Clustering and Alignment of Polymorphic Sequences for HLA-DRB1 Genotyping

Located on Chromosome 6p21, classical human leukocyte antigen genes are highly polymorphic. HLA alleles associate with a variety of phenotypes, such as narcolepsy, autoimmunity, as well as immunologic response to infectious disease. Moreover, high resolution genotyping of these loci is critical to achieving long-term survival of allogeneic transplants. Development of methods to obtain high resolution analysis of HLA genotypes will lead to improved understanding of how select alleles contribute to human health and disease risk. Genomic DNAs were obtained from a cohort of n = 383 subjects recruited as part of an Ulcerative Colitis study and analyzed for HLA-DRB1. HLA genotypes were determined using sequence specific oligonucleotide probes and by next-generation sequencing using the Roche/454 GSFLX instrument. The Clustering and Alignment of Polymorphic Sequences (CAPSeq) software application was developed to analyze next-generation sequencing data. The application generates HLA sequence specific 6-digit genotype information from next-generation sequencing data using MUMmer to align sequences and the R package diffusionMap to classify sequences into their respective allelic groups. The incorporation of Bootstrap Aggregating, Bagging to aid in sorting of sequences into allele classes resulted in improved genotyping accuracy. Using Bagging iterations equal to 60, the genotyping results obtained using CAPSeq when compared with sequence specific oligonucleotide probe characterized 4-digit genotypes exhibited high rates of concordance, matching at 759 out of 766 (99.1%) alleles. © 2013 Ringquist et al

Patterns of impact resulting from a 'sit less, move more' web-based program in sedentary office employees.

PURPOSE: Encouraging office workers to 'sit less and move more' encompasses two public health priorities. However, there is little evidence on the effectiveness of workplace interventions for reducing sitting, even less about the longer term effects of such interventions and still less on dual-focused interventions. This study assessed the short and mid-term impacts of a workplace web-based intervention (Walk@WorkSpain, W@WS; 2010-11) on self-reported sitting time, step counts and physical risk factors (waist circumference, BMI, blood pressure) for chronic disease. METHODS: Employees at six Spanish university campuses (n=264; 42±10 years; 171 female) were randomly assigned by worksite and campus to an Intervention (used W@WS; n=129; 87 female) or a Comparison group (maintained normal behavior; n=135; 84 female). This phased, 19-week program aimed to decrease occupational sitting time through increased incidental movement and short walks. A linear mixed model assessed changes in outcome measures between the baseline, ramping (8 weeks), maintenance (11 weeks) and follow-up (two months) phases for Intervention versus Comparison groups. RESULTS: A significant 2 (group) × 2 (program phases) interaction was found for self-reported occupational sitting (F[3]=7.97, p=0.046), daily step counts (F[3]=15.68, p=0.0013) and waist circumference (F[3]=11.67, p=0.0086). The Intervention group decreased minutes of daily occupational sitting while also increasing step counts from baseline (446±126; 8,862±2,475) through ramping (+425±120; 9,345±2,435), maintenance (+422±123; 9,638±3,131) and follow-up (+414±129; 9,786±3,205). In the Comparison group, compared to baseline (404±106), sitting time remained unchanged through ramping and maintenance, but decreased at follow-up (-388±120), while step counts diminished across all phases. The Intervention group significantly reduced waist circumference by 2.1cms from baseline to follow-up while the Comparison group reduced waist circumference by 1.3cms over the same period. CONCLUSIONS: W@WS is a feasible and effective evidence-based intervention that can be successfully deployed with sedentary employees to elicit sustained changes on "sitting less and moving more"

Targeted Disruption of the Low-Affinity Leukemia Inhibitory Factor-Receptor Gene Causes Placental, Skeletal, Neural and Metabolic Defects and Results in Perinatal Death

The low-affinity receptor for leukemia inhibitory factor (LIFR)* interacts with gp130 to induce an intracellular signal cascade, The LIFR-gp130 heterodimer is implicated in the function of diverse systems, Normal placentation is disrupted in LIFR mutant animals, which leads to poor intrauterine nutrition but allows fetuses to continue to term. Fetal bone volume is reduced greater than three-fold and the number of osteoclasts is increased six-fold, resulting in severe osteopenia of perinatal bone. Astrocyte numbers are reduced in the spinal cord and brain stem. Late gestation fetal livers contain relatively high stores of glycogen, indicating a metabolic disorder. Hematologic and primordial germ cell compartments appear normal. Pleiotropic defects in the mutant animals preclude survival beyond the day of birth

Library 2.0: the effectiveness of social media as a marketing tool for libraries in educational institutions

In an attempt to market their services and connect with potential users, and particularly young people, many libraries are opening accounts on social media platforms. Research suggests a contradiction between the advice relating to marketing and that regarding the use of social media in libraries, with the former emphasising the importance of the user at the centre of all considerations and the latter placing library staff as central to decisions. In this work we attempt to re-address this imbalance by surveying the current state of library activity on Twitter and, by means of questionnaires, investigate the experiences and motivations of librarians (n=58) in using social media and whether students (n=498) are willing to engage with the library in this manner and why. Our findings confirm that libraries in the sector are indeed struggling to foster interest in their social media activities and go some way to understanding why this is so, leading to a number of conclusions and recommendations for practitioners

The challenges of communicating research evidence in practice: perspectives from UK health visitors and practice nurses

<p>Background: Health practitioners play a pivotal role in providing patients with up-to-date evidence and health information. Evidence-based practice and patient-centred care are transforming the delivery of healthcare in the UK. Health practitioners are increasingly balancing the need to provide evidence-based information against that of facilitating patient choice, which may not always concur with the evidence base. There is limited research exploring how health practitioners working in the UK, and particularly those more autonomous practitioners such as health visitors and practice nurses working in community practice settings, negotiate this challenge. This research provides a descriptive account of how health visitors and practice nurses negotiate the challenges of communicating health information and research evidence in practice.</p> <p>Methods: A total of eighteen in-depth telephone interviews were conducted in the UK between September 2008 and May 2009. The participants comprised nine health visitors and nine practice nurses, recruited via adverts on a nursing website, posters at a practitioner conference and through recommendation. Thematic analysis, with a focus on constant comparative method, was used to analyse the data.</p> <p>Results: The data were grouped into three main themes: communicating evidence to the critically-minded patient; confidence in communicating evidence; and maintaining the integrity of the patient-practitioner relationship. These findings highlight some of the daily challenges that health visitors and practice nurses face with regard to the complex and dynamic nature of evidence and the changing attitudes and expectations of patients. The findings also highlight the tensions that exist between differing philosophies of evidence-based practice and patient-centred care, which can make communicating about evidence a daunting task.</p> <p>Conclusions: If health practitioners are to be effective at communicating research evidence, we suggest that more research and resources need to be focused on contextual factors, such as how research evidence is negotiated, appraised and communicated within the dynamic patient-practitioner relationship.</p&gt

High prevalence of lung cancer in a surgical cohort of lung cancer patients a decade after smoking cessation

<p>Abstract</p> <p>Background</p> <p>This study was designed to assess the prevalence of smoking at time of lung cancer diagnosis in a surgical patient cohort referred for cardiothoracic surgery.</p> <p>Methods</p> <p>Retrospective study of lung cancer patients (n = 626) referred to three cardiothoracic surgeons at a tertiary care medical center in Southern California from January 2006 to December 2008. Relationships among years of smoking cessation, smoking status, and tumor histology were analyzed with Chi-square tests.</p> <p>Results</p> <p>Seventy-seven percent (482) had a smoking history while 11.3% (71) were current smokers. The length of smoking cessation to cancer diagnosis was <1 year for 56 (13.6%), 1-10 years for 110 (26.8%), 11-20 years for 87 (21.2%), 21-30 years for 66 (16.1%), 31-40 years for 44 (10.7%), 41-50 years for 40 (9.7%) and 51-60 years for 8 (1.9%). The mean cessation was 18.1 ± 15.7 years (n = 411 former smokers). Fifty-nine percent had stage 1 disease and 68.0% had adenocarcinoma. Squamous cell carcinoma was more prevalent in smokers (15.6% vs. 8.3%, p = 0.028); adenocarcinoma was more prevalent in never-smokers (79.9% versus 64.3%, p = 0.0004). The prevalence of adenocarcinoma varied inversely with pack year (p < 0.0001) and directly with years of smoking cessation (p = 0.0005).</p> <p>Conclusions</p> <p>In a surgical lung cancer cohort, the majority of patients were smoking abstinent greater than one decade before the diagnosis of lung cancer.</p

A whole system approach to increasing children's physical activity in a multi-ethnic UK city: a process evaluation protocol

Background Engaging in regular physical activity requires continued complex decision-making in varied and dynamic individual, social and structural contexts. Widespread shortfalls of physical activity interventions suggests the complex underlying mechanisms of change are not yet fully understood. More insightful process evaluations are needed to design and implement more effective approaches. This paper describes the protocol for a process evaluation of the JU:MP programme, a whole systems approach to increasing physical activity in children and young people aged 5–14 years in North Bradford, UK. Methods This process evaluation, underpinned by realist philosophy, aims to understand the development and implementation of the JU:MP programme and the mechanisms by which JU:MP influences physical activity in children and young people. It also aims to explore behaviour change across wider policy, strategy and neighbourhood systems. A mixed method data collection approach will include semi-structured interview, observation, documentary analysis, surveys, and participatory evaluation methods including reflections and ripple effect mapping. Discussion This protocol offers an innovative approach on the use of process evaluation feeding into an iterative programme intended to generate evidence-based practice and deliver practice-based evidence. This paper advances knowledge regarding the development of process evaluations for evaluating systems interventions, and emphasises the importance of process evaluation

Correction to: A whole system approach to increasing children's physical activity in a multi-ethnic UK city: a process evaluation protocol

Background Engaging in regular physical activity requires continued complex decision-making in varied and dynamic individual, social and structural contexts. Widespread shortfalls of physical activity interventions suggests the complex underlying mechanisms of change are not yet fully understood. More insightful process evaluations are needed to design and implement more effective approaches. This paper describes the protocol for a process evaluation of the JU:MP programme, a whole systems approach to increasing physical activity in children and young people aged 5–14 years in North Bradford, UK. Methods This process evaluation, underpinned by realist philosophy, aims to understand the development and implementation of the JU:MP programme and the mechanisms by which JU:MP influences physical activity in children and young people. It also aims to explore behaviour change across wider policy, strategy and neighbourhood systems. A mixed method data collection approach will include semi-structured interview, observation, documentary analysis, surveys, and participatory evaluation methods including reflections and ripple effect mapping. Discussion This protocol offers an innovative approach on the use of process evaluation feeding into an iterative programme intended to generate evidence-based practice and deliver practice-based evidence. This paper advances knowledge regarding the development of process evaluations for evaluating systems interventions, and emphasises the importance of process evaluation