Physical activity, sedentary time and physical capability in early old age: British birth cohort study

To investigate the associations of time spent sedentary, in moderate-to-vigorous-intensity physical activity (MVPA) and physical activity energy expenditure (PAEE) with physical capability measures at age 60-64 years

What influences the speed of prototyping? An empirical investigation of twenty software startups

It is essential for startups to quickly experiment business ideas by building tangible prototypes and collecting user feedback on them. As prototyping is an inevitable part of learning for early stage software startups, how fast startups can learn depends on how fast they can prototype. Despite of the importance, there is a lack of research about prototyping in software startups. In this study, we aimed at understanding what are factors influencing different types of prototyping activities. We conducted a multiple case study on twenty European software startups. The results are two folds, firstly we propose a prototype-centric learning model in early stage software startups. Secondly, we identify factors occur as barriers but also facilitators for prototyping in early stage software startups. The factors are grouped into (1) artifacts, (2) team competence, (3) collaboration, (4) customer and (5) process dimensions. To speed up a startups progress at the early stage, it is important to incorporate the learning objective into a well-defined collaborative approach of prototypingComment: This is the author's version of the work. Copyright owner's version can be accessed at doi.org/10.1007/978-3-319-57633-6_2, XP2017, Cologne, German

Therapeutic benefits of distal ventricular pacing in mid-cavity obstructive hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) mid-cavity obstruction (LVMCO) often experience severe drug-refractory symptoms thought to be related to intraventricular obstruction. We tested whether ventricular pacing, guided by invasive haemodynamic assessment, reduced LVMCO and improved refractory symptoms. METHODS: Between December 2008 and December 2017, 16 HCM patients with severe refractory symptoms and LVMCO underwent device implantation with haemodynamic pacing study to assess the effect on invasively defined LVMCO gradients. The effect on the gradient of atrioventricular (AV) synchronous pacing from sites including right ventricular (RV) apex and middle cardiac vein (MCV) was retrospectively assessed. RESULTS: Invasive haemodynamic data were available in 14 of 16 patients. Mean pre-treatment intracavitary gradient was 77 ± 22 mmHg (in sinus rhythm) versus 21 ± 21 mmHg during pacing from optimal ventricular site (95% CI: -70.86 to -40.57, p < 0.0001). Optimal pacing site was distal MCV in 12/16 (86%), RV apex in 1/16 and via epicardial LV lead in 1/16. Pre-pacing Doppler-derived gradients were significantly higher than at follow-up (47 ± 15 versus 24 ± 16 mmHg, 95% CI: -37.19 to -13.73, p < 0.001). Median baseline NYHA class was 3, which had improved by ⩾1 NYHA class in 13 of 16 patients at 1-year post-procedure (p < 0.001). The mean follow-up duration was 4.6 ± 2.7 years with the following outcomes: 8/16 (50%) had continued symptomatic improvement, 4/16 had symptomatic decline and 4/16 died. Contributors to symptomatic decline included chronic atrial fibrillation (AF) (n = 5), phrenic nerve stimulation (n = 3) and ventricular ectopy (n = 1). CONCLUSION: In drug-refractory symptomatic LVMCO, distal ventricular pacing can reduce intracavitary obstruction and may provide long-term symptomatic relief in patients with limited treatment options. A haemodynamic pacing study is an effective strategy for identifying optimal pacing site and configuration

Intestinal helminth co-infection is an unrecognised risk factor for increased pneumococcal carriage density and invasive disease.

Infection with Streptococcus pneumoniae is the leading cause of death in children and burden of disease is greatest where helminth infections are also common. We investigated the impact of intestinal helminth co-infection on pneumococcal carriage; a risk factor for invasive disease. We used a mouse co-infection model and clinical data to assess the impact of co-infection on carriage density. Co-infection in mice was associated with increased pneumococcal carriage density and dissemination into lungs. Helminth-infected children also exhibited increased carriage density as compared to uninfected children. Anthelmintic treatment may be a cost-effective method of reducing pneumococcal disease burden in lower-income countries

Whipworm and roundworm infections

Trichuriasis and ascariasis are neglected tropical diseases caused by the gastrointestinal dwelling nematodes Trichuris trichiura (a whipworm) and Ascaris lumbricoides (a roundworm), respectively. Both parasites are staggeringly prevalent, particularly in tropical and subtropical areas, and are associated with substantial morbidity. Infection is initiated by ingestion of infective eggs, which hatch in the intestine. Thereafter, T. trichiura larvae moult within intestinal epithelial cells, with adult worms embedded in a partially intracellular niche in the large intestine, whereas A. lumbricoides larvae penetrate the gut mucosa and migrate through the liver and lungs before returning to the lumen of the small intestine, where adult worms dwell. Both species elicit type 2 anti-parasite immunity. Diagnosis is typically based on clinical presentation (gastrointestinal symptoms and inflammation) and the detection of eggs or parasite DNA in the faeces. Prevention and treatment strategies rely on periodic mass drug administration (generally with albendazole or mebendazole) to at-risk populations and improvements in water, sanitation and hygiene. The effectiveness of drug treatment is very high for A. lumbricoides infections, whereas cure rates for T. trichiura infections are low. Novel anthelminthic drugs are needed, together with vaccine development and tools for diagnosis and assessment of parasite control in the field

Bidirectional association between physical activity and muscular strength in older adults: Results from the UK Biobank study.

BACKGROUND: The relationship between physical activity and muscular strength has not been examined in detail among older adults. The objective of this study was to examine the associations between physical activity and hand grip strength among adults aged ≥ 60 years. METHODS: Using data from the UK Biobank study, we included 66 582 men and women with complete baseline data and 6599 with 4.5 years of follow-up data. We used multiple linear regression models to examine the cross-sectional, longitudinal and bidirectional associations between moderate-to-vigorous physical activity (MVPA) and grip strength, adjusting for potential confounding by age, sex, height, weight, health status, education level, smoking status, Townsend deprivation index and retirement status. RESULTS: In cross-sectional analyses, grip strength and MVPA were linearly and positively associated with each other. Longitudinally, baseline MVPA was not associated with grip strength at follow-up {difference between quintile [Q] 5 and Q1 = 0.40 [95% confidence interval (CI): -0.14, 0.94]kg}, whereas baseline grip strength was associated with MVPA at follow-up [Q5 vs Q1 = 7.15 (1.18, 13.12) min/day]. People who maintained/increased time spent in MVPA did not experience any benefit in grip strength [0.08 (-0.20, 0.37) kg] whereas those who increased their grip strength spent 3.69 (0.20, 7.17) min/day extra in MVPA. CONCLUSION: Promotion of strength-training activities may enable and maintain participation in regular physical activity among older adults.This work was supported by the Medical Research Council [Programme number: MC_UU_12015/4] and has been conducted using the UK Biobank Resource.This is the final version of the article. It first appeared from Oxford University Press via https://doi.org/10.1093/ije/dyw05

Human helminth therapy to treat inflammatory disorders - where do we stand?

Parasitic helminths have evolved together with the mammalian immune system over many millennia and as such they have become remarkably efficient modulators in order to promote their own survival. Their ability to alter and/or suppress immune responses could be beneficial to the host by helping control excessive inflammatory responses and animal models and pre-clinical trials have all suggested a beneficial effect of helminth infections on inflammatory bowel conditions, MS, asthma and atopy. Thus, helminth therapy has been suggested as a possible treatment method for autoimmune and other inflammatory disorders in humans

Electrostatically gated membrane permeability in inorganic protocells

Although several strategies are now available to produce functional microcompartments analogous to primitive cell-like structures, little progress has been made in generating protocell constructs with self-controlled membrane permeability. Here we describe the preparation of water-dispersible colloidosomes based on silica nanoparticles and delineated by a continuous semipermeable inorganic membrane capable of self-activated, electrostatically gated permeability. We use crosslinking and covalent grafting of a pH-responsive copolymer to generate an ultrathin elastic membrane that exhibits selective release and uptake of small molecules. This behaviour, which depends on the charge of the copolymer coronal layer, serves to trigger enzymatic dephosphorylation reactions specifically within the protocell aqueous interior. This system represents a step towards the design and construction of alternative types of artificial chemical cells and protocell models based on spontaneous processes of inorganic self-organization

The selective phosphodiesterase 4 inhibitor roflumilast and phosphodiesterase 3/4 inhibitor pumafentrine reduce clinical score and TNF expression in experimental colitis in mice.

The specific inhibition of phosphodiesterase (PDE)4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-γ (IFNγ) production and CD69 expression. Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-α (TNFα) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNFα production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFNγ compared to no treatment in vivo. These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice