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In Brazil, Leishmania amazonensis is the etiological agent of cutaneous and diffuse cutaneous leishmaniasis. The state of Maranhão in the Northeast of Brazil is prevalent for these clinical forms of the disease and also has high rates of HIV infection. Here, we characterized the drug susceptibility of a L . amazonensis clinical isolate from a 46-year-old man with diffuse cutaneous leishmaniasis coinfected with HIV from this endemic area. This patient underwent several therapeutic regimens with meglumine antimoniate, liposomal amphotericin B, and pentamidine, without success. In vitro susceptibility assays against promastigotes and intracellular amastigotes demonstrated that this isolate had low susceptibility to amphotericin B, when compared with the reference strain of this species that is considered susceptible to antileishmanial drugs. Additionally, we investigated whether the low in vitro susceptibility would affect the in vivo response to amphotericin B treatment. The drug was effective in reducing the lesion size and parasite burden in mice infected with the reference strain, whereas those infected with the clinical isolate and a resistant line (generated experimentally by stepwise selection) were refractory to amphotericin B treatment. To evaluate whether the isolate was intrinsically resistant to amphotericin B in animals, infected mice were treated with other drugs that had not been used in the treatment of the patient (miltefosine, paromomycin, and a combination of both). Our findings demonstrated that all drug schemes were able to reduce lesion size and parasite burden in animals infected with the clinical isolate, confirming the amphotericin B-resistance phenotype. These findings indicate that the treatment failure observed in the patient may be associated with amphotericin B resistance, and demonstrate the potential emergence of amphotericin B-resistant L . amazonensis isolates in an area of Brazil endemic for cutaneous leishmaniasis.

Past model studies have projected a global decrease in marine net primary production (NPP) over the 21st century, but these studies focused on the multi-model mean rather than on the large inter-model differences. Here, we analyze model-simulated changes in NPP for the 21st century under IPCC's high-emission scenario RCP8.5. We use a suite of nine coupled carbon–climate Earth system models with embedded marine ecosystem models and focus on the spread between the different models and the underlying reasons. Globally, NPP decreases in five out of the nine models over the course of the 21st century, while three show no significant trend and one even simulates an increase. The largest model spread occurs in the low latitudes (between 30° S and 30° N), with individual models simulating relative changes between −25 and +40 %. Of the seven models diagnosing a net decrease in NPP in the low latitudes, only three simulate this to be a consequence of the classical interpretation, i.e., a stronger nutrient limitation due to increased stratification leading to reduced phytoplankton growth. In the other four, warming-induced increases in phytoplankton growth outbalance the stronger nutrient limitation. However, temperature-driven increases in grazing and other loss processes cause a net decrease in phytoplankton biomass and reduce NPP despite higher growth rates. One model projects a strong increase in NPP in the low latitudes, caused by an intensification of the microbial loop, while NPP in the remaining model changes by less than 0.5 %. While models consistently project increases NPP in the Southern Ocean, the regional inter-model range is also very substantial. In most models, this increase in NPP is driven by temperature, but it is also modulated by changes in light, macronutrients and iron as well as grazing. Overall, current projections of future changes in global marine NPP are subject to large uncertainties and necessitate a dedicated and sustained effort to improve the models and the concepts and data that guide their development.

The sinking of particulate organic carbon (POC) is a key component of the ocean carbon cycle and plays an important role in the global climate system. However, the processes controlling the fraction of primary production that is exported from the euphotic zone (export ratio) and how much of it survives respiration in the mesopelagic to be sequestered in the deep ocean (transfer efficiency) are not well understood. In this study, we use a three-dimensional, coupled physical–biogeochemical model (CCSM–BEC; Community Climate System Model–ocean Biogeochemical Elemental Cycle) to investigate the processes controlling the export of particulate organic matter from the euphotic zone and its flux to depth. We also compare model results with sediment trap data and other parameterizations of POC flux to depth to evaluate model skill and gain further insight into the causes of error and uncertainty in POC flux estimates. In the model, export ratios are mainly a function of diatom relative abundance and temperature while absolute fluxes and transfer efficiency are driven by mineral ballast composition of sinking material. The temperature dependence of the POC remineralization length scale is modulated by denitrification under low O2 concentrations and lithogenic (dust) fluxes. Lithogenic material is an important control of transfer efficiency in the model, but its effect is restricted to regions of strong atmospheric dust deposition. In the remaining regions, CaCO3 content of exported material is the main factor affecting transfer efficiency. The fact that mineral ballast composition is inextricably linked to plankton community structure results in correlations between export ratios and ballast minerals fluxes (opal and CaCO3), and transfer efficiency and diatom relative abundance that do not necessarily reflect ballast or direct ecosystem effects, respectively. This suggests that it might be difficult to differentiate between ecosystem and ballast effects in observations. The model's skill in reproducing sediment trap observations is equal to or better than that of other parameterizations. However, the sparseness and relatively large uncertainties of sediment trap data makes it difficult to accurately evaluate the skill of the model and other parameterizations. More POC flux observations, over a wider range of ecological regimes, are necessary to thoroughly evaluate and test model results and better understand the processes controlling POC flux to depth in the ocean.

Objective Visceral leishmaniasis (VL) is an endemic parasitic disease in Latin America, and its clinical picture is aggravated in coinfections with the human immunodeficiency virus (HIV). The objective of this study was to investigate clinical factors and laboratory variables associated with VL relapse and death in VL/HIV coinfected patients. Methods A prospective longitudinal study was conducted from January 2013 to July 2020 among 169 patients coinfected with VL and HIV. The outcomes investigated were the occurrence of VL relapse and death. Chi-square test, Mann–Whitney test and logistic regression models were used for statistical analysis. Results The occurrence rates were 41.4% for VL relapse and 11.2% for death. Splenomegaly and adenomegaly were associated with the increased risk of VL relapse. Patients with VL relapse had higher levels of urea ( p  = .005) and creatinine ( p  < .001). Patients who died had lower red blood cell counts ( p  = .012), hemoglobin ( p  = .017) and platelets ( p  < .001). The adjusted model showed that antiretroviral therapy for more than 6 months was associated with a decrease in VL relapse, and adenomegaly was associated with an increase in VL relapse. In addition, edema, dehydration, poor general health status, and paleness were associated with an increase in hospital death. Conclusion The findings suggest that adenomegaly, antiretroviral therapy, and renal abnormalities can be associated with VL relapse, while hematological abnormalities, and clinical manifestations like paleness, and edema can be associated with an increased odds of hospital death. Trial registration number: The study was submitted to the Ethics and Research Committee of the Federal University of Maranhão (Protocol: 409.351).

The response of ocean phytoplankton community structure to climate change depends, among other factors, upon species competition for nutrients and light, as well as the increase in surface ocean temperature. We propose an analytical framework linking changes in nutrients, temperature and light with changes in phytoplankton growth rates, and we assess our theoretical considerations against model projections (1980–2100) from a global Earth System model. Our proposed \"critical nutrient hypothesis\" stipulates the existence of a critical nutrient threshold below (above) which a nutrient change will affect small phytoplankton biomass more (less) than diatom biomass, i.e. the phytoplankton with lower half-saturation coefficient K are influenced more strongly in low nutrient environments. This nutrient threshold broadly corresponds to 45° S and 45° N, poleward of which high vertical mixing and inefficient biology maintain higher surface nutrient concentrations and equatorward of which reduced vertical mixing and more efficient biology maintain lower surface nutrients. In the 45° S–45° N low nutrient region, decreases in limiting nutrients – associated with increased stratification under climate change – are predicted analytically to decrease more strongly the specific growth of small phytoplankton than the growth of diatoms. In high latitudes, the impact of nutrient decrease on phytoplankton biomass is more significant for diatoms than small phytoplankton, and contributes to diatom declines in the northern marginal sea ice and subpolar biomes. In the context of our model, climate driven increases in surface temperature and changes in light are predicted to have a stronger impact on small phytoplankton than on diatom biomass in all ocean domains. Our analytical predictions explain reasonably well the shifts in community structure under a modeled climate-warming scenario. Climate driven changes in nutrients, temperature and light have regionally varying and sometimes counterbalancing impacts on phytoplankton biomass and structure, with nutrients and temperature dominant in the 45° S–45° N band and light-temperature effects dominant in the marginal sea-ice and subpolar regions. As predicted, decreases in nutrients inside the 45° S–45° N \"critical nutrient\" band result in diatom biomass decreasing more than small phytoplankton biomass. Further stratification from global warming could result in geographical shifts in the \"critical nutrient\" threshold and additional changes in ecology.

Highly prevalent conditions with multiple and complex underlying etiologies are a challenge to public health. Undernutrition, for example, affects 20% of children in the developing world. The cause and consequence of poor nutrition are multifaceted. Undernutrition has been associated with half of all deaths worldwide in children aged <5 years; in addition, its pernicious long-term effects in early childhood have been associated with cognitive and physical growth deficits across multiple generations and have been thought to suppress immunity to further infections and to reduce the efficacy of childhood vaccines. The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health (MAL-ED) Study, led by the Fogarty International Center of the National Institutes of Health and the Foundation for the National Institutes of Health, has been established at sites in 8 countries with historically high incidence of diarrheal disease and undernutrition. Central to the study is the hypothesis that enteropathogen infection contributes to undernutrition by causing intestinal inflammation and/or by altering intestinal barrier and absorptive function. It is further postulated that this leads to growth faltering and deficits in cognitive development. The effects of repeated enteric infection and undernutrition on the immune response to childhood vaccines is also being examined in the study. MAL-ED uses a prospective longitudinal design that offers a unique opportunity to directly address a complex system of exposures and health outcomes in the community—rather than the relatively rarer circumstances that lead to hospitalization—during the critical period of development of the first 2 years of life. Among the factors being evaluated are enteric infections (with or without diarrhea) and other illness indicators, micronutrient levels, diet, socioeconomic status, gut function, and the environment. MAL-ED aims to describe these factors, their interrelationships, and their overall impact on health outcomes in unprecedented detail, and to make individual, site-specific, and generalized recommendations regarding the nature and timing of possible interventions aimed at improving child health and development in these resource-poor settings.

There are a number of hypotheses concerning the environmental controls on marine nitrogen fixation (NF). Most of these hypotheses have not been assessed against direct measurements on the global scale. In this study, we use ~ 500 depth-integrated field measurements of NF covering the Pacific and Atlantic oceans to test whether the spatial variance of these measurements can be explained by the commonly hypothesized environmental controls, including measurement-based surface solar radiation, mixed layer depth, average solar radiation in the mixed layer, sea surface temperature, wind speed, surface nitrate and phosphate concentrations, surface excess phosphate (P*) concentration and subsurface minimum dissolved oxygen (in upper 500 m), as well as model-based P* convergence and atmospheric dust deposition. By conducting simple linear regression and stepwise multiple linear regression (MLR) analyses, surface solar radiation (or sea surface temperature) and subsurface minimum dissolved oxygen are identified as the predictors that explain the most spatial variance in the observed NF data, although it is unclear why the observed NF decreases when the level of subsurface minimum dissolved oxygen is higher than ~ 150 μM. Dust deposition and wind speed do not appear to influence the spatial patterns of NF on global scale. The weak correlation between the observed NF and the P* convergence and concentrations suggests that the available data currently remain insufficient to fully support the hypothesis that spatial variability in denitrification is the principal control on spatial variability in marine NF. By applying the MLR-derived equation, we estimate the global-integrated NF at 74 (error range 51–110) Tg N yr−1 in the open ocean, acknowledging that it could be substantially higher as the 15N2-assimilation method used by most of the field samples underestimates NF. More field NF samples in the Pacific and Indian oceans, particularly in the oxygen minimum zones, are needed to reduce uncertainties in our conclusion.

We report on the discovery of circular polarization modulated with a period of 1.943 ± 0.002 hr in the cataclysmic variable V1082 Sgr. These findings unambiguously reveal the rotation of a magnetic white dwarf and establish its intermediate polar nature. Along with its extraordinary long orbital period (Porb) of 20.8 hr, the spin period (Pspin) places this system in an extreme position of the Pspin versus Porb distribution. The circular polarization phase diagram has a single peak and an amplitude smaller than 1%. These data were used to model the postshock region of the accretion flow on the white dwarf surface using the CYCLOPS code. We obtained a magnetic field in the white dwarf pole of 11 MG and a magnetospheric radius consistent with the coupling region at around 2–3 white dwarf radii. The Pspin/Porb value and the estimated magnetic field momentum suggest that V1082 Sgr could be out of spin equilibrium or in a spin-up state, possibly in a stream accretion mode.

Recent research has quantified the contributions of CO2 and CH4 emissions traced to the products of major fossil fuel companies and cement manufacturers to global atmospheric CO2, surface temperature, and sea level rise. This work has informed societal considerations of the climate responsibilities of these major industrial carbon producers. Here, we extend this work to historical (1880-2015) and recent (1965-2015) acidification of the world's ocean. Using an energy balance carbon-cycle model, we find that emissions traced to the 88 largest industrial carbon producers from 1880-2015 and 1965-2015 have contributed ∼55% and ∼51%, respectively, of the historical 1880-2015 decline in surface ocean pH. As ocean acidification is not spatially uniform, we employ a three-dimensional ocean model and identify five marine regions with large declines in surface water pH and aragonite saturation state over similar historical (average 1850-1859 to average 2000-2009) and recent (average 1960-1969 to average of 2000-2009) time periods. We characterize the biological and socioeconomic systems in these regions facing loss and damage from ocean acidification in the context of climate change and other stressors. Such analysis can inform societal consideration of carbon producer responsibility for current and near-term risks of further loss and damage to human communities dependent on marine ecosystems and fisheries vulnerable to ocean acidification.

IntroductionThe use of contralateral prophylactic mastectomy (CPM) continues to grow despite the absence of evidence supporting a survival benefit. This study’s objectives were to (1) describe the trends in the rates of unilateral and bilateral mastectomy (BM) in women diagnosed with unilateral breast cancer (UBC) in Ontario, Canada from 1991 to 2013, and (2) identify factors associated with BM to treat UBC.MethodsThis retrospective cohort analysis included all women aged 18 and older diagnosed with UBC between January 1991 and December 2013. Health administrative data from the Institute for Clinical Evaluative Sciences, the Ontario Cancer Registry, and the Discharge Abstract Database were used to identify all breast cancer and mastectomy cases. Age-adjusted mastectomy rates were plotted over time. Univariable and multivariable analyses included clinically significant covariates.ResultsFrom 1991 to 2013 there were 172,165 cases of UBC and 64,886 mastectomies (37.7%) performed in Ontario. 13.6% of the mastectomies were bilateral. BM rates increased over sixfold (from 4 to 25%) across all age groups under age 70 over a 23-year period. On multivariable analysis, younger age, higher income, rural community, earlier breast cancer stage, lobular histology, availability of reconstruction and teaching hospitals were associated with increased odds of BM.ConclusionsThis is the largest population study of breast cancer patients in Canada and shows an increasing rate of BM for UBC. The results are similar to those already described in the US and highlight the importance of continued efforts to promote efficient communication and evidence-based decision-making prior to breast surgery.