Contribution of caregiver and child anxiety and depressive symptoms to child asthma-related quality of life.

BACKGROUND: Depression and anxiety negatively affect asthma-related quality of life (QoL). Yet, little is known regarding mood and asthma-related factors that best uniquely explain asthma-related QoL in children. OBJECTIVE: This cross-sectional study evaluated the unique variance explained by caregiver and child depressive and anxiety symptom severity in child asthma-related QoL, apart from that explained by demographics and asthma control. METHODS: Children aged 7 to 17 years with asthma (n = 205) and their caregivers with major depressive disorder were included. A 3-stage hierarchical linear regression analysis was conducted with the Pediatric Asthma Quality of Life Questionnaire total scores considered as the outcome. Predictors included demographic characteristics (stage 1); asthma control assessed by the Asthma Control Test (stage 2); and caregiver depression and anxiety (Hamilton Rating Scale for Depression and the Spielberger State/Trait Anxiety Scale) and child depression and anxiety (Children's Depression Inventory and the Screen for Child Anxiety-Related Disorders) (stage 3). RESULTS: Demographic characteristics accounted for only 5.5% of the Pediatric Asthma Quality of Life Questionnaire scores. Asthma control significantly increased variance explained in QoL to 32.6%, whereas caregiver and child depression and anxiety symptoms significantly increased variance explained to 42.6%. Child anxiety was found to uniquely explain the largest proportion of variance in QoL (rs2 = 0.584). CONCLUSION: After adjusting variance in QoL for demographic characteristics and asthma control, caregiver and child depression and anxiety measures significantly increased the proportion of variance explained in a child's asthma-related QoL. In addition to better asthma control, child and caregiver depression and anxiety should be addressed to increase child asthma-related QoL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02809677.

Imaging review of spontaneous renal hemorrhage.

Spontaneous renal hemorrhage (SRH) is a diagnostic challenge and a significant cause of morbidity, and sometimes mortality. Early identification is essential to institute lifesaving and reno-protective interventions. In this review, we classify spontaneous renal hemorrhage by location, presentation and etiology. We also discuss the diagnostic approach to renal hemorrhage and optimum imaging modalities to arrive at the diagnosis. Finally, we review strategies to avoid missing a diagnosis of SRH and discuss the pitfalls of imaging in the presence of renal hemorrhage.

Adaptable and comprehensive vulnerability assessments for water resources systems in a rapidly changing world.

Comprehensive and adaptive approaches to vulnerability assessment are crucial for guiding effective adaptation in global water resources systems. A common approach to quantify vulnerability is through indicators, which capture the 'spirit of vulnerability' while retaining practical ease-of-use benefits. However, a comprehensive meta-analysis of reveals two specific limitations of global indicator-based vulnerability assessments for water resources systems: 1) vulnerability is influenced by complex interactions among multi-domain factors, for which indicator quality and data vary; and 2) vulnerability is dynamic and evolves over time, an aspect overlooked in most approaches. In response to these identified challenges, we propose a new dynamic "build-your-own" approach to vulnerability assessment. Our approach focuses on correcting for the identified gaps and biases in indicators and data to improve assessment comprehensiveness. This approach also incorporates guidance around adapting assessments over time to better reflect vulnerability under changing conditions. The open-source nature of our approach and underlying data can facilitate the development and customization of indicator-based vulnerability assessments for diverse applications, supporting practical and relevant planning for more resilient water resources systems.

Analysis of risk evaluation and mitigation strategies for teratogenic drugs: Variation in primary and secondary prevention measures.

In an analysis of risk evaluation and mitigation strategies for teratogenic drugs, Ameet Sarpatwari, Beatrice Brown and Aaron Kesselheim explore the variation in primary and secondary prevention measures.

Endothelial Toll-like receptor 4 is required for microglia activation in the murine retina after systemic lipopolysaccharide exposure.

BACKGROUND: Clustering of microglia around the vasculature has been reported in the retina and the brain after systemic administration of lipopolysaccharides (LPS) in mice. LPS acts via activation of Toll-like receptor 4 (TRL4), which is expressed in several cell types including microglia, monocytes and vascular endothelial cells. The purpose of this study was to investigate the effect of systemic LPS in the pigmented mouse retina and the involvement of endothelial TLR4 in LPS-induced retinal microglia activation. METHODS: C57BL/6J, conditional knockout mice that lack Tlr4 expression selectively on endothelial cells (TekCre-posTlr4loxP/loxP) and TekCre-negTlr4loxP/loxP mice were used. The mice were injected with 1 mg/kg LPS via the tail vein once per day for a total of 4 days. Prior to initiation of LPS injections and approximately 5 h after the last injection, in vivo imaging using fluorescein angiography and spectral-domain optical coherence tomography was performed. Immunohistochemistry, flow cytometry, electroretinography and transmission electron microscopy were utilized to investigate the role of endothelial TLR4 in LPS-induced microglia activation and retinal function. RESULTS: Activation of microglia, infiltration of monocyte-derived macrophages, impaired ribbon synapse organization and retinal dysfunction were observed after the LPS exposure in C57BL/6J and TekCre-negTlr4loxP/loxP mice. None of these effects were observed in the retinas of conditional Tlr4 knockout mice after the LPS challenge. CONCLUSIONS: The findings of the present study suggest that systemic LPS exposure can have detrimental effects in the healthy retina and that TLR4 expressed on endothelial cells is essential for retinal microglia activation and retinal dysfunction upon systemic LPS challenge. This important finding provides new insights into the role of microglia-endothelial cell interaction in inflammatory retinal disease.

The root of the problem: diverse vulnerability to xylem cavitation found within the root system of wheat plants.

The propagation of xylem embolism throughout the root systems of drought-affected plants remains largely unknown, despite this process being comparatively well characterized in aboveground tissues. We used optical and X-ray imaging to capture xylem embolism propagation across the intact root systems of bread wheat (Triticum aestivum L. 'Krichauff') plants subjected to drying. Patterns in vulnerability to xylem cavitation were examined to investigate whether vulnerability may vary based on root size and placement across the entire root system. Individual plants exhibited similar mean whole root system vulnerabilities to xylem cavitation but showed enormous 6 MPa variation within their component roots (c. 50 roots per plant). Xylem cavitation typically initiated in the smallest, peripheral parts of the root system and moved inwards and upwards towards the root collar last, although this trend was highly variable. This pattern of xylem embolism spread likely results in the sacrifice of replaceable small roots while preserving function in larger, more costly central roots. A distinct pattern of embolism-spread belowground has implications for how we understand the impact of drought in the root system as a critical interface between plant and soil.

Resistant xylem from roots to peduncles sustains reproductive water supply after drought-induced cavitation of wheat leaves.

BACKGROUND AND AIMS: Many annual grasses exhibit drought-avoiding life cycles in which rapid reproduction must be completed before soil water is exhausted. This strategy would seem to require a hydraulic system capable of sustaining reproduction at all costs to the rest of the plant, yet little is known about the whole-plant structure of hydraulic vulnerability in grasses. METHODS: We examine vulnerability to water-stress-induced xylem cavitation in roots, flag leaves, and basal and apical regions of peduncles of wheat (Triticum aestivum L. 'Krichauff') to understand the staged failure of xylem function in severe drought. The functionality of segmented vulnerabilities is tested by conducting rehydration experiments after acute dehydration. KEY RESULTS: We show that water supply to peduncles is more drought resistant than in leaves due to greater xylem cavitation resistance, ensuring a pathway of water can be maintained from the roots to the reproductive tissues even after severe water deficit. Differential rehydration of peduncles compared to leaves following drought confirmed the functionality of xylem supply from roots to seed after water stress sufficient to completely cavitate flag leaf vessels. CONCLUSIONS: These results demonstrate that a proportion of the hydraulic pathway between roots and seeds remains functional under extreme dehydration, suggesting that vulnerability traits in this key grass species reflect its reproductive strategy.

Patient satisfaction with telemedicine in the Philippines during the COVID-19 pandemic: a mixed methods study.

BACKGROUND: The capacity to deliver essential health services has been negatively impacted by the COVID-19 pandemic, particularly due to lockdown restrictions. Telemedicine provides a safe, efficient, and effective alternative that addresses the needs of patients and the health system. However, there remain implementation challenges and barriers to patient adoption in resource-limited settings as in the Philippines. This mixed methods study aimed to describe patient perspectives and experiences with telemedicine services, and explore the factors that influence telemedicine use and satisfaction. METHODS: An online survey consisting of items adapted from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Clinician & Group Adult Visit Survey 4.0 (beta) and the Telehealth Usability Questionnaire (TUQ) was completed by 200 participants aged 18 to 65 years residing in the Philippines. A subsample of 16 participants was interviewed to provide further insights on their experiences. We used descriptive statistics to analyze survey data and thematically analyzed data from interviews guided by the principles of grounded theory. RESULTS: Participants were generally satisfied with telemedicine, and found it to be an efficient and convenient means of receiving healthcare. About 3 in 5 perceived telemedicine as affordable, with some finding telemedicine costs to be high and comparable to in-person consultations. Our results suggest that participants preferred telemedicine services, especially in cases where they feel that their condition is not urgent and does not need extensive physical examination. Safety against COVID-19, privacy, accessibility, and availability of multiple communication platforms contributed to patient satisfaction with telemedicine. Negative perceptions of patients on quality of care and service related to their telemedicine provider, inherent limitations of telemedicine in the diagnosis and management of patients, perceived high costs especially for mental health conditions, and poor connectivity and other technological issues were barriers to telemedicine use and satisfaction. CONCLUSION: Telemedicine is viewed as a safe, efficient, and affordable alternative to receiving care. Expectations of patients on costs and outcomes need to be managed by providers to increase satisfaction. Continued adoption of telemedicine will require improvements in technology infrastructure and technical support for patients, training and performance evaluation of providers to ensure quality of care and service, better patient communication to meet patient needs, and integration of telemedicine services in remote areas that have limited access to medical services. Telemedicine, to realize its full potential, should be centered in health equity - addressing patient barriers and needs, reducing health disparities across population groups and settings, and providing quality services to all.

Attitudes and practices associated with pubic hair grooming behaviours: A cross-sectional study.

BACKGROUND: Female pubic hair grooming (PHG) habits have changed in the last 20 years. Most studies present findings around female PHG attitudes, practices, and behaviours, lacking data on male attitudes and practices. AIMS: We explored the attitudes and practices of PHG from male and female perspectives. MATERIALS AND METHODS: A cross-sectional convenience survey was conducted online with 1560 male and female young adult participants aged 18 to 25 years. The study was conducted over two time periods (2014 and 2021). The survey explored attitudes, practices, and behaviours around PHG. Descriptive statistics included frequencies and proportions for categorical variables and the median for continuous variables. Males and females were compared using the χ2 test or Fisher's exact test for categorical variables. We used logistic regression to explore independent factors of PHG. RESULTS: Seventy-two percent (n = 471/728) of females and 64.7% (n = 257/728) of males were likely to engage in PHG. Participants were more likely to groom their pubic hair for reasons associated with religion (adjusted odds ratio (aOR): 9.01, 95% CI: 2.87-28.2), comfort when wearing clothing (aOR: 3.85, 95% CI: 1.52-9.71), a neater and cleaner genital appearance (aOR: 3.90, 95% CI: 1.62-9.41) and before attending a healthcare consultation (aOR: 4.79, 95% CI: 2.27-10.09). Moreover, twice as many females compared with male groomers reported watching pornography (69.7% vs 30.3%). CONCLUSION: Several factors can influence PHG. Our findings demonstrate that the reasons participants engage in PHG practices are for hygiene, aesthetics, comfort, and sexual satisfaction.

The biobehavioral family model and the family relational assessment protocol: Map and GPS for family systems training.

The Biobehavioral Family Model (BBFM) was developed and evolved as a heuristic research model to support the investigation of pathways by which family relational function impacts individual family member wellbeing and disorder. Recently, the BBFM and its related assessment approach, the Family Relational Process Assessment Protocol (FRAP), have emerged as tools for clinical practice and training. The BBFM model will be presented, along with definitions of the dimensions constructed in the model, and research evidence in support of the model. To illustrate how the BBFM and FRAP are used in training, instructions for conducting the FRAP will be presented. Then, transcripts from two contrasting families participating in one of the interaction tasks will illustrate how, in training, the FRAP is interpreted through the BBFM lens to illuminate how these patterns of family relationship impact the identified patient. Finally, three applications of this training approach will exemplify the use of the BBFM and FRAP in the context of a Child and Adolescent Psychiatry Fellowship, a Family Medicine Fellowship, and a Family Therapy Training Program in Istanbul, Turkey. Limitations and future directions for the application of the BBFM in the exploration of multicultural aspects of family function for clinical and training purposes will be discussed.

Reproductive water supply is prioritized during drought in tomato.

Reproductive success largely defines the fitness of plant species. Understanding how heat and drought affect plant reproduction is thus key to predicting future plant fitness under rising global temperatures. Recent work suggests reproductive tissues are highly vulnerable to water stress in perennial plants where reproductive sacrifice could preserve plant survival. However, most crop species are annuals where such a strategy would theoretically reduce fitness. We examined the reproductive strategy of tomato (Solanum lycopersicum var. Rheinlands Ruhm) to determine whether water supply to fruits is prioritized above vegetative tissues during drought. Using optical methods, we mapped xylem cavitation and tissue shrinkage in vegetative and reproductive organs during dehydration to determine the priority of water flow under acute water stress. Stems and peduncles of tomato showed significantly greater xylem cavitation resistance than leaves. This maintenance of intact water supply enabled tomato fruit to continue to expand during acute water stress, utilizing xylem water made available by tissue collapse and early cavitation of leaves. Here, tomato plants prioritize water supply to reproductive tissues, maintaining fruit development under drought conditions. These results emphasize the critical role of water transport in shaping life history and suggest a broad relevance of hydraulic prioritization in plant ecology.

Linear Growth Spurts are Preceded by Higher Weight Gain Velocity and Followed by Weight Slowdowns Among Rural Children in Burkina Faso: A Longitudinal Study.

BACKGROUND: The temporal relationship between length (linear) and weight (ponderal) growth in early life is important to support optimal nutrition program design. Studies based on measures of attained size have established that wasting often precedes stunting, but such studies do not capture responsiveness of growth to previous compared with current conditions. As a result, the temporality of linear and ponderal growth relationships remain unclear. OBJECTIVES: We used growth velocity indicators to assess the temporal bidirectional relationships between linear and ponderal growth in children. METHODS: Using monthly anthropometric measurements from 5039 Burkinabè children enrolled at 6 months of age and followed until 28 months from August 2014 to December 2016, we employed multilevel mixed-effects models to investigate concurrent and lagged associations between linear and ponderal growth velocity, controlling for time trends, seasonality, and morbidity. RESULTS: Faster ponderal growth is associated with faster concurrent and subsequent linear growth (0.21-0.72 increase in length velocity z-score per unit increase in weight velocity z-score), while faster linear growth is associated with slower future weight gain (0.009-0.02 decrease in weight velocity z-score per unit increase in length velocity z-score), especially among children 9-14 months. Ponderal growth slows around the same time as peaks in morbidity, followed roughly a month later by slower linear growth. CONCLUSIONS: Use of velocity measures to assess temporal dependencies between linear and ponderal growth demonstrate that the same growth-limiting conditions likely affect both length and weight velocity, that slow ponderal growth likely limits subsequent linear growth, and that linear growth spurts may not be accompanied by sufficient increases in dietary intake to avoid slowdowns in weight gain.

Trends in the Quality of Evidence Supporting FDA Drug Approvals: Results from a Literature Review.

CONTEXT: New drug approvals in the United States must be supported by substantial evidence from "adequate and well-controlled" trials. The Food and Drug Administration (FDA) has flexibility in how it applies this standard. METHODS: The authors conducted a systematic literature review of studies evaluating the design and outcomes of the key trials supporting new drug approvals in the United States. They extracted data on the trial characteristics, endpoint types, and expedited regulatory pathways. FINDINGS: Among 48 publications eligible for inclusion, 30 covered trial characteristics, 23 covered surrogate measures, and 30 covered regulatory pathways. Trends point toward less frequent randomization, double-blinding, and active controls, with variation by drug type and indication. Surrogate measures are becoming more common but are not consistently well correlated with clinical outcomes. Drugs approved through expedited regulatory pathways often have less rigorous trial design characteristics. CONCLUSIONS: The characteristics of trials used to approve new drugs have evolved over the past two decades along with greater use of expedited regulatory pathways and changes in the nature of drugs being evaluated. While flexibility in regulatory standards is important, policy changes can emphasize high-quality data collection before or after FDA approval.

An application of the Biobehavioral Family Model: Examining the impact of maternal depression on child asthma mediated by insecure attachment and child depression.

OBJECTIVE: Child asthma disparities are prevalent in socio-economically stressed single-parent families. Stress impacts childhood asthma mediated by immune and autonomic pathways, but specific family stress pathways are not well established. This study tests the hypothesis, derived from a version of the Biobehavioral Family Model, that single parent maternal depression impacts child asthma mediated by insecure attachment and child depression. METHODS: In a cross-sectional study, children with asthma (age 7-17 years old) from a socio-economically disadvantaged population and their single parent mothers (N = 202) were assessed for depression and attachment security. Child asthma disease activity was assessed by symptom report and lung function tests. Structural equation modeling (SEM) was used to test a model in which caregiver depression impacts child asthma disease activity mediated by insecure attachment and child depression. RESULTS: SEM results indicated that maternal depression statistically predicted child depression (ß = 0.21, p < 0.01) and insecure mother-child attachment (ß = 0.17, p < 0.05). In addition, insecure attachment statistically predicted child depression (ß = 0.50, p < 0.001). Child depression mediated the adverse effects of maternal depression and insecure attachment on child asthma disease activity (ß = 0.43, p < 0.01). There was no direct effect of insecure attachment on child asthma. CONCLUSION: In single-parent families, maternal depression may impact child asthma disease activity, mediated serially by insecure attachment and child depression. Longitudinal and/or intervention studies are needed to establish a causal effect. These findings suggest that caregiver depression and parent-child relationships may be important targets for family intervention. These interventions may help improve child asthma outcomes and reduce health disparities.

Body Composition Changes in Children during Treatment for Moderate Acute Malnutrition: Findings from a 4-Arm Cluster-Randomized Trial in Sierra Leone.

BACKGROUND: Measures that better describe "healthy" and sustainable recovery during nutritional treatment of children with moderate acute malnutrition (MAM) are needed. OBJECTIVES: We compared changes to body composition among children receiving 1 of 4 specialized nutritious food (SNFs) during treatment of MAM and by recovery and relapse outcomes. METHODS: The study was nested within a prospective, cluster-randomized, community-based, cost-effectiveness trial assessing 4 SNFs to treat children aged 6-59 mo with MAM [midupper arm circumference (MUAC) ≥11.5 cm and <12.5 cm without bipedal edema] in Sierra Leone. Biweekly SNF rations (1 of 3 fortified-blended foods or a lipid-based nutrient supplement) were given until children recovered (MUAC ≥12.5 cm), or up to 7 rations (∼12 wk). Deuterium dilution was used to estimate fat-free mass (FFM) and fat mass (FM) at enrollment and after 4 wk of treatment to ensure similar treatment exposure among the participants. Another MUAC measurement was performed among recovered children 4 wk after program exit to determine whether recovery was sustained. ANOVA, paired t tests, and linear regression models were used to determine significant differences in changes from baseline to 4 wk. RESULTS: Among 312 analyzed participants, mean baseline weight comprised ∼80% FFM; mean weight gained after 4 wk comprised ∼82% FFM. Changes in FM and FFM among 4 SNFs were similar. Children who recovered gained more weight (241%), FFM (179%), and weight-for-height z score (0.44 compared with 0) compared with those who did not recover; sustainers gained 150% more weight. FM gains were positive among recovered children and sustainers, as well as negative among those who did not recover or sustain recovery, but not significantly different. CONCLUSIONS: Four SNFs had similar effects on body composition in children after 4 wk of treatment for MAM, showing a healthy pattern of weight gain, the majority being FFM. Differential responses to treatment underscore a need for further research to provide targets for healthy, sustainable recovery. This trial was registered at clinicaltrials.gov as NCT03146897.

Fortified blended flour supplements displace plain cereals in feeding of young children.

Lipid-based nutritional supplements (LNS) and fortified blended flours (FBF) are widely used to increase the nutrient density of children's diets and improve their health, but their effectiveness could be modified by displacement of other foods. We reanalysed data from a cost-effectiveness trial comparing impacts on anthropometry of three FBFs (Corn Soy Blend Plus [CSB+], Corn Soy Whey Blend [CSWB], SuperCereal Plus [SC+]) and one LNS (Ready-to-use Supplementary Food [RUSF]) among infants aged 7-23 months in Burkina Faso. Using dietary diversity data from a single 24-h recall period (n = 1,591 children, observed once over 18-month study period), we fit logistic regression models to estimate differences in intake of each food group making up the infant and young child minimum dietary diversity score and linear models to test for differences in dietary diversity score among children in each supplement arm. We tested for differences in breastfeeding time using the subsample for which breastfeeding was observed (n = 176). Children who consumed one of the three FBFs had lower odds of consuming household grains, roots and tubers compared with the LNS consumers (odds ratios [ORs] = 0.35-0.47; 95% confidence intervals [CIs]: 0.20-1.05). Consumption of other foods, dietary diversity and breastfeeding did not differ significantly at the 5% significance level. FBFs displaced the household's own cereals more than LNS, with no difference in the child's consumption of other more nutrient-rich family foods. Given limited stomach capacity and feeding time, providing fortified cereals may help improve children's overall diet quality in settings where children would otherwise be fed nutrient-poor root crops or cereal grains.

EQUINE SARCOIDS IN CAPTIVE WILD EQUIDS: DIAGNOSTIC AND CLINICAL MANAGEMENT OF 16 CASES-A POSSIBLE PREDISPOSITION OF THE EUROPEAN COHORT OF SOMALI WILD ASS (EQUUS AFRICANUS SOMALIENSIS)?

Equine sarcoids (ES) were diagnosed in 12 Somali wild asses (SWA) (Equus africanus somaliensis) from 10 different institutions of the SWA European Endangered Species Programme from 1976 to 2019. Samples of surgically excised masses, biopsies, or necropsy samples were submitted for histologic and virologic analysis. In addition, tissue samples from one onager (Equus hemionus onager), one kulan (Equus hemionus kulan), and two Hartmann's mountain zebras (HMZ) (Equus zebra hartmannae) were examined. Histology confirmed the diagnosis of ES exhibiting the typical microscopic features. Polymerase chain reaction detected bovine papillomavirus type 1 (BPV1) DNA in eight SWA samples and bovine papillomavirus type 2 (BPV2) DNA in one SWA sample. The onager, kulan, and one HMZ sample tested positive for BPV1. The other HMZ tested positive for BPV1 and BPV2. This is the first report of ES in an onager. Surgical excision was the treatment elected by most veterinarians. A follow-up survey of the cases over several years after clinical diagnosis and therapy revealed variable individual outcome with ES recurrence in four cases. Three SWA and the kulan were euthanized due to the severity of the lesions. Nine affected SWA were males with seven having a sarcoid located at the prepuce. Because a genetic disposition is a risk factor for the development of ES in horses, this may also be true for endangered wild equids with few founder animals in their studbook history. Innovative approaches regarding therapy and prevention of ES in wild equids are therefore highly encouraged.

Impact of stakeholder perspectives on cost-effectiveness estimates of four specialized nutritious foods for preventing stunting and wasting in children 6-23 months in Burkina Faso.

BACKGROUND: Multiple specialized nutritious food options are programmed for supplementation in humanitarian and development settings. However, comparative cost-effectiveness evidence is lacking, let alone incorporation of perspectives from uncompensated stakeholders. A Burkina Faso trial evaluated the cost-effectiveness of Corn Soy Blend Plus w/ oil (CSB+ w/oil, reference arm), Corn Soy Whey Blend w/oil (CSWB w/oil), Super Cereal Plus (SC+), and Ready-to-Use Supplementary Food (RUSF) in reducing stunting and wasting among children 6-23 months old. This paper presents cost-effectiveness findings from multiple stakeholders' perspectives, including caregivers and program volunteers. METHODS: An activity-based costing with ingredients approach was used to summarize cost of the 18-month-long blanket supplementary feeding for each enrolled child (in 2018 USD). Time data were collected using self-reported and observational instruments. Cost-effectiveness relative to CSB+ w/oil assessed incremental cost per enrolled child against incremental outcomes: prevalence of stunting at 23 months of age and number of months of wasting. Two combined perspectives were compared: program (donor, implementer, and volunteer) versus program and caregiver (adding caregiver). RESULTS: A total of 6112 children were enrolled. While similar effectiveness was found in three arms (CSWB w/oil was less effective), costs differed. Product cost and caregiver time to prepare study foods were major drivers of cross-arm cost differences from the respective combined perspective. The two major drivers were used to construct uncertainty ranges of cost per enrolled child from program and caregiver perspective: $317 ($279- $355) in CSB+ w/oil, $350 ($327- $373) in CSWB w/oil, $387 ($371- $403) in RUSF, and $434 ($365- $503) in SC+. Cost from program and caregiver perspective was a substantial increase from program perspective. CSB+ w/oil was most cost-effective in reducing stunting and wasting, and this main finding was robust to changing perspectives and all corresponding sensitivity analyses when uncompensated time was valued at minimum wage ($0.36/h). The break-even point for uncompensated time valuation is >$0.84/h, where RUSF became the most cost-effective from the program and caregiver perspective. Relative cost-effectiveness rankings among the other three arms depended on choice of perspectives, and were sensitive to values assigned to product cost, international freight cost, opportunity cost of time, and outcomes of a hypothetical control. Volunteer opportunity cost did not affect arm comparisons, but lack of compensation resulted in negative financial consequences for caregivers. CONCLUSIONS: Evaluating cost-effectiveness by incorporating uncompensated stakeholders provided crucial implementation insights around nutrition products and programming. TRIAL REGISTRATION: Trial registration number: NCT02071563. Name of registry: ClinicalTrials.gov URL of registry: https://clinicaltrials.gov/ct2/show/NCT02071563?type=Intr&cond=Malnutrition&cntry=BF&draw=2&rank=9 Date of registration: February 26, 2014. Date of enrollment of first participant: July 2014.

Multisectoral community development in Nepal has greater effects on child growth and diet than nutrition education alone.

OBJECTIVE: To compare the impact on child diet and growth of a multisectoral community intervention v. nutrition education and livestock management training alone. DESIGN: Longitudinal community-based randomized trial involving three groups of villages assigned to receive: (i) Full Package community development activities, delivered via women's groups; (ii) livestock training and nutrition education alone (Partial Package); or (iii) no intervention (Control). Household surveys, child growth monitoring, child and household diet quality measures (diet diversity (DD), animal-source food (ASF) consumption) were collected at five visits over 36 months. Mixed-effect linear regression and Poisson models used survey round, treatment group and group-by-round interaction to predict outcomes of interest, adjusted for household- and child-specific characteristics. SETTING: Banke, Nepal. PARTICIPANTS: Households (n 974) with children aged 1-60 months (n 1333). RESULTS: Children in Full Package households had better endline anthropometry (weight-for-age, weight-for-height, mid-upper-arm-circumference Z-scores), DD, and more consumption of ASF, after adjusting for household- and child-specific characteristics. By endline, compared with Partial Package or Control groups, Full Package households demonstrated preferential child feeding practices and had significantly more improvement in household wealth and hygiene habits. CONCLUSIONS: In this longitudinal study, a comprehensive multisectoral intervention was more successful in improving key growth indicators as well as diet quality in young children. Provision of training in livestock management and nutrition education alone had limited effect on these outcomes. Although more time-consuming and costly to administer, incorporating nutrition training with community social capital development was associated with better child growth and nutrition outcomes than isolated training programmes alone.

Phenotypic Screens Reveal Posaconazole as a Rapidly Acting Amebicidal Combination Partner for Treatment of Primary Amoebic Meningoencephalitis.

Naegleria fowleri is the causative agent of primary amoebic meningoencephalitis (PAM), which is fatal in >97% of cases. In this study, we aimed to identify new, rapidly acting drugs to increase survival rates. We conducted phenotypic screens of libraries of Food and Drug Administration-approved compounds and the Medicines for Malaria Venture Pathogen Box and validated 14 hits (defined as a 50% inhibitory concentration of <1 µM). The hits were then prioritized by assessing the rate of action and efficacy in combination with current drugs used to treat PAM. Posaconazole was found to inhibit amoeba growth within the first 12 hours of exposure, which was faster than any currently used drug. In addition, posaconazole cured 33% of N. fowleri-infected mice at a dose of 20 mg/kg and, in combination with azithromycin, increased survival by an additional 20%. Fluconazole, which is currently used for PAM therapy, was ineffective in vitro and vivo. Our results suggest posaconazole could replace fluconazole in the treatment of PAM.