Comparative population structure of <i>Plasmodium malariae</i> and <i>Plasmodium falciparum</i> under different transmission settings in Malawi

&lt;b&gt;Background:&lt;/b&gt; Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. &lt;BR/&gt; &lt;b&gt;Methods:&lt;/b&gt; Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI), population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. &lt;BR/&gt; &lt;b&gt;Results:&lt;/b&gt; Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008) and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11) and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission setting. &lt;BR/&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The extent of similarity between P. falciparum and P. malariae population structure described by the high level of multiple infection, the lack of significant population differentiation or haplotype clustering and lack of linkage disequilibrium is surprising given the differences in the biological features of these species that suggest a reduced potential for out-crossing and transmission in P. malariae. The absence of a rise in P. malariae MOI with increased transmission or a reduction in MOI with age could be explained by differences in the duration of infection or degree of immunity compared to P. falciparum

Strengthen causal models for better conservation outcomes for human well-being

This is the final version. Available from the publisher via the DOI in this record.All data files are available on github at www.github.com/scheng87/ toc.Background Understanding how the conservation of nature can lead to improvement in human conditions is a research area with significant growth and attention. Progress towards effective conservation requires understanding mechanisms for achieving impact within complex social-ecological systems. Causal models are useful tools for defining plausible pathways from conservation actions to impacts on nature and people. Evaluating the potential of different strategies for delivering co-benefits for nature and people will require the use and testing of clear causal models that explicitly define the logic and assumptions behind cause and effect relationships. Objectives and methods In this study, we outline criteria for credible causal models and systematically evaluated their use in a broad base of literature (~1,000 peer-reviewed and grey literature articles from a published systematic evidence map) on links between nature-based conservation actions and human well-being impacts. Results Out of 1,027 publications identified, only ~20% of articles used any type of causal models to guide their work, and only 14 total articles fulfilled all criteria for credibility. Articles rarely tested the validity of models with empirical data. Implications Not using causal models risks poorly defined strategies, misunderstanding of potential mechanisms for affecting change, inefficient use of resources, and focusing on implausible efforts for achieving sustainability.Science for Nature and People Partnership (SNAPP)National Institute for Health Research (NIHR

Identifying the science and technology dimensions of emerging public policy issues through horizon scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security

A G1-like state allows HIV-1 to bypass SAMHD1 restriction in macrophages

An unresolved question is how HIV‐1 achieves efficient replication in terminally differentiated macrophages despite the restriction factor SAMHD1. We reveal inducible changes in expression of cell cycle‐associated proteins including MCM2 and cyclins A, E, D1/D3 in macrophages, without evidence for DNA synthesis or mitosis. These changes are induced by activation of the Raf/MEK/ERK kinase cascade, culminating in upregulation of CDK1 with subsequent SAMHD1 T592 phosphorylation and deactivation of its antiviral activity. HIV infection is limited to these G1‐like phase macrophages at the single‐cell level. Depletion of SAMHD1 in macrophages decouples the association between infection and expression of cell cycle‐associated proteins, with terminally differentiated macrophages becoming highly susceptible to HIV‐1. We observe both embryo‐derived and monocyte‐derived tissue‐resident macrophages in a G1‐like phase at frequencies approaching 20%, suggesting how macrophages sustain HIV‐1 replication in vivo. Finally, we reveal a SAMHD1‐dependent antiretroviral activity of histone deacetylase inhibitors acting via p53 activation. These data provide a basis for host‐directed therapeutic approaches aimed at limiting HIV‐1 burden in macrophages that may contribute to curative interventions

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Age-related differences in 1p and 19q deletions in oligodendrogliomas

BACKGROUND: Recent reports indicate that anaplastic oligodendrogliomas frequently show allelic losses on chromosome arms 1p and 19q, and that these deletions are associated with better chemotherapeutic response and overall patient survival. Because of the diversified genetic makeup of the population and the centralized provincial referral system for brain tumor patients in Manitoba, the epidemiological features of such tumors sometimes differ from the published data acquired from non-community based settings. In this study, we assessed the prevalence of allelic deletions for chromosome arms 1p and 19q in anaplastic and in low-grade oligodendrogliomas in the Manitoba population. METHODS: Loss of heterozygosity (LOH) analysis of brain tumors was carried out using 4 microsatellite markers (D1S508, D1S2734, D19S219 and D19S412) and a PCR based assay. The tumors were consecutively acquired during the period September 1999–March 2001 and a total of 63 tumors were assessed. RESULTS: We found that allelic loss of chromosome 1p and 19q was higher in oligodendrogliomas than in other diffuse gliomas and that for anaplastic oligodendrogliomas, younger patients exhibited significantly more deletions than older patients (>60 years of age). CONCLUSIONS: These studies suggest that age may be a factor in the genetic alterations of oligodendrogliomas. In addition, these studies demonstrate that this assay can easily be carried out in a cost-effective manner in a small tertiary center

How many births in sub-Saharan Africa and South Asia will not be attended by a skilled birth attendant between 2011 and 2015?

<p>Abstract</p> <p>Background</p> <p>The fifth Millennium Development Goal target for 90% of births in low and middle income countries to have a skilled birth attendant (SBA) by 2015 will not be met. In response to this, policy has focused on increasing SBA access. However, reducing maternal mortality also requires policies to prevent deaths among women giving birth unattended. We aimed to generate estimates of the absolute number of non-SBA births between 2011 and 2015 in South Asia and sub-Saharan Africa, given optimistic assumptions of future trends in SBA attendance. These estimates could be used by decision makers to inform the extent to which reductions in maternal mortality will depend on policies aimed specifically at those women giving birth unattended.</p> <p>Methods</p> <p>For each country within South Asia and sub-Saharan Africa we estimated recent trends in SBA attendance and used these as the basis for three increasingly optimistic projections for future changes in SBA attendance. For each country we obtained estimates for the current SBA attendance in rural and urban settings and forecasts for the number of births and changes in rural/urban population over 2011-2015. Based on these, we calculated estimates for the number of non-SBA births for 2011-2015 under a variety of scenarios.</p> <p>Results</p> <p>Conservative estimates are that there will be between 130 and 180 million non-SBA births in South Asia and sub-Saharan Africa from 2011 to 2015 (90% of these in rural areas). Currently, there are more non-SBA births per year in South Asia than sub-Saharan Africa, but our projections suggest that the regions will have approximately the same number of non-SBA births by 2015. We also present results for each of the six countries currently accounting for more than 50% of global maternal deaths.</p> <p>Conclusions</p> <p>Over the next five years, many millions of women within South Asia and sub-Saharan Africa will give birth without an SBA. Efforts to improve access to skilled attendance should be accompanied by interventions to improve the safety of non-attended deliveries.</p

A case study for teaching information literacy skills

<p>Abstract</p> <p>Background</p> <p>The Internet has changed contemporary workplace skills, resulting in a need for proficiency with specific digital, online and web-based technologies within the fields of medicine, dentistry and public health. Although younger students, generally under 30 years of age, may appear inherently comfortable with the use of technology-intensive environments and digital or online search methods, competence in information literacy among these students may be lacking.</p> <p>Methods</p> <p>This project involved the design and assessment of a research-based assignment to help first-year, graduate-level health science students to develop and integrate information literacy skills with clinical relevance.</p> <p>Results</p> <p>One cohort of dental students (n = 78) was evaluated for this project and the results demonstrate that although all students were able to provide the correct response from the content-specific, or technology-independent, portion of the assignment, more than half (54%) were unable to demonstrate competence with a web-based, technology-dependent section of this assignment. No correlation was found between any demographic variable measured (gender, age, or race).</p> <p>Conclusion</p> <p>More evidence is emerging that demonstrates the need for developing curricula that integrates new knowledge and current evidence-based practices and technologies, traditionally isolated from graduate and health-care curricula, that can enhance biomedical and clinical training for students. This study provides evidence, critical for the evaluation of new practices, which can promote and facilitate the integration of information literacy into the curriculum.</p