bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of triage testing for facility-based systematic screening of tuberculosis among Ugandan adults
Authors: Murray Matthew , Cattamanchi Adithya , Denkinger Claudia , van't Hoog Anja , Pai Madhukar , Dowdy David 
Published: September 2016

BackgroundSystematic screening is often proposed as a way to improve case finding for tuberculosis (TB), but the cost-effectiveness of specific strategies for systematic screening remains poorly studied.MethodsWe constructed a Markov-based decision analytic model to analyse the cost-effectiveness of triage testing for TB in Uganda, compared against passive case detection with Xpert MTB/RIF. We assumed a triage algorithm whereby all adults presenting to healthcare centres would be screened for cough, and those with cough of at least 2 weeks would receive the triage test, with positive triage results confirmed by Xpert MTB/RIF. We adopted the perspective of the TB control sector, using a primary outcome of the cost per year of life gained (YLG) over a lifetime time horizon.ResultsSystematic screening in a population with a 5% underlying prevalence of TB was estimated to cost US$610 per YLG (95% uncertainty range US$200–US$1859) with chest X-ray (CXR) (US$5 per test, specificity 0.67), or US$588 (US$221–US$1746) with C reactive protein (CRP) (US$3 per test, specificity 0.59). In addition to the cost and specificity of the triage test, cost-effectiveness was most sensitive to the underlying prevalence of TB, monthly risk of mortality in people with untreated TB and the proportion of patients with TB who would be treated in the absence of systematic screening.ConclusionsTo optimise the cost-effectiveness of facility-based systematic screening of TB with a triage test, it must be carried out in a high-risk population, or use triage tests that are cheaper or more specific than CXR or CRP.
Assessing the independent and combined effects of subsidies for antimalarials and rapid diagnostic testing on fever management decisions in the retail sector: results from a factorial randomised trial in western Kenya
Authors: Prudhomme O'Meara Wendy , Mohanan Manoj , Laktabai Jeremiah , Lesser Adriane , Platt Alyssa , Maffioli Elisa , Turner Elizabeth L , Menya Diana 
Published: September 2016

ObjectivesThere is an urgent need to understand how to improve targeting of artemisinin combination therapy (ACT) to patients with confirmed malaria infection, including subsidised ACTs sold over-the-counter. We hypothesised that offering an antimalarial subsidy conditional on a positive malaria rapid diagnostic test (RDT) would increase uptake of testing and improve rational use of ACTs.MethodsWe designed a 2×2 factorial randomised experiment evaluating 2 levels of subsidy for RDTs and ACTs. Between July 2014 and June 2015, 444 individuals with a malaria-like illness who had not sought treatment were recruited from their homes. We used scratch cards to allocate participants into 4 groups in a ratio of 1:1:1:1. Participants were eligible for an unsubsidised or fully subsidised RDT and 1 of 2 levels of ACT subsidy (current retail price or an additional subsidy conditional on a positive RDT). Treatment decisions were documented 1 week later. Our primary outcome was uptake of malaria testing. Secondary outcomes evaluated ACT consumption among those with a negative test, a positive test or no test.ResultsOffering a free RDT increased the probability of testing by 18.6 percentage points (adjusted probability difference (APD), 95% CI 5.9 to 31.3). An offer of a conditional ACT subsidy did not have an additional effect on the probability of malaria testing when the RDT was free (APD=2.7; 95% CI −8.6 to 14.1). However, receiving the conditional ACT subsidy increased the probability of taking an ACT following a positive RDT by 19.5 percentage points (APD, 95% CI 2.2 to 36.8). Overall, the proportion who took ACT following a negative test was lower than those who took ACT without being tested, indicated improved targeting among those who were tested.ConclusionsBoth subsidies improved appropriate fever management, demonstrating the impact of these costs on decision making. However, the conditional ACT subsidy did not increase testing. We conclude that each of the subsidies primarily impacts the most immediate decision.Trial registration numberNCT02199977.
When are clinical trials beneficial for study patients and future patients? A factorial vignette-based survey of institutional review board members
Authors: Mhaskar Rahul , Miladinovic Branko , Guterbock Thomas M , Djulbegovic Benjamin 
Published: September 2016

ObjectiveThe ethicists believe that the goal of clinical research is to benefit future and not current (trial) patients. Many clinicians believe that the clinical trial enrolment offers best management for their patients. The objective of our study was to identify the situations when a clinical trial is beneficial for the patients enrolled in the trial and future patients.DesignFactorial vignette-based cross-sectional survey via the internet.ParticipantsInstitutional review board (IRB) members of the US Medical Schools.Main outcome measuresEach participant was invited to review 9 clinical vignettes related to (1) study approval and (2) the assessment if the study is designed to help future or current patients more.ResultsA total of 232 IRB members from 42 institutions participated. When considering approval of the trial, we found that uncertainty about treatment effects (OR=1.13; 95% CI 1.08 to 1.19) and requirement for continuation of standard therapy (OR=3.84; 95% CI 2.7 to 5.55) were the only statistically significant factors affecting IRB members' decisions to approve the study. The odds of IRB members approving a trial increased when a trial proposed to enrol patients with life-threatening versus chronic debilitating disease (OR=2.04; 95% CI 1.47 to 2.86). We also found that similar factors affected judgements related to the assessment whether the trial will benefit future or current patients more—(1) future patients: uncertainty (OR=1.27; 95% CI 1.18 to 1.37); continuation of standard treatment (OR=1.66; 95% CI 1.07 to 2.56); seriousness of condition (OR=1.78; 95% CI 1.15 to 2.28); (2) current patients: uncertainty (OR=1.54; 95% CI 1.4 to 1.7); continuation of standard therapy (OR=2.17; 95% CI 1.39 to 3.44).ConclusionsIRB members view the proposed studies to be beneficial for current patients and future patients if there is uncertainty regarding treatment effects and if studies do not require stopping the current treatment. This finding supports the design and use of pragmatic trials which may reduce therapeutic misconception and improve trial enrolment, speeding up therapeutic discoveries.
School restrictions on outdoor activities and weight status in adolescent children after Japan’s 2011 Fukushima Nuclear Power Plant disaster: a mid-term to long-term retrospective analysis
Authors: Nomura Shuhei , Blangiardo Marta , Tsubokura Masaharu , Ochi Sae , Hodgson Susan 
Published: September 2016

ObjectiveRadiation fears following Japan's 2011 Fukushima nuclear disaster affected levels of physical activity in local children. We assessed the postdisaster versus predisaster weight status in school children and evaluated to what extent school restrictions on outdoor activities that were intended to reduce radiation exposure risk affected child weight.ParticipantsWe considered children aged 13–15 years from 4 of the 5 secondary schools in Soma City (n=1030, 99.1% of all children in the city), located in 35–50 km from the Fukushima nuclear plant, postdisaster (2012 and 2015) and predisaster (2010).MethodsWeight status, in terms of body mass index (BMI), percentage of overweight (POW) and incidence of obesity and underweight (defined as a POW ≥20% and ≤−20%, respectively) were examined and compared predisaster and postdisaster using regression models. We also constructed models to assess the impact of school restrictions on outdoor activity on weight status.ResultsAfter adjustment for covariates, a slight decrease in mean BMI and POW was detected in females in 2012 (−0.37, 95% CI −0.68 to −0.06; and −1.97, 95% CI −3.57 to −0.36, respectively). For male children, obesity incidence increased in 2012 (OR for obesity: 1.45, 95% CI 1.02 to 2.08). Compared with predisaster weight status, no significant weight change was identified in 2015 in either males or females. School restrictions on outdoor activities were not significantly associated with weight status.Conclusions4 years following the disaster, weight status has recovered to the predisaster levels for males and females; however, a slight decrease in weight in females and a slight increase in risk of obesity were observed in males 1 year following the disaster. Our findings could be used to guide actions taken during the early phase of a radiological disaster to manage the postdisaster health risks in adolescent children.
What's Really New with NewSQL?
Authors: Pavlo Andrew , Aslett Matthew 
Published: September 2016

A new class of database management systems (DBMSs) called NewSQL tout their ability to scale modern on-line transaction processing (OLTP) workloads in a way that is not possible with legacy systems. The term NewSQL was first used by one of the authors of this article in a 2011 business analysis report discussing the rise of new database systems as challengers to these established vendors (Oracle, IBM, Microsoft). The other author was working on what became one of the first examples of a NewSQL DBMS. Since then several companies and research projects have used this term (rightly and wrongly) to describe their systems.
Given that relational DBMSs have been around for over four decades, it is justifiable to ask whether the claim of NewSQL's superiority is actually true or whether it is simply marketing. If they are indeed able to get better performance, then the next question is whether there is anything scientifically new about them that enables them to achieve these gains or is it just that hardware has advanced so much that now the bottlenecks from earlier years are no longer a problem.
To do this, we first discuss the history of databases to understand how NewSQL systems came about. We then provide a detailed explanation of what the term NewSQL means and the different categories of systems that fall under this definition.
CCR2 Influences T Regulatory Cell Migration to Tumors and Serves as a Biomarker of Cyclophosphamide Sensitivity
Authors: Loyher Pierre-Louis , Rochefort Juliette , Baudesson de Chanville Camille , Hamon Pauline , Lescaille Géraldine , Bertolus Chloé , Guillot-Delost Maude , Krummel Matthew F. , Lemoine François M. , Combadière Christophe , Boissonnas Alexandre 
Published: September 2016

AbstractThe CCL2 chemokine receptor CCR2 drives cancer by mediating the recruitment of monocytes and myeloid-derived suppressor cells to the tumor microenvironment. In this study, we extend the significance of CCR2 in this setting by identifying a new role for it in mediating recruitment of CD4+ T regulatory cells (Treg). Following tumor initiation, an expanded population of CCR2+ Tregs required CCR2 expression to traffic between draining lymph nodes (dLN) and the tumor. This Treg subset was enriched in the fraction of tumor antigen–specific cells in the dLN, where they displayed an activated immunosuppressive phenotype. Notably, in mouse models, low-dose cyclophosphamide treatment preferentially depleted CCR2+ Treg, enhancing priming of tumor-specific CD8+ T cells. In the MMTV-PyMT transgenic mouse model of breast cancer and in oral squamous cell carcinoma patients, tumor development was associated with decreased blood frequency and inversely increased tumor frequency of CCR2+ Tregs. Our results define a novel subset of CCR2+ Treg involved in tumoral immune escape, and they offer evidence that this Treg subset may be preferentially eradicated by low-dose cyclophosphamide treatment. Cancer Res; 76(22); 6483–94. ©2016 AACR.
Kinase Regulation of Human MHC Class I Molecule Expression on Cancer Cells
Authors: Brea Elliott J. , Oh Claire Y. , Manchado Eusebio , Budhu Sadna , Gejman Ron S. , Mo George , Mondello Patrizia , Han James E. , Jarvis Casey A. , Ulmert David , Xiang Qing , Chang Aaron Y. , Garippa Ralph J. , Merghoub Taha , Wolchok Jedd D. , Rosen Neal , Lowe Scott W. , Scheinberg David A. 
Published: September 2016

Abstract
The major histocompatibility complex I (MHC-1) presents antigenic peptides to tumor-specific CD8+ T cells. The regulation of MHC-I by kinases is largely unstudied, even though many patients with cancer are receiving therapeutic kinase inhibitors. Regulators of cell-surface HLA amounts were discovered using a pooled human kinome shRNA interference–based approach. Hits scoring highly were subsequently validated by additional RNAi and pharmacologic inhibitors. MAP2K1 (MEK), EGFR, and RET were validated as negative regulators of MHC-I expression and antigen presentation machinery in multiple cancer types, acting through an ERK output–dependent mechanism; the pathways responsible for increased MHC-I upon kinase inhibition were mapped. Activated MAPK signaling in mouse tumors in vivo suppressed components of MHC-I and the antigen presentation machinery. Pharmacologic inhibition of MAPK signaling also led to improved peptide/MHC target recognition and killing by T cells and TCR-mimic antibodies. Druggable kinases may thus serve as immediately applicable targets for modulating immunotherapy for many diseases. Cancer Immunol Res; 4(11); 936–47. ©2016 AACR.
Angina and Future Cardiovascular Events in Stable Patients With Coronary Artery Disease: Insights From the Reduction of Atherothrombosis for Continued Health (REACH) Registry
Authors: Eisen Alon , Bhatt Deepak L. , Steg P. Gabriel , Eagle Kim A. , Goto Shinya , Guo Jianping , Smith Sidney C. , Ohman E. Magnus , Scirica Benjamin M. ,   the REACH Registry Investigators
Published: September 2016

Background
The extent to which angina is associated with future cardiovascular events in patients with coronary artery disease has long been debated.

Methods and Results

Included were outpatients with established coronary artery disease who were enrolled in the
REACH
registry and were followed for 4 years. Angina at baseline was defined as necessitating episodic or permanent antianginal treatment. The primary end point was the composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included heart failure, cardiovascular hospitalizations, and coronary revascularization. The independent association between angina and first/total events was examined using Cox and logistic regression models. Out of 26 159 patients with established coronary artery disease, 13 619 (52%) had angina at baseline. Compared with patients without angina, patients with angina were more likely to be older, female, and had more heart failure and polyvascular disease (
P
<0.001 for each). Compared with patients without angina, patients with angina had higher rates of first primary end‐point event (14.2% versus 16.3%, unadjusted hazard ratio 1.19,
CI
1.11–1.27,
P
<0.001; adjusted hazard ratio 1.06,
CI
0.99–1.14,
P
=0.11), and total primary end‐point events (adjusted risk ratio 1.08,
CI
1.01–1.16,
P
=0.03). Patients with angina were at increased risk for heart failure (adjusted odds ratio 1.17,
CI
1.06–1.28,
P
=0.002), cardiovascular hospitalizations (adjusted odds ratio 1.29,
CI
1.21–1.38,
P
<0.001), and coronary revascularization (adjusted odds ratio 1.23,
CI
1.13–1.34,
P
<0.001).

Conclusions
Patients with stable coronary artery disease and angina have higher rates of future cardiovascular events compared with patients without angina. After adjustment, angina was only weakly associated with cardiovascular death, myocardial infarction, or stroke, but significantly associated with heart failure, cardiovascular hospitalization, and coronary revascularization.
Souvenirs à voir ou à entendre
Authors: Sardin Pascale 
Published: September 2016

Among Beckett’s dramaticules, That Time emphasizes most strongly the desire of the elderly to tell their memories. Questioning our ability to listen, this dramaticule creates a disjunction between seeing and hearing – the former inviting an immediate enjoyment of meaning, the latter privileging resonance, sharing, and duration. In Robert Wilson’s production of Krapp’s Last Tape, the denial of aging is a consequence of his decision to let seeing dominate at the expense of hearing, and this choice leads us to bring up the question of the reparative function of theater.
What environmental factors influence resumption of valued activities post stroke: a systematic review of qualitative and quantitative findings
Authors: Jellema Sandra , van Hees Suzanne , Zajec Jana , van der Sande Rob , Nijhuis- van der Sanden Maria WG , Steultjens Esther MJ 
Published: September 2016

Objective: Identify the environmental factors that influence stroke-survivors’ reengagement in personally valued activities and determine what specific environmental factors are related to specific valued activity types. Data sources: PubMed, CINAHL and PsycINFO were searched until June 2016 using multiple search-terms for stroke, activities, disability, and home and community environments. Review methods: An integrated mixed-method systematic review of qualitative, quantitative and mixed-design studies was conducted. Two researchers independently identified relevant studies, assessed their methodological quality and extracted relevant findings. To validly compare and combine the various findings, all findings were classified and grouped by environmental category and level of evidence. Results: The search yielded 4024 records; 69 studies were included. Most findings came from low-evidence-level studies such as single qualitative studies. All findings were consistent in that the following factors facilitated reengagement post-stroke: personal adapted equipment; accessible environments; transport; services; education and information. Barriers were: others’ negative attitudes and behaviour; long distances and inconvenient environmental conditions (such as bad weather). Each type of valued activity, such as mobility or work, had its own pattern of environmental influences, social support was a facilitator to all types of activities. Although in many qualitative studies others’ attitudes, behaviour and stroke-related knowledge were seen as important for reengagement, these factors were hardly studied quantitatively. Conclusion: A diversity of environmental factors was related to stroke-survivors’ reengagement. Most findings came from low-evidence-level studies so that evidence on causal relationships was scarce. In future, more higher-level-evidence studies, for example on the attitudes of significant others, should be conducted.
Palliative care for Parkinson’s disease: Patient and carer’s perspectives explored through qualitative interview
Authors: Fox Siobhan , Cashell Alison , Kernohan W George , Lynch Marie , McGlade Ciara , O’Brien Tony , O’Sullivan Sean S , Foley Mary J , Timmons Suzanne 
Published: September 2016

Background: Palliative care is recommended for non-malignant illnesses, including Parkinson’s disease. However, past research with healthcare workers highlights unmet palliative needs in this population and referral rates to Specialist Palliative Care are low. Some healthcare workers perceive a ‘fear’ in their patients about introducing palliative care. However, less is known about the views of people with Parkinson’s disease and their carers about palliative care. Aim: (1) To explore the palliative care and related issues most affecting people with Parkinson’s disease and their families and (2) to examine perceptions about/understanding of palliative care. Design: This was a qualitative study; semi-structured interviews were conducted, transcribed and analysed using thematic analysis. Setting/participants: A total of 31 people participated, both people with Parkinson’s disease ( n = 19) and carers ( n = 12), across three Movement Disorder Clinics in the Republic of Ireland. Results: People with Parkinson’s disease and their carers were unfamiliar with the term palliative care. When informed of the role of palliative care, most felt that they would benefit from this input. People with Parkinson’s disease and carers experienced a high illness burden and wanted extra support. Crises requiring Specialist Palliative Care involvement may occur at diagnosis and later, with advancing illness. Participants wanted more information about palliative care and especially further supports to address their psychosocial needs. Conclusion: A holistic palliative care approach could address the complex physical and psychosocial symptoms experienced by people with Parkinson’s disease and their carers, and people with Parkinson’s disease and their carers are open to palliative care. Further research needs to explore how palliative care can be introduced into the routine care for people with Parkinson’s disease.
Estrogen receptor alpha gene (ESR1) polymorphism can contribute to clinical findings in systemic lupus erythematosus patients
Authors: Drehmer M N , Andrade D , Pereira I A , Marrero A R , Muniz Y C N , de Souza I R , Löfgren S E 
Published: September 2016

Background Estrogens have a modulatory effect on several immune responses, many of which are correlated to autoimmune diseases. Estrogens act through binding to their receptors, and an overexpression of these receptors has been identified in patients with different autoimmune diseases. Here we analyzed the association of a putative functional genetic variant in the main estrogen receptor (ERα) gene ( ESR1), and the susceptibility to clinical findings and severity of SLE. Methods A total of 426 individuals (266 healthy controls and 160 SLE patients) were genotyped for the polymorphism rs2234693 in the ESR1 gene. Allele and genotype frequencies were calculated and analyzed between cases and controls using Unphased software. Results The SNP rs2234693 was not associated with SLE per se but the minor allele rs2234693-C was correlated with the presence of nephritis and discoid skin rash. On the other hand, the rs2234693-CC genotype was correlated with the absence of arthritis as well as anti-ANA and anti-RNP autoantibodies. The comprehensive clinical analysis of these patients revealed a more severe status of the disease, characterized by a younger age of onset and higher number of organs involved when compared to European populations. Conclusions Minor allele rs2234693-C was associated with renal and cutaneous involvement, as well as the absence of arthritis, anti-ANA and anti-RNP autoantibodies.
Baseline EDSS proportions in MS clinical trials affect the overall outcome and power: A cautionary note
Authors: Wang Guoqiao , Cutter Gary R , Cofield Stacey S , Lublin Fred , Wolinsky Jerry S , Gustafson Tarah , Krieger Stephen , Salter Amber 
Published: September 2016

Background: In randomized clinical trials, when treatments do not work equally effectively across stratifications of participants, observed event rates may differ from those hypothesized leading to deviations in estimated power. Objectives: To investigate the effect of distributions of baseline Expanded Disability Status Scale (EDSS) proportions in relapsing-remitting multiple sclerosis (RRMS) on the trial outcome, confirmed disability progression rate (CDPR), and power. Methods: We reported CDPRs in the CombiRx trial by baseline EDSS and by groups (1st (0, 1), 2nd (1.5, 2), 3rd (2.5, 3), and 4th (⩾3.5)) and investigated the effect of different combinations of baseline EDSS proportions on the trial outcome and power. Results: There were 244 (25.4%) participants in the 1st group, 368 (38.4%) in the 2nd group, 223 (23.3%) in the 3rd group, and 124 (12.9%) in the 4th group with CDPRs of 40.1%, 13.9%, 11.2%, and 16.9%, respectively. Both CDPR and power increased when the proportion of the 1st group increased in hypothetical trials with equal sample sizes in each arm, and a 10% increase in the 1st group led to a 5% increase in power. Conclusion: Various baseline EDSS proportions yielded different CDPRs and power, suggesting caution in interpretation of treatment effects across trials that enrolled participants with different proportions of baseline EDSS.