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: Introduction: Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 Methods: The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results: Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 Conclusions: The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices., Introduction In low‐ and middle‐income settings, more than a third of HIV‐positive individuals starting antiretroviral therapy (ART) present with advanced disease (CD4 ≤ 200 cells/mm[sup.3]); over half of these have [...]

Much attention has been placed on the need to develop and evaluate complex interventions targeting public health issues, such as reproductive health. However, and as has been the case in the recent past, even well-designed trials will be flawed unless meticulous attention is paid to ensuring the most appropriate intervention is designed and developed. This requires a well-resourced and carefully planned feasibility study, incorporating both formative and process evaluation, with particular attention being paid to the context of the proposed intervention. In this paper, we describe the way in which a feasibility study helped redesign and shape a complex intervention targeting adolescent sexual health in rural Zimbabwe. By using a mixture of in-depth interviews, focus groups and participant observation with pupils, parents, teachers and education officers, we were able to show that the intervention as originally conceived was unlikely to be deliverable. Process evaluation findings from the feasibility study led to substantial changes to both the content and delivery of the proposed intervention, which is now subject to testing for effectiveness in a large community randomized trial.

Sea lamprey (Petromyzon marinus) avoid damage-released and predator chemosensory cues at night, but their response to these cues during the day is unknown. Here, we explored (i) whether sea lamprey avoid these cues during the day and (ii) the effect of water temperature on the avoidance of chemosensory alarm cues in two diurnal laboratory experiments. We hypothesized that daytime activity would be temperature-dependent and that only sea lamprey vulnerable to predation (i.e., not hiding) would behaviourally respond to chemosensory alarm cues. Ten groups of ten sea lamprey were exposed to one of a variety of potential chemosensory cues. The experiments were conducted over a range of temperatures to quantify the effect of temperature on avoidance behaviour. Consistent with our hypothesis, a higher proportion of animals were active during daytime as water temperature increased. Moving sea lamprey showed an avoidance response to 2-phenylethylamine (a compound found in mammalian urine) and human saliva once water temperatures had risen to mean (±SD) = 13.7 (± 1.4)°C. Resting and hiding sea lamprey did not show an avoidance response to any of the experimental stimuli. Pendant la nuit, les lamproies (Petromyzon marinus) evitent les signaux chimiosensoriels de predateurs ou liberes en cas de dommages, mais leur reaction a ces signaux durant le jour n'est pas connue. Nous tentons de determiner (i) si les lamproies evitent ces signaux durant le jour et (ii) l'effet de la temperature de l'eau sur l'evitement de signaux d'alarme chimiosensoriels dans le cadre de deux experiences diurnes en laboratoire. Nous avons postule que l'activite diurne depend de la temperature et que seules les lamproies vulnerables a la predation (c.-a-d. non cachees) adaptent leurs comportements en reaction a des signaux d'alarme chimiosensoriels. Dix groupes de dix lamproies ont ete exposes a un signal chimiosensoriel precis choisi parmi divers signaux possibles. Les experiences ont ete menees sur une fourchette de temperatures afin de quantifier l'effet de la temperature sur le comportement d'evitement. Conformement a notre hypothese, une plus grande proportion d'animaux etaient actifs durant le jour a mesure que la temperature augmentait. Les lamproies en mouvement presentaient une reaction d'evitement a la 2-phenylethylamine (un compose present dans l'urine de mammiferes) et a la salive humaine, une fois que la temperature de l'eau etait superieure a une valeur moyenne (±E-T) de 13,7°C (± 1,4°C). Les lamproies au repos ou cachees ne presentaient une reaction d'evitement a aucun des stimuli experimentaux. [Traduit par la Redaction], Introduction Chemosensory cues are used by prey to assess predation risk (Kats and Dill 1998). Damage-released alarm cues, a type of chemosensory cue, are discharged into an aquatic environment by [...]

Complex engineering systems (e.g. aeronautic vehicles and automobiles) consist of many different interfacing parts and are subject to numerous requirements and constraints regarding aspects of performance, manufacturability, economics, etc. Their design requires the collaboration between people from various disciplines--each retaining different, but necessary, perspectives of the system under design. Here, perspective is defined as a particular context that a human utilizes to create personally meaningful understanding. The key, then, to developing complex engineering systems lies in accommodating and negotiating different perspectives such that a comprehensive and highly integrated design is achieved. We offer a methodology for performing design that explicitly incorporates the multiplicity and diversity of perspective encountered when developing complex engineering systems. Keywords engineering design; function; perspective; microworld; living systems theory, FRAME OF REFERENCE Designing complex artefacts and processes is a challenging intellectual task, owing to the involvement of many designers who each holds different perspectives of the subject system. Here, [...]