Explore the vast range of titles available.

Blood transfusion is one of the most common procedures in patients in hospital so it is imperative that clinicians are knowledgeable about appropriate blood product administration, as well as the signs, symptoms, and management of transfusion reactions. In this Review, we, an international panel, provide a synopsis of the pathophysiology, treatment, and management of each diagnostic category of transfusion reaction using evidence-based recommendations whenever available.

Abstract Objectives The 2019 SCARED study developed the Biomedical Excellence for Safer Transfusion (BEST) criteria in an effort to standardize the decision to culture residual units in the context of suspected septic transfusion reactions (STRs). The goal of this study was to apply the BEST criteria to determine the effect on the transfusion reaction decision to culture. Methods This retrospective, single-center, cross-sectional study assessed adult transfusion reactions identified in calendar years 2013 to 2020. Reactions following transfusion of RBCs, platelets, and plasma were included, and the decisions to culture following strict application of BEST criteria were compared with decisions to culture in actual practice. Results In total, 1,068 transfusion reactions were reported and 200 (19%) suspected STRs were cultured, all with negative results; 303 (28%) reactions would have been cultured per strict application of the BEST criteria. Concordance between actual culture decision and BEST criteria recommendation was 62% for cultured components and 79% for components that were not cultured. Conclusions BEST criteria provide objective recommendations of when to culture residual units implicated in suspected STRs, but strict application of these criteria may result in increased culture rates. Clinical correlation to aid in the decision to culture is recommended.

BackgroundAutomated solid-phase antibody screening uses red blood cell (RBC) membranes immobilised on polystyrene test wells to detect RBC specific antibodies. Despite its time-saving and labour-saving benefits, this method produces a higher rate of nonspecific reactivity compared with manual screening. Solid-phase panreactivity (SPP) is characterised by panreactivity (ie, all test cells reacting) in solid-phase testing accompanied by a negative autocontrol and a lack of reactivity when the same screening cells are tested in tube. The mechanisms underlying SPP and its clinical significance remain unclear. The goals of this study were to describe the prevalence of SPP at our institution and determine the alloimmunisation and transfusion reaction rates within this population.MethodsData were collected on all patients undergoing type and screen testing over a 6-year period. Study patients undergoing subsequent transfusion were evaluated for reported transfusion reactions and development of new alloantibodies.ResultsOf the 76 051 patients studied, 0.7% demonstrated SPP of which 11% developed new alloantibodies. The transfusion reaction reporting rate among patients with SPP was 2%.ConclusionsOur data suggest that patients with SPP have higher rates of reported transfusion reactions and alloantibody development compared with those without SPP.

Adolescent females in Zimbabwe are at high risk for HIV acquisition. Shaping the Health of Adolescents in Zimbabwe (SHAZ!) was a randomized controlled trial of a combined intervention package including life-skills and health education, vocational training, micro-grants and social supports compared to life-skills and health education alone. SHAZ! was originally envisioned as a larger effectiveness trial, however, the intervention was scaled back due to contextual and economic conditions in the country at the time. SHAZ! enrolled 315 participants randomly assigned to study arm within blocks of 50 participants (158 intervention and 157 control). The intervention arm participants showed statistically significant differences from the control arm participants for several outcomes during the two years of follow up including; reduced food insecurity [IOR = 0.83 vs. COR = 0.68, p-0.02], and having their own income [IOR = 2.05 vs. COR = 1.67, p = 0.02]. Additionally, within the Intervention arm there was a lower risk of transactional sex [IOR = 0.64, 95% CI (0.50, 0.83)], and a higher likelihood of using a condom with their current partner [IOR = 1.79, 95% CI (1.23, 2.62)] over time compared to baseline. There was also evidence of fewer unintended pregnancies among intervention participants [HR = 0.61, 95% CI (0.37, 1.01)], although this relationship achieved only marginal statistical significance. Several important challenges in this study included the coordination with vocational training programs, the political and economic instability of the area at the time of the study, and the difficulty in creating a true standard of care control arm. Overall the results of the SHAZ! study suggest important potential for HIV prevention intervention packages that include vocational training and micro-grants, and lessons for further economic livelihoods interventions with adolescent females. Further work is needed to refine the intervention model, and test the impact of the intervention at scale on biological outcomes. ClinicalTrials.gov NCT02034214.

Antarctic sea-ice extent, primary productivity and ocean circulation represent interconnected systems that form important components of the global carbon cycle. Subdecadal to centennial-scale variability can influence the characteristics and interactions of these systems, but observational records are too short to evaluate the impacts of this variability over longer timescales. Here, we use a 170-m-long sediment core collected from Integrated Ocean Drilling Program Site U1357B, offshore Adélie Land, East Antarctica to disentangle the impacts of sea ice and subdecadal climate variability on phytoplankton bloom frequency over the last ~11,400 years. We apply X-ray computed tomography, Ice Proxy for the Southern Ocean with 25 carbon atoms, diatom, physical property and geochemical analyses to the core, which contains an annually resolved, continuously laminated archive of phytoplankton bloom events. Bloom events occurred annually to biennially through most of the Holocene, but became less frequent (~2–7 years) at ~4.5 ka when coastal sea ice intensified. We propose that coastal sea-ice intensification subdued annual sea-ice break-out, causing an increased sensitivity of sea-ice dynamics to subdecadal climate modes, leading to a subdecadal frequency of bloom events. Our data suggest that projected loss of coastal sea ice will impact the influence of subdecadal variability on Antarctic margin primary productivity, altering food webs and carbon-cycling processes at seasonal timescales. A mid-Holocene expansion of coastal sea ice led to phytoplankton blooms’ becoming less frequent off East Antarctica, according to a suite of annually resolved physical and geochemical analyses performed on a marine sediment core.

Hypoplastic left heart syndrome is a complex congenital heart lesion that requires a three-stage procedure for surgical palliation. This clinical trial examines two approaches to the first stage of the procedure, and the results provide important guidance for the most appropriate surgical management of this serious lesion. This clinical trial examines two approaches to the first stage of the Norwood procedure, and the results provide important guidance for the most appropriate surgical management of this serious lesion. Hypoplastic left heart syndrome and related anomalies involving a single right ventricle are characterized by hypoplasia of the left heart and the aorta, with compromised systemic cardiac output (Figure 1). Infants with the syndrome generally undergo a three-stage reconstruction culminating in the Fontan procedure. The first operation (stage I) is the Norwood procedure, in which the right ventricle is connected to a reconstructed aorta with the use of the proximal main pulmonary artery for systemic outflow. Pulmonary blood flow is reestablished by means of a shunt from the pulmonary artery to the systemic circulation. In the second operation (stage II), . . .

Chemical anomalies in polar ice core records are frequently linked to volcanism; however, without the presence of (crypto)tephra particles, links to specific eruptions remain speculative. Correlating tephras yields estimates of eruption timing and potential source volcano, offers refinement of ice core chronologies, and provides insights into volcanic impacts. Here, we report on sparse rhyolitic glass shards detected in the Roosevelt Island Climate Evolution (RICE) ice core (West Antarctica), attributed to the 1.8 ka Taupō eruption (New Zealand)—one of the largest and most energetic Holocene eruptions globally. Six shards of a distinctive geochemical composition, identical within analytical uncertainties to proximal Taupō glass, are accompanied by a single shard indistinguishable from glass of the ~25.5 ka Ōruanui supereruption, also from Taupō volcano. This double fingerprint uniquely identifies the source volcano and helps link the shards to the climactic phase of the Taupō eruption. The englacial Taupō-derived glass shards coincide with a particle spike and conductivity anomaly at 278.84 m core depth, along with trachytic glass from a local Antarctic eruption of Mt. Melbourne. The assessed age of the sampled ice is 230 ± 19 CE (95% confidence), confirming that the published radiocarbon wiggle-match date of 232 ± 10 CE (2 SD) for the Taupō eruption is robust.

Mutualistic intracellular symbiosis between bacteria and insects is a widespread phenomenon that has contributed to the global success of insects. The symbionts, by provisioning nutrients lacking from diets, allow various insects to occupy or dominate ecological niches that might otherwise be unavailable. One such insect is the glassy-winged sharpshooter (Homalodisca coagulata), which feeds on xylem fluid, a diet exceptionally poor in organic nutrients. Phylogenetic studies based on rRNA have shown two types of bacterial symbionts to be coevolving with sharpshooters: the gamma-proteobacterium Baumannia cicadellinicola and the Bacteroidetes species Sulcia muelleri. We report here the sequencing and analysis of the 686,192-base pair genome of B. cicadellinicola and approximately 150 kilobase pairs of the small genome of S. muelleri, both isolated from H. coagulata. Our study, which to our knowledge is the first genomic analysis of an obligate symbiosis involving multiple partners, suggests striking complementarity in the biosynthetic capabilities of the two symbionts: B. cicadellinicola devotes a substantial portion of its genome to the biosynthesis of vitamins and cofactors required by animals and lacks most amino acid biosynthetic pathways, whereas S. muelleri apparently produces most or all of the essential amino acids needed by its host. This finding, along with other results of our genome analysis, suggests the existence of metabolic codependency among the two unrelated endosymbionts and their insect host. This dual symbiosis provides a model case for studying correlated genome evolution and genome reduction involving multiple organisms in an intimate, obligate mutualistic relationship. In addition, our analysis provides insight for the first time into the differences in symbionts between insects (e.g., aphids) that feed on phloem versus those like H. coagulata that feed on xylem. Finally, the genomes of these two symbionts provide potential targets for controlling plant pathogens such as Xylella fastidiosa, a major agroeconomic problem, for which H. coagulata and other sharpshooters serve as vectors of transmission.

Genome integrity of induced pluripotent stem cells (iPSCs) has been extensively studied in recent years, but it is still unclear whether iPSCs contain more genomic variations than cultured somatic cells. One important question is the origin of genomic variations detected in iPSCs–whether iPSC reprogramming induces such variations. Here, we undertook a unique approach by deriving fibroblast subclones and clonal iPSC lines from the same fibroblast population and applied next-generation sequencing to compare genomic variations in these lines. Targeted deep sequencing of parental fibroblasts revealed that most variants detected in clonal iPSCs and fibroblast subclones were rare variants inherited from the parental fibroblasts. Only a small number of variants remained undetectable in the parental fibroblasts, which were thus likely to be de novo. Importantly, the clonal iPSCs and fibroblast subclones contained comparable numbers of de novo variants. Collectively, our data suggest that iPSC reprogramming is not mutagenic.

Gene transfer into hematopoietic stem cells has been used successfully for correcting lymphoid but not myeloid immunodeficiencies. Here we report on two adults who received gene therapy after nonmyeloablative bone marrow conditioning for the treatment of X-linked chronic granulomatous disease (X-CGD), a primary immunodeficiency caused by a defect in the oxidative antimicrobial activity of phagocytes resulting from mutations in gp91 phox . We detected substantial gene transfer in both individuals' neutrophils that lead to a large number of functionally corrected phagocytes and notable clinical improvement. Large-scale retroviral integration site–distribution analysis showed activating insertions in MDS1-EVI1 , PRDM16 or SETBP1 that had influenced regulation of long-term hematopoiesis by expanding gene-corrected myelopoiesis three- to four-fold in both individuals. Although insertional influences have probably reinforced the therapeutic efficacy in this trial, our results suggest that gene therapy in combination with bone marrow conditioning can be successfully used to treat inherited diseases affecting the myeloid compartment such as CGD.