bluuebunny/crossref_metadata_2025_split huggingface dataset:
GPR65 inhibits experimental autoimmune encephalomyelitis through CD4+ T cell independent mechanisms that include effects on iNKT cells
Authors: Wirasinha Rushika C , Vijayan Dipti , Smith Nicola J , Parnell Grant P , Swarbrick Alexander , Brink Robert , King Cecile , Stewart Graeme , Booth David R , Batten Marcel 
Published: January 2018

AbstractThe G protein‐coupled receptor 65 (GPR65) gene has been genetically associated with several autoimmune diseases, including multiple sclerosis (MS). GPR65 is predominantly expressed in lymphoid organs and is activated by extracellular protons. In this study, we tested whether GPR65 plays a functional role in demyelinating autoimmune disease. Using a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we found that Gpr65‐deficient mice develop exacerbated disease. CD4+ helper T cells are key drivers of EAE pathogenesis, however, Gpr65 deficiency in these cells did not contribute to the observed exacerbated disease. Instead, Gpr65 expression levels were found to be highest on invariant natural killer T (iNKT) cells. EAE severity in Gpr65‐deficient mice was normalized in the absence of iNKT cells (CD1d‐deficient mice), suggesting that GPR65 signals in iNKT cells are important for suppressing autoimmune disease. These findings provide functional support for the genetic association of GPR65 with MS and demonstrate GPR65 signals suppress autoimmune activity in EAE.
Additive centralized and Stackelberg DEA models for two‐stage system with shared resources
Authors: Ma Jianfeng , Qi Linan , Deng Lizhi 
Published: January 2018

AbstractData envelopment analysis (DEA) is a nonparametric programming method for evaluating the efficiency performance of decision making units (DMUs) with multiple inputs and outputs. The classic DEA model cannot provide accurate efficiency measurement and inefficiency sources of DMUs with complex internal structure. The network DEA approach opens the “black box” of DMU by taking its internal operations into consideration. The complexities of DMU's internal structure involve not only the organization of substages, but also the inputs allocation and the operational relations among the individual stages. This paper proposes a set of additive DEA models to evaluate and decompose the efficiency of a two‐stage system with shared inputs and operating in cooperative and Stackelberg game situations. Under the assumptions of cooperative and noncooperative gaming, the proposed models are able to highlight the effects of strategic elements on the efficiency formation of DMUs by calculating the optimal proportion of the shared inputs allocated to each stage. The case of information technology in the banking industry at the firm level, as discussed by Wang, is revisited using the developed DEA approach.
Let's get cynical about this! Recursive relationships between psychological contract breach and counterproductive work behaviour
Authors: Griep Yannick , Vantilborgh Tim 
Published: January 2018

Although counterproductive work behaviour towards the organization (CWB‐O) or supervisors (CWB‐S) is commonly treated as a reaction to psychological contract breach (PCB), we propose that the PCB‐CWB relationship is recursive and that CWB may increase the likelihood to perceive PCB through its effects on self‐esteem and subsequently on organizational cynicism. By estimating a two‐level time‐lagged mediation model on daily data from 103 US employees (904 observations), we found evidence for this hypothesized chain of events. These findings demonstrate that PCB and CWB happen with reference to past perceptions of PCB and/or CWB and future anticipations of PCB and/or CWB. We discuss suggestions for future research and novel practical implications in preventing further escalation.Practitioner points

When employees perceive that their organization has breached its obligations, employees are likely to retaliate by engaging in acts of CWB‐O and CWB‐S.

Employees are likely to suffer from reduced self‐esteem and increased cynicism when they have engaged in CWB‐S following a PC breach.

When employees become more cynical, they are more likely to perceive future PC breaches.

Based on the reciprocal nature of our findings, this study highlights the need to update existing theories, as well as indicates the need for swift interventions in the aftermath of PC breach and enactment of CWB.
Differential effects of experimental hyperthyroidism on declined immunity of broiler chicken
Authors: Khilji M. S. , Sandhu M. A. , Yousaf M. S. , Saeed A. A. , Rehman H. U. , Zaneb H. , Rashid M. A. 
Published: January 2018

SummaryThyroid hormones (THs) are involved in the development of lymphoid organs and regulation of immune function in birds. However, their role as an immune‐modulator in the hyperthyroid state is still debatable. To explore the interrelationship of thyroxine (T4) and the immune system, chicks were divided into three groups. Group I was comprised of control birds, who received the basal diet while group II and III were given diets supplemented with 5 μg and 10 μg thyroxine/kg feed, respectively, from 15 to 28 days of age. Cell‐mediated immune response was evaluated through in vitro abdominal macrophage phagocytosis assay, macrophage nitric oxide (NO) production, heterophil‐to‐lymphocyte (H:L) ratio and delayed‐type hypersensitivity response against phytohemagglutinin (PHA). Humoural immune response was assessed through serum IgG and IgM antibody production against sheep red blood cells (SRBCs) and antibody production against infectious bronchitis virus (IBV). Sampling was carried out at 7, 14 and 21 days of treatment. Results have shown higher levels (p < .001) of circulating T4 in both treatment groups compared to the control group. There was a lower (p < .05) macrophage engulfment percentage, an increase in H:L ratio (p < .001) in treated birds, while their NO production remained higher (p < .05) in thyroxine supplemented groups after bacterial lipopolysaccharide stimulation. The humoural immune response revealed a significant decline (p < .001) in IgG, IgM antibody production against SRBCs but IBV circulating antibodies increased with age. In conclusion, hyperthyroidism has a strong co‐relation with decreased immune performance of birds.
Social determinants of community-level human papillomavirus vaccination coverage in aschool-based vaccination programme
Authors: Jean Stephen , Elshafei Malak , Buttenheim Alison 
Published: January 2018

ObjectiveTo assess social patterns in human papillomavirus (HPV) vaccine coverage in a school-based, government-funded vaccination programme located within a single-payer universal healthcare system.DesignWe conducted a cross-sectional analysis of HPV vaccine uptake data for the 2013–2014 school year for 131 local authorities in England, and then evaluated the association between vaccine uptake and socioeconomic status at the aggregate level.Data sourcesHPV vaccination coverage data from Public Health England’s vaccine uptake guidance and the UK’s March 2011 Census.Main outcome measuresWe measured three-dose local authority-level vaccine series initiation to completion.ResultsWe found that in local authorities where there are more high-income families, the vaccination rate is lower than in local authorities with more low-income families. Local authorities with a higher percentage of whites, compared with non-whites, had higher HPV vaccination rates. Additionally, local authorities with more non-migrants had higher rates of vaccination. Local authorities with more education deprivation had higher rates of vaccination. Local authorities’ higher proportions of high-status occupations had worse vaccination coverage. In bivariate analyses across all the socioeconomic indicators, a 1 SD change in the indicators was associated with about a 2.25 percentage point decrease (for income, education and occupation) or increase (for race and migrant composition) in HPV dose coverage in the local authority. In multivariable analyses, only race remained as a significant predictor of HPV coverage at the local authority level.ConclusionsAcross all three doses, there are notable variations by socioeconomic status, with steep reverse gradients in three socioeconomic indicators. More quantitative and qualitative research needs to be conducted to determine the effects of the 2014 transition from a three-dose regimen to two-dose regimen on vaccination coverage, especially in groups that experience lower rates of vaccination.
Veritesting Challenges in Symbolic Execution of Java
Authors: Sharma Vaibhav , Whalen Michael W. , McCamant Stephen , Visser Willem 
Published: January 2018

Scaling symbolic execution to industrial-sized programs is an important open research problem. Veritesting is a promising technique that improves scalability by combining the advantages of static symbolic execution with those of dynamic symbolic execution. The goal of veritesting is to reduce the number of paths to explore in symbolic execution by creating formulas describing regions of code using disjunctive formulas. In previous work, veritesting was applied to binary-level symbolic execution.
Integrating veritesting with Java bytecode presents unique challenges: notably, incorporating non-local control jumps caused by runtime polymorphism, exceptions, native calls, and dynamic class loading. If these language features are not accounted for, we hypothesize that the static code regions described by veritesting are often small and may not lead to substantial reduction in paths. We examine this hypothesis by running a Soot-based static analysis on six large open-source projects used in the Defects4J collection. We find that while veritesting can be applied in thousands of regions, allowing static symbolic execution involving non-local control jumps amplifies the performance improvement obtained from veritesting. We hope to use these insights to support efficient veritesting in Symbolic PathFinder in the near future. Toward this end, we brie y address some engineering challenges to add veritesting into SPF.
Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant Treatment of Advanced Renal Cell Carcinoma
Authors: Sternberg Cora N. , Donskov Frede , Haas Naomi B. , Doehn Christian , Russo Paul , Elmeliegy Mohamed , Baneyx Guillaume , Banerjee Hiya , Aimone Paola , Motzer Robert J. 
Published: January 2018

Abstract
Purpose: PROTECT, a phase III, randomized, placebo-controlled study, evaluated pazopanib efficacy and safety in the adjuvant renal cell carcinoma setting. The relationship between pazopanib exposure (Ctrough) and efficacy and safety was evaluated.
Patients and Methods: Evaluable steady-state blood trough concentrations were collected from 311 patients at week 3 or 5 (early Ctrough) and 250 patients at week 16 or 20 (late Ctrough). Pazopanib pharmacokinetic (PK) data were analyzed via a population model approach. Relationship between Ctrough or dose intensity and disease-free survival (DFS) was explored via Kaplan–Meier and multivariate analysis. Adverse events (AE) and AE-related treatment discontinuation proportions were summarized by Ctrough quartiles.
Results: Most (&gt;90%) patients with early or late Ctrough data started on 600 mg. Mean early and late Ctrough overlapped across dose levels. Patients with higher early Ctrough quartiles achieved longer DFS (adjusted HR, 0.58; 95% confidence interval, 0.42–0.82; P = 0.002). Patients achieving early or late Ctrough &gt;20.5 μg/mL had significantly longer DFS: not estimable (NE) versus 29.5 months, P = 0.006, and NE versus 29.9 months, P = 0.008, respectively. Dose intensity up to week 8 did not correlate with DFS, consistent with population PK model–based simulations showing overlapping pazopanib exposure with 600 and 800 mg doses. The proportion of AE-related treatment discontinuation and grade 3/4 AEs, with the exception of hypertension, was not correlated to Ctrough.
Conclusions: In the adjuvant setting, higher pazopanib Ctrough was associated with improved DFS and did not increase treatment discontinuations or grade 3/4 AEs, with the exception of hypertension. Clin Cancer Res; 24(13); 3005–13. ©2018 AACR.
See related commentary by Rini, p. 2979
Are Supply Shocks Contractionary at the ZLB? Evidence from Utilization-Adjusted TFP Data
Authors: Garín Julio , Lester Robert , Sims Eric 
Published: January 2018

Abstract
The basic New Keynesian model predicts that positive supply shocks are less expansionary at the zero lower bound (ZLB) compared to periods of active monetary policy. We test this prediction empirically using Fernald's (2014) utilization-adjusted total factor productivity series, which we take as a measure of exogenous productivity. In contrast to the predictions of the model, positive productivity shocks are estimated to be more expansionary at the ZLB compared to normal times. We find that there is no significant difference in the response of expected inflation to a productivity shock at the ZLB compared to normal times.
Comparative Survival Analysis of Urea Kinetic Based Indices
Authors: Stosovic M. , Stanojevic M. , Radovic M. , Naumovic R. , Jovanovic D. , Simic S. , Marinkovic J. , Stankovic S. , Djukanovic L.J. 
Published: January 2018

Background Although urea kinetic modeling indices for measuring dialysis dose are recommended by world expert groups, it is not quite clear whether some of these are superior in predicting the outcome over others. This prospective, single-center study was carried out with the aim to compare predictive value of different indices and methods of measuring dialysis dose. Methods The analysis included 93 anuric patients having been on hemodialysis for at least 2 years who were followed-up for 75-months. The dialysis dose was measured by Kt/V (formal UKM, 3 and 2 urea samples), Kt/V (Daugirdas), Kt/V (Lowrie), eKt/V (Daugirdas), URR and TAC urea. Results Correlations between dialysis indices and survival time were significant for all indices (p<0.01) except for TAC. All indices, except for TAC urea, were significant predictors of mortality (multivariate Cox regression analysis; p<0.01) and differences of significant levels among these colinear parameters were small. Conclusion All examined indices except for TAC urea were highly predictive of patient mortality. Daugirdas and Lowrie simplified Kt/V indices are as predictive of all-cause mortality as more complex formal UKM methods in long-term patients on a 3×4h/week schedule.
Regional Citrate Anticoagulation for Hemodialysis: Calcium-Free Vs. Calcium Containing Dialysate - A Randomized Trial
Authors: Buturovic-Ponikvar J. , Cerne S. , Gubensek J. , Ponikvar R. 
Published: January 2018

Background The majority of citrate protocols for hemodialysis (HD) use calcium (Ca)-free dialysate, a limited number use dialysate with Ca, aiming to simplify the procedure. This randomized clinical study sought to compare the anticoagulant effect of citrate using Ca-free dialysate and dialysate with Ca 1.25 mmol/L. Methods Fifty HD procedures (in 5 chronic HD patients treated by chronic citrate anticoagulation) were randomly assigned to Ca-free dialysate (25 procedures) or Ca-1.25 dialysate (25 procedures), both with Mg 0.5 mmol/L, Na 138 mmol/L, and bicarbonate 28 mmol/L. Ca-free HD: 15% Na3 citrate 80 ml/hour was infused into the arterial line, and 1 M CaCl2, 14 ml/hour into the venous line. Ca-1.25 group: 15% Na3 citrate 100 ml/hour, 1 M CaCl2 2–4 ml/hour. Polyflux H dialyzers were used. Antithrombotic effect was assessed visually after HD at 3 points: dialyzer, arterial, and venous bubble traps, using a score of 5 (no clotting) to 1 (total clotting). Results Ca-free group: arterial bubble trap score 4.7 ± 0.5, dialyzer 4.5 ± 0.6, venous bubble trap 4.8 ± 0.6. Ionized calcium (iCa) at dialyzer inlet 0.34 ± 0.17, outlet 0.21 ± 0.06 mmol/L. All HDs were completed successfully. Ca-1.25 group: arterial bubble trap score 4.7 ± 0.5 (NS), dialyzer 2.6 ± 1.04 (p<0.01), venous bubble trap 2.4 ± 0.9 (p<0.01). Volume of clot in venous bubble trap was 1.9 ± 1.8 mL (range 0.5–6 mL). iCa at dialyzer inlet 0.24 ± 0.05 mmol/L (p<0.05), outlet 0.63 ± 0.11 mmol/L (p<0.01). Four of 25 HD procedures (16%) were prematurely terminated due to threatening dialyzer clotting, in 6/25 HD procedures (24%), the venous line was changed (p<0.01). Conclusion Citrate anticoagulation with Ca-1.25 dialysate resulted in significantly worse anticoagulation of dialyzer and venous bubble trap compared with Ca-free dialysate, despite higher citrate dose.
Clinical and Biomaterial Evaluation of a new Condensed Dual-Function Extracorporeal Circuit in Reoperation for Coronary Artery Bypass Surgery
Authors: Gunaydin Serdar , Mccusker Kevin , Vijay Venkataramana 
Published: January 2018

Purpose This prospective, randomized study compared the clinical performance of three types of circuits: a newly introduced, fully-coated, interchangeable open-closed circuit with a dual configuration (hard shell with a bypass shunt), reduced length, and reduced prime of less than 800 cc (CondECC); a completely coated circuit (ECC); and a similar uncoated, open circuit with standard length and prime (CONT). Methods 75 patients undergoing reoperation for coronary revascularization were randomly allocated into three groups (N=25): Group 1: CondECC with shortened tubing, components and an open-closed configuration of low priming volume with a centrifugal pump and a shunt which bypassed the reservoir for closed configuration; Group 2: ECC with a roller pump and hard-shell reservoir; Group 3: CONT. Blood samples for CBC, inflammatory mediators [Interleukin-2 (IL-2), Complement-3a (C3a)] and flow cytometry (CD11 b/CD18) were collected after induction (T1) and heparin administration (T2), 15 min after cardiopulmonary bypass (CPB) (T3), before cessation of CPB (T4), 15 min after reversal (T5), and the first postoperative day (T6). Results Leukocyte counts demonstrated significant increases at T4, T5 in CONT but remained stable in ECC and CondECC (p<0.05). Platelets were preserved better at T4, T5 in both ECC and CondECC study groups (p<0.05). IL-2 and C3a levels were significantly lower at T3, T4, T5 in CondECC and T4, T5 in ECC (p<0.05). Blood protein adsorption analysis demonstrated increased amount of microalbumin on CONT fibers (p<0.05). Conclusions The CondECC is a flexible, dual-function, open/closed configuration system that was easy to use, safe and achieved better biocompatibility when compared to coated and uncoated conventional circuits.
Blueprint for Transparency at the U.S. Food and Drug Administration: Recommendations to Advance the Development of Safe and Effective Medical Products
Authors: Sharfstein Joshua M. , Miller James Dabney , Davis Anna L. , Ross Joseph S. , McCarthy Margaret E. , Smith Brian , Chaudhry Anam , Alexander G. Caleb , Kesselheim Aaron S. 
Published: January 2018

BackgroundThe U.S. Food and Drug Administration (FDA) traditionally has kept confidential significant amounts of information relevant to the approval or non-approval of specific drugs, devices, and biologics and about the regulatory status of such medical products in FDA’s pipeline.ObjectiveTo develop practical recommendations for FDA to improve its transparency to the public that FDA could implement by rulemaking or other regulatory processes without further congressional authorization. These recommendations would build on the work of FDA’s Transparency Task Force in 2010.MethodsIn 2016-2017, we convened a team of academic faculty from Harvard Medical School, Brigham and Women’s Hospital, Yale Medical School, Yale Law School, and Johns Hopkins Bloomberg School of Public Health to develop recommendations through an iterative process of reviewing FDA’s practices, considering the legal and policy constraints on FDA in expanding transparency, and obtaining insights from independent observers of FDA.ResultsThe team developed 18 specific recommendations for improving FDA’s transparency to the public. FDA could adopt all these recommendations without further congressional action.FundingThe development of the Blueprint for Transparency at the U.S. Food and Drug Administration was funded by the Laura and John Arnold Foundation.
Perioperative Medicine: A Burgeoning Field with Profound Importance to a Modern Clinician
Authors: Gaduputi Vinaya , Chilimuri Sridhar , Changela Kinesh 
Published: January 2018

AIMS AND SCOPE This article serves in introducing the readers to the developing field of perioperative medicine. We have made an effort to come up with the latest management guidelines covering multiple subspecialties in form of a special supplement. This compendium in perioperative medicine serves as a comprehensive guide to a practicing clinician, in managing patients with various medical comorbidities undergoing surgical procedures and avoiding common pitfalls.
Epistemic injustice in psychiatry
Authors: Crichton Paul , Carel Havi , Kidd Ian James 
Published: January 2018

SummaryIt has been argued that those who suffer from medical conditions are more vulnerable to epistemic injustice (a harm done to a person in their capacity as an epistemic subject) than healthy people. This editorial claims that people with mental disorders are even more vulnerable to epistemic injustice than those with somatic illnesses. Two kinds of contributory factors are outlined, global and specific. Some suggestions are made to counteract the effects of these factors, for instance, we suggest that physicians should participate in groups where the subjective experience of patients is explored, and learn to become more aware of their own unconscious prejudices towards psychiatric patients.
Psychiatry trainees' experiences of cognitive-behavioural therapy training in a UK deanery: A qualitative analysis
Authors: Carson Amy Alice , Clark Sarah Emily 
Published: January 2018

Aims and methodTo explore core psychiatry trainees' experiences of cognitive-behavioural therapy (CBT) training by using interpretative phenomenological analysis of semi-structured interviews conducted with seven core trainee psychiatrists in Yorkshire and the Humber Deanery.ResultsFour key themes emerged: (1) barriers to training; (2) guidance, with emphasis on the importance of supervision groups; (3) acquisition of new skills and confidence; (4) personal influence on the training experience.Clinical implicationsMany trainees in Yorkshire have a positive experience of CBT training; however, some also experience barriers to acquiring the relevant skills. Further research should build on the positive factors and barriers identified here, with a view to guiding improvements in training nationwide.