Animal models of ischaemic stroke and characterisation of the ischaemic penumbra

Over the past forty years, animal models of focal cerebral ischaemia have allowed us to identify the critical cerebral blood flow thresholds responsible for irreversible cell death, electrical failure, inhibition of protein synthesis, energy depletion and thereby the lifespan of the potentially salvageable penumbra. They have allowed us to understand the intricate biochemical and molecular mechanisms within the ‘ischaemic cascade’ that initiate cell death in the first minutes, hours and days following stroke. Models of permanent, transient middle cerebral artery occlusion and embolic stroke have been developed each with advantages and limitations when trying to model the complex heterogeneous nature of stroke in humans. Yet despite these advances in understanding the pathophysiological mechanisms of stroke-induced cell death with numerous targets identified and drugs tested, a lack of translation to the clinic has hampered pre-clinical stroke research. With recent positive clinical trials of endovascular thrombectomy in acute ischaemic stroke the stroke community has been reinvigorated, opening up the potential for future translation of adjunctive treatments that can be given alongside thrombectomy/thrombolysis. This review discusses the major animal models of focal cerebral ischaemia highlighting their advantages and limitations. Acute imaging is crucial in longitudinal pre-clinical stroke studies in order to identify the influence of acute therapies on tissue salvage over time. Therefore, the methods of identifying potentially salvageable ischaemic penumbra are discussed

Cardio classics revisited: focus on the role of amlodipine

Amlodipine is a long-acting, dihydropyridine calcium antagonist now widely used for lowering of elevated blood pressure. In recent years it has been shown to be effective in reducing both blood pressure and risk of cardiovascular (CV) events when used in combination with other antihypertensive agents of different classes. Strong evidence of cardiovascular benefit has been attained for combination of amlodipine with diuretics or angiotensin converting enzyme (ACE) inhibitors in a number of high-risk CV groups, including those with established coronary artery disease, diabetes, and at risk of renal disease. Combination therapies of amlodipine with other agents eliciting renin-angiotensin-aldosterone system blockade (angiotensin II receptor blockers or renin inhibitors) have been shown to be effective blood pressure-lowering strategies, but await the results of ongoing trials for direct evidence of benefit for renal disease progression and CV morbidity and mortality

Feasibility Assessment of an EVA Glove Sensing Platform to Evaluate Potential Hand Injury Risk Factors

Injuries to the hands are common among astronauts who train for extravehicular activity (EVA). When the gloves are pressurized, they restrict movement and create pressure points during tasks, sometimes resulting in pain, muscle fatigue, abrasions, and occasionally more severe injuries such as onycholysis. A brief review of the Lifetime Surveillance of Astronaut Health's injury database reveals that 58% of total astronaut hand and arm injuries from NBL training between 1993 and 2010 occurred either to the fingernail, MCP, or fingertip. The purpose of this study was to assess the potential of using small sensors to measure force acting on the fingers and hand within pressurized gloves and other variables such as blood perfusion, skin temperature, humidity, fingernail strain, skin moisture, among others. Tasks were performed gloved and ungloved in a pressurizable glove box. The test demonstrated that fingernails saw greater transverse strain levels for tension or compression than for longitudinal strain, even during axial fingertip loading. Blood perfusion peaked and dropped as the finger deformed during finger presses, indicating an initial dispersion and decrease of blood perfusion levels. Force sensitive resistors to force plate comparisons showed similar force curve patterns as fingers were depressed, indicating suitable functionality for future testing. Strategies for proper placement and protection of these sensors for ideal data collection and longevity through the test session were developed and will be implemented going forward for future testing

Effectiveness of blood pressure-lowering drug treatment by levels of absolute risk: Post hoc analysis of the Australian National Blood Pressure Study

Objectives: In many current guidelines, blood pressure (BP)-lowering drug treatment for primary prevention of cardiovascular disease (CVD) is based on absolute risk. However, in clinical practice, therapeutic decisions are often based on BP levels alone. We sought to investigate which approach was superior by conducting a post hoc analysis of the Australian National Blood Pressure (ANBP) cohort, a seminal study establishing the efficacy of BP lowering in mild hypertensive' persons. Design: A post hoc subgroup analysis of the ANBP trial results by baseline absolute risk tertile. Setting and participants: 3244 participants aged 35-69 years in a community-based randomised placebo controlled trial of blood pressure-lowering medication. Interventions Chlorothiazide500 mg versus placebo. Primary outcome measures All-cause mortality and non-fatal events (non-fatal CVD, congestive cardiac failure, renal failure, hypertensive retinopathy or encephalopathy). Results: Treatment effects were assessed by HR, absolute risk reduction and number needed to treat. Participants had an average 5-year CVD risk in the intermediate range (10.5±6.5) with moderately elevated BP (mean 159/103 mmHg) and were middle aged (52±8 years). In a subgroup analysis, the relative effects (HR) and absolute effects (absolute risk reduction and number needed to treat) did not statistically differ across the three risk groups except for the absolute benefit in all-cause mortality (p for heterogeneity=0.04). With respect to absolute benefit, drug treatment significantly reduced the number of events in the high-risk group regarding any event with a number needed to treat of 18 (10 to 64), death from any cause with 45 (25 to 196) and major CVD events with 23 (12 to 193). Conclusion: Our analysis confirms that the benefit of treatment was substantial only in the high-risk tertile, reaffirming the rationale of treating elevated blood pressure in the setting of all risk factors rather than in isolation

Social Presence in Online Counselor Education

Outcome research in online counselor education is lacking as is the focus on online teaching andragogy. To address this gap, the Community of Inquiry framework and social presence are discussed within the context of online learning in a counselor education program. Data were collected in a counselor education program in the mid-Atlantic comparing online and on-campus learning outcomes and perceptions of social presence in the classroom. On-campus learners had significantly higher perceptions of social presence when compared with online learners, although perceived level of social presence was not correlated with learning outcomes. Implications for counselor education are discussed

Multi-Reward Learning and Sparse Rewards

Reinforcement learning has made impressive strides in solving problems in challenging domains, but problems are increasingly being described with sparse rewards. Sparse rewards directly reduce the rate at which useful feedback is provided to the learner and make it difficult to distinguish between what specific actions led to the reception of a reward. This greatly reduces the speed of learning or completely thwarts attempts at learning completely. Some combat the difficulty of learning under sparsity by using multi-reward schemes. These schemes utilize more rewards than just the true system evaluation by doing things like providing exploration incentives or abstracting away a hierarchy of policies, each with different rewards. There are also further techniques that do not rely on multiple rewards, such as reward shaping or transfer learning. A key insight is that these techniques mentioned are orthogonal: multi-reward schemes can receive further benefits by applying other techniques. This project explores various multi-reward strategies and alternative solutions to sparse rewards to find intelligent ways to combine these methods. We provide three specific examples combining intrinsic rewards and transfer learning, imitation learning and policy combination, and hierarchical reinforcement learning and reward shaping in ways that extend the current state-of-the-art. To demonstrate practical usage of these techniques, we describe the application of these techniques to a sparsely rewarded underwater manipulation problem

Spacesuit Glove-Induced Hand Trauma and Analysis of Potentially Related Risk Variables

Injuries to the hands are common among astronauts who train for extravehicular activity (EVA). When the gloves are pressurized, they restrict movement and create pressure points during tasks, sometimes resulting in pain, muscle fatigue, abrasions, and occasionally more severe injuries such as onycholysis. Glove injuries, both anecdotal and recorded, have been reported during EVA training and flight persistently through NASA's history regardless of mission or glove model. Theories as to causation such as glove-hand fit are common but often lacking in supporting evidence. Previous statistical analysis has evaluated onycholysis in the context of crew anthropometry only (Opperman et al 2010). The purpose of this study was to analyze all injuries (as documented in the medical records) and available risk factor variables with the goal to determine engineering and operational controls that may reduce hand injuries due to the EVA glove in the future. A literature review and data mining study were conducted between 2012 and 2014. This study included 179 US NASA crew who trained or completed an EVA between 1981 and 2010 (crossing both Shuttle and ISS eras) and wore either the 4000 Series or Phase VI glove during Extravehicular Mobility Unit (EMU) spacesuit EVA training and flight. All injuries recorded in medical records were analyzed in their association to candidate risk factor variables. Those risk factor variables included demographic characteristics, hand anthropometry, glove fit characteristics, and training/EVA characteristics. Utilizing literature, medical records and anecdotal causation comments recorded in crewmember injury data, investigators were able to identify several risk factors associated with increased risk of glove related injuries. Prime among them were smaller hand anthropometry, duration of individual suited exposures, and improper glove-hand fit as calculated by the difference in the anthropometry middle finger length compared to the baseline EVA glove middle finger length

Geodatabase Development to Support Hyperspectral Imagery Exploitation

Geodatabase development for coastal studies conducted by the Naval Research Laboratory (NRL) is essential to support the exploitation of hyperspectral imagery (HSI). NRL has found that the remote sensing and mapping science community benefits from coastal classifications that group coastal types based on similar features. Selected features in project geodatabases relate to significant biological and physical forces that shape the coast. The project geodatabases help researchers understand factors that are necessary for imagery post processing, especially those features having a high degree of temporal and spatial variability. NRL project geodatabases include a hierarchy of environmental factors that extend from shallow water bottom types and beach composition to inland soil and vegetation characteristics. These geodatabases developed by NRL allow researchers to compare features among coast types. The project geodatabases may also be used to enhance littoral data archives that are sparse. This paper highlights geodatabase development for recent remote sensing experiments in barrier island, coral, and mangrove coast types