bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilising Family‐Based Designs for Detecting Rare Variant Disease Associations
Authors: Preston Mark D. , Dudbridge Frank 
Published: February 2014

SummaryRare genetic variants are thought to be important components in the causality of many diseases but discovering these associations is challenging. We demonstrate how best to use family‐based designs to improve the power to detect rare variant disease associations. We show that using genetic data from enriched families (those pedigrees with greater than one affected member) increases the power and sensitivity of existing case–control rare variant tests. However, we show that transmission‐ (or within‐family‐) based tests do not benefit from this enrichment. This means that, in studies where a limited amount of genotyping is available, choosing a single case from each of many pedigrees has greater power than selecting multiple cases from fewer pedigrees. Finally, we show how a pseudo‐case–control design allows a greater range of statistical tests to be applied to family data.
CMV Infection, TLR‐2 and ‐4 Expression, and Cytokine Profiles in Early‐Onset Preeclampsia with HELLP Syndrome
Authors: Xie Fang , von Dadelszen Peter , Nadeau Joseph 
Published: February 2014

ProblemCytomegalovirus (CMV) infection was previously reported in pregnancy complications. However, its seroprevalence and associated Toll‐like receptor (TLR) expression in early‐onset preeclampsia (EOPE) with hemolysis, elevated liver enzyme and low platelets syndrome (HELLPs) are unexplored.Method of studyA case–control study was performed to examine maternal CMV antibodies, neutrophil Toll‐like receptor (TLR)‐2 and ‐4 expression as well as the cytokine profile in EOPE with HELLPs (EOPE‐HELLPs) (n = 10), late‐onset preeclampsia (LOPE) (n = 20), normal pregnancy (n = 60), and non‐pregnancy (n = 20) controls.ResultsEOPE‐HELLPs had significantly increased CMV IgG sero‐positivity, upregulated TLR‐2/‐4 mRNA expression, increased serum IL‐6 and TNF‐α, and reduced IL‐10 compared with matched normal and non‐pregnancy controls. No significant difference was observed between LOPE and normal pregnancy controls.ConclusionWe observed a significant association between CMV IgG sero‐positivity and innate immune response in EOPE‐HELLPs. Our data suggest that CMV infection may be a risk factor for this disorder.
Why Indians Vote: Reflections on Rights, Citizenship, and Democracy from a Tamil Nadu Village
Authors: Carswell Grace , De Neve Geert 
Published: February 2014

AbstractThis paper contributes to an empirical and theoretical understanding of democracy and political participation in India through an ethnographic study of the meanings attached to voting in rural Tamil Nadu. Based on a study of voting in a rural constituency during the 2009 national elections, the paper explores the variety of motivations that compel people to vote. It explores how voting is informed by popular understandings of rights and duties as citizens, programmatic policies and their local implementation, commitment to caste and party loyalties, and authority of charismatic leaders. The paper explores the roots of the political consciousness and rights awareness that underpin high levels of electoral participation. It suggests that elections form unique moments that allow ordinary people to experience an individual sense of citizenship and of democracy itself while at the same time allowing them to pursue projects of recognition, respect and assertion as members of communities. It is precisely this dual feature that makes voting so enduringly attractive to India's contemporary electorate.
Primitive Accumulation and the Production of Abstract Space: Nineteenth‐century Mire Reclamation on Gotland
Authors: Mels Tom 
Published: February 2014

AbstractIn Henri Lefebvre's work, abstract space entails qualitatively new ways of envisioning and strategically arranging the sites within which capital accumulation and everyday life are to unfold. This paper sets out to delineate how this premise can be profitably used to decipher contested tactics of primitive accumulation. Arguing from a particular case—nineteenth‐century reclamation of mires on the island of Gotland, Sweden—the paper explores how primitive accumulation was made possible through the conjunction of three spatialities, representing three key lines of struggle over abstract space. The abstraction and avowed homogeneity of space was produced and regulated by concurrent ideological maneuvers against customary practice, leveled by scientific discourse, and pursued through a legally endorsed material transformation of nature.
Efficacy of Prophylactic Intra‐Aortic Balloon Pump Therapy in Chronic Heart Failure Patients Undergoing Cardiac Surgery
Authors: Yildirim Yalin , Pecha Simon , Kubik Mathias , Alassar Yousuf , Deuse Tobias , Hakmi Samer , Reichenspurner Hermann 
Published: February 2014

AbstractThis study investigated the efficacy of prophylactic intraoperative intra‐aortic balloon pump (IABP) usage in chronic heart failure patients with severely reduced left ventricular function undergoing elective cardiac surgery. Between January 2008 and December 2012, 107 patients with severely reduced left ventricular ejection fraction (LVEF <35%) received prophylactic intraoperative IABP implantation during open‐heart surgery. Surgical procedures performed were isolated coronary artery bypass grafting (CABG) in 35 patients (32.7%), aortic valve replacement in 12 (11.2%), mitral valve repair or replacement in 15 (14.0%), combined valve and CABG procedures in 27 (25.2%), and other surgical procedures in 18 (16.8%). Results and outcomes were compared with those in a propensity score‐matched cohort of 107 patients who underwent cardiac surgery without intraoperative IABP implantation. Matching criteria were age, gender, LVEF, and surgical procedure. Duration of intensive care unit (ICU) stay, duration of hospital stay, and 30‐day mortality were markers of outcome. In the IABP group, mean patient age was 69.1 ± 13.7 years; 66.4% (70) were male. All IABPs were placed intraoperatively. Mean duration of IABP application time was 42.4 ± 8.7 h. IABP‐related complications occurred in five patients (4.7%), including one case of inguinal bleeding, one case of mesenteric ischemia, and ischemia of the lower limb in three patients. No stroke or major bleeding occurred during IABP support. Mean durations of ICU and hospital stay were 3.38 ± 2.15 days and 7.69 ± 2.02 days, respectively, in the IABP group, and 4.20 ± 3.14 days and 8.57 ± 3.26 days in the control group, showing statistically significant reductions in duration of ICU and hospital stay in the IABP group (ICU stay, P = 0.036; hospital stay, P = 0.015). Thirty‐day survival rates were 92.5 and 94.4% in the IABP and control group, respectively, showing no statistically significant difference (P = 0.75). IABP usage in chronic heart failure patients with severely reduced LVEF undergoing cardiac surgery was safe and resulted in shorter ICU and hospital stay but did not influence 7‐ and 30‐day survival rates.
Sleep fragmentation and increased periodic limb movements are more common in children with nocturnal enuresis
Authors: Dhondt K , Baert E , Van Herzeele C , Raes A , Groen L‐A , Hoebeke P , Vande Walle J 
Published: February 2014

AbstractAimTo determine sleep fragmentation in children with nocturnal enuresis (NE).MethodsPaediatricians assessed NE parameters in children referred to an enuresis clinic. Control subjects, matched by age and gender and without incontinence or (un)treated NE, were recruited from the paediatric sleep clinic regardless of their sleep problem. Sleep was investigated by one overnight video‐polysomnography in both groups.ResultsThe study group comprised 67 children with proven NE (50 boys and 17 girls between six and 16 years: 11.1 ± 2.8 SD). They were matched with 67 control subjects (47 boys and 20 girls aged between six and 16 years: 11.0 ± 2.9 SD). Children with NE had a higher incidence of periodic limb movements associated with cortical arousals in their sleep. They displayed significant higher periodic limb movement index, arousal index and awakening index than the control group.ConclusionChildren with NE displayed higher sleep fragmentation and periodic limb movements in sleep than the control children with a possible sleep disorder without NE. The findings emphasise the central involvement of the pathophysiology of NE and the multifactorial nature of the condition.
Review article: bacteria and pathogenesis of disease in the upper gastrointestinal tract – beyond the era of Helicobacter pylori
Authors: Walker M. M. , Talley N. J. 
Published: February 2014

SummaryBackgroundStudy of the upper gastrointestinal microbiome has shown that other bacteria besides Helicobacter pylori flourish despite the hostile environment. Whilst H. pylori is the most studied bacteria in this region with a defined role in inflammation and neoplasia, it is apparent that other bacteria may contribute to UGI disease.AimTo review current knowledge of bacteria inhabiting the oesophagus, stomach and duodenum.MethodsPublished studies on the upper gastrointestinal microbiome (extracted from PubMed during the last 20 years).ResultsThe stomach is a hostile environment for bacteria; however, recent studies categorising the microbiota have shown surprising results. Helicobacter pylori has been intensively studied since 1984 and recent sequencing analysis of other gastric microbiota shows that H. pylori is not alone. Composition can be influenced by acid suppression, gastritis and abundance of H. pylori. Eradication of H. pylori, whilst decreasing gastric cancer is associated with an increase in asthma, reflux and obesity. A future approach may be to selectively eradicate bacteria which predispose to inflammation and cancer as opposed to a comprehensive knockout policy. In the oesophagus, viridans streptococci are the most common bacteria influenced by both oral and gastric bacteria. Oesophagitis and Barrett's oesophagus are characterised by a significant decrease in Gram‐positive bacteria and an increase in Gram‐negative bacteria. An inverse association of H. pylori and oesophageal adenocarcinoma is described. The duodenal microbiome has been shown to influence small intestinal bacterial overgrowth, irritable bowel syndrome and coeliac disease. The numbers of bacteria recoverable by culture are variable in the stomach mucosa and gastric juice, typically 102–104 colony‐forming units (CFU)/g or mL and in the oesophagus, up to 104 bacteria per mm2 mucosal surface. In the small bowel, in health, 103 CFU/mL are normal.ConclusionThis review highlights current knowledge of upper gastrointestinal bacteria and associations with disease.
Improved prediction of tacrolimus concentrations early after kidney transplantation using theory‐based pharmacokinetic modelling
Authors: Størset Elisabet , Holford Nick , Hennig Stefanie , Bergmann Troels K. , Bergan Stein , Bremer Sara , Åsberg Anders , Midtvedt Karsten , Staatz Christine E. 
Published: February 2014

AimsThe aim was to develop a theory‐based population pharmacokinetic model of tacrolimus in adult kidney transplant recipients and to externally evaluate this model and two previous empirical models.MethodsData were obtained from 242 patients with 3100 tacrolimus whole blood concentrations. External evaluation was performed by examining model predictive performance using Bayesian forecasting.ResultsPharmacokinetic disposition parameters were estimated based on tacrolimus plasma concentrations, predicted from whole blood concentrations, haematocrit and literature values for tacrolimus binding to red blood cells. Disposition parameters were allometrically scaled to fat free mass. Tacrolimus whole blood clearance/bioavailability standardized to haematocrit of 45% and fat free mass of 60 kg was estimated to be 16.1 l h−1 [95% CI 12.6, 18.0 l h−1]. Tacrolimus clearance was 30% higher (95% CI 13, 46%) and bioavailability 18% lower (95% CI 2, 29%) in CYP3A5 expressers compared with non‐expressers. An Emax model described decreasing tacrolimus bioavailability with increasing prednisolone dose. The theory‐based model was superior to the empirical models during external evaluation displaying a median prediction error of −1.2% (95% CI −3.0, 0.1%). Based on simulation, Bayesian forecasting led to 65% (95% CI 62, 68%) of patients achieving a tacrolimus average steady‐state concentration within a suggested acceptable range.ConclusionA theory‐based population pharmacokinetic model was superior to two empirical models for prediction of tacrolimus concentrations and seemed suitable for Bayesian prediction of tacrolimus doses early after kidney transplantation.
Pharmacodynamic Modelling of Placebo and Buprenorphine Effects on Event‐Related Potentials in Experimental Pain
Authors: Juul Rasmus V. , Foster David J.R. , Upton Richard N. , Andresen Trine , Graversen Carina , Drewes Asbjørn M. , Christrup Lona L. , Kreilgaard Mads 
Published: February 2014

AbstractThe purpose of the study was to investigate placebo and buprenorphine effects on event‐related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine in a cross‐over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration‐effect models were fitted to data using non‐linear mixed‐effects modelling implemented in NONMEM (V7.2.0.). Pharmacodynamic models were developed to adequately describe both placebo and buprenorphine ERP data. Models predicted significant placebo effects, but did not predict significant effects related to buprenorphine concentration. Models revealed that ERPs varied both between subjects and between study occasions. ERPs were found to be reproducible within subjects and occasions as population variance was found to be eight times higher than the unexplained variances. Between‐subject variance accounted for more than 75% of the population variance. In conclusion, pharmacodynamic modelling was successfully implemented to allow for placebo and variability correction in ERP of experimental pain. Improved outcome of ERP studies can be expected if variation between subjects and study occasions can be identified and described.
Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance
Authors: San Francisco Ignacio F. , Rojas Pablo A. , DeWolf William C. , Morgentaler Abraham 
Published: February 2014

ObjectiveTo determine whether total testosterone and free testosterone levels predict disease reclassification in a cohort of men with prostate cancer (PCa) on active surveillance (AS).Patients and MethodsTotal testosterone and free testosterone concentrations were determined at the time the men began the AS protocol. Statistical analysis was performed using Student's t‐test and a chi‐squared test to compare groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using univariate logistic regression. Receiver–operator characteristic curves were generated to determine the investigated testosterone thresholds. Kaplan–Meier curves were used to estimate time to disease reclassification. A Cox proportional hazard regression model was used for multivariate analysis.ResultsA total of 154 men were included in the AS cohort, of whom 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone levels than those who were not reclassified (0.75 vs 1.02 ng/dL, P = 0.03). Men with free testosterone levels <0.45 ng/dL had a higher rate of disease reclassification than patients with free testosterone levels ≥0.45 (P = 0.032). Free testosterone levels <0.45 ng/dL were associated with a several‐fold increase in the risk of disease reclassification (OR 4.3, 95% CI 1.25–14.73). Multivariate analysis showed that free testosterone and family history of PCa were independent predictors of disease reclassification.ConclusionsFree testosterone levels were lower in men with PCa who had reclassification during AS. Men with moderately severe reductions in free testosterone level are at increased risk of disease reclassification.
Bladder reconstruction using scaffold‐less autologous smooth muscle cell sheet engineering: early histological outcomes for autoaugmentation cystoplasty
Authors: Talab Saman S. , Kajbafzadeh Abdol‐Mohammad , Elmi Azadeh , Tourchi Ali , Sabetkish Shabnam , Sabetkish Nastaran , Monajemzadeh Maryam 
Published: February 2014

ObjectiveTo investigate the feasibility of a new approach for cystoplasty using autologous smooth muscle cell (SMC) sheet and scaffold‐less bladder tissue engineering with the main focus on histological outcomes in a rabbit model.Materials and MethodsIn all, 24 rabbits were randomly divided into two groups. In the experimental group, SMCs were obtained from the bladder muscular layer, labelled with PKH‐26, and seeded on temperature‐responsive culture dishes. Contiguous cell sheets were noninvasively harvested by reducing the temperature and triple‐layer cell‐dense tissues were constructed. After partial detrusorectomy, the engineered tissue was transplanted onto the urothelial diverticulum. The control group underwent partial detrusorectomy followed by peritoneal fat coverage. At 2, 4, and 12 weeks the rabbits were humanely killed and haematoxylin and eosin, Masson's trichrome, cluster of differentiation 34 (CD34), CD31, CD3, CD68, α‐smooth muscle actin (α‐SMA), picrosirius red, and pentachrome staining were used to evaluate bladder reconstruction.ResultsAt 2 weeks after SMC‐sheet grafting, PKH‐26 labelled SMCs were evident in the muscular layer. At 4 weeks, 79.1% of the cells in the muscular layer were PKH‐positive cells. The portion of the muscular layer increased in the experimental group during the follow‐up and was similar to normal bladder tissue after 12 weeks. α‐SMA staining showed well organised muscle at 4 and 12 weeks. CD34+ endothelial progenitor cells and CD31+ microvessels increased continuously and peaked 4 and 12 weeks after grafting, respectively.ConclusionIn the present study, we show that autologous SMC‐sheet grafting has the potential for reliable bladder reconstruction and is technically feasible with a favourable evolution over the 12 weeks following implantation. Our findings could pave the way toward future bladder tissue engineering using the SMC‐sheet technique.
Venous thromboembolism (VTE) prophylaxis and urological pelvic cancer surgery: a UK national audit
Authors: Pridgeon Simon , Allchorne Paula , Turner Bruce , Peters John , Green James 
Published: February 2014

ObjectivesTo evaluate the use of post‐discharge venous thromboembolism (VTE) prophylaxis in UK pelvic cancer centres consistent with national guidelines.MethodsData was collected from healthcare professionals from 64 UK pelvic cancer centres.ResultsAfter radical cystectomy (RC), all cancer centres routinely use low‐molecular‐weight heparin (LMWH) in the perioperative period. After RC 67% of cancer centres use post‐discharge LMWH routinely. After radical prostatectomy (RP), 98% of units use perioperative LMWH VTE prophylaxis routinely. After RP, 61% of hospitals always use post‐discharge LMWH. In all, 27% of all UK cancer centres reported deaths or serious VTE complications from urological pelvic cancer surgery in the last 2 years.ConclusionsThe National Institute for Health and Care Excellence (NICE) issued explicit guidance of VTE prophylaxis after pelvic and abdominal cancer surgery. Conversion of national guidance into local policy is ≈60% for UK pelvic cancer centres. A lack of good quality evidence is cited as a reason for not adhering to NICE guidance.
Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation
Authors: Hassan Samia , Eldeeb Khalil , Millns Paul J , Bennett Andrew J , Alexander Stephen P H , Kendall David A 
Published: February 2014

Background and PurposeMicroglial cells are important mediators of the immune response in the CNS. The phytocannabinoid, cannabidiol (CBD), has been shown to have central anti‐inflammatory properties, and the purpose of the present study was to investigate the effects of CBD and other phytocannabinoids on microglial phagocytosis.Experimental ApproachPhagocytosis was assessed by measuring ingestion of fluorescently labelled latex beads by cultured microglial cells. Drug effects were probed using single‐cell Ca2+ imaging and expression of mediator proteins by immunoblotting and immunocytochemistry.Key ResultsCBD (10 μM) enhanced bead phagocytosis to 175 ± 7% control. Other phytocannabinoids, synthetic and endogenous cannabinoids were without effect. The enhancement was dependent upon Ca2+ influx and was abolished in the presence of EGTA, the Ca2+ channel inhibitor SKF96365, the transient receptor potential (TRP) channel blocker ruthenium red, and the TRPV1 antagonists capsazepine and AMG9810. CBD produced a sustained increase in intracellular Ca2+ concentration in BV‐2 microglia and this was abolished by ruthenium red. CBD rapidly increased the expression of TRPV2 and TRPV1 proteins and caused a translocation of TRPV2 to the cell membrane. Wortmannin blocked CBD enhancement of BV‐2 cell phagocytosis, suggesting that it is mediated by PI3K signalling downstream of the Ca2+ influx.Conclusions and ImplicationsThe TRPV‐dependent phagocytosis‐enhancing effect of CBD suggests that pharmacological modification of TRPV channel activity could be a rational approach to treating neuroinflammatory disorders involving changes in microglial function and that CBD is a potential starting point for future development of novel therapeutics acting on the TRPV receptor family.
Negotiating belonging following migration: Exploring the relationship between place and identity in Francophone minority communities
Authors: Huot Suzanne , Dodson Belinda , Rudman Debbie Laliberte 
Published: February 2014

AbstractA qualitative study was conducted within the Francophone minority community (FMC) of London, Ontario to explore the integration experiences of French‐speaking immigrants from visible minority groups. We address how shifts to place and identity experienced following international migration influenced the study participants' negotiation of belonging within the host community. The ethnographic approach to research was guided by a theoretical framework drawing on geographical and sociological literature critically attending to power and place. Findings focus upon the negotiation of two key tensions influencing belonging. First we address the tension between Canada's official bilingualism and the Francophone immigrants' lived bilingualism within the local FMC. We then discuss the research participants' everyday experiences of displacement and exclusion as embedded within a context of official multiculturalism. The findings serve to illustrate ways in which belonging is negotiated in relation to the politics of place.