Platelet-rich plasmapheresis in cardiac surgery: A meta-analysis of the effect on transfusion requirements

AbstractObjective:Our purpose was to determine whether intraoperative platelet-rich plasmapheresis in cardiac surgery is effective in reducing the proportion of patients exposed to allogeneic red cell transfusions. Methods: A systematic search for prospective, randomized trials of platelet-rich plasmapheresis in cardiac surgery, using MEDLINE, HEALTHSTAR, Current Contents, “Biological Abstracts,” and EMBASE/Excerpta Medica up to August 1997, was completed. Trials were included if they reported either the proportion of patients exposed to allogeneic red cells or the units of allogeneic red cells transfused. Trials were abstracted by 2 independent investigators and the quality of trial design was assessed with the use of a validated scale. Results: Seventeen references met the inclusion criteria (1369 patients [675 control: 694 platelet-rich plasmapheresis]). Platelet-rich plasmapheresis reduced the likelihood of exposure to allogeneic red cells in cardiac surgery (odds ratio 0.44; 95% confidence interval 0.27, 0.72, P = .001). Platelet-rich plasmapheresis had a small but statistically significant effect on both the volume of blood lost in the first 24 hours (weighted mean difference –102 mL; 95% confidence interval –148, –55 mL, P < .0001) and the mean units transfused (weighted mean difference –0.33 units; 95% confidence interval –0.43, –0.23, P < .0001). However, platelet-rich plasmapheresis was only marginally effective (odds ratio 0.83, 95% confidence interval 0.34, 2.01, P = .68) for “good” quality trials, whereas it appeared very effective in trials with poor methodologic quality (odds ratio 0.33, 95% confidence interval 0.17, 0.62, P = .0007). Conclusions: Although platelet-rich plasmapheresis appeared effective in decreasing the proportion of patients receiving transfusions after cardiac operations, the quality of most of the supporting trials was low and the benefit was small in trials of good quality. Further clinical trials should be completed. (J Thorac Cardiovasc Surg 1998;116:641-7

Missing Transverse-Doppler Effect in Time-Dilation Experiments with High-Speed Ions

Recent experiments with high-speed ions have investigated potential deviations from the time-dilation predicted by special relativity (SR). The main contribution of this article is to show that the SR predictions are matched by the experimental results only when the transverse Doppler effect in the observed emissions from the ions are neglected in the analysis. However, the Doppler effect in the emission cannot be neglected because it is similar to the time dilation effect. Thus, the article highlights the need to consider Doppler emission effects when validating SR time dilation using high-speed ion experiments.Comment: 3 pages, 3 figure

Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization

Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed

Domestic chicken diversity: Origin, distribution, and adaptation

Chicken is the most numerous among the domesticated livestock species. Across cultures, religions, and societies, chicken is widely accepted with little or no taboo compared to other domestic animals. Its adaptability to diverse environmental conditions and demonstrated potential for breeding improvement provide a unique genetic resource for addressing the challenges of food security in a world impacted by climatic change and human population growth. Recent studies, shedding new knowledge on the chicken genomes, have helped reconstruct its past evolutionary history. Here, we review the literature concerning the origin, dispersion, and adaptation of domestic chicken. We highlight the role of human and natural selection in shaping the diversity of the species and provide a few examples of knowledge gaps that may be the focus of future research

Looking forward through the past: identification of 50 priority research questions in palaeoecology

1. Priority question exercises are becoming an increasingly common tool to frame future agendas in conservation and ecological science. They are an effective way to identify research foci that advance the field and that also have high policy and conservation relevance. 2. To date, there has been no coherent synthesis of key questions and priority research areas for palaeoecology, which combines biological, geochemical and molecular techniques in order to reconstruct past ecological and environmental systems on time-scales from decades to millions of years. 3. We adapted a well-established methodology to identify 50 priority research questions in palaeoecology. Using a set of criteria designed to identify realistic and achievable research goals, we selected questions from a pool submitted by the international palaeoecology research community and relevant policy practitioners. 4. The integration of online participation, both before and during the workshop, increased international engagement in question selection. 5. The questions selected are structured around six themes: human–environment interactions in the Anthropocene; biodiversity, conservation and novel ecosystems; biodiversity over long time-scales; ecosystem processes and biogeochemical cycling; comparing, combining and synthesizing information from multiple records; and new developments in palaeoecology. 6. Future opportunities in palaeoecology are related to improved incorporation of uncertainty into reconstructions, an enhanced understanding of ecological and evolutionary dynamics and processes and the continued application of long-term data for better-informed landscape management

Health Care Utilization During the COVID-19 Pandemic Among Individuals Born Preterm

Importance: Limited data exist on pediatric health care utilization during the COVID-19 pandemic among children and young adults born preterm. Objective: To investigate differences in health care use related to COVID-19 concerns during the pandemic among children and young adults born preterm vs those born at term. Design, Setting, and Participants: In this cohort study, questionnaires regarding COVID-19 and health care utilization were completed by 1691 mother-offspring pairs from 42 pediatric cohorts in the National Institutes of Health Environmental Influences on Child Health Outcomes Program. Children and young adults (ages 1-18 years) in these analyses were born between 2003 and 2021. Data were recorded by the August 31, 2021, data-lock date and were analyzed between October 2021 and October 2022. Exposures: Premature birth (<37 weeks' gestation). Main Outcomes and Measures: The main outcome was health care utilization related to COVID-19 concerns (hospitalization, in-person clinic or emergency department visit, phone or telehealth evaluations). Individuals born preterm vs term (≥37 weeks' gestation) and differences among preterm subgroups of individuals (<28 weeks', 28-36 weeks' vs ≥37 weeks' gestation) were assessed. Generalized estimating equations assessed population odds for health care used and related symptoms, controlling for maternal age, education, and psychiatric disorder; offspring history of bronchopulmonary dysplasia (BPD) or asthma; and timing and age at COVID-19 questionnaire completion. Results: Data from 1691 children and young adults were analyzed; among 270 individuals born preterm, the mean (SD) age at survey completion was 8.8 (4.4) years, 151 (55.9%) were male, and 193 (71.5%) had a history of BPD or asthma diagnosis. Among 1421 comparison individuals with term birth, the mean (SD) age at survey completion was 8.4 (2.4) years, 749 (52.7%) were male, and 233 (16.4%) had a history of BPD or asthma. Preterm subgroups included 159 individuals (58.5%) born at less than 28 weeks' gestation. In adjusted analyses, individuals born preterm had a significantly higher odds of health care utilization related to COVID-19 concerns (adjusted odds ratio [aOR], 1.70; 95% CI, 1.21-2.38) compared with term-born individuals; similar differences were also seen for the subgroup of individuals born at less than 28 weeks' gestation (aOR, 2.15; 95% CI, 1.40-3.29). Maternal history of a psychiatric disorder was a significant covariate associated with health care utilization for all individuals (aOR, 1.44; 95% CI, 1.17-1.78). Conclusions and Relevance: These findings suggest that during the COVID-19 pandemic, children and young adults born preterm were more likely to have used health care related to COVID-19 concerns compared with their term-born peers, independent of a history of BPD or asthma. Further exploration of factors associated with COVID-19-related health care use may facilitate refinement of care models

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease