Evaluation of a gender-sensitive physical activity programme for inactive men in Ireland: Protocol paper for a pragmatic controlled trial

The excess burden of ill-health, mortality and premature death experienced by many men, and poorer men in particular, across the developed world has prompted calls for the development of gender sensitised health related services for men. An emergent body of evidence indicates that successful public health work with men can be accomplished when it utilises elements with which men are familiar and secure. In particular, physical activity (PA) is proven here to be a useful ‘hook’ to engage men. ‘Men on the Move’ (MoM) is a community-based PA programme designed to engage inactive men to improve their overall health and well-being. The MoM programme was delivered by practitioner partnerships in diverse communities and among diverse groups of men under ‘real world’ conditions to assess both its efficacy and replicability with a view to scaling-up the programme nationally for population wide impact. Establishing appropriate protocols is critical when conducting research that translates into practice, is replicable in practice and can be disseminated at a population level. The purpose of this paper is to detail the protocols used in the design, implementation and evaluation of the MoM programme. Specifically, the process of engaging men in a community based PA intervention and sustaining that engagement over the 12 weeks and the protocols used to evaluate the impact of participation in MoM on biopsychosocial health up to 52 weeks will be outlined. If the intervention proves successful, gender-sensitive community based PA interventions for men could be a promising avenue to address their health needs. These findings may be of support to both practitioners endeavouring to engage men and others engaged in translational research to ensure their research translates to meaningful action in practice

The impact of a gender-specific physical activity intervention on the fitness and fatness profile of men in Ireland

Background: Amid increasing concerns about rising obesity rates and unhealthy lifestyle behaviours, physical activity (PA) is seen as a prophylactic to many chronic conditions affecting men. Men respond best to community-based PA programmes, using gender-specific promotional and delivery strategies. ‘Men on the Move’ (MOM) was developed on this basis and targeted inactive adult men in Ireland. Methods: Sedentary men (n=927; age=50.7±10.9yr; Weight=92.7±16.0kg; METS=6.06±2.13) were recruited across 8 counties; 4 ‘intervention group’ (IG; n=501), and 4 ‘comparison-in-waiting group’ (CG; n=426). The MOM programme involved structured group exercise twice weekly for 12 weeks, along with health-related workshops with the groups maintained up to 52W. Primary outcome measures (aerobic fitness, bodyweight and waist circumference (WC)) together with self-administered questionnaires were used to gather participant data at baseline, 12, 26 and 52 weeks (W). Results: Results show a net positive effect on aerobic fitness, bodyweight and WC, with significant (p<0.05) net change scores observed in the IG compared to the CG (METS: 12W=+2.20, 26W=+1.89, 52W=+0.92; Weight: 12W=-1.72kg, 26W=-1.95kg, 52W=-1.89kg; WC: 12W=-4.54cm, 26W=-2.69cm, 52W=-3.16cm). The corresponding reduction in cardiovascular disease risk is particularly significant in the context of a previously inactive and overweight cohort. The high ‘dropout’ (42.7% presenting at 52W) however, is of particular concern, with ‘dropouts’ having lower levels of aerobic fitness and higher bodyweight/WC at baseline. Conclusions: Notwithstanding dropout issues, findings address an important gap in public health practice by informing the translational scale-up of a small controllable gender-specific PA intervention, MOM, to a national population based PA intervention targeting inactive men

Determine TB-LAM point-of-care tuberculosis assay predicts poor outcomes in outpatients during their first year of antiretroviral therapy in South Africa.

BACKGROUND: Determine TB-LAM is the first point-of-care test (POC) for HIV-associated tuberculosis (TB) and rapidly identifies TB in those at high-risk for short-term mortality. While the relationship between urine-LAM and mortality has been previously described, the outcomes of those undergoing urine-LAM testing have largely been assessed during short follow-up periods within diagnostic accuracy studies. We therefore sought to assess the relationship between baseline urine-LAM results and subsequent hospitalization and mortality under real-world conditions among outpatients in the first year of ART. METHODS: Consecutive, HIV-positive adults with a CD4 count < 100 cells/uL presenting for ART initiation were enrolled. TB diagnoses and outcomes (hospitalization, loss-to-follow and mortality) were recorded during the first year following enrolment. Baseline urine samples were retrospectively tested using the urine-LAM POC assay. Kaplan Meier survival curves were used to assess the cumulative probability of hospitalization or mortality in the first year of follow-up, according to urine-LAM status. Cox regression analyses were performed to determine independent predictors of hospitalization and mortality at  three months and one year of follow-up. RESULTS: 468 patients with a median CD4 count of 59 cells/uL were enrolled. There were 140 patients (29.9%) with newly diagnosed TB in the first year of follow-up of which 79 (56.4%) were microbiologically-confirmed. A total of 18% (n = 84) required hospital admission and 12.2% (n = 57) died within a year of study entry. 38 out of 468 (8.1%) patients retrospectively tested urine-LAM positive - including 19.0% of those with microbiologically-proven TB diagnoses (n = 15/79) and 23.0% (n = 14/61) of those with clinical-only TB diagnoses; 9 of 38 (23.7%) of patients retrospectively testing LAM positive were never diagnosed with TB under routine program conditions. Among all patients (n = 468) in the first year of follow-up, a positive urine-LAM result was strongly associated with all-cause hospitalization and mortality with a corresponding adjusted hazard ratio (aHR) of 3.7 (95%CI, 1.9-7.1) and 2.6 (95%, 1.2-5.7), respectively. CONCLUSIONS: Systematic urine-LAM testing among ART-naïve HIV-positive outpatients with CD4 counts < 100 cells/uL detected TB cases that were missed under routine programme conditions and was highly predictive for subsequent hospitalization and mortality in the first year of ART

Transposon Mutagenesis in Chlamydia trachomatis Identifies CT339 as a ComEC Homolog Important for DNA Uptake and Lateral Gene Transfer

Transposon mutagenesis is a widely applied and powerful genetic tool for the discovery of genes associated with selected phenotypes. Chlamydia trachomatis is a clinically significant, obligate intracellular bacterium for which many conventional genetic tools and capabilities have been developed only recently. This report describes the successful development and application of a Himar transposon mutagenesis system for generating single-insertion mutant clones of C. trachomatis. This system was used to generate a pool of 105 transposon mutant clones that included insertions in genes encoding flavin adenine dinucleotide (FAD)-dependent monooxygenase (C. trachomatis 148 [ct148]), deubiquitinase (ct868), and competence-associated (ct339) proteins. A subset of Tn mutant clones was evaluated for growth differences under cell culture conditions, revealing that most phenocopied the parental strain; however, some strains displayed subtle and yet significant differences in infectious progeny production and inclusion sizes. Bacterial burden studies in mice also supported the idea that a FAD-dependent monooxygenase (ct148) and a deubiquitinase (ct868) were important for these infections. The ct339 gene encodes a hypothetical protein with limited sequence similarity to the DNA-uptake protein ComEC. A transposon insertion in ct339 rendered the mutant incapable of DNA acquisition during recombination experiments. This observation, along with in situ structural analysis, supports the idea that this protein is playing a role in the fundamental process of lateral gene transfer similar to that of ComEC. In all, the development of the Himar transposon system for Chlamydia provides an effective genetic tool for further discovery of genes that are important for basic biology and pathogenesis aspects.S.D.L., Z.E.D., K.S.H., S.B., R.J.S., and P.S.H. were funded by NIH (AI126785)J.W. and P.S.H. were supported by NIH AI125929. P.S.H. was also supported by P20GM113117Support for genomic sequencing was supplemented by P20GM10363

Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

Co-evolutionary analysis suggests a role for TLR9 in papillomavirus restriction

Upon infection, DNA viruses can be sensed by pattern recognition receptors (PRRs) leading to the activation of type I and III interferons, aimed at blocking infection. Therefore, viruses must inhibit these signaling pathways, avoid being detected, or both. Papillomavirus virions are trafficked from early endosomes to the Golgi apparatus and wait for the onset of mitosis to complete nuclear entry. This unique subcellular trafficking strategy avoids detection by cytoplasmic PRRs, a property that may contribute to establishment of infection. However, as the capsid uncoats within acidic endosomal compartments, the viral DNA may be exposed to detection by toll-like receptor (TLR) 9. In this study we characterize two new papillomaviruses from bats and use molecular archeology to demonstrate that their genomes altered their nucleotide composition to avoid detection by TLR9, providing evidence that TLR9 acts as a PRR during papillomavirus infection. Furthermore, we demonstrate that TLR9, like other components of the innate immune system, is under evolutionary selection in bats, providing the first direct evidence for co-evolution between papillomaviruses and their hosts

Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study.

BACKGROUND: Retrospective data suggest that cryptococcal antigen (CrAg) screening in patients with late-stage human immunodeficiency virus (HIV) initiating antiretroviral therapy (ART) may reduce cryptococcal disease and deaths. Prospective data are limited. METHODS: CrAg was measured using lateral flow assays (LFA) and latex agglutination (LA) tests in 645 HIV-positive, ART-naive patients with CD4 counts ≤100 cells/µL in Cape Town, South Africa. CrAg-positive patients were offered lumbar puncture (LP) and treated with antifungals. Patients were started on ART between 2 and 4 weeks and followed up for 1 year. RESULTS: A total of 4.3% (28/645) of patients were CrAg positive in serum and plasma with LFA. These included 16 also positive by urine LFA (2.5% of total screened) and 7 by serum LA (1.1% of total). In 4 of 10 LFA-positive cases agreeing to LP, the cerebrospinal fluid (CSF) CrAg LFA was positive. A positive CSF CrAg was associated with higher screening plasma/serum LFA titers.Among the 28 CrAg-positive patients, mortality was 14.3% at 10 weeks and 25% at 12 months. Only 1 CrAg-positive patient, who defaulted from care, died from cryptococcal meningitis (CM). Mortality in CrAg-negative patients was 11.5% at 1 year. Only 2 possible CM cases were identified in CrAg-negative patients. CONCLUSIONS: CrAg screening of individuals initiating ART and preemptive fluconazole treatment of CrAg-positive patients resulted in markedly fewer cases of CM compared with historic unscreened cohorts. Studies are needed to refine management of CrAg-positive patients who have high mortality that does not appear to be wholly attributable to cryptococcal disease

Software Citation Implementation Challenges

The main output of the FORCE11 Software Citation working group (https://www.force11.org/group/software-citation-working-group) was a paper on software citation principles (https://doi.org/10.7717/peerj-cs.86) published in September 2016. This paper laid out a set of six high-level principles for software citation (importance, credit and attribution, unique identification, persistence, accessibility, and specificity) and discussed how they could be used to implement software citation in the scholarly community. In a series of talks and other activities, we have promoted software citation using these increasingly accepted principles. At the time the initial paper was published, we also provided guidance and examples on how to make software citable, though we now realize there are unresolved problems with that guidance. The purpose of this document is to provide an explanation of current issues impacting scholarly attribution of research software, organize updated implementation guidance, and identify where best practices and solutions are still needed

Economic evaluation of ‘Men on the Move’, a ‘real world’ community-based physical activity programme for men

Background Physical activity (PA) interventions capable of producing health benefits cost effectively are a public health priority across the Western world. ‘Men on the Move’ (MOM), a community-based PA intervention for men, demonstrated significant health benefits up to 52-weeks (W) post-baseline. This article details the economic evaluation of MOM with a view to determining its cost-effectiveness as a public health intervention to be rolled out nationally in Ireland. Methods Cost-effectiveness was determined by comparing the costs (direct and indirect) of the programme to its benefits, which were captured as the impact on quality-adjusted life-years (QALYs). For the benefits, cost–utility analysis was conducted by retrospectively adapting various health-related measures of participants to generate health states using Brazier et al.’s (2002) short form-6D algorithm. This in turn allowed for ‘utility measures’ to be generated, from which QALYs were derived. Results Findings show MOM to be cost-effective in supporting an ‘at risk’ cohort of men achieves significant improvements in aerobic fitness, weight loss and waist reduction. The total cost per participant (€125.82 for each of the 501 intervention participants), the QALYs gained (11.98 post-12-W intervention, or 5.3% health improvement per participant) and estimated QALYs ratio costs of €3723 represents a cost-effective improvement when compared to known QALY guidelines. Conclusions The analysis shows that the cost per QALY achieved by MOM is significantly less than the existing benchmarks of £20 000 and €45 000 in the UK and Ireland respectively, demonstrating MOM to be cost-effective

Reaching beyond the ‘worried well’: pre-adoption characteristics of participants in ‘Men on the Move’, a community-based physical activity programme

Background Issues surrounding gender and men’s health have become an increasing focus of public health globally. Unhealthy lifestyles and lower engagement in health promotion initiatives contributed to lower life expectancy and higher mortality rates among men. This study presents the pre-adoption characteristics of men who registered for ‘Men on the Move’—a community-based physical activity (CBPA) programme, to ascertain whether the programme reached its intended target group, i.e. ‘at-risk’ adult men who did not meet physical activity (PA) guidelines and were likely to have multiple risk factors for cardiovascular disease (CVD). Methods Multiple recruitment strategies were adopted to engage the target group and baseline data collection included a range of demographic, self-report and outcome measures. Results The recruitment strategy succeeded in reaching the target group, with the majority (n = 927) presenting being previously inactive (89.0%), overweight/obese (89.7%) and having multiple CVD risk factors (53.1% ≥ 2 risk factors). However, the strategy was less successful in engaging ‘hard-to-reach’ groups, with the majority being middle-aged, white, married/cohabiting, educated and employed. Conclusions A gender-sensitized, partnership and community outreach recruitment strategy can maximize the reach and recruitment of an ‘at-risk’ cohort for CBPA initiatives, but more targeted approaches are needed to recruit marginalized groups of men