Variable bites and dynamic populations : new insights in Leishmania transmission

Leishmaniasis is a neglected tropical disease which kills an estimated 50,000 people each year, with its deadly impact confined mainly to lower to middle income countries. Leishmania parasites are transmitted to human hosts by sand fly vectors during blood feeding. Recent experimental work shows that transmission is modulated by the patchy landscape of infection in the host's skin, and the parasite population dynamics within the vector. Here we assimilate these new findings into a simple probabilistic model for disease transmission which replicates recent experimental results, and assesses their relative importance. The results of subsequent simulations, describing random parasite uptake and dynamics across multiple blood meals, show that skin heterogeneity is important for transmission by short-lived flies, but that for longer-lived flies with multiple bites the population dynamics within the vector dominate transmission probability. Our results indicate that efforts to reduce fly lifespan beneath a threshold of around two weeks may be especially helpful in reducing disease transmission

Exercise rejuvenates microglia and reverses T cell accumulation in the aged female mouse brain

Slowing and/or reversing brain ageing may alleviate cognitive impairments. Previous studies have found that exercise may mitigate cognitive decline, but the mechanisms underlying this remain largely unclear. Here we provide unbiased analyses of single‐cell RNA sequencing data, showing the impacts of exercise and ageing on specific cell types in the mouse hippocampus. We demonstrate that exercise has a profound and selective effect on aged microglia, reverting their gene expression signature to that of young microglia. Pharmacologic depletion of microglia further demonstrated that these cells are required for the stimulatory effects of exercise on hippocampal neurogenesis but not cognition. Strikingly, allowing 18‐month‐old mice access to a running wheel did by and large also prevent and/or revert T cell presence in the ageing hippocampus. Taken together, our data highlight the profound impact of exercise in rejuvenating aged microglia, associated pro‐neurogenic effects and on peripheral immune cell presence in the ageing female mouse brain

Towards person-centered quality care for children with life-limiting and life-threatening illness: self-reported symptoms, concerns and priority outcomes from a multi-country qualitative study

Abstract Background: Paediatric life-limiting and life-threatening conditionslife-limiting conditions place significant strain on children, families and health systems. Given high service use among this population, it is essential that care addresses their main symptoms and concerns. Aim: This study aimed to identify the symptoms, concerns, and other outcomes that matter to children with life-limiting conditions and their families in sub-Saharan Africa.Setting and participants: Cross-sectional qualitative study in Kenya, Namibia, South Africa and Uganda. Children/caregivers of children aged 0-17 years with life-limiting conditions were purposively sampled by age, sex, and diagnosis. Children aged 7 and above self-reported; caregiver proxies reported for children below 7 and those aged 7 and above unable to self-report.Results: 120 interviews were conducted with children with life-limiting conditions (n=61 age range 7-17 years), and where self-report was not possible caregivers (n=59) of children (age range 0-17). Conditions included advanced HIV (22%), cancer (19%), heart disease (16%) endocrine, blood and immune disorders (13%), neurological conditions (12%), sickle cell anaemia (10%) and renal disease (8%). Outcomes identified included: physical concerns – pain and symptom distress; psycho-social concerns – family and social relationships, ability to engage with age-appropriate activities (e.g., play, school attendance); existential concerns – worry about death, and loss of ambitions,health care quality– child- and adolescent-friendly services. Priority psycho-social concerns and health service factors varied by age.Conclusion: This study bridges an important knowledge gap regarding symptoms, concerns and outcomes that matter to children living with life-limiting conditions and their families and informs service development and evaluation

Association of the degree of adiposity and duration of obesity with measures of cardiac structure and function: The CARDIA study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109634/1/oby20865.pd

Acute effects of nicotine on visual search tasks in young adult smokers

Rationale Nicotine is known to improve performance on tests involving sustained attention and recent research suggests that nicotine may also improve performance on tests involving the strategic allocation of attention and working memory. Objectives We used measures of accuracy and response latency combined with eye-tracking techniques to examine the effects of nicotine on visual search tasks. Methods In experiment 1 smokers and non-smokers performed pop-out and serial search tasks. In experiment 2, we used a within-subject design and a more demanding search task for multiple targets. In both studies, 2-h abstinent smokers were asked to smoke one of their own cigarettes between baseline and tests. Results In experiment 1, pop-out search times were faster after nicotine, without a loss in accuracy. Similar effects were observed for serial searches, but these were significant only at a trend level. In experiment 2, nicotine facilitated a strategic change in eye movements resulting in a higher proportion of fixations on target letters. If the cigarette was smoked on the first trial (when the task was novel), nicotine additionally reduced the total number of fixations and refixations on all letters in the display. Conclusions Nicotine improves visual search performance by speeding up search time and enabling a better focus of attention on task relevant items. This appears to reflect more efficient inhibition of eye movements towards task irrelevant stimuli, and better active maintenance of task goals. When the task is novel, and therefore more difficult, nicotine lessens the need to refixate previously seen letters, suggesting an improvement in working memory

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine

The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed

Mitigation of Moral Hazard and Adverse Selection in Venture Capital Financing: The Influence of the Country’s Institutional Setting

A venture capitalist (VC) needs to trade off benefits and costs when attempting to mitigate agency problems in their investor-investee relationship. We argue that signals of ventures complement the VC’s capacity to screen and conduct a due diligence during the pre-investment phase, but its attractiveness may diminish in institutional settings supporting greater transparency. Similarly, whereas a VC may opt for contractual covenants to curb potential opportunism by ventures in the post-investment phase, this may only be effective in settings supportive of shareholder rights enforcement. Using an international sample of VC contracts, our study finds broad support for these conjectures. It delineates theoretical and practical implications for how investors can best deploy their capital in different institutional settings whilst nurturing their relationships with entrepreneurs

Researching Memory in Early Modern Studies

This essay pursues the study of early modern memory across a chronologically, conceptually and thematically broad canvas in order to address key questions about the historicity of memory and the methodologies of memory studies. First, what is the value for our understanding of early modern memory practices of transporting the methodologies of contemporary memory studies backwards, using them to study the memorial culture of a time before living memory? Second, what happens to the cross-disciplinary project of memory studies when it is taken to a distant period, one that had its own highly self-conscious and much debated cultures of remembering? Drawing on evidence and debates from a range of disciplinary locations, but primarily focusing on literary and historical studies, the essay interrogates crucial differences and commonalities between memory studies and early modern studies