Deletion of AMPK minimizes graft-versus-host disease through an early impact on effector donor T cells.

Allogeneic hematopoietic stem cell transplantation is a viable treatment for multiple hematologic diseases, but its application is often limited by graft-versus-host disease (GVHD), where donor T cells attack host tissues in the skin, liver, and gastrointestinal tract. Here, we examined the role of the cellular energy sensor AMP kinase (AMPK) in alloreactive T cells during GVHD development. Early posttransplant, AMPK activity increased more than 15-fold in allogeneic T cells, and transplantation of T cells deficient in both AMPKα1 and AMPKα2 decreased GVHD severity in multiple disease models. Importantly, a lack of AMPK lessened GVHD without compromising antileukemia responses or impairing lymphopenia-driven immune reconstitution. Mechanistically, absence of AMPK decreased both CD4+ and CD8+ effector T cell numbers as early as day 3 posttransplant, while simultaneously increasing regulatory T cell (Treg) percentages. Improvements in GVHD resulted from cell-intrinsic perturbations in conventional effector T cells as depletion of donor Tregs had minimal impact on AMPK-related improvements. Together, these results highlight a specific role for AMPK in allogeneic effector T cells early posttransplant and suggest that AMPK inhibition may be an innovative approach to mitigate GVHD while preserving graft-versus-leukemia responses and maintaining robust immune reconstitution.

Financial Implications of Early Hospital Discharge After AML-Like Induction Chemotherapy: A 4-Year Retrospective Analysis.

BACKGROUND: Early hospital discharge (EHD) after intensive acute myeloid leukemia (AML) induction chemotherapy has become routine at the University of Washington/Seattle Cancer Care Alliance over the past several years. We assessed the financial implications of EHD over the first 4 years after its broad adoption for patients with AML and other high-grade myeloid neoplasms undergoing AML-like induction chemotherapy. PATIENTS AND METHODS: We retrospectively compared charges between 189 patients with EHD who received all postinduction inpatient/outpatient care within our care system between August 2014 and July 2018 and 139 medically matched control patients who remained hospitalized for logistical reasons. Charges from the day of initial discharge (patients with EHD) or end of chemotherapy (control patients) until blood count recovery, additional chemotherapy or care transition, hospital discharge (for control patients only), an elapse of 42 days, or death were extracted from financial databases and separated into categories: facility/provider, emergency department, transfusions, laboratory, imaging, pharmacy, and miscellaneous. RESULTS: Combined charges averaged $4,157/day (range, $905-$13,119/day) for patients with EHD versus $9,248/day (range, $4,363-$48,522/day) for control patients (P<.001). The EHD cohort had lower mean facility/provider, transfusion, laboratory, and pharmacy charges but not imaging or miscellaneous charges. During readmissions, there was no statistically significant difference in daily inpatient charges between the EHD and control cohorts. After multivariable adjustment, average charges were $3,837/day lower for patients with EHD (P<.001). CONCLUSIONS: Together with previous data from our center showing that EHD is safe and associated with reduced healthcare resource utilization, this study further supports this care approach for AML and other high-grade myeloid neoplasms if infrastructure is available to enable close outpatient follow-up.

Evaluation of MODIS surrogates for meteorological humidity data in east Africa.

Satellite remote sensing technology has shown promising results in characterizing the environment in which plants and animals thrive. Remote sensing scientists, biologists, and epidemiologists are adopting remotely sensed imagery to compensate for the paucity of weather information measured by weather stations. With measured humidity from three stations as baselines, our study reveals that Normalised Difference Vegetation Index (NDVI) and atmosphere saturation deficits at the 780 hPa pressure level (DMODIS), both of which were derived from the MODerate-resolution Imaging Spectroradiometer (MODIS) sensor, were significantly correlated with station saturation deficits (Dstn)(ȣrȣ = 0.42-0.63, p < 0.001). These metrics have the potential to estimate saturation deficits over east Africa. Four to nine days of lags were found in the NDVI responding to Dstn. For the daily estimations of Dstn, DMODIS had a better performance than the NDVI. However, both of them poorly explained the variances in daily Dstn using simple regression models (adj. R2 = 0.17-0.39). When the estimation temporal scale was changed to 16-day, their performances were similar, and both were better than daily estimations. For Dstn estimations at coarser geographic scales, given that many factors such as soil, vegetation, slope, aspect, and wind speed might complicate the NDVI response lags and model construction, DMODIS is more favourable as a proxy of the saturation deficit over ground due to its simple relationship with Dstn.

Climate Change and Risk Projection: Dynamic Spatial Models of Tsetse and African Trypanosomiasis in Kenya.

African trypanosomiasis, otherwise known as sleeping sickness in humans and nagana in animals, is a parasitic protist passed cyclically by the tsetse fly. Despite more than a century of control and eradication efforts, the fly remains widely distributed across Africa and coextensive with other prevalent diseases. Control and planning are hampered by spatially and temporally variant vector distributions, ecologically irrelevant boundaries, and neglect. Tsetse are particularly well suited to move into previously disease-free areas under climate change scenarios, placing unprepared populations at risk. Here we present the modeling framework ATcast, which combines a dynamically downscaled regional climate model with a temporally and spatially dynamic species distribution model to predict tsetse populations over space and time. These modeled results are integrated with Kenyan population data to predict, for the period 2050 to 2059, exposure potential to tsetse and, by association, sleeping sickness and nagana across Kenya.

Protecting the Amazon with protected areas.

This article addresses climate-tipping points in the Amazon Basin resulting from deforestation. It applies a regional climate model to assess whether the system of protected areas in Brazil is able to avoid such tipping points, with massive conversion to semiarid vegetation, particularly along the south and southeastern margins of the basin. The regional climate model produces spatially distributed annual rainfall under a variety of external forcing conditions, assuming that all land outside protected areas is deforested. It translates these results into dry season impacts on resident ecosystems and shows that Amazonian dry ecosystems in the southern and southeastern basin do not desiccate appreciably and that extensive areas experience an increase in precipitation. Nor do the moist forests dry out to an excessive amount. Evidently, Brazilian environmental policy has created a sustainable core of protected areas in the Amazon that buffers against potential climate-tipping points and protects the drier ecosystems of the basin. Thus, all efforts should be made to manage them effectively.

The spatial pattern and mechanisms of heat-content change in the North Atlantic.

The total heat gained by the North Atlantic Ocean over the past 50 years is equivalent to a basinwide increase in the flux of heat across the ocean surface of 0.4 +/- 0.05 watts per square meter. We show, however, that this basin has not warmed uniformly: Although the tropics and subtropics have warmed, the subpolar ocean has cooled. These regional differences require local surface heat flux changes (+/-4 watts per square meter) much larger than the basinwide average. Model investigations show that these regional differences can be explained by large-scale, decadal variability in wind and buoyancy forcing as measured by the North Atlantic Oscillation index. Whether the overall heat gain is due to anthropogenic warming is difficult to confirm because strong natural variability in this ocean basin is potentially masking such input at the present time.