Myocardial Fibrosis in Heart Failure: Anti-Fibrotic Therapies and the Role of Cardiovascular Magnetic Resonance in Drug Trials

All heart muscle diseases that cause chronic heart failure finally converge into one dreaded pathological process that is myocardial fibrosis. Myocardial fibrosis predicts major adverse cardiovascular events and death, yet we are still missing the targeted therapies capable of halting and/or reversing its progression. Fundamentally it is a problem of disproportionate extracellular collagen accumulation that is part of normal myocardial ageing and accentuated in certain disease states. In this article we discuss the role of cardiovascular magnetic resonance (CMR) imaging biomarkers to track fibrosis and collate results from the most promising animal and human trials of anti-fibrotic therapies to date. We underscore the ever-growing role of CMR in determining the efficacy of such drugs and encourage future trialists to turn to CMR when designing their surrogate study endpoints

Efficient HTTP based I/O on very large datasets for high performance computing with the libdavix library

Remote data access for data analysis in high performance computing is commonly done with specialized data access protocols and storage systems. These protocols are highly optimized for high throughput on very large datasets, multi-streams, high availability, low latency and efficient parallel I/O. The purpose of this paper is to describe how we have adapted a generic protocol, the Hyper Text Transport Protocol (HTTP) to make it a competitive alternative for high performance I/O and data analysis applications in a global computing grid: the Worldwide LHC Computing Grid. In this work, we first analyze the design differences between the HTTP protocol and the most common high performance I/O protocols, pointing out the main performance weaknesses of HTTP. Then, we describe in detail how we solved these issues. Our solutions have been implemented in a toolkit called davix, available through several recent Linux distributions. Finally, we describe the results of our benchmarks where we compare the performance of davix against a HPC specific protocol for a data analysis use case.Comment: Presented at: Very large Data Bases (VLDB) 2014, Hangzho

Infection prevention and control compliance in Tanzanian outpatient facilities: a cross-sectional study with implications for the control of COVID-19.

BACKGROUND: As coronavirus disease 2019 (COVID-19) spreads, weak health systems must not become a vehicle for transmission through poor infection prevention and control practices. We assessed the compliance of health workers with infection prevention and control practices relevant to COVID-19 in outpatient settings in Tanzania, before the pandemic. METHODS: This study was based on a secondary analysis of cross-sectional data collected as part of a randomised controlled trial in private for-profit dispensaries and health centres and in faith-based dispensaries, health centres, and hospitals, in 18 regions. We observed provider-patient interactions in outpatient consultation rooms, laboratories, and dressing rooms, and categorised infection prevention and control practices into four domains: hand hygiene, glove use, disinfection of reusable equipment, and waste management. We calculated compliance as the proportion of indications (infection risks) in which a health worker performed a correct action, and examined associations between compliance and health worker and facility characteristics using multilevel mixed-effects logistic regression models. FINDINGS: Between Feb 7 and April 5, 2018, we visited 228 health facilities, and observed at least one infection prevention and control indication in 220 facilities (118 [54%] dispensaries, 66 [30%] health centres, and 36 [16%] hospitals). 18 710 indications were observed across 734 health workers (49 [7%] medical doctors, 214 [29%] assistant medical officers or clinical officers, 106 [14%] nurses or midwives, 126 [17%] clinical assistants, and 238 [32%] laboratory technicians or assistants). Compliance was 6·9% for hand hygiene (n=8655 indications), 74·8% for glove use (n=4915), 4·8% for disinfection of reusable equipment (n=841), and 43·3% for waste management (n=4299). Facility location was not associated with compliance in any of the infection prevention and control domains. Facility level and ownership were also not significantly associated with compliance, except for waste management. For hand hygiene, nurses and midwives (odds ratio 5·80 [95% CI 3·91-8·61]) and nursing and medical assistants (2·65 [1·67-4·20]) significantly outperformed the reference category of assistant medical officers or clinical officers. For glove use, nurses and midwives (10·06 [6·68-15·13]) and nursing and medical assistants (5·93 [4·05-8·71]) also significantly outperformed the reference category. Laboratory technicians performed significantly better in glove use (11·95 [8·98-15·89]), but significantly worse in hand hygiene (0·27 [0·17-0·43]) and waste management (0·25 [0·14-0·44] than the reference category. Health worker age was negatively associated with correct glove use and female health workers were more likely to comply with hand hygiene. INTERPRETATION: Health worker infection prevention and control compliance, particularly for hand hygiene and disinfection, was inadequate in these outpatient settings. Improvements in provision of supplies and health worker behaviours are urgently needed in the face of the current pandemic. FUNDING: UK Medical Research Council, Economic and Social Research Council, Department for International Development, Global Challenges Research Fund, Wellcome Trust

Conceptualizing cultures of violence and cultural change

The historiography of violence has undergone a distinct cultural turn as attention has shifted from examining violence as a clearly defined (and countable) social problem to analysing its historically defined 'social meaning'. Nevertheless, the precise nature of the relationship between 'violence' and 'culture' is still being established. How are 'cultures of violence' formed? What impact do they have on violent behaviour? How do they change? This essay examines some of the conceptual aspects of the relationship between culture and violence. It brings together empirical research into nineteenth-century England with recent research results from other European contexts to examine three aspects of the relationship between culture and violence. These are organised under the labels 'seeing violence', 'identifying the violent' and 'changing violence'. Within a particular society, narratives regarding particular kinds of behaviour shape cultural attitudes. The notion 'violence' is thus defined in relation to physically aggressive acts as well as by being connected to other kinds of attitudes and contexts. As a result, the boundaries between physical aggression which is legitimate and that which is illegitimate (and thus 'violence') are set. Once 'violence' is defined, particular cultures form ideas about who is responsible for it: reactions to violence become associated with social arrangements such as class and gender as well as to attitudes toward the self. Finally, cultures of violence make efforts to tame or eradicate illegitimate forms of physical aggression. This process is not only connected to the development of new forms of power (e.g., new policing or punishment strategies) but also to less tangible cultural influences which aim at changing the behaviour defined as violence (in particular among the social groups identified as violent). Even if successful, this three-tiered process of seeing violence, identifying the violent and changing violence continues anew, emphasising the ways that cultures of violence develop through a continuous process of reevaluation and reinvention

Antibacterial Composite Materials Based on the Combination of Polyhydroxyalkanoates With Selenium and Strontium Co-substituted Hydroxyapatite for Bone Regeneration.

Due to the threat posed by the rapid growth in the resistance of microbial species to antibiotics, there is an urgent need to develop novel materials for biomedical applications capable of providing antibacterial properties without the use of such drugs. Bone healing represents one of the applications with the highest risk of postoperative infections, with potential serious complications in case of bacterial contaminations. Therefore, tissue engineering approaches aiming at the regeneration of bone tissue should be based on the use of materials possessing antibacterial properties alongside with biological and functional characteristics. In this study, we investigated the combination of polyhydroxyalkanoates (PHAs) with a novel antimicrobial hydroxyapatite (HA) containing selenium and strontium. Strontium was chosen for its well-known osteoinductive properties, while selenium is an emerging element investigated for its multi-functional activity as an antimicrobial and anticancer agent. Successful incorporation of such ions in the HA structure was obtained. Antibacterial activity against Staphylococcus aureus 6538P and Escherichia coli 8739 was confirmed for co-substituted HA in the powder form. Polymer-matrix composites based on two types of PHAs, P(3HB) and P(3HO-co-3HD-co-3HDD), were prepared by the incorporation of the developed antibacterial HA. An in-depth characterization of the composite materials was conducted to evaluate the effect of the filler on the physicochemical, thermal, and mechanical properties of the films. In vitro antibacterial testing showed that the composite samples induce a high reduction of the number of S. aureus 6538P and E. coli 8739 bacterial cells cultured on the surface of the materials. The films are also capable of releasing active ions which inhibited the growth of both Gram-positive and Gram-negative bacteria

Assessing cognitive dysfunction in Parkinson's disease: An online tool to detect visuo-perceptual deficits.

BackgroundPeople with Parkinson's disease (PD) who develop visuo-perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuo-perceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo-perceptual deficits in PD.ObjectiveWe developed an online platform to test visuo-perceptual function. We hypothesised that (1) visuo-perceptual deficits in PD could be detected using online tests, (2) object perception would be preferentially affected, and (3) these deficits would be caused by changes in perception rather than response bias.MethodsWe assessed 91 people with PD and 275 controls. Performance was compared using classical frequentist statistics. We then fitted a hierarchical Bayesian signal detection theory model to a subset of tasks.ResultsPeople with PD were worse than controls at object recognition, showing no deficits in other visuo-perceptual tests. Specifically, they were worse at identifying skewed images (P < .0001); at detecting hidden objects (P = .0039); at identifying objects in peripheral vision (P < .0001); and at detecting biological motion (P = .0065). In contrast, people with PD were not worse at mental rotation or subjective size perception. Using signal detection modelling, we found this effect was driven by change in perceptual sensitivity rather than response bias.ConclusionsOnline tests can detect visuo-perceptual deficits in people with PD, with object recognition particularly affected. Ultimately, visuo-perceptual tests may be developed to identify at-risk patients for clinical trials to slow PD dementia. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Concurrent adaptation to opposing visual displacements during an alternating movement.

It has been suggested that, during tasks in which subjects are exposed to a visual rotation of cursor feedback, alternating bimanual adaptation to opposing rotations is as rapid as unimanual adaptation to a single rotation (Bock et al. in Exp Brain Res 162:513–519, 2005). However, that experiment did not test strict alternation of the limbs but short alternate blocks of trials. We have therefore tested adaptation under alternate left/right hand movement with opposing rotations. It was clear that the left and right hand, within the alternating conditions, learnt to adapt to the opposing displacements at a similar rate suggesting that two adaptive states were formed concurrently. We suggest that the separate limbs are used as contextual cues to switch between the relevant adaptive states. However, we found that during online correction the alternating conditions had a significantly slower rate of adaptation in comparison to the unimanual conditions. Control conditions indicate that the results are not directly due the alternation between limbs or to the constant switching of vision between the two eyes. The negative interference may originate from the requirement to dissociate the visual information of these two alternating displacements to allow online control of the two arms

LiftUpp: Support to Develop Learner Performance

Various motivations exist to move away from the simple assessment of knowledge towards the more complex assessment and development of competence. However, to accommodate such a change, high demands are put on the supporting e-infrastructure in terms of intelligently collecting and analysing data. In this paper, we discuss these challenges and how they are being addressed by LiftUpp, a system that is now used in 70% of UK dental schools, and is finding wider applications in physiotherapy, medicine and veterinary science. We describe how data is collected for workplace-based development in dentistry using a dedicated iPad app, which enables an integrated approach to linking and assessing work flows, skills and learning outcomes. Furthermore, we detail how the various forms of collected data can be fused, visualized and integrated with conventional forms of assessment. This enables curriculum integration, improved real-time student feedback, support for administration, and informed instructional planning. Together these facets contribute to better support for the development of learners' competence in situated learning setting, as well as an improved experience. Finally, we discuss several directions for future research on intelligent teaching systems that are afforded by using the design present within LiftUpp.Comment: Short 4-page version to appear at AIED 201