Good Health at Low Cost 25 years on: lessons for the future of health systems strengthening.

In 1985, the Rockefeller Foundation published Good health at low cost to discuss why some countries or regions achieve better health and social outcomes than do others at a similar level of income and to show the role of political will and socially progressive policies. 25 years on, the Good Health at Low Cost project revisited these places but looked anew at Bangladesh, Ethiopia, Kyrgyzstan, Thailand, and the Indian state of Tamil Nadu, which have all either achieved substantial improvements in health or access to services or implemented innovative health policies relative to their neighbours. A series of comparative case studies (2009-11) looked at how and why each region accomplished these changes. Attributes of success included good governance and political commitment, effective bureaucracies that preserve institutional memory and can learn from experience, and the ability to innovate and adapt to resource limitations. Furthermore, the capacity to respond to population needs and build resilience into health systems in the face of political unrest, economic crises, and natural disasters was important. Transport infrastructure, female empowerment, and education also played a part. Health systems are complex and no simple recipe exists for success. Yet in the countries and regions studied, progress has been assisted by institutional stability, with continuity of reforms despite political and economic turmoil, learning lessons from experience, seizing windows of opportunity, and ensuring sensitivity to context. These experiences show that improvements in health can still be achieved in countries with relatively few resources, though strategic investment is necessary to address new challenges such as complex chronic diseases and growing population expectations

The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial

Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients

An aqueous non-heme Fe(iv)oxo complex with a basic group in the second coordination sphere

The Fe(IV)oxo complex of a coordinatively flexible multidentate mono-carboxylato ligand is obtained by the one electron oxidation of a low spin Fe(III) precursor in water

Improving mental health and psychosocial wellbeing in humanitarian settings: Reflections on research funded through R2HC

From Springer Nature via Jisc Publications RouterMajor knowledge gaps remain concerning the most effective ways to address mental health and psychosocial needs of populations affected by humanitarian crises. The Research for Health in Humanitarian Crisis (R2HC) program aims to strengthen humanitarian health practice and policy through research. As a significant portion of R2HC’s research has focused on mental health and psychosocial support interventions, the program has been interested in strengthening a community of practice in this field. Following a meeting between grantees, we set out to provide an overview of the R2HC portfolio, and draw lessons learned. In this paper, we discuss the mental health and psychosocial support-focused research projects funded by R2HC; review the implications of initial findings from this research portfolio; and highlight four remaining knowledge gaps in this field. Between 2014 and 2019, R2HC funded 18 academic-practitioner partnerships focused on mental health and psychosocial support, comprising 38% of the overall portfolio (18 of 48 projects) at a value of approximately 7.2 million GBP. All projects have focused on evaluating the impact of interventions. In line with consensus-based recommendations to consider a wide range of mental health and psychosocial needs in humanitarian settings, research projects have evaluated diverse interventions. Findings so far have both challenged and confirmed widely-held assumptions about the effectiveness of mental health and psychosocial interventions in humanitarian settings. They point to the importance of building effective, sustained, and diverse partnerships between scholars, humanitarian practitioners, and funders, to ensure long-term program improvements and appropriate evidence-informed decision making. Further research needs to fill knowledge gaps regarding how to: scale-up interventions that have been found to be effective (e.g., questions related to integration across sectors, adaptation of interventions across different contexts, and optimal care systems); address neglected mental health conditions and populations (e.g., elderly, people with disabilities, sexual minorities, people with severe, pre-existing mental disorders); build on available local resources and supports (e.g., how to build on traditional, religious healing and community-wide social support practices); and ensure equity, quality, fidelity, and sustainability for interventions in real-world contexts (e.g., answering questions about how interventions from controlled studies can be transferred to more representative humanitarian contexts).All studies described here were funded by Elrha’s Research for Health in Humanitarian Crises (R2HC) Programme, which aims to improve health outcomes by strengthening the evidence base for public health interventions in humanitarian crises.14pubpu

Setting priorities for humanitarian water, sanitation and hygiene research: a meeting report

Recent systematic reviews have highlighted a paucity of rigorous evidence to guide water, sanitation and hygiene (WASH) interventions in humanitarian crises. In June 2017, the Research for Health in Humanitarian Crises (R2HC) programme of Elhra, convened a meeting of representatives from international response agencies, research institutions and donor organisations active in the field of humanitarian WASH to identify research priorities, discuss challenges conducting research and to establish next steps. Topics including cholera transmission, menstrual hygiene management, and acute undernutrition were identified as research priorities. Several international response agencies have existing research programmes; however, a more cohesive and coordinated effort in the WASH sector would likely advance this field of research. This report shares the conclusions of that meeting and proposes a research agenda with the aim of strengthening humanitarian WASH policy and practice

Novel Primate Model of Serotonin Transporter Genetic Polymorphisms Associated with Gene Expression, Anxiety and Sensitivity to Antidepressants

This is the final version of the article. It first appeared from Nature Publishing Group via https://dx.doi.org/10.1038/npp.2016.41Genetic polymorphisms in the repeat upstream region of the serotonin transporter gene (SLC6A4) are associated with individual differences in stress reactivity, vulnerability to affective disorders and response to pharmacotherapy. However, the molecular, neurodevelopmental and psychopharmacological mechanisms underlying the link between SLC6A4 polymorphisms and the emotionally vulnerable phenotype are not fully understood. Thus, using the marmoset monkey Callithrix jacchus we characterize here a new neurobiological model to help to address these questions. We first sequenced the marmoset SLC6A4 promoter and identified a double nucleotide polymorphism (−2053AC/CT) and two single nucleotide polymorphisms (−2022C/T and −1592G/C) within the repeat upstream region. We showed their association with gene expression using in vivo quantitative PCR and with affective behavior using a primate test of anxiety (human intruder test). The low-expressing haplotype (AC/C/G) was linked with high anxiety whilst the high-expressing one (CT/T/C) was associated with an active coping strategy in response to threat. Pharmacological challenge with an acute dose of the selective serotonin reuptake inhibitor (SSRI), citalopram, revealed a genotype-dependent behavioral response. Whilst individuals homozygous for the high anxiety-related haplotype AC/C/G exhibited a dose-dependent, anxiogenic response, individuals homozygous for the low anxiety-related haplotype CT/T/C showed an opposing, dose-dependent anxiolytic effect. These findings provide a novel genetic and behavioral primate model to study the molecular, neurodevelopmental and psychopharmacological mechanisms that underlie genetic variation-associated complex behaviors, with specific implications for the understanding of normal and abnormal serotonin actions and the development of personalized pharmacological treatments for psychiatric disorders.Work was supported by an MRC Programme (ACR; G0901884) and performed within the Behavioural and Clinical Neuroscience Institute, University of Cambridge, funded jointly by the Wellcome Trust and MRC. AMS was supported by a McDonnell Foundation grant (PI’s: E. Phelps, T.W. Robbins; Co-Investigators: ACR and J. LeDoux; 22002015501) and currently supported by MRC; YS supported by the Long Term Student Support Program provided by Osaka University and the Ministry of Education, Culture, Sports, Science and Technology of Japan; HC supported by MRC Career Development Award and ACFS/MI supported by grants from the MRC and Wellcome Trust. GC supported by the Behavioural and Clinical Neuroscience Institute, Cambridge, United Kingdom. EHSS was self-funded

Improving mental health and psychosocial wellbeing in humanitarian settings: reflections on research funded through R2HC

Major knowledge gaps remain concerning the most effective ways to address mental health and psychosocial needs of populations affected by humanitarian crises. The Research for Health in Humanitarian Crisis (R2HC) program aims to strengthen humanitarian health practice and policy through research. As a significant portion of R2HC’s research has focused on mental health and psychosocial support interventions, the program has been interested in strengthening a community of practice in this field. Following a meeting between grantees, we set out to provide an overview of the R2HC portfolio, and draw lessons learned. In this paper, we discuss the mental health and psychosocial support-focused research projects funded by R2HC; review the implications of initial findings from this research portfolio; and highlight four remaining knowledge gaps in this field. Between 2014 and 2019, R2HC funded 18 academic-practitioner partnerships focused on mental health and psychosocial support, comprising 38% of the overall portfolio (18 of 48 projects) at a value of approximately 7.2 million GBP. All projects have focused on evaluating the impact of interventions. In line with consensus-based recommendations to consider a wide range of mental health and psychosocial needs in humanitarian settings, research projects have evaluated diverse interventions. Findings so far have both challenged and confirmed widely-held assumptions about the effectiveness of mental health and psychosocial interventions in humanitarian settings. They point to the importance of building effective, sustained, and diverse partnerships between scholars, humanitarian practitioners, and funders, to ensure long-term program improvements and appropriate evidence-informed decision making. Further research needs to fill knowledge gaps regarding how to: scale-up interventions that have been found to be effective (e.g., questions related to integration across sectors, adaptation of interventions across different contexts, and optimal care systems); address neglected mental health conditions and populations (e.g., elderly, people with disabilities, sexual minorities, people with severe, pre-existing mental disorders); build on available local resources and supports (e.g., how to build on traditional, religious healing and community-wide social support practices); and ensure equity, quality, fidelity, and sustainability for interventions in real-world contexts (e.g., answering questions about how interventions from controlled studies can be transferred to more representative humanitarian contexts)

Regulation of the Fruit-Specific PEP Carboxylase SlPPC2 Promoter at Early Stages of Tomato Fruit Development

The SlPPC2 phosphoenolpyruvate carboxylase (PEPC; EC 4.1.1.31) gene from tomato (Solanum lycopersicum) is differentially and specifically expressed in expanding tissues of developing tomato fruit. We recently showed that a 1966 bp DNA fragment located upstream of the ATG codon of the SlPPC2 gene (GenBank AJ313434) confers appropriate fruit-specificity in transgenic tomato. In this study, we further investigated the regulation of the SlPPC2 promoter gene by analysing the SlPPC2 cis-regulating region fused to either the firefly luciferase (LUC) or the β-glucuronidase (GUS) reporter gene, using stable genetic transformation and biolistic transient expression assays in the fruit. Biolistic analyses of 5′ SlPPC2 promoter deletions fused to LUC in fruits at the 8th day after anthesis revealed that positive regulatory regions are mostly located in the distal region of the promoter. In addition, a 5′ UTR leader intron present in the 1966 bp fragment contributes to the proper temporal regulation of LUC activity during fruit development. Interestingly, the SlPPC2 promoter responds to hormones (ethylene) and metabolites (sugars) regulating fruit growth and metabolism. When tested by transient expression assays, the chimeric promoter:LUC fusion constructs allowed gene expression in both fruit and leaf, suggesting that integration into the chromatin is required for fruit-specificity. These results clearly demonstrate that SlPPC2 gene is under tight transcriptional regulation in the developing fruit and that its promoter can be employed to drive transgene expression specifically during the cell expansion stage of tomato fruit. Taken together, the SlPPC2 promoter offers great potential as a candidate for driving transgene expression specifically in developing tomato fruit from various tomato cultivars