Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity

New Findings

What is the central question of this study?Exercise performance is limited during hypoxia by a critical reduction in cerebral and skeletal tissue oxygenation. To what extent an elevation in systemic free radical accumulation contributes to microvascular deoxygenation and the corresponding reduction in maximal aerobic capacity remains unknown.What is the main finding and its importance?We show that altered free radical metabolism is not a limiting factor for exercise performance in hypoxia, providing important insight into the fundamental mechanisms involved in the control of vascular oxygen transport.

Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduced maximal aerobic capacity (). Eleven healthy men were randomly assigned single-blind to an incremental semi-recumbent cycling test to determine  in both normoxia (21% O_{2) and hypoxia (12% O2) separated by a week. Continuous-wave near-infrared spectroscopy was employed to monitor concentration changes in oxy- and deoxyhaemoglobin in the left vastus lateralis muscle and frontal cerebral cortex. Antecubital venous blood samples were obtained at rest and at  to determine oxidative (ascorbate radical by electron paramagnetic resonance spectroscopy), nitrosative (nitric oxide metabolites by ozone-based chemiluminescence and 3-nitrotyrosine by enzyme-linked immunosorbent assay) and inflammatory stress biomarkers (soluble intercellular/vascular cell adhesion 1 molecules by enzyme-linked immunosorbent assay). Hypoxia was associated with increased cerebral and muscle tissue deoxygenation and lower  (P < 0.05 versus normoxia). Despite an exercise-induced increase in oxidative–nitrosative–inflammatory stress, hypoxia per se did not have an additive effect (P > 0.05 versus normoxia). Consequently, we failed to observe correlations between any metabolic, haemodynamic and cardiorespiratory parameters (P > 0.05). Collectively, these findings suggest that altered free radical metabolism cannot explain the elevated microvascular deoxygenation and corresponding lower  in hypoxia. Further research is required to determine whether free radicals when present in excess do indeed contribute to the premature termination of exercise in hypoxia.}

Portraying Human Dignity

I consider whether Diego Velázquez (1599-1660) in his painting Las Meninas has conveyed several aspects of the idea of human dignity in ways that not only echo some aspects of contemporary philosophical and legal analysis, but transcend them, bringing into our understanding aspects of dignity, and the controversy surrounding it, that otherwise might be underestimated.

Adaptive utilitarianism, social enterprises and urban regeneration

Social enterprises have been placed at the centre of Big Society politics and an emphasis on the local as a site for experimentation and service delivery. Nationally, this has been supported by legislation in community transfer and procurement, social finance and new intermediaries to strengthen skills and loan readiness. This paper examines the role of social enterprises involved in urban development in Northern Ireland and highlights the multiple ethics, legitimation strategies and modalities that are necessary for sustainable forms of progressive regeneration. The paper concludes by stressing the possibilities of a more independent and reformist social economy and how this offers some practical alternatives to the enthusiasm for neoliberal policies in the local state.

Seven key actions to eradicate rheumatic heart disease in Africa: the Addis Ababa communiqué

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain major causes of heart failure, stroke and death among African women and children, despite being preventable and imminently treatable. From 21 to 22 February 2015, the Social Cluster of the Africa Union Commission (AUC) hosted a consultation with RHD experts convened by the Pan-African Society of Cardiology (PASCAR) in Addis Ababa, Ethiopia, to develop a 'roadmap' of key actions that need to be taken by governments to eliminate ARF and eradicate RHD in Africa. Seven priority areas for action were adopted: (1) create prospective disease registers at sentinel sites in affected countries to measure disease burden and track progress towards the reduction of mortality by 25% by the year 2025, (2) ensure an adequate supply of high-quality benzathine penicillin for the primary and secondary prevention of ARF/RHD, (3) improve access to reproductive health services for women with RHD and other non-communicable diseases (NCD), (4) decentralise technical expertise and technology for diagnosing and managing ARF and RHD (including ultrasound of the heart), (5) establish national and regional centres of excellence for essential cardiac surgery for the treatment of affected patients and training of cardiovascular practitioners of the future, (6) initiate national multi-sectoral RHD programmes within NCD control programmes of affected countries, and (7) foster international partnerships with multinational organisations for resource mobilisation, monitoring and evaluation of the programme to end RHD in Africa. This Addis Ababa communiqué has since been endorsed by African Union heads of state, and plans are underway to implement the roadmap in order to end ARF and RHD in Africa in our lifetime.

Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study)

AIMS: Rheumatic heart disease (RHD) accounts for over a million premature deaths annually; however, there is little contemporary information on presentation, complications, and treatment.

METHODS AND RESULTS: This prospective registry enrolled 3343 patients (median age 28 years, 66.2% female) presenting with RHD at 25 hospitals in 12 African countries, India, and Yemen between January 2010 and November 2012. The majority (63.9%) had moderate-to-severe multivalvular disease complicated by congestive heart failure (33.4%), pulmonary hypertension (28.8%), atrial fibrillation (AF) (21.8%), stroke (7.1%), infective endocarditis (4%), and major bleeding (2.7%). One-quarter of adults and 5.3% of children had decreased left ventricular (LV) systolic function; 23% of adults and 14.1% of children had dilated LVs. Fifty-five percent (n = 1761) of patients were on secondary antibiotic prophylaxis. Oral anti-coagulants were prescribed in 69.5% (n = 946) of patients with mechanical valves (n = 501), AF (n = 397), and high-risk mitral stenosis in sinus rhythm (n = 48). However, only 28.3% (n = 269) had a therapeutic international normalized ratio. Among 1825 women of childbearing age (12-51 years), only 3.6% (n = 65) were on contraception. The utilization of valvuloplasty and valve surgery was higher in upper-middle compared with lower-income countries.

CONCLUSION: Rheumatic heart disease patients were young, predominantly female, and had high prevalence of major cardiovascular complications. There is suboptimal utilization of secondary antibiotic prophylaxis, oral anti-coagulation, and contraception, and variations in the use of percutaneous and surgical interventions by country income level.

Assessment of the impact speed and angle conditions for the EN1317 barrier tests

Roadside safety barriers designs are tested with passenger cars in Europe using standard EN1317 in which the impact angle for normal, high and very high containment level tests is 20°. In comparison to EN1317, the US standard MASH has higher impact angles for cars and pickups (25°) and different vehicle masses. Studies in Europe (RISER) and the US have shown values for the 90th percentile impact angle of 30°–34°. Thus, the limited evidence available suggests that the 20° angle applied in EN 1317 may be too low.
The first goal of this paper is to use the US NCHRP database (Project NCHRP 17–22) to assess the distribution of impact angle and collision speed in recent ROR accidents. Second, based on the findings of the statistical analysis and on analysis of impact angles and speeds in the literature, an LS-DYNA finite element analysis was carried out to evaluate the normal containment level of concrete barriers in non-standard collisions. The FE model was validated against a crash test of a portable concrete barrier carried out at the UK Transport Research Laboratory (TRL).
The accident data analysis for run-off road accidents indicates that a substantial proportion of accidents have an impact angle in excess of 20°. The baseline LS-DYNA model showed good comparison with experimental acceleration severity index (ASI) data and the parametric analysis indicates a very significant influence of impact angle on ASI. Accordingly, a review of European run-off road accidents and the configuration of EN 1317 should be performed.

Comparison of Parallelised R-matrix codes for electron impact excitation of Cr II

A comparison of collision strengths and effective collision strengths has been undertaken for the Cr II ion based on the model of Wasson et al [2010 A & A. 524 A35]. Calculations have been completed using the Breit-Pauli, RMATRX II and DARC suites of codes.

Peace by Piece: (Re) imagining Division in Belfast’s Contested Spaces through Memory

This paper investigates processes and actions of diversifying memories of division in Northern Ireland’s political conflict known as the Troubles. Societal division is manifested in its built fabric and territories that have been adopted by predominant discourses of a fragmented society in Belfast; the unionist east and the nationalist west. The aim of the paper is to explore current approaches in planning contested spaces that have changed over time, leading to success in many cases. The argument is that divided cities, like Belfast, feature spatial images and memories of division that range from physical, clear-cut segregation to manifested actions of violence and have become influential representations in the community’s associative memory. While promoting notions of ‘re-imaging’ by current councils demonstrates a total erasure of the Troubles through cleansing its local collective memory, there yet remains an attempt to communicate a different tale of the city’s socio-economic past, to elaborate its supremacy for shaping future lived memories. Yet, planning Belfast’s contested areas is still suffering from a poor understanding of the context and its complexity against overambitious visions.