Establishment of a self-propagating population of the African malaria vector Anopheles arabiensis under semi-field conditions

Background: The successful control of insect disease vectors relies on a thorough understanding of their ecology and behaviour. However, knowledge of the ecology of many human disease vectors lags behind that of agricultural pests. This is partially due to the paucity of experimental tools for investigating their ecology under natural conditions without risk of exposure to disease. Assessment of vector life-history and demographic traits under natural conditions has also been hindered by the inherent difficulty of sampling these seasonally and temporally varying populations with the limited range of currently available tools. Consequently much of our knowledge of vector biology comes from studies of laboratory colonies, which may not accurately represent the genetic and behavioural diversity of natural populations. Contained semi-field systems (SFS) have been proposed as more appropriate tools for the study of vector ecology. SFS are relatively large, netting-enclosed, mesocosms in which vectors can fly freely, feed on natural plant and vertebrate host sources, and access realistic resting and oviposition sites. Methods: A self-replicating population of the malaria vector Anopheles arabiensis was established within a large field cage (21 x 9.1 x 7.1 m) at the Ifakara Health Institute, Tanzania that mimics the natural habitat features of the rural village environments where these vectors naturally occur. Offspring from wild females were used to establish this population whose life-history, behaviour and demography under semi-field conditions was monitored over 24 generations. Results: This study reports the first successful establishment and maintenance of an African malaria vector population under SFS conditions for multiple generations (> 24). The host-seeking behaviour, time from blood feeding to oviposition, larval development, adult resting and swarming behaviour exhibited by An. arabiensis under SFS conditions were similar to those seen in nature. Conclusions: This study presents proof-of-principle that populations of important African malaria vectors can be established within environmentally realistic, contained semi-field settings. Such SFS will be valuable tools for the experimental study of vector ecology and assessment of their short-term ecological and longer-term evolutionary responses to existing and new vector control interventions

Paper 3: Selecting rapid review methods for complex questions related to health policy and system issues

Approaches for rapid reviews that focus on streamlining systematic review methods are not always suitable for exploring complex policy questions, as developing and testing theories to explain these complexities requires configuring diverse qualitative, quantitative, and mixed methods studies. Our objective was therefore to provide a guide to selecting approaches for rapidly (i.e., within days to months) addressing complex questions related to health policy and system issues. We provide a two-stage, transdisciplinary collaborative process to select a rapid review approach to address complex policy questions, which consists of scoping the breadth and depth of the literature and then selecting an optimal approach to synthesis. The first stage (scoping the literature) begins with a discussion with the stakeholders requesting evidence to identify and refine the question for the review, which is then used to conduct preliminary searches and conceptually map the documents identified. In the second stage (selection of an optimal approach), further stakeholder consultation is required to refine and tailor the question and approach to identifying relevant documents to include. The approach to synthesizing the included documents is then guided by the final question, the breadth and depth of the literature, and the time available and can include a static or evolving conceptual framework to code and analyze a range of evidence. For areas already covered extensively by existing systematic reviews, the focus can be on summarizing and integrating the review findings, resynthesizing the primary studies, or updating the search and reanalyzing one or more of the systematic reviews. The choice of approaches for conducting rapid reviews is intertwined with decisions about how to manage projects, the amount of work to be done, and the knowledge already available, and our guide offers support to help make these strategic decisions

The value of molecular stratification for CEBPA_DM and NPM1_MUT_FLT3_WT genotypes in older patients with acute myeloid leukaemia

Older adult patients (≥60 years) with acute myeloid leukaemia (AML) are generally considered to be poor-risk and there is limited information available regarding risk stratification based on molecular characterization in this age group, particularly for the double-mutant CEBPA (CEBPADM) genotype. To investigate whether a molecular favourable-risk genotype can be identified, we investigated CEBPA, NPM1 and FLT3 status and prognostic impact in a cohort of 301 patients aged 60 years or more with intermediate-risk cytogenetics, all treated intensively. Overall survival (OS) at 1 year was highest in the 12 patients (4%) that were CEBPADM compared to the 76 (28%) with a mutant NPM1 and wild-type FLT3 (NPM1MUTFLT3WT) genotype or all other patients (75%, 54%, 33% respectively), with median survival 15·2, 13·6 and 6·6 months, although the benefit was short-term (OS at 3 years 17%, 29%, 12% respectively). Combination of the CEBPADM and NPM1MUTFLT3WT genotype patients defined a molecular group with favourable prognosis (P < 0·0001 in multivariate analysis), with 57% of patients alive at 1 year compared to 33% for all other patients. Knowledge of genotype in older cytogenetically intermediate-risk patients might influence therapy decisions

Systematic review and meta-analysis of effects of community-delivered positive youth development interventions on violence outcomes

Background We systematically reviewed and meta-analysed evaluations testing the effectiveness of positive youth development (PYD) interventions for reducing violence in young people. Methods Two reviewers working independently screened records, assessed full-text studies for inclusion and extracted data. Outcomes were transformed to Cohen's d. Quality assessment of included evaluations was undertaken using the Cochrane risk of bias tool. Effect sizes were combined using multilevel meta-analysis. We searched 21 databases, including MEDLINE, PsycINFO, CINAHL and CENTRAL, and hand-searched key journals and websites. We included studies where the majority of participants were aged 11–18 years and where interventions were delivered in community (not clinical or judicial) settings outside of normal school hours. We excluded studies targeting predefined physical and mental health conditions or parents/carers alongside young people. We defined violence as perpetration or victimisation of physical violence including violent crime. Results Three randomised trials were included in this systematic review. Included evaluations each had design flaws. Meta-analyses suggested that PYD interventions did not have a statistically significant effect on violence outcomes across all time points (d=0.021, 95% CI −0.050 to 0.093), though interventions did have a statistically significant short-term effect (d=0.076, 95% CI 0.013 to 0.140). Conclusions Our meta-analyses do not offer evidence of PYD interventions in general having effects of public health significance in reducing violence among young people. Evaluations did not consistently report theories of change or implementation fidelity, so it is unclear if our meta-analyses provide evidence that the PYD theory of change is ineffective in reducing violence among young people

How Do Contextual Factors Influence Implementation and Receipt of Positive Youth Development Programs Addressing Substance Use and Violence? A Qualitative Meta-Synthesis of Process Evaluations

Objective:Positive youth development (PYD) often aims to prevent tobacco, alcohol, and drugs use and violence. We systematically reviewed PYD interventions, synthesizing process, and outcomes evidence. Synthesis of outcomes, published elsewhere, found no overall evidence of reducing substance use or violence but notable variability of fidelity. Our synthesis of process evaluations examined how implementation varied and was influenced by context.Data Source:Process evaluations of PYD aiming to reduce substance use and violence.Study Inclusion Criteria:Overall review published since 1985; written in English; focused on youth aged 11 to 18 years; focused on interventions addressing multiple positive assets; reported on theory, process, or outcomes; and concerned with reducing substance use or violence. Synthesis of process evaluations examined how implementation varies with or is influenced by context.Data Extraction:Two reviewers in parallel.Data Synthesis:Thematic synthesis.Results:We identified 12 reports. Community engagement enhanced program appeal. Collaboration with other agencies could broaden the activities offered. Calm but authoritative staff increased acceptability. Staff continuity underpinned diverse activities and durable relationships. Empowering participants were sometimes in tension with requiring them to engage in diverse activities.Conclusion:Our systematic review identified factors that might help improve the fidelity and acceptability of PYD interventions. Addressing these might enable PYD to fulfill its potential as a means of promoting health

The effects of Positive Youth Development interventions on substance use, violence and inequalities: systematic review of theories of change, processes and outcomes

BackgroundPositive Youth Development (PYD) delivered outside school aims to enable young people to develop positive assets such as relationships and confidence, rather than to merely address risk. Existing reviews of PYD effects on substance use or violence are old and unsystematic.ObjectivesTo systematically review evidence to answer the following questions: what theories of change inform PYD interventions addressing substance use and violence? What characteristics of participants and contexts are identified as barriers to and facilitators of implementation and receipt in process evaluations of PYD? What is the effectiveness and cost-effectiveness of PYD in reducing substance use and violence? What characteristics of participants and contexts appear to moderate, or are necessary and sufficient for, PYD effectiveness?Data sourcesA total of 21 bibliographic databases; 35 websites and contacting authors.Review methodsWe included reports published in English since 1985 and reporting on theories of change, as well as process, outcome and economic evaluations of PYD targeting 11- to 18-year-olds and addressing substance use or violence. References were screened on title/abstract and, where appropriate, on full report. Data extraction and quality assessment used Critical Appraisal Skills Programme, Evidence for Policy and Practice Information and Co-ordinating Centre and Cochrane tools. Theories of change and process evaluations were qualitatively metasynthesised. Outcome evaluations were synthesised narratively and meta-analytically.Results32,394 unique references were identified and 48 were included. A total of 16 reports described theories, 13 (10 studies) evaluated processes and 25 (10 studies) evaluated outcomes.Theories of changePYD interventions aim to offer opportunities for young people to develop positive ‘assets’ such as skills and confidence. These are theorised to promote and be promoted by young people’s ‘intentional self-regulation’, which involves reflecting on behaviour; determining goals; using existing resources to pursue these; and redirecting effort when thwarted. This enables ‘developmental regulation’, namely individuals capitalising on other opportunities to promote personal development. Positive assets thus accrued reduce health risks by reducing the impact on individuals of environmental risk or by ameliorating the impact of such risks. The literature offers limited insights beyond these general ideas.Process evaluationsCommunity engagement ensured that programmes were accessible and appealing. Staff capacity and continuity were crucial factors but often challenging when programmes could not offer full-time jobs. Tensions arose between a desire to empower participants to choose activities and a requirement for them to undertake a breadth of activities.Outcome evaluationsMeta-analyses of all combined outcomes and of short-term alcohol use, illicit drug use and smoking found no significant effects. There were small, statistically significant, short-term effects for an omnibus measure of substance use and for violence. We could not undertake metaregression to assess sociodemographic moderators but narrative synthesis suggested no clear pattern of effects by sex. We found no economic evaluations.LimitationsInsufficient studies precluded qualitative comparative analyses.ConclusionsHow PYD might promote health is currently undertheorised. Implementation can be challenging. We found little evidence that current PYD interventions delivered outside school reduce substance use or violence. However, these may not constitute a test of the effectiveness of the PYD model, as some included interventions that, although meeting our inclusion criteria, were not exemplars of PYD.Future workFurther evaluations should assess interventions employing PYD theory of change.Study registrationThis study is registered as PROSPERO CRD42013005439.FundingThe National Institute for Health Research Public Health Research programme.</jats:sec

Tools for delivering entomopathogenic fungi to malaria mosquitoes: effects of delivery surfaces on fungal efficacy and persistence.

BACKGROUND\ud \ud Entomopathogenic fungi infection on malaria vectors increases daily mortality rates and thus represents a control measure that could be used in integrated programmes alongside insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS). Before entomopathogenic fungi can be integrated into control programmes, an effective delivery system must be developed.\ud \ud METHODS\ud \ud The efficacy of Metarhizium anisopliae ICIPE-30 and Beauveria bassiana I93-825 (IMI 391510) (2 × 10(10) conidia m(-2)) applied on mud panels (simulating walls of traditional Tanzanian houses), black cotton cloth and polyester netting was evaluated against adult Anopheles gambiae sensu stricto. Mosquitoes were exposed to the treated surfaces 2, 14 and 28 d after conidia were applied. Survival of mosquitoes was monitored daily.\ud \ud RESULTS\ud \ud All fungal treatments caused a significantly increased mortality in the exposed mosquitoes, descending with time since fungal application. Mosquitoes exposed to M. anisopliae conidia on mud panels had a greater daily risk of dying compared to those exposed to conidia on either netting or cotton cloth (p < 0.001). Mosquitoes exposed to B. bassiana conidia on mud panels or cotton cloth had similar daily risk of death (p = 0.14), and a higher risk than those exposed to treated polyester netting (p < 0.001). Residual activity of fungi declined over time; however, conidia remained pathogenic at 28 d post application, and were able to infect and kill 73 - 82% of mosquitoes within 14 d.\ud \ud CONCLUSION\ud \ud Both fungal isolates reduced mosquito survival on immediate exposure and up to 28 d after application. Conidia were more effective when applied on mud panels and cotton cloth compared with polyester netting. Cotton cloth and mud, therefore, represent potential substrates for delivering fungi to mosquitoes in the field

The incidence of scarring on the dorsum of the hand

When undertaking image comparison of the hand between accused and perpetrator, it is not unusual for scars to be identified on the back of the hand. To investigate the occurrence of scarring in a discreet sample, a database of 238 individuals was examined, and the dorsum of the right and left hands was gridded for each individual. The position, size and type of scar were recorded within each grid. It was found that, in general, males exhibited a higher incidence of scarring than females. However, males were more likely to show scarring on their left hand whereas females were more likely to exhibit scarring on their right hand. Contrary to the literature, scarring was not most prevalent along the borders of the hand but occurred more frequently in association with the index and middle finger corridor regions. Surgical scars were rare as were large scars whereas linear scars smaller than 6 mm were the most frequently identified. Close to half of the sample did not exhibit scarring on one hand. The importance of understanding the pattern of scarring on the back of the hand is discussed in the light of forensic image comparison analysis

Treatment response and remission in a double-blind, randomized, head-to-head study of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit hyperactivity disorder

The Author(s) 2014. This article is published with open access at Springerlink.com Objectives A secondary objective of this head-to-head study of lisdexamfetamine dimesylate (LDX) and ato-moxetine (ATX) was to assess treatment response rates in children and adolescents with attention-deficit hyperactiv-ity disorder (ADHD) and an inadequate response to methylphenidate (MPH). The primary efficacy and safety outcomes of the study, SPD489-317 (ClinicalTrials.gov NCT01106430), have been published previously. Methods In this 9-week, double-blind, active-controlled study, patients aged 6–17 years with a previous inadequate response to MPH were randomized (1:1) to dose-optimized LDX (30, 50 or 70 mg/day) or ATX (patients \70 kg: 0.5–1.2 mg/kg/day, not to exceed 1.4 mg/kg/day; patients C70 kg: 40, 80 or 100 mg/day). Treatment response was a secondary efficacy outcome and was predefined as a reduction from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score of at least 25, 30 or 50 %. Sustained response was predefined as a reduction from baseline in ADHD-RS-IV total score (C25, C30 or C50 %) or a Clinical Global Impressions (CGI)–Improvement (CGI–I) score of 1 or 2 throughout weeks 4–9. CGI– Severity (CGI–S) scores were also assessed, as an indicator of remission. Results A total of 267 patients were enrolled (LDX, n = 133; ATX, n = 134) and 200 completed the study (LDX, n = 99; ATX, n = 101). By week 9, significantly (p \ 0.01) greater proportions of patients receiving LDX than ATX met the response criteria of a reduction from baseline in ADHD-RS-IV total score of at least 25 % (90.5 vs. 76.7 %), 30 % (88.1 vs. 73.7 %) or 50 % (73.0 vs. 50.4 %). Sustained response rates were also signifi-cantly (p \ 0.05) higher among LDX-treated patient

Access to housing subsidies, housing status, drug use and HIV risk among low-income U.S. urban residents

<p>Abstract</p> <p>Background</p> <p>Much research has shown an association between homelessness and unstable housing and HIV risk but most has relied on relatively narrow definitions of housing status that preclude a deeper understanding of this relationship. Fewer studies have examined access to housing subsidies and supportive housing programs among low-income populations with different personal characteristics. This paper explores personal characteristics associated with access to housing subsidies and supportive housing, the relationship between personal characteristics and housing status, and the relationship between housing status and sexual risk behaviors among low-income urban residents.</p> <p>Methods</p> <p>Surveys were conducted with 392 low-income residents from Hartford and East Harford, Connecticut through a targeted sampling plan. We measured personal characteristics (income, education, use of crack, heroin, or cocaine in the last 6 months, receipt of welfare benefits, mental illness diagnosis, arrest, criminal conviction, longest prison term served, and self-reported HIV diagnosis); access to housing subsidies or supportive housing programs; current housing status; and sexual risk behaviors. To answer the aims above, we performed univariate analyses using Chi-square or 2-sided ANOVA's. Those with significance levels above (0.10) were included in multivariate analyses. We performed 2 separate multiple regressions to determine the effects of personal characteristics on access to housing subsidies and access to supportive housing respectively. We used multinomial main effects logistic regression to determine the effects of housing status on sexual risk behavior.</p> <p>Results</p> <p>Being HIV positive or having a mental illness predicted access to housing subsidies and supportive housing, while having a criminal conviction was not related to access to either housing subsidies or supportive housing. Drug use was associated with poorer housing statuses such as living on the street or in a shelter, or temporarily doubling up with friends, acquaintances or sex partners. Living with friends, acquaintances or sex partners was associated with greater sexual risk than those living on the street or in other stable housing situations.</p> <p>Conclusions</p> <p>Results suggest that providing low-income and supportive housing may be an effective structural HIV prevention intervention, but that the availability and accessibility of these programs must be increased.</p