bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database
Authors: Møller Pål , Seppälä Toni T , Bernstein Inge , Holinski-Feder Elke , Sala Paulo , Gareth Evans D , Lindblom Annika , Macrae Finlay , Blanco Ignacio , Sijmons Rolf H , Jeffries Jacqueline , Vasen Hans F A , Burn John , Nakken Sigve , Hovig Eivind , Rødland Einar Andreas , Tharmaratnam Kukatharmini , de Vos tot Nederveen Cappel Wouter H , Hill James , Wijnen Juul T , Jenkins Mark A , Green Kate , Lalloo Fiona , Sunde Lone , Mints Miriam , Bertario Lucio , Pineda Marta , Navarro Matilde , Morak Monika , Renkonen-Sinisalo Laura , Valentin Mev Dominguez , Frayling Ian M , Plazzer John-Paul , Pylvanainen Kirsi , Genuardi Maurizio , Mecklin Jukka-Pekka , Moeslein Gabriela , Sampson Julian R , Capella Gabriel 
Published: July 2017

BackgroundMost patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival.Objective and designThis observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age.Results3119 patients were followed for a total of 24 475 years. Cumulative incidences at 75 years (risks) for colorectal cancer were 46%, 43% and 15% in path_MLH1, path_MSH2 and path_MSH6 carriers; for endometrial cancer 43%, 57% and 46%; for ovarian cancer 10%, 17% and 13%; for upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancers 21%, 10% and 7%; for urinary tract cancers 8%, 25% and 11%; for prostate cancer 17%, 32% and 18%; and for brain tumours 1%, 5% and 1%, respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper gastrointestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder 93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had lower risk for cancer.ConclusionCarriers of different path_MMR variants exhibit distinct patterns of cancer risk and survival as they age. Risk estimates for counselling and planning of surveillance and treatment should be tailored to each patient’s age, gender and path_MMR variant. We have updated our open-access website www.lscarisk.org to facilitate this.
Shock-absorbing aggregates beneath playground equipment: grain properties and moisture content
Authors: Jäniskangas Tapani , Pylkkänen Kari P K , Kolisoja Pauli 
Published: July 2017

ObjectivesTo assess the influence of grain size distribution and moisture condition on aggregates’Setting and methodsImpact attenuation of sands and gravels was tested using a guided headform with a uniaxial accelerometer inside. The result for impact attenuation was the acceleration value of the headform measured from four different drop heights and the Head Injury Criterion (HIC) calculated from it. The acceptable HIC value of a shock-absorbing layer is <1000, that is, less than the critical fall height. Tests were conducted with both dry and wet materials.ResultsThe impact attenuation of a shock-absorbing layer made of loose aggregate is determined mainly by the following material factors: maximum grain size, median grain size, uniformity coefficient, fines content, grain shape and moisture content. In addition, the moisture content of aggregate, especially sands, has a major impact on its impact attenuation capacity. Of the studied sands, coarse and gravelly ones had the best impact attenuation properties. Most of the examined sands were uniformly graded. None of the grain properties of gravels proved more significant than the others. Yet, open-graded gravel (dominant grain size 4–8 mm) containing a small amount (about10%) of sand fraction 0.06–0.6 mm, but with hardly any coarse sand (0.6–2 mm), was found to have good impact attenuation.ConclusionsThis study shows that the aggregates for shock-absorbing layer should always be tested wet in laboratory conditions corresponding the most critical situation. Standards should include a procedure for wet testing of aggregates.
The impact of bivalent HPV vaccine on cervical intraepithelial neoplasia by deprivation in Scotland: reducing the gap
Authors: Cameron Ross L , Kavanagh Kimberley , Cameron Watt D , Robertson Chris , Cuschieri Kate , Ahmed Syed , Pollock Kevin G 
Published: July 2017

BackgroundCervical cancer disproportionately affects women from lower socioeconomic backgrounds. A human papillomavirus (HPV) vaccination programme was introduced in Scotland in 2008 with uptake being lower and inequitable in a catch-up cohort run for the first three years of the programme compared with the routine programme. The socioeconomic differences in vaccine uptake have the potential to further increase the inequality gap in regards to cervical disease.MethodsVaccination status was linked to demographic, cytological and colposcopic data, which are routinely collected by the Scottish HPV surveillance system. Incidence rates and relative risk of cervical intraepithelial neoplasia (CIN) 1, 2 and 3 in unvaccinated and vaccinated women were stratified by birth year and deprivation status using Poisson regression.ResultsWomen who received three doses of HPV vaccine have significantly decreased risk of CIN 1, 2 and 3. Vaccine effectiveness was greater in those women from the most deprived backgrounds against CIN 2 and 3 lesions. Compared with the most deprived, unvaccinated women, the relative risk of CIN 3 in fully vaccinated women in the same deprivation group was 0.29 (95% CI 0.2 to 0.43) compared with 0.62 (95% CI 0.4 to 0.97) in vaccinated women in the least-deprived group.ConclusionsThe HPV vaccine is associated with significant reductions in both low-grade and high-grade CIN for all deprivation categories. However, the effect on high-grade disease was most profound in the most-deprived women. These data are welcoming and allay the concern that inequalities in cervical cancer may persist or increase following the introduction of the vaccine in Scotland.
Identification of biomarkers of response to abatacept in patients with SLE using deconvolution of whole blood transcriptomic data from a phase IIb clinical trial
Authors: Bandyopadhyay Somnath , Connolly Sean E , Jabado Omar , Ye June , Kelly Sheila , Maldonado Michael A , Westhovens Rene , Nash Peter , Merrill Joan T , Townsend Robert M 
Published: July 2017

ObjectiveTo characterise patients with active SLE based on pretreatment gene expression-defined peripheral immune cell patterns and identify clusters enriched for potential responders to abatacept treatment.MethodsThis post hoc analysis used baseline peripheral whole blood transcriptomic data from patients in a phase IIb trial of intravenous abatacept (~10 mg/kg/month). Cell-specific genes were used with a published deconvolution algorithm to identify immune cell proportions in patient samples, and unsupervised consensus clustering was generated. Efficacy data were re-analysed.ResultsPatient data (n=144: abatacept: n=98; placebo: n=46) were grouped into four main clusters (C) by predominant characteristic cells: C1—neutrophils; C2—cytotoxic T cells, B-cell receptor-ligated B cells, monocytes, IgG memory B cells, activated T helper cells; C3—plasma cells, activated dendritic cells, activated natural killer cells, neutrophils; C4—activated dendritic cells, cytotoxic T cells. C3 had the highest baseline total British Isles Lupus Assessment Group (BILAG) scores, highest antidouble-stranded DNA autoantibody levels and shortest time to flare (TTF), plus trends in favour of response to abatacept over placebo: adjusted mean difference in BILAG score over 1 year, −4.78 (95% CI −12.49 to 2.92); median TTF, 56 vs 6 days; greater normalisation of complement component 3 and 4 levels. Differential improvements with abatacept were not seen in other clusters, except for median TTF in C1 (201 vs 109 days).ConclusionsImmune cell clustering segmented disease severity and responsiveness to abatacept. Definition of immune response cell types may inform design and interpretation of SLE trials and treatment decisions.Trial registration numberNCT00119678; results.
The combined effects of job demand and control, effort-reward imbalance and work-family conflicts on the risk of major depressive episode: a 4-year longitudinal study
Authors: Nigatu Yeshambel T , Wang JianLi 
Published: July 2017

PurposeWork-related psychosocial factors may precipitate the onset of depression. In occupational mental health research, there are three widely used theoretical models, namely, job demand and control (JD-C), effort-reward imbalance (ERI) and work-family conflicts (WFC). However, the interaction between these models and their combined effect on the risk of major depression in the workplace is largely unknown. The aim of this study is to examine the longitudinal combined effects of JD-C, ERI and WFC on the risk of major depression in the working population.MethodsLongitudinal data (2008-2013) were collected on randomly selected participants (n=4200) from the working population of the province of Alberta, Canada, at baseline and 1-, 2-, 3- and 4-year follow-up. Data about JD-C, ERI, WFC and major depression were collected by trained interviewers using a computer-assisted telephone interviewing method. Generalised estimating equations for longitudinal modelling were used.ResultsThere was an independent association between high ERI and high WFC at tx and major depression at tx+1 (OR 1.56, 95% CI 1.25 to 1.96; OR 1.33, 95% CI 1.16 to 1.52), respectively. The combined effects of JD-C and ERI, ERI and WFC, and WFC and JD-C on the risk of major depression were as follows: OR 1.71, 95% CI 1.22 to 2.42, OR 2.47, 95% CI 1.99 to 3.49 and OR 2.21, 95% CI 1.48 to 3.30, respectively. The relative excess risks attributable to the interactions were statistically non-significant.ConclusionsWork-related psychosocial factors are associated with increased risk of major depression over time, but their combined effect is not synergistic. The effects of the factors depicted in the three occupational health models on the risk of major depression appear to be additive.
Migration and work in postwar Australia: mortality profile comparisons between Australian and Italian workers exposed to blue asbestos at Wittenoom
Authors: Reid Alison , Merler Enzo , Peters Susan , Jayasinghe Nimashi , Bressan Vittoria , Franklin Peter , Brims Fraser , de Klerk Nicholas H , Musk Arthur W 
Published: July 2017

ObjectivesThree hundred and thirty thousand Italians arrived in Australia between 1945 and 1966, many on assisted passage schemes where the worker agreed to a 2-year unskilled employment contract. Italians were the largest of 52 migrant groups employed at the Wittenoom blue asbestos mining and milling operation. We compare mortality from asbestos-related diseases among Italian and Australian workers employed at Wittenoom.MethodsA cohort of 6500 male workers was established from employment records and followed up at state and national mortality and cancer registries. SMRs were calculated to compare mortality with the Western Australian male population. Time-varying Cox proportional hazards models compared the risk of mesothelioma between Australian and Italian workers.Results1031 Italians and 3465 Australians worked at Wittenoom between 1943 and 1966. Duration of employment was longer for the Italian workers, although the concentration of exposure was similar. The mesothelioma mortality rate per 100 000 was higher in Italians (184, 95% CI 148 to 229) than Australians (128, 95% CI 111 to 149). The risk of mesothelioma was greater than twofold (HR 2.27, 95% CI 1.43 to 3.60) in Italians at the lowest asbestos exposure category (<10 fibre years/per mL).ConclusionsA hierarchy in migration, isolation and a shortage of workers led to Italians at Wittenoom incurring higher cumulative exposure to blue asbestos and subsequently a greater rate of malignant mesothelioma than Australian workers.ImpactPoor working conditions and disparities between native and foreign-born workers has had a detrimental and differential impact on the long-term health of the workforce.
Gated metabolic myocardial imaging, a surrogate for dual perfusion-metabolism imaging by positron emission tomography
Authors: AlMohammad Abdallah , Norton Murdoch Y , Welch Andrew E , Sharp Peter F , Walton Stephen 
Published: July 2017

ObjectivePerfusion-metabolism mismatch pattern on positron emission tomography (PET) predicts hibernating myocardium. We assess the ECG-gated metabolic PET as a surrogate for the perfusion-metabolism mismatch pattern on PET imaging.Methods13N-Ammonia (NH3) and18F-fluorodeoxyglucose (FDG) are respectively perfusion and metabolism PET tracers. We used ECG gating to acquire FDG-PET to collect wall thickening (mechanical) data. These allow detection of metabolic activity in regions with reduced contraction (metabolism-mechanical mismatch pattern). We had two data sets on each patient: perfusion-metabolism and metabolism-mechanical data sets. We tested the hypothesis that metabolism-mechanical pattern on PET could predict perfusion-metabolism mismatch pattern.ResultsWe studied 55 patients (48 males), mean age 62 years. All were in sinus rhythm, and had impaired left ventricular contraction. Perfusion-metabolism mismatch pattern was found in 26 patients. Metabolism-mechanical mismatch pattern was found in 25 patients. The results were concordant in 52 patients (95%). As a surrogate for perfusion-metabolism mismatch pattern, demonstration of metabolism-mechanical mismatch pattern is highly sensitive (92%) and specific (97%). In this cohort, the positive and negative predictive accuracy of the new method are 96% and 93%, respectively.ConclusionMetabolism-mechanical mismatch pattern could predict perfusion-metabolism mismatch pattern in patients with myocardial viability criteria on PET. Prospective validation against the gold standard of improved myocardial contraction after revascularisation is needed.
The recognition and management of sepsis and septic shock: a guide for non-intensivists
Authors: Keeley Alexander , Hine Paul , Nsutebu Emmanuel 
Published: July 2017

ABSTRACTSepsis is common, often fatal and requires rapid interventions to improve outcomes. While the optimal management of sepsis in the intensive care setting is the focus of extensive research interest, the mainstay of the recognition and initial management of sepsis will occur outside the intensive care setting. Therefore, it is key that institutions and clinicians remain well informed of the current updates in sepsis management and continue to use them to deliver appropriate and timely interventions to enhance patient survival. This review discusses the latest updates in sepsis care including the new consensus definition of sepsis, the outcome of the proCESS, ProMISe and ARISE trials of early goal directed therapy (EGDT), and the most recent guidelines from the Surviving Sepsis Campaign.
Surgical shunts compared with endoscopic sclerotherapy for the treatment of variceal bleeding in adults with portal hypertension: a systematic review and meta-analysis
Authors: Tian Lu , He Yunjun , Li Donglin , Zhang Hongkun 
Published: July 2017

AbstractAimPortal hypertension is a common complication of chronic liver disease and can cause variceal bleeding which is associated with high mortality. Choices for the treatment of variceal bleeding include surgical shunts and endoscopic sclerotherapy. The aim of this study was to compare the efficacy of surgical shunts and endoscopic sclerotherapy in treating variceal bleeding due to portal hypertension.DesignSystematic review and meta-analysis.SettingMedline, PubMed, Cochrane and Google Scholar databases were searched until 12 February 2015, for relevant randomised control trials. Twenty studies with a total of 1540 participants were included.PatientsPatients with variceal bleeding due to portal hypertension.InterventionsSurgical shunts compared to endoscopic sclerotherapy.Main outcome measuresRates of rebleeding, survival and hepatoencephalopathy, and length of hospital stay.ResultsPooled data for 17 studies showed that the rate of rebleeding was significantly more frequent with sclerotherapy compared with surgical shunt therapy (OR 3.99, 95% CI 2.98 to 5.33, p&lt;0.001). The sclerotherapy patient group compared with the shunt group was less likely to develop hepatoencephalopathy (15 studies: pooled OR 0.53, 95% CI 0.31 to 0.91, p=0.021) and had shorter hospital stays (pooled mean difference−4.32, 95% CI− 7.97 to −0.66, p=0.021). No significant difference in the survival rate was observed between the two groups (seven studies: OR 1.01, 95% CI 0.63 to 1.62, p=0.964).ConclusionThis analysis indicated that the two types of treatment have similar mortality rates but differed with respect to rebleeding rate, incidence of hepatoencephalopathy and length of hospital stay.
Systematic review and meta-analysis: tools for the information age
Authors: Weatherall Mark 
Published: July 2017

ABSTRACTThe amount of available biomedical information is vast and growing. Natural limitations of the way clinicians and researchers approach this treasure trove of information comprise difficulties locating the information, and once located, cognitive biases may lead to inappropriate use of the information. Systematic reviews and meta-analyses represent important tools in the information age to improve knowledge and action. Systematic reviews represent a census approach to identifying literature to avoid non-response bias. They are a necessary prelude to producing combined quantitative summaries of associations or treatment effects. Meta-analysis comprises the arithmetical techniques for producing combined summaries from individual study reports. Careful, thoughtful and rigorous use of these tools is likely to enhance knowledge and action. Use of standard guidelines, such as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, or embedding these activities within collaborative groups such as the Cochrane Collaboration, are likely to lead to more useful systematic review and meta-analysis reporting.
Female and younger subjects have lower adherence in PrEP trials: a meta-analysis with implications for the uptake of PrEP service to prevent HIV
Authors: Yun Ke , Xu Jun-jie , Zhang Jing , Li Jia-ming , Hu Qing-hai , Chu Zhen-xing , Jiang Yong-jun , Geng Wen-qing , Shang Hong , Wang Ning 
Published: July 2017

ObjectiveTo estimate the medicine-taking compliance (MTC) level, explore its facilitators and barriers, and quantify the association between MTC level and pre-exposure prophylaxis (PrEP) protective efficacy in individuals at risk of acquiring HIV being administered oral PrEP.DesignMeta-analysis.Data sourcesWe searched PubMed, Cochrane and Embase databases for published randomized controlled trials (RCTs) pertaining to MTC of oral PrEP for HIV prevention up to 16 January 2017.Review methodsThe pooled proportion of MTC and risk ratio (RR) of HIV incidences between intervention group and control group were estimated.ResultsWe identified 10 eligible studies with 24 193 participants. The overall pooled MTC for oral HIV PrEP was 59.9% (95% CI 43.1% to 74.6%). Subgroup analyses revealed that the MTC level of participants aged <30 years was lower than those equal or older than 30 years (34.9% vs 69.6%, p<0.001); those studies that enrolled only women as participants had lower MTC than those only recruiting either only men or both men and women (31.3% vs 71.7% and 31.3% vs 71.0%, all p<0.01). Additionally, the HIV infection risk increased as the MTC level declines, with the incidence RRs being 0.28 (95% CI 0.19 to 0.41), 0.42 (95% CI 0.29 to 0.62) and 0.75 (95% CI 0.45 to 1.25) in the good (≥80%), moderate (60%~80%) and poor (<60%) MTC subgroups, respectively (linear trend test p<0.01).ConclusionAccording to the pooled proportion, the MTC of oral HIV PrEP is almost moderate, and its proportion in women and younger participants was relatively low. The protective efficacy of oral PrEP for HIV prevention increased with MTC level. These findings indicated that it is necessary to identify measures to enhance MTC of oral PrEP in future clinical usage, especially in women and younger participants with high HIV infection risk.
Comparison of a structured home-based rehabilitation programme with conventional supervised pulmonary rehabilitation: a randomised non-inferiority trial
Authors: Horton Elizabeth J , Mitchell Katy E , Johnson-Warrington Vicki , Apps Lindsay D , Sewell Louise , Morgan Mike , Taylor Rod S , Singh Sally J 
Published: July 2017

BackgroundStandardised home-based pulmonary rehabilitation (PR) programmes offer an alternative model to centre-based supervised PR for which uptake is currently poor. We determined if a structured home-based unsupervised PR programme was non-inferior to supervised centre-based PR for participants with COPD.MethodsA total of 287 participants with COPD who were referred to PR (187 male, mean (SD) age 68 (8.86) years, FEV1% predicted 48.34 (17.92)) were recruited. They were randomised to either centre-based PR or a structured unsupervised home-based PR programme including a hospital visit with a healthcare professional trained in motivational interviewing, a self-management manual and two telephone calls. Fifty-eight (20%) withdrew from the centre-based group and 51 (18%) from the home group. The primary outcome was dyspnoea domain in the chronic respiratory disease questionnaire (Chronic Respiratory Questionnaire Self-Report; CRQ-SR) at 7 weeks. Measures were taken blinded. We undertook a modified intention-to-treat (mITT) complete case analysis, comparing groups according to original random allocation and with complete data at follow-up. The non-inferiority margin was 0.5 units.ResultsThere was evidence of significant gains in CRQ-dyspnoea at 7 weeks in both home and centre-based groups. There was inconclusive evidence that home-based PR was non-inferior to PR in dyspnoea (mean group difference, mITT: −0.24, 95% CI −0.61 to 0.12, p=0.18), favouring the centre group at 7 weeks.ConclusionsThe standardised home-based programme provides benefits in dyspnoea. Further evidence is needed to definitively determine if the health benefits of the standardised home-based programme are non-inferior or equivalent to supervised centre-based rehabilitation.Trial registration numberISRCTN81189044.