Increased hydrogen production by Escherichia coli strain HD701 in comparison with the wild-type parent strain MC4100

Hydrogen production by Escherichia coli is mediated by the formate hydrogenlyase (FHL) complex. E. coli strain HD701 cannot synthesize the FHL complex repressor, Hyc A. Consequently, it has an up-regulated FHL system and can, therefore, evolve hydrogen at a greater rate than its parental wild type, E. coli MC4100. Resting cells of E. coli strain HD701 and MC4100 were set up in batch mode in\ud phosphate buffered saline (PBS) to decouple growth from hydrogen production at the expense of sugar solutions of varying composition. Strain HD701 evolved several times more hydrogen than MC4100 at glucose concentrations ranging from 3 to 200 mM. The difference in the amount of H2 evolved by both strains decreased as the concentration of glucose increased. The highest rate of H2 evolution by strain HD701was 31ml h−1 ODunit −1 l−1 at a glucose concentration of 100 mM.With strain MC4100, the highest ratewas 16ml h−1 ODunit −1 l−1 under these conditions. Experiments using industrial wastes with a high sugar content yielded similar results. In each case, strain HD701\ud evolved hydrogen at a faster rate than the wild type, showing a possible potential for commercial hydrogen production

Dietary nitrate modulates cerebral blood flow parameters and cognitive performance in humans: A double-blind, placebo-controlled, crossover investigation.

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Nitrate derived from vegetables is consumed as part of a normal diet and is reduced endogenously via nitrite to nitric oxide. It has been shown to improve endothelial function, reduce blood pressure and the oxygen cost of sub-maximal exercise, and increase regional perfusion in the brain. The current study assessed the effects of dietary nitrate on cognitive performance and prefrontal cortex cerebral blood-flow (CBF) parameters in healthy adults. In this randomised, double-blind, placebo-controlled, parallel-groups study, 40 healthy adults received either placebo or 450 ml beetroot juice (~5.5 mmol nitrate). Following a 90 minute drink/absorption period, participants performed a selection of cognitive tasks that activate the frontal cortex for 54 min. Near-Infrared Spectroscopy (NIRS) was used to monitor CBF and hemodynamics, as indexed by concentration changes in oxygenated and deoxygenated-haemoglobin, in the frontal cortex throughout. The bioconversion of nitrate to nitrite was confirmed in plasma by ozone-based chemi-luminescence. Dietary nitrate modulated the hemodynamic response to task performance, with an initial increase in CBF at the start of the task period, followed by consistent reductions during the least demanding of the three tasks utilised. Cognitive performance was improved on the serial 3s subtraction task. These results show that single doses of dietary nitrate can modulate the CBF response to task performance and potentially improve cognitive performance, and suggest one possible mechanism by which vegetable consumption may have beneficial effects on brain function

Phase I clinical and pharmacokinetic study of PM01183 (a tetrahydroisoquinoline, Lurbinectedin) in combination with gemcitabine in patients with advanced solid tumors

Background To determine the recommended dose (RD) of a combination of PM01183 and gemcitabine in patients with advanced solid tumors. Methods Forty-five patients received escalating doses of PM01183/gemcitabine on Days 1 and 8 every 3 weeks (d1,8 q3wk) following a standard 3 + 3 design. Results PM01183 3.5 mg flat dose (FD)/gemcitabine 1000 mg/m(2) was the highest dose level tested. Dose-limiting toxicities (DLTs) were mostly hematological and resulted in the expansion of a lower dose level (PM01183 3.5 mg FD/gemcitabine 800 mg/m(2)); 19 patients at this dose level were evaluable but >30% had DLT and >20% had febrile neutropenia. No DLT was observed in 11 patients treated at PM01183 3.0 mg FD/gemcitabine 800 mg/m(2), which was defined as the RD. This regimen was feasible and tolerable with manageable toxicity; mainly grade 3/4 myelosuppression. Non-hematological toxicity comprised fatigue, nausea, vomiting, and transaminases increases. Fifteen (33%) patients received ≥6 cycles with no cumulative hematological toxicity. Pharmacokinetic analysis showed no evidence of drug-drug interaction. Nine of 38 patients had response as per RECIST (complete [3%] and partial [21%]), for an overall response rate (ORR) of 24% (95% Confidence Interval [CI] 12-40%). Eleven patients (29%) had disease stabilization ≥4 months. Responses were durable (median of 8.5 months): overall median progression-free survival (PFS) was 4.2 months (95% CI, 2.7-6.5 months). Conclusions The RD for this combination is PM01183 3.0 mg FD (or 1.6 mg/m(2))/gemcitabine 800 mg/m(2) d1,8 q3wk. This schedule is well tolerated and has antitumor activity in several advanced solid tumor types

Barriers and facilitators to adherence to group exercise in institutionalized older people living with dementia: a systematic review

Objectives Research suggests targeted exercise is important for people living with dementia, especially those living in residential care. The aim of this review was to collect and synthesize evidence on the known barriers and facilitators to adherence to group exercise of institutionalized older people living with dementia. Methods We searched all available electronic databases. Additionally, we searched trial registries (clinicaltrial.gov, and WHO ICTRP) for ongoing studies. We searched for and included papers from January 1990 until September 2017 in any language. We included randomized, non-randomized trials. Studies were not eligible if participants were either healthy older people or people suffering from dementia but not living in an institution. Studies were also excluded if they were not focused on barriers and facilitators to adherence to group exercise. Results Using narrative analysis, we identified the following themes for barriers: bio-medical reasons and mental wellbeing and physical ability, relationships dynamics, and socioeconomic reasons. The facilitators were grouped under the following thematic frames: bio-medical benefits and benefits related to physical ability, feelings and emotions and confidence improvements, therapist and group relationships dynamics and activity related reasons. Conclusions We conclude that institutionalized older people living with dementia, even those who are physically frail, incontinent and/or have mild dementia can demonstrate certain level of exercise adherence, and therefore can respond positively to exercise programs. Tailored, individually-adjusted and supported physical activity, led by a knowledgeable, engaging and well communicating therapist/facilitator improves the adherence to group exercise interventions of institutionalized older people living with dementia

Half a degree additional warming, prognosis and projected impacts (HAPPI): Background and experimental design

Abstract. The Intergovernmental Panel on Climate Change (IPCC) has accepted the invitation from the UNFCCC to provide a special report on the impacts of global warming of 1.5 °C above pre-industrial levels and on related global greenhouse-gas emission pathways. Many current experiments in, for example, the Coupled Model Inter-comparison Project (CMIP), are not specifically designed for informing this report. Here, we document the design of the half a degree additional warming, projections, prognosis and impacts (HAPPI) experiment. HAPPI provides a framework for the generation of climate data describing how the climate, and in particular extreme weather, might differ from the present day in worlds that are 1.5 and 2.0 °C warmer than pre-industrial conditions. Output from participating climate models includes variables frequently used by a range of impact models. The key challenge is to separate the impact of an additional approximately half degree of warming from uncertainty in climate model responses and internal climate variability that dominate CMIP-style experiments under low-emission scenarios.Large ensembles of simulations (&gt;  50 members) of atmosphere-only models for three time slices are proposed, each a decade in length: the first being the most recent observed 10-year period (2006–2015), the second two being estimates of a similar decade but under 1.5 and 2 °C conditions a century in the future. We use the representative concentration pathway 2.6 (RCP2.6) to provide the model boundary conditions for the 1.5 °C scenario, and a weighted combination of RCP2.6 and RCP4.5 for the 2 °C scenario. </jats:p

A cluster randomised feasibility study of an adolescent incentive intervention to increase uptake of HPV vaccination.

BACKGROUND: Uptake of human papillomavirus (HPV) vaccination is suboptimal among some groups. We aimed to determine the feasibility of undertaking a cluster randomised controlled trial (RCT) of incentives to improve HPV vaccination uptake by increasing consent form return. METHODS: An equal-allocation, two-arm cluster RCT design was used. We invited 60 London schools to participate. Those agreeing were randomised to either a standard invitation or incentive intervention arm, in which Year 8 girls had the chance to win a £50 shopping voucher if they returned a vaccination consent form, regardless of whether consent was provided. We collected data on school and parent participation rates and questionnaire response rates. Analyses were descriptive. RESULTS: Six schools completed the trial and only 3% of parents opted out. The response rate was 70% for the girls' questionnaire and 17% for the parents'. In the intervention arm, 87% of girls returned a consent form compared with 67% in the standard invitation arm. The proportion of girls whose parents gave consent for vaccination was higher in the intervention arm (76%) than the standard invitation arm (61%). CONCLUSIONS: An RCT of an incentive intervention is feasible. The intervention may improve vaccination uptake but a fully powered RCT is needed.British Journal of Cancer advance online publication: 22 August 2017; doi:10.1038/bjc.2017.284 www.bjcancer.com

Elephants in pyjamas: testing the weak central coherence account of autism spectrum disorders using a syntactic disambiguation task

According to the weak central coherence (CC) account individuals with autism spectrum disorders (ASD) exhibit enhanced local processing and weak part-whole integration. CC was investigated in the verbal domain. Adolescents, recruited using a 2 (ASD status) by 2 (language impairment status) design, completed an aural forced choice comprehension task involving syntactically ambiguous sentences. Half the picture targets depicted the least plausible interpretation, resulting in longer RTs across groups. These were assumed to reflect local processing. There was no ASD by plausibility interaction and consequently little evidence for weak CC in the verbal domain when conceptualised as enhanced local processing. Furthermore, there was little evidence that the processing of syntactically ambiguous sentences differed as a function of ASD or language-impairment status

Hands behind your back: effects of arm posture on tactile attention in the space behind the body

Previous research has shown that tactile-spatial information originating from the front of the body is remapped from an anatomical to an external-spatial coordinate system, guided by the availability of visual information early in development. Comparably little is known about regions of space for which visual information is not typically available, such as the space behind the body. This study tests for the first time the electrophysiological correlates of the effects of proprioceptive information on tactile-attentional mechanisms in the space behind the back. Observers were blindfolded and tactually cued to detect infrequent tactile targets on either their left or right hand and to respond to them either vocally or with index finger movements. We measured event-related potentials (ERPs) to tactile probes on the hands in order to explore tactile-spatial attention when the hands were either held close together or far apart behind the observer's back. Results show systematic effects of arm posture on tactile-spatial attention different from those previously found for front space. While attentional selection is typically more effective for hands placed far apart than close together in front space, we found that selection occurred more rapidly for close than far hands behind the back, during both covert attention and movement preparation tasks. This suggests that proprioceptive space may ‘wrap’ around the body, following the hands as they extend horizontally from the front body midline to the centre of the back

Higher vegetable protein consumption, assessed by an isoenergetic macronutrient exchange model, is associated with a lower presence of overweight and obesity in the web-based Food4me European study

The objective was to evaluate differences in macronutrient intake and to investigate the possible association between consumption of vegetable protein and the risk of overweight/obesity, within the Food4Me randomised, online intervention. Differences in macronutrient consumption among the participating countries grouped by EU Regions (Western Europe, British Isles, Eastern Europe and Southern Europe) were assessed. Relation of protein intake, within isoenergetic exchange patterns, from vegetable or animal sources with risk of overweight/obesity was assessed through the multivariate nutrient density model and a multivariate-adjusted logistic regression.A total of 2413 subjects who completed the Food4Me screening were included, with self-reported data on age, weight, height, physical activity and dietary intake. As success rates on reducing overweight/obesity are very low, form a public health perspective, the elaboration of policies for increasing intakes of vegetable protein and reducing animal protein and sugars, may be a method of combating overweight/obesity at a population level