Central America Field Epidemiology Training Program (CA FETP): a pathway to sustainable public health capacity development

The Central America Field Epidemiology Training Program (CA FETP) is a public health capacity-building training programme aimed at developing high-caliber field epidemiologists at various levels of the public health system. It began in 2000 as part of the effort to rebuild public health infrastructure in six Central American and Caribbean countries following the devastation of Hurricanes Mitch and Georges in late 1998. Since then, the CA FETP has evolved from one regional training programme managed by CDC to several national FETPs with each country assuming ownership of its domestic programme. The curriculum is competency-based, and is divided into a three-tiered training pyramid that corresponds to the needs at the local, district and central levels of the health system. Trainees at each tier spend about 20% of their time in the classroom and 80% in the field implementing what they have learned while being mentored by graduates of the programme. FETP trainees have responded to multiple natural disasters and conducted hundreds of investigations including surveillance evaluations, outbreak responses and planned studies. Also graduates of the CA FETP are assuming influential positions in their respective ministries. As countries meet the challenge of institutionalizing their programmes, the CA FETP concept will increasingly be recognized as a model for sustainable public health capacity development

A SPION-eicosane protective coating for water soluble capsules : evidence for on-demand drug release triggered by magnetic hyperthermia

An orally-administered system for targeted, on-demand drug delivery to the gastrointestinal (GI) tract is highly desirable due to the high instances of diseases of that organ system and harsh mechanical and physical conditions any such system has to endure. To that end, we present an iron oxide nanoparticle/wax composite capsule coating using magnetic hyperthermia as a release trigger. The coating is synthesised using a simple dip-coating process from pharmaceutically approved materials using a gelatin drug capsule as a template. We show that the coating is impervious to chemical conditions within the GI tract and is completely melted within two minutes when exposed to an RF magnetic field under biologically-relevant conditions. The overall simplicity of action, durability and non-toxic and inexpensive nature of our system demonstrated herein are key for successful drug delivery systems

Disruption of the acetate kinase (ack) gene of Clostridium acetobutylicum results in delayed acetate production

In microorganisms, the enzyme acetate kinase (AK) catalyses the formation of ATP from ADP by de-phosphorylation of acetyl phosphate into acetic acid. A mutant strain of Clostridium acetobutylicum lacking acetate kinase activity is expected to have reduced acetate and acetone production compared to the wild type. In this work, a C. acetobutylicum mutant strain with a selectively disrupted ack gene, encoding AK, was constructed and genetically and physiologically characterized. The ack− strain showed a reduction in acetate kinase activity of more than 97% compared to the wild type. The fermentation profiles of the ack− and wild-type strain were compared using two different fermentation media, CGM and CM1. The latter contains acetate and has a higher iron and magnesium content than CGM. In general, fermentations by the mutant strain showed a clear shift in the timing of peak acetate production relative to butyrate and had increased acid uptake after the onset of solvent formation. Specifically, in acetate containing CM1 medium, acetate production was reduced by more than 80% compared to the wild type under the same conditions, but both strains produced similar final amounts of solvents. Fermentations in CGM showed similar peak acetate and butyrate levels, but increased acetoin (60%), ethanol (63%) and butanol (16%) production and reduced lactate (−50%) formation by the mutant compared to the wild type. These findings are in agreement with the proposed regulatory function of butyryl phosphate as opposed to acetyl phosphate in the metabolic switch of solventogenic clostridia

Influence of wiring cost on the large-scale architecture of human cortical connectivity

In the past two decades some fundamental properties of cortical connectivity have been discovered: small-world structure, pronounced hierarchical and modular organisation, and strong core and rich-club structures. A common assumption when interpreting results of this kind is that the observed structural properties are present to enable the brain's function. However, the brain is also embedded into the limited space of the skull and its wiring has associated developmental and metabolic costs. These basic physical and economic aspects place separate, often conflicting, constraints on the brain's connectivity, which must be characterized in order to understand the true relationship between brain structure and function. To address this challenge, here we ask which, and to what extent, aspects of the structural organisation of the brain are conserved if we preserve specific spatial and topological properties of the brain but otherwise randomise its connectivity. We perform a comparative analysis of a connectivity map of the cortical connectome both on high- and low-resolutions utilising three different types of surrogate networks: spatially unconstrained (‘random’), connection length preserving (‘spatial’), and connection length optimised (‘reduced’) surrogates. We find that unconstrained randomisation markedly diminishes all investigated architectural properties of cortical connectivity. By contrast, spatial and reduced surrogates largely preserve most properties and, interestingly, often more so in the reduced surrogates. Specifically, our results suggest that the cortical network is less tightly integrated than its spatial constraints would allow, but more strongly segregated than its spatial constraints would necessitate. We additionally find that hierarchical organisation and rich-club structure of the cortical connectivity are largely preserved in spatial and reduced surrogates and hence may be partially attributable to cortical wiring constraints. In contrast, the high modularity and strong s-core of the high-resolution cortical network are significantly stronger than in the surrogates, underlining their potential functional relevance in the brain

Fatal Dengue in Patients with Sickle Cell Disease or Sickle Cell Anemia in Curaçao: Two Case Reports

<p>Fatal Dengue in Patients with Sickle Cell Disease or Sickle Cell Anemia in Curaçao: Two Case Reports</p

Targeted Genome-Wide Enrichment of Functional Regions

Only a small fraction of large genomes such as that of the human contains the functional regions such as the exons, promoters, and polyA sites. A platform technique for selective enrichment of functional genomic regions will enable several next-generation sequencing applications that include the discovery of causal mutations for disease and drug response. Here, we describe a powerful platform technique, termed “functional genomic fingerprinting” (FGF), for the multiplexed genomewide isolation and analysis of targeted regions such as the exome, promoterome, or exon splice enhancers. The technique employs a fixed part of a uniquely designed Fixed-Randomized primer, while the randomized part contains all the possible sequence permutations. The Fixed-Randomized primers bind with full sequence complementarity at multiple sites where the fixed sequence (such as the splice signals) occurs within the genome, and multiplex amplify many regions bounded by the fixed sequences (e.g., exons). Notably, validation of this technique using cardiac myosin binding protein-C (MYBPC3) gene as an example strongly supports the application and efficacy of this method. Further, assisted by genomewide computational analyses of such sequences, the FGF technique may provide a unique platform for high-throughput sample production and analysis of targeted genomic regions by the next-generation sequencing techniques, with powerful applications in discovering disease and drug response genes

Brane-World Gravity

The observable universe could be a 1+3-surface (the "brane") embedded in a 1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model particles and fields trapped on the brane while gravity is free to access the bulk. At least one of the \textit{d} extra spatial dimensions could be very large relative to the Planck scale, which lowers the fundamental gravity scale, possibly even down to the electroweak ($\sim$ TeV) level. This revolutionary picture arises in the framework of recent developments in M theory. The 1+10-dimensional M theory encompasses the known 1+9-dimensional superstring theories, and is widely considered to be a promising potential route to quantum gravity. At low energies, gravity is localized at the brane and general relativity is recovered, but at high energies gravity "leaks" into the bulk, behaving in a truly higher-dimensional way. This introduces significant changes to gravitational dynamics and perturbations, with interesting and potentially testable implications for high-energy astrophysics, black holes, and cosmology. Brane-world models offer a phenomenological way to test some of the novel predictions and corrections to general relativity that are implied by M theory. This review analyzes the geometry, dynamics and perturbations of simple brane-world models for cosmology and astrophysics, mainly focusing on warped 5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover the simplest brane-world models in which 4-dimensional gravity on the brane is modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004) "Brane-World Gravity", 119 pages, 28 figures, the update contains new material on RS perturbations, including full numerical solutions of gravitational waves and scalar perturbations, on DGP models, and also on 6D models. A published version in Living Reviews in Relativit

Mental Health and Wellbeing Implications of the COVID-19 Quarantine for Disabled and Disadvantaged Children and Young People: Evidence from a Cross-cultural Study in Zambia and Sierra Leone

Background The mental health impact of the COVID-19 pandemic and quarantining on children and young people (CYP) living in low- and middle-income countries (LMICs) has yet to be fully comprehended. CYP in LMICs are at utmost risk, given the COVID-19-related restrictions and social distancing measures, resulting in reduced access to school-based services for nutritional and mental health needs. This study examined mental health of CYP during the first COVID-19 lockdown in Zambia and Sierra Leone. Method A total of 468 disabled and disadvantaged CYP aged 12 to 25 completed a planning tool that comprised the short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), as well as open-ended questions covering social connectedness, physical distancing and educational challenges during the lockdown. The community coaches screened individuals and families who could be eligible to receive emergency aid, and based on a convenience sample following distribution of aid, recipients were invited to complete the online planning tool. Results The data showed that participants in the global south have increasing anxieties and fears centred on accessing offline educational resources and income loss in the family effecting food security and their ability to return to education. Mean (SD) SWEMWBS scores for all participants in Zambia and Sierra Leone, were 19.61 (3.45) and 21.65 (2.84), respectively. Mental well-being scores were lower in females, children aged 12-14 and participants with two or more disabilities. Factors significantly associated with poor mental wellbeing in the sample were: type of disability, nationality, peer relationships, connection to others during the pandemic, knowledge about COVID-19, worry about the long-term impact of COVID-19, and the types of self-isolating. Conclusion The study shows that participants who self-reported low levels of COVID-19 health literacy also scored low on the mental wellbeing self-assessment. Yet, despite undoubted limited resources, these CYP are doing well in identifying their needs and maintaining hope in the face of the problems associated with COVID-19 in countries where stigma persists around mental ill-health

Patterns of adherence to and compliance with the Portuguese smoke-free law in the leisure-hospitality sector

CIEC – Research Centre on Child Studies, UM (FCT R&D 317)Background: In 2008, the Portuguese smoke-free law came into effect including partial bans in the leisure-hospitality (LH) sector. The objective of the study is to assess the prevalence of smoking control policies (total ban, smoking permission and designated smoking areas) adopted by the LH sector in Portugal. The levels of noncompliance with each policy are investigated as well as the main factors associated with smoking permission and noncompliance with the law. Methods: Cross-sectional study conducted between January 2010 and May 2011. A random sample of venues was selected from the Portuguese LH sector database, proportionally stratified according to type, size and geographical area. All venues were assessed in loco by an observer. The independent effects of venues’ characteristics on smoking permission and the level of noncompliance with the law were explored using logistic regression. Results: Overall, 1.412 venues were included. Total ban policy was adopted by 75.9% of venues, while 8.4% had designated smoking areas. Smoking ban was more prevalent in restaurants (85.9%). Only 29.7% of discos/bars/pubs opted for complete ban. Full or partial smoking permission was higher in discos/bar/pubs (OR = 7.37; 95%CI 4.87 to 11.17). Noncompliance with the law was higher in venues allowing smoking and lower in places with complete ban (33.6% and 7.6% respectively, p, 0.001). Discos/bars/pubs with full smoking permission had the highest level of noncompliance (OR = 3.31; 95%CI 1.40 to 7.83). Conclusions: Our findings show a high adherence to smoking ban policy by the Portuguese LH sector. Nonetheless, one quarter of the venues is fully or partially permissive towards smoking, with the discos/bars/pubs considerably contributing to this situation. Venues with smoking permission policies were less compliant with the legislation. The implementation of a comprehensive smoke-free law, without any exceptions, is essential to effectively protect people from the second hand smoke.The work is part of a large Epidemiological Study on the Portuguese Tobacco Control Policy, developed by the Instituto de Medicina Preventiva da Faculdade de Medicina de Lisboa and supported, in its preliminary part, by the Direccao Geral da Saude (DGS) and, in the second part, by the national funding institution Fundacao para a Ciencia e Tecnologia (FCT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript