Cytonuclear discordance in the Florida Everglades invasive Burmese python (Python bivittatus) population reveals possible hybridization with the Indian python (P. molurus)

The invasive Burmese python (Python bivittatus) has been reproducing in the Florida Everglades since the 1980s. These giant constrictor snakes have caused a precipitous decline in small mammal populations in southern Florida following escapes or releases from the commercial pet trade. To better understand the invasion pathway and genetic composition of the population, two mitochondrial (mtDNA) loci across 1,398 base pairs were sequenced on 426 snakes and 22 microsatellites were assessed on 389 snakes. Concatenated mtDNA sequences produced six haplotypes with an average nucleotide and haplotype diversity of π = 0.002 and h = 0.097, respectively. Samples collected in Florida from morphologically identified P. bivittatus snakes were similar to published cytochrome oxidase 1 and cytochrome b sequences from both P. bivittatus and Python molurus and were highly divergent (genetic distances of 5.4% and 4.3%, respectively). The average number of microsatellite alleles and expected heterozygosity were NA = 5.50 and HE = 0.60, respectively. Nuclear Bayesian assignment tests supported two genetically distinct groups and an admixed group, not geographically differentiated. The effective population size (NE = 315.1) was lower than expected for a population this large, but reflected the low genetic diversity overall. The patterns of genetic diversity between mtDNA and microsatellites were disparate, indicating nuclear introgression of separate mtDNA lineages corresponding to cytonuclear discordance. The introgression likely occurred prior to the invasion, but genetic information on the native range and commercial trade is needed for verification. Our finding that the Florida python population is comprised of distinct lineages suggests greater standing variation for adaptation and the potential for broader areas of suitable habitat in the invaded range

Key factors leading to reduced recruitment and retention of health professionals in remote areas of Ghana: a qualitative study and proposed policy solutions

Background: The ability of many countries to achieve national health goals such as the Millennium Development Goals remains hindered by inadequate and poorly distributed health personnel, including doctors. The distribution of doctors in Ghana is highly skewed, with a majority serving in two major metropolitan areas (Accra and Kumasi), and inadequate numbers in remote and rural districts. Recent policies increasing health worker salaries have reduced migration of doctors out of Ghana, but made little difference to distribution within the country. This qualitative study was undertaken to understand how practicing doctors and medical leaders in Ghana describe the key factors reducing recruitment and retention of health professionals into remote areas, and to document their proposed policy solutions. Methods: In-depth interviews were carried out with 84 doctors and medical leaders, including 17 regional medical directors and deputy directors from across Ghana, and 67 doctors currently practicing in 3 regions (Greater Accra, Brong Ahafo, and Upper West); these 3 regions were chosen to represent progressively more remote distances from the capital of Accra. Results and discussion: All participants felt that rural postings must have special career or monetary incentives given the loss of locum (i.e. moonlighting income), the higher workload, and professional isolation of remote assignments. Career 'death' and prolonged rural appointments were a common fear, and proposed policy solutions focused considerably on career incentives, such as guaranteed promotion or a study opportunity after some fixed term of service in a remote or hardship area. There was considerable stress placed on the need for rural doctors to have periodic contact with mentors through rural rotation of specialists, or remote learning centers, and reliable terms of appointment with fixed end-points. Also raised, but given less emphasis, were concerns about the adequacy of clinical equipment in remote facilities, and remote accommodations. Conclusions: In-depth discussions with doctors suggest that while salary is important, it is career development priorities that are keeping doctors in urban centers. Short-term service in rural areas would be more appealing if it were linked to special mentoring and/or training, and led to career advancement

For money or service? a cross-sectional survey of preference for financial versus non-financial rural practice characteristics among ghanaian medical students

Abstract Background Health worker shortage and maldistribution are among the biggest threats to health systems in Africa. New medical graduates are prime targets for recruitment to deprived rural areas. However, little research has been done to determine the influence of workers' background and future plans on their preference for rural practice incentives and characteristics. The purpose of this study was to identify determinants of preference for rural job characteristics among fourth year medical students in Ghana. Methods We asked fourth-year Ghanaian medical students to rank the importance of rural practice attributes including salary, infrastructure, management style, and contract length in considering future jobs. We used bivariate and multivariate ordinal logistic regression to estimate the association between attribute valuation and students' socio-demographic background, educational experience, and future career plans. Results Of 310 eligible fourth year medical students, complete data was available for 302 students (97%). Students considering emigration ranked salary as more important than students not considering emigration, while students with rural living experience ranked salary as less important than those with no rural experience. Students willing to work in a rural area ranked infrastructure as more important than students who were unwilling, while female students ranked infrastructure as less important than male students. Students who were willing to work in a rural area ranked management style as a more important rural practice attribute than those who were unwilling to work in a rural area. Students studying in Kumasi ranked contract length as more important than those in Accra, while international students ranked contract length as less important than Ghanaian students. Conclusions Interventions to improve rural practice conditions are likely to be more persuasive than salary incentives to Ghanaian medical students who are willing to work in rural environments a priori. Policy experiments should test the impact of these interventions on actual uptake by students upon graduation.http://deepblue.lib.umich.edu/bitstream/2027.42/112499/1/12913_2011_Article_1837.pd

Protective Antibody and CD8+ T-Cell Responses to the Plasmodium falciparum Circumsporozoite Protein Induced by a Nanoparticle Vaccine

Background The worldwide burden of malaria remains a major public health problem due, in part, to the lack of an effective vaccine against the Plasmodium falciparum parasite. An effective vaccine will most likely require the induction of antigen specific CD8+ and CD4+ T-cells as well as long-lasting antibody responses all working in concert to eliminate the infection. We report here the effective modification of a self-assembling protein nanoparticle (SAPN) vaccine previously proven effective in control of a P. berghei infection in a rodent model to now present B- and T-cell epitopes of the human malaria parasite P. falciparum in a platform capable of being used in human subjects. Methodology/Principal Findings To establish the basis for a SAPN-based vaccine, B- and CD8+ T-cell epitopes from the P. falciparum circumsporozoite protein (PfCSP) and the universal CD4 T-helper epitope PADRE were engineered into a versatile small protein (∼125 amino acids) that self-assembles into a spherical nanoparticle repetitively displaying the selected epitopes. P. falciparum epitope specific immune responses were evaluated in mice using a transgenic P. berghei malaria parasite of mice expressing the human malaria full-length P. falciparum circumsporozoite protein (Tg-Pb/PfCSP). We show that SAPN constructs, delivered in saline, can induce high-titer, long-lasting (1 year) protective antibody and poly-functional (IFNγ+, IL-2+) long-lived central memory CD8+ T-cells. Furthermore, we demonstrated that these Ab or CD8+ T–cells can independently provide sterile protection against a lethal challenge of the transgenic parasites. Conclusion The SAPN construct induces long-lasting antibody and cellular immune responses to epitope specific sequences of the P. falciparum circumsporozoite protein (PfCSP) and prevents infection in mice by a transgenic P. berghei parasite displaying the full length PfCSP

Willingness to work in rural areas and the role of intrinsic versus extrinsic professional motivations - a survey of medical students in Ghana

<p>Abstract</p> <p>Background</p> <p>Retaining health workers in rural areas is challenging for a number of reasons, ranging from personal preferences to difficult work conditions and low remuneration. This paper assesses the influence of intrinsic and extrinsic motivation on willingness to accept postings to deprived areas among medical students in Ghana.</p> <p>Methods</p> <p>A computer-based survey involving 302 fourth year medical students was conducted from May-August 2009. Logistic regression was used to assess the association between students' willingness to accept rural postings and their professional motivations, rural exposure and family parental professional and educational status (PPES).</p> <p>Results</p> <p>Over 85% of students were born in urban areas and 57% came from affluent backgrounds. Nearly two-thirds of students reported strong intrinsic motivation to study medicine. After controlling for demographic characteristics and rural exposure, motivational factors did not influence willingness to practice in rural areas. High family PPES was consistently associated with lower willingness to work in rural areas.</p> <p>Conclusions</p> <p>Although most Ghanaian medical students are motivated to study medicine by the desire to help others, this does not translate into willingness to work in rural areas. Efforts should be made to build on intrinsic motivation during medical training and in designing rural postings, as well as favour lower PPES students for admission.</p

Burmese pythons in Florida: A synthesis of biology, impacts, and management tools

Burmese pythons (Python molurus bivittatus) are native to southeastern Asia, however, there is an established invasive population inhabiting much of southern Florida throughout the Greater Everglades Ecosystem. Pythons have severely impacted native species and ecosystems in Florida and represent one of the most intractable invasive-species management issues across the globe. The difficulty stems from a unique combination of inaccessible habitat and the cryptic and resilient nature of pythons that thrive in the subtropical environment of southern Florida, rendering them extremely challenging to detect. Here we provide a comprehensive review and synthesis of the science relevant to managing invasive Burmese pythons. We describe existing control tools and review challenges to productive research, identifying key knowledge gaps that would improve future research and decision making for python control. (119 pp

Improving educational achievement and anaemia of school children: design of a cluster randomised trial of school-based malaria prevention and enhanced literacy instruction in Kenya

BACKGROUND: Improving the health of school-aged children can yield substantial benefits for cognitive development and educational achievement. However, there is limited experimental evidence on the benefits of school-based malaria prevention or how health interventions interact with other efforts to improve education quality. This study aims to evaluate the impact of school-based malaria prevention and enhanced literacy instruction on the health and educational achievement of school children in Kenya. DESIGN: A factorial, cluster randomised trial is being implemented in 101 government primary schools on the coast of Kenya. The interventions are (i) intermittent screening and treatment of malaria in schools by public health workers and (ii) training workshops and support for teachers to promote explicit and systematic literacy instruction. Schools are randomised to one of four groups: receiving either (i) the malaria intervention alone; (ii) the literacy intervention alone; (iii) both interventions combined; or (iv) control group where neither intervention is implemented. Children from classes 1 and 5 are randomly selected and followed up for 24 months. The primary outcomes are educational achievement and anaemia, the hypothesised mediating variables through which education is affected. Secondary outcomes include malaria parasitaemia, school attendance and school performance. A nested process evaluation, using semi-structured interviews, focus group discussion and a stakeholder analysis will investigate the community acceptability, feasibility and cost-effectiveness of the interventions. DISCUSSION: Across Africa, governments are committed to improve health and education of school-aged children, but seek clear policy and technical guidance as to the optimal approach to address malaria and improved literacy. This evaluation will be one of the first to simultaneously evaluate the impact of health and education interventions in the improvement of educational achievement. Reflection is made on the practical issues encountered in conducting research in schools in Africa. TRIAL REGISTRATION: National Institutes of Health NCT00878007

Lack of Association of Interferon Regulatory Factor 1 with Severe Malaria in Affected Child-Parental Trio Studies across Three African Populations

Interferon Regulatory Factor 1 (IRF-1) is a member of the IRF family of transcription factors, which have key and diverse roles in the gene-regulatory networks of the immune system. IRF-1 has been described as a critical mediator of IFN-gamma signalling and as the major player in driving TH1 type responses. It is therefore likely to be crucial in both innate and adaptive responses against intracellular pathogens such as Plasmodium falciparum. Polymorphisms at the human IRF1 locus have been previously found to be associated with the ability to control P. falciparum infection in populations naturally exposed to malaria. In order to test whether genetic variation at the IRF1 locus also affects the risk of developing severe malaria, we performed a family-based test of association for 18 Single Nucleotide Polymorphisms (SNPs) across the gene in three African populations, using genotype data from 961 trios consisting of one affected child and his/her two parents (555 from The Gambia, 204 from Kenya and 202 from Malawi). No significant association with severe malaria or severe malaria subphenotypes (cerebral malaria and severe malaria anaemia) was observed for any of the SNPs/haplotypes tested in any of the study populations. Our results offer no evidence that the molecular pathways regulated by the transcription factor IRF-1 are involved in the immune-based pathogenesis of severe malaria

The MOBILIZE Boston Study: Design and methods of a prospective cohort study of novel risk factors for falls in an older population

<p>Abstract</p> <p>Background</p> <p>Falls are the sixth leading cause of death in elderly people in the U.S. Despite progress in understanding risk factors for falls, many suspected risk factors have not been adequately studied. Putative risk factors for falls such as pain, reductions in cerebral blood flow, somatosensory deficits, and foot disorders are poorly understood, in part because they pose measurement challenges, particularly for large observational studies.</p> <p>Methods</p> <p>The MOBILIZE Boston Study (MBS), an NIA-funded Program Project, is a prospective cohort study of a unique set of risk factors for falls in seniors in the Boston area. Using a door-to-door population-based recruitment, we have enrolled 765 persons aged 70 and older. The baseline assessment was conducted in 2 segments: a 3-hour home interview followed within 4 weeks by a 3-hour clinic examination. Measures included pain, cerebral hemodynamics, and foot disorders as well as established fall risk factors. For the falls follow-up, participants return fall calendar postcards to the research center at the end of each month. Reports of falls are followed-up with a telephone interview to assess circumstances and consequences of each fall. A second assessment is performed 18 months following baseline.</p> <p>Results</p> <p>Of the 2382 who met all eligibility criteria at the door, 1616 (67.8%) agreed to participate and were referred to the research center for further screening. The primary reason for ineligibility was inability to communicate in English. Results from the first 600 participants showed that participants are largely representative of seniors in the Boston area in terms of age, sex, race and Hispanic ethnicity. The average age of study participants was 77.9 years (s.d. 5.5) and nearly two-thirds were women. The study cohort was 78% white and 17% black. Many participants (39%) reported having fallen at least once in the year before baseline.</p> <p>Conclusion</p> <p>Our results demonstrate the feasibility of conducting comprehensive assessments, including rigorous physiologic measurements, in a diverse population of older adults to study non-traditional risk factors for falls and disability. The MBS will provide an important new data resource for examining novel risk factors for falls and mobility problems in the older population.</p

Comparative Transcriptional and Genomic Analysis of Plasmodium falciparum Field Isolates

Mechanisms for differential regulation of gene expression may underlie much of the phenotypic variation and adaptability of malaria parasites. Here we describe transcriptional variation among culture-adapted field isolates of Plasmodium falciparum, the species responsible for most malarial disease. It was found that genes coding for parasite protein export into the red cell cytosol and onto its surface, and genes coding for sexual stage proteins involved in parasite transmission are up-regulated in field isolates compared with long-term laboratory isolates. Much of this variability was associated with the loss of small or large chromosomal segments, or other forms of gene copy number variation that are prevalent in the P. falciparum genome (copy number variants, CNVs). Expression levels of genes inside these segments were correlated to that of genes outside and adjacent to the segment boundaries, and this association declined with distance from the CNV boundary. This observation could not be explained by copy number variation in these adjacent genes. This suggests a local-acting regulatory role for CNVs in transcription of neighboring genes and helps explain the chromosomal clustering that we observed here. Transcriptional co-regulation of physical clusters of adaptive genes may provide a way for the parasite to readily adapt to its highly heterogeneous and strongly selective environment