The Influence of Unilateral Electrical Muscle Stimulation on Motor Unit Activity Patterns in Atrophic Human Quadriceps

The efficacy of electrical muscle stimulation to restore motor function was investigated in fifteen males who described prior knee surgery/injury. Persisting strength imbalance between limbs related also to reduction in cross-sectional area of the affected quadriceps, as assessed by computed tomography of the midthigh. Subjects underwent a four-week programme of daily electro-motor stimulation with repeated assessment of force production by the knee extensors, correlated with surface electro-myography. Results showed no change in quadriceps cross-sectional area over the course of the study, however, significant improvements in force production for both limbs were achieved, accompanied by alteration in motor unit activity patterns to suggest that neural efficiency of motor unit activation (synchronization) may account for the improvements, as opposed to a marked morphological contribution

The impact of vaccination on COVID-19 Outbreaks in the United States

Background: Global vaccine development efforts have been accelerated in response to the devastating COVID-19 pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States (US). Methods: We developed an agent-based model of SARS-CoV-2 transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, while children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection, and specified 10% pre-existing population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current non-pharmaceutical interventions in the US. Results: Vaccination reduced the overall attack rate to 4.6% (95% CrI: 4.3% - 5.0%) from 9.0% (95% CrI: 8.4% - 9.4%) without vaccination, over 300 days. The highest relative reduction (54-62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-ICU hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3% - 66.7%), 65.6% (95% CrI: 62.2% - 68.6%), and 69.3% (95% CrI: 65.5% - 73.1%), respectively, across the same period. Conclusions: Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with non-pharmaceutical interventions is essential to achieve this impact.Integrative Biolog

Setting the standard: multidisciplinary hallmarks for structural, equitable and tracked antibiotic policy

There is increasing concern globally about the enormity of the threats posed by antimicrobial resistance (AMR) to human, animal, plant and environmental health. A proliferation of international, national and institutional reports on the problems posed by AMR and the need for antibiotic stewardship have galvanised attention on the global stage. However, the AMR community increasingly laments a lack of action, often identified as an ‘implementation gap’. At a policy level, the design of internationally salient solutions that are able to address AMR’s interconnected biological and social (historical, political, economic and cultural) dimensions is not straightforward. This multidisciplinary paper responds by asking two basic questions: (A) Is a universal approach to AMR policy and antibiotic stewardship possible? (B) If yes, what hallmarks characterise ‘good’ antibiotic policy? Our multistage analysis revealed four central challenges facing current international antibiotic policy: metrics, prioritisation, implementation and inequality. In response to this diagnosis, we propose three hallmarks that can support robust international antibiotic policy. Emerging hallmarks for good antibiotic policies are: Structural, Equitable and Tracked. We describe these hallmarks and propose their consideration should aid the design and evaluation of international antibiotic policies with maximal benefit at both local and international scale

Three Novel Downstream Promoter Elements Regulate MHC Class I Promoter Activity in Mammalian Cells

BACKGROUND: MHC CLASS I TRANSCRIPTION IS REGULATED BY TWO DISTINCT TYPES OF REGULATORY PATHWAYS: 1) tissue-specific pathways that establish constitutive levels of expression within a given tissue and 2) dynamically modulated pathways that increase or decrease expression within that tissue in response to hormonal or cytokine mediated stimuli. These sets of pathways target distinct upstream regulatory elements, have distinct basal transcription factor requirements, and utilize discrete sets of transcription start sites within an extended core promoter. METHODOLOGY/PRINCIPAL FINDINGS: We studied regulatory elements within the MHC class I promoter by cellular transfection and in vitro transcription assays in HeLa, HeLa/CIITA, and tsBN462 of various promoter constructs. We have identified three novel MHC class I regulatory elements (GLE, DPE-L1 and DPE-L2), located downstream of the major transcription start sites, that contribute to the regulation of both constitutive and activated MHC class I expression. These elements located at the 3' end of the core promoter preferentially regulate the multiple transcription start sites clustered at the 5' end of the core promoter. CONCLUSIONS/SIGNIFICANCE: Three novel downstream elements (GLE, DPE-L1, DPE-L2), located between +1 and +32 bp, regulate both constitutive and activated MHC class I gene expression by selectively increasing usage of transcription start sites clustered at the 5' end of the core promoter upstream of +1 bp. Results indicate that the downstream elements preferentially regulate TAF1-dependent, relative to TAF1-independent, transcription

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

‘Race’ Talk! Tensions and Contradictions in Sport and PE

Background: The universal sport discourses of inclusion, belonging, meritocracy, agency, and equality are so widespread that few challenge them. It is clear from the most cursory interest in sport, PE and society that the lived reality is quite different and ambiguous. Racial disparities in the leadership and administration of sport are commonplace world wide; yet from research into ‘race’ in sport and PE the public awareness of these issues is widespread, where many know that racism takes place it is always elsewhere For many this racism is part of the game and something that enables an advantage to be stolen, for others it is trivial and not worthy of deeper thought. This paper explores the contradictions and tensions of the author’s experience of how sport and PE students talk about ‘race’. ‘Race’ talk is considered here in the context of passive everyday ‘race’ talk, dominant discourses in sporting cultures, and colour-blindness. This paper focuses on the pernicious yet persistent nature of ‘race’ talk while demystifying its multifarious, spurious, and more persuasive daily iterations. Theoretical framework: Drawing on Guinier and Torres’ (2003) ideas of resistance through political race consciousness and Bonilla-Silva’s (2010) notion of colour-blindness the semantics of ‘race’ and racialisation in sport and PE are interrogated through the prism of Critical Race Theory (CRT). Critical race scholarship has been used in sport and PE to articulate a political application of ‘race’ as a starting point for critical activism, to disrupt whiteness, and to explore the implications of ‘race’ and racism. CRT is used here to centre ‘race’ and racialised relations where disciplines have consciously or otherwise excluded them. Importantly, the centreing of ‘race’ by critical race scholars has advanced a strategic and pragmatic engagement with this slippery concept that recognises its paradoxical but symbolic location in social relations. Discussion: Before exploring ‘race’ talk in the classroom, using images from the sport media as a pedagogical tool, the paper considers how effortlessly ‘race’ is recreated and renewed. The paper then turns to explore how the effortless turn to everyday ‘race’ talk in the classroom can be viewed as an opportunity to disrupt common racialised assumptions with the potential to implicate those that passively engage in it. Further the diagnostic, aspirational and activist goals of political race consciousness are established as vehicles for a positive sociological experience in the classroom. Conclusion: The work concludes with a pragmatic consideration of the uses and dangers of passive everyday ‘race’ talk and the value of a political race consciousness in sport and PE. Part of the explanation for the perpetuation of ‘race’ talk and the relative lack of concern with its impact in education and wider society is focused on how the sovereignty of sport and PE trumps wider social concerns of ‘race’ and racism because of at least four factors 1) the liberal left discourses of sporting utopianism 2) the ‘race’ logic that pervades sport, based upon the perceived equal access and fairness of sport as it coalesces with the, 3) 'incontrovertible facts' of black and white superiority [and inferiority] in certain sports, ergo the racial justifications for patterns of activity in sport and PE 4) the racist logic of the Right perpetuated through a biological reductionism in sport and PE discourses. Keywords: ‘Race’ Talk; Critical Race Theory; Political Race Consciousnes

Search for gravitational waves associated with the InterPlanetary Network short gamma ray bursts

We outline the scientific motivation behind a search for gravitational waves associated with short gamma ray bursts detected by the InterPlanetary Network (IPN) during LIGO's fifth science run and Virgo's first science run. The IPN localisation of short gamma ray bursts is limited to extended error boxes of different shapes and sizes and a search on these error boxes poses a series of challenges for data analysis. We will discuss these challenges and outline the methods to optimise the search over these error boxes.Comment: Methods paper; Proceedings for Eduardo Amaldi 9 Conference on Gravitational Waves, July 2011, Cardiff, U

Past as global trade governance prelude: reconfiguring debate about reform of the multilateral trading system

This paper peers backwards into the history of the multilateral trading system and its development over the past half century as a means of considering what may lie beyond the horizon for the future of global trade governance. Its purpose is to underscore the necessity and urgency for root-and-branch reform of the multilateral trading system. It achieves this by comparing and contrasting the global trading system of 50 years ago with its modern-day equivalent and its likely future counterpart half-a-century hence. In so doing, the paper throws into sharp relief not only the inadequacies of global trade governance today but also the damaging consequences of not fundamentally reforming the system in the near future, with a particular emphasis on the past, present and future development of the world’s poorest and most marginalised countries

Community-Centered Responses to Ebola in Urban Liberia: The View from Below

The West African Ebola epidemic has demonstrated that the existing range of medical and epidemiological responses to emerging disease outbreaks is insufficient, especially in post-conflict contexts with exceedingly poor healthcare infrastructures. This study provides baseline information on community-based epidemic control priorities and identifies innovative local strategies for containing EVD in Liberia.In this study the authors analyzed data from the 2014 Ebola outbreak in Monrovia and Montserrado County, Liberia. The data were collected for the purposes of program design and evaluation by the World Health Organization (WHO) and the Government of Liberia (GOL), in order to identify: (1) local knowledge about EVD, (2) local responses to the outbreak, and (3) community based innovations to contain the virus. At the time of data collection, the international Ebola response had little insight into how much local Liberian communities knew about Ebola, and how communities managed the epidemic when they could not get access to care due to widespread hospital and clinic closures. Methods included 15 focus group discussions with community leaders from areas with active Ebola cases. Participants were asked about best practices and what they were currently doing to manage EVD in their respective communities, with the goal of developing conceptual models of local responses informed by local narratives. Findings reveal that communities responded to the outbreak in numerous ways that both supported and discouraged formal efforts to contain the spread of the disease. This research will inform global health policy for both this, and future, epidemic and pandemic responses