Prevalence of and Factors Associated with Negative Microscopic Diagnosis of Cutaneous Leishmaniasis in Rural Peru.

Cutaneous leishmaniasis is endemic to South America where diagnosis is most commonly conducted via microscopy. Patients with suspected leishmaniasis were referred for enrollment by the Ministry of Health (MoH) in Lima, Iquitos, Puerto Maldonado, and several rural areas of Peru. A 43-question survey requesting age, gender, occupation, characterization of the lesion(s), history of leishmaniasis, and insect-deterrent behaviors was administered. Polymerase chain reaction (PCR) was conducted on lesion materials at the Naval Medical Research Unit No. 6 in Lima, and the results were compared with those obtained by the MoH using microscopy. Factors associated with negative microscopy and positive PCR results were identified using

Capital account regulations and the trading system: a compatibility review

This repository item contains a single issue of the Pardee Center Task Force Reports, a publication series that began publishing in 2009 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. Spanish version produced by the Center for the Study of State and Society, Buenos Aires. Portuguese version coordinated by Daniela Magalhaes Prates, a contributing author of the report, in collaboration with Ana Trivellato (translator), and Maria Inês Amorozo (graphic designer).This report is the product of the Pardee Center Task Force on Regulating Capital Flows for Long-Run Development and builds on the Task Force´s first report published in March 2012. The Pardee Center Task Force was convened initially in September 2011 as consensus was emerging that the global financial crisis has re-confirmed the need to regulate cross-border finance. The March 2012 report argues that international financial institutions – and in particular the International Monetary Fund – need to support measures that would allow capital account regulations (CARs) to become a standard and effective part of the macroeconomic policy toolkit. Yet some policymakers and academics expressed concern that many nations — and especially developing countries — may not have the flexibility to adequately deploy such regulations because of trade and investment treaties they are party to. In June 2012, the Pardee Center, with the Center for the Study of State and Society (CEDES) in Argentina and Global Development and Environment Institute (GDAE) at Tufts University, convened a second Task Force workshop in Buenos Aires specifically to review agreements at the WTO and various Free Trade Agreements (FTAs) and Bilateral Investment Treaties (BITs) for the extent to which the trading regime is compatible with the ability to deploy effective capital account regulations. This report presents the findings of that review, and highlights a number of potential incompatibilities found between the trade and investment treaties and the ability to deploy CARs. It also highlights an alarming lack of policy space to use CARs under a variety of FTAs and BITs—especially those involving the United States. Like the first report, it was written by an international group of experts whose goal is to help inform discussions and decisions by policymakers at the IMF and elsewhere that will have implications for the economic health and development trajectories for countries around the world

Modelling the spatial extent of post-fire sedimentation threat to estimate the impacts of fire on waterways and aquatic species

Aim: Fires can severely impact aquatic fauna, especially when attributes of soil, topography, fire severity and post-fire rainfall interact to cause substantial sedimentation. Such events can cause immediate mortality and longer-term changes in food resources and habitat structure. Approaches for estimating fire impacts on terrestrial species (e.g. intersecting fire extent with species distributions) are inappropriate for aquatic species as sedimentation can carry well downstream of the fire extent, and occur long after fire. Here, we develop an approach for estimating the spatial extent of fire impacts for aquatic systems, across multiple catchments. Location: Southern Australian bioregions affected by the fires in 2019–2020 that burned >10 million ha of temperate and subtropical forests. Methods: We integrated an existing soil erosion model with fire severity mapping and rainfall data to estimate the spatial extent of post-fire sedimentation threat in waterways and in basins and the potential exposure of aquatic species to this threat. We validated the model against field observations of sedimentation events after the 2019–20 fires. Results: While fires overlapped with ~27,643 km of waterways, post-fire sedimentation events potentially occurred across ~40,449 km. In total, 55% (n = 85) of 154 basins in the study region may have experienced substantial post-fire sedimentation. Ten species—including six Critically Endangered—were threatened by post-fire sedimentation events across 100% of their range. The model increased the estimates for potential impact, compared to considering fire extent alone, for >80% of aquatic species. Some species had distributions that did not overlap with the fire extent, but that were entirely exposed to post-fire sedimentation threat. Conclusions: Compared with estimating the overlap of fire extent with species' ranges, our model improves estimates of fire-related threats to aquatic fauna by capturing the complexities of fire impacts on hydrological systems. The model provides a method for quickly estimating post-fire sedimentation threat after future fires in any fire-prone region, thus potentially improving conservation assessments and informing emergency management interventions

Reduced Insulin-like Growth Factor I Receptor and Altered Insulin Receptor Isoform mRNAs in Normal Mucosa Predict Colorectal Adenoma Risk

Hyperinsulinemia resulting from obesity and insulin resistance is associated with increased risk of many cancers, but the biology underlying this risk is unclear. We hypothesized that increased mRNA levels of the insulin-like growth factor 1 receptor (IGF1R) versus the insulin receptor (IR) or elevated ratio of IR-A:IR-B isoforms in normal rectal mucosa would predictadenoma risk, particularly in individuals with high body mass index (BMI) or plasma insulin

Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation

Despite evidence for the impact of insulin on intestinal epithelial physiology and pathophysiology, the expression patterns, roles, and regulation of insulin receptor (IR) and IR isoforms in the intestinal epithelium are not well characterized. IR-A is thought to mediate the proliferative effects of insulin or insulin growth factors (IGFs) in fetal or cancer cells. IR-B is considered to be the metabolic receptor for insulin in specialized tissues. This study used a novel Sox9-EGFP reporter mouse that permits isolation of intestinal epithelial stem cells (IESCs), progenitors, enteroendocrine cells and differentiated lineages, the ApcMin/+ mouse model of precancerous adenoma and normal human intestinal and colorectal cancer (CRC) cell lines. We tested the hypothesis that there is differential expression of IR-A or IR-B in stem and tumor cells versus differentiated intestinal epithelial cells (IECs) and that IR-B impacts cell proliferation. Our findings provide evidence that IR-B expression is significantly lower in highly proliferative IESCs and progenitor cells versus post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus differentiated Caco-2 cells. IR-B is also reduced in ApcMin/+ tumors and highly tumorigenic CRC cells. These differences in IR-B were accompanied by altered levels of mRNAs encoding muscleblind-like 2 (MBNL2), a known regulator of IR alternative splicing. Forced IR-B expression in subconfluent and undifferentiated Caco-2 cells reduced proliferation and increased biomarkers of differentiation. Our findings indicate that the impact of insulin on different cell types in the intestinal epithelium might differ depending on relative IR-B∶ IR-A expression levels and provide new evidence for the roles of IR-B to limit proliferation of CRC cells

Impaired expression of metallothioneins contributes to allergen-induced inflammation in patients with atopic dermatitis

Regulation of cutaneous immunity is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance versus inflammation in atopic dermatitis, we utilise a human in vivo allergen challenge study, exposing atopic dermatitis patients to house dust mite. Here we analyse transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of cutaneous immunocytes revealed a distinct dichotomy in atopic dermatitis patient responsiveness to house dust mite challenge. Our study shows that reactivity to house dust mite was associated with high basal levels of TNF-expressing cutaneous Th17 T cells, and documents the presence of hub structures where Langerhans cells and T cells co-localised. Mechanistically, we identify expression of metallothioneins and transcriptional programmes encoding antioxidant defences across all skin cell types, that appear to protect against allergen-induced inflammation. Furthermore, single nucleotide polymorphisms in the MTIX gene are associated with patients who did not react to house dust mite, opening up possibilities for therapeutic interventions modulating metallothionein expression in atopic dermatitis

Caldera resurgence during the 2018 eruption of Sierra Negra volcano, Galápagos Islands.

Recent large basaltic eruptions began after only minor surface uplift and seismicity, and resulted in caldera subsidence. In contrast, some eruptions at Galápagos Island volcanoes are preceded by prolonged, large amplitude uplift and elevated seismicity. These systems also display long-term intra-caldera uplift, or resurgence. However, a scarcity of observations has obscured the mechanisms underpinning such behaviour. Here we combine a unique multiparametric dataset to show how the 2018 eruption of Sierra Negra contributed to caldera resurgence. Magma supply to a shallow reservoir drove 6.5 m of pre-eruptive uplift and seismicity over thirteen years, including an Mw5.4 earthquake that triggered the eruption. Although co-eruptive magma withdrawal resulted in 8.5 m of subsidence, net uplift of the inner-caldera on a trapdoor fault resulted in 1.5 m of permanent resurgence. These observations reveal the importance of intra-caldera faulting in affecting resurgence, and the mechanisms of eruption in the absence of well-developed rift systems

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures