bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of overstated abstract conclusions on clinicians: a web-based randomised controlled trial
Authors: Shinohara Kiyomi , Aoki Takuya , So Ryuhei , Tsujimoto Yasushi , Suganuma Aya M , Kise Morito , Furukawa Toshi A 
Published: December 2017

ObjectivesTo investigate whether overstatements in abstract conclusions influence primary care physicians’ evaluations when they read reports of randomised controlled trials (RCTs)DesignRCT setting: This study was a parallel-group randomised controlled survey, conducted online while masking the study hypothesis.ParticipantsVolunteers were recruited from members of the Japan Primary Care Association in January 2017. We sent email invitations to 7040 primary care physicians. Among the 787 individuals who accessed the website, 622 were eligible and automatically randomised into ‘without overstatement’ (n=307) and ‘with overstatement’ (n=315) groups.InterventionsWe selected five abstracts from published RCTs with at least one non-significant primary outcome and overstatement in the abstract conclusion. To construct a version without overstatement, we rewrote the conclusion sections. The methods and results sections were standardised to provide the necessary information of primary outcome information when it was missing in the original abstract. Participants were randomly assigned to read an abstract either with or without overstatements and asked to evaluate the benefit of the intervention.Outcome measuresThe primary outcome was the participants’ evaluation of the benefit of the intervention discussed in the abstract, on a scale from 0 to 10. A secondary outcome was the validity of the conclusion.ResultsThere was no significant difference between the groups with respect to their evaluation of the benefit of the intervention (mean difference: 0.07, 95% CI −0.28 to 0.42, p=0.69). Participants in the ‘without’ group considered the study conclusion to be more valid than those in the ‘with’ group (mean difference: 0.97, 95% CI 0.59 to 1.36, P<0.001).ConclusionThe overstatements in abstract conclusions did not significantly influence the primary care physicians’ evaluations of the intervention effect when necessary information about the primary outcomes was distinctly reported.Trial registration numberUMIN000025317; Pre-results.
Comparing four service delivery models for adolescent girls and young women through the ‘Girl Power’ study: protocol for a multisite quasi-experimental cohort study
Authors: Rosenberg Nora E , Pettifor Audrey E , Myers Laura , Phanga Twambilile , Marcus Rebecca , Bhushan Nivedita Latha , Madlingozi Nomtha , Vansia Dhrutika , Masters Avril , Maseko Bertha , Mtwisha Lulu , Kachigamba Annie , Tang Jennifer , Hosseinipour Mina C , Bekker Linda-Gail 
Published: December 2017

IntroductionIn sub-Saharan Africa, adolescent girls and young women (AGYW) face a range of sexual and reproductive health (SRH) challenges. Clinical, behavioural and structural interventions have each reduced these risks and improved health outcomes. However, combinations of these interventions have not been compared with each other or with no intervention at all. The ‘Girl Power’ study is designed to systematically make these comparisons.Methods and analysisFour comparable health facilities in Malawi and South Africa (n=8) were selected and assigned to one of the following models of care: (1)Standard of care: AGYW can receive family planning, HIV testing and counselling (HTC), and sexually transmitted infection (STI) syndromic management in three separate locations with three separate queues with the general population. No youth-friendly spaces, clinical modifications or trainings are offered, (2)Youth-Friendly Health Services (YFHS): AGYW are meant to receive integrated family planning, HTC and STI services in dedicated youth spaces with youth-friendly modifications and providers trained in YFHS, (3)YFHS+behavioural intervention (BI): In addition to YFHS, AGYW can attend 12 monthly theory-driven, facilitator-led, interactive sessions on health, finance and relationships, (4)YFHS+BI+conditional cash transfer (CCT): in addition to YFHS and BI, AGYW receive up to 12 CCTs conditional on monthly BI session attendance.At each clinic, 250 AGYW 15–24 years old (n=2000 total) will be consented, enrolled and followed for 1 year. Each participant will complete a behavioural survey at enrolment, 6 months and 12 months . All clinical, behavioural and CCT services will be captured. Outcomes of interest include uptake of each package element and reduction in HIV risk behaviours. A qualitative substudy will be conducted.Ethics/disseminationThis study has received ethical approval from the University of North Carolina Institutional Review Board, the University of Cape Town Human Research Ethics Committee and Malawi’s National Health Sciences Research Committee. Study plans, processes and findings will be disseminated to stakeholders, in peer-reviewed journals and at conferences.
Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn’s disease (ANDANTE I and II)
Authors: Danese Silvio , Vermeire Séverine , Hellstern Paul , Panaccione Remo , Rogler Gerhard , Fraser Gerald , Kohn Anna , Desreumaux Pierre , Leong Rupert W , Comer Gail M , Cataldi Fabio , Banerjee Anindita , Maguire Mary K , Li Cheryl , Rath Natalie , Beebe Jean , Schreiber Stefan 
Published: December 2017

ObjectiveNeutralising pro-inflammatory interleukin-6 (IL-6) may effectively treat Crohn’s disease (CD). Effects of PF-04236921, an anti-IL-6 antibody, in adults with CD are reported.DesignParallel-group, dose-ranging, double-blind trial with 4-week screening and 12-week treatment periods. After induction, patients entered 28-week follow-up or 48-week open-label extension (OLE) with 28-week follow-up. Adults with confirmed CD and inadequate response to anti-tumour necrosis factor (TNF) therapy were included. Induction study: 249 patients randomised 1:1:1:1 to placebo, PF-04236921 10, 50 or 200 mg by subcutaneous injection on days 1 and 28. OLE study: PF-04236921 50 mg every 8 weeks up to six doses followed by 28-week follow-up.Results247 patients were randomised and received treatment in the induction study. The 200 mg dose was discontinued due to safety findings in another study (NCT01405196) and was not included in the primary efficacy analysis. Crohn’s Disease Activity Index (CDAI)-70 response rates with PF-04236921 50 mg were significantly greater than placebo at weeks 8 (49.3% vs 30.6%, P<0.05) and 12 (47.4% vs 28.6%, P<0.05) and met the primary end point. Week 12 CDAI remission rates with PF-04236921 50 mg and placebo were 27.4% and 10.9%, respectively (16.5% difference; P<0.05). 191 subjects received treatment in the OLE. Common treatment-emergent and serious adverse events in both studies included worsening CD, abdominal pain and nasopharyngitis.ConclusionsPF-04236921 50 mg induced clinical response and remission in refractory patients with moderate-to-severe CD following failure of anti-TNF therapy. GI abscess and perforation were observed, a specific focus of attention during future clinical development.Trial registration numberNCT01287897 and NCT01345318.
Viruses causing lower respiratory symptoms in young children: findings from the ORChID birth cohort
Authors: Sarna Mohinder , Lambert Stephen B , Sloots Theo P , Whiley David M , Alsaleh Asma , Mhango Lebogang , Bialasiewicz Seweryn , Wang David , Nissen Michael D , Grimwood Keith , Ware Robert S 
Published: December 2017

IntroductionViral acute respiratory infections (ARIs) cause substantial child morbidity. Sensitive molecular-based assays aid virus detection, but the clinical significance of positive tests remains uncertain as some viruses may be found in both acutely ill and healthy children. We describe disease-pathogen associations of respiratory viruses and quantify virus-specific attributable risk of ARIs in healthy children during the first 2 years of life.MethodsOne hundred fifty-eight term newborn babies in Brisbane, Australia, were recruited progressively into a longitudinal, community-based, birth cohort study conducted between September 2010 and October 2014. A daily tick-box diary captured predefined respiratory symptoms from birth until their second birthday. Weekly parent-collected nasal swabs were batch-tested for 17 respiratory viruses by PCR assays, allowing calculation of virus-specific attributable fractions in the exposed (AFE) to determine the proportion of virus-positive children whose ARI symptoms could be attributed to that particular virus.ResultsOf 8100 nasal swabs analysed, 2646 (32.7%) were virus-positive (275 virus codetections, 3.4%), with human rhinoviruses accounting for 2058/2646 (77.8%) positive swabs. Viruses were detected in 1154/1530 (75.4%) ARI episodes and in 984/4308 (22.8%) swabs from asymptomatic periods. Respiratory syncytial virus (AFE: 68% (95% CI 45% to 82%)) and human metapneumovirus (AFE: 69% (95% CI 43% to 83%)) were strongly associated with higher risk of lower respiratory symptoms.DiscussionThe strong association of respiratory syncytial virus and human metapneumovirus with ARIs and lower respiratory symptoms in young children managed within the community indicates successful development of vaccines against these two viruses should provide substantial health benefits.
Numerical groundwater modelling in karst
Authors: Kresic Neven , Panday Sorab 
Published: December 2017

Abstract
The success of translating a conceptual site model for a karst site into a numerical groundwater model will depend on both the experience of the user and the capabilities and limitations of the selected computer program. Despite its numerous advantages, even MODFLOW – probably the most widely used, tested and verified modelling program currently available – has conceptual limitations that many karst hydrogeologists have to deal with on a routine basis while searching for an equivalent porous medium approach that may work. This includes assigning very high values of hydraulic conductivity to those model cells known, or suspected, to contain highly transmissive conduits, or assigning an unreasonable, very low effective porosity to the model cells with virtual ‘conduits’ to simulate high groundwater velocities. A new version of MODFLOW called MODFLOW-USG (UnStructured Grid) has been developed and released to the public domain. This new version retains full compatibility with previous versions of MODFLOW while taking advantage of unstructured grids and finite volume numerical solutions. It enables hydrogeologists to accurately translate even the most complex conceptual site models in karst into a numerical environment, thus eliminating the need for various surrogate modelling solutions based on an equivalent porous medium approach.
Carbon and hydrogen isotopic compositions of
n
-alkanes as a tool in petroleum exploration
Authors: Pedentchouk Nikolai , Turich Courtney 
Published: December 2017

Abstract

Compound-specific isotope analysis (CSIA) of individual organic compounds is a powerful but underutilized tool in petroleum exploration. When integrated with other organic geochemical methodologies it can provide evidence of fluid histories including source, maturity, charge history and reservoir processes that can support field development planning and exploration efforts. The purpose of this chapter is to provide a review of the methodologies used for generating carbon and hydrogen isotope data for mid- and high-molecular-weight
n
-alkanes.

We discuss the factors that control stable carbon and hydrogen isotope compositions of
n
-alkanes and related compounds in sedimentary and petroleum systems and review current and future applications of this methodology for petroleum exploration. We discuss basin-specific case studies that demonstrate the usefulness of CSIA either when addressing particular aspects of petroleum exploration (e.g. charge evaluation, source rock–oil correlation, and investigation of maturity and in-reservoir processes) or when this technique is used to corroborate interpretations from integrated petroleum systems analysis, providing unique insights which may not be revealed when using other methods. CSIA of
n
-alkanes and related
n
-alkyl structures can provide independent data to strengthen petroleum systems concepts from generation and expulsion of fluids from source rock, to charge history, connectivity, and in-reservoir processes.
The isotopic structures of geological organic compounds
Authors: Eiler John M. , Clog Matthieu , Lawson Michael , Lloyd Max , Piasecki Alison , Ponton Camilo , Xie Hao 
Published: December 2017

Abstract

Organic compounds are ubiquitous in the Earth's surface, sediments and many rocks, and preserve records of geological, geochemical and biological history; they are also critical natural resources and major environmental pollutants. The naturally occurring stable isotopes of volatile elements (D,
13
C,
15
N,
17,18
O,
33,34,36
S) provide one way of studying the origin, evolution and migration of geological organic compounds. The study of bulk stable isotope compositions (i.e. averaged across all possible molecular isotopic forms) is well established and widely practised, but frequently results in non-unique interpretations. Increasingly, researchers are reading the organic isotopic record with greater depth and specificity by characterizing stable isotope ‘structures’ – the proportions of site-specific and multiply substituted isotopologues that contribute to the total rare-isotope inventory of each compound. Most of the technologies for measuring stable isotope structures of organic molecules have been only recently developed and to date have been applied only in an exploratory way. Nevertheless, recent advances have demonstrated that molecular isotopic structures provide distinctive records of biosynthetic origins, conditions and mechanisms of chemical transformation during burial, and forensic fingerprints of exceptional specificity. This paper provides a review of this young field, which is organized to follow the evolution of molecular isotopic structure from biosynthesis, through diagenesis, catagenesis and metamorphism.
Testing clumped isotopes as a reservoir characterization tool: a comparison with fluid inclusions in a dolomitized sedimentary carbonate reservoir buried to 2–4 km
Authors: MacDonald John M. , John Cédric M. , Girard Jean-Pierre 
Published: December 2017

Abstract

Constraining basin thermal history is a key part of reservoir characterization in carbonate rocks. Conventional palaeothermometric approaches cannot always be used: fluid inclusions may be reset or not present, while δ
18
O palaeothermometry requires an assumption on the parent fluid composition. The clumped isotope palaeothermometer, however, is a promising technique for constraining the thermal history of basins. In this study, we test if clumped isotopes record temperatures of recrystallization in deeply-buried dolomitic reservoirs, through comparison with fluid-inclusion data. The studied reservoir is the Cretaceous Pinda Formation, offshore Angola, a deeply-buried dolomitized sedimentary carbonate hydrocarbon reservoir. It provides an ideal test case as samples from industry wells are available over a relatively wide burial depth range of
c.
2000–4000 m below seafloor (mbsf) and the constituent dolomites are relatively homogeneous.

Across this depth range, fluid-inclusion homogenization temperatures for the Pinda Formation record a range of temperatures from
c.
110 to 170°C, increasing with depth. These closely match present-day ambient well temperatures, indicating recent resetting of the fluid inclusions. Clumped isotopes, however, record temperatures significantly (
c.
20–60°C) below fluid-inclusion and well temperatures for the seven samples analysed. The deepest five samples (
c.
2800–3700 mbsf) record clumped isotope temperatures of around 100–120°C, interpreted to represent a deep burial recrystallization event responsible for a massive (re)dolomitization of the reservoir. The lower clumped isotope temperatures (65 and 82°C) of the shallower (2055 and 2740 mbsf) samples are interpreted to represent physical mixing of two dolomite generations due to incomplete burial recrystallization of an early shallow dolomite. Determination of temperature through clumped isotopes allows calculation of the parent fluid δ
18
O values. In the five deepest samples, the fluid δ
18
O values of 3.7–6.5‰ cluster around the modern-day porewater composition (5‰), suggesting that burial dolomitization occurred in the presence of evolved brine. Mineral δ
18
O values of
c
. −7 to −4.5‰ are lower than pristine Cretaceous marine dolomite and are in accordance with burial recrystallization. Clumped isotopes are therefore interpreted to record temperatures corresponding to open-system burial recrystallization events. This study shows that clumped isotopes are a valuable tool in characterizing the thermal history of deeply-buried (>2000 m) carbonate hydrocarbon reservoirs.
Discovery of IDO1 Inhibitors: From Bench to Bedside
Authors: Prendergast George C. , Malachowski William P. , DuHadaway James B. , Muller Alexander J. 
Published: December 2017

AbstractSmall-molecule inhibitors of indoleamine 2,3-dioxygenase-1 (IDO1) are emerging at the vanguard of experimental agents in oncology. Here, pioneers of this new drug class provide a bench-to-bedside review on preclinical validation of IDO1 as a cancer therapeutic target and on the discovery and development of a set of mechanistically distinct compounds, indoximod, epacadostat, and navoximod, that were first to be evaluated as IDO inhibitors in clinical trials. As immunometabolic adjuvants to widen therapeutic windows, IDO inhibitors may leverage not only immuno-oncology modalities but also chemotherapy and radiotherapy as standards of care in the oncology clinic. Cancer Res; 77(24); 6795–811. ©2017 AACR.
Global Pulmonary Vascular Remodeling in Pulmonary Hypertension Associated With Heart Failure and Preserved or Reduced Ejection Fraction
Authors: Fayyaz Ahmed U. , Edwards William D. , Maleszewski Joseph J. , Konik Ewa A. , DuBrock Hilary M. , Borlaug Barry A. , Frantz Robert P. , Jenkins Sarah M. , Redfield Margaret M. 
Published: December 2017

Background:
We hypothesized that pulmonary venous hypertension in heart failure (HF) leads to predominate remodeling of pulmonary veins and that the severity of venous remodeling is associated with the severity of pulmonary hypertension (PH) in HF.

Methods:
Patients with HF (n=108; 53 preserved and 55 reduced ejection fraction) with PH (HF-PH; pulmonary artery systolic pressure [PASP] ≥40 mm Hg) were compared to normal controls (n=12) and patients with primary pulmonary veno-occlusive disease (PVOD; n=17). In lung specimens from autopsy (control, HF-PH, and 7 PVOD) or surgery (10 PVOD), quantitative histomorphometry was performed in all analyzable arteries (n=4949), veins (n=7630), and small indeterminate vessels (IV; n=2168) to define percent medial thickness (arteries) and percent intimal thickness (%IT) (arteries, veins, and IV) relative to external diameter.

Results:

The average arterial percent medial thickness (control, 6.9; HF-PH, 11.0; PVOD, 15.0), arterial %IT (control, 4.9; HF-PH, 14.9; PVOD, 31.1), venous %IT (control, 14.0; HF-PH, 24.9; PVOD, 43.9), and IV %IT (control, 10.6; HF-PH, 25.8; PVOD, 50.0) in HF-PH were higher than controls (
P
<0.0001 for all) but lower than PVOD (
P
≤0.005 for all). PASP (mm Hg) was lower in HF-PH (median, 59 [interquartile range, 50–70]) than in PVOD (median, 91 [interquartile range, 82–103]). PASP correlated with arterial percent medial thickness (
r
=0.41) and arterial %IT (
r
=0.35) but more strongly with venous %IT (
r
=0.49) and IV %IT (
r
=0.55) (
P
<0.0001 for all). Associations between PASP and venous or IV %IT remained significant after adjusting for arterial percent medial thickness and %IT and did not vary by HF type. In patients with right heart catheterization (30 HF-PH, 14 PVOD), similar associations between the transpulmonary gradient and pulmonary vascular remodeling existed, with numerically stronger associations for venous and IV %IT. Although the PASP was slightly higher in patients with HF-PH with right ventricular dysfunction, pulmonary vascular remodeling was not more severe. Pulmonary vascular remodeling severity was associated with reductions in the diffusing capacity of the lungs.

Conclusions:
In HF, PH is associated with global pulmonary vascular remodeling, but the severity of PH correlates most strongly with venous and small IV intimal thickening, similar to the pattern observed in PVOD. These findings expand our understanding of the pathobiology of PH in HF.
Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry
Authors: Alabas Oras A , Gale Chris P , Hall Marlous , Rutherford Mark J. , Szummer Karolina , Lawesson Sofia Sederholm , Alfredsson Joakim , Lindahl Bertil , Jernberg Tomas 
Published: December 2017

Background
This study assessed sex differences in treatments, all‐cause mortality, relative survival, and excess mortality following acute myocardial infarction.

Methods and Results
A population‐based cohort of all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART [Swedish Web System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies]) from 2003 to 2013 was included in the analysis. Excess mortality rate ratios (EMRRs), adjusted for clinical characteristics and guideline‐indicated treatments after matching by age, sex, and year to background mortality data, were estimated. Although there were no sex differences in all‐cause mortality adjusted for age, year of hospitalization, and comorbidities for ST‐segment–elevation myocardial infarction (STEMI) and non‐STEMI at 1 year (mortality rate ratio: 1.01 [95% confidence interval (CI), 0.96–1.05] and 0.97 [95% CI, 0.95–0.99], respectively) and 5 years (mortality rate ratio: 1.03 [95% CI, 0.99–1.07] and 0.97 [95% CI, 0.95–0.99], respectively), excess mortality was higher among women compared with men for STEMI and non‐STEMI at 1 year (EMRR: 1.89 [95% CI, 1.66–2.16] and 1.20 [95% CI, 1.16–1.24], respectively) and 5 years (EMRR: 1.60 [95% CI, 1.48–1.72] and 1.26 [95% CI, 1.21–1.32], respectively). After further adjustment for the use of guideline‐indicated treatments, excess mortality among women with non‐STEMI was not significant at 1 year (EMRR: 1.01 [95% CI, 0.97–1.04]) and slightly higher at 5 years (EMRR: 1.07 [95% CI, 1.02–1.12]). For STEMI, adjustment for treatments attenuated the excess mortality for women at 1 year (EMRR: 1.43 [95% CI, 1.26–1.62]) and 5 years (EMRR: 1.31 [95% CI, 1.19–1.43]).

Conclusions
Women with acute myocardial infarction did not have statistically different all‐cause mortality, but had higher excess mortality compared with men that was attenuated after adjustment for the use of guideline‐indicated treatments. This suggests that improved adherence to guideline recommendations for the treatment of acute myocardial infarction may reduce premature cardiovascular death among women.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02952417.