38 research outputs found

    Nighttime removal of NOx in the summer marine boundary layer

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    The nitrate radical, NO3, and dinitrogen pentoxide, N2O5, are two important components of nitrogen oxides that occur predominantly at night in the lower troposphere. Because a large fraction of NO2 reacts to form NO3 and N2O5 during the course of a night, their fate is an important determining factor to the overall fate of NOx (=NO and NO2). As a comprehensive test of nocturnal nitrogen oxide chemistry, concentrations of O3, NO, NO2, NO3, N2O5, HNO3 and a host of other relevant compounds, aerosol abundance and composition, and meteorological conditions were measured in the marine boundary layer from the NOAA research vessel Ronald H. Brown off the East Coast of the United States as part of the New England Air Quality Study (NEAQS) during the summer of 2002. The results confirm the prominent role of NO3 and N2O5 in converting NOx to HNO3 at night with an efficiency on par with daytime photochemical conversion. The findings demonstrate the large role of nighttime chemistry in determining the NOx budget and consequent production of ozone. INDEX TERMS: 0322 Atmospheric Composition and Structure: Constituent sources and sinks; 0345 Atmospheric Composition and Structure: Pollution—urban and regional (0305); 0365 Atmospheric Composition and Structure: Troposphere—composition and chemistry. Citation: Brown, S. S., et al. (2004), Nighttime removal of NOx in the summer marine boundary layer, Geophys. Res. Lett., 31, L07108, doi:10.1029/2004GL01941

    Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, <scp>genotype–phenotype</scp> correlations and common mechanisms

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    Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (&gt;60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS‐like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or “DTRs”). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype–phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population

    Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency

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    -linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations in IL2RG encoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1

    Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

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    Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

    Year-to-year variation in cone production in Wollemia nobilis (Wollemi Pine)

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    Seed production varies from year-to-year in most species. Factors influencing this variation can include pollination and dispersal mechanisms, seed predation and resource availability. Here we examine a long-term (12– year) photographic record of seed cone production for the Australian endemic conifer Wollemia nobilis (Araucariaceae). Coefficient of variation (a commonly used measure of variation in seed production) was low for the two trees analysed, compared with published values for other polycarpic plants. Nevertheless, cone production decreased with increasing spring minimum temperatures (during pollination) and increased with summer total rainfall (during cone initiation). Hence, Wollemia nobilis cone production was correlated with weather, in line with the resource-matching hypothesis. Impacts of variation in cone production on the Wollemia nobilis population are likely to be buffered by the shade-tolerant, slow-growing juvenile life stage of Wollemia nobilis

    Green plants in the red : a baseline global assessment for the IUCN Sampled Red List Index for Plants

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    Plants provide fundamental support systems for life on Earth and are the basis for all terrestrial ecosystems; a decline in plant diversity will be detrimental to all other groups of organisms including humans. Decline in plant diversity has been hard to quantify, due to the huge numbers of known and yet to be discovered species and the lack of an adequate baseline assessment of extinction risk against which to track changes. The biodiversity of many remote parts of the world remains poorly known, and the rate of new assessments of extinction risk for individual plant species approximates the rate at which new plant species are described. Thus the question 'How threatened are plants?' is still very difficult to answer accurately. While completing assessments for each species of plant remains a distant prospect, by assessing a randomly selected sample of species the Sampled Red List Index for Plants gives, for the first time, an accurate view of how threatened plants are across the world. It represents the first key phase of ongoing efforts to monitor the status of the world's plants. More than 20% of plant species assessed are threatened with extinction, and the habitat with the most threatened species is overwhelmingly tropical rain forest, where the greatest threat to plants is anthropogenic habitat conversion, for arable and livestock agriculture, and harvesting of natural resources. Gymnosperms (e.g. conifers and cycads) are the most threatened group, while a third of plant species included in this study have yet to receive an assessment or are so poorly known that we cannot yet ascertain whether they are threatened or not. This study provides a baseline assessment from which trends in the status of plant biodiversity can be measured and periodically reassessed.Publisher PDFPeer reviewe

    Effect of preoperative pain and depressive symptoms on the risk of postoperative delirium: a prospective cohort study

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    Background Preoperative pain and depression predispose patients to delirium. We investigated whether pain and depressive symptoms interact to increase the risk of delirium.Methods We enrolled 459 people without dementia, who were aged 70 years or older and were scheduled for elective orthopaedic surgery between June, 2010, and August, 2013. At baseline, participants reported their current pain and the average and worst pain in the previous 7 days, on a scale of 0-10. Depressive symptoms before surgery were assessed with the 15-item geriatric depression scale and chart. Delirium after surgery was assessed with the confusion assessment method and chart. We used multivariable analysis to assess the relation between preoperative pain and postoperative delirium stratified by the presence of depressive symptoms.Findings Delirium was reported in 106 (23%) of patients, and was significantly more frequent in those with depressive symptoms at baseline than in those without (relative risk [RR] 1.6, 95% CI 1.2-2.3). Preoperative pain was associated with an increased adjusted risk of delirium across all pain measures (RR 1.07-1.08 per 1-point increase in pain). In stratified analyses, patients with depressive symptoms had a 21% increased risk of delirium for each 1-point increase in worst pain score, which indicated a significant interaction (p(interaction)=0.049). Similarly, a 13% increased risk of delirium was seen per 1-point increase in average pain score, but the interaction was not significant.Interpretation Preoperative pain and depressive symptoms are associated with increased risk of delirium, independently and with substantial interaction, which suggests a cumulative effect. These factors should be assessed before surgery
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