Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England

Objective Severe vitamin D deficiency is a recognised cause of skeletal muscle fatigue and myopathy. The aim of this study was to examine whether chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with altered circulating vitamin D metabolites. Design Cohort study. Setting UK university hospital, recruiting from April 2014 to April 2015. Participants Ninety-two patients with CFS/ME and 94 age-matched healthy controls (HCs). Main outcome measures The presence of a significant association between CFS/ME, fatigue and vitamin D measures. Results No evidence of a deficiency in serum total 25(OH) vitamin D (25(OH)D2 and 25(OH)D3 metabolites) was evident in individuals with CFS/ME. Liquid chromatography tandem mass spectrometry (LC–MS/MS) analysis revealed that total 25(OH)D was significantly higher (p=0.001) in serum of patients with CFS/ME compared with HCs (60.2 and 47.3 nmol/L, respectively). Analysis of food/ supplement diaries with WinDiets revealed that the higher total 25(OH) vitamin D concentrations observed in the CFS/ ME group were associated with increased vitamin D intake through use of supplements compared with the control group. Analysis of Chalder Fatigue Questionnaire data revealed no association between perceived fatigue and vitamin D levels. Conclusions Low serum concentrations of total 25(OH) D do not appear to b

Association of the 894G>T polymorphism in the endothelial nitric oxide synthase gene with risk of acute myocardial infarction

Background: This study was designed to investigate the association of the 894G>T polymorphism in the eNOS gene with risk of acute myocardial infarction (AMI), extent of coronary artery disease (CAD) on coronary angiography, and in-hospital mortality after AMI. Methods: We studied 1602 consecutive patients who were enrolled in the GEMIG study. The control group was comprised by 727 individuals, who were randomly selected from the general adult population. Results: The prevalence of the Asp298 variant of eNOS was not found to be significantly and independently associated with risk of AMI (RR = 1.08, 95%CI = 0.77–1.51, P = 0.663), extent of CAD on angiography (OR = 1.18, 95%CI = 0.63–2.23, P = 0.605) and in-hospital mortality (RR = 1.08, 95%CI = 0.29–4.04, P = 0.908). Conclusion: In contrast to previous reports, homozygosity for the Asp298 variant of the 894G>T polymorphism in the eNOS gene was not found to be associated with risk of AMI, extent of CAD and in-hospital mortality after AM

Reproducibility of scientific workflows execution using cloud-aware provenance (ReCAP)

© 2018, Springer-Verlag GmbH Austria, part of Springer Nature. Provenance of scientific workflows has been considered a mean to provide workflow reproducibility. However, the provenance approaches adopted so far are not applicable in the context of Cloud because the provenance trace lacks the Cloud information. This paper presents a novel approach that collects the Cloud-aware provenance and represents it as a graph. The workflow execution reproducibility on the Cloud is determined by comparing the workflow provenance at three levels i.e., workflow structure, execution infrastructure and workflow outputs. The experimental evaluation shows that the implemented approach can detect changes in the provenance traces and the outputs produced by the workflow

Water dispersible microbicidal cellulose acetate phthalate film

BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP

'It gives me my freedom’: technology and responding to bodily limitations in Motor Neuron Disease

People living with Motor Neuron Disease (MND) experience profound and rapidly progressing impairment. In order to maintain their physical and social functioning, people so affected employ a range of technologies and technological aids (body auxiliaries) to enhance their life and maintain wellbeing. Using a phenomenological study design, we explored the experiences of 42 men and women who had been diagnosed with MND. Although many participants initially resisted the adoption of aids (often-electronic devices that enabled continued participation in daily life) or tools (the instruments that allowed achievement of specific tasks), such technologies offered a way for people with MND to overcome, to some extent, the limitations posed by their physical degeneration. Through generating a sense of ‘normality’, these kinds of ‘enabling’ technologies promoted social engagement and the maintenance of valued relationships or activities. Technologies can provide people with MND with some positive experiences within a way of being-in-the-world that has become so difficult and challenging

Fractional deuteration applied to biomolecular solid-state NMR spectroscopy

Solid-state Nuclear Magnetic Resonance can provide detailed insight into structural and dynamical aspects of complex biomolecules. With increasing molecular size, advanced approaches for spectral simplification and the detection of medium to long-range contacts become of critical relevance. We have analyzed the protonation pattern of a membrane-embedded ion channel that was obtained from bacterial expression using protonated precursors and D2O medium. We find an overall reduction of 50% in protein protonation. High levels of deuteration at Hα and Hβ positions reduce spectral congestion in (1H,13C,15N) correlation experiments and generate a transfer profile in longitudinal mixing schemes that can be tuned to specific resonance frequencies. At the same time, residual protons are predominantly found at amino-acid side-chain positions enhancing the prospects for obtaining side-chain resonance assignments and for detecting medium to long-range contacts. Fractional deuteration thus provides a powerful means to aid the structural analysis of complex biomolecules by solid-state NMR

Integrating BDI agents with Agent-based simulation platforms

Agent-Based Models (ABMs) is increasingly being used for exploring and supporting decision making about social science scenarios involving modelling of human agents. However existing agent-based simulation platforms (e.g., SWARM, Repast) provide limited support for the simulation of more complex cognitive agents required by such scenarios. We present a framework that allows Belief-Desire Intention (BDI) cognitive agents to be embedded in an ABM system. Architecturally, this means that the "brains" of an agent can be modelled in the BDI system in the usual way, while the "body" exists in the ABM system. The architecture is exible in that the ABM can still have non-BDI agents in the simulation, and the BDI-side can have agents that do not have a physical counterpart (such as an organisation). The framework addresses a key integration challenge of coupling event-based BDI systems, with time-stepped ABM systems. Our framework is modular and supports integration off-the-shelf BDI systems with off-the-shelf ABM systems. The framework is Open Source, and all integrations and applications are available for use by the modelling community

Service planning and delivery outcomes of home adaptations for ageing in the UK

In response to the impact of demographic change on the healthcare system, ‘ageing in place’ was introduced as a national policy to support elderly people living independently in their homes. Housing adaptation is essential for successful independent living and has been given increased political priority. However, adaptation policies and practice vary regionally, reflecting statutory limits, policy choices and local planning. This study investigated the current status of adaptation provision in different regions in the UK and assessed the effectiveness of local service planning and management. A mixed-methods sequential explanatory research strategy was employed. In the first quantitative phase, a questionnaire survey was carried out involving all 378 local authorities in England, Scotland and Wales. This was followed by a second qualitative phase involving individual interviews with five professionals and two clients and a focus group meeting with six key stakeholders. The study found that the current number of adaptations was relatively small compared with potential demands in most local areas, as was funding for adaptations. On the operational side, the adaptation process was fragmented, involving different service groups in many local authorities. There were disconnections between these groups, which often caused inefficiencies and poor effectiveness. Moving forward, local authorities need to have a clear vision of the overall need for adaptations and allocate sufficient resources. Practical guidelines are also needed for better integrated working and performance management

The effect of lengthening contractions on neuromuscular junction structure in adult and old mice

Skeletal muscles of old mice demonstrate a profound inability to regenerate fully following damage. Such a failure could be catastrophic to older individuals where muscle loss is already evident. Degeneration and regeneration of muscle fibres following contraction-induced injury in adult and old mice are well characterised, but little is known about the accompanying changes in motor neurons and neuromuscular junctions (NMJs) following this form of injury although defective re-innervation of muscle following contraction-induced damage has been proposed to play a role in sarcopenia. This study visualised and quantified structural changes to motor neurons and NMJs in Extensor digitorum longus (EDL) muscles of adult and old Thy1-YFP transgenic mice during regeneration following contraction-induced muscle damage. Data demonstrated that the damaging contraction protocol resulted in substantial initial disruption to NMJs in muscles of adult mice, which was reversed entirely within 28 days following damage. In contrast, in quiescent muscles of old mice, ∼15 % of muscle fibres were denervated and ∼80 % of NMJs showed disruption. This proportion of denervated and partially denervated fibres remained unchanged following recovery from contraction-induced damage in muscles of old mice although ∼25 % of muscle fibres were completely lost by 28 days post-contractions. Thus, in old mice, the failure to restore full muscle force generation that occurs following damage does not appear to be due to any further deficit in the percentage of disrupted NMJs, but appears to be due, at least in part, to the complete loss of muscle fibres following damag