bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nodding syndrome in Kitgum District, Uganda: association with conflict and internal displacement
Authors: Landis Jesa L , Palmer Valerie S , Spencer Peter S 
Published: November 2014

ObjectivesTo test for any temporal association of Nodding syndrome with wartime conflict, casualties and household displacement in Kitgum District, northern Uganda.MethodsData were obtained from publicly available information reported by the Ugandan Ministry of Health (MOH), the Armed Conflict Location & Event Data (ACLED) Project of the University of Sussex in the UK, peer-reviewed publications in professional journals and other sources.ResultsReports of Nodding syndrome began to appear in 1997, with the first recorded cases in Kitgum District in 1998. Cases rapidly increased annually beginning in 2001, with peaks in 2003–2005 and 2008, 5–6 years after peaks in the number of wartime conflicts and deaths. Additionally, peaks of Nodding syndrome cases followed peak influxes 5–7 years earlier of households into internal displacement camps.ConclusionsPeaks of Nodding syndrome reported by the MOH are associated with, but temporally displaced from, peaks of wartime conflicts, deaths and household internment, where infectious disease was rampant and food insecurity rife.
Seeking the source ofPseudomonas aeruginosainfections in a recently opened hospital: an observational study using whole-genome sequencing
Authors: Quick Joshua , Cumley Nicola , Wearn Christopher M , Niebel Marc , Constantinidou Chrystala , Thomas Chris M , Pallen Mark J , Moiemen Naiem S , Bamford Amy , Oppenheim Beryl , Loman Nicholas J 
Published: November 2014

ObjectivesPseudomonas aeruginosais a common nosocomial pathogen responsible for significant morbidity and mortality internationally. Patients may become colonised or infected withP. aeruginosaafter exposure to contaminated sources within the hospital environment. The aim of this study was to determine whether whole-genome sequencing (WGS) can be used to determine the source in a cohort of burns patients at high risk ofP. aeruginosaacquisition.Study designAn observational prospective cohort study.SettingBurns care ward and critical care ward in the UK.ParticipantsPatients with >7% total burns by surface area were recruited into the study.MethodsAll patients were screened forP. aeruginosaon admission and samples taken from their immediate environment, including water. Screening patients who subsequently developed a positiveP. aeruginosamicrobiology result were subject to enhanced environmental surveillance. All isolates ofP. aeruginosawere genome sequenced. Sequence analysis looked at similarity and relatedness between isolates.ResultsWGS for 141P. aeruginosaisolates were obtained from patients, hospital water and the ward environment. Phylogenetic analysis revealed eight distinct clades, with a single clade representing the majority of environmental isolates in the burns unit. Isolates from three patients had identical genotypes compared with water isolates from the same room. There was clear clustering of water isolates by room and outlet, allowing the source of acquisitions to be unambiguously identified. Whole-genome shotgun sequencing of biofilm DNA extracted from a thermostatic mixer valve revealed this was the source of aP. aeruginosasubpopulation previously detected in water. In the remaining two cases there was no clear link to the hospital environment.ConclusionsThis study reveals that WGS can be used for source tracking ofP. aeruginosain a hospital setting, and that acquisitions can be traced to a specific source within a hospital ward.
Estimating the incidence, prevalence and true cost of asthma in the UK: secondary analysis of national stand-alone and linked databases in England, Northern Ireland, Scotland and Wales—a study protocol
Authors: Mukherjee Mome , Gupta Ramyani , Farr Angela , Heaven Martin , Stoddart Andrew , Nwaru Bright I , Fitzsimmons Deborah , Chamberlain George , Bandyopadhyay Amrita , Fischbacher Colin , Dibben Christopher , Shields Michael , Phillips Ceri , Strachan David , Davies Gwyneth , McKinstry Brian , Sheikh Aziz 
Published: November 2014

IntroductionAsthma is now one of the most common long-term conditions in the UK. It is therefore important to develop a comprehensive appreciation of the healthcare and societal costs in order to inform decisions on care provision and planning. We plan to build on our earlier estimates of national prevalence and costs from asthma by filling the data gaps previously identified in relation to healthcare and broadening the field of enquiry to include societal costs. This work will provide the first UK-wide estimates of the costs of asthma. In the context of asthma for the UK and its member countries (ie, England, Northern Ireland, Scotland and Wales), we seek to: (1) produce a detailed overview of estimates of incidence, prevalence and healthcare utilisation; (2) estimate health and societal costs; (3) identify any remaining information gaps and explore the feasibility of filling these and (4) provide insights into future research that has the potential to inform changes in policy leading to the provision of more cost-effective care.Methods and analysisSecondary analyses of data from national health surveys, primary care, prescribing, emergency care, hospital, mortality and administrative data sources will be undertaken to estimate prevalence, healthcare utilisation and outcomes from asthma. Data linkages and economic modelling will be undertaken in an attempt to populate data gaps and estimate costs. Separate prevalence and cost estimates will be calculated for each of the UK-member countries and these will then be aggregated to generate UK-wide estimates.Ethics and disseminationApprovals have been obtained from the NHS Scotland Information Services Division's Privacy Advisory Committee, the Secure Anonymised Information Linkage Collaboration Review System, the NHS South-East Scotland Research Ethics Service and The University of Edinburgh's Centre for Population Health Sciences Research Ethics Committee. We will produce a report for Asthma-UK, submit papers to peer-reviewed journals and construct an interactive map.
Intravenous fluid prescribing: Improving prescribing practices and documentation in line with NICE CG174 guidance
Authors: Sansom Luke Thomas , Duggleby Luke 
Published: November 2014

AbstractIntravenous (IV) fluid prescribing is a common occurrence in inpatient settings; it has been repeatedly demonstrated that high levels of mortality and morbidity are associated with inappropriate IV fluid prescribing. IV fluid prescriptions are often completed by the most junior and inexperienced members of the clinical team. In recognition of the issues surrounding IV fluid prescribing and in an effort to combat the issues surrounding current practice, the National Institute for Health and Care Excellence (NICE) published guidance in December 2013 - 'Intravenous fluid therapy in adults in hospital (CG174)'. At our hospital the approach to IV fluid prescribing amongst junior doctors was highly variable with poor awareness of the NICE guidance.We defined necessary components for the documentation of IV fluid prescriptions based upon the NICE guidance. Our initial data showed that these components were infrequently documented, with prescriptions often having no indication for IV fluid, no 24 hour plan / review, no documentation of patient weight or request for further weights, and no current or requested fluid balance charts.Lanyard cards emphasising the necessary components of an appropriate IV fluid prescription along with a copy of the NICE fluid prescribing algorithm were distributed to junior doctors on the acute admissions units. Following the introduction of the lanyard cards there was a significant increase in the documentation of the defined prescription components. Significant increases in the documentation of indication for IV fluid and patient weight, which are essential components of accurate fluid prescription, were demonstrated on both medical and surgical admissions units. Subsequently, as a result of improved documentation and consideration given to fluid prescriptions, we were able to increase the percentage of maintenance IV fluid prescriptions that conformed to NICE guidelines.As an endpoint to this intervention all new Foundation Year 1 doctors at our hospital were issued with IV fluid prescribing lanyard cards at Trust induction; the authors believe that this intervention will lead to a unified approach and a sustained improvement in IV fluid prescribing practices and prescription documentation at this hospital site.
Ward round documentation in a major trauma centre: can we improve patient safety?
Authors: Green Gemma , Aframian Arash , bernard jason 
Published: November 2014

AbstractOur objective was to improve documentation and patient safety in a major trauma centre.A retrospective audit was undertaken in March 2014. Ward round entries for each orthopaedic patients on three dates were assessed against standards and analysed. The audit was repeated in April 2014, and again in August 2014.Thorough documentation is paramount in a major trauma centre. It forms a useful record of the patients hospital stay, is a legal document and is highlighted in national guidelines. It provides a basis for good handover, ensuring continuation of care and maintaining patient safety. Resultant poor compliance with Royal College guidelines in the initial audit led to the production of a new electronic based note keeping system. A meeting was held with all staff prior to introduction.Our initial results gained 75 entries, and none showed full compliance. Mean compliance per entry was 59% (0-81%). The second attempt gained 90 entries, with 30 from the weekend. Mean compliance per entry 97%. Third attempt received 61 entries, with 27 from the weekend. Mean compliance was 96%, meaning that the improvement was being maintained.Recent distressing reports regarding patient highlighted the importance of patient. Our initial audit proved there were many areas lacking in our documentation and improvement was necessary. Prior to introducing electronic systems, the implemented change has produced improvement in documentation, and provides a useful handover tool for staff.
The Mersey Burns App: evolving a model of validation
Authors: Barnes Jamie , Duffy Annie , Hamnett Nathan , McPhail Jane , Seaton Chris , Shokrollahi Kayvan , James M Ian , McArthur Paul , Pritchard Jones Rowan 
Published: November 2014

Introduction‘Mersey Burns App’ is a smartphone/tablet application that aids in the assessment of total burn surface area (TBSA) and calculation of fluid resuscitation protocols in burns. This paper presents two studies assessing the speed and accuracy of calculations using Mersey Burns (App) in comparison with a Lund and Browder chart (paper) when a burn is assessed by medical students and clinicians.MethodsThe first study compared the speed and accuracy of TBSA and resuscitation calculation for a photograph of a burn with App and paper using burns and plastics and emergency medicine trainees and consultants. Developing on some of the feedback and results of that study, a second study was then carried out using burns-naive medical students assessing a fully simulated burn with both modalities. Preference and ease of use of each modality were assessed anonymously.ResultsThe clinician study showed a lower variance in TBSA and fluid calculations using the App (p<0.05). The student study showed no difference in mean TBSA estimations (p=0.7). Mean time to completion of calculations was faster and calculations were more likely to be correct with the App (p<0.001). Students favoured the App in the following categories: preference in emergency setting, confidence in output, accuracy, speed, ease of calculation, overall use and shading (p<0.0001).ConclusionsMersey Burns App can facilitate quicker and more accurate calculations than Lund and Browder charts. Students also preferred the App. This suggests a useful role for the App in the care of patients with burns by inexperienced staff.
First population-level effectiveness evaluation of a national programme to prevent HIV transmission from mother to child, South Africa
Authors: Goga Ameena E , Dinh Thu-Ha , Jackson Debra J , Lombard Carl , Delaney Kevin P , Puren Adrian , Sherman Gayle , Woldesenbet Selamawit , Ramokolo Vundli , Crowley Siobhan , Doherty Tanya , Chopra Mickey , Shaffer Nathan , Pillay Yogan 
Published: November 2014

BackgroundThere is a paucity of data on the national population-level effectiveness of preventing mother-to-child transmission (PMTCT) programmes in high-HIV-prevalence, resource-limited settings. We assessed national PMTCT impact in South Africa (SA), 2010.MethodsA facility-based survey was conducted using a stratified multistage, cluster sampling design. A nationally representative sample of 10 178 infants aged 4–8 weeks was recruited from 565 clinics. Data collection included caregiver interviews, record reviews and infant dried blood spots to identify HIV-exposed infants (HEI) and HIV-infected infants. During analysis, self-reported antiretroviral (ARV) use was categorised: 1a: triple ARV treatment; 1b: azidothymidine >10 weeks; 2a: azidothymidine ≤10 weeks; 2b: incomplete ARV prophylaxis; 3a: no antenatal ARV and 3b: missing ARV information. Findings were adjusted for non-response, survey design and weighted for live-birth distributions.ResultsNationally, 32% of live infants were HEI; early mother-to-child transmission (MTCT) was 3.5% (95% CI 2.9% to 4.1%). In total 29.4% HEI were born to mothers on triple ARV treatment (category 1a) 55.6% on prophylaxis (1b, 2a, 2b), 9.5% received no antenatal ARV (3a) and 5.5% had missing ARV information (3b). Controlling for other factors groups, 1b and 2a had similar MTCT to 1a (Ref; adjusted OR (AOR) for 1b, 0.98, 0.52 to 1.83; and 2a, 1.31, 0.69 to 2.48). MTCT was higher in group 2b (AOR 3.68, 1.69 to 7.97). Within group 3a, early MTCT was highest among breastfeeding mothers 11.50% (4.67% to 18.33%) for exclusive breast feeding, 11.90% (7.45% to 16.35%) for mixed breast feeding, and 3.45% (0.53% to 6.35%) for no breast feeding). Antiretroviral therapy or >10 weeks prophylaxis negated this difference (MTCT 3.94%, 1.98% to 5.90%; 2.07%, 0.55% to 3.60% and 2.11%, 1.28% to 2.95%, respectively).ConclusionsSA, a high-HIV-prevalence middle income country achieved <5% MTCT by 4–8 weeks post partum. The long-term impact on PMTCT on HIV-free survival needs urgent assessment.
Genetic Evidence of a Precisely Tuned Dysregulation in the Hypoxia Signaling Pathway during Oncogenesis
Authors: Couvé Sophie , Ladroue Charline , Laine Elodie , Mahtouk Karène , Guégan Justine , Gad Sophie , Le Jeune Hélène , Le Gentil Marion , Nuel Gregory , Kim William Y. , Lecomte Bernard , Pagès Jean-Christophe , Collin Christine , Lasne Françoise , Benusiglio Patrick R. , Bressac-de Paillerets Brigitte , Feunteun Jean , Lazar Vladimir , Gimenez-Roqueplo Anne-Paule , Mazure Nathalie M. , Dessen Philippe , Tchertanov Luba , Mole David R. , Kaelin William , Ratcliffe Peter , Richard Stéphane , Gardie Betty 
Published: November 2014

Abstract
The classic model of tumor suppression implies that malignant transformation requires full “two-hit” inactivation of a tumor-suppressor gene. However, more recent work in mice has led to the proposal of a “continuum” model that involves more fluid concepts such as gene dosage-sensitivity and tissue specificity. Mutations in the tumor-suppressor gene von Hippel-Lindau (VHL) are associated with a complex spectrum of conditions. Homozygotes or compound heterozygotes for the R200W germline mutation in VHL have Chuvash polycythemia, whereas heterozygous carriers are free of disease. Individuals with classic, heterozygous VHL mutations have VHL disease and are at high risk of multiple tumors (e.g., CNS hemangioblastomas, pheochromocytoma, and renal cell carcinoma). We report here an atypical family bearing two VHL gene mutations in cis (R200W and R161Q), together with phenotypic analysis, structural modeling, functional, and transcriptomic studies of these mutants in comparison with classical mutants involved in the different VHL phenotypes. We demonstrate that the complex pattern of disease manifestations observed in VHL syndrome is perfectly correlated with a gradient of VHL protein (pVHL) dysfunction in hypoxia signaling pathways. Thus, by studying naturally occurring familial mutations, our work validates in humans the “continuum” model of tumor suppression. Cancer Res; 74(22); 6554–64. ©2014 AACR.
A Genome-wide View of Microsatellite Instability: Old Stories of Cancer Mutations Revisited with New Sequencing Technologies
Authors: Kim Tae-Min , Park Peter J. 
Published: November 2014

Abstract
Microsatellites are simple tandem repeats that are present at millions of loci in the human genome. Microsatellite instability (MSI) refers to DNA slippage events on microsatellites that occur frequently in cancer genomes when there is a defect in the DNA-mismatch repair system. These somatic mutations can result in inactivation of tumor-suppressor genes or disrupt other noncoding regulatory sequences, thereby playing a role in carcinogenesis. Here, we will discuss the ways in which high-throughput sequencing data can facilitate genome- or exome-wide discovery and more detailed investigation of MSI events in microsatellite-unstable cancer genomes. We will address the methodologic aspects of this approach and highlight insights from recent analyses of colorectal and endometrial cancer genomes from The Cancer Genome Atlas project. These include identification of novel MSI targets within and across tumor types and the relationship between the likelihood of MSI events to chromatin structure. Given the increasing popularity of exome and genome sequencing of cancer genomes, a comprehensive characterization of MSI may serve as a valuable marker of cancer evolution and aid in a search for therapeutic targets. Cancer Res; 74(22); 6377–82. ©2014 AACR.
Chimeric Antigen Receptor T-cell Therapy to Target Hematologic Malignancies
Authors: Kenderian Saad Sirop , Ruella Marco , Gill Saar , Kalos Michael 
Published: November 2014

Abstract
Several decades of humoral immunotherapy using monoclonal antibodies and cellular immunotherapy using hematopoietic cell transplantation have recently culminated in a successful merger: the development and clinical application of genetically engineered antibody–T cell chimeras. Also known as chimeric antigen receptor T cells (CAR T cells), these entities combine the exquisite antigen specificity of antibodies with the polyfunctionality and potency of cellular immunity and are a prime example of the potential for synthetic biology to treat disease. CAR T cells overcome several of the biologic obstacles that have historically hampered immunotherapy while providing fundamental mechanistic insights into cellular immunology and revealing new challenges in genetic engineering and target selection. Results from early-phase CAR T-cell–based clinical trials demonstrate the significant potential for this approach to affect dramatic and complete clinical responses while revealing novel toxicities associated with activation of potent and specific antitumor immunity. Cancer Res; 74(22); 6383–9. ©2014 AACR.
Association of Prostate Cancer Risk Variants with Gene Expression in Normal and Tumor Tissue
Authors: Penney Kathryn L. , Sinnott Jennifer A. , Tyekucheva Svitlana , Gerke Travis , Shui Irene M. , Kraft Peter , Sesso Howard D. , Freedman Matthew L. , Loda Massimo , Mucci Lorelei A. , Stampfer Meir J. 
Published: November 2014

Abstract
Background: Numerous germline genetic variants are associated with prostate cancer risk, but their biologic role is not well understood. One possibility is that these variants influence gene expression in prostate tissue. We therefore examined the association of prostate cancer risk variants with the expression of genes nearby and genome-wide.
Methods: We generated mRNA expression data for 20,254 genes with the Affymetrix GeneChip Human Gene 1.0 ST microarray from normal prostate (N = 160) and prostate tumor (N = 264) tissue from participants of the Physicians' Health Study and Health Professionals Follow-up Study. With linear models, we tested the association of 39 risk variants with nearby genes and all genes, and the association of each variant with canonical pathways using a global test.
Results: In addition to confirming previously reported associations, we detected several new significant (P &lt; 0.05) associations of variants with the expression of nearby genes including C2orf43, ITGA6, MLPH, CHMP2B, BMPR1B, and MTL5. Genome-wide, five genes (MSMB, NUDT11, RBPMS2, NEFM, and KLHL33) were significantly associated after accounting for multiple comparisons for each SNP (P &lt; 2.5 × 10−6). Many more genes had an FDR &lt;10%, including SRD5A1 and PSCA, and we observed significant associations with pathways in tumor tissue.
Conclusions: The risk variants were associated with several genes, including promising prostate cancer candidates and lipid metabolism pathways, suggesting mechanisms for their impact on disease. These genes should be further explored in biologic and epidemiologic studies.
Impact: Determining the biologic role of these variants can lead to improved understanding of prostate cancer etiology and identify new targets for chemoprevention. Cancer Epidemiol Biomarkers Prev; 24(1); 255–60. ©2014 AACR.
Temporal Stability and Determinants of White Blood Cell DNA Methylation in the Breakthrough Generations Study
Authors: Flanagan James M. , Brook Mark N. , Orr Nick , Tomczyk Katarzyna , Coulson Penny , Fletcher Olivia , Jones Michael E. , Schoemaker Minouk J. , Ashworth Alan , Swerdlow Anthony , Brown Robert , Garcia-Closas Montserrat 
Published: November 2014

Abstract
Background: Epigenome-wide association studies (EWAS) using measurements of blood DNA methylation are performed to identify associations of methylation changes with environmental and lifestyle exposures and disease risk. However, little is known about the variation of methylation markers in the population and their stability over time, both important factors in the design and interpretation of EWAS. We aimed to identify stable variable methylated probes (VMP), i.e., markers that are variable in the population, yet stable over time.
Methods: We estimated the intraclass correlation coefficient (ICC) for each probe on the Illumina 450K methylation array in paired samples collected approximately 6 years apart from 92 participants in the Breakthrough Generations Study. We also evaluated relationships with age, reproductive and hormonal history, weight, alcohol intake, and smoking.
Results: Approximately 17% of probes had an ICC &gt; 0.50 and were considered stable VMPs (stable-VMPs). Stable-VMPs were enriched for probes located in “shores” bordering CpG islands, and at approximately 1.3 kb downstream from the transcription start site in the transition between the unmethylated promoter and methylated gene body. Both cross-sectional and longitudinal data analyses provided strong evidence for associations between changes in methylation levels and aging. Smoking-related probes at 2q37.1 and AHRR were stable-VMPs and related to time since quitting. We also observed associations between methylation and weight changes.
Conclusion: Our results provide support for the use of white blood cell DNA methylation as a biomarker of exposure in EWAS.
Impact: Larger studies, preferably with repeated measures over time, will be required to establish associations between specific probes and exposures. Cancer Epidemiol Biomarkers Prev; 24(1); 221–9. ©2014 AACR.