An ongoing case-control study to evaluate the NHS Bowel Cancer Screening Programme

© 2014 Massat et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Exploring recruitment barriers and facilitators in early cancer detection trials: the use of pre-trial focus groups

Background Recruiting to randomized controlled trials is fraught with challenges; with less than one third recruiting to their original target. In preparation for a trial evaluating the effectiveness of a blood test to screen for lung cancer (the ECLS trial), we conducted a qualitative study to explore the potential barriers and facilitators that would impact recruitment. Methods Thirty two people recruited from community settings took part in four focus groups in Glasgow and Dundee (UK). Thematic analysis was used to code the data and develop themes. Results Three sub-themes were developed under the larger theme of recruitment strategies. The first of these themes, recruitment options, considered that participants largely felt that the invitation to participate letter should come from GPs, with postal reminders and face-to-face reminders during primary care contacts. The second theme dealt with understanding randomization and issues related to the control group (where bloods were taken but not tested). Some participants struggled with the concept or need for randomization, or for the need for a control group. Some reported that they would not consider taking part if allocated to the control group, but others were motivated to take part even if allocated to the control group by altruism. The final theme considered perceived barriers to participation and included practical barriers (such as flexible appointments and reimbursement of travel expenses) and psychosocial barriers (such as feeling stigmatized because of their smoking status and worries about being coerced into stopping smoking). Conclusions Focus groups provided useful information which resulted in numerous changes to proposed trial documentation and processes. This was in order to address participants information needs, improve comprehension of the trial documentation, enhance facilitators and remove barriers to participation. The modifications made in light of these findings may enhance trial recruitment and future trials may wish to consider use of pretrial focus groups

HIV Prevalence, Risks for HIV Infection, and Human Rights among Men Who Have Sex with Men (MSM) in Malawi, Namibia, and Botswana

BACKGROUND: In the generalized epidemics of HIV in southern Sub-Saharan Africa, men who have sex with men have been largely excluded from HIV surveillance and research. Epidemiologic data for MSM in southern Africa are among the sparsest globally, and HIV risk among these men has yet to be characterized in the majority of countries. METHODOLOGY: A cross-sectional anonymous probe of 537 men recruited with non-probability sampling among men who reported ever having had sex with another man in Malawi, Namibia, and Botswana using a structured survey instrument and HIV screening with the OraQuick(c) rapid test kit. PRINCIPAL FINDINGS: The HIV prevalence among those between the ages of 18 and 23 was 8.3% (20/241); 20.0% (42/210) among those 24-29; and 35.7% (30/84) among those older than 30 for an overall prevalence of 17.4% (95% CI 14.4-20.8). In multivariate logistic regressions, being older than 25 (aOR 4.0, 95% CI 2.0-8.0), and not always wearing condoms during sex (aOR 2.6, 95% CI 1.3-4.9) were significantly associated with being HIV-positive. Sexual concurrency was common with 16.6% having ongoing concurrent stable relationships with a man and a woman and 53.7% had both male and female sexual partners in proceeding 6 months. Unprotected anal intercourse was common and the use of petroleum-based lubricants was also common when using condoms. Human rights abuses, including blackmail and denial of housing and health care was prevalent with 42.1% (222/527) reporting at least one abuse. CONCLUSIONS: MSM are a high-risk group for HIV infection and human rights abuses in Malawi, Namibia, and Botswana. Concurrency of sexual partnerships with partners of both genders may play important roles in HIV spread in these populations. Further epidemiologic and evaluative research is needed to assess the contribution of MSM to southern Africa's HIV epidemics and how best to mitigate this. These countries should initiate and adequately fund evidence-based and targeted HIV prevention programs for MSM

DNA Ligase C and Prim-PolC participate in base excision repair in mycobacteria

Prokaryotic Ligase D is a conserved DNA repair apparatus processing DNA double-strand breaks in stationary phase. An orthologous Ligase C (LigC) complex also co-exists in many bacterial species but its function is unknown. Here, we show that the LigC complex interacts with core BER enzymes in vivo and demonstrate that together these factors constitute an excision repair apparatus capable of repairing damaged bases and abasic sites. The polymerase component, which contains a conserved C-terminal structural loop, preferentially binds to and fills-in short gapped DNA intermediates with RNA and LigC ligates the resulting nicks to complete repair. Components of the LigC complex, like LigD, are expressed upon entry into stationary phase and cells lacking either of these pathways exhibit increased sensitivity to oxidising genotoxins. Together, these findings establish that the LigC complex is directly involved in an excision repair pathway(s) that repairs DNA damage with ribonucleotides during stationary phase

Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae

F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA+ B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA+ B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity

Altered T Cell Memory and Effector Cell Development in Chronic Lymphatic Filarial Infection That Is Independent of Persistent Parasite Antigen

Chronic lymphatic filarial (LF) infection is associated with suppression of parasite-specific T cell responses that persist even following elimination of infection. While several mechanisms have been implicated in mediating this T cell specific downregulation, a role for alterations in the homeostasis of T effector and memory cell populations has not been explored. Using multiparameter flow cytometry, we investigated the role of persistent filarial infection on the maintenance of T cell memory in patients from the filarial-endemic Cook Islands. Compared to filarial-uninfected endemic normals (EN), microfilaria (mf) positive infected patients (Inf) had a reduced CD4 central memory (TCM) compartment. In addition, Inf patients tended to have more effector memory cells (TEM) and fewer effector cells (TEFF) than did ENs giving significantly smaller TEFF ∶ TEM ratios. These contracted TCM and TEFF populations were still evident in patients previously mf+ who had cleared their infection (CLInf). Moreover, the density of IL-7Rα, necessary for T memory cell maintenance (but decreased in T effector cells), was significantly higher on memory cells of Inf and CLInf patients, although there was no evidence for decreased IL-7 or increased soluble IL7-Rα, both possible mechanisms for signaling defects in memory cells. However, effector cells that were present in Inf and CLInf patients had lower percentages of HLA-DR suggesting impaired function. These changes in T cell populations appear to reflect chronicity of infection, as filarial-infected children, despite the presence of active infection, did not show alterations in the frequencies of these T cell phenotypes. These data indicate that filarial-infected patients have contracted TCM compartments and a defect in effector cell development, defects that persist even following clearance of infection. The fact that these global changes in memory and effector cell compartments do not yet occur in infected children makes early treatment of LF even more crucial

The use of bibliometrics for assessing research : possibilities, limitations and adverse effects

Researchers are used to being evaluated: publications, hiring, tenure and funding decisions are all based on the evaluation of research. Traditionally, this evaluation relied on judgement of peers but, in the light of limited resources and increased bureaucratization of science, peer review is getting more and more replaced or complemented with bibliometric methods. Central to the introduction of bibliometrics in research evaluation was the creation of the Science Citation Index (SCI)in the 1960s, a citation database initially developed for the retrieval of scientific information. Embedded in this database was the Impact Factor, first used as a tool for the selection of journals to cover in the SCI, which then became a synonym for journal quality and academic prestige. Over the last 10 years, this indicator became powerful enough to influence researchers’ publication patterns in so far as it became one of the most important criteria to select a publication venue. Regardless of its many flaws as a journal metric and its inadequacy as a predictor of citations on the paper level, it became the go-to indicator of research quality and was used and misused by authors, editors, publishers and research policy makers alike. The h-index, introduced as an indicator of both output and impact combined in one simple number, has experienced a similar fate, mainly due to simplicity and availability. Despite their massive use, these measures are too simple to capture the complexity and multiple dimensions of research output and impact. This chapter provides an overview of bibliometric methods, from the development of citation indexing as a tool for information retrieval to its application in research evaluation, and discusses their misuse and effects on researchers’ scholarly communication behavior

Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways

Signal transmission by the noncanonical IkappaB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IKKɛ, requires interaction with adapter proteins such as TRAF associated NF-κB activator (TANK). Although increased expression or dysregulation of both kinases has been described for a variety of human cancers, this study shows that deregulated expression of the TANK protein is frequently occurring in glioblastomas (GBMs). The functional relevance of TANK was analyzed in a panel of GBM-derived cell lines and revealed that knockdown of TANK arrests cells in the S-phase and prohibits tumor cell migration. Deregulated TANK expression affects several signaling pathways controlling cell proliferation and the inflammatory response. Interference with stoichiometrically assembled signaling complexes by overexpression or silencing of TANK prevented constitutive interferon-regulatory factor 3 (IRF3) phosphorylation. Knockdown of TANK frequently prevents constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). TANK-mediated ERK1/2 activation is independent from the canonical MAP kinase or ERK kinase (MEK) 1/2-mediated pathway and utilizes an alternative pathway that uses a TBK1/IKKɛ/Akt signaling axis, thus identifying a novel pathway suitable to block constitutive ERK1/2 activity.Peer reviewe

Developing a Professional Studies Curriculum to Support Veterinary Professional Identity Formation

Professional studies teaching in medical and veterinary education is undergoing a period of change. Traditional approaches, aiming to teach students professional values and behaviors, are being enhanced by curricula designed to support students' professional identity formation. This development offers the potential for improving student engagement and graduates' mental well-being. The veterinary professional identity associated with emotional resilience and success in practice incorporates complexity in professional decision making and the importance of context on behaviors and actions. The veterinarian must make decisions that balance the sometimes conflicting needs of patient, clients, veterinarian, and practice; their subsequent actions are influenced by environmental challenges such as financial limitations, or stress and fatigue caused by a heavy workload. This article aims to describe how curricula can be designed to support the development of such an identity in students. We will review relevant literature from medical education and the veterinary profession to describe current best practices for supporting professional identity formation, and then present the application of these principles using the curriculum at the Royal Veterinary College (RVC) as a case study. Design of a “best practice” curriculum includes sequential development of complex thinking rather than notions of a single best solution to a problem. It requires managing a hidden curriculum that tends to reinforce a professional identity conceived solely on clinical diagnosis and treatment. It includes exposure to veterinary professionals with different sets of professional priorities, and those who work in different environments. It also includes the contextualization of taught content through reflection on workplace learning opportunities

Impact of Environmental Parameters on Marathon Running Performance

PURPOSE: The objectives of this study were to describe the distribution of all runners' performances in the largest marathons worldwide and to determine which environmental parameters have the maximal impact. METHODS: We analysed the results of six European (Paris, London, Berlin) and American (Boston, Chicago, New York) marathon races from 2001 to 2010 through 1,791,972 participants' performances (all finishers per year and race). Four environmental factors were gathered for each of the 60 races: temperature (°C), humidity (%), dew point (°C), and the atmospheric pressure at sea level (hPA); as well as the concentrations of four atmospheric pollutants: NO(2)-SO(2)-O(3) and PM(10) (μg x m(-3)). RESULTS: All performances per year and race are normally distributed with distribution parameters (mean and standard deviation) that differ according to environmental factors. Air temperature and performance are significantly correlated through a quadratic model. The optimal temperatures for maximal mean speed of all runners vary depending on the performance level. When temperature increases above these optima, running speed decreases and withdrawal rates increase. Ozone also impacts performance but its effect might be linked to temperature. The other environmental parameters do not have any significant impact. CONCLUSIONS: The large amount of data analyzed and the model developed in this study highlight the major influence of air temperature above all other climatic parameter on human running capacity and adaptation to race conditions