The underexplored frontier of ice giant dynamos
Philosophical transactions - Royal Society. Mathematical, Physical and engineering sciences/Philosophical transactions - Royal Society. Mathematical, physical and engineering sciences,
12/2020
Journal Article
Abstract Objectives This study evaluated the safety and effectiveness of self-expanding transcatheter aortic valve replacement (TAVR) in patients with surgical valve failure (SVF). Background ...Self-expanding TAVR is superior to medical therapy for patients with severe native aortic valve stenosis at increased surgical risk. Methods The CoreValve U.S. Expanded Use Study was a prospective, nonrandomized study that enrolled 233 patients with symptomatic SVF who were deemed unsuitable for reoperation. Patients were treated with self-expanding TAVR and evaluated for 30-day and 1-year outcomes after the procedure. An independent core laboratory was used to evaluate serial echocardiograms for valve hemodynamics and aortic regurgitation. Results SVF occurred through stenosis (56.4%), regurgitation (22.0%), or a combination (21.6%). A total of 227 patients underwent attempted TAVR and successful TAVR was achieved in 225 (99.1%) patients. Patients were elderly (76.7 ± 10.8 years), had a Society of Thoracic Surgeons Predicted Risk of Mortality score of 9.0 ± 6.7%, and were severely symptomatic (86.8% New York Heart Association functional class III or IV). The all-cause mortality rate was 2.2% at 30 days and 14.6% at 1 year; major stroke rate was 0.4% at 30 days and 1.8% at 1 year. Moderate aortic regurgitation occurred in 3.5% of patients at 30 days and 7.4% of patients at 1 year, with no severe aortic regurgitation. The rate of new permanent pacemaker implantation was 8.1% at 30 days and 11.0% at 1 year. The mean valve gradient was 17.0 ± 8.8 mm Hg at 30 days and 16.6 ± 8.9 mm Hg at 1 year. Factors significantly associated with higher discharge mean aortic gradients were surgical valve size, stenosis as modality of SVF, and presence of surgical valve prosthesis patient mismatch (all p < 0.001). Conclusions Self-expanding TAVR in patients with SVF at increased risk for surgery was associated with a low 1-year mortality and major stroke rate, significantly improved aortic valve hemodynamics, and low rates of moderate and no severe residual aortic regurgitation, with improved quality of life.
Under the Kigali Amendment to the Montreal Protocol, new controls are being implemented to reduce emissions of HFC-23 (CHFFormula: see text), a by-product during the manufacture of HCFC-22 ...(CHClFFormula: see text). Starting in 2015, China and India, who dominate global HCFC-22 production (75% in 2017), set out ambitious programs to reduce HFC-23 emissions. Here, we estimate that these measures should have seen global emissions drop by 87% between 2014 and 2017. Instead, atmospheric observations show that emissions have increased and in 2018 were higher than at any point in history (15.9 Formula: see text). Given the magnitude of the discrepancy between expected and observation-inferred emissions, it is likely that the reported reductions have not fully materialized or there may be substantial unreported production of HCFC-22, resulting in unaccounted-for HFC-23 by-product emissions. The difference between reported and observation-inferred estimates suggests that an additional ~309 Tg Formula: see text-equivalent emissions were added to the atmosphere between 2015 and 2017.
Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain.
...To determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery.
Prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations.
Obstructive sleep apnea was classified as mild (respiratory event index REI 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring.
The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications.
Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 SD, 9 years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio HR, 1.49 95% CI, 1.19-2.01; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 95% CI, 1.49-3.34; P = .001) and not among those with moderate OSA (adjusted HR, 1.47 95% CI, 0.98-2.09; P = .07) or mild OSA (adjusted HR, 1.36 95% CI, 0.97-1.91; P = .08) (P = .01 for interaction). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 95% CI, 15.5-27.7 minutes) was longer than in those without (10.2 95% CI, 7.8-10.9 minutes) (P < .001). No significant interaction effects on perioperative outcomes were observed with type of anesthesia, use of postoperative opioids, and supplemental oxygen therapy.
Among at-risk adults undergoing major noncardiac surgery, unrecognized severe obstructive sleep apnea was significantly associated with increased risk of 30-day postoperative cardiovascular complications. Further research would be needed to assess whether interventions can modify this risk.
Population-based studies following trajectories of depression in autism spectrum disorders (ASD) from childhood into early adulthood are rare. The role of genetic confounding and of potential ...environmental intermediaries, such as bullying, in any associations is unclear.
To compare trajectories of depressive symptoms from ages 10 to 18 years for children with or without ASD and autistic traits, to assess associations between ASD and autistic traits and an International Statistical Classification of Diseases, 10th Revision (ICD-10) depression diagnosis at age 18 years, and to explore the importance of genetic confounding and bullying.
Longitudinal study of participants in the Avon Longitudinal Study of Parents and Children birth cohort in Bristol, United Kingdom, followed up through age 18 years. Data analysis was conducted from January to November 2017.
Depressive symptoms were assessed using the Short Mood and Feelings Questionnaire (SMFQ) at 6 time points between ages 10 and 18 years. An ICD-10 depression diagnosis at age 18 years was established using the Clinical Interview Schedule-Revised. Exposures were ASD diagnosis and 4 dichotomized autistic traits (social communication, coherence, repetitive behavior, and sociability). An autism polygenic risk score was derived using the Psychiatric Genomics Consortium autism discovery genome-wide association study summary data. Bullying was assessed at ages 8, 10, and 13 years.
The maximum sample with complete data was 6091 for the trajectory analysis (48.8% male) and 3168 for analysis of depression diagnosis at age 18 years (44.4% male). Children with ASD and autistic traits had higher average SMFQ depressive symptom scores than the general population at age 10 years (eg, for social communication 5.55 95% CI, 5.16-5.95 vs 3.73 95% CI, 3.61-3.85, for ASD 7.31 95% CI, 6.22-8.40 vs 3.94 95% CI, 3.83-4.05, remaining elevated in an upward trajectory until age 18 years (eg, for social communication 7.65 95% CI, 6.92-8.37 vs 6.50 95% CI, 6.29-6.71, for ASD 7.66 95% CI, 5.96-9.35 vs 6.62 95% CI, 6.43-6.81). Social communication impairments were associated with depression at age 18 years (adjusted relative risk, 1.68; 95% CI, 1.05-2.70), and bullying explained a substantial proportion of this risk. There was no evidence of confounding by the autism polygenic risk score. Analysis in larger samples using multiple imputation led to similar but more precise results.
Children with ASD and ASD traits have higher depressive symptom scores than the general population by age 10 years, which persist to age 18 years, particularly in the context of bullying. Social communication impairments are an important autistic trait in relation to depression. Bullying, as an environmental intermediary, could be a target for interventions.
Global emissions of the ozone-depleting gas HCFC-141b (1,1-dichloro-1-fluoroethane, CH3CCl2F) derived from measurements of atmospheric mole fractions increased between 2017 and 2021 despite a fall in ...reported production and consumption of HCFC-141b for dispersive uses.
HCFC-141b is a controlled substance under the Montreal Protocol, and its phase-out is currently underway, after a peak in reported consumption and production in developing (Article 5) countries in 2013.
If reported production and consumption are correct, our study suggests that the 2017–2021 rise is due to an increase in emissions from the bank when appliances containing HCFC-141b reach the end of their life, or from production of HCFC-141b not reported for dispersive uses.
Regional emissions have been estimated between 2017–2020 for all regions where measurements have sufficient sensitivity to emissions.
This includes the regions of northwestern Europe, east Asia, the United States and Australia, where emissions decreased by a total of 2.3 ± 4.6 Gg yr−1, compared to a mean global increase of 3.0 ± 1.2 Gg yr−1 over the same period.
Collectively these regions only account for around 30 % of global emissions in 2020.
We are not able to pinpoint the source regions or specific activities responsible for the recent global emission rise.
Impressive results have been achieved by adoptively transferring T-cells expressing CD19-specific CARs with binding domains from murine mAbs to treat B-cell malignancies. T-cell mediated immune ...responses specific for peptides from the murine scFv antigen-binding domain of the CAR can develop in patients and result in premature elimination of CAR T-cells increasing the risk of tumor relapse. As fully human scFv might reduce immunogenicity, we generated CD19-specific human scFvs with similar binding characteristics as the murine FMC63-derived scFv using human Ab/DNA libraries. CARs were constructed in various formats from several scFvs and used to transduce primary human T-cells. The resulting CD19-CAR T-cells were specifically activated by CD19-positive tumor cell lines and primary chronic lymphocytic leukemia cells, and eliminated human lymphoma xenografts in immunodeficient mice. Certain fully human CAR constructs were superior to the FMC63-CAR, which is widely used in clinical trials. Imaging of cell surface distribution of the human CARs revealed no evidence of clustering without target cell engagement, and tonic signaling was not observed. To further reduce potential immunogenicity of the CARs, we also modified the fusion sites between different CAR components. The described fully human CARs for a validated clinical target may reduce immune rejection compared with murine-based CARs.
Cellular movement is controlled by small GTPases, such as RhoA. Although migration is crucial for cancer cell invasion, the specific role of RhoA in tumor formation is unclear. Inducing skin tumors ...in mice with a keratinocyte-restricted loss of RhoA, we observed increased tumor frequency, growth and invasion. In vitro invasion assays revealed that in the absence of RhoA cell invasiveness is increased in a Rho-associated protein kinase (ROCK) activation and cell contraction-dependent manner. Surprisingly, loss of RhoA causes increased Rho signaling via overcompensation by RhoB because of reduced lysosomal degradation of RhoB in Gamma-aminobutyric acid receptor-associated protein (GABARAP)+ autophagosomes and endosomes. In the absence of RhoA, RhoB relocalized to the plasma membrane and functionally replaced RhoA with respect to invasion, clonogenic growth and survival. Our data demonstrate for the first time that RhoA is a tumor suppressor in 7,12-dimethylbenzaanthracene/12-O-tetradecanoylphorbol 13-acetate skin carcinogenesis and identify Rho signaling dependent on RhoA and RhoB as a potent driver of tumor progression.
The Eastern Arc Mountains are renown in Africa for high concentrations of endemic species of animals and plants. Thirteen separate mountain blocks comprise the Eastern Arc, supporting around 3300
km
...2 of sub-montane, montane and upper montane forest, less than 30% of the estimated original forested area. At least 96 vertebrate species are endemic, split as follows: 10 mammal, 19 bird, 29 reptile and 38 amphibian species. This includes four endemic or nearly endemic species of primate – the Sanje Mangabey, the Iringa Red Colobus, the Mountain Galago and the new Kipunji monkey that forms its own monotypic genus. A further 71 vertebrate species are near-endemic. At least 800 vascular plant species are endemic, almost 10% of these being trees. These endemics include the majority of the species of African violet –
Saintpaulia, a well-known flowering plant in Western households. An additional 32 species of bryophytes are also endemic. Many hundreds of invertebrates are also likely to be endemic, with data for butterflies, millipedes and dragonflies indicating potential trends in importance. Seventy-one of the endemic or near-endemic vertebrates are threatened by extinction (8 critical, 27 endangered, 36 vulnerable), with an additional seven wide ranging threatened species. Hundreds of plant species are also threatened. Most Eastern Arc endemics are closed-forest specialists and comprise taxa with an ancient history and those of more recent origin, including some possessing ancient affinities with taxa from West Africa, Madagascar, and even South America and Southeast Asia. Mountain block prioritisation for biodiversity conservation shows that Udzungwas, East Usambaras and Ulugurus are the most important blocks, with other important blocks being the Ngurus and West Usambaras. Rankings are correlated closely with the area of remaining forest. Most of the remaining forest is found within nearly 150 Government Forest Reserves, with 106 of these managed nationally for water catchment, biodiversity and soil conservation and where forest exploitation is not allowed. Outside these areas most forest has been cleared, except in small village burial/sacred sites, a few Village Forest Reserves, and inaccessible areas. In most Eastern Arc Mountains the local populations have not encroached beyond the reserve boundaries to develop farms, but forest resources within the boundaries are used for fuel and building materials and some forests are heavily degraded. Fire is also a problem as it enters and destroys forests during the dry seasons. The future of the biodiversity on the Eastern Arc Mountains is closely tied to management policies and capacity of the Tanzania Forestry and Beekeeping Division, Tanzania National Parks Authority, and Kenya Forest Department. Supporting these agencies in their mandated job is an essential conservation investment over the longer term.
The 2013 US Veterans Administration/Department of Defense Clinical Practice Guidelines (VA/DoD CPG) require comprehensive suicide risk assessments for VA/DoD patients with mental disorders but ...provide minimal guidance on how to carry out these assessments. Given that clinician-based assessments are not known to be strong predictors of suicide, we investigated whether a precision medicine model using administrative data after outpatient mental health specialty visits could be developed to predict suicides among outpatients. We focused on male nondeployed Regular US Army soldiers because they account for the vast majority of such suicides. Four machine learning classifiers (naive Bayes, random forests, support vector regression and elastic net penalized regression) were explored. Of the Army suicides in 2004-2009, 41.5% occurred among 12.0% of soldiers seen as outpatient by mental health specialists, with risk especially high within 26 weeks of visits. An elastic net classifier with 10-14 predictors optimized sensitivity (45.6% of suicide deaths occurring after the 15% of visits with highest predicted risk). Good model stability was found for a model using 2004-2007 data to predict 2008-2009 suicides, although stability decreased in a model using 2008-2009 data to predict 2010-2012 suicides. The 5% of visits with highest risk included only 0.1% of soldiers (1047.1 suicides/100 000 person-years in the 5 weeks after the visit). This is a high enough concentration of risk to have implications for targeting preventive interventions. An even better model might be developed in the future by including the enriched information on clinician-evaluated suicide risk mandated by the VA/DoD CPG to be recorded.
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