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The surge of human genetic information, enabled by increasingly facile and economically feasible genomic technologies, has accelerated discoveries on the relationship of germline genetic variation to hematologic diseases. For example, germline variation in GATA2, encoding a vital transcriptional regulator of multilineage hematopoiesis, creates a predisposition to bone marrow failure and acute myeloid leukemia termed GATA2 deficiency syndrome. More than 300 GATA2 variants representing missense, truncating, and noncoding enhancer mutations have been documented. Although these variants can diminish GATA2 expression and/or function, the functional ramifications of many variants are unknown. Studies using genetic rescue and knockin mouse systems have established that GATA2 mutations differentially affect molecular processes in distinct target genes and within a single target cell. Considering that target genes for a transcription factor can differ in sensitivity to altered levels of the factor, and transcriptional mechanisms are often cell type specific, the context-dependent consequences of GATA2 mutations in experimental systems portend the complex phenotypes and interindividual variation of GATA2 deficiency syndrome. This review documents GATA2 human genetics and the state of efforts to traverse from physiological insights to pathogenic mechanisms.Systems-based hematology is dedicated to improving care delivery for patients with blood disorders. First defined by the American Society of Hematology in 2015, the idea of a systems-based hematologist arose from evolving pressures in the health care system and increasing recognition of opportunities to optimize the quality and cost effectiveness of hematologic care. In this review, we begin with a proposed framework to formalize the discussion of the range of initiatives within systems-based hematology. Classification by 2 criteria, project scope and method of intervention, facilitates comparison between initiatives and supports dialogue for future efforts. Next, we present published examples of successful systems-based initiatives in the field of hematology, including efforts to improve stewardship in the diagnosis and management of complex hematologic disorders (eg, heparin-induced thrombocytopenia and thrombophilias), the development of programs to promote appropriate use of hematologic therapies (eg, blood products, inferior vena cava filters, and anticoagulation), changes in care delivery infrastructure to improve access to hematologic expertise (eg, electronic consultation and disorder-specific care pathways), and others. The range of projects illustrates the broad potential for interventions and highlights different metrics used to quantify improvements in care delivery. We conclude with a discussion about future directions for the field of systems-based hematology, including extension to malignant disorders and the need to define, expand, and support career pathways.
High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region.

A CoC with the following 4 stages was constructed number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit.

We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were 86%, 93%, 93%, 74%; for people who inject drugs 94%, 88%, 85%, 70%; and for heterosexuals 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries.

The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control.
The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. learn more Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control.Intense bottom-ice algal blooms, often dominated by diatoms, are an important source of food for grazers, organic matter for export during sea ice melt, and dissolved organic carbon. Sea-ice diatoms have a number of adaptations, including accumulation of compatible solutes, that allows them to inhabit this highly variable environment characterized by extremes in temperature, salinity, and light. In addition to protecting them from extreme conditions, these compounds present a labile, nutrient-rich source of organic matter, and include precursors to climate active compounds (e.g., dimethyl sulfide [DMS]), which are likely regulated with environmental change. Here, intracellular concentrations of 45 metabolites were quantified in three sea-ice diatom species and were compared to two temperate diatom species, with a focus on compatible solutes and free amino acid pools. There was a large diversity of metabolite concentrations between diatoms with no clear pattern identifiable for sea-ice species. Concentrations of some compatible solutes (isethionic acid, homarine) approached 1 M in the sea-ice diatoms, Fragilariopsis cylindrus and Navicula cf. perminuta, but not in the larger sea-ice diatom, Nitzschia lecointei or in the temperate diatom species. The differential use of compatible solutes in sea-ice diatoms suggests different adaptive strategies and highlights which small organic compounds may be important in polar biogeochemical cycles.
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