiling of an Early Acetaminophen Response

    PubMed Central

    Bushel, Pierre R.; Fannin, Rick D.; Gerrish, Kevin; Watkins, Paul B.; Paules, Richard S.

    2018-01-01

    Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24 hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. PMID:26927286

  10. Phase-Amplitude Response Functions for Transient-State Stimuli

    PubMed Central

    2013-01-01

    Abstract The phase response curve (PRC) is a powerful tool to study the effect of a perturbation on the phase of an oscillator, assuming that all the dynamics can be explained by the phase variable. However, factors like the rate of convergence to the oscillator, strong forcing or high stimulation frequency may invalidate the above assumption and raise the question of how is the phase variation away from an attractor. The concept of isochrons turns out to be crucial to answer this question; from it, we have built up Phase Response Functions (PRF) and, in the present paper, we complete the extension of advancement functions to the transient states by defining the Amplitude Response Function (ARF) to control changes in the transversal variables. Based on the knowledge of both the PRF and the ARF, we study the case of a pulse-train stimulus, and compare the predictions given by the PRC-approach (a 1D map) to those given by the PRF-ARF-approach (a 2D map); we observe differences up to two orders of magnitude in favor of the 2D predictions, especially when the stimulation frequency is high or the strength of the stimulus is large. We also explore the role of hyperbolicity of the limit cycle as well as geometric aspects of the isochrons. Summing up, we aim at enlightening the contribution of transient effects in predicting the phase response and showing the limits of the phase reduction approach to prevent from falling into wrong predictions in synchronization problems. List of Abbreviations PRC phase response curve, phase resetting curve. PRF phase response function. ARF amplitude response function. PMID:23945295

  11. Early Intervention Services for Early-Phase Psychosis - Centre for integrative psychiatry in Psychiatric Hospital "Sveti Ivan", Croatia.

    PubMed

    Matić, Katarina; Gereš, Natko; Gerlach, Josefina; Prskalo-Čule, Diana; Zadravec Vrbanc, Tihana; Lovretić, Vanja; Librenjak, Dina; Vuk Pisk, Sandra; Ivezić, Ena; Šimunović Filipčić, Ivona; Jeleč, Vjekoslav; Filipčić, Igor

    2018-06-01

    There is a growing body of evidence suggesting that early and effective management in the critical early years of schizophrenia can improve long-term outcomes. The objective of this study was to evaluate time to relapse of the patients with early-phase psychosis treated in the Centre for integrative psychiatry (CIP). We performed a retrospective cohort study on the sample of 373 early-phase psychosis patients admitted to Psychiatric Hospital "Sveti Ivan", Zagreb Croatia: from January 1, 2015 to December 31, 2017. The primary outcome was time to relapse. Patients who were admitted to group psychotherapeutic program after the end of acute treatment had 70% lower hazard for relapse (HR=0.30; 95% CI 0.16-0.58). Patients who were included first in the psychotherapeutic program and then treated and controlled in the daily hospital had 74% lower hazard for relapse (HR=0.26; 95% CI 0.10-0.67). In early-phase psychosis, integrative early intervention service has relevant beneficial effects compare to treatment as usual. These results justified the implementation of multimodal early intervention services in treatment of patients with early-phase psychosis.

  12. The acute phase response and exercise: court and field sports

    PubMed Central

    Fallon, K; Fallon, S; Boston, T

    2001-01-01

    Objective—To determine the presence or absence of an acute phase response after training for court and field sports. Participants—All members of the Australian women's soccer team (n = 18) and all members of the Australian Institute of Sport netball team (n = 14). Methods—Twelve acute phase reactants (white blood cell count, neutrophil count, platelet count, serum iron, ferritin, and transferrin, percentage transferrin saturation, α1 antitrypsin, caeruloplasmin, α2 acid glycoprotein, C reactive protein, and erythrocyte sedimentation rate) were measured during a rest period and after moderate and heavy training weeks in members of elite netball and women's soccer teams. Results—Responses consistent with an acute phase response were found in five of 24 tests in the soccer players, and in three of 24 tests in the netball players. Responses in the opposite direction were found in seven of 24 tests in the soccer players and two of 24 tests in the netballers. The most sensitive reactant measured, C reactive protein, did not respond in a manner typical of an acute phase response. Conclusion—An acute phase response does not seem to occur as a consequence of the levels of training typical of elite female netball and soccer teams. This has implications for the interpretation of biochemical variables in these groups. Key Words: acute phase response; iron; plasma proteins; inflammation PMID:11375875

  13. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

  14. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

  15. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

  16. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

  17. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

  18. Endothelial gaps and adherent leukocytes in allergen-induced early- and late-phase plasma leakage in rat airways.

    PubMed Central

    Baluk, P.; Bolton, P.; Hirata, A.; Thurston, G.; McDonald, D. M.

    1998-01-01

    Exposure of sensitized individuals to antigen can induce allergic responses in the respiratory tract, manifested by early and late phases of vasodilatation, plasma leakage, leukocyte influx, and bronchoconstriction. Similar responses can occur in the skin, eye, and gastrointestinal tract. The early-phase response involves mast cell mediators and the late-phase response is leukocyte dependent, but the mechanism of leakage is not understood. We sought to identify the leaky blood vessels, to determine whether these vessels contained endothelial gaps, and to analyze the relationship of the gaps to adherent leukocytes, using biotinylated lectins or silver nitrate to stain the cells in situ and Monastral blue as a tracer to quantify plasma leakage. Most of the leakage occurred in postcapillary venules (< 40-microns diameter), whereas most of the leukocyte migration (predominantly neutrophils) occurred in collecting venules. Capillaries and arterioles did not leak. Endothelial gaps were found in the leaky venules, both by silver nitrate staining and by scanning electron microscopy, and 94% of the gaps were distinct from sites of leukocyte adhesion or migration. We conclude that endothelial gaps contribute to both early and late phases of plasma leakage induced by antigen, but most leakage occurs upstream to sites of leukocyte adhesion. Images Figure 3 Figure 5 Figure 6 Figure 7 PMID:9626051

  19. Early response to psychological trauma--what GPs can do.

    PubMed

    Wade, Darryl; Howard, Alexandra; Fletcher, Susan; Cooper, John; Forbes, David

    2013-09-01

    There is a high prevalence of psychological trauma exposure among primary care patients. General practitioners are well placed to provide appropriate support for patients coping with trauma. This article outlines an evidence-based early response to psychological trauma. Psychological first aid is the preferred approach in providing early assistance to patients who have experienced a traumatic event. General practitioners can be guided by five empirically derived principles in their early response: promoting a sense of safety, calming, self efficacy, connectedness and hope. Structured psychological interventions, including psychological debriefing, are not routinely recommended in the first few weeks following trauma exposure. General practitioner self care is an important aspect of providing post-trauma patient care.

  20. Early Twentieth Century Responses to the Drug Problem.

    ERIC Educational Resources Information Center

    Pfennig, Dennis Joseph

    1991-01-01

    Describes early twentieth-century responses to the drug problem in the United States. Discusses pressure from the media and reformers to control the availability of drugs such as opium and cocaine that were widely available in over-the-counter medications. Focuses on New York State, which took the lead in enacting drug control legislation. (DK)

  1. A Comparison of Responsive Interventions on Kindergarteners' Early Reading Achievement

    ERIC Educational Resources Information Center

    Little, Mary E.; Rawlinson, D'Ann; Simmons, Deborah C.; Kim, Minjung; Kwok, Oi-man; Hagan-Burke, Shanna; Simmons, Leslie E.; Fogarty, Melissa; Oslund, Eric; Coyne, Michael D.

    2012-01-01

    This study compared the effects of Tier 2 reading interventions that operated in response-to-intervention contexts. Kindergarten children (N = 90) who were identified as at risk for reading difficulties were stratified by school and randomly assigned to receive (a) Early Reading Intervention (ERI; Pearson/Scott Foresman, 2004) modified in response…

  2. A Framework for Providing Culturally Responsive Early Intervention Services

    ERIC Educational Resources Information Center

    Bradshaw, Wendy

    2013-01-01

    The purpose of this article is to provide a framework that offers a way for early intervention (EI) service providers to better meet the needs of the culturally diverse children and families they serve. This framework was created to organize existing research and literature on cultural responsiveness in a way that fit the unique context of EI. The…

  3. The Reasons behind Early Adolescents' Responses to Peer Victimization

    ERIC Educational Resources Information Center

    Bellmore, Amy; Chen, Wei-Ting; Rischall, Emily

    2013-01-01

    Victims of school-based peer harassment face a range of risks including psycho-social, physical, and academic harm. The aim of the present study was to examine the behavioral coping responses used by early adolescents when they face peer victimization. To meet this aim, 216 sixth grade students (55% girls) from two urban middle schools and 254…

  4. Simple uncertainty propagation for early design phase aircraft sizing

    NASA Astrophysics Data System (ADS)

    Lenz, Annelise

    Many designers and systems analysts are aware of the uncertainty inherent in their aircraft sizing studies; however, few incorporate methods to address and quantify this uncertainty. Many aircraft design studies use semi-empirical predictors based on a historical database and contain uncertainty -- a portion of which can be measured and quantified. In cases where historical information is not available, surrogate models built from higher-fidelity analyses often provide predictors for design studies where the computational cost of directly using the high-fidelity analyses is prohibitive. These surrogate models contain uncertainty, some of which is quantifiable. However, rather than quantifying this uncertainty, many designers merely include a safety factor or design margin in the constraints to account for the variability between the predicted and actual results. This can become problematic if a designer does not estimate the amount of variability correctly, which then can result in either an "over-designed" or "under-designed" aircraft. "Under-designed" and some "over-designed" aircraft will likely require design changes late in the process and will ultimately require more time and money to create; other "over-designed" aircraft concepts may not require design changes, but could end up being more costly than necessary. Including and propagating uncertainty early in the design phase so designers can quantify some of the errors in the predictors could help mitigate the extent of this additional cost. The method proposed here seeks to provide a systematic approach for characterizing a portion of the uncertainties that designers are aware of and propagating it throughout the design process in a procedure that is easy to understand and implement. Using Monte Carlo simulations that sample from quantified distributions will allow a systems analyst to use a carpet plot-like approach to make statements like: "The aircraft is 'P'% likely to weigh 'X' lbs or less, given the

  5. The bradykinin B2 receptor in the early immune response against Listeria infection.

    PubMed

    Kaman, Wendy E; Wolterink, Arthur F W M; Bader, Michael; Boele, Linda C L; van der Kleij, Desiree

    2009-02-01

    The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B(2) (B(2)R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B(2)R (B(2)R(-/-) mice) were shown to suffer from increased hepatic bacterial burden and concomitant dramatic weight loss during infection with Listeria monocytogenes. Levels of cytokines known to play a pivotal role in the early phase immune response against L. monocytogenes, IL-12p70 and IFN-gamma, were reduced in B(2)R(-/-) mice. To extend these findings to the human system, we show that bradykinin potentiates the production of IL-12p70 in human monocyte-derived dendritic cells. Thus, we show that bradykinin and the B(2)R play a role in early innate immune functions during bacterial infection.

  6. Glassy phases and driven response of the phase-field-crystal model with random pinning.

    PubMed

    Granato, E; Ramos, J A P; Achim, C V; Lehikoinen, J; Ying, S C; Ala-Nissila, T; Elder, K R

    2011-09-01

    We study the structural correlations and the nonlinear response to a driving force of a two-dimensional phase-field-crystal model with random pinning. The model provides an effective continuous description of lattice systems in the presence of disordered external pinning centers, allowing for both elastic and plastic deformations. We find that the phase-field crystal with disorder assumes an amorphous glassy ground state, with only short-ranged positional and orientational correlations, even in the limit of weak disorder. Under increasing driving force, the pinned amorphous-glass phase evolves into a moving plastic-flow phase and then, finally, a moving smectic phase. The transverse response of the moving smectic phase shows a vanishing transverse critical force for increasing system sizes.

  7. Sex differences in acute hormonal and subjective response to naltrexone: the impact of menstrual cycle phase

    PubMed Central

    Roche, Daniel J.O.; King, Andrea C.

    2015-01-01

    Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n = 46 women) participated in two morning sessions in which they received 50 mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n = 23) or luteal phase of the MC. Serum cortisol, prolactin, and luteinizing hormone (LH), salivary cortisol, and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women. PMID:25459893

  8. Efficient runner safety assessment during early design phase and root cause analysis

    NASA Astrophysics Data System (ADS)

    Liang, Q. W.; Lais, S.; Gentner, C.; Braun, O.

    2012-11-01

    Fatigue related problems in Francis turbines, especially high head Francis turbines, have been published several times in the last years. During operation the runner is exposed to various steady and unsteady hydraulic loads. Therefore the analysis of forced response of the runner structure requires a combined approach of fluid dynamics and structural dynamics. Due to the high complexity of the phenomena and due to the limitation of computer power, the numerical prediction was in the past too expensive and not feasible for the use as standard design tool. However, due to continuous improvement of the knowledge and the simulation tools such complex analysis has become part of the design procedure in ANDRITZ HYDRO. This article describes the application of most advanced analysis techniques in runner safety check (RSC), including steady state CFD analysis, transient CFD analysis considering rotor stator interaction (RSI), static FE analysis and modal analysis in water considering the added mass effect, in the early design phase. This procedure allows a very efficient interaction between the hydraulic designer and the mechanical designer during the design phase, such that a risk of failure can be detected and avoided in an early design stage.The RSC procedure can also be applied to a root cause analysis (RCA) both to find out the cause of failure and to quickly define a technical solution to meet the safety criteria. An efficient application to a RCA of cracks in a Francis runner is quoted in this article as an example. The results of the RCA are presented together with an efficient and inexpensive solution whose effectiveness could be proven again by applying the described RSC technics. It is shown that, with the RSC procedure developed and applied as standard procedure in ANDRITZ HYDRO such a failure is excluded in an early design phase. Moreover, the RSC procedure is compatible with different commercial and open source codes and can be easily adapted to apply for

  9. Estimating disease prevalence from two-phase surveys with non-response at the second phase

    PubMed Central

    Gao, Sujuan; Hui, Siu L.; Hall, Kathleen S.; Hendrie, Hugh C.

    2010-01-01

    SUMMARY In this paper we compare several methods for estimating population disease prevalence from data collected by two-phase sampling when there is non-response at the second phase. The traditional weighting type estimator requires the missing completely at random assumption and may yield biased estimates if the assumption does not hold. We review two approaches and propose one new approach to adjust for non-response assuming that the non-response depends on a set of covariates collected at the first phase: an adjusted weighting type estimator using estimated response probability from a response model; a modelling type estimator using predicted disease probability from a disease model; and a regression type estimator combining the adjusted weighting type estimator and the modelling type estimator. These estimators are illustrated using data from an Alzheimer’s disease study in two populations. Simulation results are presented to investigate the performances of the proposed estimators under various situations. PMID:10931514

  10. Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections

    PubMed Central

    Yu, Yanbao; Kwon, Keehwan; Tsitrin, Tamara; Sikorski, Patricia; Nelson, Karen E.; Pieper, Rembert

    2017-01-01

    Neutrophils have an important role in the antimicrobial defense and resolution of urinary tract infections (UTIs). Our research suggests that a mechanism known as neutrophil extracellular trap (NET) formation is a defense strategy to combat pathogens that have invaded the urinary tract. A set of human urine specimens with very high neutrophil counts had microscopic evidence of cellular aggregation and lysis. Deoxyribonuclease I (DNase) treatment resulted in disaggregation of such structures, release of DNA fragments and a proteome enriched in histones and azurophilic granule effectors whose quantitative composition was similar to that of previously described in vitro-formed NETs. The effector proteins were further enriched in DNA-protein complexes isolated in native PAGE gels. Immunofluorescence microscopy revealed a flattened morphology of neutrophils associated with decondensed chromatin, remnants of granules in the cell periphery, and myeloperoxidase co-localized with extracellular DNA, features consistent with early-phase NETs. Nuclear staining revealed that a considerable fraction of bacterial cells in these structures were dead. The proteomes of two pathogens, Staphylococcus aureus and Escherichia coli, were indicative of adaptive responses to early-phase NETs, specifically the release of virulence factors and arrest of ribosomal protein synthesis. Finally, we discovered patterns of proteolysis consistent with widespread cleavage of proteins by neutrophil elastase, proteinase 3 and cathepsin G and evidence of citrullination in many nuclear proteins. PMID:28129394

  11. Presence of early stage cancer does not impair the early protein metabolic response to major surgery

    PubMed Central

    Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

    2017-01-01

    Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the

  12. Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

    PubMed

    Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

    2017-06-01

    Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after

  13. Early Childhood Program: Summary of Context Analysis Phase.

    ERIC Educational Resources Information Center

    Southwest Educational Development Lab., Austin, TX.

    Progress made in the field of early childhood development during the past decade is examined to provide the background and rationale for tree programs funded by the National Institute of Education (NIE) in 1974: a parenting information center, a multimedia child care training package, and television spots related to child rearing principles. The…

  14. Stomatal Blue Light Response Is Present in Early Vascular Plants.

    PubMed

    Doi, Michio; Kitagawa, Yuki; Shimazaki, Ken-ichiro

    2015-10-01

    Light is a major environmental factor required for stomatal opening. Blue light (BL) induces stomatal opening in higher plants as a signal under the photosynthetic active radiation. The stomatal BL response is not present in the fern species of Polypodiopsida. The acquisition of a stomatal BL response might provide competitive advantages in both the uptake of CO2 and prevention of water loss with the ability to rapidly open and close stomata. We surveyed the stomatal opening in response to strong red light (RL) and weak BL under the RL with gas exchange technique in a diverse selection of plant species from euphyllophytes, including spermatophytes and monilophytes, to lycophytes. We showed the presence of RL-induced stomatal opening in most of these species and found that the BL responses operated in all euphyllophytes except Polypodiopsida. We also confirmed that the stomatal opening in lycophytes, the early vascular plants, is driven by plasma membrane proton-translocating adenosine triphosphatase and K(+) accumulation in guard cells, which is the same mechanism operating in stomata of angiosperms. These results suggest that the early vascular plants respond to both RL and BL and actively regulate stomatal aperture. We also found three plant species that absolutely require BL for both stomatal opening and photosynthetic CO2 fixation, including a gymnosperm, C. revoluta, and the ferns Equisetum hyemale and Psilotum nudum. © 2015 American Society of Plant Biologists. All Rights Reserved.

  15. Evaluating cardiac risk: exposure response analysis in early clinical drug development.

    PubMed

    Grenier, Julie; Paglialunga, Sabina; Morimoto, Bruce H; Lester, Robert M

    2018-01-01

    The assessment of a drug's cardiac liability has undergone considerable metamorphosis by regulators since International Council for Harmonization of Technical Requirement for Pharmaceuticals for Human Use E14 guideline was introduced in 2005. Drug developers now have a choice in how proarrhythmia risk can be evaluated; the options include a dedicated thorough QT (TQT) study or exposure response (ER) modeling of intensive electrocardiogram (ECG) captured in early clinical development. The alternative approach of ER modeling was incorporated into a guidance document in 2015 as a primary analysis tool which could be utilized in early phase dose escalation studies as an option to perform a dedicated TQT trial. This review will describe the current state of ER modeling of intensive ECG data collected during early clinical drug development; the requirements with regard to the use of a positive control; and address the challenges and opportunities of this alternative approach to assessing QT liability.

  16. Early stage response problem for post-disaster incidents

    NASA Astrophysics Data System (ADS)

    Kim, Sungwoo; Shin, Youngchul; Lee, Gyu M.; Moon, Ilkyeong

    2018-07-01

    Research on evacuation plans for reducing damages and casualties has been conducted to advise defenders against threats. However, despite the attention given to the research in the past, emergency response management, designed to neutralize hazards, has been undermined since planners frequently fail to apprehend the complexities and contexts of the emergency situation. Therefore, this study considers a response problem with unique characteristics for the duration of the emergency. An early stage response problem is identified to find the optimal routing and scheduling plan for responders to prevent further hazards. Due to the complexity of the proposed mathematical model, two algorithms are developed. Data from a high-rise building, called Central City in Seoul, Korea, are used to evaluate the algorithms. Results show that the proposed algorithms can procure near-optimal solutions within a reasonable time.

  17. Response of two-phase droplets to intense electromagnetic radiation

    NASA Technical Reports Server (NTRS)

    Spann, James F.; Maloney, Daniel J.; Lawson, William F.; Casleton, Kent H.

    1993-01-01

    The response of two-phase droplets to intense radiant heating is studied to determine the incident power that is required for causing explosive boiling in the liquid phase. The droplets studied consist of strongly absorbing coal particles dispersed in a weakly absorbing water medium. Experiments are performed by confining droplets (radii of 37, 55, and 80 microns) electrodynamically and irradiating them from two sides with pulsed laser beams. Emphasis is placed on the transition region from accelerated droplet vaporization to droplet superheating and explosive boiling. The time scale observed for explosive boiling is more than 2 orders of magnitude longer than published values for pure liquids. The delayed response is the result of energy transfer limitations between the absorbing solid phase and the surrounding liquid.

  18. Early prediction of blonanserin response in Japanese patients with schizophrenia.

    PubMed

    Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

    2014-01-01

    Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (P<0.0001) and in positive (P<0.0001), negative (P<0.0001), and general subscale scores (P<0.0001). In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores) were 88.9% and 94.1%, respectively. The specificities were 80.0% and 51.6%, respectively. Our results suggest that the blonanserin response at week 4 could predict the later response at week 8.

  19. Early prediction of blonanserin response in Japanese patients with schizophrenia

    PubMed Central

    Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

    2014-01-01

    Background Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. Methods An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Results Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (P<0.0001) and in positive (P<0.0001), negative (P<0.0001), and general subscale scores (P<0.0001). In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores) were 88.9% and 94.1%, respectively. The specificities were 80.0% and 51.6%, respectively. Conclusion Our results suggest that the blonanserin response at week 4 could predict the later response at week 8. PMID:25285009

  20. Phase-shifting response to light in older adults

    PubMed Central

    Kim, Seong Jae; Benloucif, Susan; Reid, Kathryn Jean; Weintraub, Sandra; Kennedy, Nancy; Wolfe, Lisa F; Zee, Phyllis C

    2014-01-01

    Abstract Age-related changes in circadian rhythms may contribute to the sleep disruption observed in older adults. A reduction in responsiveness to photic stimuli in the circadian timing system has been hypothesized as a possible reason for the advanced circadian phase in older adults. This project compared phase-shifting responses to 2 h of broad-spectrum white light at moderate and high intensities in younger and older adults. Subjects included 29 healthy young (25.1 ± 4.1 years; male to female ratio: 8: 21) and 16 healthy older (66.5 ± 6.0 years; male to female ratio: 5: 11) subjects, who participated in two 4-night and 3-day laboratory stays, separated by at least 3 weeks. Subjects were randomly assigned to one of three different time-points, 8 h before (−8), 3 h before (−3) or 3 h after (+3) the core body temperature minimum (CBTmin) measured on the baseline night. For each condition, subjects were exposed in a randomized order to 2 h light pulses of two intensities (2000 lux and 8000 lux) during the two different laboratory stays. Phase shifts were analysed according to the time of melatonin midpoint on the nights before and after light exposure. Older subjects in this study showed an earlier baseline phase and lower amplitude of melatonin rhythm compared to younger subjects, but there was no evidence of age-related changes in the magnitude or direction of phase shifts of melatonin midpoint in response to 2 h of light at either 2000 lux or 8000 lux. These results indicate that the acute phase-shifting response to moderate- or high-intensity broad spectrum light is not significantly affected by age. PMID:24144880

  1. Early Childhood Technology Integrated Instructional System (EC-TIIS) Phase 1: A Final Report

    ERIC Educational Resources Information Center

    Hutinger, Patricia; Robinson, Linda; Schneider, Carol

    2004-01-01

    The Early Childhood Technology Integrated Instructional System (EC-TIIS), a Steppingstones of Technology Innovation Phase 1--Development project, was developed by the Center for Best Practices in Early Childhood (the Center) at Western Illinois University as an online instructional system. EC-TIIS' ultimate goal was to improve technology services…

  2. Istanbul Earthquake Early Warning and Rapid Response System

    NASA Astrophysics Data System (ADS)

    Erdik, M. O.; Fahjan, Y.; Ozel, O.; Alcik, H.; Aydin, M.; Gul, M.

    2003-12-01

    As part of the preparations for the future earthquake in Istanbul a Rapid Response and Early Warning system in the metropolitan area is in operation. For the Early Warning system ten strong motion stations were installed as close as possible to the fault zone. Continuous on-line data from these stations via digital radio modem provide early warning for potentially disastrous earthquakes. Considering the complexity of fault rupture and the short fault distances involved, a simple and robust Early Warning algorithm, based on the exceedance of specified threshold time domain amplitude levels is implemented. The band-pass filtered accelerations and the cumulative absolute velocity (CAV) are compared with specified threshold levels. When any acceleration or CAV (on any channel) in a given station exceeds specific threshold values it is considered a vote. Whenever we have 2 station votes within selectable time interval, after the first vote, the first alarm is declared. In order to specify the appropriate threshold levels a data set of near field strong ground motions records form Turkey and the world has been analyzed. Correlations among these thresholds in terms of the epicenter distance the magnitude of the earthquake have been studied. The encrypted early warning signals will be communicated to the respective end users by UHF systems through a "service provider" company. The users of the early warning signal will be power and gas companies, nuclear research facilities, critical chemical factories, subway system and several high-rise buildings. Depending on the location of the earthquake (initiation of fault rupture) and the recipient facility the alarm time can be as high as about 8s. For the rapid response system one hundred 18 bit-resolution strong motion accelerometers were placed in quasi-free field locations (basement of small buildings) in the populated areas of the city, within an area of approximately 50x30km, to constitute a network that will enable early

  3. 78 FR 5816 - Guidance for Industry on Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    .... The guidance provides recommendations on when and how genomic principles should be considered and... recommendations on when and how genomic principles should be considered and applied in early-phase clinical... the larger, later adequate, and well-controlled trials (phase 3) that are needed to support marketing...

  4. Relationship between Duration of Untreated Psychosis and Intrinsic Corticostriatal Connectivity in Patients with Early Phase Schizophrenia.

    PubMed

    Sarpal, Deepak K; Robinson, Delbert G; Fales, Christina; Lencz, Todd; Argyelan, Miklos; Karlsgodt, Katherine H; Gallego, Juan A; John, Majnu; Kane, John M; Szeszko, Philip R; Malhotra, Anil K

    2017-10-01

    Patients with first-episode psychosis experience psychotic symptoms for a mean of up to 2 years prior to initiation of treatment, and long duration of untreated psychosis (DUP) is associated with poor clinical outcomes. Meanwhile, evidence compiled from numerous studies suggests that longer DUP is not associated with structural brain abnormalities. To date, few studies have examined the relationship between DUP and functional neuroimaging measures. In the present study, we used seed-based resting-state functional connectivity to examine the impact of DUP on corticostriatal circuitry. We included 83 patients with early phase schizophrenia and minimal exposure to antipsychotic drugs (<2 years), who underwent resting state scanning while entering 12 weeks of prospective treatment with second-generation antipsychotic drugs. Functional connectivity maps of the striatum were generated and examined in relation to DUP as a covariate. Mediation analyses were performed on a composite measure of corticostriatal connectivity derived from the significant results of our DUP analysis. We found that longer DUP correlated with worse response to treatment as well as overall decreased functional connectivity between striatal nodes and specific regions within frontal and parietal cortices. Moreover, the relationship between DUP and treatment response was significantly mediated by corticostriatal connectivity. Our results indicate that variation in corticostriatal circuitry may play a role in the relationship between longer DUP and worsened response to treatment. Future prospective studies are necessary to further characterize potential causal links between DUP, striatal circuitry and clinical outcomes.

  5. Early-life inflammation, immune response and ageing.

    PubMed

    Khan, Imroze; Agashe, Deepa; Rolff, Jens

    2017-03-15

    Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

  6. Early life adversity influences stress response association with smoking relapse.

    PubMed

    al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

    2017-11-01

    We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

  7. Early-life inflammation, immune response and ageing

    PubMed Central

    2017-01-01

    Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. PMID:28275145

  8. Survival of Campylobacter jejuni during Stationary Phase: Evidence for the Absence of a Phenotypic Stationary-Phase Response

    PubMed Central

    Kelly, Alison F.; Park, Simon F.; Bovill, Richard; Mackey, Bernard M.

    2001-01-01

    When Campylobacter jejuni NCTC 11351 was grown microaerobically in rich medium at 39°C, entry into stationary phase was followed by a rapid decline in viable numbers to leave a residual population of 1% of the maximum number or less. Loss of viability was preceded by sublethal injury, which was seen as a loss of the ability to grow on media containing 0.1% sodium deoxycholate or 1% sodium chloride. Resistance of cells to mild heat stress (50°C) or aeration was greatest in exponential phase and declined during early stationary phase. These results show that C. jejuni does not mount the normal phenotypic stationary-phase response which results in enhanced stress resistance. This conclusion is consistent with the absence of rpoS homologues in the recently reported genome sequence of this species and their probable absence from strain NCTC 11351. During prolonged incubation of C. jejuni NCTC 11351 in stationary phase, an unusual pattern of decreasing and increasing heat resistance was observed that coincided with fluctuations in the viable count. During stationary phase of Campylobacter coli UA585, nonmotile variants and those with impaired ability to form coccoid cells were isolated at high frequency. Taken together, these observations suggest that stationary-phase cultures of campylobacters are dynamic populations and that this may be a strategy to promote survival in at least some strains. Investigation of two spontaneously arising variants (NM3 and SC4) of C. coli UA585 showed that a reduced ability to form coccoid cells did not affect survival under nongrowth conditions. PMID:11319108

  9. Observable induced gravitational waves from an early matter phase

    SciT

    Alabidi, Laila; Sasaki, Misao; Kohri, Kazunori

    2013-05-01

    Assuming that inflation is succeeded by a phase of matter domination, which corresponds to a low temperature of reheating T{sub r} < 10{sup 9}GeV, we evaluate the spectra of gravitational waves induced in the post-inflationary universe. We work with models of hilltop-inflation with an enhanced primordial scalar spectrum on small scales, which can potentially lead to the formation of primordial black holes. We find that a lower reheat temperature leads to the production of gravitational waves with energy densities within the ranges of both space and earth based gravitational wave detectors.

  10. Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT

    DTIC Science & Technology

    2016-08-01

    AWARD NUMBER: W81XWH-12-1-0138 TITLE: Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT PRINCIPAL INVESTIGATOR...NUMBER W81XWH-12-1-0138 Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...method for early detection of amyloid plaque in Alzheimer’s disease , with three Specific Aims: #1 Develop and optimize an x-ray PCCT to explore the

  11. Phase Transitions in the Early Universe: The Cosmology of Non-Minimal Scalar Sectors

    NASA Astrophysics Data System (ADS)

    Kost, Jeffrey D.

    Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically--such as during cosmological mass-generating phase transitions--the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this thesis, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system--often by many orders of magnitude--but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "re-overdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings. In the second part of this thesis, we proceed to study the early-universe cosmology of a Kaluza-Klein (KK

  12. Early visual processing is enhanced in the midluteal phase of the menstrual cycle.

    PubMed

    Lusk, Bethany R; Carr, Andrea R; Ranson, Valerie A; Bryant, Richard A; Felmingham, Kim L

    2015-12-01

    Event-related potential (ERP) studies have revealed an early attentional bias in processing unpleasant emotional images in women. Recent neuroimaging data suggests there are significant differences in cortical emotional processing according to menstrual phase. This study examined the impact of menstrual phase on visual emotional processing in women compared to men. ERPs were recorded from 28 early follicular women, 29 midluteal women, and 27 men while they completed a passive viewing task of neutral and low- and high- arousing pleasant and unpleasant images. There was a significant effect of menstrual phase in early visual processing, as midluteal women displayed significantly greater P1 amplitude at occipital regions to all visual images compared to men. Both midluteal and early follicular women displayed larger N1 amplitudes than men (although this only reached significance for the midluteal group) to the visual images. No sex or menstrual phase differences were apparent in later N2, P3, or LPP. A condition effect demonstrated greater P3 and LPP amplitude to highly-arousing unpleasant images relative to all other stimuli conditions. These results indicate that women have greater early automatic visual processing compared to men, and suggests that this effect is particularly strong in women in the midluteal phase at the earliest stage of visual attention processing. Our findings highlight the importance of considering menstrual phase when examining sex differences in the cortical processing of visual stimuli. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Evasion of Early Antiviral Responses by Herpes Simplex Viruses

    PubMed Central

    Suazo, Paula A.; Ibañez, Francisco J.; Retamal-Díaz, Angello R.; Paz-Fiblas, Marysol V.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.

    2015-01-01

    Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs) must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency. PMID:25918478

  14. Analysis of gene expression during parabolic flights reveals distinct early gravity responses in Arabidopsis roots.

    PubMed

    Aubry-Hivet, D; Nziengui, H; Rapp, K; Oliveira, O; Paponov, I A; Li, Y; Hauslage, J; Vagt, N; Braun, M; Ditengou, F A; Dovzhenko, A; Palme, K

    2014-01-01

    Plant roots are among most intensively studied biological systems in gravity research. Altered gravity induces asymmetric cell growth leading to root bending. Differential distribution of the phytohormone auxin underlies root responses to gravity, being coordinated by auxin efflux transporters from the PIN family. The objective of this study was to compare early transcriptomic changes in roots of Arabidopsis thaliana wild type, and pin2 and pin3 mutants under parabolic flight conditions and to correlate these changes to auxin distribution. Parabolic flights allow comparison of transient 1-g, hypergravity and microgravity effects in living organisms in parallel. We found common and mutation-related genes differentially expressed in response to transient microgravity phases. Gene ontology analysis of common genes revealed lipid metabolism, response to stress factors and light categories as primarily involved in response to transient microgravity phases, suggesting that fundamental reorganisation of metabolic pathways functions upstream of a further signal mediating hormonal network. Gene expression changes in roots lacking the columella-located PIN3 were stronger than in those deprived of the epidermis and cortex cell-specific PIN2. Moreover, repetitive exposure to microgravity/hypergravity and gravity/hypergravity flight phases induced an up-regulation of auxin responsive genes in wild type and pin2 roots, but not in pin3 roots, suggesting a critical function of PIN3 in mediating auxin fluxes in response to transient microgravity phases. Our study provides important insights towards understanding signal transduction processes in transient microgravity conditions by combining for the first time the parabolic flight platform with the transcriptome analysis of different genetic mutants in the model plant, Arabidopsis. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  15. Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

    NASA Astrophysics Data System (ADS)

    Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

    2016-06-01

    Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

  16. Diffusion MRI in early cancer therapeutic response assessment

    PubMed Central

    Galbán, C. J.; Hoff, B. A.; Chenevert, T. L.; Ross, B. D.

    2016-01-01

    Imaging biomarkers for the predictive assessment of treatment response in patients with cancer earlier than standard tumor volumetric metrics would provide new opportunities to individualize therapy. Diffusion-weighted MRI (DW-MRI), highly sensitive to microenvironmental alterations at the cellular level, has been evaluated extensively as a technique for the generation of quantitative and early imaging biomarkers of therapeutic response and clinical outcome. First demonstrated in a rodent tumor model, subsequent studies have shown that DW-MRI can be applied to many different solid tumors for the detection of changes in cellularity as measured indirectly by an increase in the apparent diffusion coefficient (ADC) of water molecules within the lesion. The introduction of quantitative DW-MRI into the treatment management of patients with cancer may aid physicians to individualize therapy, thereby minimizing unnecessary systemic toxicity associated with ineffective therapies, saving valuable time, reducing patient care costs and ultimately improving clinical outcome. This review covers the theoretical basis behind the application of DW-MRI to monitor therapeutic response in cancer, the analytical techniques used and the results obtained from various clinical studies that have demonstrated the efficacy of DW-MRI for the prediction of cancer treatment response. PMID:26773848

  17. Mixed response and time-to-event endpoints for multistage single-arm phase II design.

    PubMed

    Lai, Xin; Zee, Benny Chung-Ying

    2015-06-04

    The objective of phase II cancer clinical trials is to determine if a treatment has sufficient activity to warrant further study. The efficiency of a conventional phase II trial design has been the object of considerable debate, particularly when the study regimen is characteristically cytostatic. At the time of development of a phase II cancer trial, we accumulated clinical experience regarding the time to progression (TTP) for similar classes of drugs and for standard therapy. By considering the time to event (TTE) in addition to the tumor response endpoint, a mixed-endpoint phase II design may increase the efficiency and ability of selecting promising cytotoxic and cytostatic agents for further development. We proposed a single-arm phase II trial design by extending the Zee multinomial method to fully use mixed endpoints with tumor response and the TTE. In this design, the dependence between the probability of response and the TTE outcome is modeled through a Gaussian copula. Given the type I and type II errors and the hypothesis as defined by the response rate (RR) and median TTE, such as median TTP, the decision rules for a two-stage phase II trial design can be generated. We demonstrated through simulation that the proposed design has a smaller expected sample size and higher early stopping probability under the null hypothesis than designs based on a single-response endpoint or a single TTE endpoint. The proposed design is more efficient for screening new cytotoxic or cytostatic agents and less likely to miss an effective agent than the alternative single-arm design.

  18. Nonlinearity response correction in phase-shifting deflectometry

    NASA Astrophysics Data System (ADS)

    Nguyen, Manh The; Kang, Pilseong; Ghim, Young-Sik; Rhee, Hyug-Gyo

    2018-04-01

    Owing to the nonlinearity response of digital devices such as screens and cameras in phase-shifting deflectometry, non-sinusoidal phase-shifted fringe patterns are generated and additional measurement errors are introduced. In this paper, a new deflectometry technique is described for overcoming these problems using a pre-distorted pattern combined with an advanced iterative algorithm. The experiment results show that this method can reconstruct the 3D surface map of a sample without fringe print-through caused by the nonlinearity response of digital devices. The proposed technique is verified by measuring the surface height variations in a deformable mirror and comparing them with the measurement result obtained using a coordinate measuring machine. The difference between the two measurement results is estimated to be less than 13 µm.

  19. Elastic Properties and Enhanced Piezoelectric Response at Morphotropic Phase Boundaries

    PubMed Central

    Cordero, Francesco

    2015-01-01

    The search for improved piezoelectric materials is based on the morphotropic phase boundaries (MPB) between ferroelectric phases with different crystal symmetry and available directions for the spontaneous polarization. Such regions of the composition x−T phase diagrams provide the conditions for minimal anisotropy with respect to the direction of the polarization, so that the polarization can easily rotate maintaining a substantial magnitude, while the near verticality of the TMPBx boundary extends the temperature range of the resulting enhanced piezoelectricity. Another consequence of the quasi-isotropy of the free energy is a reduction of the domain walls energies, with consequent formation of domain structures down to nanoscale. Disentangling the extrinsic and intrinsic contributions to the piezoelectricity in such conditions requires a high level of sophistication from the techniques and analyses for studying the structural, ferroelectric and dielectric properties. The elastic characterization is extremely useful in clarifying the phenomenology and mechanisms related to ferroelectric MPBs. The relationship between dielectric, elastic and piezoelectric responses is introduced in terms of relaxation of defects with electric dipole and elastic quadrupole, and extended to the response near phase transitions in the framework of the Landau theory. An account is provided of the anelastic experiments, from torsional pendulum to Brillouin scattering, that provided new important information on ferroelectric MPBs, including PZT, PMN-PT, NBT-BT, BCTZ, and KNN-based systems. PMID:28793707

  20. In search of a phase response curve for lithium chloride

    SciT

    Readey, M.A.; Groh, K.R.; Ehret, C.F.

    1987-01-01

    Male rats were free-run, and one day later were exposed to a single, punctate dose of 5 mM LiCl/kg body weight by injection at one of eight equally spaced times throughout the 24-h period. For each of the six days following injection, a separate phase response curve was derived from core-temperature chronograms. Unlike the classical response induced by chronobiotics such as dexamethasone, alpha-methyl-para-tyrosine, and theophylline, statistically significant phase shifts for lithium were observed only on the first day following injection. These induced phase changes were not permanent, but instead were transient. By the sixth day of free-run, all experimental ratsmore » had drifted to the control acrophase; i.e., by the end of the experiment, most of the treated rats again had phase and confidence arcs not significantly different from their controls. The confidence arcs of the acrophases of the individual animals on the subsequent days post injection reveal that in this experiment, lithium was transiently dyschronogenic rather than definitively chronobiotic. The results suggest that punctate rather than chronic administration of lithium, followed by strict orthochronal administration of traditional zeitgebers, would be an effective way of restoring circadian synchrony in an internally desynchronized system. 122 refs.« less

  1. Quantitative Proteomic Profiling of Early and Late Responses to Salicylic Acid in Cucumber Leaves

    PubMed Central

    Li, Liang; Shang, Qing-Mao

    2016-01-01

    Salicylic acid (SA) is an important phytohormone that plays vital regulatory roles in plant growth, development, and stress responses. However, studies on the molecular mechanism of SA, especially during the early SA responses, are lagging behind. In this study, we initiated a comprehensive isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to explore the early and late SA-responsive proteins in leaves of cucumber (Cucumis sativus L.) seedlings. Upon SA application through the roots, endogenous SA accumulated in cucumber leaves. By assaying the changes in marker gene expression and photosynthetic rate, we collected samples at 12 h and 72 h post treatment (hpt) to profile the early and late SA responsiveness, respectively. The iTRAQ assay followed by tandem mass spectrometry revealed 135 differentially expressed proteins (DEPs) at 12 hpt and 301 DEPs at 72 hpt. The functional categories for these SA-responsive proteins included in a variety of biochemical processes, including photosynthesis, redox homeostasis, carbohydrate and energy metabolism, lipid metabolism, transport, protein folding and modification, proteolysis, cell wall organization, and the secondary phenylpropanoid pathway. Conclusively, based on the abundant changes of these DEPs, together with their putative functions, we proposed a possible SA-responsive protein network. It appears that SA could elicit reactive oxygen species (ROS) production via enhancing the photosynthetic electron transferring, and then confer some growth-promoting and stress-priming effects on cells during the late phase, including enhanced photosynthesis and ROS scavenging, altered carbon metabolic flux for the biosynthesis of amino acids and nucleotides, and cell wall reorganization. Overall, the present iTRAQ assay provides higher proteome coverage and deepened our understanding of the molecular basis of SA-responses. PMID:27551830

  2. Early Peritoneal Immune Response during Echinococcus granulosus Establishment Displays a Biphasic Behavior

    PubMed Central

    Mourglia-Ettlin, Gustavo; Marqués, Juan Martín; Chabalgoity, José Alejandro; Dematteis, Sylvia

    2011-01-01

    Background Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice. Principal Findings Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13). Conclusions Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies

  3. Enhancing early child care quality and learning for toddlers at risk: the responsive early childhood program.

    PubMed

    Landry, Susan H; Zucker, Tricia A; Taylor, Heather B; Swank, Paul R; Williams, Jeffrey M; Assel, Michael; Crawford, April; Huang, Weihua; Clancy-Menchetti, Jeanine; Lonigan, Christopher J; Phillips, Beth M; Eisenberg, Nancy; Spinrad, Tracy L; de Villiers, Jill; de Villiers, Peter; Barnes, Marcia; Starkey, Prentice; Klein, Alice

    2014-02-01

    Despite reports of positive effects of high-quality child care, few experimental studies have examined the process of improving low-quality center-based care for toddler-age children. In this article, we report intervention effects on child care teachers' behaviors and children's social, emotional, behavioral, early literacy, language, and math outcomes as well as the teacher-child relationship. The intervention targeted the use of a set of responsive teacher practices, derived from attachment and sociocultural theories, and a comprehensive curriculum. Sixty-five childcare classrooms serving low-income 2- and 3-year-old children were randomized into 3 conditions: business-as-usual control, Responsive Early Childhood Curriculum (RECC), and RECC plus explicit social-emotional classroom activities (RECC+). Classroom observations showed greater gains for RECC and RECC+ teachers' responsive practices including helping children manage their behavior, establishing a predictable schedule, and use of cognitively stimulating activities (e.g., shared book reading) compared with controls; however, teacher behaviors did not differ for focal areas such as sensitivity and positive discipline supports. Child assessments demonstrated that children in the interventions outperformed controls in areas of social and emotional development, although children's performance in control and intervention groups was similar for cognitive skills (language, literacy, and math). Results support the positive impact of responsive teachers and environments providing appropriate support for toddlers' social and emotional development. Possible explanations for the absence of systematic differences in children's cognitive skills are considered, including implications for practice and future research targeting low-income toddlers.

  4. Intracranial baroreflex yielding an early cushing response in human.

    PubMed

    Schmidt, E A; Czosnyka, Z; Momjian, S; Czosnyka, M; Bech, R A; Pickard, J D

    2005-01-01

    The Cushing response is a pre-terminal sympatho-adrenal systemic response to very high ICP. Animal studies have demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response. Infusion studies are routine procedures to investigate, by infusing CSF space with saline, the cerebrospinal fluid (CSF) biophysics in patients suspected of hydrocephalus. Our study aims at assessing systemic and cerebral haemodynamic changes during moderate rise of ICP in human. Infusion studies were performed in 34 patients. This is a routine test perform in patients presenting with symptoms of NPH during their pre-shunting assessment. Arterial blood pressure (ABP) and cerebral blood flow velocity (FV) were non-invasively monitored with photoplethysmography and transcranial Doppler. The rise in ICP (8.2 +/- 5.1 mmHg to 25 +/- 8.3 mmHg) was followed by a significant rise in ABP (106.6 +/- 29.7 mmHg to 115.2 +/- 30.1 mmHg), drop in CPP (98.3 +/- 29 mmHg to 90.2 +/- 30.7 mmHg) and decrease in FV (55.6 +/- 17 cm/s to 51.1 +/- 16.3 cm/s). Increasing ICP did not alter heart rate (70.4 +/- 10.4/min to 70.3 +/- 9.1/min) but augmented the heart rate variance (0.046 +/- 0.058 to 0.067 +/- 0.075/min). In a population suspected of hydrocephalus, our study demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response, demonstrating an early Cushing response in human and a putative intracranial baroreflex.

  5. Auto-inhibitory regulation of angiotensin II functionality in hamster aorta during the early phases of dyslipidemia.

    PubMed

    Pereira, Priscila Cristina; Pernomian, Larissa; Côco, Hariane; Gomes, Mayara Santos; Franco, João José; Marchi, Kátia Colombo; Hipólito, Ulisses Vilela; Uyemura, Sergio Akira; Tirapelli, Carlos Renato; de Oliveira, Ana Maria

    2016-06-15

    Emerging data point the crosstalk between dyslipidemia and renin-angiotensin system (RAS). Advanced dyslipidemia is described to induce RAS activation in the vasculature. However, the interplay between early dyslipidemia and the RAS remains unexplored. Knowing that hamsters and humans have a similar lipid profile, we investigated the effects of early and advanced dyslipidemia on angiotensin II-induced contraction. Cumulative concentration-response curves for angiotensin II (1.0pmol/l to 1.0µmol/l) were obtained in the hamster thoracic aorta. We also investigated the modulatory action of NAD(P)H oxidase on angiotensin II-induced contraction using ML171 (Nox-1 inhibitor, 0.5µmol/l) and VAS2870 (Nox-4 inhibitor, 5µmol/l). Early dyslipidemia was detected in hamsters treated with a cholesterol-rich diet for 15 days. Early dyslipidemia decreased the contraction induced by angiotensin II and the concentration of Nox-4-derived hydrogen peroxide. Advanced dyslipidemia, observed in hamsters treated with cholesterol-rich diet for 30 days, restored the contractile response induced by angiotensin II by compensatory mechanism that involves Nox-4-mediated oxidative stress. The hyporresponsiveness to angiotensin II may be an auto-inhibitory regulation of the angiotensinergic function during early dyslipidemia in an attempt to reduce the effects of the upregulation of the vascular RAS during the advanced stages of atherogenesis. The recovery of vascular angiotensin II functionality during the advanced phases of dyslipidemia is the result of the upregulation of redox-pro-inflammatory pathway that might be most likely involved in atherogenesis progression rather than in the recovery of vascular function. Taken together, our findings show the early phase of dyslipidemia may be the most favorable moment for effective atheroprotective therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Development of Environmental Load Estimation Model for Road Drainage Systems in the Early Design Phase

    NASA Astrophysics Data System (ADS)

    Park, Jin-Young; Lee, Dong-Eun; Kim, Byung-Soo

    2017-10-01

    Due to the increasing concern about climate change, efforts to reduce environmental load are continuously being made in construction industry, and LCA (life cycle assessment) is being presented as an effective method to assess environmental load. Since LCA requires information on construction quantity used for environmental load estimation, however, it is not being utilized in the environmental review in the early design phase where it is difficult to obtain such information. In this study, computation system for construction quantity based on standard cross section of road drainage facilities was developed to compute construction quantity required for LCA using only information available in the early design phase to develop and verify the effectiveness of a model that can perform environmental load estimation. The result showed that it is an effective model that can be used in the early design phase as it revealed a 13.39% mean absolute error rate.

  7. Response to Early AED Therapy and Its Prognostic Implications

    PubMed Central

    French, Jacqueline A.

    2002-01-01

    Determining the prognosis of patients when they first present with epilepsy is a difficult task. Several clinical studies have shed light on this very important topic. Potential predictors of the refractory state, including seizure etiology, duration of epilepsy before treatment, and epilepsy type, have not been successful indicators of long-term outcome. One predictor of the refractory state appears to be early response to AED therapy. Inadequate seizure control after initial treatment is a poor prognostic sign. Recent research into genetic causes of the refractory state has included investigation of the multiple drug resistance gene, and polymorphisms at drug targets. More work is needed to determine the causes and predictors of drug resistance. PMID:15309146

  8. Infusing Culturally Responsive Science Curriculum into Early Childhood Teacher Preparation

    NASA Astrophysics Data System (ADS)

    Yoon, Jiyoon; Martin, Leisa A.

    2017-08-01

    Previous research studies in early childhood teacher education have indicated that teacher candidates are not adequately prepared to demonstrate the knowledge and skills needed to teach science to all children including culturally and linguistically diverse students. To address this issue, the researchers provided 31 early childhood teacher candidates with instructions through a culturally responsive science education curriculum that integrates American and Korean science curriculum corresponding to the American and Korean standards for teacher education. The results showed a statistically significant increase in their Personal Science Teaching Efficacy (PSTE). In addition, the teacher candidates were able to create a multicultural/diverse lesson in the developing and proficiency levels based on Ambrosio's lesson matrix. This study provides teacher candidates' knowledge as well as an additional resource for developing their self-efficacy and understanding the role of multicultural/diverse lesson planning for science instruction. Also, teacher candidates could be better prepared by understanding how other countries approach science education and integrating this knowledge to enrich their own science instruction.

  9. Evaluation of measles-rubella vaccination for mothers in early puerperal phase.

    PubMed

    Hisano, Michi; Kato, Tatsuo; Inoue, Eisuke; Sago, Haruhiko; Yamaguchi, Koushi

    2016-02-24

    The postpartum period is an ideal opportunity to vaccinate mothers with inadequate immunity to vaccine-preventable diseases including measles and rubella. A prospective study of measles-rubella (MR) vaccination in the early puerperal phase was conducted in 171 mothers, who had insufficient antibody titers when screened for immunity to measles (≤ 1:4 on the neutralization test [NT]) or rubella (≤ 1:16 on the hemagglutination inhibition [HI] test) during pregnancy. To evaluate the efficacy of MR vaccination in the postpartum period, we determined their post-vaccination antibody titers and immune responses to vaccination, and investigated the association between these and their prolactin (PRL) levels and Th1/Th2 ratios at the time of vaccination. We also examined the passage of viral RNA and antigen into breast milk. Of the 169 participants who completed the study schedule, 117 and 101 had low antibody titers against measles and rubella, respectively. In the measles-seronegative group, the antibody-positive rate was 87% on the NT assay, and the NT geometric mean antibody titer was 11.4 (95% confidence interval [CI], 10.0-13.0). In the rubella-seronegative group, the antibody-positive rate was 88% on the HI test assay, and the HI geometric mean antibody titer was 64.0 (95% CI, 53.9-76.0). There was no association between the post-vaccination antibody titers and the PRL levels or Th1/Th2 ratios at the time of vaccination. In the rubella-seronegative group, subjects with higher Th1/Th2 ratios showed higher rates of responsiveness than those with lower ratios (P=0.045). Although measles virus RNA was isolated from the breast milk of two vaccinated mothers, breastfeeding was not associated with clinical disease in any infants. MR vaccination in the early puerperal phase is considered an effective way to prevent the diseases, regardless of the mother's immunological status and hormonal milieu. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Computation of the phase response curve: a direct numerical approach.

    PubMed

    Govaerts, W; Sautois, B

    2006-04-01

    Neurons are often modeled by dynamical systems--parameterized systems of differential equations. A typical behavioral pattern of neurons is periodic spiking; this corresponds to the presence of stable limit cycles in the dynamical systems model. The phase resetting and phase response curves (PRCs) describe the reaction of the spiking neuron to an input pulse at each point of the cycle. We develop a new method for computing these curves as a by-product of the solution of the boundary value problem for the stable limit cycle. The method is mathematically equivalent to the adjoint method, but our implementation is computationally much faster and more robust than any existing method. In fact, it can compute PRCs even where the limit cycle can hardly be found by time integration, for example, because it is close to another stable limit cycle. In addition, we obtain the discretized phase response curve in a form that is ideally suited for most applications. We present several examples and provide the implementation in a freely available Matlab code.

  11. Three steps to writing adaptive study protocols in the early phase clinical development of new medicines

    PubMed Central

    2014-01-01

    This article attempts to define terminology and to describe a process for writing adaptive, early phase study protocols which are transparent, self-intuitive and uniform. It provides a step by step guide, giving templates from projects which received regulatory authorisation and were successfully performed in the UK. During adaptive studies evolving data is used to modify the trial design and conduct within the protocol-defined remit. Adaptations within that remit are documented using non-substantial protocol amendments which do not require regulatory or ethical review. This concept is efficient in gathering relevant data in exploratory early phase studies, ethical and time- and cost-effective. PMID:24980283

  12. HannaH phase III randomised study: Association of total pathological complete response with event-free survival in HER2-positive early breast cancer treated with neoadjuvant-adjuvant trastuzumab after 2 years of treatment-free follow-up.

    PubMed

    Jackisch, Christian; Hegg, Roberto; Stroyakovskiy, Daniil; Ahn, Jin-Seok; Melichar, Bohuslav; Chen, Shin-Cheh; Kim, Sung-Bae; Lichinitser, Mikhail; Starosławska, Elżbieta; Kunz, Georg; Falcon, Silvia; Chen, Shou-Tung; Crepelle-Fléchais, Aulde; Heinzmann, Dominik; Shing, Mona; Pivot, Xavier

    2016-07-01

    In the phase III, open-label, randomised HannaH study, fixed-dose neoadjuvant-adjuvant subcutaneous trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer was non-inferior to standard weight-based intravenous infusion in terms of serum trough concentration and pathological complete response (pCR). Evidence suggests that pCR, particularly total pCR (tpCR), is likely to predict clinical benefit. We report associations between tpCR and event-free survival (EFS) from HannaH (the largest population from a single study of patients presenting with newly diagnosed HER2-positive breast cancer treated with neoadjuvant-adjuvant trastuzumab to date) plus long-term efficacy and safety. Eligible patients received four cycles of neoadjuvant docetaxel followed by four cycles of fluorouracil/epirubicin/cyclophosphamide administered concurrently with 3-weekly subcutaneous (600 mg fixed dose) or intravenous trastuzumab (8 mg/kg loading, 6 mg/kg maintenance doses). Post-surgery, patients received adjuvant trastuzumab as randomised to complete 1 year of standard treatment. In exploratory analyses, we used Cox regression to assess associations between tpCR and EFS. EFS rates per subgroup were estimated using the Kaplan-Meier method. Three-year EFS rates were 76% for subcutaneous and 73% for intravenous trastuzumab (unstratified hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69-1.30; intention-to-treat population). Three-year overall survival rates were 92% for subcutaneous and 90% for intravenous trastuzumab (unstratified HR 0.76, 95% CI 0.44-1.32). tpCR was associated with a reduced risk of an EFS event: subcutaneous arm HR 0.38 (95% CI 0.22-0.65); intravenous arm HR 0.32 (95% CI 0.18-0.60). Results were similar for subgroups, including oestrogen receptor status. The few additional adverse events occurring during treatment-free follow-up were balanced between arms. Long-term efficacy supports the established non-inferiority of

  13. Cognitive effects of bilateral high frequency repetitive transcranial magnetic stimulation in early phase psychosis: a pilot study.

    PubMed

    Francis, Michael M; Hummer, Tom A; Vohs, Jenifer L; Yung, Matthew G; Visco, Andrew C; Mehdiyoun, Nikki F; Kulig, Teresa C; Um, Miji; Yang, Ziyi; Motamed, Mehrdad; Liffick, Emily; Zhang, Ying; Breier, Alan

    2018-05-31

    Cognitive dysfunction is a core facet of schizophrenia that is present early in the course of the illness and contributes to diminished functioning and outcomes. Repetitive transcranial magnetic stimulation (rTMS) is a relatively new neuropsychiatric intervention. Initially used in treatment resistant depression, investigators are now studying rTMS for other psychiatric diseases such as schizophrenia. In this study we examined the effect of high frequency rTMS on cognitive function in a group of individuals with early phase psychosis. Twenty subjects were randomized (1:1) in double-blind fashion to rTMS or sham condition. Over two weeks subjects underwent ten sessions of high frequency, bilateral, sequential rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Prior to beginning and following completion of study treatment, subjects completed a cognitive assessment and magnetic resonance imaging. Subjects receiving rTMS, compared to sham treatment, displayed improvement on a standardized cognitive battery both immediately following the course of study treatment and at follow-up two weeks later. Imaging results revealed that left frontal cortical thickness at baseline was correlated with treatment response. The study treatment was found to be safe and well tolerated. These results suggest that rTMS may hold promise for the treatment of cognitive dysfunction in the early phase of psychosis, and that MRI may provide biomarkers predicting response to the treatment.

  14. Collective phase response curves for heterogeneous coupled oscillators

    NASA Astrophysics Data System (ADS)

    Hannay, Kevin M.; Booth, Victoria; Forger, Daniel B.

    2015-08-01

    Phase response curves (PRCs) have become an indispensable tool in understanding the entrainment and synchronization of biological oscillators. However, biological oscillators are often found in large coupled heterogeneous systems and the variable of physiological importance is the collective rhythm resulting from an aggregation of the individual oscillations. To study this phenomena we consider phase resetting of the collective rhythm for large ensembles of globally coupled Sakaguchi-Kuramoto oscillators. Making use of Ott-Antonsen theory we derive an asymptotically valid analytic formula for the collective PRC. A result of this analysis is a characteristic scaling for the change in the amplitude and entrainment points for the collective PRC compared to the individual oscillator PRC. We support the analytical findings with numerical evidence and demonstrate the applicability of the theory to large ensembles of coupled neuronal oscillators.

  15. Phase response curves for models of earthquake fault dynamics

    SciT

    Franović, Igor, E-mail: franovic@ipb.ac.rs; Kostić, Srdjan; Perc, Matjaž

    We systematically study effects of external perturbations on models describing earthquake fault dynamics. The latter are based on the framework of the Burridge-Knopoff spring-block system, including the cases of a simple mono-block fault, as well as the paradigmatic complex faults made up of two identical or distinct blocks. The blocks exhibit relaxation oscillations, which are representative for the stick-slip behavior typical for earthquake dynamics. Our analysis is carried out by determining the phase response curves of first and second order. For a mono-block fault, we consider the impact of a single and two successive pulse perturbations, further demonstrating how themore » profile of phase response curves depends on the fault parameters. For a homogeneous two-block fault, our focus is on the scenario where each of the blocks is influenced by a single pulse, whereas for heterogeneous faults, we analyze how the response of the system depends on whether the stimulus is applied to the block having a shorter or a longer oscillation period.« less

  16. The early epigenetic response to ozone: impacts on DNA ...

    EPA Pesticide Factsheets

    Epigenetics have been increasingly recognized as a mechanism linking environment and gene expression. Despite awareness of the role of DNA methylation and hydroxymethylation as potential drivers of the response to air pollutants, very little work has been performed investigating the direct epigenetic effects following exposure to ambient air pollution. Thus the purpose of this study was to investigate the early epigenetic response to ozone in comparison to the epigenetic modifier 5-aza-2'-deoxycytidine (5-Aza) in rats. 12 week old, male Long-Evans rats (n=16) were exposed to 4 hours of whole-body 1.0 ppm ozone or air and immediately euthanized. A subset of animals were additionally treated with 5-Aza (n=16) to serve as an epigenetic control to ozone exposure. Neither 5-Aza nor ozone by itself induced changes to the global methylome or hydroxmethylome of the lung measured by ELISA. Despite this finding, ozone exposure induced a significant increase in the activity of the DNA methyltransferase enzymes in the lung which was reversed with 5-Aza treatment. Interestingly, a significant interaction between 5-Aza treatment and ozone exposure was found in a large array of data. The interaction between 5-Aza and ozone produced indicators of pulmonary edema and elevated lung damage. Along with these adverse changes, expression of major epigenetic enzymes (Tet 1-3, Dnmt3 a-b) were found to be perturbed in both the lung and hepatic tissues. While ozone exposure appears to in

  17. Implementing Effective Mission Systems Engineering Practices During Early Project Formulation Phases

    NASA Technical Reports Server (NTRS)

    Moton, Tryshanda

    2016-01-01

    Developing and implementing a plan for a NASA space mission can be a complicated process. The needs, goals, and objectives of any proposed mission or technology must be assessed early in the Project Life Cycle. The key to successful development of a space mission or flight project is the inclusion of systems engineering in early project formulation, namely during Pre-phase A, Phase A, and Phase B of the NASA Project Life Cycle. When a space mission or new technology is in pre-development, or "pre-Formulation", feasibility must be determined based on cost, schedule, and risk. Inclusion of system engineering during project formulation is key because in addition to assessing feasibility, design concepts are developed and alternatives to design concepts are evaluated. Lack of systems engineering involvement early in the project formulation can result in increased risks later in the implementation and operations phases of the project. One proven method for effective systems engineering practice during the pre-Formulation Phase is the use of a mission conceptual design or technology development laboratory, such as the Mission Design Lab (MDL) at NASA's Goddard Space Flight Center (GSFC). This paper will review the engineering process practiced routinely in the MDL for successful mission or project development during the pre-Formulation Phase.

  18. Differential Contributions of Ventral and Dorsal Striatum to Early and Late Phases of Cognitive Set Reconfiguration

    PubMed Central

    Sleezer, Brianna J.; Hayden, Benjamin Y.

    2017-01-01

    Flexible decision-making, a defining feature of human cognition, is typically thought of as a canonical pFC function. Recent work suggests that the striatum may participate as well; however, its role in this process is not well understood. We recorded activity of neurons in both the ventral (VS) and dorsal (DS) striatum while rhesus macaques performed a version of the Wisconsin Card Sorting Test, a classic test of flexibility. Our version of the task involved a trial-and-error phase before monkeys could identify the correct rule on each block. We observed changes in firing rate in both regions when monkeys switched rules. Specifically, VS neurons demonstrated switch-related activity early in the trial-and-error period when the rule needed to be updated, and a portion of these neurons signaled information about the switch context (i.e., whether the switch was intradimensional or extradimensional). Neurons in both VS and DS demonstrated switch-related activity at the end of the trial-and-error period, immediately before the rule was fully established and maintained, but these signals did not carry any information about switch context. We also observed associative learning signals (i.e., specific responses to options associated with rewards in the presentation period before choice) that followed the same pattern as switch signals (early in VS, later in DS). Taken together, these results endorse the idea that the striatum participates directly in cognitive set reconfiguration and suggest that single neurons in the striatum may contribute to a functional handoff from the VS to the DS during reconfiguration processes. PMID:27417204

  19. Discrimination of timbre in early auditory responses of the human brain.

    PubMed

    Seol, Jaeho; Oh, MiAe; Kim, June Sic; Jin, Seung-Hyun; Kim, Sun Il; Chung, Chun Kee

    2011-01-01

    The issue of how differences in timbre are represented in the neural response still has not been well addressed, particularly with regard to the relevant brain mechanisms. Here we employ phasing and clipping of tones to produce auditory stimuli differing to describe the multidimensional nature of timbre. We investigated the auditory response and sensory gating as well, using by magnetoencephalography (MEG). Thirty-five healthy subjects without hearing deficit participated in the experiments. Two different or same tones in timbre were presented through conditioning (S1)-testing (S2) paradigm as a pair with an interval of 500 ms. As a result, the magnitudes of auditory M50 and M100 responses were different with timbre in both hemispheres. This result might support that timbre, at least by phasing and clipping, is discriminated in the auditory early processing. The second response in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left hemisphere, whereas both M50 and M100 responses to S2 only in the right hemisphere reflected whether two stimuli in a pair were the same or not. Both M50 and M100 magnitudes were different with the presenting order (S1 vs. S2) for both same and different conditions in the both hemispheres. Our results demonstrate that the auditory response depends on timbre characteristics. Moreover, it was revealed that the auditory sensory gating is determined not by the stimulus that directly evokes the response, but rather by whether or not the two stimuli are identical in timbre.

  20. Macrophage function in murine allogeneic bone marrow radiation chimeras in the early phase after transplantation

    SciT

    Roesler, J.; Baccarini, M.; Vogt, B.

    1989-08-01

    We tested several of the functions of macrophages (M phi) in the early phase after allogeneic bone marrow transfer to get information about this important aspect of the nonspecific immune system in the T-cell-deficient recipient. On days 3-5 after transfer, the number of M phi was reduced in the spleen, liver, lungs, and peritoneal cavity (Pe). The phagocytosis of sheep red blood cells (SRBC) by these M phi was normal or even enhanced, as in the case of Pe-M phi. Already on days 8-12 after transfer, the number of M phi in spleen and liver exceeded that of controls, whereasmore » the number was still reduced in lungs and Pe. We examined their ability to kill P815 tumor cells, to produce tumor necrosis factor-alpha (TNF alpha), to phagocytose SRBC, to produce reactive oxygen intermediates (ROI) in vitro and to kill Listeria monocytogenes in vivo. Most functions were normal and often even enhanced, depending on the organ origin, but the ability of Pe-M phi to produce ROI was reduced. Proliferative response to macrophage colony-stimulating factor (M-CSF) and killing of YAC-1 tumor cells revealed a high frequency of macrophage precursor cells in the spleen and liver and a high natural killer (NK) activity in the liver. Altogether, enhanced nonspecific immune function, especially preactivated M phi, may enable chimeras to survive attacks by opportunistic pathogens.« less

  1. 2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

    PubMed

    2015-12-01

    The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  2. Optimizing the early phase development of new analgesics by human pain biomarkers.

    PubMed

    Arendt-Nielsen, Lars; Hoeck, Hans Christian

    2011-11-01

    Human pain biomarkers are based on standardized acute activation of pain pathways/mechanisms and quantitative assessment of the evoked responses. This approach can be applied to healthy volunteers, to pain patients, and before and after pharmacological interventions to help understanding and profile the mode of action (proof-of-concept) of new and existing analgesic compounds. Standardized stimuli of different modalities can be applied to different tissues (multimodal and multi-tissue) for profiling analgesic compounds with respect to modulation of pain transduction, transmission, specific mechanisms and processing. This approach substantiates which specific compounds may work in particular clinical pain conditions. Human pain biomarkers can be translational and may bridge animal findings in clinical pain conditions, which in turn can provide new possibilities for designing more successful clinical trials. Biomarker based proof-of-concept drug studies in either volunteers or selected patient populations provide inexpensive, fast and reliable mechanism-based information about dose-efficacy relationships. This is important information in the early drug development phase and for designing large expensive clinical trials.

  3. Men Managing, Not Teaching Foundation Phase: Teachers, Masculinity and the Early Years of Primary Schooling

    ERIC Educational Resources Information Center

    Moosa, Shaaista; Bhana, Deevia

    2017-01-01

    In this article we argue that eliminating the divisions of labour between men and women could work towards counteracting gender inequality within professions. Globally women are over-represented in the teaching of young children in the early years of primary school, or Foundation Phase (FP), as it is known in South Africa. We are concerned to go…

  4. Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use.

    PubMed

    Lucero, J; Harlow, B L; Barbieri, R L; Sluss, P; Cramer, D W

    2001-10-01

    To examine the effects of alcohol, caffeine, and tobacco use on early follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG). Cross-sectional study. Academic medical center. Four hundred ninety-eight women selected from the general population, ages 36-45, who were not currently pregnant, breast feeding, or using exogenous hormones. A general questionnaire assessing demography, anthropometry, and smoking habits and a standardized dietary questionnaire assessing food and beverage frequencies, including sources of alcohol and caffeine. FSH, LH, E2, and SHBG levels measured during the early follicular phase of the menstrual cycle. Significant associations observed in a univariate analysis included age > or =40 and current smoking associated with higher FSH; higher body mass index (BMI) associated with lower SHBG levels; and daily alcohol use, cholesterol consumption greater than the median, and coffee use >1 cup/d associated with higher E2 levels. In a multivariate model, total caffeine use was significantly associated with E2 levels after adjustment for age, BMI, total calories, current smoking, alcohol, cholesterol consumption, and day of sampling. Early follicular phase E2 increased from 28.2 pg/mL for women consuming < or =100 mg of caffeine to 45.2 pg/mL for women consuming > or =500 mg of caffeine per day, about a 70% increase. Coffee consumption and total caffeine use may increase early follicular phase E2 levels independent of related habits of alcohol or tobacco use.

  5. Webcam Delivery of the Lidcombe Program for Early Stuttering: A Phase I Clinical Trial

    ERIC Educational Resources Information Center

    O'Brian, Sue; Smith, Kylie; Onslow, Mark

    2014-01-01

    Purpose: The Lidcombe Program is an operant treatment for early stuttering shown with meta-analysis to have a favorable odds ratio. However, many clients are unable to access the treatment because of distance and lifestyle factors. In this Phase I trial, we explored the potential efficacy, practicality, and viability of an Internet webcam Lidcombe…

  6. 77 FR 36958 - Proposed Requirements-Race to the Top-Early Learning Challenge; Phase 2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-20

    ... DEPARTMENT OF EDUCATION 34 CFR Chapter II DEPARTMENT OF HEALTH AND HUMAN SERVICES 45 CFR Subtitle... Requirements--Race to the Top--Early Learning Challenge; Phase 2 AGENCY: Department of Education and Department of Health and Human Services. ACTION: Proposed requirements. SUMMARY: The Secretary of Education and...

  7. Phase III Early Restoration Meeting - Port Arthur, TX | NOAA Gulf Spill

    Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

  8. Phase III Early Restoration Meeting - Panama City, FL | NOAA Gulf Spill

    Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

  9. Teachers' Beliefs on Foreign Language Teaching Practices in Early Phases of Primary Education: A Case Study

    ERIC Educational Resources Information Center

    Caner, Mustafa; Subasi, Gonca; Kara, Selma

    2010-01-01

    The purpose of the study was to examine whether teacher beliefs would play a role in their actual practices while teaching target language in early phases of primary education, principally, in kindergarten and first grades in a state school. As it is a very broad research area, the researchers exclusively analyzed teaching practices and teaching…

  10. Robust Entrainment of Circadian Oscillators Requires Specific Phase Response Curves

    PubMed Central

    Pfeuty, Benjamin; Thommen, Quentin; Lefranc, Marc

    2011-01-01

    The circadian clocks keeping time in many living organisms rely on self-sustained biochemical oscillations entrained by external cues, such as light, to the 24-h cycle induced by Earth's rotation. However, environmental cues are unreliable due to the variability of habitats, weather conditions, or cue-sensing mechanisms among individuals. A tempting hypothesis is that circadian clocks have evolved so as to be robust to fluctuations in the signal that entrains them. To support this hypothesis, we analyze the synchronization behavior of weakly and periodically forced oscillators in terms of their phase response curve (PRC), which measures phase changes induced by a perturbation applied at different times of the cycle. We establish a general relationship between the robustness of key entrainment properties, such as stability and oscillator phase, on the one hand, and the shape of the PRC as characterized by a specific curvature or the existence of a dead zone, on the other hand. The criteria obtained are applied to computational models of circadian clocks and account for the disparate robustness properties of various forcing schemes. Finally, the analysis of PRCs measured experimentally in several organisms strongly suggests a case of convergent evolution toward an optimal strategy for maintaining a clock that is accurate and robust to environmental fluctuations. PMID:21641300

  11. Estimation of the phase response curve from Parkinsonian tremor.

    PubMed

    Saifee, Tabish A; Edwards, Mark J; Kassavetis, Panagiotis; Gilbertson, Tom

    2016-01-01

    Phase response curves (PRCs), characterizing the response of an oscillator to weak external perturbation, have been estimated from a broad range of biological oscillators, including single neurons in vivo. PRC estimates, in turn, provide an intuitive insight into how oscillatory systems become entrained and how they can be desynchronized. Here, we explore the application of PRC theory to the case of Parkinsonian tremor. Initial attempts to establish a causal effect of subthreshold transcranial magnetic stimulation applied to primary motor cortex on the filtered tremor phase were unsuccessful. We explored the possible explanations of this and demonstrate that assumptions made when estimating the PRC in a traditional setting, such as a single neuron, are not arbitrary when applied to the case of tremor PRC estimation. We go on to extract the PRC of Parkinsonian tremor using an iterative method that requires varying the definition of the tremor cycle and estimating the PRC at multiple peristimulus time samples. Justification for this method is supported by estimates of PRC from simulated single neuron data. We provide an approach to estimating confidence limits for tremor PRC and discuss the interpretational caveats introduced by tremor harmonics and the intrinsic variability of the tremor's period. Copyright © 2016 the American Physiological Society.

  12. Estimation of the phase response curve from Parkinsonian tremor

    PubMed Central

    Saifee, Tabish A.; Edwards, Mark J.; Kassavetis, Panagiotis

    2015-01-01

    Phase response curves (PRCs), characterizing the response of an oscillator to weak external perturbation, have been estimated from a broad range of biological oscillators, including single neurons in vivo. PRC estimates, in turn, provide an intuitive insight into how oscillatory systems become entrained and how they can be desynchronized. Here, we explore the application of PRC theory to the case of Parkinsonian tremor. Initial attempts to establish a causal effect of subthreshold transcranial magnetic stimulation applied to primary motor cortex on the filtered tremor phase were unsuccessful. We explored the possible explanations of this and demonstrate that assumptions made when estimating the PRC in a traditional setting, such as a single neuron, are not arbitrary when applied to the case of tremor PRC estimation. We go on to extract the PRC of Parkinsonian tremor using an iterative method that requires varying the definition of the tremor cycle and estimating the PRC at multiple peristimulus time samples. Justification for this method is supported by estimates of PRC from simulated single neuron data. We provide an approach to estimating confidence limits for tremor PRC and discuss the interpretational caveats introduced by tremor harmonics and the intrinsic variability of the tremor's period. PMID:26561596

  13. Challenges and perspective of drug repurposing strategies in early phase clinical trials.

    PubMed

    Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

    2015-01-01

    Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

  14. Unimpaired endogenous pain inhibition in the early phase of complex regional pain syndrome.

    PubMed

    Kumowski, N; Hegelmaier, T; Kolbenschlag, J; Maier, C; Mainka, T; Vollert, J; Enax-Krumova, E

    2017-05-01

    The complex regional pain syndrome (CRPS) is characterized by distal generalisation of pain beyond the initial trauma. This might be the result of impaired endogenous pain inhibition. We compared Conditioned Pain Modulation (CPM) between patients with CRPS (n = 24; pain: 4.5 ± 2.2, NRS 0-10; disease duration <1 year), neuralgia (n = 17; pain: 5.5 ± 1.1) and healthy subjects (n = 23) and its correlation with loss and gain of function as assessed by Quantitative Sensory Testing (QST). CPM was assessed with heat as test stimulus (TS) and cold water as conditioning stimulus (CS). The early CPM-effect was calculated as difference between heat pain during and before conditioning, the late CPM-effect, 5 minutes after and before conditioning, respectively. Heat pain decreased comparably after CS in all groups, resulting in a significant CPM-effect (healthy: -12.5 ± 12.4, NRS 0-100; CRPS: -14.7 ± 15.7; neuralgia: -7.9 ± 9.8; p < 0.001). When compared to healthy subjects, heat pain declined significantly steeper in CRPS patients (healthy: -2.0 ± 5.5, NRS 0-100/10 s; CRPS: -6.3 ± 8.1; p < 0.05). Only CRPS patients demonstrated a late CPM effect (-6.0 ± 9.0, p < 0.005). Neither spontaneous pain nor any QST parameter correlated with CPM, with the exception of a decreased cold pain threshold, which correlated with an enhanced CPM in CRPS patients only (r = -0.456, p < 0.05). An impairment of endogenous pain inhibition does not explain the extent of pain in the early stage of CRPS or in neuralgia. The unexpectedly high CPM in CRPS patients might result from activation of the intact descending pathways in response to central sensitization, as cold hyperalgesia correlated with the CPM-effect. Conditioned pain modulation (CPM) is not impaired in the early phase of complex regional pain syndrome (CRPS) and neuralgia. Only in CRPS higher CPM was associated with lower cold pain thresholds. © 2017 European Pain Federation - EFIC®.

  15. Mycobacterium tuberculosis manipulates pulmonary APCs subverting early immune responses.

    PubMed

    Garcia-Romo, Gina S; Pedroza-Gonzalez, Alexander; Lambrecht, Bart N; Aguilar-Leon, Diana; Estrada-Garcia, Iris; Hernandez-Pando, Rogelio; Flores-Romo, Leopoldo

    2013-03-01

    Alveolar macrophages (AM) and dendritic cells (DCs) are the main antigen presenting cells (APCs) in the respiratory tract. Whereas macrophages have been extensively studied in tuberculosis, in situ interactions of DC with Mycobacterium tuberculosis (Mtb) are poorly explored. We aimed to characterize lung APCs during pulmonary tuberculosis in Balb/C mice infected with Mtb H37Rv. Mtb-infection via the airways induced a delayed and continuous accumulation of DCs and AM in the lungs. While lung DCs increased after day 3 post-infection, macrophages increased after 2-3 weeks. Although both populations accumulated in lungs during the infection, DCs decreased in the late stages. Infection induced differential expression of co-stimulatory molecules in these lung APCs, decreasing to basal levels in both APCs in the late stages. A remarkable segregation was found regarding bacillary burden. Many macrophages contained numerous bacilli, but DC contained scarce mycobacteria or none. Mtb-infection also induced delayed accumulation of DC in draining lymph nodes. This delayed recruitment was not associated with a lack of IL-12p40, which was detected from day 3 post-infection. Although AM and lung DCs behave differently during pulmonary tuberculosis, Mtb apparently manipulates both lung APCs subverting early protective responses resulting in disease progression. Copyright © 2012 Elsevier GmbH. All rights reserved.

  16. Language experience enhances early cortical pitch-dependent responses

    PubMed Central

    Krishnan, Ananthanarayan; Gandour, Jackson T.; Ananthakrishnan, Saradha; Vijayaraghavan, Venkatakrishnan

    2014-01-01

    Pitch processing at cortical and subcortical stages of processing is shaped by language experience. We recently demonstrated that specific components of the cortical pitch response (CPR) index the more rapidly-changing portions of the high rising Tone 2 of Mandarin Chinese, in addition to marking pitch onset and sound offset. In this study, we examine how language experience (Mandarin vs. English) shapes the processing of different temporal attributes of pitch reflected in the CPR components using stimuli representative of within-category variants of Tone 2. Results showed that the magnitude of CPR components (Na-Pb and Pb-Nb) and the correlation between these two components and pitch acceleration were stronger for the Chinese listeners compared to English listeners for stimuli that fell within the range of Tone 2 citation forms. Discriminant function analysis revealed that the Na-Pb component was more than twice as important as Pb-Nb in grouping listeners by language affiliation. In addition, a stronger stimulus-dependent, rightward asymmetry was observed for the Chinese group at the temporal, but not frontal, electrode sites. This finding may reflect selective recruitment of experience-dependent, pitch-specific mechanisms in right auditory cortex to extract more complex, time-varying pitch patterns. Taken together, these findings suggest that long-term language experience shapes early sensory level processing of pitch in the auditory cortex, and that the sensitivity of the CPR may vary depending on the relative linguistic importance of specific temporal attributes of dynamic pitch. PMID:25506127

  17. Early phase drugs and biologicals clinical trials on worldwide leading causes of death: a descriptive analysis.

    PubMed

    Dal-Ré, Rafael

    2011-06-01

    To describe the global effort targeting the major causes of mortality in terms of "open" early phase clinical trials with drugs and biologicals. Sixteen of the 20 leading causes of death were chosen; 9 of these were also amongst the top 10 causes of death in low-income countries. Studies were identified from the ClinicalTrials.gov database and included phase 1 and/or 2 "interventional" "open" trials, i.e. those recruiting or about to start recruitment. Trials were considered in terms of sponsorship [industry, universities and other organisations (UNO), and US federal agencies (NIH included)], genders and age groups included, and whether they were conducted with drugs and/or biologicals. The search was performed in March 2010. A total of 2,298 (824 phase 1; 1,474 phase 2) trials were retrieved. Of these, 67% were on trachea, bronchus, and lung cancers (25%); diabetes mellitus (15%); colon and rectum cancers (14%); and HIV/AIDS (12%). In contrast, only 4% were trials on diarrhoeal disease, nephrosis and nephritis, liver cirrhosis, and prematurity and low birth weight. UNO were the first source of funding. Fifty-two percent of phase 1 non-cancer trials were on healthy volunteers. Twenty-nine percent of all trials were co-funded. There were 4.6 times as many drug trials as those with biologicals. Only 7% were conducted with a combination of drugs and biologicals, the majority (78%) on cancers. Discrimination in terms of gender or age group was not observed. Four of the 16 diseases considered represented 2/3 of early phase trials. Cancers were a top priority for all sponsors. Increasing attention should be given to conditions with current and projected global high mortality rates that had few "open" early phase trials.

  18. High-response piezoelectricity modeled quantitatively near a phase boundary

    NASA Astrophysics Data System (ADS)

    Newns, Dennis M.; Kuroda, Marcelo A.; Cipcigan, Flaviu S.; Crain, Jason; Martyna, Glenn J.

    2017-01-01

    Interconversion of mechanical and electrical energy via the piezoelectric effect is fundamental to a wide range of technologies. The discovery in the 1990s of giant piezoelectric responses in certain materials has therefore opened new application spaces, but the origin of these properties remains a challenge to our understanding. A key role is played by the presence of a structural instability in these materials at compositions near the "morphotropic phase boundary" (MPB) where the crystal structure changes abruptly and the electromechanical responses are maximal. Here we formulate a simple, unified theoretical description which accounts for extreme piezoelectric response, its observation at compositions near the MPB, accompanied by ultrahigh dielectric constant and mechanical compliances with rather large anisotropies. The resulting model, based upon a Landau free energy expression, is capable of treating the important domain engineered materials and is found to be predictive while maintaining simplicity. It therefore offers a general and powerful means of accounting for the full set of signature characteristics in these functional materials including volume conserving sum rules and strong substrate clamping effects.

  19. Phenological behaviour of early spring flowering trees in Spain in response to recent climate changes

    NASA Astrophysics Data System (ADS)

    Hidalgo-Galvez, M. D.; García-Mozo, H.; Oteros, J.; Mestre, A.; Botey, R.; Galán, C.

    2018-04-01

    This research reports the phenological trends of four early spring and late winter flowering trees in Spain (south Europe) from a recent period (1986-2012). The studied species were deciduous trees growing in different climatic areas: hazel ( Corylus avellana L.), willow ( Salix alba L.), ash ( Fraxinus angustifolia Vahl.) and white mulberry ( Morus alba L.). We analysed the response to climate and the trends of the following phenophases observed at the field: budburst, leaf unfolding, flowering, fruit ripening, fruit harvesting, leaf colour change and leaf-fall. The study was carried out in 17 sampling sites in the country with the aim of detecting the recent phenological response to the climate of these species, and the possible effect of climate change. We have observed differences in the phenological response to climate depending on each species. Sixty-one percent of studied sites suffered an advance of early spring phenophases, especially budburst on average by -0.67 days and flowering on average by -0.15 days during the studied period, and also in the subsequent fruit ripening and harvesting phases on average by -1.06 days. By contrast, it has been detected that 63% of sampling sites showed a delay in autumn vegetative phases, especially leaf-fall events on average by +1.15 days. The statistic correlation analysis shows in the 55% of the studied localities that phenological advances are the consequence of the increasing trend detected for temperature—being minimum temperature the most influential factor—and in the 52% of them, phenological advances occurred by rainfall variations. In general, leaf unfolding and flowering from these species showed negative correlations in relation to temperature and rainfall, whereas that leaf colour change and leaf-fall presented positive correlations. The results obtained have a great relevance due to the fact that they can be considered as reliable bio-indicators of the impact of the recent climate changes in southern

  20. Decrease in early right alpha band phase synchronization and late gamma band oscillations in processing syntax in music.

    PubMed

    Ruiz, María Herrojo; Koelsch, Stefan; Bhattacharya, Joydeep

    2009-04-01

    The present study investigated the neural correlates associated with the processing of music-syntactical irregularities as compared with regular syntactic structures in music. Previous studies reported an early ( approximately 200 ms) right anterior negative component (ERAN) by traditional event-related-potential analysis during music-syntactical irregularities, yet little is known about the underlying oscillatory and synchronization properties of brain responses which are supposed to play a crucial role in general cognition including music perception. First we showed that the ERAN was primarily represented by low frequency (<8 Hz) brain oscillations. Further, we found that music-syntactical irregularities as compared with music-syntactical regularities, were associated with (i) an early decrease in the alpha band (9-10 Hz) phase synchronization between right fronto-central and left temporal brain regions, and (ii) a late ( approximately 500 ms) decrease in gamma band (38-50 Hz) oscillations over fronto-central brain regions. These results indicate a weaker degree of long-range integration when the musical expectancy is violated. In summary, our results reveal neural mechanisms of music-syntactic processing that operate at different levels of cortical integration, ranging from early decrease in long-range alpha phase synchronization to late local gamma oscillations. 2008 Wiley-Liss, Inc.

  1. Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases.

    PubMed

    Tan, Shu-Yin; Hang, Fu; Purvarshi, Gowreesunkur; Li, Min-Qing; Meng, Da-Hua; Huang, Ling-Ling

    2015-10-01

    To evaluate the predictive value of three-dimensional (3D)-power Doppler sonography on recurrent miscarriage. The study patients were divided into a recurrent miscarriage group (30 cases) and a normal pregnancy group (21 cases). Measurement of endometrial thickness was performed using two-dimensional transvaginal ultrasound in the midluteal phase. The endometrial volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in midluteal and placenta volume, as well as the VI, FI, and VFI of early pregnancy were measured using Virtual Organ Computer-aided Analysis of 3D-power Doppler ultrasound. Endometrial thickness, endometrial volume, endometrial vascular data, VI, FI, and VFI of the midluteal phase were lower in the recurrent miscarriage group compared with the normal pregnancy group (p < 0.05). Placental volume, VI, and VFI during early pregnancy were lower in the miscarriage group compared with the normal pregnancy group (p < 0.05). There was no significant change in FI between the recurrent miscarriage and control groups during early pregnancy (p > 0.05). The predictive accuracy of endometrial thickness, endometrial volume, VI, FI, and VFI in the midluteal phase, and placenta volume, VI, FI, and VFI in early pregnancy as measured by the receiver operating characteristic curve to predict miscarriage before 12 gestational weeks in participants was 0.681, 0.876, 0.770, 0.720, 0.879, 0.771, 0.907, 0.592, respectively. The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage. Copyright © 2015. Published by Elsevier B.V.

  2. Hormone phase influences sympathetic responses to high levels of lower body negative pressure in young healthy women.

    PubMed

    Usselman, Charlotte W; Nielson, Chantelle A; Luchyshyn, Torri A; Gimon, Tamara I; Coverdale, Nicole S; Van Uum, Stan H M; Shoemaker, J Kevin

    2016-11-01

    We tested the hypothesis that sympathetic responses to baroreceptor unloading may be affected by circulating sex hormones. During lower body negative pressure at -30, -60, and -80 mmHg, muscle sympathetic nerve activity (MSNA), heart rate, and blood pressure were recorded in women who were taking (n = 8) or not taking (n = 9) hormonal contraceptives. All women were tested twice, once during the low-hormone phase (i.e., the early follicular phase of the menstrual cycle and the placebo phase of hormonal contraceptive use), and again during the high-hormone phase (i.e., the midluteal phase of the menstrual cycle and active phase of contraceptive use). During baroreceptor unloading, the reductions in stroke volume and resultant increases in MSNA and total peripheral resistance were greater in high-hormone than low-hormone phases in both groups. When normalized to the fall in stroke volume, increases in MSNA were no longer different between hormone phases. While stroke volume and sympathetic responses were similar between women taking and not taking hormonal contraceptives, mean arterial pressure was maintained during baroreceptor unloading in women not taking hormonal contraceptives but not in women using hormonal contraceptives. These data suggest that differences in sympathetic activation between hormone phases, as elicited by lower body negative pressure, are the result of hormonally mediated changes in the hemodynamic consequences of negative pressure, rather than centrally driven alterations to sympathetic regulation. Copyright © 2016 the American Physiological Society.

  3. Ventilatory gas exchange and early response to cardiac resynchronization therapy.

    PubMed

    Kim, Chul-Ho; Olson, Lyle J; Shen, Win K; Cha, Yong-Mei; Johnson, Bruce D

    2015-11-01

    Cardiac resynchronization therapy (CRT) is an accepted intervention for chronic heart failure (HF), although approximately 30% of patients are non-responders. The purpose of this study was to determine whether exercise respiratory gas exchange obtained before CRT implantation predicts early response to CRT. Before CRT implantation, patients were assigned to either a mild-moderate group (Mod G, n = 33, age 67 ± 10 years) or a moderate-severe group (Sev G, n = 31, age 67 ± 10 years), based on abnormalities in exercise gas exchange. Severity of impaired gas exchange was based on a score from the measures of VE/VCO(2) slope, resting PETCO(2) and change of PETCO(2) from resting to peak. All measurements were performed before and 3 to 4 months after CRT implantation. Although Mod G did not have improved gas exchange (p > 0.05), Sev G improved significantly (p < 0.05) post-CRT. In addition, Mod G did not show improved right ventricular systolic pressure (RSVP; pre vs post: 37 ± 14 vs 36 ± 11 mm Hg, p > 0.05), yet Sev G showed significantly improved RVSP, by 23% (50 ± 14 vs 42 ± 12 mm Hg, p < 0.05). Both groups had improved left ventricular ejection fraction (p < 0.05), New York Heart Association class (p < 0.05) and quality of life (p < 0.05), but no significant differences were observed between groups (p > 0.05). No significant changes were observed in brain natriuretic peptide in either group post-CRT. Based on pre-CRT implantation ventilatory gas exchange, subjects with the most impaired values appeared to have more improvement post-CRT, possibly associated with a decrease in RVSP. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  4. 78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ..., choosing a study population, using a control group and blinding, dose selection, treatment plans...] Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular... document entitled ``Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

  5. Culturally Responsive Literacy Practices in an Early Childhood Community

    ERIC Educational Resources Information Center

    Bennett, Susan V.; Gunn, AnnMarie Alberton; Gayle-Evans, Guda; Barrera, Estanislado S.; Leung, Cynthia B.

    2018-01-01

    Early childhood educators continue to see an increase in their culturally diverse student population. As our country continues to grow as a multicultural nation, it is imperative that our early childhood classrooms embrace this rich diversity and provide experiences that affirm all students, families and communities. We (teacher educators)…

  6. Distribution of Endogenous NO Regulates Early Gravitropic Response and PIN2 Localization in Arabidopsis Roots.

    PubMed

    París, Ramiro; Vazquez, María M; Graziano, Magdalena; Terrile, María C; Miller, Nathan D; Spalding, Edgar P; Otegui, Marisa S; Casalongué, Claudia A

    2018-01-01

    High-resolution and automated image analysis of individual roots demonstrated that endogenous nitric oxide (NO) contribute significantly to gravitropism of Arabidopsis roots. Lowering of endogenous NO concentrations strongly reduced and even reversed gravitropism, resulting in upward bending, without affecting root growth rate. Notably, the asymmetric accumulation of NO along the upper and lower sides of roots correlated with a positive gravitropic response. Detection of NO by the specific DAF-FM DA fluorescent probe revealed that NO was higher at the lower side of horizontally-oriented roots returning to initial values 2 h after the onset of gravistimulation. We demonstrate that NO promotes plasma membrane re-localization of PIN2 in epidermal cells, which is required during the early root gravitropic response. The dynamic and asymmetric localization of both auxin and NO is critical to regulate auxin polar transport during gravitropism. Our results collectively suggest that, although auxin and NO crosstalk occurs at different levels of regulation, they converge in the regulation of PIN2 membrane trafficking in gravistimulated roots, supporting the notion that a temporally and spatially coordinated network of signal molecules could participate in the early phases of auxin polar transport during gravitropism.

  7. Early Risk Reduction Phase 1 FLIR/Laser Designator Window. Revision

    DTIC Science & Technology

    1991-12-31

    Sandwich-Type FLIR Windows," Air Force AFWAL-TR-83- 4122, Nov 1983. 4-1 Hughes Danbury Optical Systems Final Report, "ATA Window Technology Program," PRBll...Risk Reduction -- Phase I, Optical Properties Measurement Techniques of Three Wide Band Window Materials," 22 August 1991. xii I i 86PR0869 30... Optical Systems, Lexington, MA, 02173, 1 Feb 1991. 5-7 McDonnell Aircraft Company Technical Memorandum TM 256.91.0056.01, "Early Risk Reduction -- Phase

  8. Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

    PubMed

    Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

    2015-03-01

    Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

  9. Factors associated with a positive attitude towards change among employees during the early phase of a downsizing process.

    PubMed

    Svensen, Erling; Neset, Gunnar; Eriksen, Hege R

    2007-04-01

    Most research on organizational changes in working life, including downsizing, focuses on the negative attitudes and negative consequences of the change. The aim of this study was to evaluate if the employee's previous learning experience and characteristics of the working environment were associated with positive attitudes towards organizational change. The 467 employees (73.5% males) working in a global oil company in the early phases of a downsizing process were asked to answer a questionnaire with demographic variables, perception of the working environment, and attitude to change (93% response rate). Corporate social responsibility (CSR), involvement and participation, team leadership and team effectiveness were important factors related to positive attitudes towards organizational change. Non-leaders and older employees were positive to change. We conclude that employees' perceptions of their psychosocial working environment, in particular the CSR, were highly related to their attitude to organizational change.

  10. Perspectives and Open Problems in the Early Phases of Left-Right Patterning

    PubMed Central

    Vandenberg, Laura N.; Levin, Michael

    2009-01-01

    Summary Embryonic left-right (LR) patterning is a fascinating aspect of embryogenesis. The field currently faces important questions about the origin of LR asymmetry, the mechanisms by which consistent asymmetry is imposed on the scale of the whole embryo, and the degree of conservation of early phases of LR patterning among model systems. Recent progress on planar cell polarity and cellular asymmetry in a variety of tissues and species provides a new perspective on the early phases of LR patterning. Despite the huge diversity in body-plans over which consistent LR asymmetry is imposed, and the apparent divergence in molecular pathways that underlie laterality, the data reveal conservation of physiological modules among phyla and a basic scheme of cellular chirality amplified by a planar cell polarity-like pathway over large cell fields. PMID:19084609

  11. Ultra-Early Phase pathologies of Alzheimer's disease and other neurodegenerative diseases.

    PubMed

    Okazawa, Hitoshi

    2017-01-01

    The concept of neurodegenerative diseases and the therapeutics targeting these intractable diseases are changing rapidly. Protein aggregation as the top of pathological cascade is now challenged, and many alternative ideas are proposed. Early molecular pathologies before microscopic detection of diseases protein aggregates, which I propose to call "Ultra-Early Phase pathologies or phase 0 pathologies", are the focus of research that might explain the failures of clinical trials with anti-Aβ antibodies against Alzheimer's disease. In this review article, I summarize the critical issues that should be successfully and consistently answered by a new concept of neurodegeneration. For reevaluating old concepts and reconstructing a new concept of neurodegeneration that will replace the old ones, non-biased comprehensive approaches including proteome combined with systems biology analyses will be a powerful tool. I introduce our recent efforts in this orientation that have reached to the stage of non-clinical proof of concept applicable to clinical trials.

  12. Imaging of early acceleration phase of the 2013-2014 Boso slow slip event

    NASA Astrophysics Data System (ADS)

    Fukuda, J.; Kato, A.; Obara, K.; Miura, S.; Kato, T.

    2014-12-01

    Based on GPS and seismic data, we examine the spatiotemporal evolution of a slow slip event (SSE) and associated seismic activity that occurred off the Boso peninsula, central Japan, from December 2013 to January 2014. We use GPS data from 71 stations of the GEONET and 6 stations operated by Earthquake Research Institute of the University of Tokyo and Tohoku University around the Boso peninsula. We apply a modified version of the Network Inversion Filter to the GPS time series at the 77 stations to estimate the spatiotemporal evolution of daily cumulative slip and slip rate on the subducting Philippine Sea plate. In addition, we create an improved earthquake catalog by applying a matched filter technique to continuous seismograms and examine the spatiotemporal relations between slow slip and seismicity. We find that the SSE started in early December 2013. The spatiotemporal evolution of slow slip and seismicity is divided into two distinct phases, an earlier slow phase from early to 30 December 2013 (Phase I) and a subsequent faster phase from 30 December 2013 to 9 January 2014 (Phase II). During Phase I, slip accelerated slowly up to a maximum rate of 1.6 m/yr with potentially accelerating along-strike propagation at speeds on the order of 1 km/day or less and no accompanying seismicity. On the other hand, during Phase II, slip accelerated rapidly up to a maximum rate of 4.5 m/yr and then rapidly decelerated. The slip front propagated along strike at a constant speed of ~10 km/day. During the Phase II, slow slip was accompanied by seismic swarm activity that was highly correlated in space and time with slip rate, suggesting that the swarm activity was triggered by stress loading due to slow slip. Early slow acceleration of slip has not been identified in the past Boso SSEs in 1996, 2002, 2007, and 2011. It is not clear at this point whether the past Boso SSEs started with slow acceleration similarly to the 2013-2014 SSE. The transition from the slow to the

  13. Impact of incretin on early-phase insulin secretion and glucose excursion.

    PubMed

    Shen, Jie; Chen, Zhi; Chen, Chaofeng; Zhu, Xiao; Han, Yajuan

    2013-10-01

    This study investigated the impact of incretin on early-phase insulin secretion and glucose excursion. The normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) groups included 16, 8, and 19 subjects, respectively. Subjects underwent continuous glucose monitoring for 3 days, followed by an oral glucose tolerance test. Plasma glucose, insulin, glucagon, total glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-l (GLP-1) levels were measured at 30-min increments for 2 h after glucose intake. Differences with P < 0.05 were considered statistically significant. The area under the curve (AUC) of total GIP (120-min GIP-AUC) of the T2DM group was significantly lower than those of the NGT and IGT groups. The 120-min GLP-1-AUC of the NGT group was significantly larger than those of the T2DM and IGT groups. The early-phase insulin secretion index (ΔI30/ΔG30) of the T2DM group was significantly lower than those of the NGT and IGT groups. Mean amplitudes of glycemic excursions (MAGEs) went in the order of NGT < IGT < T2DM (P < 0.01, IGT vs. NGT; P < 0.001, T2DM vs. IGT). The 120-min GIP-AUC was negatively correlated with MAGE (r = -0.464), but uncorrelated with ΔI30/ΔG30. The 120-min GLP-1-AUC was positively correlated with ΔI30/ΔG30 (r = 0.580), but negatively correlated with MAGE (r = -0.606). Incretin may ameliorate glucose excursions, and GLP-1 may exert them by promoting early-phase insulin secretion. No correlation was observed between GIP secretion and early-phase insulin secretion.

  14. Effects of temperature on early-phase transmission of Yersina pestis by the flea, Xenopsylla cheopis.

    PubMed

    Schotthoefer, Anna M; Bearden, Scott W; Vetter, Sara M; Holmes, Jennifer; Montenieri, John A; Graham, Christine B; Woods, Michael E; Eisen, Rebecca J; Gage, Kenneth L

    2011-03-01

    Sharp declines in human and animal cases of plague, caused by the bacterium Yersinia pestis (Yersin), have been observed when outbreaks coincide with hot weather. Failure of biofilm production, or blockage, to occur in the flea, as temperatures reach 30 degrees C has been suggested as an explanation for these declines. Recent work demonstrating efficient flea transmission during the first few days after fleas have taken an infectious blood meal, in the absence of blockage (e.g., early-phase transmission), however, has called this hypothesis into question. To explore the potential effects of temperature on early-phase transmission, we infected colony-reared Xenopsylla cheopis (Rothchild) fleas with a wild-type strain of plague bacteria using an artificial feeding system, and held groups of fleas at 10, 23, 27, and 30 degrees C. Naive Swiss Webster mice were exposed to fleas from each of these temperatures on days 1-4 postinfection, and monitored for signs of infection for 21 d. Temperature did not significantly influence the rates of transmission observed for fleas held at 23, 27, and 30 degrees C. Estimated per flea transmission efficiencies for these higher temperatures ranged from 2.32 to 4.96% (95% confidence interval [CI]: 0.96-8.74). In contrast, no transmission was observed in mice challenged by fleas held at 10 degrees C (per flea transmission efficiency estimates, 0-1.68%). These results suggest that declines in human and animal cases during hot weather are not related to changes in the abilities of X. cheopis fleas to transmit Y. pestis infections during the early-phase period. By contrast, transmission may be delayed or inhibited at low temperatures, indicating that epizootic spread of Y. pestis by X. cheopis via early-phase transmission is unlikely during colder periods of the year.

  15. The Role of Early-Phase Transmission in the Spread of Yersinia pestis

    PubMed Central

    EISEN, REBECCA J.; DENNIS, DAVID T.; GAGE, KENNETH L.

    2015-01-01

    Early-phase transmission (EPT) of Yersinia pestis by unblocked fleas is a well-documented, replicable phenomenon with poorly defined mechanisms. We review evidence demonstrating EPT and current knowledge on its biological and biomechanical processes. We discuss the importance of EPT in the epizootic spread of Y. pestis and its role in the maintenance of plague bacteria in nature. We further address the role of EPT in the epidemiology of plague. PMID:26336267

  16. Proteomic analysis of early phase of conidia germination in Aspergillus nidulans.

    PubMed

    Oh, Young Taek; Ahn, Chun-Seob; Kim, Jeong Geun; Ro, Hyeon-Su; Lee, Chang-Won; Kim, Jae Won

    2010-03-01

    In order to investigate proteins involved in early phase of conidia germination, proteomic analysis was performed using two-dimensional gel electrophoresis (2D-GE) in conjunction with MALDI-TOF mass spectrometry (MS). The expression levels of 241 proteins varied quantitatively with statistical significance (P<0.05) at the early phase of the germination stage. Out of these 57 were identified by MALDI-TOF MS. Through classification of physiological functions from Conserved Domain Database analysis, among the identified proteins, 21, 13, and 6 proteins were associated with energy metabolism, protein synthesis, and protein folding process, respectively. Interestingly, eight proteins, which are involved in detoxification of reactive oxygen species (ROS) including catalase A, thioredoxin reductase, and mitochondrial peroxiredoxin, were also identified. The expression levels of the genes were further confirmed using Northern blot and reverse transcriptase (RT)-PCR analyses. This study represents the first proteomic analysis of early phase of conidia germination and will contribute to a better understanding of the molecular events involved in conidia germination process. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  17. RECIST response and variation of circulating tumour cells in phase 1 trials: A prospective multicentric study.

    PubMed

    Massard, Christophe; Borget, Isabelle; Farace, Françoise; Aspeslagh, Sandrine; Le Deley, Marie-Cécile; Le Tourneau, Christophe; Bidard, François-Clement; Pierga, Jean-Yves; Dieras, Veronique; Hofman, Paul; Spano, Jean-Philippe; Ferte, Charles; Lacroix, Ludovic; Soria, Jean-Charles

    2017-09-01

    Circulating tumour cell (CTC) counting could be a new biomarker for better evaluation of tumour response to molecules tested in phase I trials. Consenting patients with advanced metastatic cancer referred to various phase I units were enrolled prospectively in this study. CTCs from 7.5 ml of whole blood drawn at baseline and after starting experimental therapy were counted using the CellSearch system, and tumour response was assessed using RECIST 1.1 criteria at baseline and 2 months after treatment initiation. Between March 2010 and May 2013, a total of 326 patients were enrolled, among whom 214 were evaluable (49% male, median age = 56; main cancer types: lung [28], colon [53], ovarian [18], breast [28]). At baseline, we detected ≥1 CTC/7.5 ml in 113/214 patients (53%), and at day 30, we observed ≥1 CTC/7.5 ml in 103/214 patients (48%). Two months after treatment initiation, 11 (5%) of the 214 patients were classified as having a partial response, with no CTCs in 9 of them or a decrease in the CTC count after therapy. In contrast, among the 104 patients (49%) classified as having progressive disease, 38 patients had a higher CTC count. The remaining 99 patients (49%), 33 of whom (33%) had a lower CTC count, were classified as having stable disease. The sensitivity and specificity of CTC variation for predicting progressive disease were 41% (32-51%) and 80% (73-88%) respectively. An early CTC change following therapy does not correlate with RECIST response in patients with advanced cancer enrolled in phase I trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

    PubMed Central

    2013-01-01

    Background A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Methods/Design Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. Discussion We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into

  19. Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use.

    PubMed

    Bernier, Denise; Cookey, Jacob; McAllindon, David; Bartha, Robert; Hanstock, Christopher C; Newman, Aaron J; Stewart, Sherry H; Tibbo, Philip G

    2013-10-17

    A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding

  20. Mitochondrial and Chloroplast Stress Responses Are Modulated in Distinct Touch and Chemical Inhibition Phases1[OPEN

    PubMed Central

    Ivanova, Aneta; Millar, A. Harvey; Whelan, James

    2016-01-01

    Previous studies have identified a range of transcription factors that modulate retrograde regulation of mitochondrial and chloroplast functions in Arabidopsis (Arabidopsis thaliana). However, the relative importance of these regulators and whether they act downstream of separate or overlapping signaling cascades is still unclear. Here, we demonstrate that multiple stress-related signaling pathways, with distinct kinetic signatures, converge on overlapping gene sets involved in energy organelle function. The transcription factor ANAC017 is almost solely responsible for transcript induction of marker genes around 3 to 6 h after chemical inhibition of organelle function and is a key regulator of mitochondrial and specific types of chloroplast retrograde signaling. However, an independent and highly transient gene expression phase, initiated within 10 to 30 min after treatment, also targets energy organelle functions, and is related to touch and wounding responses. Metabolite analysis demonstrates that this early response is concurrent with rapid changes in tricarboxylic acid cycle intermediates and large changes in transcript abundance of genes encoding mitochondrial dicarboxylate carrier proteins. It was further demonstrated that transcription factors AtWRKY15 and AtWRKY40 have repressive regulatory roles in this touch-responsive gene expression. Together, our results show that several regulatory systems can independently affect energy organelle function in response to stress, providing different means to exert operational control. PMID:27208304

  1. Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS

    PubMed Central

    Watanabe, Hama; Shitara, Yoshihiko; Aoki, Yoshinori; Inoue, Takanobu; Tsuchida, Shinya; Takahashi, Naoto; Taga, Gentaro

    2017-01-01

    A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants. PMID:28196885

  2. Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

    ERIC Educational Resources Information Center

    Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

    2010-01-01

    Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

  3. Test Design Optimization in CAT Early Stage with the Nominal Response Model

    ERIC Educational Resources Information Center

    Passos, Valeria Lima; Berger, Martijn P. F.; Tan, Frans E.

    2007-01-01

    The early stage of computerized adaptive testing (CAT) refers to the phase of the trait estimation during the administration of only a few items. This phase can be characterized by bias and instability of estimation. In this study, an item selection criterion is introduced in an attempt to lessen this instability: the D-optimality criterion. A…

  4. Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation

    PubMed Central

    2012-01-01

    Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors. PMID:22731117

  5. Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

    PubMed

    Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

    2012-06-25

    Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

  6. Congestion-Responsive On-Ramp Metering : Before and After Studies - Phase 1

    DOT National Transportation Integrated Search

    2016-07-06

    The objective of this project was to develop recommendations toward a statewide policy of congestion responsive freeway ramp metering operation. The research is performed in two phases. In phase 1, alternative ramp metering activation strategies were...

  7. Elevated Amygdala Response to Faces following Early Deprivation

    ERIC Educational Resources Information Center

    Tottenham, N.; Hare, T. A.; Millner, A.; Gilhooly, T.; Zevin, J. D.; Casey, B. J.

    2011-01-01

    A functional neuroimaging study examined the long-term neural correlates of early adverse rearing conditions in humans as they relate to socio-emotional development. Previously institutionalized (PI) children and a same-aged comparison group were scanned using functional magnetic resonance imaging (fMRI) while performing an Emotional Face Go/Nogo…

  8. Adaptive neuroplastic responses in early and late hemispherectomized monkeys.

    PubMed

    Burke, Mark W; Kupers, Ron; Ptito, Maurice

    2012-01-01

    Behavioural recovery in children who undergo medically required hemispherectomy showcase the remarkable ability of the cerebral cortex to adapt and reorganize following insult early in life. Case study data suggest that lesions sustained early in childhood lead to better recovery compared to those that occur later in life. In these children, it is possible that neural reorganization had begun prior to surgery but was masked by the dysfunctional hemisphere. The degree of neural reorganization has been difficult to study systematically in human infants. Here we present a 20-year culmination of data on our nonhuman primate model (Chlorocebus sabeus) of early-life hemispherectomy in which behavioral recovery is interpreted in light of plastic processes that lead to the anatomical reorganization of the early-damaged brain. The model presented here suggests that significant functional recovery occurs after the removal of one hemisphere in monkeys with no preexisting neurological dysfunctions. Human and primate studies suggest a critical role for subcortical and brainstem structures as well as corticospinal tracts in the neuroanatomical reorganization which result in the remarkable behavioral recovery following hemispherectomy. The non-human primate model presented here offers a unique opportunity for studying the behavioral and functional neuroanatomical reorganization that underlies developmental plasticity.

  9. Investigating Early Years Teachers' Understanding and Response to Children's Preconceptions

    ERIC Educational Resources Information Center

    Kambouri, Maria

    2016-01-01

    This paper focuses on young children's scientific preconceptions and discusses teachers' identification of these preconceptions when teaching science in the early years, on which research is still limited. This paper is based on the theoretical framework of constructivism and it defines preconceptions as children's erroneous concepts prior to…

  10. Hot, humid air increases cellular influx during the late-phase response to nasal challenge with antigen.

    PubMed

    Assanasen, P; Baroody, F M; Naureckas, E; Naclerio, R M

    2001-12-01

    Inhalation of hot, humid air (HHA: 37 degrees C, > 95% relative humidity (RH)) partially inhibits the early response to nasal challenge with antigen. To investigate whether HHA inhibited the late-phase response to nasal challenge with antigen and increased hyper-responsiveness of the nasal mucosa to histamine. Twenty subjects with seasonal allergic rhinitis, outside of their allergy season, participated in a randomized, 2-way cross-over study. The subjects continuously breathed room air (25 degrees C, 30% RH) or HHA delivered via a face mask during the entire experiment. Subjects were challenged intranasally with antigen 1 h after beginning conditioning. The response was monitored by symptoms and nasal lavage at 2-h intervals after the last antigen challenge. Eight hours after antigen challenge, nasal challenge with histamine was performed. Exposure to HHA significantly increased nasal mucosal temperature from baseline without affecting nasal secretion osmolality. HHA significantly inhibited antigen-induced sneezes, congestion, pruritus, and human serum albumin levels during the early response to antigen challenge. HHA exposure, however, was associated with an 8-fold increase in the eosinophil influx and a 15-fold increase in the levels of eosinophil cationic protein during the late-phase response compared to room air. There were no significant differences in nasal hyper-responsiveness to histamine during either exposure. HHA partially decreases the early response to nasal challenge with antigen, but dramatically increases eosinophil influx. Increasing eosinophil number had no effects on the hyper-responsiveness to histamine. We speculate that the physical conditions of air differentially impact the stages of allergic inflammation.

  11. Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

    PubMed

    Kawakami, Kohsaku

    2009-09-01

    Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

  12. Functional neuroanatomical correlates of episodic memory impairment in early phase psychosis

    PubMed Central

    Hummer, Tom A.; Vohs, Jenifer L.; Yung, Matthew G.; Liffick, Emily; Mehdiyoun, Nicole F.; Radnovich, Alexander J.; McDonald, Brenna C.; Saykin, Andrew J.; Breier, Alan

    2015-01-01

    Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n=35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness. PMID:25749917

  13. Early Immune Responses in Rainbow Trout Liver upon Viral Hemorrhagic Septicemia Virus (VHSV) Infection

    PubMed Central

    Castro, Rosario; Abós, Beatriz; Pignatelli, Jaime; von Gersdorff Jørgensen, Louise; González Granja, Aitor; Buchmann, Kurt; Tafalla, Carolina

    2014-01-01

    Among the essential metabolic functions of the liver, in mammals, a role as mediator of systemic and local innate immunity has also been reported. Although the presence of an important leukocyte population in mammalian liver is well documented, the characterization of leukocyte populations in the teleost liver has been only scarcely addressed. In the current work, we have confirmed the presence of IgM+, IgD+, IgT+, CD8α+, CD3+ cells, and cells expressing major histocompatibility complex (MHC-II) in rainbow trout (Oncorhynchus mykiss) liver by flow cytometry and/or immunohistochemistry analysis. Additionally, the effect of viral hemorrhagic septicemia virus (VHSV) on the liver immune response was assessed. First, we studied the effect of viral intraperitoneal injection on the transcription of a wide selection of immune genes at days 1, 2 and 5 post-infection. These included a group of leukocyte markers genes, pattern recognition receptors (PRRs), chemokines, chemokine receptor genes, and other genes involved in the early immune response and in acute phase reaction. Our results indicate that T lymphocytes play a key role in the initial response to VHSV in the liver, since CD3, CD8, CD4, perforin, Mx and interferon (IFN) transcription levels were up-regulated in response to VHSV. Consequently, flow cytometry analysis of CD8α+ cells in liver and spleen at day 5 post-infection revealed a decrease in the number of CD8α+ cells in the spleen and an increased population in the liver. No differences were found however in the percentages of B lymphocyte (IgM+ or IgD+) populations. In addition, a strong up-regulation in the transcription levels of several PRRs and chemokines was observed from the second day of infection, indicating an important role of these factors in the response of the liver to viral infections. PMID:25338079

  14. Muscle contributions to knee extension in the early stance phase in patients with knee osteoarthritis.

    PubMed

    Ogaya, Shinya; Kubota, Ryo; Chujo, Yuta; Hirooka, Eiko; Kwang-Ho, Kim; Hase, Kimitaka

    2017-10-01

    The aim of this study was to analyze individual muscle contributions to knee angular acceleration using a musculoskeletal simulation analysis and evaluate knee extension mechanics in the early stance phase in patients with knee osteoarthritis (OA). The subjects comprised 15 patients with medial knee OA and 14 healthy elderly individuals. All participants underwent gait performance test using 8 infrared cameras and two force plates to measure the kinetic and kinematic data. The simulation was driven by 92 Hill-type muscle-tendon units of the lower extremities and a trunk with 23° of freedom. We analyzed each muscle contribution to knee angular acceleration in the 5%-15% and 15%-25% periods of the stance phase (% SP) using an induced acceleration analysis. We compared accelerations by individual muscles between the two groups using an analysis of covariance for controlling gait speed. Patients with knee OA had a significantly lesser knee extension acceleration by the vasti muscles and higher knee acceleration by hip adductors than those in controls in 5-15% SP. In addition, knee OA resulted in significantly lesser knee extension acceleration by the vasti muscles in 15-25% SP. These results indicate that patients with knee OA have decreased dependency on the vasti muscles to control knee movements during early stance phase. Hip adductor muscles, which mainly control mediolateral motion, partly compensate for the weak knee extension by the vasti muscles in patients with knee OA. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Early feeding and early life housing conditions influence the response towards a noninfectious lung challenge in broilers.

    PubMed

    Simon, K; de Vries Reilingh, G; Bolhuis, J E; Kemp, B; Lammers, A

    2015-09-01

    Early life conditions such as feed and water availability immediately post hatch (PH) and housing conditions may influence immune development and therefore immune reactivity later in life. The current study addressed the consequences of a combination of these 2 early life conditions for immune reactivity, i.e., the specific antibody response towards a non-infectious lung challenge. Broiler chicks received feed and water either immediately p.h. or with a 72 h delay and were either reared in a floor or a cage system. At 4 weeks of age, chicks received either an intra-tracheally administered Escherichia coli lipopolysaccharide (LPS)/Human Serum Albumin (HUSA) challenge or a placebo, and antibody titers were measured up to day 14 after administration of the challenge. Chicks housed on the floor and which had a delayed access to feed p.h. showed the highest antibody titers against HuSA. These chicks also showed the strongest sickness response and poorest performance in response to the challenge, indicating that chicks with delayed access to feed might be more sensitive to an environment with higher antigenic pressure. In conclusion, results from the present study show that early life feeding strategy and housing conditions influence a chick's response to an immune challenge later in life. These 2 early life factors should therefore be taken into account when striving for a balance between disease resistance and performance in poultry. © 2015 Poultry Science Association Inc.

  16. The Effects of Responsive Stimulation in Early Infancy.

    ERIC Educational Resources Information Center

    Ramey, Craig T.; Finkelstein, Neal W.

    This study investigated whether infants who were given increased amounts of response-contingent stimulation would evidence positive and nonspecific transfer of learning to situations requiring new responses to control environmental events. Subjects were thirty 3-month-old biologically normal home-reared infants. Infants in the group assigned to a…

  17. The scaffold protein Nde1 safeguards the brain genome during S phase of early neural progenitor differentiation

    PubMed Central

    Houlihan, Shauna L; Feng, Yuanyi

    2014-01-01

    Successfully completing the S phase of each cell cycle ensures genome integrity. Impediment of DNA replication can lead to DNA damage and genomic disorders. In this study, we show a novel function for NDE1, whose mutations cause brain developmental disorders, in safeguarding the genome through S phase during early steps of neural progenitor fate restrictive differentiation. Nde1 mutant neural progenitors showed catastrophic DNA double strand breaks concurrent with the DNA replication. This evoked DNA damage responses, led to the activation of p53-dependent apoptosis, and resulted in the reduction of neurons in cortical layer II/III. We discovered a nuclear pool of Nde1, identified the interaction of Nde1 with cohesin and its associated chromatin remodeler, and showed that stalled DNA replication in Nde1 mutants specifically occurred in mid-late S phase at heterochromatin domains. These findings suggest that NDE1-mediated heterochromatin replication is indispensible for neuronal differentiation, and that the loss of NDE1 function may lead to genomic neurological disorders. DOI: http://dx.doi.org/10.7554/eLife.03297.001 PMID:25245017

  18. Breakpoint Forcing Revisited: Phase Between Forcing and Response

    NASA Astrophysics Data System (ADS)

    Contardo, S.; Symonds, G.; Dufois, F.

    2018-02-01

    Using the breakpoint forcing model, for long wave generation in the surf zone, expressions for the phase difference between the breakpoint-forced long waves and the incident short wave groups are obtained. Contrary to assumptions made in previous studies, the breakpoint-forced long waves and incident wave groups are not in phase and outgoing breakpoint-forced long waves and incident wave groups are not π out of phase. The phase between the breakpoint-forced long wave and the incident wave group is shown to depend on beach geometry and wave group parameters. The breakpoint-forced incoming long wave lags behind the wave group, by a phase smaller than π/2. The phase lag decreases as the beach slope decreases and the group frequency increases, approaching approximately π/16 within reasonable limits of the parameter space. The phase between the breakpoint-forced outgoing long wave and the wave group is between π/2 and π and it increases as the beach slope decreases and the group frequency increases, approaching 15π/16 within reasonable limits of the parameter space. The phase between the standing long wave (composed of the incoming long wave and its reflection) and the incident wave group tends to zero when the wave group is long compared to the surf zone width. These results clarify the phase relationships in the breakpoint forcing model and provide a new base for the identification of breakpoint forcing signal from observations, laboratory experiments and numerical modeling.

  19. Restoration of energy level in the early phase of acute pediatric pancreatitis.

    PubMed

    Mosztbacher, Dóra; Farkas, Nelli; Solymár, Margit; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Czimmer, József; Márta, Katalin; Mikó, Alexandra; Rumbus, Zoltán; Varjú, Péter; Hegyi, Péter; Párniczky, Andrea

    2017-02-14

    Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better

  20. Restoration of energy level in the early phase of acute pediatric pancreatitis

    PubMed Central

    Mosztbacher, Dóra; Farkas, Nelli; Solymár, Margit; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Czimmer, József; Márta, Katalin; Mikó, Alexandra; Rumbus, Zoltán; Varjú, Péter; Hegyi, Péter; Párniczky, Andrea

    2017-01-01

    Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better

  1. Ultrastructural Complexity of Nuclear Components During Early Apoptotic Phases in Breast Cancer Cells

    PubMed Central

    Castelli, Christian; Losa, Gabriele A.

    2001-01-01

    Fractal morphometry was used to investigate the ultrastructural features of the plasma membrane, perinuclear membrane and nuclear chromatin in SK‐BR‐3 human breast cancer cells undergoing apoptosis. Cells were incubated with 1 μM calcimycin (A23187) for 24 h. Cells in the early stage of apoptosis had fractal dimension (FD) values indicating that their plasma membranes were less rough (lower FD) than those of control cells, while their perinuclear membranes were unaffected. Changes of the chromatin texture within the entire nucleus and in selected nuclear domains were more pronounced in treated cells. This confirms that the morphological reorganization imputable to a loss of structural complexity (reduced FD) occurs in the early stage of apoptosis, is accompanied by the inhibition of distinct enzymatic events and precedes the onset of conventional cellular markers, which can only be detected during the active phases of the apoptotic process. PMID:11790854

  2. Numerical investigation of the early flight phase in ski-jumping.

    PubMed

    Gardan, N; Schneider, A; Polidori, G; Trenchard, H; Seigneur, J M; Beaumont, F; Fourchet, F; Taiar, R

    2017-07-05

    The purpose of this study is to develop a numerical methodology based on real data from wind tunnel experiments to investigate the effect of the ski jumper's posture and speed on aerodynamic forces in a wide range of angles of attack. To improve our knowledge of the aerodynamic behavior of the ski jumper and his equipment during the early flight phase of the ski jump, we applied CFD methodology to evaluate the influence of angle of attack (α=14°, 21.5°, 29°, 36.5° and 44°) and speed (u=23, 26 and 29m/s) on aerodynamic forces in the situation of stable attitude of the ski jumper's body and skis. The standard k-ω turbulence model was used to investigate both the influence of the ski jumper's posture and speed on aerodynamic performance during the early flight phase. Numerical results show that the ski jumper's speed has very little impact on the lift and drag coefficients. Conversely, the lift and drag forces acting on the ski jumper's body during the early flight phase of the jump are strongly influenced by the variations of the angle of attack. The present results suggest that the greater the ski jumper's angle of inclination, with respect to the relative flow, the greater the pressure difference between the lower and upper parts of the skier. Further studies will focus on the dependency of the parameters with both the angle of attack α and the body-ski angle β as control variables. It will be possible to test and optimize different ski jumping styles in different ski jumping hills and investigate different environmental conditions such as temperature, altitude or crosswinds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Dispositional optimism and therapeutic expectations in early-phase oncology trials.

    PubMed

    Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P

    2016-04-15

    Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P<.0001), but was not associated with the therapeutic misconception (Spearman r, -0.075; P = .329). Dispositional optimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (P<.0001) were found to be independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have

  4. A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.

    PubMed

    Vormoor, B; Veal, G J; Griffin, M J; Boddy, A V; Irving, J; Minto, L; Case, M; Banerji, U; Swales, K E; Tall, J R; Moore, A S; Toguchi, M; Acton, G; Dyer, K; Schwab, C; Harrison, C J; Grainger, J D; Lancaster, D; Kearns, P; Hargrave, D; Vormoor, J

    2017-06-01

    Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies. © 2016 Wiley Periodicals, Inc.

  5. The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis.

    PubMed

    Scalfari, Antonio; Romualdi, Chiara; Nicholas, Richard S; Mattoscio, Miriam; Magliozzi, Roberta; Morra, Aldo; Monaco, Salvatore; Muraro, Paolo A; Calabrese, Massimiliano

    2018-05-16

    To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS). In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS. Fifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP. Extensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy. © 2018 American Academy of Neurology.

  6. Communication and Alert Maintenance Program for Early Response Act

    THOMAS, 112th Congress

    Rep. Richardson, Laura [D-CA-37

    2011-09-07

    House - 09/27/2011 Referred to the Subcommittee on Emergency Preparedness, Response and Communications. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  7. Early and late mammalian responses to heavy charged particles

    NASA Technical Reports Server (NTRS)

    Ainsworth, E. J.

    1986-01-01

    This overview summarizes murine results on acute lethality responses, inactivation of marrow CFU-S and intestinal microcolonies, testes weight loss, life span shortening, and posterior lens opacification in mice irradiated with heavy charged particles. RBE-LET relationships for these mammalian responses are compared with results from in vitro studies. The trend is that the maximum RBE for in vivo responses tends to be lower and occurs at a lower LET than for inactivation of V79 and T-1 cells in culture. Based on inactivation cross sections, the response of CFU-S in vivo conforms to expectations from earlier studies with prokaryotic systems and mammalian cells in culture. Effects of heavy ions are compared with fission spectrum neutrons, and the results are consistent with the interpretation that RBEs are lower than for fission neutrons at about the same LET, probably due to differences in track structure.

  8. The Impact of Early Design Phase Risk Identification Biases on Space System Project Performance

    NASA Technical Reports Server (NTRS)

    Reeves, John D., Jr.; Eveleigh, Tim; Holzer, Thomas; Sarkani, Shahryar

    2012-01-01

    Risk identification during the early design phases of complex systems is commonly implemented but often fails to result in the identification of events and circumstances that truly challenge project performance. Inefficiencies in cost and schedule estimation are usually held accountable for cost and schedule overruns, but the true root cause is often the realization of programmatic risks. A deeper understanding of frequent risk identification trends and biases pervasive during space system design and development is needed, for it would lead to improved execution of existing identification processes and methods.

  9. Extinct radioactivities - A three-phase mixing model. [for early solar system abundances

    NASA Technical Reports Server (NTRS)

    Clayton, D. D.

    1983-01-01

    A new class of models is advanced for interpreting the relationship of radioactive abundances in the early solar system to their average concentration in the interstellar medium. The model assumes that fresh radioactivities are ejected from supernovae into the hot interstellar medium, and that the time scales for changes of phase into molecular clouds determine how much survives for formation therein of the solar system. A more realistic and physically motivated understanding of the low observed concentrations of I-129, Pu-244, and Pd-107 may result.

  10. PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat.

    PubMed

    Fernández-Blanco, Joan Antoni; Fernández-Blanco, Juan A; Hollenberg, Morley D; Martínez, Vicente; Vergara, Patri

    2013-02-15

    Proteinase-activated receptor-2 (PAR-2) and mast cell (MC) mediators contribute to inflammatory and functional gastrointestinal disorders. We aimed to characterize jejunal PAR-2-mediated responses and the potential MC involvement in the early and late phases of a rat model of postinfectious gut dysfunction. Jejunal tissues of control and Trichinella spiralis-infected (14 and 30 days postinfection) rats, treated or not with the MC stabilizer, ketotifen, were used. Histopathology and immunostaining were used to characterize inflammation, PAR-2 expression, and mucosal and connective tissue MCs. Epithelial barrier function (hydroelectrolytic transport and permeability) and motility were assessed in vitro in basal conditions and after PAR-2 activation. Intestinal inflammation on day 14 postinfection (early phase) was significantly resolved by day 30 (late phase) although MC counts and epithelial permeability remained increased. PAR-2-mediated ion transport (Ussing chambers, in vitro) and epithelial surface PAR-2 expression were reduced in the early phase, with a trend toward normalization during the late phase. In control conditions, PAR-2 activation (organ bath) induced biphasic motor responses (relaxation followed by excitation). At 14 days postinfection, spontaneous contractility and PAR-2-mediated relaxations were enhanced; motor responses were normalized on day 30. Postinfectious changes in PAR-2 functions were not affected by ketotifen treatment. We concluded that, in the rat model of Trichinella spiralis infection, alterations of intestinal PAR-2 function and expression depend on the inflammatory phase considered. A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction.

  11. Response of two-phase droplets to intense electromagnetic radiation

    NASA Technical Reports Server (NTRS)

    Spann, James F.; Maloney, Daniel J.; Lawson, William F.; Casleton, Kent H.

    1993-01-01

    The behavior of two-phase droplets subjected to high intensity radiation pulses is studied. Droplets are highly absorbing solids in weakly absorbing liquid medium. The objective of the study was to define heating thresholds required for causing explosive boiling and secondary atomization of the fuel droplet. The results point to mechanisms for energy storage and transport in two-phase systems.

  12. Expectations of Benefit in Early-Phase Clinical Trials: Implications for Assessing the Adequacy of Informed Consent

    PubMed Central

    Weinfurt, Kevin P.; Seils, Damon M.; Tzeng, Janice P.; Compton, Kate L.; Sulmasy, Daniel P.; Astrow, Alan B.; Solarino, Nicholas A.; Schulman, Kevin A.; Meropol, Neal J.

    2009-01-01

    Background Participants in early-phase clinical trials have reported high expectations of benefit from their participation. There is concern that participants misunderstand the trials to which they have consented. Such concern is based on assumptions about what patients mean when they respond to questions about likelihood of benefit. Methods Participants were 27 women and 18 men in early-phase oncology trials at 2 academic medical centers in the United States. To determine whether expectations of benefit differ depending on how patients are queried, we randomly assigned participants to 1 of 3 interviews corresponding to 3 questions about likelihood of benefit: frequency-type, belief-type, and vague. In semistructured interviews, we queried participants about how they understood and answered the question. Participants then answered and discussed one of the other questions. Results Expectations of benefit in response to the belief-type question were significantly greater than expectations in response to the frequency-type and vague questions (P = .02). The most common justifications involved positive attitude (n = 27 [60%]) and references to physical health (n = 23 [51%]). References to positive attitude were most common among participants with higher (> 70%) expectations (n = 11 [85%]) and least common among those with lower (< 50%) expectations (n = 3 [27%]). Conclusions The wording of questions about likelihood of benefit shapes the expectations that patients express. Also, patients who express high expectations may not do so to communicate understanding, but rather to register optimism. Ongoing research will clarify the meaning of high expectations and examine methods for assessing understanding in this context. PMID:18378940

  13. Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

    PubMed

    Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

    2016-10-01

    Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. Copyright © 2016 Elsevier Ltd. All rights

  14. The Low-luminosity Type IIP Supernova 2016bkv with Early-phase Circumstellar Interaction

    NASA Astrophysics Data System (ADS)

    Nakaoka, Tatsuya; Kawabata, Koji S.; Maeda, Keiichi; Tanaka, Masaomi; Yamanaka, Masayuki; Moriya, Takashi J.; Tominaga, Nozomu; Morokuma, Tomoki; Takaki, Katsutoshi; Kawabata, Miho; Kawahara, Naoki; Itoh, Ryosuke; Shiki, Kensei; Mori, Hiroki; Hirochi, Jun; Abe, Taisei; Uemura, Makoto; Yoshida, Michitoshi; Akitaya, Hiroshi; Moritani, Yuki; Ueno, Issei; Urano, Takeshi; Isogai, Mizuki; Hanayama, Hidekazu; Nagayama, Takahiro

    2018-06-01

    We present optical and near-infrared observations of a low-luminosity (LL) Type IIP supernova (SN) 2016bkv from the initial rising phase to the plateau phase. Our observations show that the end of the plateau is extended to ≳140 days since the explosion, indicating that this SN takes one of the longest times to finish the plateau phase among Type IIP SNe (SNe IIP), including LL SNe IIP. The line velocities of various ions at the middle of the plateau phase are as low as 1000–1500 km s‑1, which is the lowest even among LL SNe IIP. These measurements imply that the ejecta mass in SN 2016bkv is larger than that of the well-studied LL IIP SN 2003Z. In the early phase, SN 2016bkv shows a strong bump in the light curve. In addition, the optical spectra in this bump phase exhibit a blue continuum accompanied by a narrow Hα emission line. These features indicate an interaction between the SN ejecta and the circumstellar matter (CSM) as in SNe IIn. Assuming the ejecta–CSM interaction scenario, the mass loss rate is estimated to be ∼ 1.7× {10}-2 {M}ȯ yr‑1 within a few years before the SN explosion. This is comparable to or even larger than the largest mass loss rate observed for the Galactic red supergiants (∼ {10}-3 {M}ȯ yr‑1 for VY CMa). We suggest that the progenitor star of SN 2016bkv experienced a violent mass loss just before the SN explosion.

  15. A tale of two timescales: Mixing, mass generation, and phase transitions in the early universe

    NASA Astrophysics Data System (ADS)

    Dienes, Keith R.; Kost, Jeff; Thomas, Brooks

    2016-02-01

    Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically—such as during cosmological mass-generating phase transitions—the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this paper, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system—often by many orders of magnitude—but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "reoverdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings.

  16. Feasibility study for early removal of HEU from CPP-651-Phase II

    SciT

    Smith, C.V.; Henry, R.; Milligan, C.

    1997-09-01

    A two-phase feasibility study was initiated in late 1996 to identify a way to expedite the removal of SNM from the CPP-651 vault. The first phase of this study provided preliminary information that appeared promising, but needed additional detailed planning and evaluate to validate the concepts and conclusions. The focus of Phase 2 was to provide the validation via resource-loaded schedules and more detailed cost estimates. Section 1 describes the purpose and objectives of the Phase 2 tasks and the programmatic drivers that influence related CPP-651 high-enriched uranium (HEU) management issues. Section 2 identifies the evaluation criteria and methodology andmore » the transfer issues and barriers preventing shipment. Section 3 provides site-specific background information for the CPP-651 facility and the Idaho National Engineering and Environmental Laboratory (INEEL) and describes the development of the basic material removal schedule, the proposed base case plan for removal of SNM, and the proposed HEU material management/shipping issues and strategies. Section 4 identifies the proposed options for accelerated removal of SNM and how they were evaluated via detailed scheduling, resource histograms, and cost analysis. Section 5 summarizes principal tasks for implementing this plan and other related HEU CPP-651 management issues that require continued planning efforts to assure successful implementation of this proposed early removal strategy.« less

  17. Early Childhood Settings in 15 Countries: What Are Their Structural Characteristics? The IEA Preprimary Project, Phase 2.

    ERIC Educational Resources Information Center

    Olmsted, Patricia P., Ed.; Montie, Jeanne, Ed.

    This is the second of four monographs reporting the findings of Phase 2 of the International Association for the Evaluation of Educational Achievement (IEA) Preprimary Project, which presents data on the physical characteristics of children's early childhood settings. Early childhood settings were documented in the following 15 countries: (1)…

  18. Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice.

    PubMed

    Park, Hyo-Jin; Park, Sun-Ji; Koo, Deog-Bon; Lee, Sang-Rae; Kong, Il-Keun; Ryoo, Jae-Woong; Park, Young-Il; Chang, Kyu-Tae; Lee, Dong-Seok

    2014-09-15

    We examined whether the three unfolded protein response (UPR) signaling pathways, which are activated in response to endoplasmic reticulum (ER)-stress, are involved in progesterone production in the luteal cells of the corpus luteum (CL) during the mouse estrous cycle. The luteal phase of C57BL/6 female mice (8 weeks old) was divided into two stages: the functional stage (16, 24, and 48 h) and the regression stage (72 and 96 h). Western blotting and reverse transcription (RT)-PCR were performed to analyze UPR protein/gene expression levels in each stage. We investigated whether ER stress affects the progesterone production by using Tm (0.5 μg/g BW) or TUDCA (0.5 μg/g BW) through intra-peritoneal injection. Our results indicate that expressions of Grp78/Bip, p-eIF2α/ATF4, p50ATF6, and p-IRE1/sXBP1 induced by UPR activation were predominantly maintained in functional and early regression stages of the CL. Furthermore, the expression of p-JNK, CHOP, and cleaved caspase3 as ER-stress mediated apoptotic factors increased during the regression stage. Cleaved caspase3 levels increased in the late-regression stage after p-JNK and CHOP expression in the early-regression stage. Additionally, although progesterone secretion and levels of steroidogenic enzymes decreased following intra-peritoneal injection of Tunicamycin, an ER stress inducer, the expression of Grp78/Bip, p50ATF6, and CHOP dramatically increased. These results suggest that the UPR signaling pathways activated in response to ER stress may play important roles in the regulation of the CL function. Furthermore, our findings enhance the understanding of the basic mechanisms affecting the CL life span. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Worldwide isotope ratios of the Fukushima release and early-phase external dose reconstruction

    PubMed Central

    Chaisan, Kittisak; Smith, Jim T.; Bossew, Peter; Kirchner, Gerald; Laptev, Gennady V.

    2013-01-01

    Measurements of radionuclides (RNs) in air made worldwide following the Fukushima accident are quantitatively compared with air and soil measurements made in Japan. Isotopic ratios RN:137Cs of 131I, 132Te, 134,136Cs, are correlated with distance from release. It is shown, for the first time, that both within Japan and globally, ratios RN:137Cs in air were relatively constant for primarily particle associated radionuclides (134,136Cs; 132Te) but that 131I shows much lower local (<80 km) isotope ratios in soils relative to 137Cs. Derived isotope ratios are used to reconstruct external dose rate during the early phase post-accident. Model “blind” tests show more than 95% of predictions within a factor of two of measurements from 15 sites to the north, northwest and west of the power station. It is demonstrated that generic isotope ratios provide a sound basis for reconstruction of early-phase external dose rates in these most contaminated areas. PMID:24018776

  20. Diffusion-weighted MR imaging findings of kidneys in patients with early phase of obstruction.

    PubMed

    Bozgeyik, Zulkif; Kocakoc, Ercan; Sonmezgoz, Fitnet

    2009-04-01

    Diffusion-weighted (DW) magnetic resonance (MR) imaging is an MR technique used to show molecular diffusion. The apparent diffusion coefficient (ADC), as a quantitative parameter calculated from the DW MR images. The purpose of this study is to evaluate the ability of DW MR imaging in early phase of obstruction due to urolithiasis. Twenty-six patients with acute dilatation of the pelvicalyceal system detected by intravenous urography were included in this study. MR imaging was performed using a 1.5 T whole-body superconducting MR scanner. DW imaging can be performed using single-shot spin-echo, echo-planar imaging (EPI) sequences with the following diffusion gradient b values: 100, 600, 1000 s/mm(2). Circular region of interest (ROI) was placed in the renal parenchyma for the measurement of ADC values in the normal and obstructed kidney. For statistical analyses, Paired t test were used. In spite of obstructed kidneys had the lower ADC values compared to normal kidneys, these alterations were statistically insignificant. We did not observe significantly different ADC values of early phase of obstructed kidneys compared to normal kidneys.

  1. Unknown loads affect force production capacity in early phases of bench press throws.

    PubMed

    Hernández Davó, J L; Sabido Solana, R; Sarabia Marínm, J M; Sánchez Martos, Á; Moya Ramón, M

    2015-10-01

    Explosive strength training aims to improve force generation in early phases of movement due to its importance in sport performance. The present study examined the influence of lack of knowledge about the load lifted in explosive parameters during bench press throws. Thirteen healthy young men (22.8±2.0 years) participated in the study. Participants performed bench press throws with three different loads (30, 50 and 70% of 1 repetition maximum) in two different conditions (known and unknown loads). In unknown condition, loads were changed within sets in each repetition and participants did not know the load, whereas in known condition the load did not change within sets and participants had knowledge about the load lifted. Results of repeated-measures ANOVA revealed that unknown conditions involves higher power in the first 30, 50, 100 and 150 ms with the three loads, higher values of ratio of force development in those first instants, and differences in time to reach maximal rate of force development with 50 and 70% of 1 repetition maximum. This study showed that unknown conditions elicit higher values of explosive parameters in early phases of bench press throws, thereby this kind of methodology could be considered in explosive strength training.

  2. The early phase of /see symbol/ production development in adult Japanese learners of English.

    PubMed

    Saito, Kazuya; Munro, Murray J

    2014-12-01

    Although previous research indicates that Japanese speakers' second language (L2) perception and production of English /see symbol/ may improve with increased L2 experience, relatively little is known about the fine phonetic details of their /see symbol/ productions, especially during the early phase of L2 speech learning. This cross-sectional study examined acoustic properties of word-initial /see symbol/ from 60 Japanese learners with a length of residence of between one month and one year in Canada. Their performance was compared to that of 15 native speakers of English and 15 low-proficiency Japanese learners of English. Formant frequencies (F2 and F3) and F1 transition durations were evaluated under three task conditions--word reading, sentence reading, and timed picture description. Learners with as little as two to three months of residence demonstrated target-like F2 frequencies. In addition, increased LOR was predictive of more target-like transition durations. Although the learners showed some improvement in F3 as a function of LOR, they did so mainly at a controlled level of speech production. The findings suggest that during the early phase of L2 segmental development, production accuracy is task-dependent and is influenced by the availability of L1 phonetic cues for redeployment in L2.

  3. Internal Dose from Food and Drink Ingestion in the Early Phase after the Accident

    NASA Astrophysics Data System (ADS)

    Kawai, Masaki; Yoshizawa, Nobuaki; Hirakawa, Sachiko; Murakami, Kana; Takizawa, Mari; Sato, Osamu; Takagi, Shunji; Miyatake, Hirokazu; Takahashi, Tomoyuki; Suzuki, Gen

    2017-09-01

    Activity concentrations in food and drink, represented by water and vegetables, have been monitored continuously since the Fukushima Daiichi Nuclear Power Plant accident, with a focus on radioactive cesium. On the other hand, iodine-131 was not measured systematically in the early phase after the accident. The activity concentrations of iodine-131 in food and drink are important to estimate internal exposure due to ingestion pathway. When the internal dose from ingestion in the evacuation areas is estimated, water is considered as the main ingestion pathway. In this study, we estimated the values of activity concentrations in water in the early phase after the accident, using a compartment model as an estimation method. The model uses measurement values of activity concentration and deposition rate of iodine-131 onto the ground, which is calculated from an atmospheric dispersion simulation. The model considers how drinking water would be affected by radionuclides deposited into water. We estimated the activity concentrations of water on Kawamata town and Minamisouma city during March of 2011 and the committed effective doses were 0.08 mSv and 0.06 mSv. We calculated the transfer parameters in the model for estimating the activity concentrations in the areas with a small amount of measurement data. In addition, we estimated the committed effective doses from vegetables using atmospheric dispersion simulation and FARMLAND model in case of eating certain vegetables as option information.

  4. A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials.

    PubMed

    Mukherjee, Som D; Coombes, Megan E; Levine, Mitch; Cosby, Jarold; Kowaleski, Brenda; Arnold, Andrew

    2011-10-01

    In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.

  5. Analysis of Loss-of-Coolant Accidents in the NIST Research Reactor - Early Phase

    SciT

    Baek, Joo S.; Diamond, David

    A study of the fuel temperature during the early phase of a loss-of-coolant accident (LOCA) in the NIST research reactor (NBSR) was completed. Previous studies had been reported in the preliminary safety analysis report for the conversion of the NBSR from high-enriched uranium (HEU) fuel to low-enriched (LEU) fuel. Those studies had focused on the most vulnerable LOCA situation, namely, a double-ended guillotine break in the time period after reactor trip when water is drained from either the coolant channels inside the fuel elements or the region outside the fuel elements. The current study fills in a gap in themore » analysis which is the early phase of the event when there may still be water present but the reactor is at power or immediately after reactor trip and pumps have tripped. The calculations were done, for both the current HEU-fueled core and the proposed LEU core, with the TRACE thermal-hydraulic systems code. Several break locations and different break sizes were considered. In all cases the increase in the clad (or fuel meat) temperature was relatively small so that a large margin to the temperature threshold for blistering (the Safety Limit for the NBSR) remained.« less

  6. Acute lipophilicity-dependent effect of intravascular simvastatin in the early phase of focal cerebral ischemia.

    PubMed

    Beretta, S; Pastori, C; Sala, G; Piazza, F; Ferrarese, C; Cattalini, A; de Curtis, M; Librizzi, L

    2011-05-01

    The acute effects of simvastatin lactone (lipophilic) and simvastatin acid (hydrophilic) on transient focal ischemia were assessed using the isolated guinea pig brain maintained in vitro by arterial perfusion. This new model of cerebral ischemia allows the assessment of the very early phase of the ischemic process, with the functional preservation of the vascular and neuronal compartments and the blood-brain barrier (bbb). The middle cerebral artery was transiently tied for 30 min followed by reperfusion for 60 min. Statins (nanomolar doses) were administered by intravascular continuous infusion starting 60 min before ischemia induction. Brain cortical activity and arterial vascular tone were continuously recorded. At the end of the experiment immunoreactivity for microtubule-associated protein 2 (MAP-2), expression of survival kinases (ERK and Akt) and total anti-oxidant capacity were assayed. Brains treated with simvastatin lactone showed i) reduced amplitude and delayed onset of ischemic depressions, ii) preservation of MAP-2 immunoreactivity, iii) activation of ERK signaling in the ischemic hemisphere and iv) increase in whole-brain anti-oxidant capacity. Treatment with the bbb-impermeable simvastatin acid was ineffective on the above-mentioned parameters. Vascular resistance recordings and Akt signaling were unchanged by any statin treatment. Our findings suggest that intravascular-delivered simvastatin exerts an acute lipophilicity-dependent protective effect in the early phase of cerebral ischemia. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Frameworks for Response to Intervention in Early Childhood: Description and Implications

    ERIC Educational Resources Information Center

    Communication Disorders Quarterly, 2014

    2014-01-01

    In February, 2013, the Division of Early Childhood, the National Association for the Education of Young Children, and the National Head Start Association released a collaborative paper to provide clarification and assistance regarding the relationship of response to intervention (RTI) with the field of early childhood (EC). In addition to…

  8. Response to Therapy Following Retreatment of Serofast Early Syphilis Patients With Benzathine Penicillin

    PubMed Central

    Seña, Arlene C.; Wolff, Mark; Behets, Frieda; Van Damme, Kathleen; Martin, David H.; Leone, Peter; McNeil, Linda; Hook, Edward W.

    2013-01-01

    Persistent nontreponemal titers after treatment are common among patients with early syphilis. We retreated 82 human immunodeficiency virus–negative early syphilis participants who were serofast at 6 months using benzathine penicillin. Only 27% exhibited serological response after retreatment and after an additional 6 months of follow-up. PMID:23118269

  9. Multidecadal response of naturally regenerated southern pine to early competition control and commercial thinning

    Andrew S. Nelson; Don C. Bragg

    2016-01-01

    Multidecadal responses to early competition control are poorly documented in naturally regenerated southern pine stands. This study examined the effects of the following early herbicide treatments in thinned southern pine stands through age 31: (1) no control (CK), (2) herbaceous vegetation control only (HC), (3) woody vegetation control only (WC), and (4) total (woody...

  10. Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives.

    PubMed

    Subbiah, Vivek; Chuang, Hubert H; Gambhire, Dhiraj; Kairemo, Kalevi

    2017-02-15

    In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of "omics in radiology"-radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

  11. Skin manifestations in sulfur mustard exposed victims with ophthalmologic complications: Association between early and late phase.

    PubMed

    Hejazi, Somayeh; Soroush, Mohammadreza; Moradi, Ahmad; Khalilazar, Sara; Mousavi, Batool; Firooz, Alireza; Younespour, Shima

    2016-01-01

    Sulfur mustard (SM) was used during the Iraq-Iran war (1980-1988). Exposed veterans continue to suffer from its ocular, skin, and respiratory complications. We aimed to evaluate associations between early (at the time of acute exposure) and decades later skin manifestations in individuals with severe ophthalmologic complications secondary to sulfur mustard exposure. One hundred forty-nine veterans with severe ocular injuries were evaluated for acute and chronic skin complications. Logistic regression models were used to examine the associations between early and late skin manifestations. Late skin complaints were observed in nearly all survivors who had early skin lesions (131 out of 137; 95.62%). Seven out of 12 patients (58.33%) who did not have early skin lesions ultimately developed late skin complications. There was a significant relationship between the presence of lesions at the time of exposure and developing late skin complaints (two-sided Fisher's exact test, OR = 15.59, p < 0.001). There was an association between having at least one early skin lesion and occurrence of late skin complications. Survivors with blisters at the time of chemical exposure were more likely to complain of itching (95% CI: 3.63-25.97, p < 0.001), burning (OR = 11.16; 95% CI: 2.97-41.89, p < 0.001), pigmentation changes (OR = 10.17; 95% CI: 2.54-40.75, p = 0.001), dryness (OR = 6.71, 95% CI: 1.22-37.01, p = 0.03) or cherry angioma (OR = 2.59; 95% CI:1.21-5.55, p = 0.01) during the late phase. Using multivariate logistic models, early blisters remained significantly associated with latent skin complaints. Of note, the genitalia and great flexure areas were the most involved anatomical sites for both early and late skin lesions in SM exposed survivors. According to this study, the presence of blisters at the time of exposure to SM is the most important predictor of developing dermatologic complications decades later in patients with severe ophthalmologic

  12. Extracorporeal Shock Wave Therapy Suppresses the Early Proinflammatory Immune Response to a Severe Cutaneous Burn Injury

    DTIC Science & Technology

    2009-02-01

    Burn wound model Mice were anaesthetised using isoflurane inha- lation. After shaving the dorsum, the exposed skin was washed gently with room...Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn injury* Thomas A Davis, Alexander...S, Peoples GE, Tadaki D, Elster EA. Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn

  13. Enabling Parametric Optimal Ascent Trajectory Modeling During Early Phases of Design

    NASA Technical Reports Server (NTRS)

    Holt, James B.; Dees, Patrick D.; Diaz, Manuel J.

    2015-01-01

    During the early phases of engineering design, the costs committed are high, costs incurred are low, and the design freedom is high. It is well documented that decisions made in these early design phases drive the entire design's life cycle. In a traditional paradigm, key design decisions are made when little is known about the design. As the design matures, design changes become more difficult -- in both cost and schedule -- to enact. Indeed, the current capability-based paradigm that has emerged because of the constrained economic environment calls for the infusion of knowledge acquired during later design phases into earlier design phases, i.e. bring knowledge acquired during preliminary and detailed design into pre-conceptual and conceptual design. An area of critical importance to launch vehicle design is the optimization of its ascent trajectory, as the optimal trajectory will be able to take full advantage of the launch vehicle's capability to deliver a maximum amount of payload into orbit. Hence, the optimal ascent trajectory plays an important role in the vehicle's affordability posture as the need for more economically viable access to space solutions are needed in today's constrained economic environment. The problem of ascent trajectory optimization is not a new one. There are several programs that are widely used in industry that allows trajectory analysts to, based on detailed vehicle and insertion orbit parameters, determine the optimal ascent trajectory. Yet, little information is known about the launch vehicle early in the design phase - information that is required of many different disciplines in order to successfully optimize the ascent trajectory. Thus, the current paradigm of optimizing ascent trajectories involves generating point solutions for every change in a vehicle's design parameters. This is often a very tedious, manual, and time-consuming task for the analysts. Moreover, the trajectory design space is highly non-linear and multi

  14. Welcome to the Twilight Zone: a forgotten early phase of human evolutionary studies.

    PubMed

    Delisle, Richard G

    2012-06-01

    The field of paleoanthropology arose out of a strange and unacknowledged early phase of development prior to about the 1930s. It is often assumed that a key pillar of the discipline, the unity of humankind--the notion that humans are clearly separated phylogenetically (genealogically) from other non-human primates--was widely accepted from the inception of paleoanthropology around 1860. However, a final consensus on this fundamental question only appeared later on in the 20th century. This paper will focus on two key areas of disagreement, which reveal the unsettled state of this question during this early period: the question of uncertainty with respect to the number, identity and boundary of primate species (including humans) which prevailed in the 18th, 19th and early 20th centuries; and the matter of uncertainty with respect to the nature of the phylogenetic relationships among the various human populations and the other primate species which prevailed between 1864 and 1931. Consideration of these matters reveals that the modern research structure that paleoanthropologists take for granted today is much more recent than believed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Unraveling the origins of electromechanical response in mixed-phase Bismuth Ferrite

    SciT

    Vasudevan, Rama K; Okatan, M. B.; Liu, Y. Y.

    The origin of giant electromechanical response in a mixed-phase rhombohedral-tetragonal BiFeO3 thin film is probed using sub-coercive scanning probe microscopy based multiple-harmonic measurements. Significant contributions to the strain arise from a second-order harmonic response localized at the phase boundaries. Strain and dissipation data, backed by thermodynamic calculations suggest that the source of the enhanced electromechanical response is the motion of phase boundaries. These findings elucidate the key role of labile phase boundaries, both natural and artificial, in achieving thin films with giant electromechanical properties.

  16. Early cytokine modulation after the rapid induction phase of sublingual immunotherapy with mite monomeric allergoids.

    PubMed

    Di Gioacchino, M; Perrone, A; Petrarca, C; Di Claudio, F; Mistrello, G; Falagiani, P; Dadorante, V; Verna, N; Braga, M; Ballone, E; Cavallucci, E

    2008-01-01

    The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (p<0.0002) after treatment in group B patients, and this effect was higher (p=0.05) compared to group A patients. Furthermore, at the end of SLIT induction TNF-alpha, IL-4 and IFN-gamma production were reduced in group B patients (p<0.05, p=0.062 and p=0.060, respectively). The rapid induction scheme of sublingual immunotherapy induces an early immune suppression more effectively than the slower one. The rapid induction scheme should be the preferential way to start sublingual immunotherapy, particularly when monomeric allergoids are utilized.

  17. Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual

    PubMed Central

    Massett, Holly A.; Mishkin, Grace; Rubinstein, Larry; Ivy, S. Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A.; Abrams, Jeffrey S.

    2016-01-01

    Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAPs) received for slow-accruing Phase 1 and 2 trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for Phase 1 trials and 66 for Phase 2 trials. Primary reasons cited for slow accrual were safety/toxicity (Phase 1: 48%), design/protocol concerns (Phase 1: 42%, Phase 2: 33%), and eligibility criteria (Phase 1: 41%, Phase 2: 35%). The most commonly proposed corrective actions were adding institutions (Phase 1: 43%, Phase 2: 85%) and amending the trial to change eligibility or design (Phase 1: 55%, Phase 2: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (Phase 1=48; Phase 2=46). Of these, 67% of Phase 1 and 70% of Phase 2 trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial lifecycles, but it may be more beneficial to invest in earlier accrual planning. PMID:27401246

  18. Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual.

    PubMed

    Massett, Holly A; Mishkin, Grace; Rubinstein, Larry; Ivy, S Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A; Abrams, Jeffrey S

    2016-11-15

    Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. ©2016 AACRSee related commentary by Mileham and Kim, p. 5397. ©2016 American Association for Cancer Research.

  19. Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

    PubMed Central

    Aigbirhio, Franklin I.; Fryer, Tim D.; Menon, David K.; Warburton, Elizabeth A.; Baron, Jean-Claude

    2015-01-01

    Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1–6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD. PMID:26439113

  20. Study design and early result of a phase I study of SABR for early-stage glottic cancer.

    PubMed

    Yu, Tosol; Wee, Chan Woo; Choi, Noorie; Wu, Hong-Gyun; Kang, Hyun-Cheol; Park, Jong Min; Kim, Jung-In; Kim, Jin Ho; Kwon, Tack-Kyun; Chung, Eun-Jae

    2018-05-14

    Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. 2b. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

  1. IL-21 Is an Antitolerogenic Cytokine of the Late-Phase Alloimmune Response

    PubMed Central

    Petrelli, Alessandra; Carvello, Michele; Vergani, Andrea; Lee, Kang Mi; Tezza, Sara; Du, Ming; Kleffel, Sonja; Chengwen, Liu; Mfarrej, Bechara G.; Hwu, Patrick; Secchi, Antonio; Leonard, Warren J.; Young, Deborah; Sayegh, Mohamed H.; Markmann, James F.; Zajac, Allan J.; Fiorina, Paolo

    2011-01-01

    OBJECTIVE Interleukin-21 (IL-21) is a proinflammatory cytokine that has been shown to affect Treg/Teff balance. However, the mechanism by which IL-21 orchestrates alloimmune response and interplays with Tregs is still unclear. RESEARCH DESIGN AND METHODS The interplay between IL-21/IL-21R signaling, FoxP3 expression, and Treg survival and function was evaluated in vitro in immunologically relevant assays and in vivo in allogenic and autoimmune models of islet transplantation. RESULTS IL-21R expression decreases on T cells and B cells in vitro and increases in the graft in vivo, while IL-21 levels increase in vitro and in vivo during anti-CD3/anti-CD28 stimulation/allostimulation in the late phase of the alloimmune response. In vitro, IL-21/IL-21R signaling (by using rmIL-21 or genetically modified CD4+ T cells [IL-21 pOrf plasmid–treated or hIL-21-Tg mice]) enhances the T-cell response during anti-CD3/anti-CD28 stimulation/allostimulation, prevents Treg generation, inhibits Treg function, induces Treg apoptosis, and reduces FoxP3 and FoxP3-dependent gene transcripts without affecting FoxP3 methylation status. In vivo targeting of IL-21/IL-21R expands intragraft and peripheral Tregs, promotes Treg neogenesis, and regulates the antidonor immune response, whereas IL-21/IL-21R signaling in Doxa-inducible ROSA-rtTA-IL-21-Tg mice expands Teffs and FoxP3− cells. Treatment with a combination of mIL-21R.Fc and CTLA4-Ig (an inhibitor of the early alloimmune response) leads to robust graft tolerance in a purely alloimmune setting and prolonged islet graft survival in NOD mice. CONCLUSIONS IL-21 interferes with different checkpoints of the FoxP3 Treg chain in the late phase of alloimmune response and, thus, acts as an antitolerogenic cytokine. Blockade of the IL-21/IL-21R pathway could be a precondition for tolerogenic protocols in transplantation. PMID:22013017

  2. Effect of anabolic implants on adrenal cortisol synthesis in feedlot beef cattle implanted early or late in the finishing phase.

    PubMed

    Gifford, C A; Branham, K A; Ellison, J O; Gómez, B I; Lemley, C O; Hart, C G; Krehbiel, C R; Bernhard, B C; Maxwell, C L; Goad, C L; Hallford, D M; Hernandez Gifford, J A

    2015-01-01

    Implantation of anabolic steroids to increase growth rate in beef cattle impacts adrenal glucocorticoid production. The mechanism by which combination androgen and estrogen implants reduce cortisol biosynthesis in heifers is not clear. The objective of this study was to identify whether pituitary or adrenal gene expression and liver enzyme activity may contribute to altered serum cortisol concentrations in heifers receiving a combination implant. On d 0 of a 122-d finishing phase, 187 predominantly Angus heifers (361 kg) approximately 14 months old were randomly assigned to one of three implant groups: (1) non-implanted control, (2) implanted at the beginning of the finishing phase (d 0; early implant) with a combination implant (200mg TBA+20mg E2; Revalor 200®), and (3) implanted during the late stage of the finishing phase (d 56; late implant) with Revalor 200®. At d 56, body weight (BW) was greater (P<0.0001) for the early implanted heifers (456 ± 1.9 kg) compared to 437 and 435 (± 1.8) kg for control and late implanted heifers, respectively. Final BW (d 122) was similar between both implanted groups and heavier than non-implanted controls (P<0.0001). Serum cortisol was similar among groups at d 0 (P=0.86) however, by d 28 heifers receiving the combination implant had reduced (P<0.05) serum cortisol concentrations (31.2 ng/mL) compared to controls (49.4 ng/mL) and late (48.2 ng/mL) groups. On d 84 cortisol was similar (P=0.75) among implanted heifers and was less (P<0.01) than non-implanted heifers. Expression of pituitary and adrenal genes involved in glucocorticoid synthesis was evaluated at d 28/29 or 84/85; however, despite decreased serum cortisol in implanted heifers, no change in mRNA expression was demonstrated. Liver CYP3A enzyme activity at d 28/29 was decreased 59% in early implanted heifers compared to control heifers (P=0.01). Additionally, at d 84/85 AKR1C activity was greatest (P=0.01) in control heifers compared to both implanted groups. Data

  3. The progamic phase of an early-divergent angiosperm, Annona cherimola (Annonaceae)

    PubMed Central

    Lora, J.; Hormaza, J. I.; Herrero, M.

    2010-01-01

    Background and Aims Recent studies of reproductive biology in ancient angiosperm lineages are beginning to shed light on the early evolution of flowering plants, but comparative studies are restricted by fragmented and meagre species representation in these angiosperm clades. In the present study, the progamic phase, from pollination to fertilization, is characterized in Annona cherimola, which is a member of the Annonaceae, the largest extant family among early-divergent angiosperms. Beside interest due to its phylogenetic position, this species is also an ancient crop with a clear niche for expansion in subtropical climates. Methods The kinetics of the reproductive process was established following controlled pollinations and sequential fixation. Gynoecium anatomy, pollen tube pathway, embryo sac and early post-fertilization events were characterized histochemically. Key Results A plesiomorphic gynoecium with a semi-open carpel shows a continuous secretory papillar surface along the carpel margins, which run from the stigma down to the obturator in the ovary. The pollen grains germinate in the stigma and compete in the stigma-style interface to reach the narrow secretory area that lines the margins of the semi-open stylar canal and is able to host just one to three pollen tubes. The embryo sac has eight nuclei and is well provisioned with large starch grains that are used during early cellular endosperm development. Conclusions A plesiomorphic simple gynoecium hosts a simple pollen–pistil interaction, based on a support–control system of pollen tube growth. Support is provided through basipetal secretory activity in the cells that line the pollen tube pathway. Spatial constraints, favouring pollen tube competition, are mediated by a dramatic reduction in the secretory surface available for pollen tube growth at the stigma–style interface. This extramural pollen tube competition contrasts with the intrastylar competition predominant in more recently derived

  4. Flow Test to Predict Early Hypotony and Hypertensive Phase After Ahmed Glaucoma Valve (AGV) Surgical Implantation.

    PubMed

    Cheng, Jason; Beltran-Agullo, Laura; Buys, Yvonne M; Moss, Edward B; Gonzalez, Johanna; Trope, Graham E

    2016-06-01

    To assess the validity of a preimplantation flow test to predict early hypotony [intraocular pressure (IOP)≤5 mm Hg on 2 consecutive visits and hypertensive phase (HP) (IOP>21 mm Hg) after Ahmed Glaucoma Valve (AGV) implantation. Prospective interventional study on patients receiving an AGV. A preimplantation flow test using a gravity-driven reservoir and an open manometer was performed on all AGVs. Opening pressure (OP) and closing pressure (CP) were defined as the pressure at which fluid was seen to flow or stop flowing through the AGV, respectively. OP and CP were measured twice per AGV. Patients were followed for 12 weeks. In total, 20 eyes from 19 patients were enrolled. At 12 weeks the mean IOP decreased from 29.2±9.1 to 16.8±5.2 mm Hg (P<0.01). The mean AGV OP was 17.5±5.4 mm Hg and the mean CP was 6.7±2.3 mm Hg. Early (within 2 wk postoperative) HP occurred in 37% and hypotony in 16% of cases. An 18 mm Hg cutoff for the OP gave a sensitivity of 0.71, specificity of 0.83, positive predictive value of 0.71, and negative predictive value of 0.83 for predicting an early HP. A 7 mm Hg cutoff for the CP yielded a sensitivity of 1.0, specificity of 0.38, positive predictive value of 0.23, and negative predictive value of 1.0 for predicting hypotony. Preoperative OP and CP may predict early hypotony or HP and may be used as a guide as to which AGV valves to discard before implantation surgery.

  5. Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice.

    PubMed

    Seki, Ekihiro; Tsutsui, Hiroko; Tsuji, Noriko M; Hayashi, Nobuki; Adachi, Keishi; Nakano, Hiroki; Futatsugi-Yumikura, Shizue; Takeuchi, Osamu; Hoshino, Katsuaki; Akira, Shizuo; Fujimoto, Jiro; Nakanishi, Kenji

    2002-10-01

    Listeria monocytogenes (LM), a facultative intracellular Gram-positive bacterium, often causes lethal infection of the host. In this study we investigated the molecular mechanism underlying LM eradication in the early phase of infection. Upon infection with LM, both IL-12 and IL-18 were produced, and then they synergistically induced IFN-gamma production, leading to normal LM clearance in the host. IFN-gamma knockout (KO) mice were highly susceptible to LM infection. IL-12/IL-18 double knockout mice were also highly susceptible. Their susceptibility was less than that of IFN-gamma KO mice, but more than that of single IL-12 or IL-18 KO mice. Mice deficient in myeloid differentiation factor 88 (MyD88), an essential adaptor molecule used by signal transduction pathways of all members of the Toll-like receptor (TLR) family, showed an inability to produce IL-12 and IFN-gamma following LM infection and were most susceptible to LM. Furthermore, MyD88-deficient, but not IFN-gamma-deficient, Kupffer cells could not produce TNF-alpha in response to LM in vitro, indicating the importance of MyD88-dependent TNF-alpha production for host defense. As TLR2 KO, but not TLR4 KO, mice showed partial impairment in their capacity to produce IL-12, IFN-gamma, and TNF-alpha, TLR2 activation partly contributed to the induction of IL-12-mediated IFN-gamma production. These results indicated a critical role for TLRs/MyD88-dependent IL-12/TNF-alpha production and for IL-12- and IL-18-mediated IFN-gamma production in early phase clearance of LM.

  6. Response surface method in geotechnical/structural analysis, phase 1

    NASA Astrophysics Data System (ADS)

    Wong, F. S.

    1981-02-01

    In the response surface approach, an approximating function is fit to a long running computer code based on a limited number of code calculations. The approximating function, called the response surface, is then used to replace the code in subsequent repetitive computations required in a statistical analysis. The procedure of the response surface development and feasibility of the method are shown using a sample problem in slop stability which is based on data from centrifuge experiments of model soil slopes and involves five random soil parameters. It is shown that a response surface can be constructed based on as few as four code calculations and that the response surface is computationally extremely efficient compared to the code calculation. Potential applications of this research include probabilistic analysis of dynamic, complex, nonlinear soil/structure systems such as slope stability, liquefaction, and nuclear reactor safety.

  7. Response of an all digital phase-locked loop

    NASA Technical Reports Server (NTRS)

    Garodnick, J.; Greco, J.; Schilling, D. L.

    1974-01-01

    An all digital phase-locked loop (DPLL) is designed, analyzed, and tested. Three specific configurations are considered, generating first, second, and third order DPLL's; and it is found, using a computer simulation of a noise spike, and verified experimentally, that of these configurations the second-order system is optimum from the standpoint of threshold extension. This substantiates results obtained for analog PLL's.

  8. Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

    NASA Astrophysics Data System (ADS)

    Race, Margaret; Conley, Catharine

    discussed by the study participants to date have set the agenda for additional work that will continue for at least another year, culminating in a final report that should be useful to current and new nations and partnerships in planning human missions beyond LEO. In addition, over the past two years, NASA has made progress in integrating planetary protection considerations into mission designs along with other important human, environmental and science needs. Details about planetary protection have also been incorporated into the latest Addendum of the Design Reference Architecture (DRA) for human missions to Mars. Other ongoing studies of Mars human mission architecture, technologies and operations have likewise been integrating PP requirements and guidelines into cross-cutting measures of various types. An important objective of all these studies is to proactively gather and communicate PP information to the broad community of planners, engineers and assorted partners who are facing the challenges of future human exploration missions. By analyzing ways to integrate PP provisions effectively into early mission phases in synergism with other needs, these projects and studies will help ensure that all institutions and organizations avoid releasing harmful contamination on bodies with biological potential, thereby ensuring protection of the Earth and astronauts throughout their missions and safeguarding the integrity of science exploration—all in compliance with the 1967 Outer Space Treaty.

  9. Response trajectories reveal conflict phase in image-word mismatch.

    PubMed

    van Vugt, Floris T; Cavanagh, Patrick

    2012-02-01

    In the present study, response trajectories were used in a picture–word conflict task to determine the timing of intermediate processing stages that are relatively inaccessible to response time measures. A marker was placed above or below the word ABOVE or BELOW so that its location was congruent or in conflict with the word's meaning. To report either word location(above or below the marker) or word meaning, participants moved a mouse upward toward the appropriate top left or right answer corner on the display screen.Their response trajectories showed a number of distinctive features: First, at about 200 ms after stimulus onset(the "decision moment"), the trajectory abruptly began to arc toward the appropriate answer corner; second,when the word's meaning and position were in conflict,the trajectory showed an interruption that continued until the conflict was resolved. By varying the SOA of the word and marker onsets, we found that the word meaning and word position became available at approximately 325 ms and 251 ms, respectively, after their onsets, and that the delay to resolve conflicts was about 138 ms. The timing of these response trajectory events was more stable than any extracted from the final response times, demonstrating the power of response trajectories to reveal processing stages that are only poorly resolved, if at all, by response time measures [added].

  10. Early immune response and regulation of IL-2 receptor subunits

    NASA Technical Reports Server (NTRS)

    Hughes-Fulford, Millie; Sugano, Eiko; Schopper, Thomas; Li, Chai-Fei; Boonyaratanakornkit, J. B.; Cogoli, Augusto

    2005-01-01

    MAPK pathways plays a role in early T-cell activation and induction of IL-2, IL-2R(alpha) and IFN(gamma) gene expression.

  11. Early immune response and regulation of IL-2 receptor subunits.

    PubMed

    Hughes-Fulford, Millie; Sugano, Eiko; Schopper, Thomas; Li, Chai-Fei; Boonyaratanakornkit, J B; Cogoli, Augusto

    2005-09-01

    MAPK pathways plays a role in early T-cell activation and induction of IL-2, IL-2R(alpha) and IFN(gamma) gene expression.

  12. Recruitment of DNA polymerase eta by FANCD2 in the early response to DNA damage.

    PubMed

    Fu, Dechen; Dudimah, Fred Duafalia; Zhang, Jun; Pickering, Anna; Paneerselvam, Jayabal; Palrasu, Manikandan; Wang, Hong; Fei, Peiwen

    2013-03-01

    How Fanconi anemia (FA) protein D2 (FANCD2) performs DNA damage repair remains largely elusive. We report here that translesion synthesis DNA polymerase (pol) eta is a novel mediator of FANCD2 function. We found that wild type (wt) FANCD2, not K561R (mt) FANCD2, can interact with pol eta. Upon DNA damage, the interaction of pol eta with FANCD2 occurs earlier than that with PCNA, which is in concert with our finding that FANCD2 monoubiquitination peaks at an earlier time point than that of PCNA monoubiquitination. FANCD2-null FA patient cells (PD20) carrying histone H2B-fused pol eta and wtFANCD2, respectively, show a similar tendency of low Mitomycin C (MMC) sensitivity, while cells transfected with empty vector control or pol eta alone demonstrate a similar high level of MMC sensitivity. It therefore appears that FANCD2 monoubiquitination plays a similar anchor role as histone to bind DNA in regulating pol eta. Collectively, our study indicates that, in the early phase of DNA damage response, FANCD2 plays crucial roles in recruiting pol eta to the sites of DNA damage for repair.

  13. Recruitment of DNA polymerase eta by FANCD2 in the early response to DNA damage

    PubMed Central

    Fu, Dechen; Dudimah, Fred Duafalia; Zhang, Jun; Pickering, Anna; Paneerselvam, Jayabal; Palrasu, Manikandan; Wang, Hong; Fei, Peiwen

    2013-01-01

    How Fanconi anemia (FA) protein D2 (FANCD2) performs DNA damage repair remains largely elusive. We report here that translesion synthesis DNA polymerase (pol) eta is a novel mediator of FANCD2 function. We found that wild type (wt) FANCD2, not K561R (mt) FANCD2, can interact with pol eta. Upon DNA damage, the interaction of pol eta with FANCD2 occurs earlier than that with PCNA, which is in concert with our finding that FANCD2 monoubiquitination peaks at an earlier time point than that of PCNA monoubiquitination. FANCD2-null FA patient cells (PD20) carrying histone H2B-fused pol eta and wtFANCD2, respectively, show a similar tendency of low Mitomycin C (MMC) sensitivity, while cells transfected with empty vector control or pol eta alone demonstrate a similar high level of MMC sensitivity. It therefore appears that FANCD2 monoubiquitination plays a similar anchor role as histone to bind DNA in regulating pol eta. Collectively, our study indicates that, in the early phase of DNA damage response, FANCD2 plays crucial roles in recruiting pol eta to the sites of DNA damage for repair. PMID:23388460

  14. Predictors of Responsiveness to Early Literacy Intervention: A 10-Year Update

    ERIC Educational Resources Information Center

    Lam, Elizabeth A.; McMaster, Kristen L.

    2014-01-01

    The purpose of this review was to update previous reviews on factors related to students' responsiveness to early literacy intervention. The 14 studies in this synthesis used experimental designs, provided small-group or one-on-one reading interventions, and analyzed factors related to responsiveness to those interventions. Participants were…

  15. Evidence-Based Early Reading Practices within a Response to Intervention System

    ERIC Educational Resources Information Center

    Bursuck, Bill; Blanks, Brooke

    2010-01-01

    Many students who experience reading failure are inappropriately placed in special education. A promising response to reducing reading failure and the overidentification of students for special education is Response to Intervention (RTI), a comprehensive early detection and prevention system that allows teachers to identify and support struggling…

  16. Early-Time Solution of the Horizontal Unconfined Aquifer in the Buildup Phase

    NASA Astrophysics Data System (ADS)

    Gravanis, Elias; Akylas, Evangelos

    2017-10-01

    We derive the early-time solution of the Boussinesq equation for the horizontal unconfined aquifer in the buildup phase under constant recharge and zero inflow. The solution is expressed as a power series of a suitable similarity variable, which is constructed so that to satisfy the boundary conditions at both ends of the aquifer, that is, it is a polynomial approximation of the exact solution. The series turns out to be asymptotic and it is regularized by resummation techniques that are used to define divergent series. The outflow rate in this regime is linear in time, and the (dimensionless) coefficient is calculated to eight significant figures. The local error of the series is quantified by its deviation from satisfying the self-similar Boussinesq equation at every point. The local error turns out to be everywhere positive, hence, so is the integrated error, which in turn quantifies the degree of convergence of the series to the exact solution.

  17. HISPASAT launch and early operations phases: Computation and monitoring of geostationary satellite positioning

    NASA Technical Reports Server (NTRS)

    Brousse, Pascal; Desprairies, Arnaud

    1993-01-01

    Since 1974, CNES, the French National Space Agency, has been involved in the geostationary launch and early operations phases (LEOP) of moving satellites from a transfer orbit delivered by a launcher to a geostationary point. During the operations and their preparation, the Flight Dynamics Center (FDC), part of CNES LEOP facilities, is in charge of the space mechanics aspects. What is noteworthy about the Spanish HISPASAT satellite positioning is that all the operations were performed on the customer's premises, and consequently the FDC was duplicated in Madrid, Spain. The first part of this paper is the FDC presentation: its role, its hardware configuration, and its space dynamics ground control system called MERCATOR. The second part of this paper details the preparation used by the FDC for the HISPASAT mission: hardware and software installation in Madrid, integration with the other entities, and technical and operational qualifications. The third part gives results concerning flight dynamics aspects and operational activities.

  18. Children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood.

    PubMed

    Leppert, Katherine A; Kushner, Marissa; Smith, Victoria C; Lemay, Edward P; Dougherty, Lea R

    2016-12-01

    This study examined the stability of children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood. Ninety-six children (51 males) completed stress-inducing laboratory tasks and provided five salivary cortisol samples in early (W1) and middle (W2) childhood. Although W1 cortisol responses did not predict W2 cortisol responses, children's cortisol responses demonstrated change: compared to their W1 cortisol responses, children's W2 cortisol responses demonstrated an increased slope and more negative quadratic curvature. Furthermore, child psychiatric symptoms at W1 moderated the stability of children's cortisol responses. Children with fewer preschool psychiatric symptoms demonstrated greater inter-individual and intra-individual stability, whereas children with higher preschool psychiatric symptoms and comorbidity demonstrated systematic inter-individual and intra-individual instability in cortisol responses over time. Findings suggest a developmental shift toward increasing cortisol stress responses from early to middle childhood and highlight preschool psychopathology as a moderator of stability in children's cortisol responses over time. © 2016 Wiley Periodicals, Inc.

  19. Cognitive function in early clinical phase huntington disease after rivastigmine treatment.

    PubMed

    Sešok, Sanja; Bolle, Nika; Kobal, Jan; Bucik, Valentin; Vodušek, David B

    2014-09-01

    In Huntington disease (HD) patients receiving rivastigmine treatment improvement of behavioral symptoms and of cognitive function (assessed with screening diagnostic instruments) has been reported. The aim of the present study was to verify such improvement in cognitive function by cognitive function assessment with a detailed neuropsychological battery covering all relevant cognitive systems expected to be impaired in early phase HD. Eighteen (18) HD patients entered the study and were randomly allocated to the rivastigmine and placebo group. All subjects underwent neuropsychological assessment at baseline. Follow-up neuropsychological assessment was applied after 6 months of rivastigmine or placebo treatment. Eighteen (18) healthy controls entered the study to control for practice effect and underwent neuropsychological assessment at baseline and after 6 months, without treatment. The neuropsychological battery consisted of assessment tools that are sensitive to cognitive impairment seen in early phase HD: CTMT, SDMT, Stroop (attention and information control), RFFT, TOL, Verbal fluency (executive functioning), CVLT-II, RCFT (learning and memory). Effect of rivastigmine and possible effect of practice was assessed using the mixed ANOVA model. No statistically significant effect of rivastigmine treatment on cognitive function in HD patients was detected. There was no evidence for practice or placebo effect. Detailed neuropsychological assessment did not confirm previously reported effect of rivastigmine treatment on cognitive function in HD patients. The limitations of our study are, in particular, small sample size and the lack of a single measure of relevant cognitive functioning in HD patients. Instead of focusing solely on statistical significance, a clinical relevance study is proposed to clarify the issue of rivastigmine effects in HD.

  20. Serum Uromodulin Levels in Prediction of Acute Kidney Injury in the Early Phase of Acute Pancreatitis.

    PubMed

    Kuśnierz-Cabala, Beata; Gala-Błądzińska, Agnieszka; Mazur-Laskowska, Małgorzata; Dumnicka, Paulina; Sporek, Mateusz; Matuszyk, Aleksandra; Gil, Krzysztof; Ceranowicz, Piotr; Walocha, Jerzy; Kucharz, Jakub; Pędziwiatr, Michał; Bartuś, Krzysztof; Trąbka, Rafał; Kuźniewski, Marek

    2017-06-14

    In health, uromodulin is the main protein of urine. Serum uromodulin concentrations (sUMOD) have been shown to correlate with kidney function. Acute kidney injury (AKI) is among the main complications of severe acute pancreatitis (AP). No reports exist on sUMOD in patients with AP, including the diagnostic usefulness for early prediction of AP severity. We measured sUMOD during first 72 h of AP. Sixty-six adult patients with AP were recruited at the surgical ward of the District Hospital in Sucha Beskidzka, Poland. AP was diagnosed according to the Revised Atlanta Classification. Blood samples were collected at 24, 48 and 72 h of AP, and sUMOD concentrations were measured with enzyme-linked immunosorbent test. sUMOD decreased non-significantly during the study. Patients with severe AP had non-significantly lower sUMOD concentrations than those with mild disease. Significant positive correlation was observed between sUMOD and estimated glomerular filtration rate on each day of the study and negative correlations were shown between sUMOD and age, serum creatinine, cystatin C and urea. Patients with AKI tended to have lower sUMOD. Although sUMOD correlated significantly with kidney function in the early phase of AP, measuring sUMOD did not allow to reliably predict AP severity or development of AKI.

  1. Use of activated protein C has no avail in the early phase of acute pancreatitis.

    PubMed

    Akay, Sinan; Ozutemiz, Omer; Yenisey, Cigdem; Simsek, Nilufer Genc; Yuce, Gul; Batur, Yucel

    2008-01-01

    Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancreatitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activities were collected, and blood for serum amylase, urea, creatinine, and interleukin-6 measurements was withdrawn. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435+/-432 U/L vs. 27,426+/-118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970+/-323 pg/mL vs. 330+/-368 pg/mL, respectively). In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions.

  2. Carbachol improves secretion in the early phase after rabbit submandibular gland transplantation.

    PubMed

    Shi, L; Cong, X; Zhang, Y; Ding, C; Ding, Q W; Fu, F Y; Wu, L L; Yu, G Y

    2010-05-01

    To investigate the changes in the muscarinic receptor signaling pathway with submandibular gland (SMG) transplantation and whether carbachol improves secretion in transplanted SMGs. SMG autotransplantation was performed in a rabbit model. Carbachol (1 microM) was infused into the transplanted glands from postoperative day 1-7. The expression of the M1 and M3 muscarinic receptors, aquaporin-5 (AQP5), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was measured by RT-PCR, immunoblotting or immunofluorescence. The content of inositol 1, 4, 5-trisphosphate (IP(3)) was measured by radioimmunoassay. Salivary flow of the transplanted SMGs was decreased after transplantation. As well, the expressions of M1 and M3 receptors and their downstream signaling molecules, IP(3), p-ERK1/2 and AQP5, were all reduced. Atrophy of acinar cells was shown in transplanted glands. However, all these alterations were reversed after carbachol treatment for 7 days. Furthermore, carbachol directly increased the mRNA expression of AQP5 and phosphorylation of ERK1/2 in cultured neonatal rabbit SMG cells. A lack of acetylcholine and downregulation of the muscarinic receptor signaling pathway is involved in the early hypofunction of transplanted SMGs. Carbachol treatment could be a new therapeutic strategy to improve secretion and prevent the obstruction of Wharton's duct in the early phase after SMG transplantation.

  3. Wide-field phase imaging for the endoscopic detection of dysplasia and early-stage esophageal cancer

    NASA Astrophysics Data System (ADS)

    Fitzpatrick, C. R. M.; Gordon, G. S. D.; Sawyer, T. W.; Wilkinson, T. D.; Bohndiek, S. E.

    2018-02-01

    Esophageal cancer has a 5-year survival rate below 20%, but can be curatively resected if it is detected early. At present, poor contrast for early lesions in white light imaging leads to a high miss rate in standard-of- care endoscopic surveillance. Early lesions in the esophagus, referred to as dysplasia, are characterized by an abundance of abnormal cells with enlarged nuclei. This tissue has a different refractive index profile to healthy tissue, which results in different light scattering properties and provides a source of endogenous contrast that can be exploited for advanced endoscopic imaging. For example, point measurements of such contrast can be made with scattering spectroscopy, while optical coherence tomography generates volumetric data. However, both require specialist interpretation for diagnostic decision making. We propose combining wide-field phase imaging with existing white light endoscopy in order to provide enhanced contrast for dysplasia and early-stage cancer in an image format that is familiar to endoscopists. Wide-field phase imaging in endoscopy can be achieved using coherent illumination combined with phase retrieval algorithms. Here, we present the design and simulation of a benchtop phase imaging system that is compatible with capsule endoscopy. We have undertaken preliminary optical modelling of the phase imaging setup, including aberration correction simulations and an investigation into distinguishing between different tissue phantom scattering coefficients. As our approach is based on phase retrieval rather than interferometry, it is feasible to realize a device with low-cost components for future clinical implementation.

  4. Early improvements in anxiety, depression, and anger/hostility symptoms and response to antidepressant treatment.

    PubMed

    Farabaugh, Amy; Sonawalla, Shamsah; Johnson, Daniel P; Witte, Janet; Papakostas, George I; Goodness, Tracie; Clain, Alisabet; Baer, Lee; Mischoulon, David; Fava, Maurizio; Harley, Rebecca

    2010-08-01

    The purpose of this study was to examine whether treatment response to fluoxetine by depressed outpatients was predicted by early improvement on any of 3 subscales (Anxiety, Depression, and Anger/Hostility) of the Symptom Questionnaire (SQ). We evaluated 169 depressed outpatients (52.6% female) between ages 18 and 65 (mean age, 40.3 +/- 10.6 years) meeting DSM-IIIR criteria for major depressive disorder (MDD). All patients completed the SQ at baseline (week 0) and at weeks 2, 4, and 8 of treatment with fluoxetine 20 mg/d. We defined treatment response as a > or= 50% reduction in score on the 17-item Hamilton Rating Scale for Depression, and early improvement on 3 SQ subscales (Anxiety, Depression, and Anger/Hostility) as a >30% reduction in score by week 2. The percentage of patients with significant early improvement in anger was significantly greater than the percentage of those with early improvements in anxiety or depression. When early improvement on the Anxiety, Depression, and Anger/Hostility subscales of the SQ were assessed independently by logistic regression, all 3 subscales were predictors of response to treatment. Early improvement in anger, anxiety, and depressive symptoms may predict response to antidepressant treatment among outpatients with MDD.

  5. Assessment of early warning system performance and improvements since it is in operational phase in Romania

    NASA Astrophysics Data System (ADS)

    Ionescu, Constantin; Marmureanu, Alexandru; Marmureanu, Gheorghe; Ortansa Cioflan, Carmen

    2017-04-01

    Earthquake represents a major natural disaster for Romanian territory. The main goal following the occurrence of a strong earthquake is to minimize the total number of fatalities. A rapid early warning system (REWS) was developed in Romania in order to provide 25-35 seconds warning time to Bucharest facilities for the earthquakes with M>5.0. The system consists of four components: a network of strong motion sensors installed in the epicentral area, a redundant communication network, an automatic analyzing system located in the Romanian Data Centre and an alert distribution system. The detection algorithm is based on the magnitude computation using strong motion data and rapid evaluation and scaling relation between the maximum P-wave acceleration measured in the epicentral area and the higher ground motion amplitude recorded in Bucharest. In order to reduce the damages caused by earthquakes, the exploitation of the up to date technology is very important. The information is the key point in the disaster management, and the internet is one of the most used instrument, implying also low costs. The Rapid Early Warning System was expanded to cover all countries affected by major earthquakes originating in the Vrancea seismic area and reduce their impact on existing installations of national interest in neighbouring Romania and elsewhere. REWS provides an efficient instrument for prevention and reaction based on the integrated system for seismic detection in South-Eastern Europe. REWS has been operational since 2013 and sends alert the authorities, hazardous facilities in Romania and Bulgaria (NPP, emergency response agencies etc.) and to public via twitter and some smartphone applications developed in the house. Also, NIEP is part of the UNESCO initiative case on developing a platform on earthquake early warning systems (IP-MEP) that aims to promote and strengthen the development of earthquake early warning systems in earthquake-prone regions of the world by sharing

  6. Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair

    PubMed Central

    Reumann, Marie K.; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Steven B.; Lukashova, Lyudmila; Boskey, Adele L.; Mayer-Kuckuk, Philipp

    2011-01-01

    Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1−/− mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1−/− mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1−/− callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. PMID:21726677

  7. Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.

    PubMed

    Reumann, Marie K; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Stephen B; Lukashova, Lyudmila; Boskey, Adele L; Mayer-Kuckuk, Philipp

    2011-10-01

    Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Health responsibility and workplace health promotion among women: early detection of cancer.

    PubMed

    Kushnir, T; Rabinowitz, S; Melamed, S; Weisberg, E; Ribak, J

    1995-01-01

    The importance of health responsibility as one aspect of a health-promoting lifestyle has been emphasized repeatedly. Yet there are only a few empirical studies of its role in preventive behavior. We examined the relationship between health responsibility and early-detection practices for breast and cervical cancer. A group of 253 women employees of a large industrial company participated in a cancer screening program subsidized by the employer. They completed questionnaires assessing health responsibility and reported early-detection practices: frequency of breast self-examination and physician breast examinations, frequency of Pap tests, and time lapsed since last Pap test and breast examinations. Health responsibility was a significant independent predictor of breast examination indicators but not of Pap tests. Education level was an important predictor for Pap tests, and age predicted most early-detection practices. The findings lend some support to the role of health responsibility in initiating breast examinations. Better prediction of early-detection practices could be achieved by adding cognitive and emotional components to the existing responsibility scale and by distinguishing between retrospective and prospective responsibility.

  9. Strontium ranelate causes osteophytes overgrowth in a model of early phase osteoarthritis.

    PubMed

    Chu, Jian-Guo; Dai, Mu-Wei; Wang, Yu; Tian, Fa-Ming; Song, Hui-Ping; Xiao, Ya-Ping; Shao, Li-Tao; Zhang, Ying-Ze; Zhang, Liu

    2017-02-10

    Osteoarthritis (OA) involves cartilage changes as well as modifications of subchondral bone and synovial tissues. Strontium ranelate (SR), an anti-osteoporosis compound, which is currently in phase III clinical trial for treatment of OA. Evidences suggest that SR preferably deposited in osteophyte, other than in subchondral bone in early phase of OA. This phenomenon raises concern about its utility for OA treatment as a disease-modifying drug. To evaluate the effect of SR on cartilage, subchondral bone mass and subchondral trabecular bone structure in medial meniscectomized (MNX) guinea pigs. Thirty-six 3-month-old male Dunkin Hartley albino guinea pigs received either sham or medial meniscectomy operations. One week after the procedure, meniscectomized animals began 12 weeks of SR (625 mg/kg, daily) treatment by oral gavage for MNX + SR group, or normal saline for MNX + V group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. Both OARSI scores (P = 0.523 for marcoscopic scores, P = 0.297 for histological scores) and Cartilage thickness (P = 0.335) in MNX + SR group were comparable to MNX + V group. However, osteophyte sizes were larger in MNX + SR group (P = 0.014), and collapsed osteophytes in MNX + SR group (7 by 12) were significantly more than in MNX + V group (1 by 12) (P = 0.027), while immunohistochemistry indicates catabolic changes in osteophyte/plateau junction. Micro-CT analysis showed bone mineral density (BMD) (P = 0.001), bone volume fraction (BV/TV) (P = 0.008), trabecular spacing (Tb.Sp) (P = 0.020), trabecular thickness (Tb.Th) (P = 0.012) and structure model index (SMI) (P = 0.005) levels to be significantly higher in the MNX + SR group than in the MNX + V group. SR (625 mg/kg/day) did not protect cartilage from degeneration in MNX guinea pigs but subchondral bone was significantly enhanced. In early

  10. Effect Anticipation Affects Perceptual, Cognitive, and Motor Phases of Response Preparation: Evidence from an Event-Related Potential (ERP) Study

    PubMed Central

    Harrison, Neil R.; Ziessler, Michael

    2016-01-01

    The anticipation of action effects is a basic process that can be observed even for key-pressing responses in a stimulus-response paradigm. In Ziessler et al.’s (2012) experiments participants first learned arbitrary effects of key-pressing responses. In the test phase an imperative stimulus determined the response, but participants withheld the response until a Go-stimulus appeared. Reaction times (RTs) were shorter if the Go-stimulus was compatible with the learned response effect. This is strong evidence that effect representations were activated during response planning. Here, we repeated the experiment using event-related potentials (ERPs), and we found that Go-stimulus locked ERPs depended on the compatibility relationship between the Go-stimulus and the response effect. In general, this supports the interpretation of the behavioral data. More specifically, differences in the ERPs between compatible and incompatible Go-stimuli were found for the early perceptual P1 component and the later frontal P2 component. P1 differences were found only in the second half of the experiment and for long stimulus onset asynchronies (SOAs) between imperative stimulus and Go-stimulus, i.e., when the effect was fully anticipated and the perceptual system was prepared for the effect-compatible Go-stimulus. P2 amplitudes, likely associated with evaluation and conflict detection, were larger when Go-stimulus and effect were incompatible; presumably, incompatibility increased the difficulty of effect anticipation. Onset of response-locked lateralized readiness potentials (R-LRPs) occurred earlier under incompatible conditions indicating extended motor processing. Together, these results strongly suggest that effect anticipation affects all (i.e., perceptual, cognitive, and motor) phases of response preparation. PMID:26858621

  11. Effect Anticipation Affects Perceptual, Cognitive, and Motor Phases of Response Preparation: Evidence from an Event-Related Potential (ERP) Study.

    PubMed

    Harrison, Neil R; Ziessler, Michael

    2016-01-01

    The anticipation of action effects is a basic process that can be observed even for key-pressing responses in a stimulus-response paradigm. In Ziessler et al.'s (2012) experiments participants first learned arbitrary effects of key-pressing responses. In the test phase an imperative stimulus determined the response, but participants withheld the response until a Go-stimulus appeared. Reaction times (RTs) were shorter if the Go-stimulus was compatible with the learned response effect. This is strong evidence that effect representations were activated during response planning. Here, we repeated the experiment using event-related potentials (ERPs), and we found that Go-stimulus locked ERPs depended on the compatibility relationship between the Go-stimulus and the response effect. In general, this supports the interpretation of the behavioral data. More specifically, differences in the ERPs between compatible and incompatible Go-stimuli were found for the early perceptual P1 component and the later frontal P2 component. P1 differences were found only in the second half of the experiment and for long stimulus onset asynchronies (SOAs) between imperative stimulus and Go-stimulus, i.e., when the effect was fully anticipated and the perceptual system was prepared for the effect-compatible Go-stimulus. P2 amplitudes, likely associated with evaluation and conflict detection, were larger when Go-stimulus and effect were incompatible; presumably, incompatibility increased the difficulty of effect anticipation. Onset of response-locked lateralized readiness potentials (R-LRPs) occurred earlier under incompatible conditions indicating extended motor processing. Together, these results strongly suggest that effect anticipation affects all (i.e., perceptual, cognitive, and motor) phases of response preparation.

  12. THE ACUTE PHASE RESPONSE INDUCED BY BRONCHOSCOPY WITH LAVAGE

    EPA Science Inventory

    Bronchoscopy has been used to evaluate the inflammatory responses in vitro and in vivo. The procedure may affect acute inflammation in the lower respiratory tract. We reviewed consecutive bronchoscopies done in normal healthy non-smokers between April, 1998 and April, 2004. The...

  13. Free Trehalose Accumulation in Dormant Mycobacterium smegmatis Cells and Its Breakdown in Early Resuscitation Phase

    PubMed Central

    Shleeva, Margarita O.; Trutneva, Kseniya A.; Demina, Galina R.; Zinin, Alexander I.; Sorokoumova, Galina M.; Laptinskaya, Polina K.; Shumkova, Ekaterina S.; Kaprelyants, Arseny S.

    2017-01-01

    Under gradual acidification of growth medium resulting in the formation of dormant Mycobacterium smegmatis, a significant accumulation of free trehalose in dormant cells was observed. According to 1H- and 13C-NMR spectroscopy up to 64% of total organic substances in the dormant cell extract was represented by trehalose whilst the trehalose content in an extract of active cells taken from early stationary phase was not more than 15%. Trehalose biosynthesis during transition to the dormant state is provided by activation of genes involved in the OtsA-OtsB and TreY-TreZ pathways (according to RT-PCR). Varying the concentration of free trehalose in dormant cells by expression of MSMEG_4535 coding for trehalase we found that cell viability depends on trehalose level: cells with a high amount of trehalose survive much better than cells with a low amount. Upon resuscitation of dormant M. smegmatis, a decrease of free trehalose and an increase in glucose concentration occurred in the early period of resuscitation (after 2 h). Evidently, breakdown of trehalose by trehalase takes place at this time as a transient increase in trehalase activity was observed between 1 and 3 h of resuscitation. Activation of trehalase was not due to de novo biosynthesis but because of self-activation of the enzyme from the inactive state in dormant cells. Because, even a low concentration of ATP (2 mM) prevents self-activation of trehalase in vitro and after activation the enzyme is still sensitive to ATP we suggest that the transient character of trehalase activation in cells is due to variation in intracellular ATP concentration found in the early resuscitation period. The negative influence of the trehalase inhibitor validamycin A on the resuscitation of dormant cells proves the importance of trehalase for resuscitation. These experiments demonstrate the significance of free trehalose accumulation for the maintenance of dormant mycobacterial viability and the involvement of trehalose

  14. The acute-phase response impairs host defence against Enterococcus faecium peritonitis

    PubMed Central

    Leendertse, Masja; Willems, Rob J L; Giebelen, Ida A J; van den Pangaart, Petra S; Bonten, Marc J M; van der Poll, Tom

    2009-01-01

    Enterococcus faecium is an emerging pathogen that causes infections in hospitalized patients with various co-morbid diseases. These underlying diseases are often associated with an acute-phase response that renders patients vulnerable to nosocomial infections. To study the influence of the acute-phase response induced by sterile tissue injury on host defence against E. faecium, mice were injected subcutaneously with either turpentine or casein 1 day before intraperitoneal infection with E. faecium. Control mice were subcutaneously injected with saline or sodium bicarbonate, respectively. Turpentine and casein induced an acute-phase response as reflected by increases in the plasma concentrations of interleukin-6, serum amyloid P and C3. A pre-existent acute-phase response in mice was associated with a strongly reduced capacity to clear E. faecium, resulting in prolonged bacteraemia for several days. The inflammatory response to E. faecium was impaired in mice with an acute-phase response, as shown by reduced capacity to mount a neutrophilic leucocytosis in peripheral blood and by decreased local cytokine concentrations. These data indicate that the acute-phase response impairs host defence against E. faecium, suggesting that this condition may contribute to the increased vulnerability of critically ill patients to enterococcal infections. PMID:19175794

  15. Study on stress-strain response of multi-phase TRIP steel under cyclic loading

    NASA Astrophysics Data System (ADS)

    Dan, W. J.; Hu, Z. G.; Zhang, W. G.; Li, S. H.; Lin, Z. Q.

    2013-12-01

    The stress-strain response of multi-phase TRIP590 sheet steel is studied in cyclic loading condition at room temperature based on a cyclic phase transformation model and a multi-phase mixed kinematic hardening model. The cyclic martensite transformation model is proposed based on the shear-band intersection, where the repeat number, strain amplitude and cyclic frequency are used to control the phase transformation process. The multi-phase mixed kinematic hardening model is developed based on the non-linear kinematic hardening rule of per-phase. The parameters of transformation model are identified with the relationship between the austenite volume fraction and the repeat number. The parameters in Kinematic hardening model are confirmed by the experimental hysteresis loops in different strain amplitude conditions. The responses of hysteresis loop and stress amplitude are evaluated by tension-compression data.

  16. Cortisol Response to Psychosocial Stress in Chinese Early Puberty Girls: Possible Role of Depressive Symptoms.

    PubMed

    Sun, Ying; Deng, Fang; Liu, Yang; Tao, Fang-Biao

    2015-01-01

    Objective. The present study aimed at investigating unique patterns of salivary cortisol reactivity and recovery in response to a social stressor among girls with early puberty and exploring possible role of depressive symptom in this association. Design. Case-control study. Patients. Fifty-six girls with early puberty and age- and body mass index- (BMI-) matched normal puberty controls (n = 56) were selected. Measurements. Salivary cortisol was measured in response to the Groningen Social Stress Test for Children. Results. Girls with early puberty had higher cortisol concentration at the end of the GSST (C3), cortisol concentration 20 min after the end of the GSST (C4), and AUC increment (AUCi) compared to non-early puberty girls. Depressive symptoms correlated with blunted HPA reactivity among girls with early puberty. Conclusion. This study demonstrated the disturbance effect of objectively examined early pubertal timing on HPA axis responses. It also suggested that stress reactivity might be blunted for individuals with depressive symptoms.

  17. Organ-specific defence strategies of pepper (Capsicum annuum L.) during early phase of water deficit.

    PubMed

    Sziderics, Astrid Heide; Oufir, Mouhssin; Trognitz, Friederike; Kopecky, Dieter; Matusíková, Ildikó; Hausman, Jean-Francois; Wilhelm, Eva

    2010-03-01

    Drought is one of the major factors that limits crop production and reduces yield. To understand the early response of plants under nearly natural conditions, pepper plants (Capsicum annuum L.) were grown in a greenhouse and stressed by withholding water for 1 week. Plants adapted to the decreasing water content of the soil by adjustment of their osmotic potential in root tissue. As a consequence of drought, strong accumulation of raffinose, glucose, galactinol and proline was detected in the roots. In contrast, in leaves the levels of fructose, sucrose and also galactinol increased. Due to the water deficit cadaverine, putrescine, spermidine and spermine accumulated in leaves, whereas the concentration of polyamines was reduced in roots. To study the molecular basis of these responses, a combined approach of suppression subtractive hybridisation and microarray technique was performed on the same material. A total of 109 unique ESTs were detected as responsive to drought, while additional 286 ESTs were selected from the bulk of rare transcripts on the array. The metabolic profiles of stressed pepper plants are discussed with respect to the transcriptomic changes detected, while attention is given to the differences between defence strategies of roots and leaves.

  18. Acoustic Response of Microbubbles Derived from Phase-Change Nanodroplet

    NASA Astrophysics Data System (ADS)

    Kawabata, Ken-ichi; Asami, Rei; Azuma, Takashi; Umemura, Shin-ichiro

    2010-07-01

    An in vitro feasibility test for a novel ultrasound therapy using a type of superheated perfluorocarbon droplet, phase-change nanodroplet (PCND), was performed in gel phantoms with the goal of high selectivity and low invasiveness. Measurements of broadband signal emission revealed that a triggering ultrasound pulse (peak negative pressure of 2.4 MPa) reduces the pressure threshold for cavitation induced by a subsequent ultrasound exposure at an order of magnitude from 2.4 to 0.2 MPa. The maximum allowed interval between the two ultrasound exposures for inducing cavitation with 100- and 1,000-cycle triggering ultrasound was about 100 and 500 ms, respectively. The echo signal increases induced by the triggering ultrasound with 100- and 1000-cycles were enhanced and suppressed by the subsequent ultrasound exposure, respectively. This different behavior seemed to be due to the presence of enlarged free bubbles, which should be avoided for the localization of therapeutic effects.

  19. Exposure to dim light at night during early development increases adult anxiety-like responses.

    PubMed

    Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J

    2014-06-22

    Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior

  20. An ATM-independent S-phase checkpoint response involves CHK1 pathway

    NASA Technical Reports Server (NTRS)

    Zhou, Xiang-Yang; Wang, Xiang; Hu, Baocheng; Guan, Jun; Iliakis, George; Wang, Ya

    2002-01-01

    After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent pathway that controls the slow response to regulate the S-phase checkpoint after ionizing radiation in mammalian cells. The slow response of S-phase checkpoint, which is resistant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphorylation, is much stronger in CHK1 overexpressed cells, and it could be abolished by Chk1 antisense oligonucleotides. These results provide evidence that the ATM-independent slow response of S-phase checkpoint involves CHK1 pathway.

  1. Multimodal Responses of Self-Organized Circuitry in Electronically Phase Separated Materials

    DOE PAGES

    Herklotz, Andreas; Guo, Hangwen; Wong, Anthony T.; ...

    2016-07-13

    When confining an electronically phase we separated manganite film to the scale of its coexisting self-organized metallic and these insulating domains allows resistor-capacitor circuit-like responses while providing both electroresistive and magnetoresistive switching functionality.

  2. Effect of menstrual cycle phase on the ventilatory response to rising body temperature during exercise.

    PubMed

    Hayashi, Keiji; Kawashima, Takayo; Suzuki, Yuichi

    2012-07-01

    To examine the effect of menstrual cycle on the ventilatory sensitivity to rising body temperature, ten healthy women exercised for ~60 min on a cycle ergometer at 50% of peak oxygen uptake during the follicular and luteal phases of their cycle. Esophageal temperature, mean skin temperature, mean body temperature, minute ventilation, and tidal volume were all significantly higher at baseline and during exercise in the luteal phase than the follicular phase. On the other hand, end-tidal partial pressure of carbon dioxide was significantly lower during exercise in the luteal phase than the follicular phase. Plotting ventilatory parameters against esophageal temperature revealed there to be no significant menstrual cycle-related differences in the slopes or intercepts of the regression lines, although minute ventilation and tidal volume did significantly differ during exercise with mild hyperthermia. To evaluate the cutaneous vasodilatory response, relative laser-Doppler flowmetry values were plotted against mean body temperature, which revealed that the mean body temperature threshold for cutaneous vasodilation was significantly higher in the luteal phase than the follicular phase, but there were no significant differences in the sensitivity or peak values. These results suggest that the menstrual cycle phase influences the cutaneous vasodilatory response during exercise and the ventilatory response at rest and during exercise with mild hyperthermia, but it does not influence ventilatory responses during exercise with moderate hyperthermia.

  3. Differential involvement of IL-6 in the early and late phase of 1-methylnicotinamide (MNA) release in Concanavalin A-induced hepatitis.

    PubMed

    Sternak, Magdalena; Jakubowski, Andrzej; Czarnowska, Elzbieta; Slominska, Ewa M; Smolenski, Ryszard T; Szafarz, Malgorzata; Walczak, Maria; Sitek, Barbara; Wojcik, Tomasz; Jasztal, Agnieszka; Kaminski, Karol; Chlopicki, Stefan

    2015-09-01

    Exogenous 1-methylnicotinamide (MNA) displays anti-inflammatory activity. The aim of this work was to characterize the profile of release of endogenous MNA during the initiation and progression of murine hepatitis induced by Concanavalin A (ConA). In particular we aimed to clarify the role of interleukin-6 (IL-6) as well as the energy state of hepatocytes in MNA release in early and late phases of ConA-induced hepatitis in mice. Hepatitis was induced by ConA in IL-6(+/+) and IL-6(-/-) mice, and various parameters of liver inflammation and injury, as well as the energy state of hepatocytes, were analysed in relation to MNA release. The decrease in ATP/ADP and NADH/NAD ratios, cytokine release (IL-6, IFN-ɤ), acute phase response (e.g. haptoglobin) and liver injury (alanine aminotransaminase, ALT) were all blunted in ConA-induced hepatitis in IL-6(-/-) mice as compared to IL-6(+/+) mice. The release of MNA in response to Con A was also significantly blunted in IL-6(-/-) mice as compared to IL-6(+/+) mice in the early stage of ConA-induced hepatitis. In turn, nicotinamide N-methyltransferase (NNMT) and aldehyde oxidase (AO) activities were blunted in the liver and MNA plasma concentration was elevated to similar degree in the late stage after Concanavalin A in IL-6(+/+) and IL-6(-/-) mice. In conclusion, we demonstrated that in ConA-induced hepatitis, early, but not late MNA release was IL-6-dependent. Our results suggest that in the initiation and early hepatitis, MNA release is linked to the energy deficit/impaired redox status in hepatocytes, while in a later phase, MNA release is rather linked to the systemic inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. A technique to calibrate spatial light modulator for varying phase response over its spatial regions

    NASA Astrophysics Data System (ADS)

    Gupta, Deepak K.; Tata, B. V. R.; Ravindran, T. R.

    2018-05-01

    Holographic Optical Tweezers (HOTs) employ the technique of beam shaping and holography in an optical manipulation system to create a multitude of focal spots for simultaneous trapping and manipulation of sub-microscopic particles. The beam shaping is accomplished by the use of a phase only liquid crystal spatial light modulator (SLM). The efficiency and the uniformity in the generated traps greatly depend on the phase response behavior of SLMs. In addition the SLMs are found to show different phase response over its different spatial regions, due to non-flat structure of SLMs. Also the phase responses are found to vary over different spatial regions due to non-uniform illumination (Gaussian profile of incident laser). There are various techniques to calibrate for the varying phase response by characterizing the phase modulation at various sub-sections. We present a simple and fast technique to calibrate the SLM suffering with spatially varying phase response. We divide the SLM into many sub-sections and optimize the brightness and gamma of each sub-section for maximum diffraction efficiency. This correction is incorporated in the Weighted Gerchberg Saxton (WGS) algorithm for generation of holograms.

  5. [Inflammasome and its role in immunological and inflammatory response at early stage of burns].

    PubMed

    Zhang, Fang; Li, Jiahui; Xia, Zhaofan

    2014-06-01

    Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.

  6. Sudden blast phase in chronic myeloid leukemia developed during nilotinib therapy after major molecular response was achieved.

    PubMed

    Okada, Yosuke; Sato, Ken; Kobayashi, Shinichi; Nagao, Shigeki; Takano, Kosuke; Teramoto, Masahiro; Tachi, Noriaki; Kawamura, Toshikuni; Horiuchi, Toshikatsu; Kato, Shoichiro; Saga, Reina; Maekawa, Takaaki; Yamamura, Takeshi; Watanabe, Junichi; Kobayashi, Ayako; Kimura, Fumihiko

    2018-04-01

    Sudden blast phase (SBP) is a rare event in which patients with chronic myeloid leukemia (CML) in complete cytogenetic response (CCyR) rapidly progress to the blast phase. Few patients on second-generation tyrosine kinase inhibitors (2nd TKIs) have been reported to develop SBP. Here, we report a 45-year-old man diagnosed with CML in the chronic phase in April 2008 and immediately started on imatinib therapy. He achieved CCyR 12 months after starting imatinib therapy. Imatinib was followed by treatment with the 2nd TKIs nilotinib and dasatinib from January 2011 to yield a better response. He achieved major molecular response (MMR) during dasatinib therapy in February 2012, but did not tolerate dasatinib well; hence, he was switched to nilotinib in July 2012. In December 2015, he presented at our hospital with fever and lumbago. A complete blood count revealed a white blood cell count of 30,500/µL with 60% blasts, leading to diagnosis of SBP. After dasatinib therapy and conventional chemotherapy, he again achieved MMR. This case demonstrates that SBP may occur after achieving MMR on treatment with 2nd TKIs. Continuous careful monitoring is required for the early detection of SBP, even in patients who have achieved MMR.

  7. Early-phase prandial insulin secretion: its role in the pathogenesis of type 2 diabetes mellitus and its modulation by repaglinide.

    PubMed

    Owens, D R; Cozma, L S; Luzio, S D

    2002-12-01

    The major contributory factor to increasing hyperglycaemia in established Type 2 diabetes mellitus (T2DM) appears to be the progressive delay and attenuation of the prandial insulin response. An important consequence of this derangement is that hepatic glucose production is no longer suppressed during times of prandial glucose intake. Together with a relative impairment in the rate of peripheral glucose disposal, this leads to supra-physiological plasma glucose excursions, which may damage the vasculature. An obvious therapeutic strategy, therefore, would be to increase insulin availability when most needed--in the early prandial phase. In experiments with exogenous insulin interventions, peak post-prandial blood glucose increments were curtailed without undue increases in total insulin exposure. However, available evidence suggests that the sulphonylurea glibenclamide does not effectively alter early-phase prandial insulin release but predominately increases late-phase and basal insulin output, thus incurring the risk of hypoglycaemia. The novel insulin secretagogue repaglinide, by contrast, augments early-phase prandial insulin secretion when taken before meals, as shown by studies in non-diabetic people and patients with newly diagnosed, previously untreated T2DM. Repaglinide exerts its greatest effect on the insulin secretion rate during the first 30 min after a meal is started, thereby going some way to restoring the early insulin secretion curve seen after a meal in non-diabetic people. No residual secretagogue activity is seen 4 hr after taking a single dose of up to 2 mg. Prandial glucose regulation with repaglinide could be associated with lower post-prandial glucose excursions and less risk of post-prandial hypoglycaemia than glibenclamide.

  8. Use of activated protein C has no avail in the early phase of acute pancreatitis

    PubMed Central

    Ozutemiz, Omer; Yenisey, Cigdem; Genc Simsek, Nilufer; Yuce, Gul; Batur, Yucel

    2008-01-01

    Objectives. Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Subjects and method. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancratitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activites were collected, and blood for serum amylase, urea, creatinine, and inleukin-6 measurements was withdrawn. Results. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435±432 U/L vs. 27,426±118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970±323 pg/mL vs. 330±368 pg/mL, respectively). Conclusion. In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions. PMID:19088933

  9. Psychosocial Interventions in Reducing Cannabis Use in Early Phase Psychosis: A Canadian Survey of Treatments Offered.

    PubMed

    Aydin, Cristina; Tibbo, Philip G; Ursuliak, Zenovia

    2016-06-01

    Cannabis use in people with early phase psychosis (EPP) can have a significant impact on long-term outcomes. The purpose of this investigation was to describe current cannabis use treatment practices in English-speaking early intervention services (EISs) in Canada and determine if their services are informed by available evidence. Thirty-five Canadian English-speaking EISs for psychosis were approached to complete a survey through email, facsimile, or online in order to collect information regarding their current cannabis use treatment practices. Data were acquired from 27 of the 35 (78%) programs approached. Only 12% of EISs offered formal services that targeted cannabis use, whereas the majority (63%) of EISs offered informal services for all substance use, not specifically cannabis. In programs with informal services, individual patient psychoeducation (86%) was slightly more common than individual motivational interviewing (MI) (76%) followed by group patient psychoeducation (52%) and information handouts (52%). Thirty-seven percent of EISs offered formal services for substance use, and compared to programs with informal services, more MI, cognitive-behavioural therapy, and family services were offered, with individual treatment modalities more common than groups. No EISs used contingency management, even though it has some preliminary evidence in chronic populations. Evidence-based service implementation barriers included appropriate training and administrative support. While most English-speaking Canadian EIS programs offer individual MI and psychoeducation, which is in line with the available literature, there is room for improvement in cannabis treatment services based on current evidence for both people with EPP and their families. © The Author(s) 2016.

  10. Genetic influences on phase synchrony of brain oscillations supporting response inhibition.

    PubMed

    Müller, Viktor; Anokhin, Andrey P; Lindenberger, Ulman

    2017-05-01

    Phase synchronization of neuronal oscillations is a fundamental mechanism underlying cognitive processing and behavior, including context-dependent response production and inhibition. Abnormalities in neural synchrony can lead to abnormal information processing and contribute to cognitive and behavioral deficits in neuropsychiatric disorders. However, little is known about genetic and environmental contributions to individual differences in cortical oscillatory dynamics underlying response inhibition. This study examined heritability of event-related phase synchronization of brain oscillations in 302 young female twins including 94 MZ and 57 DZ pairs performing a cued Go/No-Go version of the Continuous Performance Test (CPT). We used the Phase Locking Index (PLI) to assess inter-trial phase clustering (synchrony) in several frequency bands in two time intervals after stimulus onset (0-300 and 301-600ms). Response inhibition (i.e., successful response suppression in No-Go trials) was characterized by a transient increase in phase synchronization of delta- and theta-band oscillations in the fronto-central midline region. Genetic analysis showed significant heritability of the phase locking measures related to response inhibition, with 30 to 49% of inter-individual variability being accounted for by genetic factors. This is the first study providing evidence for heritability of task-related neural synchrony. The present results suggest that PLI can serve as an indicator of genetically transmitted individual differences in neural substrates of response inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. The tonic response to the infant knee jerk as an early sign of cerebral palsy.

    PubMed

    Hamer, Elisa G; La Bastide-Van Gemert, Sacha; Boxum, Anke G; Dijkstra, Linze J; Hielkema, Tjitske; Jeroen Vermeulen, R; Hadders-Algra, Mijna

    2018-04-01

    Early identification of infants at risk of cerebral palsy (CP) is desirable in order to provide early intervention. We previously demonstrated differences in knee jerk responses between 3-month-old high risk and typically developing infants. To improve early identification by investigating whether the presence of tonic responses (continuous muscle activity occurring after the typical phasic response), clonus or contralateral responses to the knee jerk during infancy is associated with CP. Longitudinal EMG-study. We included 34 high-risk infants (median gestational age 31.9 weeks) who participated in the LEARN2MOVE 0-2 years trial. Video-recorded knee jerk EMG-assessments were performed during infancy (1-4 times). Developmental outcome was assessed at 21 months corrected age (CA). Binomial generalized estimating equations models with repeated measurements were fitted using predictor variables. Infants who later were diagnosed with CP (n = 18) showed more often than infants who were not diagnosed with CP i) tonic responses - from 4 months CA onwards, ii) clonus - from 13 months CA onwards, and iii) contralateral responses - from 15 months CA onwards. The main limitation is the relatively small sample size. The assessment of tonic responses to the knee jerk using EMG may be a valuable add-on tool to appraise a high risk of CP. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Negative affective spillover from daily events predicts early response to cognitive therapy for depression.

    PubMed

    Cohen, Lawrence H; Gunthert, Kathleen C; Butler, Andrew C; Parrish, Brendt P; Wenze, Susan J; Beck, Judith S

    2008-12-01

    This study evaluated the predictive role of depressed outpatients' (N = 62) affective reactivity to daily stressors in their rates of improvement in cognitive therapy (CT). For 1 week before treatment, patients completed nightly electronic diaries that assessed daily stressors and negative affect (NA). The authors used multilevel modeling to compute each patient's within-day relationship between daily stressors and daily NA (within-day reactivity), as well as the relationship between daily stressors and next-day NA (next-day reactivity; affective spillover). In growth model analyses, the authors evaluated the predictive role of patients' NA reactivity in their early (Sessions 1-4) and late (Sessions 5-12) response to CT. Within-day NA reactivity did not predict early or late response to CT. However, next-day reactivity predicted early response to CT, such that patients who had greater NA spillover in response to negative events had a slower rate of symptom change during the first 4 sessions. Affective spillover did not influence later response to CT. The findings suggest that depressed patients who have difficulty bouncing back the next day from their NA reactions to a relative increase in daily negative events will respond less quickly to the early sessions of CT.

  13. Contribution of economic evaluation to decision making in early phases of product development: a methodological and empirical review.

    PubMed

    Hartz, Susanne; John, Jürgen

    2008-01-01

    Economic evaluation as an integral part of health technology assessment is today mostly applied to established technologies. Evaluating healthcare innovations in their early states of development has recently attracted attention. Although it offers several benefits, it also holds methodological challenges. The aim of our study was to investigate the possible contributions of economic evaluation to industry's decision making early in product development and to confront the results with the actual use of early data in economic assessments. We conducted a literature research to detect methodological contributions as well as economic evaluations that used data from early phases of product development. Economic analysis can be beneficially used in early phases of product development for various purposes including early market assessment, R&D portfolio management, and first estimations of pricing and reimbursement scenarios. Analytical tools available for these purposes have been identified. Numerous empirical works were detected, but most do not disclose any concrete decision context and could not be directly matched with the suggested applications. Industry can benefit from starting economic evaluation early in product development in several ways. Empirical evidence suggests that there is still potential left unused.

  14. An efficient early phase 2 procedure to screen medications for efficacy in smoking cessation.

    PubMed

    Perkins, Kenneth A; Lerman, Caryn

    2014-01-01

    Initial screening of new medications for potential efficacy (i.e., Food and Drug Administration (FDA) early phase 2), such as in aiding smoking cessation, should be efficient in identifying which drugs do, or do not, warrant more extensive (and expensive) clinical testing. This focused review outlines our research on development, evaluation, and validation of an efficient crossover procedure for sensitivity in detecting medication efficacy for smoking cessation. First-line FDA-approved medications of nicotine patch, varenicline, and bupropion were tested as model drugs, in three separate placebo-controlled studies. We also tested specificity of our procedure in identifying a drug that lacks efficacy, using modafinil. This crossover procedure showed sensitivity (increased days of abstinence) during week-long "practice" quit attempts with each of the active cessation medications (positive controls) versus placebo, but not with modafinil (negative control) versus placebo, as hypothesized. Sensitivity to medication efficacy signal was observed only in smokers high in intrinsic quit motivation (i.e., already preparing to quit soon) and not smokers low in intrinsic quit motivation, even if monetarily reinforced for abstinence (i.e., given extrinsic motivation). A crossover procedure requiring less time and fewer subjects than formal trials may provide an efficient strategy for a go/no-go decision whether to advance to subsequent phase 2 randomized clinical trials with a novel drug. Future research is needed to replicate our results and evaluate this procedure with novel compounds, identify factors that may limit its utility, and evaluate its applicability to testing efficacy of compounds for treating other forms of addiction.

  15. Early Change in Stroke Size Performs Best in Predicting Response to Therapy.

    PubMed

    Simpkins, Alexis Nétis; Dias, Christian; Norato, Gina; Kim, Eunhee; Leigh, Richard

    2017-01-01

    Reliable imaging biomarkers of response to therapy in acute stroke are needed. The final infarct volume and percent of early reperfusion have been used for this purpose. Early fluctuation in stroke size is a recognized phenomenon, but its utility as a biomarker for response to therapy has not been established. This study examined the clinical relevance of early change in stroke volume and compared it with the final infarct volume and percent of early reperfusion in identifying early neurologic improvement (ENI). Acute stroke patients, enrolled between 2013 and 2014 with serial magnetic resonance imaging (MRI) scans (pretreatment baseline, 2 h post, and 24 h post), who received thrombolysis were included in the analysis. Early change in stroke volume, infarct volume at 24 h on diffusion, and percent of early reperfusion were calculated from the baseline and 2 h MRI scans were compared. ENI was defined as ≥4 point decrease in National Institutes of Health Stroke Scales within 24 h. Logistic regression models and receiver operator characteristics analysis were used to compare the efficacy of 3 imaging biomarkers. Serial MRIs of 58 acute stroke patients were analyzed. Early change in stroke volume was significantly associated with ENI by logistic regression analysis (OR 0.93, p = 0.048) and remained significant after controlling for stroke size and severity (OR 0.90, p = 0.032). Thus, for every 1 mL increase in stroke volume, there was a 10% decrease in the odds of ENI, while for every 1 mL decrease in stroke volume, there was a 10% increase in the odds of ENI. Neither infarct volume at 24 h nor percent of early reperfusion were significantly associated with ENI by logistic regression. Receiver-operator characteristic analysis identified early change in stroke volume as the only biomarker of the 3 that performed significantly different than chance (p = 0.03). Early fluctuations in stroke size may represent a more reliable biomarker for response to therapy than the

  16. Creating diversified response profiles from a single quenchometric sensor element by using phase-resolved luminescence.

    PubMed

    Tehan, Elizabeth C; Bukowski, Rachel M; Chodavarapu, Vamsy P; Titus, Albert H; Cartwright, Alexander N; Bright, Frank V

    2015-01-05

    We report a new strategy for generating a continuum of response profiles from a single luminescence-based sensor element by using phase-resolved detection. This strategy yields reliable responses that depend in a predictable manner on changes in the luminescent reporter lifetime in the presence of the target analyte, the excitation modulation frequency, and the detector (lock-in amplifier) phase angle. In the traditional steady-state mode, the sensor that we evaluate exhibits a linear, positive going response to changes in the target analyte concentration. Under phase-resolved conditions the analyte-dependent response profiles: (i) can become highly non-linear; (ii) yield negative going responses; (iii) can be biphasic; and (iv) can exhibit super sensitivity (e.g., sensitivities up to 300 fold greater in comparison to steady-state conditions).

  17. Occlusion therapy improves phase-alignment of the cortical response in amblyopia.

    PubMed

    Kelly, John P; Tarczy-Hornoch, Kristina; Herlihy, Erin; Weiss, Avery H

    2015-09-01

    The visual evoked potential (VEP) generated by the amblyopic visual system demonstrates reduced amplitude, prolonged latency, and increased variation in response timing (phase-misalignment). This study examined VEPs before and after occlusion therapy (OT) and whether phase-misalignment can account for the amblyopic VEP deficits. VEPs were recorded to 0.5-4cycles/degree gratings in 10 amblyopic children (2-6years age) before and after OT. Phase-misalignment was measured by Fourier analysis across a limited bandwidth. Signal-to-noise ratios (SNRs) were estimated from amplitude and phase synchrony in the Fourier domain. Responses were compared to VEPs corrected for phase-misalignment (individual epochs shifted in time to correct for the misalignment). Before OT, amblyopic eyes (AE) had significantly more phase-misalignment, latency prolongation, and lower SNR relative to the fellow eye. Phase-misalignment contributed significantly to low SNR but less so to latency delay in the AE. After OT, phase-alignment improved, SNR improved and latency shortened in the AE. Raw averaged waveforms from the AE improved after OT, primarily at higher spatial frequencies. Correcting for phase-misalignment in the AE sharpened VEP peak responses primarily at low spatial frequencies, but could not account for VEP waveform improvements in the AE after OT at higher spatial frequencies. In summary, VEP abnormalities from the AE are associated with phase-misalignment and reduced SNR possibly related to desynchronization of neuronal activity. The effect of OT on VEP responses is greater than that accounted for by phase-misalignment and SNR alone. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Auditory-neurophysiological responses to speech during early childhood: Effects of background noise

    PubMed Central

    White-Schwoch, Travis; Davies, Evan C.; Thompson, Elaine C.; Carr, Kali Woodruff; Nicol, Trent; Bradlow, Ann R.; Kraus, Nina

    2015-01-01

    Early childhood is a critical period of auditory learning, during which children are constantly mapping sounds to meaning. But learning rarely occurs under ideal listening conditions—children are forced to listen against a relentless din. This background noise degrades the neural coding of these critical sounds, in turn interfering with auditory learning. Despite the importance of robust and reliable auditory processing during early childhood, little is known about the neurophysiology underlying speech processing in children so young. To better understand the physiological constraints these adverse listening scenarios impose on speech sound coding during early childhood, auditory-neurophysiological responses were elicited to a consonant-vowel syllable in quiet and background noise in a cohort of typically-developing preschoolers (ages 3–5 yr). Overall, responses were degraded in noise: they were smaller, less stable across trials, slower, and there was poorer coding of spectral content and the temporal envelope. These effects were exacerbated in response to the consonant transition relative to the vowel, suggesting that the neural coding of spectrotemporally-dynamic speech features is more tenuous in noise than the coding of static features—even in children this young. Neural coding of speech temporal fine structure, however, was more resilient to the addition of background noise than coding of temporal envelope information. Taken together, these results demonstrate that noise places a neurophysiological constraint on speech processing during early childhood by causing a breakdown in neural processing of speech acoustics. These results may explain why some listeners have inordinate difficulties understanding speech in noise. Speech-elicited auditory-neurophysiological responses offer objective insight into listening skills during early childhood by reflecting the integrity of neural coding in quiet and noise; this paper documents typical response properties

  19. Early-Life Persistent Vitamin D Deficiency Alters Cardiopulmonary Responses to Particulate Matter-Enhanced Atmospheric Smog in Adult Mice

    EPA Science Inventory

    This study demonstrates that early-life persistent vitamin D deficiency alters the cardiopulmonary response to smog in mice and may increase risk of adverse effects. Early life nutritional deficiencies can lead to increased cardiovascular susceptibility to environme...

  20. CD8 single-cell gene coexpression reveals three different effector types present at distinct phases of the immune response

    PubMed Central

    Peixoto, António; Evaristo, César; Munitic, Ivana; Monteiro, Marta; Charbit, Alain; Rocha, Benedita; Veiga-Fernandes, Henrique

    2007-01-01

    To study in vivo CD8 T cell differentiation, we quantified the coexpression of multiple genes in single cells throughout immune responses. After in vitro activation, CD8 T cells rapidly express effector molecules and cease their expression when the antigen is removed. Gene behavior after in vivo activation, in contrast, was quite heterogeneous. Different mRNAs were induced at very different time points of the response, were transcribed during different time periods, and could decline or persist independently of the antigen load. Consequently, distinct gene coexpression patterns/different cell types were generated at the various phases of the immune responses. During primary stimulation, inflammatory molecules were induced and down-regulated shortly after activation, generating early cells that only mediated inflammation. Cytotoxic T cells were generated at the peak of the primary response, when individual cells simultaneously expressed multiple killer molecules, whereas memory cells lost killer capacity because they no longer coexpressed killer genes. Surprisingly, during secondary responses gene transcription became permanent. Secondary cells recovered after antigen elimination were more efficient killers than cytotoxic T cells present at the peak of the primary response. Thus, primary responses produced two transient effector types. However, after boosting, CD8 T cells differentiate into long-lived killer cells that persist in vivo in the absence of antigen. PMID:17485515

  1. Monitoring early phases of orthodontic treatment by means of Raman spectroscopies

    NASA Astrophysics Data System (ADS)

    d'Apuzzo, Fabrizia; Perillo, Letizia; Delfino, Ines; Portaccio, Marianna; Lepore, Maria; Camerlingo, Carlo

    2017-11-01

    Gingival crevicular fluid (GCF) is a site-specific exudate in the gingival sulcus. GCF composition changes in response to diseases or mechanical stimuli, such as those occurring during orthodontic treatments. Raman microspectroscopy (μ-RS) and surface-enhanced Raman spectroscopy (SERS) were adopted for a GCF analysis during different initial phases of orthodontic force application. GCF samples were pooled from informed patients using paper cones. SERS spectra were obtained from GCF extracted from these cones, whereas μ-RS spectra were directly acquired on paper cones without any manipulation. The spectral characteristics of the main functional groups and the changes in cytochrome, amide III, and amide I contributions were highlighted in the different phases of orthodontic treatment with both SERS and μ-RS analysis. μ-RS directly performed on the paper cones together with proper statistical methods can offer an effective approach for the development of a tool for monitoring the processes occurring during orthodontic treatments, which may help the clinician in the choice of type of treatment individually for each patient and accelerate and improve the orthodontic therapy.

  2. Leaders' and followers' individual experiences during the early phase of simulation-based team training: an exploratory study.

    PubMed

    Meurling, Lisbet; Hedman, Leif; Felländer-Tsai, Li; Wallin, Carl-Johan

    2013-06-01

    A growing body of evidence shows that team training can develop essential team skills and contribute to better patient outcomes. Current simulation-based team training (SBTT) programmes most often include targets and feedback focused on the whole team and/or leader, ignoring the follower as a unique entity. By considering followers' individual experiences, and tailoring behavioural targets for training and feedback, SBTT could be improved. Our aim was to explore the individual experiences and behaviours of leaders and followers during the early phase of SBTT, and we hypothesised that leaders and followers would show different responses. Medical students (n=54) participated in half-day SBTT including three video-recorded scenarios. Self-efficacy was assessed pretraining and post-training. For each scenario (n=36), the individual teamwork behaviours, concentration, mental strain and the team's clinical performance were recorded. Data were analysed using a mixed model allowing for participants to be their own control in their roles as leader or follower. Self-efficacy improved. In the role of leader, participants communicated to a greater extent and experienced higher mental strain and concentration than they did in the role of follower. The increased self-efficacy enables a positive learning outcome after only three scenarios. Individual experiences and behaviours differed between the role of leader and that of follower. By shedding further light on leaders' and followers' individual experiences and behaviours, targets for training and feedback could be specified in order to improve SBTT.

  3. Population Response Profiles in Early Visual Cortex Are Biased in Favor of More Valuable Stimuli

    PubMed Central

    Saproo, Sameer

    2010-01-01

    Voluntary and stimulus-driven shifts of attention can modulate the representation of behaviorally relevant stimuli in early areas of visual cortex. In turn, attended items are processed faster and more accurately, facilitating the selection of appropriate behavioral responses. Information processing is also strongly influenced by past experience and recent studies indicate that the learned value of a stimulus can influence relatively late stages of decision making such as the process of selecting a motor response. However, the learned value of a stimulus can also influence the magnitude of cortical responses in early sensory areas such as V1 and S1. These early effects of stimulus value are presumed to improve the quality of sensory representations; however, the nature of these modulations is not clear. They could reflect nonspecific changes in response amplitude associated with changes in general arousal or they could reflect a bias in population responses so that high-value features are represented more robustly. To examine this issue, subjects performed a two-alternative forced choice paradigm with a variable-interval payoff schedule to dynamically manipulate the relative value of two stimuli defined by their orientation (one was rotated clockwise from vertical, the other counterclockwise). Activation levels in visual cortex were monitored using functional MRI and feature-selective voxel tuning functions while subjects performed the behavioral task. The results suggest that value not only modulates the relative amplitude of responses in early areas of human visual cortex, but also sharpens the response profile across the populations of feature-selective neurons that encode the critical stimulus feature (orientation). Moreover, changes in space- or feature-based attention cannot easily explain the results because representations of both the selected and the unselected stimuli underwent a similar feature-selective modulation. This sharpening in the population

  4. Media Messages and Perceptions of the Affordable Care Act during the Early Phase of Implementation.

    PubMed

    Fowler, Erika Franklin; Baum, Laura M; Barry, Colleen L; Niederdeppe, Jeff; Gollust, Sarah E

    2017-02-01

    Public opinion about the Affordable Care Act (ACA) has been polarized since the law's passage. Past research suggests these conditions would make any media influence on the public limited at best. However, during the early phase of implementation, locally broadcast ACA-related media messages-in the form of paid health insurance and political advertisements and news media stories-abounded as advocates, insurance marketers, and politicians sought to shape the public's perceptions of the law. To what extent did message exposure affect ACA perceptions during the first open enrollment period? We merge data on volumes of messaging at the media market level with nationally representative survey data to examine the relationship between estimated exposure to media messaging and the public's perceptions of how informed they were about and favorable toward the ACA in October 2013. We find that higher volumes of insurance advertising and local news coverage are associated with participants' perceptions of being informed about the law. Volumes of insurance advertising and of local news coverage are also associated with participants' favorability toward the law, but the relationship varies with partisanship, supporting the growing body of research describing partisan perceptual bias. Copyright © 2017 by Duke University Press.

  5. Beam-induced pressure gradients in the early phase of proton-heated solar flares

    NASA Technical Reports Server (NTRS)

    Tamres, David H.; Canfield, Richard C.; Mcclymont, A. N.

    1986-01-01

    The pressure gradient induced in a coronal loop by proton beam momentum deposition is calculated and compared with the thermal pressure gradient arising from nonuniform deposition of beam energy; it is assumed that the transfer of momentum and energy from beam to target occurs via the Coulomb interaciton. Results are presented for both a low mean energy and a high mean energy proton beam injected at the loop apex and characterized by a power-law energy spectrum. The present treatment takes account of the breakdown of the cold target approximation for the low-energy proton beam in the corona, where the thermal speed of target electrons exceeds the beam speed. It is found that proton beam momentum deposition plays a potentially significant role in flare dynamics only in the low mean energy case and only in the corona, where it may dominate the acceleration of target material for as long as several tens of seconds. This conclusion suggest that the presence of low-energy nonthermal protons may be inferred from velocity-sensitive coronal observations in the early impulsive phase.

  6. Improved healing of extraperitoneal intestinal anastomoses in the early phase when surrounded by omentum.

    PubMed

    Pierie, J P; de Graaf, P W; van Dijk, M; Renooij, W; van Vroonhoven, T J; Obertop, H

    2000-01-01

    The extra-anatomical position of a cervical oesophagogastrostomy is a reason for impaired anastomotic healing, but transposition of the omentum that is covered with mesothelial cells may be a way to improve that. This hypothesis was tested in a rat model. An end-to-end jejuno-jejunostomy was placed subcutaneously in group I (n = 29), subcutaneously surrounded by omentum in group II (n = 29) and intra-abdominally surrounded by omentum in group III (n = 20). After 3, 7 or 14 days, the rats were sacrificed and bursting pressure (BP) of the anastomosis or jejunum was measured and the hydroxyproline (HP) level was determined. In group I 5/29, in group II 2/29 and in group III 0/20 rats died following anastomotic leakage (nonsignificant) and were excluded from other measurements. BP was decreased after 3 days in group I (60+/-9 mm Hg) compared with group II (101+/-8 mm Hg) and group III (107+/-11 mm Hg) (p = 0.002). After 7 days, BP in groups I (122+/-10 mm Hg) and II (132+/-10 mm Hg) were lower as compared with group III (230+/-8 mm Hg) (p<0.001). Differences in HP levels were not statistically significant between the groups after 3, 7 and 14 days. The healing of intestinal anastomoses in an extraperitoneal position is improved in the early phase only when surrounded by omentum. Copyright 2000 S. Karger AG, Basel

  7. Assessing gut microbiota perturbations during the early phase of infectious diarrhea in Vietnamese children

    PubMed Central

    Florez de Sessions, Paola; Jie, Song; Pham Thanh, Duy; Thompson, Corinne N.; Nguyen Ngoc Minh, Chau; Chu, Collins Wenhan; Tran, Tuan-Anh; Thomson, Nicholas R.; Thwaites, Guy E.; Rabaa, Maia A.; Hibberd, Martin; Baker, Stephen

    2018-01-01

    ABSTRACT Diarrheal diseases remain the second most common cause of mortality in young children in developing countries. Efforts have been made to explore the impact of diarrhea on bacterial communities in the human gut, but a thorough understanding has been impeded by inadequate resolution in bacterial identification and the examination of only few etiological agents. Here, by profiling an extended region of the 16S rRNA gene in the fecal microbiome, we aimed to elucidate the nature of gut microbiome perturbations during the early phase of infectious diarrhea caused by various etiological agents in Vietnamese children. Fecal samples from 145 diarrheal cases with a confirmed infectious etiology before antimicrobial therapy and 54 control subjects were analyzed. We found that the diarrheal fecal microbiota could be robustly categorized into 4 microbial configurations that either generally resembled or were highly divergent from a healthy state. Factors such as age, nutritional status, breastfeeding, and the etiology of the infection were significantly associated with these microbial community structures. We observed a consistent elevation of Fusobacterium mortiferum, Escherichia, and oral microorganisms in all diarrheal fecal microbiome configurations, proposing similar mechanistic interactions, even in the absence of global dysbiosis. We additionally found that Bifidobacterium pseudocatenulatum was significantly depleted during dysenteric diarrhea regardless of the etiological agent, suggesting that further investigations into the use of this species as a dysentery-orientated probiotic therapy are warranted. Our findings contribute to the understanding of the complex influence of infectious diarrhea on gut microbiome and identify new opportunities for therapeutic interventions. PMID:28767339

  8. Temporal Genetic Dynamics of an Invasive Species, Frankliniella occidentalis (Pergande), in an Early Phase of Establishment.

    PubMed

    Yang, Xian-Ming; Lou, Heng; Sun, Jing-Tao; Zhu, Yi-Ming; Xue, Xiao-Feng; Hong, Xiao-Yue

    2015-07-03

    Many species can successfully colonize new areas despite their propagules having low genetic variation. We assessed whether the decreased genetic diversity could result in temporal fluctuations of genetic parameters of the new populations of an invasive species, western flower thrips, Frankliniella occidentalis, using mitochondrial and microsatellite markers. This study was conducted in eight localities from four climate regions in China, where F. occidentalis was introduced in the year 2000 and had lower genetic diversity than its native populations. We also tested the level of genetic differentiation in these introduced populations. The genetic diversity of the samples at different years in the same locality was not significantly different from each other in most localities. FST and STRUCTURE analysis also showed that most temporal population comparisons from the same sites were not significantly differentiated. Our results showed that the invasive populations of F. occidentalis in China can maintain temporal stability in genetic composition at an early phase of establishment despite having lower genetic diversity than in their native range.

  9. Temporal Genetic Dynamics of an Invasive Species, Frankliniella occidentalis (Pergande), in an Early Phase of Establishment

    PubMed Central

    Yang, Xian-Ming; Lou, Heng; Sun, Jing-Tao; Zhu, Yi-Ming; Xue, Xiao-Feng; Hong, Xiao-Yue

    2015-01-01

    Many species can successfully colonize new areas despite their propagules having low genetic variation. We assessed whether the decreased genetic diversity could result in temporal fluctuations of genetic parameters of the new populations of an invasive species, western flower thrips, Frankliniella occidentalis, using mitochondrial and microsatellite markers. This study was conducted in eight localities from four climate regions in China, where F. occidentalis was introduced in the year 2000 and had lower genetic diversity than its native populations. We also tested the level of genetic differentiation in these introduced populations. The genetic diversity of the samples at different years in the same locality was not significantly different from each other in most localities. FST and STRUCTURE analysis also showed that most temporal population comparisons from the same sites were not significantly differentiated. Our results showed that the invasive populations of F. occidentalis in China can maintain temporal stability in genetic composition at an early phase of establishment despite having lower genetic diversity than in their native range. PMID:26138760

  10. The early phase of the SMBH-galaxy coevolution in low-z "young" galaxies

    NASA Astrophysics Data System (ADS)

    Nagao, Tohru

    2014-01-01

    It is now widely recognized that most galaxies have a supermassive black hole (SMBH) in their nucleus, and the evolution of SMBHs is closely related with that of their host galaxies (the SMBH-galaxy coevolution). This is suggested by the correlation in the mass of SMBHs and their host galaxies, that has been observed in low redshifts. However, the physics of the coevolution is totally unclear, that prevents us from complete understandings of the galaxy evolution. One possible strategy to tackle this issue is measuring the mass ratio between SMBHs and their host galaxies (M_BH/M_host) at high redshifs, since different scenarios predict different evolution of the ratio ofMBH/Mhost. However it is extremely challenging to measure the mass of the host of high-z quasars, given the faint surface brightness of the host at close to the glaring quasar nucleus. Here we propose a brand-new approach to assess the early phase of the SMBH-galaxy coevolution, by focusing on low-z AGN-hosting "young" galaxies. Specifically, we focus on some very metal-poor galaxies with broadline Balmer lines at z ~ 0.1 - 0.3. By examining the SMBH scaling relations in some low-z metal-poor AGNs through high-resolution IRCS imaging observations, we will discriminate various scenarios for the SMBH-galaxy coevolution.

  11. Pokemon proto-oncogene in oral cancer: potential role in the early phase of tumorigenesis.

    PubMed

    Sartini, D; Lo Muzio, L; Morganti, S; Pozzi, V; Di Ruscio, G; Rocchetti, R; Rubini, C; Santarelli, A; Emanuelli, M

    2015-05-01

    Oral squamous cell carcinoma (OSCC) represents about 90% of all oral neoplasms with a poor clinical prognosis. To improve survival of OSCC patients, it is fundamental to understand the basic molecular mechanisms characterizing oral carcinogenesis. Dysregulation of oncogenes and tumor suppressor genes seems to play a central role in tumorigenesis, including malignant transformation of the oral cavity. We analyzed the expression levels of the pro-oncogenic transcription factor Pokemon through real-time PCR, Western blot and immunohistochemistry in tumor, and normal oral tissue samples obtained from 22 patients with OSCC. The relationship between tumor characteristics and the level of Pokemon intratumor expression was also analyzed. Pokemon was significantly downregulated in OSCC. In particular, both mRNA and protein levels (tumor vs normal tissue) inversely correlated with histological grading, suggesting its potential role as a prognostic factor for OSCC. Moreover, a significant inverse correlation was found between Pokemon protein expression levels (OSCC vs normal oral mucosa) and tumor size, supporting the hypothesis that Pokemon could play an important role in the early phase of tumor expansion. This work shows that reduced expression of Pokemon is a peculiar feature of OSCC. Additional studies may establish the effective role of Pokemon in oral tumorigenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Webcam delivery of the Lidcombe program for early stuttering: a phase I clinical trial.

    PubMed

    O'Brian, Sue; Smith, Kylie; Onslow, Mark

    2014-06-01

    The Lidcombe Program is an operant treatment for early stuttering shown with meta-analysis to have a favorable odds ratio. However, many clients are unable to access the treatment because of distance and lifestyle factors. In this Phase I trial, we explored the potential efficacy, practicality, and viability of an Internet webcam Lidcombe Program service delivery model. Participants were 3 preschool children who stuttered and their parents, all of whom received assessment and treatment using webcam in their homes with no clinic attendance. At 6 months post-Stage 1 completion, all children were stuttering below 1.0% syllables stuttered. The webcam intervention was acceptable to the parents and appeared to be practical and viable, with only occasional audiovisual problems. At present, there is no reason to doubt that a webcam-delivered Lidcombe Program will be shown with clinical trials to have comparable efficacy with the clinic version. Webcam-delivered Lidcombe Program intervention is potentially efficacious, is practical and viable, and requires further exploration with comparative clinical trials and a qualitative study of parent and caregiver experiences.

  13. Biomarkers for identifying the early phases of osteoarthritis secondary to medial patellar luxation in dogs.

    PubMed

    Alam, Md Rafiqul; Ji, Joong Ryong; Kim, Min Su; Kim, Nam Soo

    2011-09-01

    The levels of tartrate resistant acid phosphatase (TRAP), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in synovial fluid (SF) and serum in cases of canine osteoarthritis (OA) were measured. OA was induced by a surgically-created medial patellar luxation in the left stifle of 24 dogs. SF and blood samples were collected at 1.5- and 3-month intervals, respectively. Every 3 months, one dog was euthanatized to collect tissue samples from both stifles. TRAP levels in SF and serum were measured using a spectrophotometer, and TRAP-positive cells in joint tissues were identified by enzyme histochemistry. MMP-2 and TIMP-2 in SF and serum were detected by Western blotting and ELISA, respectively. TRAP in SF from the stifles and serum was significantly increased (p < 0.05) after 3 months. TIMP-2 in SF and serum was significantly decreased (p < 0.05), whereas MMP-2 in SF was significantly increased (p < 0.05) during the progression of OA. Histochemistry revealed an increased number of TRAP-positive cells in tissues from OA-affected joints. Assays measuring TRAP, MMP-2, and TIMP-2 in SF and serum, and methods that detect increased numbers of TRAP-positive cells in the joint tissues can play an important role in identifying the early phases of degenerative changes in canine joint components.

  14. Assessing gut microbiota perturbations during the early phase of infectious diarrhea in Vietnamese children.

    PubMed

    The, Hao Chung; Florez de Sessions, Paola; Jie, Song; Pham Thanh, Duy; Thompson, Corinne N; Nguyen Ngoc Minh, Chau; Chu, Collins Wenhan; Tran, Tuan-Anh; Thomson, Nicholas R; Thwaites, Guy E; Rabaa, Maia A; Hibberd, Martin; Baker, Stephen

    2018-01-02

    Diarrheal diseases remain the second most common cause of mortality in young children in developing countries. Efforts have been made to explore the impact of diarrhea on bacterial communities in the human gut, but a thorough understanding has been impeded by inadequate resolution in bacterial identification and the examination of only few etiological agents. Here, by profiling an extended region of the 16S rRNA gene in the fecal microbiome, we aimed to elucidate the nature of gut microbiome perturbations during the early phase of infectious diarrhea caused by various etiological agents in Vietnamese children. Fecal samples from 145 diarrheal cases with a confirmed infectious etiology before antimicrobial therapy and 54 control subjects were analyzed. We found that the diarrheal fecal microbiota could be robustly categorized into 4 microbial configurations that either generally resembled or were highly divergent from a healthy state. Factors such as age, nutritional status, breastfeeding, and the etiology of the infection were significantly associated with these microbial community structures. We observed a consistent elevation of Fusobacterium mortiferum, Escherichia, and oral microorganisms in all diarrheal fecal microbiome configurations, proposing similar mechanistic interactions, even in the absence of global dysbiosis. We additionally found that Bifidobacterium pseudocatenulatum was significantly depleted during dysenteric diarrhea regardless of the etiological agent, suggesting that further investigations into the use of this species as a dysentery-orientated probiotic therapy are warranted. Our findings contribute to the understanding of the complex influence of infectious diarrhea on gut microbiome and identify new opportunities for therapeutic interventions.

  15. Masks as Self-Study. Challenging and Sustaining Teachers' Personal and Professional Personae in Early-Mid Career Life Phases

    ERIC Educational Resources Information Center

    Leitch, Ruth

    2010-01-01

    Drawing on previous research identifying how teachers' capacities to sustain their effectiveness in different phases of their professional lives are affected positively and/or negatively by their sense of identity, this paper illuminates three early-mid career teachers' self-study inquiries, centring on mask work. The creative development of…

  16. 78 FR 69690 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... and Gene Therapy Products; Extension of Comment Period AGENCY: Food and Drug Administration, HHS...: Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products'' that... sponsors of Investigational New Drug Applications for cellular therapy (CT) and gene therapy (GT) products...

  17. 77 FR 58359 - Applications for New Awards; Race to the Top-Early Learning Challenge; Phase 2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-20

    ... amended by section 1832(b) of Division B of Pub. L. 112-10, the Department of Defense and Full-Year... DEPARTMENT OF EDUCATION DEPARTMENT OF HEALTH AND HUMAN SERVICES Applications for New Awards; Race to the Top--Early Learning Challenge; Phase 2 AGENCY: Department of Education and Department of...

  18. 77 FR 7174 - Correction Notice for Deepwater Horizon Oil Spill; Draft Phase I Early Restoration Plan and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ... DEPARTMENT OF THE INTERIOR Fish and Wildlife Service [FWS-R4-FHC-2012-N030; FVHC98130406900Y4-XXX-FF04G01000] Correction Notice for Deepwater Horizon Oil Spill; Draft Phase I Early Restoration Plan and Environmental Assessment AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of availability and request...

  19. "Crypto-Display" in Dual-Mode Metasurfaces by Simultaneous Control of Phase and Spectral Responses.

    PubMed

    Yoon, Gwanho; Lee, Dasol; Nam, Ki Tae; Rho, Junsuk

    2018-06-26

    Although conventional metasurfaces have demonstrated many promising functionalities in light control by tailoring either phase or spectral responses of subwavelength structures, simultaneous control of both responses has not been explored yet. Here, we propose a concept of dual-mode metasurfaces that enables simultaneous control of phase and spectral responses for two kinds of operation modes of transmission and reflection, respectively. In the transmission mode, the dual-mode metasurface acts as conventional metasurfaces by tailoring phase distribution of incident light. In the reflection mode, a reflected colored image is produced under white light illumination. We also experimentally demonstrate a crypto-display as one application of the dual-mode metasurface. The crypto-display looks a normal reflective display under white light illumination but generates a hologram that reveals the encrypted phase information under single-wavelength coherent light illumination. Because two operation modes do not affect each other, the crypto-display can have applications in security techniques.

  20. Contribution of Rho kinase to the early phase of the calcium-contraction coupling in airway smooth muscle.

    PubMed

    Mbikou, Prisca; Fajmut, Ales; Brumen, Milan; Roux, Etienne

    2011-02-01

    We investigated theoretically and experimentally the role of Rho kinase (RhoK) in Ca(2+)-contraction coupling in rat airways. Isometric contraction was measured on tracheal, extrapulmonary and intrapulmonary bronchial rings. Intracellular [Ca(2+)] was recorded in freshly isolated tracheal myocytes. Stimulation by carbachol (0.3 and 10 μm) and 50 mm external KCl induced a short-time, Hill-shaped contraction obtained within 90 s, followed by a sustained or an additional delayed contraction. Responses of [Ca(2+)](i) to acetylcholine consisted in a fast peak followed by a plateau and, in 42% of the cells, superimposed Ca(2+) oscillations. The RhoK inhibitor Y27632 (10 μm) did not alter the [Ca(2+)](i) response. Whatever the agonist, Y27632 did not modify the basal tension but decreased the amplitude of the short-duration response, without altering the additional delayed contraction. The Myosin Light Chain Phosphatase (MLCP) inhibitor calyculin A increased the basal tension and abolished the effect of RhoK. KN93 (Ca(2+)-calmodulin-dependent protein kinase II inhibitor) and DIDS (inhibitor of Ca(2+)-activated Cl(-) channels) had no influence on the RhoK effect. We built a theoretical model of Ca(2+)-dependent active/inactive RhoK ratio and subsequent RhoK-dependent MLCP inactivation, which was further coupled with a four-state model of the contractile apparatus and Ca(2+)-dependent MLCK activation. The model explains the time course of the short-duration contraction and the role of RhoK by Ca(2+)-dependent activation of MLCK and RhoK, which inactivates MLCP. Oscillatory and non-oscillatory [Ca(2+)](i) responses result in a non-oscillatory contraction, the amplitude of which is encoded by the plateau value and oscillation frequency. In conclusion, Ca(2+)-dependent but CaMK II-independent RhoK activation contributes to the early phase of the contractile response via MLCP inhibition.

  1. Exploring Higher Education's Response to the Early Childhood Education Teacher Shortage

    ERIC Educational Resources Information Center

    Matczak, Melissa L.

    2017-01-01

    This qualitative single case study attempt is to explore how one institution of higher education can be responsive in meeting the needs of a teacher shortage in early childhood education and the factors impacting (hindering and helping) the collaborative partner process of designing an Applied Bachelor's in Science Degree in Elementary Education…

  2. Designing a Measurement Framework for Response to Intervention in Early Childhood Programs

    ERIC Educational Resources Information Center

    McConnell, Scott R.; Wackerle-Hollman, Alisha K.; Roloff, Tracy A.; Rodriguez, Michael

    2014-01-01

    The overall architecture and major components of a measurement system designed and evaluated to support Response to Intervention (RTI) in the areas of language and literacy in early childhood programs are described. Efficient and reliable measurement is essential for implementing any viable RTI system, and implementing such a system in early…

  3. Effectiveness of Community-Based Early Intervention Based on Pivotal Response Treatment

    ERIC Educational Resources Information Center

    Smith, Isabel M.; Flanagan, Helen E.; Garon, Nancy; Bryson, Susan E.

    2015-01-01

    Preschoolers (n = 118) with autism spectrum disorder (ASD) participated in this prospective effectiveness study of an early intervention program. Treatment entailed parent training and therapist-implemented components, incorporating Pivotal Response Treatment and Positive Behaviour Support. Standardized ability and behavioural measures were…

  4. The Confluence of Adverse Early Experience and Puberty on the Cortisol Awakening Response

    ERIC Educational Resources Information Center

    Quevedo, Karina; Johnson, Anna E.; Loman, Michelle L.; LaFavor, Theresa L.; Gunnar, Megan

    2012-01-01

    Associations between early deprivation/neglect in the form of institutional care with the cortisol awakening response (CAR) were examined as a function of pubertal status among 12- and 13-year-old postinstitutionalized youth. CARs indexed hypothalamic-pituitary-adrenocortical reactivity. Postinstitutionalized youth were compared to youth adopted…

  5. Early Detection Rapid Response Program Targets New Noxious Weed Species in Washington State

    ERIC Educational Resources Information Center

    Andreas, Jennifer E.; Halpern, Alison D.; DesCamp, Wendy C.; Miller, Timothy W.

    2015-01-01

    Early detection, rapid response is a critical component of invasive plant management. It can be challenging, however, to detect new invaders before they become established if landowners cannot identify species of concern. In order to increase awareness, eye-catching postcards were developed in Washington State as part of a noxious weed educational…

  6. Caregiver Responsiveness during Preschool Supports Cooperation in Kindergarten: Moderation by Children's Early Compliance

    ERIC Educational Resources Information Center

    Pratt, Megan E.; Lipscomb, Shannon T.; McClelland, Megan M.

    2016-01-01

    Research Findings: The current study examined how children's parent-reported compliance at age 3 (36 months) moderated the effects of 2 dimensions of directly observed early care and education (ECE) process quality (positivity/responsivity and cognitive stimulation) during the prekindergarten year (54 months) on teacher reports of children's…

  7. Psychosocial Responses During Different Phases of Sport-Injury Rehabilitation: A Qualitative Study

    PubMed Central

    Clement, Damien; Arvinen-Barrow, Monna; Fetty, Tera

    2015-01-01

    Context: Athletic trainers have traditionally conceptualized rehabilitation programs in terms of 3 distinct physiologic phases; however, these phases appear to neglect athletes' psychosocial responses to their injuries. Objective: To document injured athletes' psychosocial responses during the different phases of injury rehabilitation. Design: Qualitative study. Setting: National Collegiate Athletic Association Division II university in the mid-Atlantic region of the United States. Patients or Other Participants: A total of 8 previously injured athletes (4 men and 4 women) participated in the study. Data Collection and Analysis: We collected participant data by using semistructured interviews, transcribed verbatim and analyzed by directed content analysis. Established themes were triangulated to determine trustworthiness. Results: Initially, athletes' cognitive appraisals were predominately negative in nature, leading to negative emotions. These appraisals changed after diagnosis and when moving to the reaction-to-rehabilitation phase and the reaction-to-sport phase. During the reaction-to-rehabilitation phase, athletes reported mixed cognitive appraisals and identified frustration as the main emotional response. When returning to sport, athletes reflected on the lessons learned, yet they expressed some doubts related to their ability to return to play. These cognitive appraisals served as a precursor to the resulting emotional responses of nervousness and reinjury anxiety, as well as excitement. Throughout the various phases of rehabilitation, athletes reported seeking out social support: initially from significant others and then from their athletic trainers during the reaction-to-rehabilitation phase. Conclusions: The results appear to support the use of the integrated model of psychological response to sport injury and the rehabilitation process and the 3 phases of rehabilitation as a framework for understanding how physical and psychosocial factors may

  8. Development of Phase Locking and Frequency Representation in the Infant Frequency-Following Response

    ERIC Educational Resources Information Center

    Van Dyke, Katlyn B.; Lieberman, Rachel; Presacco, Alessandro; Anderson, Samira

    2017-01-01

    Purpose: This study investigates the development of phase locking and frequency representation in infants using the frequency-following response to consonant-vowel syllables. Method: The frequency-following response was recorded in 56 infants and 15 young adults to 2 speech syllables (/ba/ and /ga/), which were presented in randomized order to the…

  9. 40 CFR 35.6570 - Use of the same engineer during subsequent phases of response.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Use of the same engineer during... Agreement § 35.6570 Use of the same engineer during subsequent phases of response. (a) If the public notice... CERCLA remedial response Cooperative Agreement may use the engineer procured to conduct any or all of the...

  10. 40 CFR 35.6570 - Use of the same engineer during subsequent phases of response.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Use of the same engineer during... Agreement § 35.6570 Use of the same engineer during subsequent phases of response. (a) If the public notice... CERCLA remedial response Cooperative Agreement may use the engineer procured to conduct any or all of the...

  11. 40 CFR 35.6570 - Use of the same engineer during subsequent phases of response.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Use of the same engineer during... Agreement § 35.6570 Use of the same engineer during subsequent phases of response. (a) If the public notice... CERCLA remedial response Cooperative Agreement may use the engineer procured to conduct any or all of the...

  12. Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

    PubMed

    McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J

    2015-01-15

    Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights

  13. Cardiovascular response to short-term fasting in menstrual phases in young women: an observational study.

    PubMed

    Ohara, Kumiko; Okita, Yoshimitsu; Kouda, Katsuyasu; Mase, Tomoki; Miyawaki, Chiemi; Nakamura, Harunobu

    2015-08-28

    Menstrual cycle-related symptoms are an important health issue for many women, and some may affect cardiac autonomic regulation. In the present study, we evaluated the cardiovascular and physiological stress response to 12-h short-term fasting in the menstrual phases of healthy young women. We performed a randomized crossover study. Subjects were seven female university students (age: 22.3 ± 1.0 years). The experiments comprised four sessions: meal intake in the follicular phase, meal intake in the luteal phase, fasting in the follicular phase, and fasting in the luteal phase. All subjects participated in a total of four experimental sessions during two successive phases (follicular and luteal phase in the same menstrual cycle, or luteal phase and follicular phase in the next menstrual cycle) according to a randomized crossover design. R-R intervals were continuously recorded before and after meals, and power spectral analysis of heart rate variability was performed. Other physiological data were obtained before and 20, 40, 60, and 80 min after meal intake or after the corresponding time point of meal intake (fasting in the follicular or luteal phase). Heart rate decreased during fasting in the follicular and luteal phases. High frequency power increased during fasting in the follicular and luteal phases. In addition, salivary cortisol concentrations decreased during fasting in the luteal phase. In the present study, short-term fasting resulted in higher parasympathetic activity and lower cortisol levels in the luteal phase in these young women. These results indicate a possibility to produce an anti-stress effect in the luteal phase, which may reduce menstrual symptoms.

  14. The NRF2-KEAP1 Pathway Is an Early Responsive Gene Network in Arsenic Exposed Lymphoblastoid Cells

    PubMed Central

    Córdova, Emilio J.; Martínez-Hernández, Angélica; Uribe-Figueroa, Laura; Centeno, Federico; Morales-Marín, Mirna; Koneru, Harsha; Coleman, Matthew A.; Orozco, Lorena

    2014-01-01

    Inorganic arsenic (iAs), a major environmental contaminant, has risen as an important health problem worldwide. More detailed identification of the molecular mechanisms associated with iAs exposure would help to establish better strategies for prevention and treatment. Although chronic iAs exposures have been previously studied there is little to no information regarding the early events of exposure to iAs. To better characterize the early mechanisms of iAs exposure we conducted gene expression studies using sublethal doses of iAs at two different time-points. The major transcripts differentially regulated at 2 hrs of iAs exposure included antioxidants, detoxificants and chaperones. Moreover, after 12 hrs of exposure many of the down-regulated genes were associated with DNA replication and S phase cell cycle progression. Interestingly, the most affected biological pathway by both 2 or 12 hrs of iAs exposure were the Nrf2-Keap1 pathway, represented by the highly up-regulated HMOX1 transcript, which is transcriptionally regulated by the transcription factor Nrf2. Additional Nrf2 targets included SQSTM1 and ABCB6, which were not previously associated with acute iAs exposure. Signalling pathways such as interferon, B cell receptor and AhR route were also responsive to acute iAs exposure. Since HMOX1 expression increased early (20 min) and was responsive to low iAs concentrations (0.1 µM), this gene could be a suitable early biomarker for iAs exposure. In addition, the novel Nrf2 targets SQSTM1 and ABCB6 could play an important and previously unrecognized role in cellular protection against iAs. PMID:24516582

  15. Examination of a modified cell cycle synchronization method and bovine nuclear transfer using synchronized early G1 phase fibroblast cells.

    PubMed

    Urakawa, Manami; Ideta, Atsushi; Sawada, Tokihiko; Aoyagi, Yoshito

    2004-08-01

    Somatic cell nuclear transfer has a low success rate, due to a high incidence of fetal loss and increased perinatal morbidity/mortality. One factor that may affect the successful development of nuclear transfer embryos is the cell cycle stage of the donor cell. In order to establish a cell cycle synchronization method that can consistently produce cloned embryos and offspring, we examined the effects of different combinations of three cell treatments on the recovery rate of mitotic phase cells using bovine fetal fibroblasts. In the first experiment, we examined the recovery rate of mitotic phase cells by a combination of treatment with a metaphase arrestant (1 microM 2-methoxyestradiol), shaking the plate and selecting cells with a diameter of 20 microns. As a result, 99% of mitotic phase cells were recovered by repeating the combined treatment of metaphase arrestant and shaking, and collection of cells with a specific diameter. In the second experiment, nuclear transfer was carried out using early G1 phase cells by choosing pairs of bridged cells derived from mitotic phase cells recovered by the combined treatment of 1 microM 2-methoxyestradiol and shaking, and collection of cells with a diameter of 20 microns. The reconstructed embryos were transferred to recipient heifers to determine post-implantation development. Development of embryos reconstructed from early G1 phase cells from the >/=6 cells stage on Day 3 to the morula-blastocyst stage on Day 6 was 100%. Ten blastocysts constructed from two cell lines were transferred into 10 recipient heifers. Nine of the 10 recipients delivered single live calves. In conclusion, mitotic phase bovine fibroblast cells were easily recovered by the combined treatments of 1 microM 2-methoxyestradiol, shaking, and selecting cells of the appropriate diameter. Furthermore, nuclear transfer using cells in the early G1 phase as donor cells gave a high rate of offspring production.

  16. Atlantic Deep-water Response to the Early Pliocene Shoaling of the Central American Seaway.

    PubMed

    Bell, David B; Jung, Simon J A; Kroon, Dick; Hodell, David A; Lourens, Lucas J; Raymo, Maureen E

    2015-07-20

    The early Pliocene shoaling of the Central American Seaway (CAS), ~4.7-4.2 million years ago (mega annum-Ma), is thought to have strengthened Atlantic Meridional Overturning Circulation (AMOC). The associated increase in northward flux of heat and moisture may have significantly influenced the evolution of Pliocene climate. While some evidence for the predicted increase in North Atlantic Deep Water (NADW) formation exists in the Caribbean and Western Atlantic, similar evidence is missing in the wider Atlantic. Here, we present stable carbon (δ(13)C) and oxygen (δ(18)O) isotope records from the Southeast Atlantic-a key region for monitoring the southern extent of NADW. Using these data, together with other δ(13)C and δ(18)O records from the Atlantic, we assess the impact of the early Pliocene CAS shoaling phase on deep-water circulation. We find that NADW formation was vigorous prior to 4.7 Ma and showed limited subsequent change. Hence, the overall structure of the deep Atlantic was largely unaffected by the early Pliocene CAS shoaling, corroborating other evidence that indicates larger changes in NADW resulted from earlier and deeper shoaling phases. This finding implies that the early Pliocene shoaling of the CAS had no profound impact on the evolution of climate.

  17. Atlantic Deep-water Response to the Early Pliocene Shoaling of the Central American Seaway

    PubMed Central

    Bell, David B.; Jung, Simon J. A.; Kroon, Dick; Hodell, David A.; Lourens, Lucas J.; Raymo, Maureen E.

    2015-01-01

    The early Pliocene shoaling of the Central American Seaway (CAS), ~4.7–4.2 million years ago (mega annum-Ma), is thought to have strengthened Atlantic Meridional Overturning Circulation (AMOC). The associated increase in northward flux of heat and moisture may have significantly influenced the evolution of Pliocene climate. While some evidence for the predicted increase in North Atlantic Deep Water (NADW) formation exists in the Caribbean and Western Atlantic, similar evidence is missing in the wider Atlantic. Here, we present stable carbon (δ13C) and oxygen (δ18O) isotope records from the Southeast Atlantic-a key region for monitoring the southern extent of NADW. Using these data, together with other δ13C and δ18O records from the Atlantic, we assess the impact of the early Pliocene CAS shoaling phase on deep-water circulation. We find that NADW formation was vigorous prior to 4.7 Ma and showed limited subsequent change. Hence, the overall structure of the deep Atlantic was largely unaffected by the early Pliocene CAS shoaling, corroborating other evidence that indicates larger changes in NADW resulted from earlier and deeper shoaling phases. This finding implies that the early Pliocene shoaling of the CAS had no profound impact on the evolution of climate. PMID:26193070

  18. [Health threats and health system crises. An approach to early warning and response. 2008 SESPAS Report].

    PubMed

    Simón Soria, Fernando; Guillén Enríquez, Francisco Javier

    2008-04-01

    The world is changing more and faster than ever before. New diseases are coming to light each year, controlled diseases are reemerging as potential threats, and natural or man-made disasters are increasingly affecting human health. The "International Health Regulations (2005)" reflect the changes in the response of public health to this new situation. Surveillance of specific diseases and predefined control measures have been replaced by surveillance of public health events of international concern and control measures adapted to each situation. The public health events of international interest are characterized by their seriousness, predictability, the risk of international spread and potential for travel or trade restrictions. The development of the European Early Warning and Response System in 1998 and the creation of the European Center for Disease Prevention and Control in 2005 demonstrate political commitment in Europe, with early detection of and response to public health threats. However, timely risk evaluation and response at a national level requires improved data digitalization and accessibility, automatic notification processes, data analysis and dissemination of information, the combination of information from multiple sources and adaptation of public health services. The autonomous regions in Spain are initiating this adaptation process, but interoperability between systems and the development of guidelines for a coordinated response should be steered by the National Interregional Health Council and coordinated by the Ministry of Health. Efficient early warning systems of health threats that allow for a timely response and reduce uncertainty about information would help to minimize the risk of public health crises. The profile of public health threats is nonspecific. Early detection of threats requires access to information from multiple sources and efficient risk assessment. Key factors for improving the response to public health threats are the

  19. White matter changes in early phase schizophrenia and cannabis use: an update and systematic review of diffusion tensor imaging studies.

    PubMed

    Cookey, Jacob; Bernier, Denise; Tibbo, Philip G

    2014-07-01

    The impact of cannabis use on the brain tissue is still unclear, both in the healthy developing brain and in people with schizophrenia. The focus of this review is on white matter, the primary connective infrastructure of the brain. We systematically reviewed diffusion tensor imaging (DTI) studies of early phase schizophrenia (illness effect), of cannabis use in otherwise healthy brains (drug effect), and of early phase schizophrenia with cannabis use (combined effects). Studies had to include a healthy, non-cannabis using, control group as well as report on fractional anisotropy as it is the most commonly used DTI index. We excluded cohorts with heavy alcohol or illicit drug use and studies with a sample size of less than 20 in the clinical group. We retained 17 studies of early phase schizophrenia, which together indicate deficits in white matter integrity observed in all fiber tract families, but most frequently in association, callosal and projection fibers. In otherwise healthy cannabis users (2 studies), deficits in white matter tracts were reported mainly in callosal fibers, but also in projection and limbic fibers. In cannabis users with early phase schizophrenia (1 study), deficits in white matter integrity were also observed in all fiber tract families, except for limbic fibers. The current literature points to several families of white matter tracts being differentially affected in early phase schizophrenia. Further work is required to reveal the impact of cannabis use in otherwise healthy people as well as those with schizophrenia. Paucity of available studies as well as restricting analysis to FA values represent the main limitations of this review. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Advances in Understanding Stimulus Responsive Phase Behavior of Intrinsically Disordered Protein Polymers.

    PubMed

    Ruff, Kiersten M; Roberts, Stefan; Chilkoti, Ashutosh; Pappu, Rohit V

    2018-06-24

    Proteins and synthetic polymers can undergo phase transitions in response to changes to intensive solution parameters such as temperature, proton chemical potentials (pH), and hydrostatic pressure. For proteins and protein-based polymers, the information required for stimulus responsive phase transitions is encoded in their amino acid sequence. Here, we review some of the key physical principles that govern the phase transitions of archetypal intrinsically disordered protein polymers (IDPPs). These are disordered proteins with highly repetitive amino acid sequences. Advances in recombinant technologies have enabled the design and synthesis of protein sequences of a variety of sequence complexities and lengths. We summarize insights that have been gleaned from the design and characterization of IDPPs that undergo thermo-responsive phase transitions and build on these insights to present a general framework for IDPPs with pH and pressure responsive phase behavior. In doing so, we connect the stimulus responsive phase behavior of IDPPs with repetitive sequences to the coil-to-globule transitions that these sequences undergo at the single chain level in response to changes in stimuli. The proposed framework and ongoing studies of stimulus responsive phase behavior of designed IDPPs have direct implications in bioengineering, where designing sequences with bespoke material properties broadens the spectrum of applications, and in biology and medicine for understanding the sequence-specific driving forces for the formation of protein-based membraneless organelles as well as biological matrices that act as scaffolds for cells and mediators of cell-to-cell communication. Copyright © 2018. Published by Elsevier Ltd.

  1. Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

    PubMed

    VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

    2016-01-01

    People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

  2. Early host response in the mammary gland after experimental Streptococcus uberis challenge in heifers.

    PubMed

    de Greeff, Astrid; Zadoks, Ruth; Ruuls, Lisette; Toussaint, Mathilda; Nguyen, Thi Kim Anh; Downing, Alison; Rebel, Johanna; Stockhofe-Zurwieden, Norbert; Smith, Hilde

    2013-06-01

    Streptococcus uberis is a highly prevalent causative agent of bovine mastitis, which leads to large economic losses in the dairy industry. The aim of this study was to examine the host response during acute inflammation after experimental challenge with capsulated Strep. uberis. Gene expression in response to Strep. uberis was compared between infected and control quarters in 3 animals. All quarters (n=16) were sampled at 16 different locations. Microarray data showed that 239 genes were differentially expressed between infected and control quarters. No differences in gene expression were observed between the different locations. Microarray data were confirmed for several genes using quantitative PCR analysis. Genes differentially expressed due to early Strep. uberis mastitis represented several stages of the process of infection: (1) pathogen recognition; (2) chemoattraction of neutrophils; (3) tissue repair mechanisms; and (4) bactericidal activity. Three different pathogen recognition genes were induced: ficolins, lipopolysaccharide binding protein, and toll-like receptor 2. Calgranulins were found to be the most strongly upregulated genes during early inflammation. By histology and immunohistochemistry, we demonstrated that changes in gene expression in response to Strep. uberis were induced both in infiltrating somatic milk cells and in mammary epithelial cells, demonstrating that the latter cell type plays a role in milk production as well as immune responsiveness. Given the rapid development of inflammation or mastitis after infection, early diagnosis of (Strep. uberis) mastitis is required for prevention of disease and spread of the pathogen. Insight into host responses could help to design immunomodulatory therapies to dampen inflammation after (early) diagnosis of Strep. uberis mastitis. Future research should focus on development of these early diagnostics and immunomodulatory components for mastitis treatment. Copyright © 2013 American Dairy Science

  3. A Very Early Rehabilitation Trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial.

    PubMed

    Langhorne, Peter; Wu, Olivia; Rodgers, Helen; Ashburn, Ann; Bernhardt, Julie

    2017-09-01

    Mobilising patients early after stroke [early mobilisation (EM)] is thought to contribute to the beneficial effects of stroke unit care but it is poorly defined and lacks direct evidence of benefit. We assessed the effectiveness of frequent higher dose very early mobilisation (VEM) after stroke. We conducted a parallel-group, single-blind, prospective randomised controlled trial with blinded end-point assessment using a web-based computer-generated stratified randomisation. The trial took place in 56 acute stroke units in five countries. We included adult patients with a first or recurrent stroke who met physiological inclusion criteria. Patients received either usual stroke unit care (UC) or UC plus VEM commencing within 24 hours of stroke. The primary outcome was good recovery [modified Rankin scale (mRS) score of 0-2] 3 months after stroke. Secondary outcomes at 3 months were the mRS, time to achieve walking 50 m, serious adverse events, quality of life (QoL) and costs at 12 months. Tertiary outcomes included a dose-response analysis. Patients, outcome assessors and investigators involved in the trial were blinded to treatment allocation. We recruited 2104 (UK, n  = 610; Australasia, n  = 1494) patients: 1054 allocated to VEM and 1050 to UC. Intervention protocol targets were achieved. Compared with UC, VEM patients mobilised 4.8 hours [95% confidence interval (CI) 4.1 to 5.7 hours; p  < 0.0001] earlier, with an additional three (95% CI 3.0 to 3.5; p  < 0.0001) mobilisation sessions per day. Fewer patients in the VEM group ( n  = 480, 46%) had a favourable outcome than in the UC group ( n  = 525, 50%) (adjusted odds ratio 0.73, 95% CI 0.59 to 0.90; p  = 0.004). Results were consistent between Australasian and UK settings. There were no statistically significant differences in secondary outcomes at 3 months and QoL at 12 months. Dose-response analysis found a consistent pattern of an improved odds of efficacy and safety outcomes in

  4. A phase response curve to single bright light pulses in human subjects

    NASA Technical Reports Server (NTRS)

    Khalsa, Sat Bir S.; Jewett, Megan E.; Cajochen, Christian; Czeisler, Charles A.

    2003-01-01

    The circadian pacemaker is differentially sensitive to the resetting effects of retinal light exposure, depending upon the circadian phase at which the light exposure occurs. Previously reported human phase response curves (PRCs) to single bright light exposures have employed small sample sizes, and were often based on relatively imprecise estimates of circadian phase and phase resetting. In the present study, 21 healthy, entrained subjects underwent pre- and post-stimulus constant routines (CRs) in dim light (approximately 2-7 lx) with maintained wakefulness in a semi-recumbent posture. The 6.7 h bright light exposure stimulus consisted of alternating 6 min fixed gaze (approximately 10 000 lx) and free gaze (approximately 5000-9000 lx) exposures. Light exposures were scheduled across the circadian cycle in different subjects so as to derive a PRC. Plasma melatonin was used to determine the phase of the onset, offset, and midpoint of the melatonin profiles during the CRs. Phase shifts were calculated as the difference in phase between the pre- and post-stimulus CRs. The resultant PRC of the midpoint of the melatonin rhythm revealed a characteristic type 1 PRC with a significant peak-to-trough amplitude of 5.02 h. Phase delays occurred when the light stimulus was centred prior to the critical phase at the core body temperature minimum, phase advances occurred when the light stimulus was centred after the critical phase, and no phase shift occurred at the critical phase. During the subjective day, no prolonged 'dead zone' of photic insensitivity was apparent. Phase shifts derived using the melatonin onsets showed larger magnitudes than those derived from the melatonin offsets. These data provide a comprehensive characterization of the human PRC under highly controlled laboratory conditions.

  5. Enhanced response to ozone exposure during the follicular phase of the menstrual cycle

    SciT

    Fox, S.D.; Adams, W.C.; Brookes, K.A.

    Exposure to ozone (O[sub 3]), a toxic component of photochemical smog, results in significant airway inflammation, respiratory discomfort, and pulmonary function impairment. These effects can be reduced via pretreatment with anti-inflammatory agents. Progesterone, a gonadal steroid, is known to reduce general inflammation in the uterine endometrium. However, it is not known whether fluctuation in blood levels of progesterone, which are experienced during the normal female menstrual cycle, could alter O[sub 3] inflammatory-induced pulmonary responses. In this study, we tested the hypothesis that young, adult females are more responsive to O[sub 3] inhalation with respect to pulmonary function impairment during theirmore » follicular (F) menstrual phase when progesterone levels are lowest that during their mid-luteal (ML) phase when progesterone levels are highest. Nine subjects with normal ovarian function were exposed in random order for 1 hour each to filtered air and to 0.30 ppm O[sub 3] in their F and ML menstrual phases. Ozone responsiveness was measured by percent change in pulmonary function from pre- to postexposure. Significant gas concentration effects (filtered air versus O[sub 3]) were observed for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV[sub 1]), and forced expiratory flow between 25 and 75% of FVC (FEF[sub 25-75]), showed a significant menstrual phase and gas concentration interaction effect, with larger decrements observed in the F menstrual phase when progesterone concentrations were significantly lower. We conclude that young, adult females appear to be more responsive to acute O[sub 3] exposure during the F phase than during the ML phase of their menstrual cycles. This difference in pulmonary function response could be related to the anti-inflammatory effects of increased progesterone concentrations during the luteal phase.« less

  6. Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression.

    PubMed

    Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

    2016-11-22

    Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.

  7. Reconstruction of early phase deformations by integrated magnetic and mesotectonic data evaluation

    NASA Astrophysics Data System (ADS)

    Sipos, András A.; Márton, Emő; Fodor, László

    2018-02-01

    Markers of brittle faulting are widely used for recovering past deformation phases. Rocks often have oriented magnetic fabrics, which can be interpreted as connected to ductile deformation before cementation of the sediment. This paper reports a novel statistical procedure for simultaneous evaluation of AMS (Anisotropy of Magnetic Susceptibility) and fault-slip data. The new method analyzes the AMS data, without linearization techniques, so that weak AMS lineation and rotational AMS can be assessed that are beyond the scope of classical methods. This idea is extended to the evaluation of fault-slip data. While the traditional assumptions of stress inversion are not rejected, the method recovers the stress field via statistical hypothesis testing. In addition it provides statistical information needed for the combined evaluation of the AMS and the mesotectonic (0.1 to 10 m) data. In the combined evaluation a statistical test is carried out that helps to decide if the AMS lineation and the mesotectonic markers (in case of repeated deformation of the oldest set of markers) were formed in the same or different deformation phases. If this condition is met, the combined evaluation can improve the precision of the reconstruction. When the two data sets do not have a common solution for the direction of the extension, the deformational origin of the AMS is questionable. In this case the orientation of the stress field responsible for the AMS lineation might be different from that which caused the brittle deformation. Although most of the examples demonstrate the reconstruction of weak deformations in sediments, the new method is readily applicable to investigate the ductile-brittle transition of any rock formation as long as AMS and fault-slip data are available.

  8. Augmentation of sensory-evoked hemodynamic response in an early Alzheimer's disease mouse model.

    PubMed

    Kim, Jinho; Jeong, Yong

    2013-01-01

    Based on enlarged blood oxygen level-dependent (BOLD) responses in cognitively normal subjects at risk for Alzheimer's disease (AD), compensatory neuronal hyperactivation has been proposed as an early marker for diagnosis of AD. The BOLD response results from neurovascular coupling, i.e., hemodynamic response induced by neuronal activity. However, there has been no evidence of task-induced increases in hemodynamic response in animal models of AD. Here, we observed an augmented hemodynamic response pattern in a transgenic AβPP(SWE)/PS1ΔE9 mouse model of AD using three in vivo imaging methods: intrinsic optical signal imaging, multi-photon laser scanning microscopy, and laser Doppler flowmetry. Sensory stimulation resulted in augmented and prolonged hemodynamic responses in transgenic mice evidenced by changes in total, oxygenated, and deoxygenated hemoglobin concentration. This difference between transgenic and wild-type mice was significant at 7 months of age when amyloid plaques and cerebral amyloid angiopathy had developed but not at younger or older ages. Correspondingly, sensory stimulation-induced pial arteriole diameter was also augmented and prolonged in transgenic mice at 7 months of age. Cerebral blood flow response in transgenic mice was augmented but not prolonged. These results are consistent with the existence of BOLD signal hyperactivation in non-demented AD-risk human subjects, supporting its potential use as an early diagnostic marker of AD.

  9. Associations between adrenocortical activity and nicotine response in female smokers by menstrual phase.

    PubMed

    Huttlin, Eileen A; Allen, Alicia M; Tosun, Nicole L; Allen, Sharon S; al'Absi, Mustafa

    2015-11-01

    Previous research suggests that menstrual phase may influence smoking-related symptomatology. The present study analyzes the relationship between menstrual phase and salivary cortisol with subjective responses to nicotine among female smokers during ad libitum smoking. We hypothesize higher cortisol levels would be associated with increased positive and decreased negative subjective responses to nicotine. We also expected that these associations would vary by menstrual phase. Females aged 18-40 who smoke at least five cigarettes/day, reported regular menstrual cycles and did not use exogenous hormones or psychotropic medications were enrolled into a controlled cross-over trial. Participants completed identical data collection procedures during follicular (F) and luteal (L) phases; including self-collected salivary cortisol samples and completion of a nicotine response lab session involving administration of nicotine nasal spray and monitoring of subjective response to nicotine via the Subjective State Scale and Visual Analog Scale. Participants (n = 116) were 29.1 ± 6.9 years old and smoked an average of 12.3 ± 5.5 cigarettes daily. During F phase, higher morning cortisol was associated with decreased negative affect (r = -0.21, p = 0.03), withdrawal (r = -0.30, p < 0.01) and increased relaxation (r = 0.24, p = 0.02) after administration of nicotine nasal spray. Conversely, during L phase, higher morning cortisol was associated with a decrease in head rush (r = -0.26, p = 0.01) and urge to smoke (r = -0.21, p = 0.04) after administration of nicotine nasal spray. Similar associations between greater diurnal cortisol variation and response to nicotine were seen. These observations indicate that cortisol may have a phase-specific association with some subjective responses to nicotine in female smokers. Additional research should explore how these relationships may influence smoking cessation efforts. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected with Paracoccidioides brasiliensis

    PubMed Central

    Lopera, Damaris; Urán-Jiménez, Martha Eugenia

    2016-01-01

    Neutrophils predominate during the acute phase of the Paracoccidioides brasiliensis infection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with 1.5 × 106 or 2 × 106 P. brasiliensis yeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis. Neutrophils from mAb-treated mice were efficiently depleted (99.04%). Eighty percent of the mice treated with the mAb and infected with 1.5 × 106 yeast cells died during the first two weeks after infection. When mice were treated and infected with 2 × 106 yeast cells, 100% of them succumbed by the first week after infection. During the acute inflammatory response significant increases in numbers of eosinophils, fungal load and levels of proinflammatory cytokines/chemokines were observed in the mAb-treated mice. We also confirmed that neutrophils are an important source of IFN-γ and IL-17. These results indicate that neutrophils are essential for protection as well as being important for regulating the early inflammatory immune response in experimental pulmonary paracoccidioidomycosis. PMID:27642235

  11. Morphology effect on the light scattering and dynamic response of polymer network liquid crystal phase modulator.

    PubMed

    Xiangjie, Zhao; Cangli, Liu; Jiazhu, Duan; Jiancheng, Zeng; Dayong, Zhang; Yongquan, Luo

    2014-06-16

    Polymer network liquid crystal (PNLC) was one of the most potential liquid crystal for submillisecond response phase modulation, which was possible to be applied in submillisecond response phase only spatial light modulator. But until now the light scattering when liquid crystal director was reoriented by external electric field limited its phase modulation application. Dynamic response of phase change when high voltage was applied was also not elucidated. The mechanism that determines the light scattering was studied by analyzing the polymer network morphology by SEM method. Samples were prepared by varying the polymerization temperature, UV curing intensity and polymerization time. The morphology effect on the dynamic response of phase change was studied, in which high voltage was usually applied and electro-striction effect was often induced. The experimental results indicate that the polymer network morphology was mainly characterized by cross linked single fibrils, cross linked fibril bundles or even both. Although the formation of fibril bundle usually induced large light scattering, such a polymer network could endure higher voltage. In contrast, although the formation of cross linked single fibrils induced small light scattering, such a polymer network cannot endure higher voltage. There is a tradeoff between the light scattering and high voltage endurance. The electro-optical properties such as threshold voltage and response time were taken to verify our conclusion. For future application, the monomer molecular structure, the liquid crystal solvent and the polymerization conditions should be optimized to generate optimal polymer network morphology.

  12. Heat inactivation of Salmonella spp. in fresh poultry compost by simulating early phase of composting process.

    PubMed

    Singh, R; Kim, J; Jiang, X

    2012-05-01

    The purpose of this study was to determine the effect of moisture on thermal inactivation of Salmonella spp. in poultry litter under optimal composting conditions. Thermal inactivation of Salmonella was studied in fresh poultry compost by simulating early phase of composting process. A mixture of three Salmonella serotypes grown in Tryptic soy broth with rifampin (TSB-R) was inoculated in fresh compost with 40 or 50% moisture at a final concentration of c. 7 log CFU g(-1). The inoculated compost was kept in an environmental chamber which was programmed to rise from room temperature to target composting temperatures in 2 days. In poultry compost with optimal moisture content (50%), Salmonella spp. survived for 96, 72 and 24 h at 50, 55 and 60°C, respectively, as compared with 264, 144 and 72 h at 50, 55 and 60°C, respectively, in compost with suboptimal moisture (40%). Pathogen decline was faster during the come-up time owing to higher ammonia volatilization. Our results demonstrated that Salmonella spp. survived longer in fresh poultry compost with suboptimal moisture of 40% than in compost with optimal moisture of 50% during thermophilic composting. High nitrogen content of the poultry compost is an additional factor contributing to Salmonella inactivation through ammonia volatilization during thermal exposure. This research validated the effectiveness of the current composting guidelines on Salmonella inactivation in fresh poultry compost. Both initial moisture level and ammonia volatilization are important factors affecting microbiological safety and quality of compost product. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

  13. Hypertensive phase and early complications after Ahmed glaucoma valve implantation with intraoperative subtenon triamcinolone acetonide.

    PubMed

    Turalba, Angela V; Pasquale, Louis R

    2014-01-01

    To evaluate intraoperative subtenon triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation. Retrospective comparative case series. Forty-two consecutive cases of uncontrolled glaucoma undergoing AGV implantation: 19 eyes receiving intraoperative subtenon TA and 23 eyes that did not receive TA. A retrospective chart review was performed on consecutive pseudophakic adult patients with uncontrolled glaucoma undergoing AGV with and without intraoperative subtenon TA injection by a single surgeon. Clinical data were collected from 42 eyes and analyzed for the first 6 months after surgery. Primary outcomes included intraocular pressure (IOP) and number of glaucoma medications prior to and after AGV implantation. The hypertensive phase (HP) was defined as an IOP measurement of greater than 21 mmHg (with or without medications) during the 6-month postoperative period that was not a result of tube obstruction, retraction, or malfunction. Postoperative complications and visual acuity were analyzed as secondary outcome measures. Five out of 19 (26%) TA cases and 12 out of 23 (52%) non-TA cases developed the HP (P=0.027). Mean IOP (14.2±4.6 in TA cases versus [vs] 14.7±5.0 mmHg in non-TA cases; P=0.78), and number of glaucoma medications needed (1.8±1.3 in TA cases vs 1.6±1.1 in the comparison group; P=0.65) were similar between both groups at 6 months. Although rates of serious complications did not differ between the groups (13% in the TA group vs 16% in the non-TA group), early tube erosion (n=1) and bacterial endophthalmitis (n=1) were noted with TA but not in the non-TA group. Subtenon TA injection during AGV implantation may decrease the occurrence of the HP but does not alter the ultimate IOP outcome and may pose increased risk of serious complications within the first 6 months of surgery.

  14. Early-phase dental students' motivations and expectations concerning the study and profession of dentistry.

    PubMed

    Lalloo, R; Ayo-Yusuf, O A; Yengopal, V

    2008-05-01

    This study investigated the career choice and aspirations of early phase dental students in the four dental schools in South Africa, namely the University of the Western Cape (UWC), University of the Witwatersrand (Wits), University of Limpopo (Medunsa) and University of Pretoria (UP). Willing participants completed a self-administered questionnaire (n=184). Motivations for entering a dentistry programme were similar across race and university, with wanting a secure job most often stated as an important factor. For a third of respondents, dentistry was not a first choice. Amongst the White students, it was a first choice for 82% compared with 59% amongst Black Africans. Expected income five-years after graduation also differed significantly across race and university, with White and UP students expecting to earn considerably higher than the others. About 36% of students were concerned about the levels of personal debt related to studying, with the White and Asian students less concerned. Those who expected lower levels of income from the profession were more concerned about personal debts. Most students planned to enter general dental practice (GDP) after community service, almost all White and Wits students expressed this intention, compared with only 35% of Black Africans and 39% of Medunsa students. Orthodontics and Maxillofacial & Oral Surgery were the most popular specialities of choice. The professional attribute "Has a friendly manner and good relationship with patients" was ranked high most often. In conclusion, career advice may not need to be tailored differently for the different racial groups. There is however a need for further investigations on how to address the concerns of financial security which may be realised by the practice of dentistry, and in particular the racial disparities observed in expectations of the profession. This study further highlights the need for government financial assistance for students from under-represented groups.

  15. Factors associated with reduced early survival in the Oxford phase III medial unicompartment knee replacement.

    PubMed

    Kuipers, Bart M; Kollen, Boudewijn J; Bots, Peter C Kaijser; Burger, Bart J; van Raay, Jos J A M; Tulp, Niek J A; Verheyen, Cees C P M

    2010-01-01

    The aim of this study was to determine the prognostic value of preoperative patellofemoral osteoarthritis, BMI and age for implant survival of unicompartmental knee arthroplasty (UKA) performed in patients meeting strict admission criteria. The data and radiographs of 437 unilateral Oxford phase III procedures (Biomet, Bridgend, UK) were analysed. All procedures were carried out or supervised by 13 specialised knee surgeons in three different hospitals. The study group comprised 437 patients with a median follow of 2.6 years (0.1-7.9). The cumulative standard case survival rate at 5 years, when there were still 101 patients at risk, was 84.7% (CI-95%: 80.1-89.3%). Young age (<60 years) was associated with a 2.2-fold increased adjusted risk of revision (CI: 1.08-4.43; p=0.03). The preoperative presence of radiological features of patellofemoral osteoarthritis was associated with a 0.3-fold reduced adjusted risk of revision (CI: 0.11-0.89; p=0.03). BMI>30 kg/m(2), gender, the surgeon performing the operation (either as an individual or categorised by annual surgical UKA caseload, i.e., more or less than 10 UKAs) and the hospital in which surgery took place did not predict implant survival of UKA. We conclude that young patients (<60 years) experience an increased early risk of revision for UKA when compared to older patients (>60 years). Obesity (BMI>30 kg/m(2)) and preoperative patellofemoral osteoarthritis are not associated with a decreased implant survival and therefore should not be considered risk factors in this context.

  16. Preterm children at early adolescence and continuity and discontinuity in maternal responsiveness from infancy.

    PubMed

    Beckwith, L; Rodning, C; Cohen, S

    1992-10-01

    Patterns in mother-child interaction from infancy to age 12 were investigated in a prospective, longitudinal study of 44 English-speaking mothers and their preterm children. Maternal responsiveness was assessed by home observations during infancy and the Family Interaction Q-Sort at age 12, derived from 2 structured laboratory situations requiring cooperation of mother and child. A cluster of maternal behaviors of critical control toward the toddler was assessed at age 2 years. Children of mothers who were consistently more responsive during both infancy and early adolescence, as well as children whose mothers became more responsive by age 12, achieved higher IQ and arithmetic scores, had more positive self-esteem, and their teachers reported fewer behavioral and emotional problems than children of mothers who were consistently less responsive both during infancy and at age 12. Continuity in parenting behaviors was related to control and criticism beginning in the toddler period and not to degree of responsiveness to the infant.

  17. Early-time solution of the horizontal unconfined aquifer in the build-up phase

    NASA Astrophysics Data System (ADS)

    Gravanis, Elias; Akylas, Evangelos

    2017-04-01

    goes away. Nonetheless, no analogue of the kinematic wave or the Boussinesq separable solution exists in this case. The late time state of the build-up phase under constant recharge rate is very simply the steady state solution. Our aim is to construct the early time asymptotic solution of this problem. The solution is expressed as a power series of a suitable similarity variable, which is constructed so that to satisfy the boundary conditions at both ends of the aquifer, that is, it is a polynomial approximation of the exact solution. The series turn out to be asymptotic and it is regularized by re-summation techniques which are used to define divergent series. The outflow rate in this regime is linear in time, and the (dimensionless) coefficient is calculated to eight significant figures. The local error of the series is quantified by its deviation from satisfying the self-similar Boussinesq equation at every point. The local error turns out to be everywhere positive, hence, so is the integrated error, which in turn quantifies the degree of convergence of the series to the exact solution.

  18. Implementation of an alert and response system in Haiti during the early stage of the response to the cholera epidemic.

    PubMed

    Santa-Olalla, Patricia; Gayer, Michelle; Magloire, Roc; Barrais, Robert; Valenciano, Marta; Aramburu, Carmen; Poncelet, Jean Luc; Gustavo Alonso, Juan Carlos; Van Alphen, Dana; Heuschen, Florence; Andraghetti, Roberta; Lee, Robert; Drury, Patrick; Aldighieri, Sylvain

    2013-10-01

    The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and

  19. Implementation of an Alert and Response System in Haiti during the Early Stage of the Response to the Cholera Epidemic

    PubMed Central

    Santa-Olalla, Patricia; Gayer, Michelle; Magloire, Roc; Barrais, Robert; Valenciano, Marta; Aramburu, Carmen; Poncelet, Jean Luc; Gustavo Alonso, Juan Carlos; Van Alphen, Dana; Heuschen, Florence; Andraghetti, Roberta; Lee, Robert; Drury, Patrick; Aldighieri, Sylvain

    2013-01-01

    The start of the cholera epidemic in Haiti quickly highlighted the necessity of the implementation of an Alert and Response (A&R) System to complement the existing national surveillance system. The national system had been able to detect and confirm the outbreak etiology but required external support to monitor the spread of cholera and coordinate response, because much of the information produced was insufficiently timely for real-time monitoring and directing of a rapid, targeted response. The A&R System was designed by the Pan American Health Organization/World Health Organization in collaboration with the Haiti Ministry of Health, and it was based on a network of partners, including any institution, structure, or individual that could identify, verify, and respond to alerts. The defined objectives were to (1) save lives through early detection and treatment of cases and (2) control the spread through early intervention at the community level. The operational structure could be broken down into three principle categories: (1) alert (early warning), (2) verification and assessment of the information, and (3) efficient and timely response in coordination with partners to avoid duplication. Information generated by the A&R System was analyzed and interpreted, and the qualitative information was critical in qualifying the epidemic and defining vulnerable areas, particularly because the national surveillance system reported incomplete data for more than one department. The A&R System detected a number of alerts unrelated to cholera and facilitated rapid access to that information. The sensitivity of the system and its ability to react quickly was shown in May of 2011, when an abnormal increase in alerts coming from several communes in the Sud-Est Department in epidemiological weeks (EWs) 17 and 18 were noted and disseminated network-wide and response activities were implemented. The national cholera surveillance system did not register the increase until EWs 21 and

  20. Girls' challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms.

    PubMed

    Casement, Melynda D; Guyer, Amanda E; Hipwell, Alison E; McAloon, Rose L; Hoffmann, Amy M; Keenan, Kathryn E; Forbes, Erika E

    2014-04-01

    Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC), striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

    PubMed

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-06-07

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

  2. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals

    PubMed Central

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-01-01

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process. PMID:28590456

  3. Discrimination of speech stimuli based on neuronal response phase patterns depends on acoustics but not comprehension.

    PubMed

    Howard, Mary F; Poeppel, David

    2010-11-01

    Speech stimuli give rise to neural activity in the listener that can be observed as waveforms using magnetoencephalography. Although waveforms vary greatly from trial to trial due to activity unrelated to the stimulus, it has been demonstrated that spoken sentences can be discriminated based on theta-band (3-7 Hz) phase patterns in single-trial response waveforms. Furthermore, manipulations of the speech signal envelope and fine structure that reduced intelligibility were found to produce correlated reductions in discrimination performance, suggesting a relationship between theta-band phase patterns and speech comprehension. This study investigates the nature of this relationship, hypothesizing that theta-band phase patterns primarily reflect cortical processing of low-frequency (<40 Hz) modulations present in the acoustic signal and required for intelligibility, rather than processing exclusively related to comprehension (e.g., lexical, syntactic, semantic). Using stimuli that are quite similar to normal spoken sentences in terms of low-frequency modulation characteristics but are unintelligible (i.e., their time-inverted counterparts), we find that discrimination performance based on theta-band phase patterns is equal for both types of stimuli. Consistent with earlier findings, we also observe that whereas theta-band phase patterns differ across stimuli, power patterns do not. We use a simulation model of the single-trial response to spoken sentence stimuli to demonstrate that phase-locked responses to low-frequency modulations of the acoustic signal can account not only for the phase but also for the power results. The simulation offers insight into the interpretation of the empirical results with respect to phase-resetting and power-enhancement models of the evoked response.

  4. Early warning systems and rapid response to the deteriorating patient in hospital: A realist evaluation.

    PubMed

    McGaughey, Jennifer; O'Halloran, Peter; Porter, Sam; Trinder, John; Blackwood, Bronagh

    2017-12-01

    To test the Rapid Response Systems programme theory against actual practice components of the Rapid Response Systems implemented to identify those contexts and mechanisms which have an impact on the successful achievement of desired outcomes in practice. Rapid Response Systems allow deteriorating patients to be recognized using Early Warning Systems, referred early via escalation protocols and managed at the bedside by competent staff. Realist evaluation. The research design was an embedded multiple case study approach of four wards in two hospitals in Northern Ireland which followed the principles of Realist Evaluation. We used various mixed methods including individual and focus group interviews, observation of nursing practice between June-November 2010 and document analysis of Early Warning Systems audit data between May-October 2010 and hospital acute care training records over 4.5 years from 2003-2008. Data were analysed using NiVivo8 and SPPS. A cross-case analysis highlighted similar patterns of factors which enabled or constrained successful recognition, referral and response to deteriorating patients in practice. Key enabling factors were the use of clinical judgement by experienced nurses and the empowerment of nurses as a result of organizational change associated with implementation of Early Warning System protocols. Key constraining factors were low staffing and inappropriate skill mix levels, rigid implementation of protocols and culturally embedded suboptimal communication processes. Successful implementation of Rapid Response Systems was dependent on adopting organizational and cultural changes that facilitated staff empowerment, flexible implementation of protocols and ongoing experiential learning. © 2017 John Wiley & Sons Ltd.

  5. The Impact of Early Substance Use Disorder Treatment Response on Treatment Outcomes Among Pregnant Women With Primary Opioid Use.

    PubMed

    Tuten, Michelle; Fitzsimons, Heather; Hochheimer, Martin; Jones, Hendree E; Chisolm, Margaret S

    2018-03-13

    This study examined the impact of early patient response on treatment utilization and substance use among pregnant participants enrolled in substance use disorder (SUD) treatment. Treatment responders (TRs) and treatment nonresponders (TNRs) were compared on pretreatment and treatment measures. Regression models predicted treatment utilization and substance use. TR participants attended more treatment and had lower rates of substance use relative to TNR participants. Regression models for treatment utilization and substance use were significant. Maternal estimated gestational age (EGA) and baseline cocaine use were negatively associated with treatment attendance. Medication-assisted treatment, early treatment response, and baseline SUD treatment were positively associated with treatment attendance. Maternal EGA was negatively associated with counseling attendance; early treatment response was positively associated with counseling attendance. Predictors of any substance use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline cocaine use. The single predictor of any substance use at 2 months was early treatment nonresponse. Predictors of opioid use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline SUD treatment. Predictors of opioid use at 2 months were early treatment nonresponse, and baseline cocaine and marijuana use. Predictors of cocaine use at 1 month were early treatment nonresponse, baseline cocaine use, and baseline SUD treatment. Predictors of cocaine use at 2 months were early treatment nonresponse and baseline cocaine use. Early treatment response predicts more favorable maternal treatment utilization and substance use outcomes. Treatment providers should implement interventions to maximize patient early response to treatment.

  6. Hemiparetic stepping to the beat: asymmetric response to metronome phase shift during treadmill gait.

    PubMed

    Pelton, Trudy A; Johannsen, Leif; Huiya Chen; Wing, Alan M

    2010-06-01

    Walking in time with a metronome is associated with improved spatiotemporal parameters in hemiparetic gait; however, the mechanism linking auditory and motor systems is poorly understood. Hemiparetic cadence control with metronome synchronization was examined to determine specific influences of metronome timing on treadmill walking. A within-participant experiment examined correction processes used to maintain heel strike synchrony with the beat by applying perturbations to the timing of a metronome. Eight chronic hemiparetic participants (mean age = 70 years; standard deviation = 12) were required to synchronize heel strikes with metronome pulses set according to each individual's comfortable speed (mean 0.4 m/s). During five 100-pulse trials, a fixed-phase baseline was followed by 4 unpredictable metronome phase shifts (20% of the interpulse interval), which amounted to 10 phase shifts on each foot. Infrared cameras recorded the motion of bilateral heel markers at 120 Hz. Relative asynchrony between heel strike responses and metronome pulses was used to index compensation for metronome phase shifts. Participants demonstrated compensation for phase shifts with convergence back to pre-phase shift asynchrony. This was significantly slower when the error occurred on the nonparetic side (requiring initial correction with the paretic limb) compared with when the error occurred on the paretic side (requiring initial nonparetic correction). Although phase correction of gait is slowed when the phase shift is delivered to the nonparetic side compared with the paretic side, phase correction is still present. This may underlie the utility of rhythmic auditory cueing in hemiparetic gait rehabilitation.

  7. Phase response of the Arabidopsis thaliana circadian clock to light pulses of different wavelengths.

    PubMed

    Ohara, Takayuki; Fukuda, Hirokazu; Tokuda, Isao T

    2015-04-01

    Light is known as one of the most powerful environmental time cues for the circadian system. The quality of light is characterized by its intensity and wavelength. We examined how the phase response of Arabidopsis thaliana depends on the wavelength of the stimulus light and the type of light perturbation. Using transgenic A. thaliana expressing a luciferase gene, we monitored the rhythm of the bioluminescence signal. We stimulated the plants under constant red light using 3 light perturbation treatments: (1) increasing the red light intensity, (2) turning on a blue light while turning off the red light, and (3) turning on a blue light while keeping the red light on. To examine the phase response properties, we generated a phase transition curve (PTC), which plots the phase after the perturbation as a function of the phase before the perturbation. To evaluate the effect of the 3 light perturbation treatments, we simulated PTCs using a mathematical model of the plant circadian clock and fitted the simulated PTCs to the experimentally measured PTCs. Among the 3 treatments, perturbation (3) provided the strongest stimulus. The results indicate that the color of the stimulus light and the type of pulse administration affect the phase response in a complex manner. Moreover, the results suggest the involvement of interaction between red and blue light signaling pathways in resetting of the plant circadian clock. © 2015 The Author(s).

  8. Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity

    PubMed Central

    2013-01-01

    Introduction It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA. Methods A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2. Results A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to

  9. Robust Measurements of Phase Response Curves Realized via Multicycle Weighted Spike-Triggered Averages

    NASA Astrophysics Data System (ADS)

    Imai, Takashi; Ota, Kaiichiro; Aoyagi, Toshio

    2017-02-01

    Phase reduction has been extensively used to study rhythmic phenomena. As a result of phase reduction, the rhythm dynamics of a given system can be described using the phase response curve. Measuring this characteristic curve is an important step toward understanding a system's behavior. Recently, a basic idea for a new measurement method (called the multicycle weighted spike-triggered average method) was proposed. This paper confirms the validity of this method by providing an analytical proof and demonstrates its effectiveness in actual experimental systems by applying the method to an oscillating electric circuit. Some practical tips to use the method are also presented.

  10. Phase Synchronization and Desynchronization of Structural Response Induced by Turbulent and External Sound

    NASA Technical Reports Server (NTRS)

    Maestrello, Lucio

    2002-01-01

    Acoustic and turbulent boundary layer flow loadings over a flexible structure are used to study the spatial-temporal dynamics of the response of the structure. The stability of the spatial synchronization and desynchronization by an active external force is investigated with an array of coupled transducers on the structure. In the synchronous state, the structural phase is locked, which leads to the formation of spatial patterns while the amplitude peaks exhibit chaotic behaviors. Large amplitude, spatially symmetric loading is superimposed on broadband, but in the desynchronized state, the spectrum broadens and the phase space is lost. The resulting pattern bears a striking resemblance to phase turbulence. The transition is achieved by using a low power external actuator to trigger broadband behaviors from the knowledge of the external acoustic load inducing synchronization. The changes are made favorably and efficiently to alter the frequency distribution of power, not the total power level. Before synchronization effects are seen, the panel response to the turbulent boundary layer loading is discontinuously spatio-temporally correlated. The stability develops from different competing wavelengths; the spatial scale is significantly shorter than when forced with the superimposed external sound. When the external sound level decreases and the synchronized phases are lost, changes in the character of the spectra can be linked to the occurrence of spatial phase transition. These changes can develop broadband response. Synchronized responses of fuselage structure panels have been observed in subsonic and supersonic aircraft; results from two flights tests are discussed.

  11. Phononic band gaps and phase singularities in the ultrasonic response from toughened composites

    NASA Astrophysics Data System (ADS)

    Smith, Robert A.; Nelson, Luke J.; Mienczakowski, Martin J.

    2018-04-01

    Ultrasonic 3D characterization of ply-level features in layered composites, such as out-of-plane wrinkles and ply drops, is now possible with carefully applied analytic-signal analysis. Study of instantaneous amplitude, phase and frequency in the ultrasonic response has revealed some interesting effects, which become more problematic for 3D characterization as the inter-ply resin-layer thicknesses increase. In modern particle-toughened laminates, the thicker resin layers cause phase singularities to be observed; these are locations where the instantaneous amplitude is zero, so the instantaneous phase is undefined. The depth at which these occur has been observed experimentally to vary with resin- layer thickness, such that a phase-singularity surface is formed; beyond this surface, the ultrasonic response is reduced and significantly more difficult to interpret, so a method for removing the effect would be advantageous. The underlying physics has been studied using an analytical one-dimensional multi-layer model. This has been sufficient to determine that the cause is linked to a phononic band gap in the ultrasound transmitted through multiple equally-spaced partial reflectors. As a result, the phase singularity also depends on input-pulse center frequency and bandwidth. Various methods for overcoming the confusing effects in the data have been proposed and subsequently investigated using the analytical model. This paper will show experimental and modelled evidence of phase-singularities and phase-singularity surfaces, as well as the success of methods for reducing their effects.

  12. Sustained attention is favored by progesterone during early luteal phase and visuo-spatial memory by estrogens during ovulatory phase in young women.

    PubMed

    Solís-Ortiz, S; Corsi-Cabrera, M

    2008-08-01

    Studies examining the influence of the menstrual cycle on cognitive function have been highly contradictory. The maintenance of attention is key to successful information processing, however how it co-vary with other cognitive functions and mood in function of phases of the menstrual cycle is not well know. Therefore, neuropsychological performance of nine healthy women with regular menstrual cycles was assessed during ovulation (OVU), early luteal (EL), late luteal (LL) and menstrual (MEN) phases. Neuropsychological test scores of sustained attention, executive functions, manual coordination, visuo-spatial memory, verbal fluency, spatial ability, anxiety and depression were obtained and submitted to a principal components analysis (PCA). Five eigenvectors that accounted the 68.31% of the total variance were identified. Performance of the sustained attention was grouped in an independent eigenvector (component 1), and the scores on verbal fluency and visuo-spatial memory were grouped together in an eigenvector (component 5), which explained 17.69% and 12.03% of the total variance, respectively. The component 1 (p<0.034) and the component 5 (p<0.003) showed significant variations during the menstrual cycle. Sustained attention showed an increase in the EL phase, when the progesterone is high. Visuo-spatial memory was increased, while that verbal fluency was decreased during the OVU phase, when the estrogens levels are high. These results indicate that sustained attention is favored by early luteal phase progesterone and do not covaried with any other neuropsychological variables studied. The influence of the estrogens on visuo-spatial memory was corroborated, and covaried inversely with verbal fluency.

  13. The early response during the interaction of fungal phytopathogen and host plant.

    PubMed

    Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen; Zheng, Wenming

    2017-05-01

    Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum , rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. © 2017 The Authors.

  14. The early response during the interaction of fungal phytopathogen and host plant

    PubMed Central

    Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen

    2017-01-01

    Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum, rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. PMID:28469008

  15. Prognosis and response to laser treatment of early-onset hypertrophic port-wine stains (PWS).

    PubMed

    Passeron, Thierry; Salhi, Aicha; Mazer, Jean-Michel; Lavogiez, Céline; Mazereeuw-Hautier, Juliette; Galliot, Chrystèle; Collet-Villette, Anne-Marie; Labreze, Christine; Boon, Laurence; Hardy, Jean-Philippe; Fayard, Virginie; Livideanu, Cristina Bulai; Toubel, Gérard; Georgescou, Gabriela; Gral, Nathalie; Maza, Aude; Lacour, Jean-Philippe

    2016-07-01

    There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS). We sought to characterize patients with hypertrophic PWS presenting during childhood. Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded. A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS. As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation. PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  16. Cortisol Stress Response Variability in Early Adolescence Attachment, Affect and Sex

    PubMed Central

    Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J.; Wynne-Edwards, Katherine; Wright, Joan M.; Weinberg, Joanne

    2017-01-01

    Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic–pituitary–adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents. PMID:27468997

  17. Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

    PubMed

    Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

    2017-01-01

    Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

  18. Can early host responses to mycobacterial infection predict eventual disease outcomes?

    PubMed

    de Silva, Kumudika; Begg, Douglas J; Plain, Karren M; Purdie, Auriol C; Kawaji, Satoko; Dhand, Navneet K; Whittington, Richard J

    2013-11-01

    Diagnostic tests used for Johne's disease in sheep either have poor sensitivity and specificity or only detect disease in later stages of infection. Predicting which of the infected sheep are likely to become infectious later in life is currently not feasible and continues to be a major hindrance in disease control. We conducted this longitudinal study to investigate if a suite of diagnostic tests conducted in Mycobacterium avium subspecies paratuberculosis (MAP) exposed lambs at 4 months post infection can accurately predict their clinical status at 12 months post infection. We tracked cellular and humoral responses and quantity of MAP shedding for up to 12 months post challenge in 20 controls and 37 exposed sheep. Infection was defined at necropsy by tissue culture and disease spectrum by lesion type. Data were analysed using univariable and multivariable logistic regression models and a subset of variables from the earliest period post inoculation (4 months) was selected for predicting disease outcomes later on (12 months). Sensitivity and specificity of tests and their combinations in series and parallel were determined. Early elevation in faecal MAP DNA quantity and a lower interferon gamma (IFNγ) response were significantly associated with sheep becoming infectious as well as progressing to severe disease. Conversely, early low faecal MAP DNA and higher interleukin-10 responses were significantly associated with an exposed animal developing protective immunity. Combination of early elevated faecal MAP DNA or lower IFNγ response had the highest sensitivity (75%) and specificity (81%) for identifying sheep that would become infectious. Collectively, these results highlight the potential for combined test interpretation to aid in the early prediction of sheep susceptibility to MAP infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Perceived early-life maternal care and the cortisol response to repeated psychosocial stress.

    PubMed

    Engert, Veronika; Efanov, Simona I; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C

    2010-11-01

    In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group.

  20. Early developmental gene regulation in Strongylocentrotus purpuratus embryos in response to elevated CO₂ seawater conditions.

    PubMed

    Hammond, LaTisha M; Hofmann, Gretchen E

    2012-07-15

    Ocean acidification, or the increased uptake of CO(2) by the ocean due to elevated atmospheric CO(2) concentrations, may variably impact marine early life history stages, as they may be especially susceptible to changes in ocean chemistry. Investigating the regulatory mechanisms of early development in an environmental context, or ecological development, will contribute to increased understanding of potential organismal responses to such rapid, large-scale environmental changes. We examined transcript-level responses to elevated seawater CO(2) during gastrulation and the initiation of spiculogenesis, two crucial developmental processes in the purple sea urchin, Strongylocentrotus purpuratus. Embryos were reared at the current, accepted oceanic CO(2) concentration of 380 microatmospheres (μatm), and at the elevated levels of 1000 and 1350 μatm, simulating predictions for oceans and upwelling regions, respectively. The seven genes of interest comprised a subset of pathways in the primary mesenchyme cell gene regulatory network (PMC GRN) shown to be necessary for the regulation and execution of gastrulation and spiculogenesis. Of the seven genes, qPCR analysis indicated that elevated CO(2) concentrations only had a significant but subtle effect on two genes, one important for early embryo patterning, Wnt8, and the other an integral component in spiculogenesis and biomineralization, SM30b. Protein levels of another spicule matrix component, SM50, demonstrated significant variable responses to elevated CO(2). These data link the regulation of crucial early developmental processes with the environment that these embryos would be developing within, situating the study of organismal responses to ocean acidification in a developmental context.

  1. Perceived early-life maternal care and the cortisol response to repeated psychosocial stress

    PubMed Central

    Engert, Veronika; Efanov, Simona I.; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C.

    2010-01-01

    Background In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic–pituitary–adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. Methods In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Results Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Limitations Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. Conclusion We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group. PMID:20964960

  2. Defining and Predicting Patterns of Early Response in a Web-Based Intervention for Depression

    PubMed Central

    Arndt, Alice; Rubel, Julian; Berger, Thomas; Schröder, Johanna; Späth, Christina; Meyer, Björn; Greiner, Wolfgang; Gräfe, Viola; Hautzinger, Martin; Fuhr, Kristina; Rose, Matthias; Nolte, Sandra; Löwe, Bernd; Hohagen, Fritz; Klein, Jan Philipp; Moritz, Steffen

    2017-01-01

    Background Web-based interventions for individuals with depressive disorders have been a recent focus of research and may be an effective adjunct to face-to-face psychotherapy or pharmacological treatment. Objective The aim of our study was to examine the early change patterns in Web-based interventions to identify differential effects. Methods We applied piecewise growth mixture modeling (PGMM) to identify different latent classes of early change in individuals with mild-to-moderate depression (n=409) who underwent a CBT-based web intervention for depression. Results Overall, three latent classes were identified (N=409): Two early response classes (n=158, n=185) and one early deterioration class (n=66). Latent classes differed in terms of outcome (P<.001) and adherence (P=.03) in regard to the number of modules (number of modules with a duration of at least 10 minutes) and the number of assessments (P<.001), but not in regard to the overall amount of time using the system. Class membership significantly improved outcome prediction by 24.8% over patient intake characteristics (P<.001) and significantly added to the prediction of adherence (P=.04). Conclusions These findings suggest that in Web-based interventions outcome and adherence can be predicted by patterns of early change, which can inform treatment decisions and potentially help optimize the allocation of scarce clinical resources. PMID:28600278

  3. Establishing an early warning alert and response network following the Solomon Islands tsunami in 2013

    PubMed Central

    Bilve, Augustine; Nogareda, Francisco; Joshua, Cynthia; Ross, Lester; Betcha, Christopher; Durski, Kara; Fleischl, Juliet

    2014-01-01

    Abstract Problem On 6 February 2013, an 8.0 magnitude earthquake generated a tsunami that struck the Santa Cruz Islands, Solomon Islands, killing 10 people and displacing over 4700. Approach A post-disaster assessment of the risk of epidemic disease transmission recommended the implementation of an early warning alert and response network (EWARN) to rapidly detect, assess and respond to potential outbreaks in the aftermath of the tsunami. Local setting Almost 40% of the Santa Cruz Islands’ population were displaced by the disaster, and living in cramped temporary camps with poor or absent sanitation facilities and insufficient access to clean water. There was no early warning disease surveillance system. Relevant changes By 25 February, an EWARN was operational in five health facilities that served 90% of the displaced population. Eight priority diseases or syndromes were reported weekly; unexpected health events were reported immediately. Between 25 February and 19 May, 1177 target diseases or syndrome cases were reported. Seven alerts were investigated. No sustained transmission or epidemics were identified. Reporting compliance was 85%. The EWARN was then transitioned to the routine four-syndrome early warning disease surveillance system. Lesson learnt It was necessary to conduct a detailed assessment to evaluate the risk and potential impact of serious infectious disease outbreaks, to assess whether and how enhanced early warning disease surveillance should be implemented. Local capacities and available resources should be considered in planning EWARN implementation. An EWARN can be an opportunity to establish or strengthen early warning disease surveillance capabilities. PMID:25378746

  4. Establishing an early warning alert and response network following the Solomon Islands tsunami in 2013.

    PubMed

    Bilve, Augustine; Nogareda, Francisco; Joshua, Cynthia; Ross, Lester; Betcha, Christopher; Durski, Kara; Fleischl, Juliet; Nilles, Eric

    2014-11-01

    On 6 February 2013, an 8.0 magnitude earthquake generated a tsunami that struck the Santa Cruz Islands, Solomon Islands, killing 10 people and displacing over 4700. A post-disaster assessment of the risk of epidemic disease transmission recommended the implementation of an early warning alert and response network (EWARN) to rapidly detect, assess and respond to potential outbreaks in the aftermath of the tsunami. Almost 40% of the Santa Cruz Islands' population were displaced by the disaster, and living in cramped temporary camps with poor or absent sanitation facilities and insufficient access to clean water. There was no early warning disease surveillance system. By 25 February, an EWARN was operational in five health facilities that served 90% of the displaced population. Eight priority diseases or syndromes were reported weekly; unexpected health events were reported immediately. Between 25 February and 19 May, 1177 target diseases or syndrome cases were reported. Seven alerts were investigated. No sustained transmission or epidemics were identified. Reporting compliance was 85%. The EWARN was then transitioned to the routine four-syndrome early warning disease surveillance system. It was necessary to conduct a detailed assessment to evaluate the risk and potential impact of serious infectious disease outbreaks, to assess whether and how enhanced early warning disease surveillance should be implemented. Local capacities and available resources should be considered in planning EWARN implementation. An EWARN can be an opportunity to establish or strengthen early warning disease surveillance capabilities.

  5. Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

    PubMed Central

    Liu, Pei; Zhang, Huoming; Yu, Boying; Xiong, Liming; Xia, Yiji

    2015-01-01

    Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response. PMID:25720653

  6. Transient visual responses reset the phase of low-frequency oscillations in the skeletomotor periphery.

    PubMed

    Wood, Daniel K; Gu, Chao; Corneil, Brian D; Gribble, Paul L; Goodale, Melvyn A

    2015-08-01

    We recorded muscle activity from an upper limb muscle while human subjects reached towards peripheral targets. We tested the hypothesis that the transient visual response sweeps not only through the central nervous system, but also through the peripheral nervous system. Like the transient visual response in the central nervous system, stimulus-locked muscle responses (< 100 ms) were sensitive to stimulus contrast, and were temporally and spatially dissociable from voluntary orienting activity. Also, the arrival of visual responses reduced the variability of muscle activity by resetting the phase of ongoing low-frequency oscillations. This latter finding critically extends the emerging evidence that the feedforward visual sweep reduces neural variability via phase resetting. We conclude that, when sensory information is relevant to a particular effector, detailed information about the sensorimotor transformation, even from the earliest stages, is found in the peripheral nervous system. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  7. Massage therapy decreases cancer-related fatigue: Results from a randomized early phase trial.

    PubMed

    Kinkead, Becky; Schettler, Pamela J; Larson, Erika R; Carroll, Dedric; Sharenko, Margaret; Nettles, James; Edwards, Sherry A; Miller, Andrew H; Torres, Mylin A; Dunlop, Boadie W; Rakofsky, Jeffrey J; Rapaport, Mark Hyman

    2018-02-01

    Cancer-related fatigue (CRF) is a prevalent and debilitating symptom experienced by cancer survivors, yet treatment options for CRF are limited. In this study, we evaluated the efficacy of weekly Swedish massage therapy (SMT) versus an active control condition (light touch [LT]) and waitlist control (WLC) on persistent CRF in breast cancer survivors. This early phase, randomized, single-masked, 6-week investigation of SMT, LT, and WLC enrolled 66 female stage 0-III breast cancer survivors (age range, 32-72 years) who had received surgery plus radiation and/or chemotherapy/chemoprevention with CRF (Brief Fatigue Inventory > 25). The primary outcome was the Multidimensional Fatigue Inventory (MFI), with the National Institutes of Health PROMIS Fatigue scale secondary. Mean baseline MFI scores for 57 evaluable subjects were 62.95 for SMT, 55.00 for LT, and 60.41 for WLC. SMT resulted in a mean (standard deviation) 6-week reduction in MFI total scores of -16.50 (6.37) (n = 20) versus -8.06 (6.50) for LT (n = 20) and an increase of 5.88 (6.48) points for WLC (n = 17) (treatment-by-time P < .0001). The mean baseline PROMIS Fatigue scores were SMT, 22.25; LT, 22.05; and WLC, 23.24. The mean (standard deviation) reduction in PROMIS Fatigue scores was -5.49 (2.53) points for SMT versus -3.24 (2.57) points for LT and -0.06 (1.88) points for WLC (treatment-by-time P = .0008). Higher credibility, expectancy, and preference for SMT than for LT did not account for these results. SMT produced clinically significant relief of CRF. This finding suggests that 6 weeks of a safe, widely accepted manual intervention causes a significant reduction in fatigue, a debilitating sequela for cancer survivors. Cancer 2018;124:546-54. © 2017 American Cancer Society. © 2017 American Cancer Society.

  8. Hypertensive phase and early complications after Ahmed glaucoma valve implantation with intraoperative subtenon triamcinolone acetonide

    PubMed Central

    Turalba, Angela V; Pasquale, Louis R

    2014-01-01

    Objective To evaluate intraoperative subtenon triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation. Design Retrospective comparative case series. Participants Forty-two consecutive cases of uncontrolled glaucoma undergoing AGV implantation: 19 eyes receiving intraoperative subtenon TA and 23 eyes that did not receive TA. Methods A retrospective chart review was performed on consecutive pseudophakic adult patients with uncontrolled glaucoma undergoing AGV with and without intraoperative subtenon TA injection by a single surgeon. Clinical data were collected from 42 eyes and analyzed for the first 6 months after surgery. Main outcome measures Primary outcomes included intraocular pressure (IOP) and number of glaucoma medications prior to and after AGV implantation. The hypertensive phase (HP) was defined as an IOP measurement of greater than 21 mmHg (with or without medications) during the 6-month postoperative period that was not a result of tube obstruction, retraction, or malfunction. Postoperative complications and visual acuity were analyzed as secondary outcome measures. Results Five out of 19 (26%) TA cases and 12 out of 23 (52%) non-TA cases developed the HP (P=0.027). Mean IOP (14.2±4.6 in TA cases versus [vs] 14.7±5.0 mmHg in non-TA cases; P=0.78), and number of glaucoma medications needed (1.8±1.3 in TA cases vs 1.6±1.1 in the comparison group; P=0.65) were similar between both groups at 6 months. Although rates of serious complications did not differ between the groups (13% in the TA group vs 16% in the non-TA group), early tube erosion (n=1) and bacterial endophthalmitis (n=1) were noted with TA but not in the non-TA group. Conclusions Subtenon TA injection during AGV implantation may decrease the occurrence of the HP but does not alter the ultimate IOP outcome and may pose increased risk of serious complications within the first 6 months of surgery. PMID:25050061

  9. Early coordinated rehabilitation in acute phase after hip fracture - a model for increased patient participation.

    PubMed

    Asplin, Gillian; Carlsson, Gunnel; Zidén, Lena; Kjellby-Wendt, Gunilla

    2017-10-17

    Studies have shown that patients with hip fracture treated in a Comprehensive Geriatric Care (CGC) unit report better results in comparison to orthopaedic care. Furthermore, involving patients in their healthcare by encouraging patient participation can result in better quality of care and improved outcomes. To our knowledge no study has been performed comparing rehabilitation programmes within a CGC unit during the acute phase after hip fracture with focus on improving patients' perceived participation and subsequent effect on patients' function. A prospective, controlled, intervention performed in a CGC unit and compared with standard care. A total of 126 patients with hip fracture were recruited who were prior to fracture; community dwelling, mobile indoors and independent in personal care. Intervention Group (IG): 63 patients, mean age 82.0 years and Control Group (CG): 63 patients mean age 80.5 years. coordinated rehabilitation programme with early onset of patient participation and intensified occupational therapy and physiotherapy after hip fracture surgery. The primary outcome measure was self-reported patient participation at discharge. Secondary outcome measures were: TLS-BasicADL; Bergs Balance Scale (BBS); Falls Efficacy Scale FES(S); Short Physical Performance Battery (SPPB) and Timed Up and Go (TUG) at discharge and 1 month and ADL staircase for instrumental ADL at 1 month. At discharge a statistically significant greater number of patients in the IG reported higher levels of participation (p < 0.05) and independence in lower body hygiene (p < 0.05) and dressing (p < 0.001). There were however no statistically significant differences at discharge and 1 month between groups in functional balance and confidence, performance measures or risk for falls. This model of OT and PT coordinated inpatient rehabilitation had a positive effect on patients' perceived participation in their rehabilitation and ADL at discharge but did not appear to

  10. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial.

    PubMed

    van de Velde, Cornelis J H; Rea, Daniel; Seynaeve, Caroline; Putter, Hein; Hasenburg, Annette; Vannetzel, Jean-Michel; Paridaens, Robert; Markopoulos, Christos; Hozumi, Yasuo; Hille, Elysee T M; Kieback, Dirk G; Asmar, Lina; Smeets, Jan; Nortier, Johan W R; Hadji, Peyman; Bartlett, John M S; Jones, Stephen E

    2011-01-22

    Aromatase inhibitors improved disease-free survival compared with tamoxifen when given as an initial adjuvant treatment or after 2-3 years of tamoxifen to postmenopausal women with hormone-receptor-positive breast cancer. We therefore compared the long-term effects of exemestane monotherapy with sequential treatment (tamoxifen followed by exemestane). The Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase 3 trial was conducted in hospitals in nine countries. Postmenopausal women (median age 64 years, range 35-96) with hormone-receptor-positive breast cancer were randomly assigned in a 1:1 ratio to open-label exemestane (25 mg once a day, orally) alone or following tamoxifen (20 mg once a day, orally) for 5 years. Randomisation was by use of a computer-generated random permuted block method. The primary endpoint was disease-free survival (DFS) at 5 years. Main analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, NCT00279448, NCT00032136, and NCT00036270; NTR 267; Ethics Commission Trial27/2001; and UMIN, C000000057. 9779 patients were assigned to sequential treatment (n=4875) or exemestane alone (n=4904), and 4868 and 4898 were analysed by intention to treat, respectively. 4154 (85%) patients in the sequential group and 4186 (86%) in the exemestane alone group were disease free at 5 years (hazard ratio 0·97, 95% CI 0·88-1·08; p=0·60). In the safety analysis, sequential treatment was associated with a higher incidence of gynaecological symptoms (942 [20%] of 4814 vs 523 [11%] of 4852), venous thrombosis (99 [2%] vs 47 [1%]), and endometrial abnormalities (191 [4%] vs 19 [<1%]) than was exemestane alone. Musculoskeletal adverse events (2448 [50%] vs 2133 [44%]), hypertension (303 [6%] vs 219 [5%]), and hyperlipidaemia (230 [5%] vs 136 [3%]) were reported more frequently with exemestane alone. Treatment regimens of exemestane alone or after tamoxifen might be judged to be appropriate options for postmenopausal women with

  11. Sexually Dimorphic Responses to Early Adversity: Implications for Affective Problems and Autism Spectrum Disorder

    PubMed Central

    Davis, Elysia Poggi; Pfaff, Donald

    2014-01-01

    During gestation, development proceeds at a pace that is unmatched by any other stage of the lifecycle. For these reason the human fetus is particularly susceptible not only to organizing influences, but also to pathogenic disorganizing influences. Growing evidence suggests that exposure to prenatal adversity leads to neurological changes that underlie lifetime risks for mental illness. Beginning early in gestation, males and females show differential developmental trajectories and responses to stress. It is likely that sex-dependent organization of neural circuits during the fetal period influences differential vulnerability to mental health problems. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two developmental disorders: affective problems (greater female prevalence) and autism spectrum disorder (greater male prevalence). Recent prospective studies illustrating the neurodevelopmental consequences of fetal exposure to stress and stress hormones for males and females are considered here. Plausible biological mechanisms including the role of the sexually differentiated placenta are discussed. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two sets of developmental disorders: affective problems (greater female prevalence) and autism spectrum disorders (greater male prevalence). PMID:25038479

  12. Early stages of styrene-isoprene copolymerization in gas phase clusters probed by resonance enhanced multiphoton ionization.

    PubMed

    Mahmoud, Hatem; Germanenko, Igor N; El-Shall, M Samy

    2006-04-06

    We present direct evidence for the formation of the covalent bonded styrene (isoprene)(2) oligomer and the isoprene dimer ions following resonance ionization of the gas phase styrene-isoprene binary clusters. The application of resonance ionization to study polymerization reactions in clusters provides new information on the structure and mechanism of formation of the early stages of polymerization and holds considerable promise for the discovery of new initiation mechanisms and for the development of novel materials with unique properties.

  13. Definition of technology development missions for early space stations. Large space structures, phase 2, midterm review

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The large space structures technology development missions to be performed on an early manned space station was studied and defined and the resources needed and the design implications to an early space station to carry out these large space structures technology development missions were determined. Emphasis is being placed on more detail in mission designs and space station resource requirements.

  14. The practical application of adaptive study design in early phase clinical trials: a retrospective analysis of time savings.

    PubMed

    Lorch, U; Berelowitz, K; Ozen, C; Naseem, A; Akuffo, E; Taubel, J

    2012-05-01

    The interest in adaptive study design is evident from the growing amount of clinical research employing this model in the mid to later stages of medicines development. Little has been published on the practical application and merits of adaptive study design in early phase clinical research. This paper describes a retrospective analysis performed on a sample of 29 industry lead adaptive early phase studies commencing between 1 January 2006 and 31 December 2010 in a clinical trials unit in London, England. All studies containing at least one adaptive feature in the original protocol were included in the analysis. The scope of the analysis was to assess whether the use of adaptive study designs provided tangible benefits over the use of conventional study designs using time savings as the main measure. We conclude that the use of adaptive study design saves time in early phase research programs. This is achieved by abolishing the need for substantial amendments or by mitigating their impact on timelines and by using adaptive scheduling efficiencies.

  15. Patterns of Early and Delayed Visual Response to Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration.

    PubMed

    Stoller, Glenn L; Kokame, Gregg T; Dreyer, Richard F; Shapiro, Howard; Tuomi, Lisa L

    2016-05-12

    Understanding the range of temporal responses to ranibizumab is critical for the assessment of individualized treatment regimens for neovascular age-related macular degeneration. To examine patterns of visual and anatomical response to ranibizumab treatment. This study is a retrospective subanalysis of HARBOR (a phase 3, double-masked, multicenter, randomized, active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg ranibizumab administered monthly or on an as-needed basis (PRN) in patients with subfoveal neovascular age-related macular degeneration). A total of 1097 patients with neovascular age-related macular degeneration were randomized to intravitreal ranibizumab, 0.5 or 2.0 mg, administered monthly or as needed (PRN) with monthly monitoring. Of the 1097 patients, 1057 were included in the analysis for early responders (best-corrected visual acuity [BCVA] obtained at baseline and month 3), and 988 patients were included in the analysis for delayed responders (BCVA obtained at baseline, month 3, and month 12). The HARBOR study began July 7, 2009, with the primary 12-month end point completed on August 5, 2011, ongoing to 24 months. Data analysis for the subgroup was performed from January 4, 2013, through December 17, 2015. Patients were categorized based on BCVA outcomes as early 15-letter responders (gained ≥15 letters from baseline at month 3) or delayed 15-letter responders (did not gain ≥15 letters from baseline at month 3 but did so at month 12). Changes from baseline in BCVA and central foveal thickness (CFT). In total, 266 early and 135 delayed 15-letter responders were identified. In the 0.5-mg monthly, 0.5-mg PRN, 2.0-mg monthly, and 2.0-mg PRN treatment groups, 63 (24.0%) of 263, 65 (24.6%) of 264, 68 (25.7%) of 265, and 70 (26.4%) of 265 patients were early responders, respectively, and 40 (16.3%) of 246, 31 (12.6%) of 247, 35 (14.1%) of 248, and 29 (11.7%) of 247 patients were delayed responders, respectively. By month

  16. Divided attention can enhance early-phase memory encoding: the attentional boost effect and study trial duration.

    PubMed

    Mulligan, Neil W; Spataro, Pietro

    2015-07-01

    Divided attention during encoding typically produces marked reductions in later memory. The attentional boost effect (ABE) is a surprising variation on this phenomenon. In this paradigm, each study stimulus (e.g., a word) is presented along with a target or a distractor (e.g., different colored circles) in a detection task. Later memory is better for stimuli co-occurring with targets. The present experiments indicate that the ABE arises during an early phase of memory encoding that involves initial stimulus perception and comprehension rather than at a later phase entailing controlled, elaborative rehearsal. Experiment 1 demonstrated that the ABE was robust at a short study duration (700 ms) and did not increase with increasing study trial durations (1,500 ms and 4,000 ms). Furthermore, the target condition is boosted to the level of memory performance in a full-attention condition for the short duration but not the long duration. Both results followed from the early-phase account. This account also predicts that for very short study times (limiting the influence of late-phase controlled encoding and thus minimizing the usual negative effect of divided attention), the target condition will produce better memory than will the full-attention condition. Experiment 2 used a study time of 400 ms and found that words presented with targets lead to greater recognition accuracy than do either words presented with distractors or words in the full-attention condition. Consistent with the early-phase account, a divided attention condition actually produced superior memory than did the full-attention condition, a very unusual but theoretically predicted result. (c) 2015 APA, all rights reserved.

  17. Early improvement with pregabalin predicts endpoint response in patients with generalized anxiety disorder: an integrated and predictive data analysis.

    PubMed

    Montgomery, Stuart A; Lyndon, Gavin; Almas, Mary; Whalen, Ed; Prieto, Rita

    2017-01-01

    Generalized anxiety disorder (GAD), a common mental disorder, has several treatment options including pregabalin. Not all patients respond to treatment; quickly determining which patients will respond is an important treatment goal. Patient-level data were pooled from nine phase II and III randomized, double-blind, short-term, placebo-controlled trials of pregabalin for the treatment of GAD. Efficacy outcomes included the change from baseline in the Hamilton Anxiety Scale (HAM-A) total score and psychic and somatic subscales. Predictive modelling assessed baseline characteristics and early clinical responses to determine those predictive of clinical improvement at endpoint. A total of 2155 patients were included in the analysis (1447 pregabalin, 708 placebo). Pregabalin significantly improved the HAM-A total score compared with the placebo at endpoint, treatment difference (95% confidence interval), -2.61 (-3.21 to -2.01), P<0.0001. Pregabalin significantly improved HAM-A psychic and somatic scores compared with placebo, -1.52 (-1.85 to -1.18), P<0.0001, and -1.10 (-1.41 to -0.80), P<0.0001, respectively. Response to pregabalin in the first 1-2 weeks (≥20 or ≥30% improvement in HAM-A total, psychic or somatic score) was predictive of an endpoint greater than or equal to 50% improvement in the HAM-A total score. Pregabalin is an effective treatment option for patients with GAD. Patients with early response to pregabalin are more likely to respond significantly at endpoint.

  18. Optically addressed and submillisecond response phase only liquid crystal spatial light modulator

    NASA Astrophysics Data System (ADS)

    Zhao, Xiangjie; Duan, Jiazhu; Zhang, Dayong; Luo, Yongquan

    2014-10-01

    Liquid crystal based phase only spatial light modulator has attracted many research interests since last decades because of its superior advantage. Until now the liquid crystal spatial light modulator has been applied in many fields, but the response speed of nematic LC limited its further application. In this paper, an optically addressed phase only LC spatial light modulator was proposed based on polymer network liquid crystal. Morphology effect on the light scattering of PNLC was studied, which was mainly consisted of fiber and fiber bundles. The morphology nearly determined the light scattering and electro-optical property. Due to the high threshold voltage, to address the PNLC phase modulator was also concerned. Optical addressing method was proposed, in which BSO crystal was selected to replace one of the glass substrate. The response speed of PNLC was so fast that the reorientation of liquid crystal director will follow the change of effective voltage applied on LC layer, which was related with the voltage signal and especially with electron transport of photo-induced carriers due to diffusion and drift. The on state dynamic response of phase change was investigated. Based on this device, beam steering was also achieved by loading 488nm laser strip on the optical addressed phase only spatial light modulator.

  19. Human phase response curve to a 1 h pulse of bright white light.

    PubMed

    St Hilaire, Melissa A; Gooley, Joshua J; Khalsa, Sat Bir S; Kronauer, Richard E; Czeisler, Charles A; Lockley, Steven W

    2012-07-01

    The phase resetting response of the human circadian pacemaker to light depends on the timing of exposure and is described by a phase response curve (PRC). The current study aimed to construct a PRC for a 1 h exposure to bright white light (∼8000 lux) and to compare this PRC to a <3 lux dim background light PRC. These data were also compared to a previously completed 6.7 h bright white light PRC and a <15 lux dim background light PRC constructed under similar conditions. Participants were randomized for exposure to 1 h of either bright white light (n=18) or <3 lux dim background light (n=18) scheduled at 1 of 18 circadian phases. Participants completed constant routine (CR) procedures in dim light (<3 lux) before and after the light exposure to assess circadian phase. Phase shifts were calculated as the difference in timing of dim light melatonin onset (DLMO) during pre- and post-stimulus CRs. Exposure to 1 h of bright white light induced a Type 1 PRC with a fitted peak-to-trough amplitude of 2.20 h. No discernible PRC was observed in the <3 lux dim background light PRC. The fitted peak-to-trough amplitude of the 1 h bright light PRC was ∼40% of that for the 6.7 h PRC despite representing only 15% of the light exposure duration, consistent with previous studies showing a non-linear duration–response function for the effects of light on circadian resetting.

  20. Phase space interrogation of the empirical response modes for seismically excited structures

    NASA Astrophysics Data System (ADS)

    Paul, Bibhas; George, Riya C.; Mishra, Sudib K.

    2017-07-01

    Conventional Phase Space Interrogation (PSI) for structural damage assessment relies on exciting the structure with low dimensional chaotic waveform, thereby, significantly limiting their applicability to large structures. The PSI technique is presently extended for structure subjected to seismic excitations. The high dimensionality of the phase space for seismic response(s) are overcome by the Empirical Mode Decomposition (EMD), decomposing the responses to a number of intrinsic low dimensional oscillatory modes, referred as Intrinsic Mode Functions (IMFs). Along with their low dimensionality, a few IMFs, retain sufficient information of the system dynamics to reflect the damage induced changes. The mutually conflicting nature of low-dimensionality and the sufficiency of dynamic information are taken care by the optimal choice of the IMF(s), which is shown to be the third/fourth IMFs. The optimal IMF(s) are employed for the reconstruction of the Phase space attractor following Taken's embedding theorem. The widely referred Changes in Phase Space Topology (CPST) feature is then employed on these Phase portrait(s) to derive the damage sensitive feature, referred as the CPST of the IMFs (CPST-IMF). The legitimacy of the CPST-IMF is established as a damage sensitive feature by assessing its variation with a number of damage scenarios benchmarked in the IASC-ASCE building. The damage localization capability, remarkable tolerance to noise contamination and the robustness under different seismic excitations of the feature are demonstrated.

  1. Expression of Putative Immune Response Genes during Early Ontogeny in the Coral Acropora millepora

    PubMed Central

    Puill-Stephan, Eneour; Seneca, François O.; Miller, David J.; van Oppen, Madeleine J. H.; Willis, Bette L.

    2012-01-01

    Background Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. Methodology/Principal Findings Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes) were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR). Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A.millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria) during winnowing processes as symbioses are fine-tuned. Conclusions/Significance Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies investigating the expression of

  2. Expression of putative immune response genes during early ontogeny in the coral Acropora millepora.

    PubMed

    Puill-Stephan, Eneour; Seneca, François O; Miller, David J; van Oppen, Madeleine J H; Willis, Bette L

    2012-01-01

    Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes) were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR). Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A. millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria) during winnowing processes as symbioses are fine-tuned. Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies investigating the expression of these genes in alloimmune-challenged corals are needed to further

  3. Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide-a for early-stage cancer of the larynx: Phase Ib study.

    PubMed

    Shafirstein, Gal; Rigual, Nestor R; Arshad, Hassan; Cooper, Michele T; Bellnier, David A; Wilding, Gregory; Tan, Wei; Merzianu, Mihai; Henderson, Barbara W

    2016-04-01

    The purpose of this study was for us to report results regarding the safety of 3-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) mediated photodynamic therapy (PDT) in early laryngeal disease, and offer preliminary information on treatment responses. A single-institution, phase Ib, open label, noncomparative study of HPPH-PDT in patients with high-risk dysplasia, carcinoma in situ, and T1 squamous cell carcinoma (SCC) of the larynx. The primary outcomes were safety and maximum tolerated dose (MTD), and the secondary outcome was response. Twenty-nine patients and 30 lesions were treated. The most common adverse event (AE) was transient hoarseness of voice. Severe edema, requiring tracheostomy, was the most serious AE, which occurred in 2 patients within several hours of therapy. The MTD was 100 J/cm(2) . Patients with T1 SCC seemed to have good complete response rate (82%) to HPPH-PDT at MTD. HPPH-PDT can be safely used to treat early-stage laryngeal cancer, with potential efficacy. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E377-E383, 2016. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc.

  4. Nonlocal optical response in topological phase transitions in the graphene family

    SciT

    Rodriguez-Lopez, Pablo; de Melo Kort-Kamp, Wilton Junior; Dalvit, Diego Alejandro Roberto

    We investigate the electromagnetic response of staggered two-dimensional materials of the graphene family, including silicene, germanene, and stanene, as they are driven through various topological phase transitions using external fields. Utilizing Kubo formalism, we compute their optical conductivity tensor taking into account the frequency and wave vector of the electromagnetic excitations, and study its behavior over the full electronic phase diagram of the materials. In particular, we find that the resonant behavior of the nonlocal Hall conductivity is strongly affected by the various topological phases present in these materials. We also consider the plasmon excitations in the graphene family andmore » find that nonlocality in the optical response can affect the plasmon dispersion spectra of the various phases. Here, we find a regime of wave vectors for which the plasmon relations for phases with trivial topology are essentially indistinguishable, while those for phases with nontrivial topology are distinct and are redshifted as the corresponding Chern number increases. Finally, the expressions for the conductivity components are valid for the entire graphene family and can be readily used by others.« less

  5. Nonlocal optical response in topological phase transitions in the graphene family

    DOE PAGES

    Rodriguez-Lopez, Pablo; de Melo Kort-Kamp, Wilton Junior; Dalvit, Diego Alejandro Roberto; ...

    2018-01-22

    We investigate the electromagnetic response of staggered two-dimensional materials of the graphene family, including silicene, germanene, and stanene, as they are driven through various topological phase transitions using external fields. Utilizing Kubo formalism, we compute their optical conductivity tensor taking into account the frequency and wave vector of the electromagnetic excitations, and study its behavior over the full electronic phase diagram of the materials. In particular, we find that the resonant behavior of the nonlocal Hall conductivity is strongly affected by the various topological phases present in these materials. We also consider the plasmon excitations in the graphene family andmore » find that nonlocality in the optical response can affect the plasmon dispersion spectra of the various phases. Here, we find a regime of wave vectors for which the plasmon relations for phases with trivial topology are essentially indistinguishable, while those for phases with nontrivial topology are distinct and are redshifted as the corresponding Chern number increases. Finally, the expressions for the conductivity components are valid for the entire graphene family and can be readily used by others.« less

  6. Nonlocal optical response in topological phase transitions in the graphene family

    NASA Astrophysics Data System (ADS)

    Rodriguez-Lopez, Pablo; Kort-Kamp, Wilton J. M.; Dalvit, Diego A. R.; Woods, Lilia M.

    2018-01-01

    We investigate the electromagnetic response of staggered two-dimensional materials of the graphene family, including silicene, germanene, and stanene, as they are driven through various topological phase transitions using external fields. Utilizing Kubo formalism, we compute their optical conductivity tensor taking into account the frequency and wave vector of the electromagnetic excitations, and study its behavior over the full electronic phase diagram of the materials. In particular, we find that the resonant behavior of the nonlocal Hall conductivity is strongly affected by the various topological phases present in these materials. We also consider the plasmon excitations in the graphene family and find that nonlocality in the optical response can affect the plasmon dispersion spectra of the various phases. We find a regime of wave vectors for which the plasmon relations for phases with trivial topology are essentially indistinguishable, while those for phases with nontrivial topology are distinct and are redshifted as the corresponding Chern number increases. The expressions for the conductivity components are valid for the entire graphene family and can be readily used by others.

  7. Early response in cognitive-behavior therapy for syndromes of medically unexplained symptoms.

    PubMed

    Kleinstäuber, Maria; Lambert, Michael J; Hiller, Wolfgang

    2017-05-25

    Early dramatic treatment response suggests a subset of patients who respond to treatment before most of it has been offered. These early responders tend to be over represented among those who are well at termination and at follow-up. Early response patterns in psychotherapy have been investigated only for a few of mental disorders so far. The main aim of the current study was to examine early response after five therapy-preparing sessions of a cognitive behavior therapy (CBT) for syndromes of medically unexplained symptoms (MUS). In the context of a randomized, waiting-list controlled trial 48 patients who suffered from ≥3 MUS over ≥6 months received 5 therapy-preparing sessions and 20 sessions of CBT for somatoform disorders. They completed self-report scales of somatic symptom severity (SOMS-7 T), depression (BDI-II), anxiety (BSI), illness anxiety and behavior (IAS) at pre-treatment, after 5 therapy-preparing sessions (FU-5P) and at therapy termination (FU-20 T). The current analyses are based on data from the treatment arm only. Repeated measure ANOVAs revealed a significant decrease of depression (d = 0.34), anxiety (d = 0.60), illness anxiety (d = 0.38) and illness behavior (d = 0.42), but no change of somatic symptom severity (d = -0.03) between pre-treatment and FU-5P. Hierarchical linear multiple regression analyses showed that symptom improvements between pre-treatment and FU-5P predict a better outcome at therapy termination for depression and illness anxiety, after controlling for pre-treatment scores. Mixed-effect ANOVAs revealed significant group*time interaction effects indicating differences in the course of symptom improvement over the therapy between patients who fulfilled a reliable change (i.e., early response) during the 5 therapy-preparing sessions and patients who did not reach an early reliable change. Demographic or clinical variables at pre-treatment were not significantly correlated with differential scores between pre

  8. Modification of acute and late-phase allergic responses to ovalbumin with lipopolysaccharide.

    PubMed

    Tulic, Mark K; Holt, Patrick G; Sly, Peter D

    2002-10-01

    We have previously shown that lipopolysaccharide (LPS) exposure in sensitised animals 18 h after ovalbumin (OVA) challenge inhibits OVA-induced airway hyper-responsiveness (AHR). In the present study, we investigated the effect of LPS on OVA-induced acute and late-phase allergic responses in sensitised rats when challenged with OVA. Rats were sensitised with OVA and 11 days later challenged with 1% OVA in the presence or absence of LPS (0.5-50 microg/ml) given in the same nebulizer. Acute responses to OVA were measured each minute for 30 min after challenge. In a separate group of animals, late-phase responses to OVA were determined at 24 h. At the end of each study, Evans blue dye was injected and animals sacrificed 30 min later. Bronchoalveolar lavage was obtained to monitor inflammatory cell migration and microvascular leakage. OVA challenge in sensitised animals produced an acute response with changes in lung mechanics peaking 10.0 +/- 0.9 min after OVA and returning to baseline within 30 min. This was followed 24 h later by increased responses to methacholine chloride (MCh), inflammatory cell influx and increased Evans blue leakage into the lungs. Presence of 5 or 50 microg/ml LPS in the nebulizer during OVA challenge altered the kinetics of the acute-phase response, with an immediate decrease in lung function (time to peak decreased from 10.3 +/- 1.2 to 1.8 +/- 0.2 and 2.2 +/- 0.3 min, respectively: p < 0.001, n = 6) and a dose-dependent attenuation of late-phase AHR, cellular influx (n = 5, p < 0.001) and Evans blue leakage (n = 5, p < 0.001) at 24 h. In summary, co-administration of OVA with LPS modifies both the acute and late-phase responses to the allergen, inducing an earlier acute change in lung function and a dose-dependent inhibition of late-phase responses to the allergen. Copyright 2002 S. Karger AG, Basel

  9. Acute phase response and plasma carotenoid concentrations in older women: findings from the nun study.

    PubMed

    Boosalis, M G; Snowdon, D A; Tully, C L; Gross, M D

    1996-01-01

    This cross-sectional study investigated whether the acute phase response was associated with suppressed circulating levels of antioxidants in a population of 85 Catholic sisters (nuns) ages 77-99 y. Fasting blood was drawn to determine the presence of an acute phase response, as defined by an elevation in the serum concentration of C-reactive protein. Serum concentrations of albumin, thyroxine-binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma concentrations of carotenoids and alpha tocopherol. Results showed that the presence of an acute phase response was associated with (1) an expected significant decrease in the serum concentrations of albumin (p < 0.001) and thyroxine-binding prealbumin (p < 0.001); (2) an expected significant increase in copper (p < 0.001) and fibrinogen (p = 0.003); and (3) a significant decrease in the plasma concentrations of lycopene (p = 0.03), alpha carotene (p = 0.02), beta carotene (p = 0.02), and total carotenoids (p = 0.01). The acute phase response was associated with decreased plasma levels of the antioxidants lycopene, alpha carotene, and beta carotene. This decrease in circulating antioxidants may further compromise antioxidant status and increase oxidative stress and damage in elders.

  10. In utero exposure to lipopolysaccharide alters the postnatal acute phase response in beef heifers

    This study was designed to determine the potential effect of prenatal lipopolysaccharide (LPS) exposure on the postnatal acute phase response (APR) to an LPS challenge in heifers. Pregnant crossbred cows (n = 50) were separated into prenatal immune stimulation (PIS; n = 25; administered 0.1 microgr...

  11. Modulation of the acute phase response in feedlot steers supplemented with Saccharomyces cerevisiae

    This study was designed to determine the effect of supplementing feedlot steers with Saccharomyces cerevisiae CNCM I-1079 (SC) on the acute phase response to a lipopolysaccharide (LPS) challenge. Steers (n = 18; 266 ± 4 kilograms body weight) were separated into three treatment groups (n = 6/treatm...

  12. Brain regions involved in the development of acute phase responses accompanying fever in rabbits.

    PubMed Central

    Morimoto, A; Murakami, N; Nakamori, T; Sakata, Y; Watanabe, T

    1989-01-01

    1. The effects of microinjection of rabbit endogenous pyrogen and human recombinant interleukin-1 alpha on rectal temperature and acute phase responses were extensively examined in forty different brain regions of rabbits. The acute phase responses that were investigated were the changes in plasma levels of iron, zinc and copper concentration and the changes in circulating leucocyte count. 2. The rostral hypothalamic regions, such as nucleus broca ventralis, preoptic area and anterior hypothalamic region, responded to the microinjection of endogenous pyrogen or interleukin-1 by producing both fever and acute phase responses. 3. The microinjection of endogenous pyrogen or interleukin-1 into the rostral hypothalamic regions significantly decreased the plasma levels of iron and zinc concentration 8 and 24 h after injection. The circulating leucocyte count increased 8 h after injection. However, neither the injections of endogenous pyrogen nor interleukin-1 affected the number of red blood cells. 4. The present results show that the rostral hypothalamic regions respond directly to endogenous pyrogen or interleukin-1 with the consequent development of fever and acute phase responses. PMID:2514261

  13. Differential role of afferent and efferent renal nerves in the maintenance of early- and late-phase Dahl S hypertension

    PubMed Central

    Foss, Jason D.; Fink, Gregory D.

    2015-01-01

    Clinical data suggest that renal denervation (RDNX) may be an effective treatment for human hypertension; however, it is unclear whether this therapeutic effect is due to ablation of afferent or efferent renal nerves. We have previously shown that RDNX lowers arterial pressure in hypertensive Dahl salt-sensitive (S) rats to a similar degree observed in clinical trials. In addition, we have recently developed a method for selective ablation of afferent renal nerves (renal-CAP). In the present study, we tested the hypothesis that the antihypertensive effect of RDNX in the Dahl S rat is due to ablation of afferent renal nerves by comparing the effect of complete RDNX to renal-CAP during two phases of hypertension in the Dahl S rat. In the early phase, rats underwent treatment after 3 wk of high-NaCl feeding when mean arterial pressure (MAP) was ∼140 mmHg. In the late phase, rats underwent treatment after 9 wk of high NaCl feeding, when MAP was ∼170 mmHg. RDNX reduced MAP ∼10 mmHg compared with sham surgery in both the early and late phase, whereas renal-CAP had no antihypertensive effect. These results suggest that, in the Dahl S rat, the antihypertensive effect of RDNX is not dependent on pretreatment arterial pressure, nor is it due to ablation of afferent renal nerves. PMID:26661098

  14. Sleep Moderates the Association Between Response Inhibition and Self-Regulation in Early Childhood

    PubMed Central

    Schumacher, Allyson M.; Miller, Alison L.; Watamura, Sarah E.; Kurth, Salome; Lassonde, Jonathan M.; LeBourgeois, Monique K.

    2017-01-01

    Early childhood is a time of rapid developmental changes in sleep, cognitive control processes, and the regulation of emotion and behavior. This experimental study examined sleep-dependent effects on response inhibition and self-regulation, as well as whether acute sleep restriction moderated the association between these processes. Preschool children (N = 19; 45.6 ± 2.2 months; 11 female) followed a strict sleep schedule for at least 3 days before each of 2 morning behavior assessments: baseline (habitual nap/night sleep) and sleep restriction (missed nap/delayed bedtime). Response inhibition was evaluated via a go/no-go task. Twelve self-regulation strategies were coded from videotapes of children while attempting an unsolvable puzzle. We then created composite variables representing adaptive and maladaptive self-regulation strategies. Although we found no sleep-dependent effects on response inhibition or self-regulation measures, linear mixed-effects regression showed that acute sleep restriction moderated the relationship between these processes. At baseline, children with better response inhibition were more likely to use adaptive self-regulation strategies (e.g., self-talk, alternate strategies), and those with poorer response inhibition showed increased use of maladaptive self-regulation strategies (e.g., perseveration, fidgeting); however, response inhibition was not related to self-regulation strategies following sleep restriction. Our results showing a sleep-dependent effect on the associations between response inhibition and self-regulation strategies indicate that adequate sleep facilitates synergy between processes supporting optimal social-emotional functioning in early childhood. Although replication studies are needed, findings suggest that sleep may alter connections between maturing emotional and cognitive systems, which have important implications for understanding risk for or resilience to developmental psychopathology. PMID:27652491

  15. Early loss of the glucagon response to hypoglycemia in adolescents with type 1 diabetes.

    PubMed

    Siafarikas, Aris; Johnston, Robert J; Bulsara, Max K; O'Leary, Peter; Jones, Timothy W; Davis, Elizabeth A

    2012-08-01

    To assess the glucagon response to hypoglycemia and identify influencing factors in patients with type 1 diabetes compared with nondiabetic control subjects. Hyperinsulinemic hypoglycemic clamp studies were performed in all participants. The glucagon response to both hypoglycemia and arginine was measured, as well as epinephrine, cortisol, and growth hormone responses to hypoglycemia. Residual β-cell function was assessed using fasting and stimulated C-peptide. Twenty-eight nonobese adolescents with type 1 diabetes (14 female, mean age 14.9 years [range 11.2-19.8]) and 12 healthy control subjects (6 female, 15.3 years [12.8-18.7]) participated in the study. Median duration of type 1 diabetes was 0.66 years (range 0.01-9.9). The glucagon peak to arginine stimulation was similar between groups (P = 0.27). In contrast, the glucagon peak to hypoglycemia was reduced in the group with diabetes (95% CI): 68 (62-74) vs. 96 (87-115) pg/mL (P < 0.001). This response was greater than 3 SDs from baseline for only 7% of subjects with type 1 diabetes in comparison with 83% of control subjects and was lost at a median duration of diabetes of 8 months and as early as 1 month after diagnosis (R = -0.41, P < 0.01). There was no correlation in response with height, weight, BMI, and HbA(1c). Epinephrine, cortisol, and growth hormone responses to hypoglycemia were present in both groups. The glucagon response to hypoglycemia in adolescents with type 1 diabetes is influenced by the duration of diabetes and can be lost early in the course of the disease.

  16. Sleep Moderates the Association Between Response Inhibition and Self-Regulation in Early Childhood.

    PubMed

    Schumacher, Allyson M; Miller, Alison L; Watamura, Sarah E; Kurth, Salome; Lassonde, Jonathan M; LeBourgeois, Monique K

    2017-01-01

    Early childhood is a time of rapid developmental changes in sleep, cognitive control processes, and the regulation of emotion and behavior. This experimental study examined sleep-dependent effects on response inhibition and self-regulation, as well as whether acute sleep restriction moderated the association between these processes. Preschool children (N = 19; 45.6 ± 2.2 months; 11 female) followed a strict sleep schedule for at least 3 days before each of 2 morning behavior assessments: baseline (habitual nap/night sleep) and sleep restriction (missed nap/delayed bedtime). Response inhibition was evaluated via a go/no-go task. Twelve self-regulation strategies were coded from videotapes of children while attempting an unsolvable puzzle. We then created composite variables representing adaptive and maladaptive self-regulation strategies. Although we found no sleep-dependent effects on response inhibition or self-regulation measures, linear mixed-effects regression showed that acute sleep restriction moderated the relationship between these processes. At baseline, children with better response inhibition were more likely to use adaptive self-regulation strategies (e.g., self-talk, alternate strategies), and those with poorer response inhibition showed increased use of maladaptive self-regulation strategies (e.g., perseveration, fidgeting); however, response inhibition was not related to self-regulation strategies following sleep restriction. Our results showing a sleep-dependent effect on the associations between response inhibition and self-regulation strategies indicate that adequate sleep facilitates synergy between processes supporting optimal social-emotional functioning in early childhood. Although replication studies are needed, findings suggest that sleep may alter connections between maturing emotional and cognitive systems, which have important implications for understanding risk for or resilience to developmental psychopathology.

  17. Phytochrome-mediated germination and early development in spores of Dryopteris filix-mas L.: phase-specific and non phase-specific inhibition by staurosporine

    NASA Technical Reports Server (NTRS)

    Haas, C. J.; Scheuerlein, R.; Roux, S. J.

    1991-01-01

    The alkaloid staurosporine, currently known as the most potent inhibitor of protein kinase C, PKC, was tested for its ability to inhibit phytochrome-mediated spore germination in Dryopteris filix-mas L., evaluated by the induction of chlorophyll synthesis. Approximately half-maximal inhibition was obtained at a concentration of 10(-5) M. This effect of staurosporine was phase-specific and was found during the same period in which the presence of extracellular calcium is necessary for realization of the light signal. Furthermore, the ability of staurosporine to prevent progression of a germinated spore into early gametophyte development, evaluated by the accumulation of chlorophyll, was examined. Again, staurosporine (10(-5) M) significantly diminished chlorophyll accumulation, determined quantitatively in vivo by single-cell measurements, in a non-phase specific way. The fact that the phase-specific inhibitory effect of staurosporine in preventing germination was coincident with the phase-specific requirement of Ca2+ suggests that both Ca2+ and staurosporine affect the same step in the signal-transduction chain. A phosphorylation event catalysed by PKC or any Ca2+ -dependent protein kinase is proposed as the target of staurosporine and Ca2+.

  18. Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System.

    PubMed

    Douw, Gooske; Huisman-de Waal, Getty; van Zanten, Arthur R H; van der Hoeven, Johannes G; Schoonhoven, Lisette

    2017-09-01

    To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning Score levels not reaching this point. Dutch-early-nurse-worry-indicator-score comprises nine indicators underlying nurses' 'worry' about a patient's condition. All indicators independently show significant association with unplanned intensive care/high dependency unit admission or unexpected mortality. Prediction of this outcome improved by adding the dutch-early-nurse-worry-indicator-score indicators to an Early Warning Score based on vital signs. An observational cohort study was conducted on three surgical wards in a tertiary university-affiliated teaching hospital. Included were surgical, native-speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early-nurse-worry-indicator-score indicators every shift or when worried. Vital signs were measured according to the prevailing protocol. Unplanned intensive care/high dependency unit admission or unexpected mortality was the composite endpoint. Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators were calculated at various Early Warning Score levels in control and event groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a multiple logistic regression analysis, we calculated a weighted score and calculated sensitivity, specificity, positive predicted value and negative predicted value for each possible total score. In 3522 patients, 102 (2·9%) had an unplanned intensive care/high dependency unit admissions (n = 97) or unexpected mortality (n = 5). Patients with such events and only slightly changed vital signs had significantly higher percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators expressed than patients in the control group. Increasing number

  19. Improving the phase response of an atom interferometer by means of temporal pulse shaping

    NASA Astrophysics Data System (ADS)

    Fang, Bess; Mielec, Nicolas; Savoie, Denis; Altorio, Matteo; Landragin, Arnaud; Geiger, Remi

    2018-02-01

    We study theoretically and experimentally the influence of temporally shaping the light pulses in an atom interferometer, with a focus on the phase response of the interferometer. We show that smooth light pulse shapes allow rejecting high frequency phase fluctuations (above the Rabi frequency) and thus relax the requirements on the phase noise or frequency noise of the interrogation lasers driving the interferometer. The light pulse shape is also shown to modify the scale factor of the interferometer, which has to be taken into account in the evaluation of its accuracy budget. We discuss the trade-offs to operate when choosing a particular pulse shape, by taking into account phase noise rejection, velocity selectivity, and applicability to large momentum transfer atom interferometry.

  20. Lateral geniculate lesions block circadian phase-shift responses to a benzodiazepine.

    PubMed Central

    Johnson, R F; Smale, L; Moore, R Y; Morin, L P

    1988-01-01

    Several pharmacological treatments, including application of an excitatory neurotoxin to the lateral geniculate nucleus (LGN) and systemic administration of triazolam, a clinically effective benzodiazepine, can elicit large phase shifts in a circadian rhythm according to the time of administration. The hypothesis that the LGN might mediate the effect of triazolam on circadian clock function was tested. Bilateral lesions of the LGN, which destroyed the connection from the intergeniculate leaflet to the suprachiasmatic nucleus, blocked phase-shift responses to triazolam. The requirement of an intact LGN for triazolam to shift circadian phase suggests that the LGN may be a site through which stimuli gain access to the circadian clock to modulate rhythm phase and entrainment. Images PMID:3293053

  1. A three pulse phase response curve to three milligrams of melatonin in humans

    PubMed Central

    Burgess, Helen J; Revell, Victoria L; Eastman, Charmane I

    2008-01-01

    Exogenous melatonin is increasingly used for its phase shifting and soporific effects. We generated a three pulse phase response curve (PRC) to exogenous melatonin (3 mg) by administering it to free-running subjects. Young healthy subjects (n = 27) participated in two 5 day laboratory sessions, each preceded by at least a week of habitual, but fixed sleep. Each 5 day laboratory session started and ended with a phase assessment to measure the circadian rhythm of endogenous melatonin in dim light using 30 min saliva samples. In between were three days in an ultradian dim light (< 150 lux)–dark cycle (LD 2.5 : 1.5) during which each subject took one pill per day at the same clock time (3 mg melatonin or placebo, double blind, counterbalanced). Each individual's phase shift to exogenous melatonin was corrected by subtracting their phase shift to placebo (a free-run). The resulting PRC has a phase advance portion peaking about 5 h before the dim light melatonin onset, in the afternoon. The phase delay portion peaks about 11 h after the dim light melatonin onset, shortly after the usual time of morning awakening. A dead zone of minimal phase shifts occurred around the first half of habitual sleep. The fitted maximum advance and delay shifts were 1.8 h and 1.3 h, respectively. This new PRC will aid in determining the optimal time to administer exogenous melatonin to achieve desired phase shifts and demonstrates that using exogenous melatonin as a sleep aid at night has minimal phase shifting effects. PMID:18006583

  2. Exposure to Violence Predicting Cortisol Response During Adolescence and Early Adulthood: Understanding Moderating Factors

    PubMed Central

    Heinze, Justin E.; Miller, Alison L.; Stoddard, Sarah A.; Zimmerman, Marc A.

    2014-01-01

    Previous research on the association between violence and biological stress regulation has been largely cross-sectional, and has also focused on childhood. Using longitudinal data from a low-income, high-risk, predominantly African-American sample (n = 266; 57 % female), we tested hypotheses about the influence of cumulative exposure to violence during adolescence and early adulthood on cortisol responses in early adulthood. We found that cumulative exposure to violence predicted an attenuated cortisol response. Further, we tested whether sex, mothers’ support, or fathers’ support moderated the effect of exposure to violence on cortisol responses. We found that the effect of cumulative exposure to violence on cortisol was modified by sex; specifically, males exposed to violence exhibited a more attenuated response pattern. In addition, the effect of cumulative exposure to violence on cortisol was moderated by the presence of fathers’ support during adolescence. The findings contribute to a better understanding of how cumulative exposure to violence influences biological outcomes, emphasizing the need to understand sex and parental support as moderators of risk. PMID:24458765

  3. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

    PubMed Central

    Weckbach, Sebastian; Perl, Mario; Heiland, Tim; Braumüller, Sonja; Stahel, Philip F.; Flierl, Michael A.; Ignatius, Anita; Gebhard, Florian; Huber-Lang, Markus

    2012-01-01

    Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples. Results. Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma. PMID:22481866

  4. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence.

    PubMed

    Guyer, Amanda E; Jarcho, Johanna M; Pérez-Edgar, Koraly; Degnan, Kathryn A; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

    2015-07-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children's caregiving context. The convergence of a child's temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (M(age) = 17.89 years, N = 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development.

  5. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence

    PubMed Central

    Guyer, Amanda E.; Jarcho, Johanna M.; Pérez-Edgar, Koraly; Degnan, Kathryn A.; Pine, Daniel S.; Fox, Nathan A.; Nelson, Eric E.

    2015-01-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children’s caregiving context. The convergence of a child’s temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (Mage = 17.89 years, N= 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development. PMID:25588884

  6. [The correlation between serum uric acid level and early-phase insulin secretion in subjects with normal glucose regulation].

    PubMed

    Lu, L; Zheng, F P; Li, H

    2016-05-01

    To investigate the correlation between serum uric acid (SUA) level and early-phase insulin secretion in subjects with normal glucose regulation (NGR). Totally 367 community NGR residents confirmed by a 75g oral glucose tolerance test were enrolled. The insulin resistance index (HOMA-IR) and the early-phase insulin secretion index after a glucose load (ΔI30/ΔG30) were used to estimate the insulin sensitivity and the early-phase insulin secretion, respectively. The subjects were divided into 4 groups according to the SUA level quartiles. Differences in early-phase insulin levels, ΔI30/ΔG30, and HOMA-IR were compared among the 4 groups. Age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting insulin (FINS), 30 minutes postprandial insulin(30 minINS), 2 hours postprandial insulin(2hINS), HOMA-IR and TG levels increased across the rising categories of SUA levels, while the HDL-C was decreased across the SUA groups (P<0.01). The SUA level was positively correlated with age(r=0.157, P<0.01), BMI(r=0.262, P<0.01), waist circumference(r=0.372, P<0.01), systolic blood pressure(r=0.200, P<0.01), diastolic blood pressure(r=0.254, P<0.01), 30 minutes postprandial plasma glucose(r=0.118, P=0.023), FINS(r=0.249, P<0.01), 30minINS(r=0.189, P<0.01), 2hINS(r=0.206, P<0.01), glycosylated hemoglobin(HbA1c, r=0.106, P=0.042), HOMA-IR(r=0.244, P<0.01), TG(r=0.350, P<0.01), ΔI30/ΔG30(r=0.144, P<0.01), and negatively correlated with HDL-C level(r=-0.321, P<0.01). Multiple stepwise regression analysis showed that SUA(β=0.292, P<0.01) and HOMA-IR(β=29.821, P<0.01) were positively associated with ΔI30/ΔG30. SUA level is closely related with the early-phase insulin secretion in NGR subjects.

  7. Low-energy inelastic response in the superconducting phases of PrOs4Sb12

    NASA Astrophysics Data System (ADS)

    Setty, Chandan; Wang, Yuxuan; Phillips, Philip W.

    2017-08-01

    Recent ac susceptibility and polar Kerr effect measurements in the skutterudite superconductor PrOs4Sb12 (POS) (E. M. Levenson-Falk, E. R. Schemm, M. B. Maple, and A. Kapitulnik, arXiv:1609.07535) uncovered the nature of the superconducting double transition from a high-temperature, high-field, time-reversal symmetric phase (or the A phase) to a low-temperature, low-field, time-reversal symmetry-broken phase (or the B phase). Starting from a microscopic model, we derive a Ginzburg-Landau expansion relevant to POS that describes this entrance into the time-reversal symmetry-broken phase along the temperature axis. We also provide a study of the low-energy inelastic (Raman) response in both the A and B phases of POS, and seek additional signatures which could help reveal the exact form of the gap functions previously proposed in these phases. By appropriately manipulating the incoming and scattered light geometries, along with additional subtraction procedures and suitable assumptions, we show that one can access the various irreducible representations contained in the point group describing POS. We demonstrate how to use this technique on example order parameters proposed in POS. Depending on whether there exist nodes along the c axis, we find additional low-energy spectral weight within the superconducting gap in the Eg geometry, a feature that could pinpoint the location of nodes on the Fermi surface.

  8. Using Geo-Data Corporately on the Response Phase of Emergency Management

    NASA Astrophysics Data System (ADS)

    Demir Ozbek, E.; Ates, S.; Aydinoglu, A. C.

    2015-08-01

    Response phase of emergency management is the most complex phase in the entire cycle because it requires cooperation between various actors relating to emergency sectors. A variety of geo-data is needed at the emergency response such as; existing data provided by different institutions and dynamic data collected by different sectors at the time of the disaster. Disaster event is managed according to elaborately defined activity-actor-task-geodata cycle. In this concept, every activity of emergency response is determined with Standard Operation Procedure that enables users to understand their tasks and required data in any activity. In this study, a general conceptual approach for disaster and emergency management system is developed based on the regulations to serve applications in Istanbul Governorship Provincial Disaster and Emergency Directorate. The approach is implemented to industrial facility explosion example. In preparation phase, optimum ambulance locations are determined according to general response time of the ambulance to all injury cases in addition to areas that have industrial fire risk. Management of the industrial fire case is organized according to defined actors, activities, and working cycle that describe required geo-data. A response scenario was prepared and performed for an industrial facility explosion event to exercise effective working cycle of actors. This scenario provides using geo-data corporately between different actors while required data for each task is defined to manage the industrial facility explosion event. Following developing web technologies, this scenario based approach can be effective to use geo-data on the web corporately.

  9. Early print-tuned ERP response with minimal involvement of linguistic processing in Japanese Hiragana strings.

    PubMed

    Okumura, Yasuko; Kasai, Tetsuko; Murohashi, Harumitsu

    2014-04-16

    The act of reading leads to the development of specific neural responses for print, the most frequently reported of which is the left occipitotemporal N170 component of event-related potentials. However, it remains unclear whether this electrophysiological response solely involves print-tuned neural activities. The present study examined an early print-tuned event-related potential response with minimal involvement of linguistic processing in a nonalphabetic language. Japanese Hiragana words, nonwords, and alphanumeric symbol strings were presented rapidly and the task was to detect the change in color of a fixation cross to restrict linguistic processing. As a result, Hiragana words and nonwords elicited a larger posterior N1 than alphanumeric symbol strings bilaterally, irrespective of intercharacter spacing. The fact that this N1 was enhanced specifically for rapidly presented Hiragana strings suggests the existence of print-tuned neural processes that are relatively independent of the influence of linguistic processing.

  10. Carbohydrate-mediated responses during zygotic and early somatic embryogenesis in the endangered conifer, Araucaria angustifolia

    PubMed Central

    Elbl, Paula; De Souza, Amanda P.; Jardim, Vinicius; de Oliveira, Leandro F.; Macedo, Amanda F.; dos Santos, André L. W.; Buckeridge, Marcos S.; Floh, Eny I. S.

    2017-01-01

    Three zygotic developmental stages and two somatic Araucaria angustifolia cell lines with contrasting embryogenic potential were analyzed to identify the carbohydrate-mediated responses associated with embryo formation. Using a comparison between zygotic and somatic embryogenesis systems, the non-structural carbohydrate content, cell wall sugar composition and expression of genes involved in sugar sensing were analyzed, and a network analysis was used to identify coordinated features during embryogenesis. We observed that carbohydrate-mediated responses occur mainly during the early stages of zygotic embryo formation, and that during seed development there are coordinated changes that affect the development of the different structures (embryo and megagametophyte). Furthermore, sucrose and starch accumulation were associated with the responsiveness of the cell lines. This study sheds light on how carbohydrate metabolism is influenced during zygotic and somatic embryogenesis in the endangered conifer species, A. angustifolia. PMID:28678868

  11. How Phase 3 Early Learning Challenge States Are Leveraging ELC Funds and Other Funds to Support Inclusion. State TA Resources

    ERIC Educational Resources Information Center

    Early Learning Challenge Technical Assistance, 2017

    2017-01-01

    This resource was prepared in response to a request for information about how the six Phase 3 ELC States (Georgia, Kentucky, Michigan, New Jersey, Pennsylvania, and Vermont) are leveraging ELC funds and other State funds to support inclusion. This information will be helpful to other States as they consider how to continue to increase the quality…

  12. Early response to venlafaxine antidepressant correlates with lower ACTH levels prior to pharmacological treatment.

    PubMed

    Araya, A V; Rojas, P; Fritsch, R; Rojas, R; Herrera, L; Rojas, G; Gatica, H; Silva, H; Fiedler, J L

    2006-12-01

    A link between stressful life events and development or exacerbation of depression has been established via a large body of evidence. An alteration in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression has also been associated with an increase in cortisol secretion. As arginine-vasopressin (AVP) plays an important role in the activation of HPA axis during stress, the present study investigated ACTH and cortisol secretory response induced by an AVP-related peptide desmopressin (ddAVP) in patients with major depression. Prior to antidepressant treatment, endocrinological parameters were evaluated and correlated with the clinical response to venlafaxine treatment, which offers a dual antidepressant action. Depressive patients with no other psychiatric pathology were evaluated with 17-item Hamilton Depression Scale (HAM-D) in order to follow-up the response to venlafaxine. After 1 wk of treatment, 60% of patients reduced their initial HAM-D score to at least 25%; this group was classified as early responders. The other group (40%) started to reduce significantly their HAM-D score after 3 wk of treatment and was classified as late responders. After 6 wk of treatment both groups have reduced HAM-D score to at least 25% of the baseline score. Prior to the pharmacological treatment, both early and late responders showed salivary cortisol rhythm and urinary free cortisol (UFC) in 24-h similar to healthy subjects. However, we did observe differences in basal ACTH secretion, showing that the late responder group had higher basal ACTH than both early responders and controls. The ddAVP challenge promoted a robust secretion of ACTH only in late responders, suggesting a different sensitivity of pituitary vasopressin receptor. The differences in clinical response to venlafaxine among depressive patients seem to be related to endocrinological parameters.

  13. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

    Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

    2014-01-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

  14. Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

    PubMed

    Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

    2016-07-01

    Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

  15. Submillisecond-response and scattering-free infrared liquid crystal phase modulators.

    PubMed

    Sun, Jie; Chen, Yuan; Wu, Shin-Tson

    2012-08-27

    We demonstrate a submillisecond-response and scattering-free infrared phase modulator using a polymer network liquid crystal (PNLC). The required voltage for achieving 2π phase change at λ = 1.06 µm is 70V (or 5.8 V/μm) and the measured response time is ~200 µs at 25°C and 30 µs at 70°C. Opposite to our conventional understanding, a high viscosity LC helps to achieve small domain size during polymerization process, which in turn reduces the response time and light scattering. We use Rayleigh-Gans-Debye scattering model to analyze the voltage-on state transmission spectra. When the domain size is comparable to the wavelength, the model fits with experimental results well. But when the domain size is smaller than the wavelength, the simple Rayleigh model works well.

  16. Arsenic and Immune Response to Infection During Pregnancy and Early Life

    PubMed Central

    Attreed, Sarah E.; Navas-Acien, Ana

    2017-01-01

    Purpose of Review Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity—including the specific mechanisms in humans—is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. Recent Findings The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Summary Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines. PMID:28488132

  17. Arsenic and Immune Response to Infection During Pregnancy and Early Life.

    PubMed

    Attreed, Sarah E; Navas-Acien, Ana; Heaney, Christopher D

    2017-06-01

    Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity-including the specific mechanisms in humans-is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.

  18. Energy input and response from prompt and early optical afterglow emission in gamma-ray bursts.

    PubMed

    Vestrand, W T; Wren, J A; Wozniak, P R; Aptekar, R; Golentskii, S; Pal'shin, V; Sakamoto, T; White, R R; Evans, S; Casperson, D; Fenimore, E

    2006-07-13

    The taxonomy of optical emission detected during the critical first few minutes after the onset of a gamma-ray burst (GRB) defines two broad classes: prompt optical emission correlated with prompt gamma-ray emission, and early optical afterglow emission uncorrelated with the gamma-ray emission. The standard theoretical interpretation attributes prompt emission to internal shocks in the ultra-relativistic outflow generated by the internal engine; early afterglow emission is attributed to shocks generated by interaction with the surrounding medium. Here we report on observations of a bright GRB that, for the first time, clearly show the temporal relationship and relative strength of the two optical components. The observations indicate that early afterglow emission can be understood as reverberation of the energy input measured by prompt emission. Measurements of the early afterglow reverberations therefore probe the structure of the environment around the burst, whereas the subsequent response to late-time impulsive energy releases reveals how earlier flaring episodes have altered the jet and environment parameters. Many GRBs are generated by the death of massive stars that were born and died before the Universe was ten per cent of its current age, so GRB afterglow reverberations provide clues about the environments around some of the first stars.

  19. Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever

    PubMed Central

    Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R.

    2016-01-01

    Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (<96 h) was used to globally probe the serum metabolome to uncover early prognostic biomarkers of DHF. We identified 20 metabolites that are differentially enriched (p<0.05, fold change >1.5) in the serum, among which are two products of tryptophan metabolism–serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved

  20. Optimization of Primary Drying in Lyophilization during Early Phase Drug Development using a Definitive Screening Design with Formulation and Process Factors.

    PubMed

    Goldman, Johnathan M; More, Haresh T; Yee, Olga; Borgeson, Elizabeth; Remy, Brenda; Rowe, Jasmine; Sadineni, Vikram

    2018-06-08

    Development of optimal drug product lyophilization cycles is typically accomplished via multiple engineering runs to determine appropriate process parameters. These runs require significant time and product investments, which are especially costly during early phase development when the drug product formulation and lyophilization process are often defined simultaneously. Even small changes in the formulation may require a new set of engineering runs to define lyophilization process parameters. In order to overcome these development difficulties, an eight factor definitive screening design (DSD), including both formulation and process parameters, was executed on a fully human monoclonal antibody (mAb) drug product. The DSD enables evaluation of several interdependent factors to define critical parameters that affect primary drying time and product temperature. From these parameters, a lyophilization development model is defined where near optimal process parameters can be derived for many different drug product formulations. This concept is demonstrated on a mAb drug product where statistically predicted cycle responses agree well with those measured experimentally. This design of experiments (DoE) approach for early phase lyophilization cycle development offers a workflow that significantly decreases the development time of clinically and potentially commercially viable lyophilization cycles for a platform formulation that still has variable range of compositions. Copyright © 2018. Published by Elsevier Inc.

  1. The steroidogenic response and corpus luteum expression of the steroidogenic acute regulatory protein after human chorionic gonadotropin administration at different times in the human luteal phase.

    PubMed

    Kohen, Paulina; Castro, Olga; Palomino, Alberto; Muñoz, Alex; Christenson, Lane K; Sierralta, Walter; Carvallo, Pilar; Strauss, Jerome F; Devoto, Luigi

    2003-07-01

    This study was designed 1) to assess corpus luteum (CL) steroidogenesis in response to exogenous human chorionic gonadotropin (hCG) at different times during the luteal phase, 2) to examine the effect of hCG on steroidogenic acute regulatory protein (StAR) expression within the CL, 3) to correlate StAR expression and luteal steroidogenic responses to hCG, and 4) to determine whether endogenous LH regulates ovarian steroidogenesis in the early luteal phase. Blood was collected before and after hCG treatment for steroid and hCGbeta determinations. CL were obtained at the time of surgery to assess StAR gene and protein expression. During the early luteal phase various women received the GnRH antagonist for 24-48 h; some of them also received hCG 24 h after the GnRH antagonist. A slight steroidogenic response to hCG was observed in early luteal phase; 17alpha-hydroxyprogesterone, but not progesterone (P4), levels were significantly increased 8 h post-hCG, indicating a differential response by the granulosa and theca-lutein cells. The 1.6- and 4.4-kb StAR transcripts and the 37-kDa preprotein and 30-kDa mature StAR protein did not change post-hCG administration in early luteal phase CL. In contrast, the StAR 4.4- and 1.6-kb transcripts diminished significantly (P < 0.05) after the antagonist treatment. Immunohistochemical staining for StAR protein was weak, particularly in granulosa-lutein cells. Treatment with hCG restored StAR mRNA and protein and plasma P4 levels within 24 h in antagonist-treated women. hCG stimulated the highest plasma concentrations of P4 and estradiol in the midluteal phase, indicating its greatest steroidogenic capacity. Midluteal tissue StAR gene and protein expression increased by 1.6- and 1.4-fold after 24 h of hCG treatment, respectively. Administration of hCG resulted in the greatest increment in plasma P4 (4-fold) and 17alpha-hydroxyprogesterone (3-fold) levels over baseline in the late luteal phase. This was associated with an increase in

  2. A new Bayesian Inference-based Phase Associator for Earthquake Early Warning

    NASA Astrophysics Data System (ADS)

    Meier, Men-Andrin; Heaton, Thomas; Clinton, John; Wiemer, Stefan

    2013-04-01

    State of the art network-based Earthquake Early Warning (EEW) systems can provide warnings for large magnitude 7+ earthquakes. Although regions in the direct vicinity of the epicenter will not receive warnings prior to damaging shaking, real-time event characterization is available before the destructive S-wave arrival across much of the strongly affected region. In contrast, in the case of the more frequent medium size events, such as the devastating 1994 Mw6.7 Northridge, California, earthquake, providing timely warning to the smaller damage zone is more difficult. For such events the "blind zone" of current systems (e.g. the CISN ShakeAlert system in California) is similar in size to the area over which severe damage occurs. We propose a faster and more robust Bayesian inference-based event associator, that in contrast to the current standard associators (e.g. Earthworm Binder), is tailored to EEW and exploits information other than only phase arrival times. In particular, the associator potentially allows for reliable automated event association with as little as two observations, which, compared to the ShakeAlert system, would speed up the real-time characterizations by about ten seconds and thus reduce the blind zone area by up to 80%. We compile an extensive data set of regional and teleseismic earthquake and noise waveforms spanning a wide range of earthquake magnitudes and tectonic regimes. We pass these waveforms through a causal real-time filterbank with passband filters between 0.1 and 50Hz, and, updating every second from the event detection, extract the maximum amplitudes in each frequency band. Using this dataset, we define distributions of amplitude maxima in each passband as a function of epicentral distance and magnitude. For the real-time data, we pass incoming broadband and strong motion waveforms through the same filterbank and extract an evolving set of maximum amplitudes in each passband. We use the maximum amplitude distributions to check

  3. Cosmological QCD phase transition in steady non-equilibrium dissipative Hořava–Lifshitz early universe

    SciT

    Khodadi, M., E-mail: M.Khodadi@sbu.ac.ir; Sepangi, H.R., E-mail: hr-sepangi@sbu.ac.ir

    We study the phase transition from quark–gluon plasma to hadrons in the early universe in the context of non-equilibrium thermodynamics. According to the standard model of cosmology, a phase transition associated with chiral symmetry breaking after the electro-weak transition has occurred when the universe was about 1–10 μs old. We focus attention on such a phase transition in the presence of a viscous relativistic cosmological background fluid in the framework of non-detailed balance Hořava–Lifshitz cosmology within an effective model of QCD. We consider a flat Friedmann–Robertson–Walker universe filled with a non-causal and a causal bulk viscous cosmological fluid respectively and investigatemore » the effects of the running coupling constants of Hořava–Lifshitz gravity, λ, on the evolution of the physical quantities relevant to a description of the early universe, namely, the temperature T, scale factor a, deceleration parameter q and dimensionless ratio of the bulk viscosity coefficient to entropy density (ξ)/s . We assume that the bulk viscosity cosmological background fluid obeys the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively. -- Highlights: •In this paper we have studied quark–hadron phase transition in the early universe in the context of the Hořava–Lifshitz model. •We use a flat FRW universe with the bulk viscosity cosmological background fluid obeying the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively.« less

  4. Phase II Validation of a New Panel of Biomarkers for Early Detection of Ovarian Cancer — EDRN Public Portal

    Cancer.gov

    While all cancer patients could potentially benefit from earlier detection and prevention, the development of new screening technologies and chemoprevention for epithelial ovarian cancer (EOC) is unique in this regard. EOC is characterized by few early symptoms, presentation at an advanced stage, and poor survival. Presently there is no commercially available test that is diagnostic for either early or advanced stage epithelial ovarian cancer. The most commonly used marker, CA125, identifies a group of cell surface glycoproteins, which have uncertain biological behavior and very limited clinical utility for the detection of early stage disease. In recent years, several approaches have been used in order to develop a test for early detection, including the analysis of serum samples by SELDI-TOF and MALDI-TOF to find proteins or protein fragments of unknown identity that detect the presence/absence of cancer. Unfortunately, at the present time, none of these techniques have been shown to be adequate. Therefore, the development of a test that can detect early stages of the disease could dramatically improve treatment success and long-term survival. We have developed a new blood test based on a different approach: 1) we used known proteins related to cancer biology, 2) we characterized these proteins with several different screening steps using samples obtained from both healthy and cancer patient populations, and 3) validated the results with different techniques. Using split point analysis with four markers, 96 out of 100 EOC patients (96%) were correctly diagnosed with ovarian cancer (including 23 of 24 patients with Stage I/II EOC). In the healthy group, 6 out of 106 individuals were diagnosed incorrectly (5.6%). Working in collaboration with the Early Detection Network (EDRN/NCI/NIH), we performed Phase I discovery study confirming the potential application of this test for early detection of ovarian cancer (Preliminary results). The main objective of this pr

  5. Responsive parenting: establishing early foundations for social, communication, and independent problem-solving skills.

    PubMed

    Landry, Susan H; Smith, Karen E; Swank, Paul R

    2006-07-01

    Mothers whose infants varied in early biological characteristics (born at term, n = 120; born at very low birth weight [VLBW], n = 144) were randomized to a target group (n = 133) or developmental feedback comparison group (n = 131) to determine whether learning responsive behaviors would facilitate infant development. The target condition included videotaped examples, problem-solving activities, and mothers' critique of their own behaviors through video procedures across 10 home visits. All target versus comparison mothers showed greater increases across multiple responsiveness behaviors observed in 4 assessments conducted across 6-13 months of age; changes in emotionally supportive behaviors were strongest for target mothers of infants born at VLBW. Increased maternal responsiveness facilitated greater growth in target infants' social, emotional, communication, and cognitive competence, supporting a causal role for responsiveness on infant development. Although benefits were generally comparable across risk groups, aspects of social and emotional skills showed greater change for those born at VLBW. Evidence for responsiveness as a multidimensional construct was provided as well as the importance of different aspects of responsiveness mediating the effect of the intervention on different infant skill domains.

  6. Utilisation of helicopter emergency medical services in the early medical response to major incidents: a systematic literature review.

    PubMed

    Johnsen, Anne Siri; Fattah, Sabina; Sollid, Stephen J M; Rehn, Marius

    2016-02-09

    This systematic review identifies, describes and appraises the literature describing the utilisation of helicopter emergency medical services (HEMS) in the early medical response to major incidents. Early prehospital phase of a major incident. Systematic literature review performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Web of Science, PsycINFO, Scopus, Cinahl, Bibsys Ask, Norart, Svemed and UpToDate were searched using phrases that combined HEMS and 'major incidents' to identify when and how HEMS was utilised. The identified studies were subjected to data extraction and appraisal. The database search identified 4948 articles. Based on the title and abstract, the full text of 96 articles was obtained; of these, 37 articles were included in the review, and an additional five were identified by searching the reference lists of the 37 articles. HEMS was used to transport medical and rescue personnel to the incident and to transport patients to the hospital, especially when the infrastructure was damaged. Insufficient air traffic control, weather conditions, inadequate landing sites and failing communication were described as challenging in some incidents. HEMS was used mainly for patient treatment and to transport patients, personnel and equipment in the early medical management of major incidents, but the optimal utilisation of this specialised resource remains unclear. This review identified operational areas with improvement potential. A lack of systematic indexing, heterogeneous data reporting and weak methodological design, complicated the identification and comparison of incidents, and more systematic reporting is needed. CRD42013004473. 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. Utilisation of helicopter emergency medical services in the early medical response to major incidents: a systematic literature review

    PubMed Central

    Johnsen, Anne Siri; Fattah, Sabina; Sollid, Stephen J M; Rehn, Marius

    2016-01-01

    Objective This systematic review identifies, describes and appraises the literature describing the utilisation of helicopter emergency medical services (HEMS) in the early medical response to major incidents. Setting Early prehospital phase of a major incident. Design Systematic literature review performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Web of Science, PsycINFO, Scopus, Cinahl, Bibsys Ask, Norart, Svemed and UpToDate were searched using phrases that combined HEMS and ‘major incidents’ to identify when and how HEMS was utilised. The identified studies were subjected to data extraction and appraisal. Results The database search identified 4948 articles. Based on the title and abstract, the full text of 96 articles was obtained; of these, 37 articles were included in the review, and an additional five were identified by searching the reference lists of the 37 articles. HEMS was used to transport medical and rescue personnel to the incident and to transport patients to the hospital, especially when the infrastructure was damaged. Insufficient air traffic control, weather conditions, inadequate landing sites and failing communication were described as challenging in some incidents. Conclusions HEMS was used mainly for patient treatment and to transport patients, personnel and equipment in the early medical management of major incidents, but the optimal utilisation of this specialised resource remains unclear. This review identified operational areas with improvement potential. A lack of systematic indexing, heterogeneous data reporting and weak methodological design, complicated the identification and comparison of incidents, and more systematic reporting is needed. Trial registration number CRD42013004473. PMID:26861938

  8. Response of Late Carboniferous and Early Permian Plant Communities to Climate Change

    NASA Astrophysics Data System (ADS)

    Dimichele, William A.; Pfefferkorn, Hermann W.; Gastaldo, Robert A.

    Late Carboniferous and Early Permian strata record the transition from a cold interval in Earth history, characterized by the repeated periods of glaciation and deglaciation of the southern pole, to a warm-climate interval. Consequently, this time period is the best available analogue to the Recent in which to study patterns of vegetational response, both to glacial-interglacial oscillation and to the appearance of warm climate. Carboniferous wetland ecosystems were dominated by spore-producing plants and early gymnospermous seed plants. Global climate changes, largely drying, forced vegetational changes, resulting in a change to a seed plant-dominated world, beginning first at high latitudes during the Carboniferous, reaching the tropics near the Permo-Carboniferous boundary. For most of this time plant assemblages were very conservative in their composition. Change in the dominant vegetation was generally a rapid process, which suggests that environmental thresholds were crossed, and involved little mixing of elements from the wet and dry floras.

  9. Real-Time Surveillance in Emergencies Using the Early Warning Alert and Response Network.

    PubMed

    Cordes, Kristina M; Cookson, Susan T; Boyd, Andrew T; Hardy, Colleen; Malik, Mamunur Rahman; Mala, Peter; El Tahir, Khalid; Everard, Marthe; Jasiem, Mohamad; Husain, Farah

    2017-11-01

    Humanitarian emergencies often result in population displacement and increase the risk for transmission of communicable diseases. To address the increased risk for outbreaks during humanitarian emergencies, the World Health Organization developed the Early Warning Alert and Response Network (EWARN) for early detection of epidemic-prone diseases. The US Centers for Disease Control and Prevention has worked with the World Health Organization, ministries of health, and other partners to support EWARN through the implementation and evaluation of these systems and the development of standardized guidance. Although protocols have been developed for the implementation and evaluation of EWARN, a need persists for standardized training and additional guidance on supporting these systems remotely when access to affected areas is restricted. Continued collaboration between partners and the Centers for Disease Control and Prevention for surveillance during emergencies is necessary to strengthen capacity and support global health security.

  10. Real-Time Surveillance in Emergencies Using the Early Warning Alert and Response Network

    PubMed Central

    Cordes, Kristina M.; Cookson, Susan T.; Boyd, Andrew T.; Hardy, Colleen; Malik, Mamunur Rahman; Mala, Peter; El Tahir, Khalid; Everard, Marthe; Jasiem, Mohamad

    2017-01-01

    Humanitarian emergencies often result in population displacement and increase the risk for transmission of communicable diseases. To address the increased risk for outbreaks during humanitarian emergencies, the World Health Organization developed the Early Warning Alert and Response Network (EWARN) for early detection of epidemic-prone diseases. The US Centers for Disease Control and Prevention has worked with the World Health Organization, ministries of health, and other partners to support EWARN through the implementation and evaluation of these systems and the development of standardized guidance. Although protocols have been developed for the implementation and evaluation of EWARN, a need persists for standardized training and additional guidance on supporting these systems remotely when access to affected areas is restricted. Continued collaboration between partners and the Centers for Disease Control and Prevention for surveillance during emergencies is necessary to strengthen capacity and support global health security. PMID:29155660

  11. 7T T₂*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease.

    PubMed

    van Rooden, Sanneke; Doan, Nhat Trung; Versluis, Maarten J; Goos, Jeroen D C; Webb, Andrew G; Oleksik, Ania M; van der Flier, Wiesje M; Scheltens, Philip; Barkhof, Frederik; Weverling-Rynsburger, Annelies W E; Blauw, Gerard Jan; Reiber, Johan H C; van Buchem, Mark A; Milles, Julien; van der Grond, Jeroen

    2015-01-01

    The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(∗)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p ≤ 0.042). These data suggest that EOAD patients have an increased iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Species-driven phases and increasing structure in early-successional plant communities.

    PubMed

    Zaplata, Markus K; Winter, Susanne; Fischer, Anton; Kollmann, Johannes; Ulrich, Werner

    2013-01-01

    Successional phases describe changes in ecological communities that proceed in steps rather than continuously. Despite their importance for the understanding of ecosystem development, there still exists no reliable definition of phases and no quantitative measure of phase transitions. In order to obtain these data, we investigated primary succession in an artificial catchment (6 ha) in eastern Germany over a period of 6 years. The data set consists of records of plant species and their cover values, and initial substrate properties, both from plots in a regular grid (20 m × 20 m) suitable for spatial data analysis. Community assembly was studied by analyses of species co-occurrence and nestedness. Additionally, we correlated lognormal and log series distributions of species abundance to each community. We here introduce a new general method for detection of successional phases based on the degree of transient spatial homogeneity in the study system. Spatially coherent vegetation patterns revealed nonoverlapping partitions within this sequence of primary succession and were characterized as two distinct ecological phases. Patterns of species co-occurrence were increasingly less random, and hence the importance of demographic stochasticity and neutral community assembly decreased during the study period. Our findings highlight the spatial dimension of successional phases and quantify the degree of change between these steps. They are an element for advancing a more reliable terminology of ecological successions.

  13. F247. INTERNALIZED STIGMA HAS A STRONGER RELATIONSHIP WITH INTRINSIC MOTIVATION COMPARED TO AMOTIVATION IN EARLY PHASE AND PROLONGED SCHIZOPHRENIA

    PubMed Central

    Firmin, Ruth; Luther, Lauren; Lysaker, Paul; Vohs, Jennifer

    2018-01-01

    Abstract Background Motivation deficits predict decreased functioning in schizophrenia. Recent work suggests deficits reflect challenges in separate domains: intrinsic motivation (one’s internal drive to engage in a behavior out of enjoyment or interest) and amotivation (one’s broader decrease in motivated behavior linked to avolition and anhedonia). Internalized stigma is another determinant of functioning for people with schizophrenia that may impact motivation. However, little is known about these relationships, including which aspects of motivation it may impact nor when these links emerge. Identifying the link between these constructs may help to identify whether internalized stigma may be a novel treatment target to facilitate improvements in motivation. Methods Forty adults with early phase schizophrenia and 66 adults with prolonged schizophrenia completed measures of internalized stigma, intrinsic motivation, and amotivation. Pearson’s correlations were examined followed by Fischer’s r-to-z transformations to compare differences in the magnitude of associations between internalized stigma and intrinsic motivation and internalized stigma and amotivation among the first episode and prolonged samples. Next, we conducted stepwise regressions to examine whether internalized stigma was associated with intrinsic motivation above and beyond associations with amotivation in each sample. Results In the early phase sample, the association between internalized stigma was greater with intrinsic motivation (r=-0.48, p=.00) compared to amotivation (r=0.27, p=0.10). Associations with internalized stigma in the prolonged sample were also greater with intrinsic motivation (r=-0.30, p=0.02) versus amotivation (r=0.19, p=0.12). The ma