Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy.

Gilteritinib is the current standard of care for relapsed or refractory fms related receptor tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia in many countries, however outcomes for patients relapsing after contemporary first-line therapies (intensive chemotherapy with midostaurin, or nonintensive chemotherapy with venetoclax) are uncertain. Moreover, reported data on toxicity and health care resource use is limited. Here, we describe a large real-world cohort of 152 patients receiving single-agent gilteritinib in 38 UK hospitals.

Ocean weather, biological rates, and unexplained global ecological patterns.

As on land, oceans exhibit high temporal and spatial temperature variation. This "ocean weather" contributes to the physiological and ecological processes that ultimately determine the patterns of species distribution and abundance, yet is often unrecognized, especially in tropical oceans. Here, we tested the paradigm of temperature stability in shallow waters (<12.

Oxygen availability and body mass modulate ectotherm responses to ocean warming.

In an ocean that is rapidly warming and losing oxygen, accurate forecasting of species' responses must consider how this environmental change affects fundamental aspects of their physiology. Here, we develop an absolute metabolic index (Φ) that quantifies how ocean temperature, dissolved oxygen and organismal mass interact to constrain the total oxygen budget an organism can use to fuel sustainable levels of aerobic metabolism. We calibrate species-specific parameters of Φ with physiological measurements for red abalone (Haliotis rufescens) and purple urchin (Strongylocentrotus purpuratus).

Defective T-cell response to COVID-19 vaccination in acute myeloid leukaemia and myelodysplastic syndromes.

Limited data exist on COVID-19 vaccination efficacy in patients with acute myeloid leukemia and myelodysplasia with excess blasts (AML/MDS-EB2). We report results from a prospective study, PACE (Patients with AML and COVID-19 Epidemiology). 93 patients provided samples post-vaccine 2 or 3 (PV2, PV3).

Ocean warming favours a northern species over its southern congener, whereas preliminary metabolic evidence suggests that hybridization may promote their adaptation.

Anthropogenic-induced climate change is having profound impacts on aquatic ecosystems, and the resilience of fish populations will be determined by their response to these impacts. The northern Namibian coast is an ocean warming hotspot, with temperatures rising faster than the global average. The rapid warming in Namibia has had considerable impacts on marine fauna, such as the southern extension of the distribution of from southern Angola into northern Namibian waters, where it now overlaps and hybridizes with the closely related Namibian species, .

Breathless through Time: Oxygen and Animals across Earth's History.

AbstractOxygen levels in the atmosphere and ocean have changed dramatically over Earth history, with major impacts on marine life. Because the early part of Earth's history lacked both atmospheric oxygen and animals, a persistent co-evolutionary narrative has developed linking oxygen change with changes in animal diversity. Although it was long believed that oxygen rose to essentially modern levels around the Cambrian period, a more muted increase is now believed likely.

A Hybrid Architecture (CO-CONNECT) to Facilitate Rapid Discovery and Access to Data Across the United Kingdom in Response to the COVID-19 Pandemic: Development Study.

Background: COVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom's response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace.

Machine learning of COVID-19 clinical data identifies population structures with therapeutic potential.

Clinical outcomes for patients with COVID-19 are heterogeneous and there is interest in defining subgroups for prognostic modeling and development of treatment algorithms. We obtained 28 demographic and laboratory variables in patients admitted to hospital with COVID-19. These comprised a training cohort (n = 6099) and two validation cohorts during the first and second waves of the pandemic (n = 996; n = 1011).

Thermal tolerance, safety margins and vulnerability of coastal species: Projected impact of climate change induced cold water variability in a temperate African region.

Anthropogenic induced climate change is predicted to increase the thermal variability in coastal waters, which can have strong physiological effects on individuals and populations of marine ectotherms. The magnitude and direction of these thermal effects varies depending on species, life stage, biogeography, habitat and season. This study aimed to compare the thermal tolerance of a range of juvenile fish and adult macro-invertebrates from intertidal and estuarine habitats in a warm-temperate, thermally variable region on the south-east coast of South Africa.

Different drivers, common mechanism; the distribution of a reef fish is restricted by local-scale oxygen and temperature constraints on aerobic metabolism.

The distributions of ectothermic marine organisms are limited to temperature ranges and oxygen conditions that support aerobic respiration, quantified within the metabolic index (ϕ) as the ratio of oxygen supply to metabolic oxygen demand. However, the utility of ϕ at local scales and across heterogenous environments is unknown; yet, these scales are often where actionable management decisions are made. Here, we test if ϕ can delimit the entire distribution of marine organisms when calibrated across an appropriate temperature range and at local scales (~10 km) using the endemic reef fish, , which is found in the highly heterogenous temperature and oxygen environment along the South African coastal zone, as a model species.

The use of internal heart rate loggers in determining cardiac breakpoints of fish.

As marine environments are influenced by global warming there is a need to thoroughly understand the relationship between physiological limits and temperature in fish. One quick screening method of a physiological thermal tipping point is the temperature at which maximum heart rate (ƒ) can no longer scale predictably with warming and is referred to as the Arrhenius break temperature (T). The use of this method has been successful for freshwater fish by using external electrodes to detect an electrocardiogram (ECG), however, the properties of this equipment pose challenges in salt water when evaluating marine fish.

Implantation, orientation and validation of a commercially produced heart-rate logger for use in a perciform teleost fish.

Quantifying how the heart rate of ectothermic organisms responds to environmental conditions (e.g. water temperature) is important information to quantify their sensitivity to environmental change.

Exploitation may influence the climate resilience of fish populations through removing high performance metabolic phenotypes.

Physiological rates and processes underpin the relationships between ectothermic organisms, such as fish, and their environment. The response and persistence of fish populations in an increasingly variable ocean is dependent on the distribution and diversity of physiological phenotypes. Growing evidence suggests that fisheries exploitation can selectively target certain physiological and behavioural phenotypes, which may shift exploited populations to altered physiological states.

Very early lineage-specific chimerism after reduced intensity stem cell transplantation is highly predictive of clinical outcome for patients with myeloid disease.

Background: The importance of chimerism status in the very early period after hematopoietic stem cell transplantation is unclear. We determined PBMC and T-cell donor chimerism 50 days after transplantation and related this to disease relapse and overall survival.

Methods: 144 sequential patients underwent transplantation of which 90 had AML/MDS and 54 had lymphoma.

Progression of mycosis fungoides occurs through divergence of tumor immunophenotype by differential expression of HLA-DR.

Immunotherapy is a valuable treatment for many cancer patients, and there is considerable interest in understanding the mechanisms of immune evasion to guide appropriate management. Mycosis fungoides (MF) is a malignant disorder of skin-homing CD4 T cells, and it exhibits a highly variable clinical course during which the tumor-specific immune response may be an important determinant. An unusual feature of MF is that tumor-infiltrating lymphocytes (TILs) must attempt to control a malignant cell from within their own lineage.

The number of CD56 NK cells in the graft has a major impact on risk of disease relapse following allo-HSCT.

The graft-versus-leukemia (GVL) effect of allogeneic hemopoietic stem cell transplantation (allo-HSCT) is mediated by the donor immune system and acts to decrease the rate of disease relapse. Although studies of posttransplant immune reconstitution have identified correlates of clinical outcome, the number and profile of mature immune cells infused with the stem cell graft is also likely to be an important determinant and has been relatively poorly studied. We characterized immune cells within the stem cell graft of 107 patients who underwent T-cell-depleted allo-HSCT and related this to clinical outcome.

National Emergency Department Overcrowding Study tool is not useful in an Australian emergency department.

Objective: To determine the accuracy and usefulness of the National Emergency Department Overcrowding Study (NEDOCS) tool in an urban hospital ED in Australia by direct comparison with subjective assessment by senior ED staff.

Method: A sample of simultaneous subjective and objective data pairs were collected six times a day for a period of 3 weeks. All senior medical staff in the ED answered a brief questionnaire along with the senior charge nurse for the ED.