Adaptive Use of Information during Growth Can Explain Long-Term Effects of Early Life Experiences.

Development is a continuous process during which individuals gain information about their environment and adjust their phenotype accordingly. In many natural systems, individuals are particularly sensitive to early life experiences, even in the absence of later constraints on plasticity. Recent models have highlighted how the adaptive use of information can explain age-dependent plasticity. These models assume that information gain and phenotypic adjustments either cannot occur simultaneously or are completely independent. This assumption is not valid in the context of growth, where finding food results both in a size increase and learning about food availability. Here, we describe a simple model of growth to provide proof of principle that long-term effects of early life experiences can arise through the coupled dynamics of information acquisition and phenotypic change in the absence of direct constraints on plasticity. The increase in reproductive value from gaining information and sensitivity of behavior to experiences declines across development. Early life experiences have long-term impacts on age of maturity, yet-due to compensatory changes in behavior-our model predicts no substantial effects on reproductive success. We discuss how the evolution of sensitive windows can be explained by experiences having short-term effects on informational and phenotypic states, which generate long-term effects on life-history decisions.This research was funded by the European Union’s Seventh Framework Programme (FP7/2007-2011) under grant 259679 (IDEAL) awarded to T.U. T.W.F., A.D.H., and P.C.T. were supported by the European Research Council (ERC Advanced Grant 250209 Evomech to A. Houston). T.U. was supported by the Royal Society of London and the Knut and Alice Wallenberg Foundation. A.D.H. was supported by fellowships from the Wissenschaftskolleg zu Berlin and the Natural Environment Research Council (grant NE/L011921/1)

Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention

Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target

Perceptions about data-informed decisions: an assessment of information-use in high HIV-prevalence settings in South Africa

BACKGROUND: Information-use is an integral component of a routine health information system and essential to influence policy-making, program actions and research. Despite an increased amount of routine data collected, planning and resource-allocation decisions made by health managers for managing HIV programs are often not based on data. This study investigated the use of information, and barriers to using routine data for monitoring the prevention of mother-to-child transmission of HIV (PMTCT) programs in two high HIV-prevalence districts in South Africa. METHODS: We undertook an observational study using a multi-method approach, including an inventory of facility records and reports. The performance of routine information systems management (PRISM) diagnostic ‘Use of Information’ tool was used to assess the PMTCT information system for evidence of data use in 57 health facilities in two districts. Twenty-two in-depth interviews were conducted with key informants to investigate barriers to information use in decision-making. Participants were purposively selected based on their positions and experience with either producing PMTCT data and/or using data for management purposes. We computed descriptive statistics and used a general inductive approach to analyze the qualitative data. RESULTS: Despite the availability of mechanisms and processes to facilitate information-use in about two-thirds of the facilities, evidence of information-use (i.e., indication of some form of information-use in available RHIS reports) was demonstrated in 53% of the facilities. Information was inadequately used at district and facility levels to inform decisions and planning, but was selectively used for reporting and monitoring program outputs at the provincial level. The inadequate use of information stemmed from organizational issues such as the lack of a culture of information-use, lack of trust in the data, and the inability of program and facility managers to analyze, interpret and use information. CONCLCUSIONS: Managers’ inability to use information implied that decisions for program implementation and improving service delivery were not always based on data. This lack of data use could influence the delivery of health care services negatively. Facility and program managers should be provided with opportunities for capacity development as well as practice-based, in-service training, and be supported to use information for planning, management and decision-making

Emerging infectious disease implications of invasive mammalian species : the greater white-toothed shrew (Crocidura russula) is associated with a novel serovar of pathogenic Leptospira in Ireland

The greater white-toothed shrew (Crocidura russula) is an invasive mammalian species that was first recorded in Ireland in 2007. It currently occupies an area of approximately 7,600 km2 on the island. C. russula is normally distributed in Northern Africa and Western Europe, and was previously absent from the British Isles. Whilst invasive species can have dramatic and rapid impacts on faunal and floral communities, they may also be carriers of pathogens facilitating disease transmission in potentially naive populations. Pathogenic leptospires are endemic in Ireland and a significant cause of human and animal disease. From 18 trapped C. russula, 3 isolates of Leptospira were cultured. However, typing of these isolates by standard serological reference methods was negative, and suggested an, as yet, unidentified serovar. Sequence analysis of 16S ribosomal RNA and secY indicated that these novel isolates belong to Leptospira alstonii, a unique pathogenic species of which only 7 isolates have been described to date. Earlier isolations were limited geographically to China, Japan and Malaysia, and this leptospiral species had not previously been cultured from mammals. Restriction enzyme analysis (REA) further confirms the novelty of these strains since no similar patterns were observed with a reference database of leptospires. As with other pathogenic Leptospira species, these isolates contain lipL32 and do not grow in the presence of 8-azagunaine; however no evidence of disease was apparent after experimental infection of hamsters. These isolates are genetically related to L. alstonii but have a novel REA pattern; they represent a new serovar which we designate as serovar Room22. This study demonstrates that invasive mammalian species act as bridge vectors of novel zoonotic pathogens such as Leptospira

Tumour cells expressing single VEGF isoforms display distinct growth, survival and migration characteristics

Vascular endothelial growth factor-A (VEGF) is produced by most cancer cells as multiple isoforms, which display distinct biological activities. VEGF plays an undisputed role in tumour growth, vascularisation and metastasis; nevertheless the functions of individual isoforms in these processes remain poorly understood. We investigated the effects of three main murine isoforms (VEGF188, 164 and 120) on tumour cell behaviour, using a panel of fibrosarcoma cells we developed that express them individually under endogenous promoter control. Fibrosarcomas expressing only VEGF188 (fs188) or wild type controls (fswt) were typically mesenchymal, formed ruffles and displayed strong matrix-binding activity. VEGF164- and VEGF120-producing cells (fs164 and fs120 respectively) were less typically mesenchymal, lacked ruffles but formed abundant cell-cell contacts. On 3D collagen, fs188 cells remained mesenchymal while fs164 and fs120 cells adopted rounded/amoeboid and a mix of rounded and elongated morphologies respectively. Consistent with their mesenchymal characteristics, fs188 cells migrated significantly faster than fs164 or fs120 cells on 2D surfaces while contractility inhibitors accelerated fs164 and fs120 cell migration. VEGF164/VEGF120 expression correlated with faster proliferation rates and lower levels of spontaneous apoptosis than VEGF188 expression. Nevertheless, VEGF188 was associated with constitutively active/phosphorylated AKT, ERK1/2 and Stat3 proteins. Differences in proliferation rates and apoptosis could be explained by defective signalling downstream of pAKT to FOXO and GSK3 in fs188 and fswt cells, which also correlated with p27/p21 cyclin-dependent kinase inhibitor over-expression. All cells expressed tyrosine kinase VEGF receptors, but these were not active/activatable suggesting that inherent differences between the cell lines are governed by endogenous VEGF isoform expression through complex interactions that are independent of tyrosine kinase receptor activation. VEGF isoforms are emerging as potential biomarkers for anti-VEGF therapies. Our results reveal novel roles of individual isoforms associated with cancer growth and metastasis and highlight the importance of understanding their diverse actions

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

From PALSA PLUS to PALM PLUS: adapting and developing a South African guideline and training intervention to better integrate HIV/AIDS care with primary care in rural health centers in Malawi

<p>Abstract</p> <p>Background</p> <p>Only about one-third of eligible HIV/AIDS patients receive anti-retroviral treatment (ART). Decentralizing treatment is crucial to wider and more equitable access, but key obstacles are a shortage of trained healthcare workers (HCW) and challenges integrating HIV/AIDS care with other primary care. This report describes the development of a guideline and training program (PALM PLUS) designed to integrate HIV/AIDS care with other primary care in Malawi. PALM PLUS was adapted from PALSA PLUS, developed in South Africa, and targets middle-cadre HCWs (clinical officers, nurses, and medical assistants). We adapted it to align with Malawi's national treatment protocols, more varied healthcare workforce, and weaker health system infrastructure.</p> <p>Methods/Design</p> <p>The international research team included the developers of the PALSA PLUS program, key Malawi-based team members and personnel from national and district level Ministry of Health (MoH), professional associations, and an international non-governmental organization. The PALSA PLUS guideline was extensively revised based on Malawi national disease-specific guidelines. Advice and input was sought from local clinical experts, including middle-cadre personnel, as well as Malawi MoH personnel and representatives of Malawian professional associations.</p> <p>Results</p> <p>An integrated guideline adapted to Malawian protocols for adults with respiratory conditions, HIV/AIDS, tuberculosis, and other primary care conditions was developed. The training program was adapted to Malawi's health system and district-level supervision structure. PALM PLUS is currently being piloted in a cluster-randomized trial in health centers in Malawi (ISRCTN47805230).</p> <p>Discussion</p> <p>The PALM PLUS guideline and training intervention targets primary care middle-cadre HCWs with the objective of improving HCW satisfaction and retention, and the quality of patient care. Successful adaptations are feasible, even across health systems as different as those of South Africa and Malawi.</p

Impact of Inconsistent Policies for Transfusion-Transmitted Malaria on Clinical Practice in Ghana

Background: Policies concerning the prevention of transfusion transmitted malaria (TTM) are the responsibility of blood transfusion services and malaria control programmes. To prevent spreading drug resistance due to over-use of malaria drugs, recent malaria treatment guidelines recommend prompt parasitological confirmation before treatment is started. In contrast, blood safety policies from the World Health Organisation (WHO) recommend presumptive malaria treatment for recipients of blood in endemic countries but evidence supporting this approach is lacking. Our study documented how these conflicting policies relating to malaria transmission through blood transfusion impact on clinical practice in a teaching hospital in West Africa. Methods/Principal Findings: We randomly selected and reviewed case notes of 151 patients within 24 hours of their receiving a blood transfusion. Transfusion practices including the confirmation of diagnosis and anti-malarial treatment given were compared across three departments; Obstetrics and Gynaecology (O&amp;G), Paediatrics and Medicine. Overall, 66 (44%) of patients received malaria treatment within 24 hrs of their blood transfusion; of which only 2 (3%) received antimalarials based on a laboratory confirmation of malaria. Paediatric patients (87%) received the most anti-malarials and only 7 % and 24 % of recipients in medicine and O&amp;G respectively received anti malarials. In 51 patients (78%), the anti-malarials were prescribed at the same time as the blood transfusion and anti-malarials prescriptions exceeded the number of patient

Neuronal hypoxia in vitro: Investigation of therapeutic principles of HUCB-MNC and CD133+ stem cells

Background The therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood. Methods A human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array. Results tMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7% ± 3%). Untreated post-hypoxic control cultures showed apoptosis rates of 85% ± 11%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures. Conclusion Our data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes

Preprandial ghrelin is not affected by macronutrient intake, energy intake or energy expenditure

BACKGROUND: Ghrelin, a peptide secreted by endocrine cells in the gastrointestinal tract, is a hormone purported to have a significant effect on food intake and energy balance in humans. The influence of factors related to energy balance on ghrelin, such as daily energy expenditure, energy intake, and macronutrient intake, have not been reported. Secondly, the effect of ghrelin on food intake has not been quantified under free-living conditions over a prolonged period of time. To investigate these effects, 12 men were provided with an ad libitum cafeteria-style diet for 16 weeks. The macronutrient composition of the diets were covertly modified with drinks containing 2.1 MJ of predominantly carbohydrate (Hi-CHO), protein (Hi-PRO), or fat (Hi-FAT). Total energy expenditure was measured for seven days on two separate occasions (doubly labeled water and physical activity logs). RESULTS: Preprandial ghrelin concentrations were not affected by macronutrient intake, energy expenditure or energy intake (all P > 0.05). In turn, daily energy intake was significantly influenced by energy expenditure, but not ghrelin. CONCLUSION: Preprandial ghrelin does not appear to be influenced by macronutrient composition, energy intake, or energy expenditure. Similarly, ghrelin does not appear to affect acute or chronic energy intake under free-living conditions