The Hirschsprung's–multiple endocrine neoplasia connection

The risk of patients with Hirschsprung's disease later developing multiple endocrine neoplasia remains a matter of concern. The multiple endocrine neoplasia 2–Hirschsprung's disease association has been shown to cosegregate in Hirschsprung's disease patients with both short- and long-segment aganglionosis, although patients with long-segment aganglionosis a to carry the greatest risk. The Hirschsprung's disease–medullary thyroid carcinoma relationship also appears to be bi-directional, and activation or suppression of the rearranged during transfection gene appeared to vary over succeeding generations within the same family. Rearranged during transfection gene variations are associated with both conditions. The cosegregation of Hirschsprung's disease and multiple endocrine neoplasia 2 is particularly interesting as it involves both “switch off” and “switch on” of the rearranged during transfection proto-oncogene in the same patient. This cosegregation mostly relates to the cysteine-rich area on RET-620 (the “Janus gene”). The mechanism whereby rearranged during transfection influences gene activation in multiple endocrine neoplasia 2 is complex, but genetic variations impair the rearranged during transfection tyrosine kinase response to tyrosine kinase activation, thus appearing to dictate downstream signaling cascade responses. Better understanding of the RET-620 relationship allows for a more cost-effective method of identifying those at risk by focusing rearranged during transfection gene testing to this specific area as a “hot spot”. The clinical awareness of possible medullary thyroid carcinoma has led to timely intervention and early treatment of this chemo- and radioresistant tumor with poor prognosis. Establishment of “risk” by genetic testing has become a classic model of molecular medicine being integrated into patient care and offering rearranged during transfection-directed prophylactic surgical management. In addition, novel approaches to treatment based on this genetic knowledge have already shown early promise in randomized clinical trials

Global and National Socioeconomic Disparities in Obesity, Overweight, and Underweight Status

Objective. To examine the association between socioeconomic factors and weight status across 53 countries. Methods. Data are cross-sectional and from the long version of the World Health Survey (WHS). There were 172,625 WHS participants who provided self-reported height and weight measures and sociodemographic information. The International Classification of adult weight status was used to classify participants by body mass index (BMI): (1) underweight (<18.5), (2) normal weight (18.5–24.9), (3) overweight (25.0–29.9), and (4) obese (>30.0). Multinomial regression was used in the analyses. Results. Globally, 6.7% was underweight, 25.7% overweight, and 8.9% obese. Underweight status was least (5.8%) and obesity (9.3%) most prevalent in the richest quintile. There was variability between countries, with a tendency for lower-income quintiles to be at increased risk for underweight and reduced risk for obesity. Conclusion. International policies may require flexibility in addressing cross-national differences in the socio-economic covariates of BMI status

Catching the Brass Ring: Oil Market Diversification Potential for Canada

This paper examines the nature and structure of the Canadian oil export market in the context of world prices for heavy crude oil and the potential price differential available to Canadian producers gaining access to new overseas markets. Success in this arena will allow Canada to reap incredible economic benefits. For example, the near term benefits for increased access to Gulf Coast markets after mid-continent bottlenecks are removed, are significant, representing nearly 10$US per barrel for Canadian producers. On the Pacific Coast, the world market is represented by growing capacity for heavy crude products in emerging Asian markets including Japan, Korea and China and existing heavy crude facilities in California and the west coast. Here, in the reference scenario for California and Asia the benefits are assumed to begin in 2020. The differential value range in California in 2020 is estimated at$7.20US per barrel and escalates to $8.77US by 2030. In Asia, the benefit range is estimated to grow from$11.15US per barrel in 2020 to $13.60US in 2030. Those higher prices for Canadian heavy oil would translate into significant increases in profits, jobs and government revenues. With better access and new pipeline capacity, oil producers will see more efficient access to international markets which can add up to$131 billion to Canada’s GDP between 2016 and 2030 in the reference scenario. This amounts to over $27 billion in federal, provincial and municipal tax receipts, along with an estimated 649,000 person-years of employment. Alberta will be the principal but not sole beneficiary from increased access to world market pricing. Most provinces and territories will realize fiscal and economic gains from the distribution and sale of products reflecting reduced costs and increased access to refineries for heavy oil. The key to this change is the elimination of current bottlenecks in transport and the expansion of a network of pipelines that can move Canadian crude oil to locations reflecting minimal discounts from world market prices. As this paper demonstrates with hard facts and figures, the rewards are too great to ignore

The modern pollen-vegetation relationship of a tropical forest-savannah mosaic landscape, Ghana, West Africa

Transitions between forest and savannah vegetation types in fossil pollen records are often poorly understood due to over-production by taxa such as Poaceae and a lack of modern pollen-vegetation studies. Here, modern pollen assemblages from within a forest-savannah transition in West Africa are presented and compared, their characteristic taxa discussed, and implications for the fossil record considered. Fifteen artificial pollen traps were deployed for 1 year, to collect pollen rain from three vegetation plots within the forest-savannah transition in Ghana. High percentages of Poaceae and Melastomataceae/Combretaceae were recorded in all three plots. Erythrophleum suaveolens characterised the forest plot, Manilkara obovata the transition plot and Terminalia the savannah plot. The results indicate that Poaceae pollen influx rates provide the best representation of the forest-savannah gradient, and that a Poaceae abundance of >40% should be considered as indicative of savannah-type vegetation in the fossil record

HPTN 071 (PopART): A Cluster-Randomized Trial of the Population Impact of an HIV Combination Prevention Intervention Including Universal Testing and Treatment: Mathematical Model

BACKGROUND: The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence. METHODS AND FINDINGS: The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence. CONCLUSIONS: The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention

Standardization of Epidemiological Surveillance of Group A Streptococcal Impetigo

Impetigo is a highly contagious bacterial infection of the superficial layer of skin. Impetigo is caused by group A Streptococcus (Strep A) and Staphylococcus aureus, alone or in combination, with the former predominating in many tropical climates. Strep A impetigo occurs mainly in early childhood, and the burden varies worldwide. It is an acute, self-limited disease, but many children experience frequent recurrences that make it a chronic illness in some endemic settings. We present a standardized surveillance protocol including case definitions for impetigo including both active (purulent, crusted) and resolving (flat, dry) phases and discuss the current tests used to detect Strep A among persons with impetigo. Case classifications that can be applied are detailed, including differentiating between incident (new) and prevalent (existing) cases of Strep A impetigo. The type of surveillance methodology depends on the burden of impetigo in the community. Active surveillance and laboratory confirmation is the preferred method for case detection, particularly in endemic settings. Participant eligibility, surveillance population and additional considerations for surveillance of impetigo, including examination of lesions, use of photographs to document lesions, and staff training requirements (including cultural awareness), are addressed. Finally, the core elements of case report forms for impetigo are presented and guidance for recording the course and severity of impetigo provided

Engineering mesophase stability and structure via incorporation of cyclic terminal groups

We report on the characterisation of a number of liquid-crystalline materials featuring cyclic terminal groups, which lead to significant enhancements in the temperature range of the mesomorphic state. Materials with only short terminal chains are able to support lamellar mesophase formation by appending a large terminal cyclic unit at the end of a short spacer composed of methylene units. X-ray scattering experiments reveal that the layer spacings of the lamellar smectic phase are significantly larger when a cyclic end-group is present than for equivalent linear unsubstituted materials, but there is no effect on orientational order. Fully atomistic molecular dynamics simulations faithfully reproduce experimental layer spacings and orientational order parameters, and indicate that the cyclic terminal units spontaneously segregate into diffuse sub-layers and thus cause the increased layer spacing. This shape segregation predicted by molecular dynamics simulations is observed in the crystalline solid state by X-ray diffraction

Defining and Detecting Malaria Epidemics in the Highlands of Western Kenya

Epidemic detection algorithms are being increasingly recommended for malaria surveillance in sub-Saharan Africa. We present the results of applying three simple epidemic detection techniques to routinely collected longitudinal pediatric malaria admissions data from three health facilities in the highlands of western Kenya in the late 1980s and 1990s. The algorithms tested were chosen because they could be feasibly implemented at the health facility level in sub-Saharan Africa. Assumptions of these techniques about the normal distribution of admissions data and the confidence intervals used to define normal years were also investigated. All techniques identified two “epidemic” years in one of the sites. The untransformed Cullen method with standard confidence intervals detected the two “epidemic” years in the remaining two sites but also triggered many false alarms. The performance of these methods is discussed and comments made about their appropriateness for the highlands of western Keny

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered