The coexistence of multiple independently circulating strains in pathogen populations that undergo sexual recombination is a central question of epidemiology with profound implications for control. An agent-based model is developed that extends earlier ‘strain theory’ by addressing the var gene family of Plasmodium falciparum. The model explicitly considers the extensive diversity of multi-copy genes that undergo antigenic variation via sequential, mutually exclusive expression. It tracks the dynamics of all unique var repertoires in a population of hosts, and shows that even under high levels of sexual recombination, strain competition mediated through cross-immunity structures the parasite population into a subset of coexisting dominant repertoires of var genes whose degree of antigenic overlap depends on transmission intensity. Empirical comparison of patterns of genetic variation at antigenic and neutral sites supports this role for immune selection in structuring parasite diversity.DOI: http://dx.doi.org/10.7554/eLife.00093.001

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Background This study describes neuropsychological, medical, psychiatric and functional correlates of cognitive complaints experienced after recovery from acute COVID-19 infection. Methods Sixty participants underwent neuropsychological (NP), psychiatric, medical, functional, and quality of life assessments 6-8 months after acute COVID-19. Those seeking care cognitive complaints in a post-COVID-19 clinical program for Post-Acute Symptoms of COVID-19 (PASC) (Clinical Group, N=32) were compared to those recruited from the community who were not seeking care (Non-Clinical, N=28). A subset of participants underwent serological testing for pro-inflammatory cytokines C-Reactive Protein, Interleukin-6, and Tumor Necrosis Factor-α in order to explore correlations with neuropsychological, psychiatric and medical variables. Outcome For the entire sample, 16 (27%) had extremely low test scores (< 2 nd %ile on at least 1 NP test). The Clinical Group with cognitive complaints scored lower than age-adjusted population norms in tests of attention, processing speed, memory, and executive function, and significantly more scored in the extremely low range than the Non-Clinical Group (38% vs. 14%, p<0.04). The Clinical Group also reported higher levels of depression, anxiety, fatigue, PTSD and functional difficulties and lower quality of life. In logistic regression analysis, scoring in the extremely low range was predicted by acute COVID-19 symptoms, current depression score, number of medical comorbidities and subjective cognitive complaints in the areas of memory, language, and executive functions. IL-6 correlated with acute COVID symptoms, number of medical comorbidities, fatigue, and measures of executive function. CRP correlated with current COVID symptoms, depression score and, inversely, with quality of life. Conclusion Results suggest the existence of extremely low neuropsychological test performance experienced by some individuals months after acute COVID-19 infection, affecting multiple neurocognitive domains. This extremely low neuropsychological test performance is associated with worse acute COVID-19 symptoms, depression, medical comorbidities, functional complaints, and subjective cognitive complaints. Exploratory correlations with pro-inflammatory cytokines support further research into inflammatory mechanisms and viable treatments.

Background:Recent studies described an increase in acute kidney injury when high dose gentamicin was included in perioperative prophylaxis for orthopedic surgeries. To this effect, we compared the rate of nephrotoxicity for selected orthopedic surgeries where gentamicin was included (Gentamicin Group) to those where it was not included (Control Group) for perioperative prophylaxis and evaluated risk factors for nephrotoxicity.Methods:Spine, hip and knee surgeries performed between April 2011 and December 2013 were reviewed retrospectively. Gentamicin was given to eligible patients based on age, weight and Creatinine Clearance. Nephrotoxicity was assessed using Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria.Results:Among selected surgeries (N = 1590 in Gentamicin Group: hip = 926, spine = 600, knee = 64; N = 2587 in Control Group: hip = 980, spine = 902, knee = 705), patients’ body weight, serum creatinine, comorbidities and surgery duration were similar in Gentamicin Group and Control Group. Gentamicin median dose was 4.5 mg/kg of dosing weight. Nephrotoxicity rate was 2.5% in Gentamicin Group and 1.8% in Control Group, p = 0.17. Most cases of nephrotoxicity were Risk category by RIFLE criteria (67% in Gentamicin Group and 72% in Control Group, p = 0.49). In logistic regression, risk factors for nephrotoxicity were hospital stay >1 day prior to surgery (odds ratio = 8.1; 95% confidence interval = 2.25–28.97, p = 0.001), knee or hip surgery (odds ratio = 4.7; 95% confidence interval = 2.9–9.48, p = 0.0005) and diabetes (odds ratio = 1.95; 95% confidence interval = 1.13–3.35, p = 0.016). Receipt of gentamicin was not an independent predictor of nephrotoxicity (odds ratio = 1.5; 95% confidence interval = 0.97–2.35, p = 0.07).Conclusion:In this cohort, rate of nephrotoxicity was similar between Gentamicin Group and Control Group. Single high dose gentamicin is a safe and acceptable option for perioperative prophylaxis in eligible patients undergoing orthopedic surgeries.