bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single and mixed dyslipidaemia in Canadian primary care settings: findings from the Canadian primary care sentinel surveillance network database
Authors: Asghari Shabnam , Aref-Eshghi Erfan , Godwin Marshall , Duke Pauline , Williamson Tyler , Mahdavian Masoud 
Published: December 2015

ObjectivesDyslipidaemia is a major risk factor to cardiovascular disease (CVD)—the leading cause of death worldwide. Limited data are available about the prevalence of various dyslipidaemia in Canada. The objective of this study is to describe the prevalence of various single and mixed dyslipidaemia within the Canadian population in a primary care setting.SettingA cross-sectional study, using the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), was undertaken.ParticipantsNon-pregnant adults older than 20 years were included.Outcome measuresCanadian guidelines were used to define dyslipidaemia. Descriptive statistics and multivariate regression analyses were conducted to compare the prevalence of single/mixed dyslipidaemia.Results134 074 individuals with a mean age of 59.2 (55.8% women) were identified. 34.8% of this population had no lipid abnormality, whereas 35.8%, 17.3% and 3.2% had abnormalities in one, two and three lipid components, respectively. Approximately 86% of these patients did not receive any lipid-lowering medication. Among the medication users (14%), approximately 12% were on statin monotherapy. Statin users (n=16 036) had a lower rate of low-density lipoprotein dyslipidaemia compared to non-medication users (3% vs 17%), whereas the prevalence of high-density lipoprotein (HDL) (20% vs 12%) and triglycerides (TG) (12% vs 7%) dyslipidaemia were higher in statin users. Statin users had a greater prevalence of HDL, TG and combined HDL-TG dyslipidaemia compared to non-medication users (OR 1.44, 95% CI 1.36 to 153), (OR 1.18, 95% CI 1.10 to 1.27) and (OR 1.30, 95% CI 1.22 to 1.38), respectively, (all p values<0.0001).ConclusionsOne of every five patients in primary care settings in Canada is suffering from mixed dyslipidaemia. The overall prevalence of dyslipidaemia remains the same between treated and untreated groups, although the type of abnormal lipid component is considerably different. Among the CVD risk factors, obesity has the greatest effect on the prevalence of all types of dyslipidaemia.
Implementing guidelines to routinely prevent chronic vascular disease in primary care: the Preventive Evidence into Practice cluster randomised controlled trial
Authors: Harris Mark Fort , Parker Sharon M , Litt John , van Driel Mieke , Russell Grant , Mazza Danielle , Jayasinghe Upali W , Del Mar Chris , Lloyd Jane , Smith Jane , Zwar Nicholas , Taylor Richard , Powell Davies Gawaine 
Published: December 2015

ObjectiveTo evaluate an intervention to improve implementation of guidelines for the prevention of chronic vascular disease.Setting32 urban general practices in 4 Australian states.RandomisationStratified randomisation of practices.Participants122 general practitioners (GPs) and practice nurses (PNs) were recruited at baseline and 97 continued to 12 months. 21 848 patient records were audited for those aged 40–69 years who attended the practice in the previous 12 months without heart disease, stroke, diabetes, chronic renal disease, cognitive impairment or severe mental illness.InterventionThe practice level intervention over 6 months included small group training of practice staff, feedback on audited performance, practice facilitation visits and provision of patient education and referral information.Outcome measuresPrimary: 1. Change in proportion of patients aged 40–69 years with smoking status, alcohol intake, body mass index (BMI), waist circumference (WC), blood pressure (BP) recorded and for those aged 45–69 years with lipids, fasting blood glucose and cardiovascular risk in the medical record. 2. Change in the level of risk for each factor.Secondarychange in self-reported frequency and confidence of GPs and PNs in assessment.ResultsRisk recording improved in the intervention but not the control group for WC (OR 2.52 (95% CI 1.30 to 4.91)), alcohol consumption (OR 2.19 (CI 1.04 to 4.64)), smoking status (OR 2.24 (1.17 to 4.29)) and cardiovascular risk (OR 1.50 (1.04 to 2.18)). There was no change in recording of BP, lipids, glucose or BMI and no significant change in the level of risk factors based on audit data. The confidence but not reported practices of GPs and PNs in the intervention group improved in the assessment of some risk factors.ConclusionsThis intervention was associated with improved recording of some risk factors but no change in the level of risk at the follow-up audit.Trial registration numberAustralian and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000578808, results.
Learning from positively deviant wards to improve patient safety: an observational study protocol
Authors: Baxter Ruth , Taylor Natalie , Kellar Ian , Lawton Rebecca 
Published: December 2015

IntroductionPositive deviance is an asset-based approach to improvement which has recently been adopted to improve quality and safety within healthcare. The approach assumes that solutions to problems already exist within communities. Certain groups or individuals identify these solutions and succeed despite having the same resources as others. Within healthcare, positive deviance has previously been applied at individual or organisational levels to improve specific clinical outcomes or processes of care. This study explores whether the positive deviance approach can be applied to multidisciplinary ward teams to address the broad issue of patient safety among elderly patients.Methods and analysisPreliminary work analysed National Health Service (NHS) Safety Thermometer data from 34 elderly medical wards to identify 5 ‘positively deviant’ and 5 matched ‘comparison’ wards. Researchers are blinded to ward status. This protocol describes a multimethod, observational study which will (1) assess the concurrent validity of identifying positively deviant elderly medical wards using NHS Safety Thermometer data and (2) generate hypotheses about how positively deviant wards succeed. Patient and staff perceptions of safety will be assessed on each ward using validated surveys. Correlation and ranking analyses will explore whether this survey data aligns with the routinely collected NHS Safety Thermometer data. Staff focus groups and researcher fieldwork diaries will be completed and qualitative thematic content analysis will be used to generate hypotheses about the strategies, behaviours, team cultures and dynamics that facilitate the delivery of safe patient care. The acceptability and sustainability of strategies identified will also be explored.Ethics and disseminationThe South East Scotland Research Ethics Committee 01 approved this study (reference: 14/SS/1085) and NHS Permissions were granted from all trusts. Findings will be published in peer-reviewed, scientific journals, and presented at academic conferences.Trial registration numberThis study is registered on the UK Clinical Research Network Study Portfolio (reference number—18050).
Protocol for ACCESS: a qualitative study exploring barriers and facilitators to accessing the emergency contraceptive pill from community pharmacies in Australia
Authors: Hussainy Safeera Yasmeen , Ghosh Ayesha , Taft Angela , Mazza Danielle , Black Kirsten Isla , Clifford Rhonda , Gudka Sajni , Mc Namara Kevin Peter , Ryan Kath , Jackson John Keith 
Published: December 2015

IntroductionThe rate of unplanned pregnancy in Australia remains high, which has contributed to Australia having one of the highest abortion rates of developed countries with an estimated 1 in 5 women having an abortion. The emergency contraceptive pill (ECP) offers a safe way of preventing unintended pregnancy after unprotected sex has occurred. While the ECP has been available over-the-counter in Australian pharmacies for over a decade, its use has not significantly increased. This paper presents a protocol for a qualitative study that aims to identify the barriers and facilitators to accessing the ECP from community pharmacies in Australia.Methods and analysisData will be collected through one-on-one interviews that are semistructured and in-depth. Partnerships have been established with 2 pharmacy groups and 2 women's health organisations to aid with the recruitment of women and pharmacists for data collection purposes. Interview questions explore domains from the Theoretical Domains Framework in order to assess the factors aiding and/or hindering access to ECP from community pharmacies. Data collected will be analysed using deductive content analysis. The expected benefits of this study are that it will help develop evidence-based workforce interventions to strengthen the capacity and performance of community pharmacists as key ECP providers.Ethics and disseminationThe findings will be disseminated to the research team and study partners, who will brainstorm ideas for interventions that would address barriers and facilitators to access identified from the interviews. Dissemination will also occur through presentations and peer-reviewed publications and the study participants will receive an executive summary of the findings. The study has been evaluated and approved by the Monash Human Research Ethics Committee.
Conversion of colonoscopy to flexible sigmoidoscopy: an unintended consequence of quality measurement in endoscopy
Authors: Thompson Chris , Ismail Tariq , Radley Simon , Walt Robert , Ward Stephen Thomas 
Published: December 2015

ObjectiveTo quantify the proportion of requests for colonoscopy that are performed as flexible sigmoidoscopy and documented reasons for this in ordinary UK hospital practice. To determine the effect these requests have on colonoscopy completion rate if they are included in the denominator of the calculated rate by individual endoscopist.DesignRetrospective study of 22 months flexible sigmoidoscopy practice at a major UK teaching hospital. All flexible sigmoidoscopies performed had their associated request form examined.SettingUK NHS University Hospital.PatientsAll patients receiving outpatient flexible sigmoidoscopy from January 2013 to October 2014 with no exclusions.InterventionConversion of colonoscopy to flexible sigmoidoscopy.Main outcome measuresConversion of colonoscopy to flexible sigmoidoscopy, reason for conversion and adjusted colonoscopy completion rate.Results71 of the 3526 flexible sigmoidoscopies performed (2.0%), representing 71 of 5905 colonoscopy requests (1.2%). Conversion reason was noted only in 26 (37%) of converted cases. Adjustment of colonoscopy completion rate to include conversions pushed four of our unit's 22 endoscopists below the UK national 90% standard.ConclusionsConversion to flexible sigmoidoscopy occurs in 1.2% of patients originally booked for colonoscopy. The reason for this conversion is often unqualified and may be inappropriate. Conversion can affect the colonoscopy completion rate, and therefore, should be included in endoscopists’ overall performance statistics.
Tumour initiating cells and IGF/FGF signalling contribute to sorafenib resistance in hepatocellular carcinoma
Authors: Tovar Victoria , Cornella Helena , Moeini Agrin , Vidal Samuel , Hoshida Yujin , Sia Daniela , Peix Judit , Cabellos Laia , Alsinet Clara , Torrecilla Sara , Martinez-Quetglas Iris , Lozano Juan José , Desbois-Mouthon Christèle , Solé Manel , Domingo-Domenech Josep , Villanueva Augusto , Llovet Josep M 
Published: December 2015

ObjectiveSorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterise the role of tumour-initiating cells (T-ICs) and signalling pathways involved in sorafenib resistance.DesignHCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: (1) role of T-ICs by in vitro sphere formation and in vivo tumourigenesis assays using NOD/SCID mice, (2) activation of alternative signalling pathways and (3) efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, quantitative real-time PCR (qRT-PCR)) and protein analyses (immunohistochemistry, western blot) were conducted. A novel gene signature of sorafenib resistance was generated and tested in two independent cohorts.ResultsSorafenib-acquired resistant tumours showed significant enrichment of T-ICs (164 cells needed to create a tumour) versus sorafenib-sensitive tumours (13 400 cells) and non-treated tumours (1292 cells), p<0.001. Tumours with sorafenib-acquired resistance were enriched with insulin-like growth factor (IGF) and fibroblast growth factor (FGF) signalling cascades (false discovery rate (FDR)<0.05). In vitro, cells derived from sorafenib-acquired resistant tumours and two sorafenib-resistant HCC cell lines were responsive to IGF or FGF inhibition. In vivo, FGF blockade delayed tumour growth and improved survival in sorafenib-resistant tumours. A sorafenib-resistance 175 gene signature was characterised by enrichment of progenitor cell features, aggressive tumorous traits and predicted poor survival in two cohorts (n=442 patients with HCC).ConclusionsAcquired resistance to sorafenib is driven by T-ICs with enrichment of progenitor markers and activation of IGF and FGF signalling. Inhibition of these pathways would benefit a subset of patients after sorafenib progression.
Testing chemical weathering proxies in Miocene–Recent fluvial-derived sediments in the South China Sea
Authors: Hu Dengke , Clift Peter D. , Wan Shiming , Böning Philipp , Hannigan Robyn , Hillier Stephen , Blusztajn Jerzy 
Published: December 2015

Abstract

Reconstructing variations in the intensity of chemical weathering in river basins is crucial if we are to understand how climate change impacts environment and whether there are feedbacks between climate and weathering processes. Quantifying chemical weathering is, however, a complicated process, involving a number of competing proxies. We compare weathering records from the Pearl River delta of southern China and Ocean Drilling Program (ODP) Sites 1144 and 1146 on the northeastern slope of the South China Sea in order to test which proxies are the most widely applicable and robust. Comparison with speleothem rainfall records indicates that K/Al tracks precipitation variations most closely and out-performs the widely used Chemical Index of Alteration (CIA). Correlation of K/Al and kaolinite/illite indicates that this clay ratio is also an effective proxy of weathering intensity across all sites and timescales. Kaolinite/smectite, and to a lesser extent smectite/(illite+chlorite), are also indicative of weathering intensity, but show more scatter between sites that may be linked to provenance effects. Mg/Al is relatively immune to grain-size effects, but does not correlate well with other proxies. K/Rb is a reasonably reliable indicator of chemical weathering intensity and may be more sensitive than CIA or K/Al to weathering changes over short timescales and when weathering is not too intense.
87
Sr/
86
Sr can be useful but can be influenced by both grain size and provenance effects. In general marine archives of fluvial sediment may record variations in weathering linked to climate, but these are increasingly signals of reworking going further offshore.
Synchronous Last Glacial Maximum across the Anatolian peninsula
Authors: Akçar Naki , Yavuz Vural , Yeşilyurt Serdar , Ivy-Ochs Susan , Reber Regina , Bayrakdar Cihan , Kubik Peter W. , Zahno Conradin , Schlunegger Fritz , Schlüchter Christian 
Published: December 2015

Abstract

Uludağ is a prominent mountain in northwestern Turkey where glacial deposits have been documented in the Kovuk Valley and the glacial history has been reconstructed based on 31 cosmogenic
10
Be exposure ages from glacially transported boulders and bedrock. The results suggest that the Kovuk Glacier began advancing before 26.5±1.6 ka. It reached its maximum extent at 20.3±1.3 ka, followed by a re-advance at 19.3±1.2 ka, both during the global Last Glacial Maximum (LGM) within Marine Isotope Stage 2. The timing of the LGM glaciations in the Kovuk Valley is consistent with the investigated LGM glaciations in other mountains of Anatolia, the Mediterranean and the Alps. Based on the geomorphological ice margin reconstruction and using the accumulation/ablation area ratio (AAR) approach, the equilibrium line altitude (ELA) of the Kovuk LGM glacier was
c.
2000 m above sea level for an estimated AAR of 0.67. This indicates a
c.
1000 m lowering of the ELA for the LGM compared with the modern ELA estimate. These lines of evidence are consistent with the LGM glaciers that have been documented elsewhere in the Anatolian Mountains.

Supplementary material:
An input file for exposure age calculation in the CRONUS-Earth online calculator and an KML file for sample locations are available at
http://www.geolsoc.org.uk/SUP18878
Genomic DNA Hypomethylation and Risk of Renal Cell Carcinoma: A Case–Control Study
Authors: Mendoza- Pérez Julia , Gu Jian , Herrera Luis A. , Tannir Nizar M. , Matin Surena F. , Karam Jose A. , Huang Maosheng , Chang David W. , Wood Christopher G. , Wu Xifeng 
Published: December 2015

Abstract
Purpose: Genomic DNA hypomethylation is a hallmark of most cancer genomes, promoting genomic instability and cell transformation. In the present study, we sought to determine whether global DNA methylation in peripheral blood is associated with risk of renal cell carcinoma (RCC).
Experimental Design: A retrospective case–control study consisting of 889 RCC cases and an equal number of age, gender, and ethnicity-matched controls was applied. Global DNA methylation was measured as 5-mC% content. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for the association between DNA methylation level and the risk of RCC.
Results: The median 5-mC% was significantly lower in cases than in healthy controls (P &lt; 0.001). In multivariate logistic regression analysis, individuals in the lowest tertile (T1) of 5-mC% had higher risk of RCC with OR of 1.40 (95% CI, 1.06–1.84), compared with individuals in the highest tertile (T3; Pfor trend = 0.02). When stratified by RCC risk factors, associations between hypomethylation and increased RCC risk appeared to be stronger among males (OR, 1.61; Pfor trend = 0.01), younger age (OR, 1.47; Pfor trend = 0.03), never smokers (OR, 1.55; Pfor trend = 0.02), family history of other cancer (OR, 1.64; Pfor trend = 1.22E−03), and late stage (OR, 2.06, Pfor trend = 4.98E−04). Additionally, we observed significant interaction between gender and 5-mC% in elevating RCC risk (Pfor interaction = 0.03).
Conclusions: Our findings suggest an association between global DNA hypomethylation and RCC risk. To establish global DNA hypomethylation as a risk factor for RCC, future prospective studies are warranted. This study may provide further understanding of the etiology of RCC tumorigenesis. Clin Cancer Res; 22(8); 2074–82. ©2015 AACR.
A Phase I Study of the Anti-Activin Receptor-Like Kinase 1 (ALK-1) Monoclonal Antibody PF-03446962 in Patients with Advanced Solid Tumors
Authors: Goff Laura W. , Cohen Roger B. , Berlin Jordan D. , de Braud Filippo G. , Lyshchik Andrej , Noberasco Cristina , Bertolini Francesco , Carpentieri Marina , Stampino Corrado Gallo , Abbattista Antonello , Wang Erjan , Borghaei Hossein 
Published: December 2015

Abstract
Purpose: Objectives of this dose-finding study were to determine the MTD and recommended phase II dose (RP2D) of the first-in-class anti-activin receptor-like kinase 1 (ALK-1) monoclonal antibody PF-03446962, and assess safety and antitumor activity in patients with advanced solid tumors.
Experimental Design: This open-label, multicenter study was based on a 3+3 design. PF-03446962 was administered biweekly by intravenous infusion, at doses ranging from 0.5 to 15 mg/kg.
Results: Forty-four patients received treatment with PF-03446962. Dose-limiting toxicities observed during dose escalation included grade 3 increased amylase, grade 3/4 increased lipase, and grade 3/4 thrombocytopenia. The MTD was determined to be 10 mg/kg. The RP2D was set at 7 mg/kg for patients with advanced solid tumors, based on the observed safety, pharmacokinetics, and antitumor activity. The most-frequent treatment-related, all-grade adverse events included thrombocytopenia (20.5%), fatigue (15.9%), and nausea, increased amylase, and increased lipase (each 11.4%). Treatment-related telangiectasia was noted in 7% of patients, suggesting in vivo inhibition of the ALK-1 pathway. None of the deaths was deemed to be treatment-related. Three (6.8%) patients with advanced hepatocellular carcinoma, renal cell carcinoma, or non–small cell lung cancer achieved a partial response, and 12 (27.3%) patients had stable disease, across dose levels. Contrast-enhanced ultrasound analysis of tumor vascularity showed reduction in tumor perfusion in 2 patients with stable disease following treatment with PF-03446962.
Conclusions: The clinical activity demonstrated in this study points to PF-03446962 as a novel approach to antiangiogenic therapy, with manageable safety profile and single-agent, antitumor activity in patients with advanced solid tumors. Clin Cancer Res; 22(9); 2146–54. ©2015 AACR.
Rare Exome Sequence Variants in
CLCN6
Reduce Blood Pressure Levels and Hypertension Risk
Authors: Yu Bing , Pulit Sara L. , Hwang Shih-Jen , Brody Jennifer A. , Amin Najaf , Auer Paul L. , Bis Joshua C. , Boerwinkle Eric , Burke Gregory L. , Chakravarti Aravinda , Correa Adolfo , Dreisbach Albert W. , Franco Oscar H. , Ehret Georg B. , Franceschini Nora , Hofman Albert , Lin Dan-Yu , Metcalf Ginger A. , Musani Solomon K. , Muzny Donna , Palmas Walter , Raffel Leslie , Reiner Alex , Rice Ken , Rotter Jerome I. , Veeraraghavan Narayanan , Fox Ervin , Guo Xiuqing , North Kari E. , Gibbs Richard A. , van Duijn Cornelia M. , Psaty Bruce M. , Levy Daniel , Newton-Cheh Christopher , Morrison Alanna C. 
Published: December 2015

Background—
Rare genetic variants influence blood pressure (BP).

Methods and Results—

Whole-exome sequencing was performed on DNA samples from 17 956 individuals of European ancestry and African ancestry (14 497, first-stage discovery and 3459, second-stage discovery) to examine the effect of rare variants on hypertension and 4 BP traits: systolic BP, diastolic BP, pulse pressure, and mean arterial pressure. Tests of ≈170 000 common variants (minor allele frequency, ≥1%; statistical significance,
P
≤2.9×10
−7
) and gene-based tests of rare variants (minor allele frequency, <1%; ≈17 000 genes; statistical significance,
P
≤1.5×10
−6
) were evaluated for each trait and ancestry, followed by multiethnic meta-analyses. In the first-stage discovery, rare coding variants (splicing, stop-gain, stop-loss, nonsynonymous variants, or indels) in
CLCN6
were associated with lower diastolic BP (cumulative minor allele frequency, 1.3%;
β
=−3.20;
P
=4.1×10
−6
) and were independent of a nearby common variant (rs17367504) previously associated with BP.
CLCN6
rare variants were also associated with lower systolic BP (
β
=−4.11;
P
=2.8×10
−4
), mean arterial pressure (
β
=−3.50;
P
=8.9×10
−6
), and reduced hypertension risk (odds ratio, 0.72;
P
=0.017). Meta-analysis of the 2-stage discovery samples showed that
CLCN6
was associated with lower diastolic BP at exome-wide significance (cumulative minor allele frequency, 1.1%;
β
=−3.30;
P
=5.0×10
−7
).

Conclusions—

These findings implicate the effect of rare coding variants in
CLCN6
in BP variation and offer new insights into BP regulation.