International Research Institute for Climate and Society

The role of climate in health is currently enjoying a high profile among the international community in terms of demonstrating climate risk management and adaptation to a changing climate. The effect of climate variability and change on heath is a serious issue for most sub-Saharan African countries. Among the diseases that have public health importance in Ethiopia are malaria, meningitis and acute watery diarrhea. Understanding the relationship of climate and health in Ethiopia would be a tremendous help in early containment of these diseases. In Ethiopia, before the establishment of a Climate and Health Working Group (CHWG), which includes the Federal Ministry of Health and the National Meteorological Agency among other partners, the sharing of information among the two key players was minimal. The goal of this working group is to create a climate-informed health sector that routinely requests and uses appropriate climate information to improve the effectiveness of health interventions. In order to meet its goals, the working group, in collaboration with the International Research Institute for Climate and Society (IRI), organized a six-day training course for health professionals on climate and health. In this training, the Summer Institute course ‘Climate Information for Public Health’ (held for the past two years at IRI in New York), was adapted and implemented. The Summer Institute has involved four Ethiopian participants, one from the National Meteorological Agency (NMA), and three from the Ministry of Health. They played a key role in facilitating some of the course lectures themselves and in identifying local professionals who could also contribute to the curriculum. The general goal of the six-day training was to build the national capacity in order to utilize climate information for decision-making in the health sector at national and regional state levels. The training was comprised of three components: core lectures, practical sessions, and short recap presentations by the participants. Sixteen participants were involved in the training. The selection of the participants was done in consultation with the Federal Ministry of Health. Participants came primarily from the Public Health Emergency Management Units of regional and federal health bureaus and were chosen for their roles in the decision-making around the prevention and control of climate-sensitive diseases. Three types of evaluation were carried out, a pre- and post-test, as well as an overall evaluation. The pre- and post-test helped to evaluate the level of knowledge about climate and health before and after the training. The latter helped in evaluating the organization of the overall training. Generally, the evaluations revealed that the training helped to increase the knowledge of the links between climate and health, as well as the use of climate information for decision-making in the public health sector. This training is the first of its kind organized in Ethiopia, especially at a national level. Most of the participants agreed on the suitability of the content, design and delivery of the course and showed their interest in organizing similar training initiatives in their respective home institutions. It is possible to recommend that this training should be extended to the regional health bureau level, with the already trained participants taking the primary responsibility of facilitating these follow-on activities with the close support of the CHWG. The collaboration of the regional branch offices of the National Meteorological Agency, with respect to using climate information, would play a crucial role in this endeavor. The most important point is to sustain this training and update its contents accordingly. The future research agenda and evidence generation efforts of the CHWG and its members should also focus on other climate-sensitive diseases. Even though participants did not indicate there were always established ties to local universities in different parts of the country, these potential partnerships should be addressed in sharing the knowledge of the use of climate information for public health decision-making and in prioritizing locally important diseases. The training was held at UNECA, Addis Ababa, Ethiopia, between November 31st and December 5th, 2009. Financial and technical support was provided by IRI with funding from the Google.org sponsored project “Building Capacity to Produce and Use Climate and Environmental Information for Improving Health in East Africa”

Nuclear Localized LSR: A Novel Regulator of Breast Cancer Behavior and Tumorigenesis

Lipolysis Stimulated Lipoprotein Receptor (LSR) has been found in the plasma membrane and is believed to function in lipoprotein endocytosis and tight junctions. Given the impact of cellular metabolism and junction signaling pathways on tumor phenotypes and patient outcome, it is important to understand how LSR cellular localization mediates its functions. We conducted localization studies, evaluated DNA binding, and examined the effects of nuclear LSR in cells, xenografts, and clinical specimens. We found LSR within the membrane, cytoplasm, and the nucleus of breast cancer cells representing multiple intrinsic subtypes. Chromatin immunoprecipitation (ChIP) showed direct binding of LSR to DNA, and sequence analysis identified putative functional motifs and post-translational modifications of the LSR protein. While neither overexpression of transcript variants, nor pharmacological manipulation of post-translational modification significantly altered localization, inhibition of nuclear export enhanced nuclear localization, suggesting a mechanism for nuclear retention. Co-immunoprecipitation and proximal ligation assays indicated LSR-pericentrin interactions, presenting potential mechanisms for nuclear-localized LSR. The clinical significance of LSR was evaluated using data from over 1,100 primary breast tumors, which showed high LSR levels in basal-like tumors and tumors from African-Americans. In tumors histosections, nuclear localization was significantly associated with poor outcomes. Finally, in vivo xenograft studies revealed that basal-like breast cancer cells that over-express LSR exhibited both membrane and nuclear localization, and developed tumors with 100% penetrance, while control cells lacking LSR developed no tumors. These results show that nuclear LSR alters gene expression and may promote aggressive cancer phenotypes

Nonlinear beam cleanup in Yb-doped GRIN multimode fiber taper

We demonstrate beam self-cleaning in a tapered Ytterbium-doped graded- index multimode fiber in both active and passive configurations, without accompanying self-phase modulation induced spectral broadening or frequency conversio

Using climate information in the health sector

Many infectious and chronic diseases are either directly or indirectly sensitive to the climate. Managing this climate sensitivity more effectively requires new working relationships between the health sector and the providers of climate data and information. In Africa, where communities are particularly vulnerable, Ministries of Health and National Meteorological Services need to collaborate to reduce the burden of climaterelated ill health

In vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in Central Ethiopia

<p>Abstract</p> <p>Background</p> <p><it>In vivo </it>efficacy assessments of the first-line treatments for <it>Plasmodium falciparum </it>malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated <it>P. falciparum </it>malaria since 2004.</p> <p>Methods</p> <p>Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for <it>P. falciparum </it>in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented <it>P. falciparum </it>mono-infection were enrolled and followed according to the standard 2009 World Health Organization <it>in vivo </it>drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively.</p> <p>Results</p> <p>Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1) and 86.6% (95% CI 79.1-92.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6) and 87.3% (95% CI 79.9-92.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight <it>P. falciparum </it>patients (6.7%) presented with <it>Plasmodium vivax </it>infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the most common adverse events.</p> <p>Conclusions</p> <p>AL remains a highly effective and well-tolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia with <it>P. vivax </it>possibly from relapse or new infection was observed.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01052584">NCT01052584</a></p

Assessment of the therapeutic efficacy of a paediatric formulation of artemether-lumefantrine (Coartesiane(®)) for the treatment of uncomplicated Plasmodium falciparum in children in Zambia

BACKGROUND: Sentinel site surveillance of antimalarials by in-vivo therapeutic efficacy studies in Zambia is one of the key activities ear-marked for monitoring and evaluation. The studies are conducted annually in order to provide timely and reliable information on the status of the recommended regimens for malaria case management. The findings of the therapeutic efficacy of an artemisinin-based combination therapy of pediatric artemether-lumefantrine (Coartesiane(®)) are reported. METHOD: The design is a simple, one-arm, prospective evaluation of the clinical and parasitological response to directly observed treatment for uncomplicated malaria. The study was conducted in sentinel sites using the WHO standardized protocol for the assessment of therapeutic efficacy of antimalarial drugs (WHO 2000) in children under five years of age, weighing less than 10 Kg. The study was conducted at two clinics, one in Chongwe (Lusaka Province) and Chipata (Eastern Province). The 28-day follow-up period was used coupled with PCR genotyping for MSP1 and MSP2 in order to differentiate recrudescence from re-infections for parasites that appeared after Day 14. RESULTS: 91/111 children enrolled in the study, were successfully followed up. Artemether-lumefantrine (Coartesiane(®)) was found to produce significant gametocyte reduction. The Adequate Clinical and Parasitological Response (ACPR) was found to be 100% (95% CI 96.0;100). CONCLUSION: Coartesiane(® )was effective in treating uncomplicated malaria in Zambian children weighing less than 10 kg, an age group normally excluded from taking the tablet formulation of artemether-lumefantrine (Coartem(®))

Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study

Pre-pregnancy obesity is an established risk factor for adverse sex-specific cardiometabolic health in offspring. Epigenetic alterations, such as in DNA methylation (DNAm), are a hypothesized link; however, sex-specific epigenomic targets remain unclear. Leveraging data from the Newborn Epigenetics Study (NEST) cohort, linear regression models were used to identify CpG sites in cord blood leukocytes associated with pre-pregnancy obesity in 187 mother-female and 173 mother-male offsprings. DNAm in cord blood was measured using the Illumina HumanMethylation450k BeadChip. Replication analysis was conducted among the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Associations between pre-pregnancy obesity-associated CpG sites and offspring BMI z-score (BMIz) and blood pressure (BP) percentiles at 4–5-years of age were also examined. Maternal pre-pregnacy obesity was associated with 876 CpGs in female and 293 CpGs in male offspring (false discovery rate <5%). Among female offspring, 57 CpG sites, including the top 18, mapped to the TAPBP gene (range of effect estimates: −0.83% decrease to 4.02% increase in methylation). CpG methylation differences in the TAPBP gene were also observed among males (range of effect estimates: −0.30% decrease to 2.59% increase in methylation). While technically validated, none of the TAPBP CpG sites were replicated in ALSPAC. In NEST, methylation differences at CpG sites of the TAPBP gene were associated with BMI z-score (cg23922433 and cg17621507) and systolic BP percentile (cg06230948) in female and systolic (cg06230948) and diastolic (cg03780271) BP percentile in male offspring. Together, these findings suggest sex-specific effects, which, if causal, may explain observed sex-specific effects of maternal obesity