We have used the Whole Atmosphere Community Climate Model to produce a small (three‐member) ensemble of simulations of the period 1950–2003. Comparison of model results against available observations ...shows that for the most part, the model is able to reproduce well the observed trends in zonal mean temperature and ozone, both as regards their magnitude and their distribution in latitude and altitude. Calculated trends in water vapor, on the other hand, are not at all consistent with observations from either the HALOE satellite instrument or the Boulder, Colorado, hygrosonde data set. We show that such lack of agreement is actually to be expected because water vapor has various sources of low‐frequency variability (heating due to volcanic eruptions, the quasi‐biennial oscillation and El Niño–Southern Oscillation) that can confound the determination of secular trends. The simulations also reveal the presence of other interesting behavior, such as the lack of any significant temperature trend near the mesopause, a decrease in the stratospheric age of air, and the rare occurrence of an extremely disturbed Southern Hemisphere winter.
Future changes in the stratospheric circulation could have an important impact on northern winter tropospheric climate change, given that sea level pressure (SLP) responds not only to tropospheric ...circulation variations but also to vertically coherent variations in troposphere‐stratosphere circulation. Here we assess northern winter stratospheric change and its potential to influence surface climate change in the Coupled Model Intercomparison Project‐Phase 5 (CMIP5) multimodel ensemble. In the stratosphere at high latitudes, an easterly change in zonally averaged zonal wind is found for the majority of the CMIP5 models, under the Representative Concentration Pathway 8.5 scenario. Comparable results are also found in the 1% CO2 increase per year projections, indicating that the stratospheric easterly change is common feature in future climate projections. This stratospheric wind change, however, shows a significant spread among the models. By using linear regression, we quantify the impact of tropical upper troposphere warming, polar amplification, and the stratospheric wind change on SLP. We find that the intermodel spread in stratospheric wind change contributes substantially to the intermodel spread in Arctic SLP change. The role of the stratosphere in determining part of the spread in SLP change is supported by the fact that the SLP change lags the stratospheric zonally averaged wind change. Taken together, these findings provide further support for the importance of simulating the coupling between the stratosphere and the troposphere, to narrow the uncertainty in the future projection of tropospheric circulation changes.
Key Points
Stratospheric easterly change is common feature in future climate projections
Significant intermodel spread in stratospheric northern winter climate change
Importance of stratospheric easterly change to narrow uncertainty in SLP change
Polyglutamine (polyQ) disorders, including Huntington's disease (HD), are caused by expansion of polyQ-encoding repeats within otherwise unrelated gene products. In polyQ diseases, the pathology and ...death of affected neurons are associated with the accumulation of mutant proteins in insoluble aggregates. Several studies implicate polyQ-dependent aggregation as a cause of neurodegeneration in HD, suggesting that inhibition of neuronal polyQ aggregation may be therapeutic in HD patients. We have used a yeast-based high-throughput screening assay to identify small-molecule inhibitors of polyQ aggregation. We validated the effects of four hit compounds in mammalian cell-based models of HD, optimized compound structures for potency, and then tested them in vitro in cultured brain slices from HD transgenic mice. These efforts identified a potent compound ( IC50=10 nM) with long-term inhibitory effects on polyQ aggregation in HD neurons. Testing of this compound in a Drosophila HD model showed that it suppresses neurodegeneration in vivo, strongly suggesting an essential role for polyQ aggregation in HD pathology. The aggregation inhibitors identified in this screen represent four primary chemical scaffolds and are strong lead compounds for the development of therapeutics for human polyQ diseases.
Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti‐HLA donor‐specific antibody (DSA). Program‐specific reports (PSRs) fail to ...account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio aHR = 1.64, 95% confidence interval CI: 1.15–2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71–6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28–3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98–7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal‐quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19‐, 1.33‐ and 1.73‐fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22‐, 4.09‐ and 10.72‐fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life‐saving treatment in jeopardy of regulatory intervention.
In this 22‐center study of HLA‐incompatible live donor kidney transplants (ILDKT), the authors demonstrate the increased risk of graft loss and death associated with increasing anti‐HLA donor‐specific antibody strength, and they quantify the significantly increased risk of flagging for regulatory scrutiny by the Centers for Medicare & Medicaid Studies that is incurred by centers that perform ILDKT. See editorial by Cole and Tinckam on page 1475.
The NCAR Whole Atmosphere Community Climate Model, version 3 (WACCM3), is used to study the atmospheric response from the surface to the lower thermosphere to changes in solar and geomagnetic forcing ...over the 11‐year solar cycle. WACCM3 is a general circulation model that incorporates interactive chemistry that solves for both neutral and ion species. Energy inputs include solar radiation and energetic particles, which vary significantly over the solar cycle. This paper presents a comparison of simulations for solar cycle maximum and solar cycle minimum conditions. Changes in composition and dynamical variables are clearly seen in the middle and upper atmosphere, and these in turn affect terms in the energy budget. Generally good agreement is found between the model response and that derived from satellite observations, although significant differences remain. A small but statistically significant response is predicted in tropospheric winds and temperatures which is consistent with signals observed in reanalysis data sets.
A report from a high-volume single center indicated a survival benefit of receiving a kidney transplant from an HLA-incompatible live donor as compared with remaining on the waiting list, whether or ...not a kidney from a deceased donor was received. The generalizability of that finding is unclear.
In a 22-center study, we estimated the survival benefit for 1025 recipients of kidney transplants from HLA-incompatible live donors who were matched with controls who remained on the waiting list or received a transplant from a deceased donor (waiting-list-or-transplant control group) and controls who remained on the waiting list but did not receive a transplant (waiting-list-only control group). We analyzed the data with and without patients from the highest-volume center in the study.
Recipients of kidney transplants from incompatible live donors had a higher survival rate than either control group at 1 year (95.0%, vs. 94.0% for the waiting-list-or-transplant control group and 89.6% for the waiting-list-only control group), 3 years (91.7% vs. 83.6% and 72.7%, respectively), 5 years (86.0% vs. 74.4% and 59.2%), and 8 years (76.5% vs. 62.9% and 43.9%) (P<0.001 for all comparisons with the two control groups). The survival benefit was significant at 8 years across all levels of donor-specific antibody: 89.2% for recipients of kidney transplants from incompatible live donors who had a positive Luminex assay for anti-HLA antibody but a negative flow-cytometric cross-match versus 65.0% for the waiting-list-or-transplant control group and 47.1% for the waiting-list-only control group; 76.3% for recipients with a positive flow-cytometric cross-match but a negative cytotoxic cross-match versus 63.3% and 43.0% in the two control groups, respectively; and 71.0% for recipients with a positive cytotoxic cross-match versus 61.5% and 43.7%, respectively. The findings did not change when patients from the highest-volume center were excluded.
This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from deceased donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).
Invasive methods requiring general anaesthesia are needed to sample the lung microbiota in young children who do not expectorate. This poses substantial challenges to longitudinal study of paediatric ...airway microbiota. Non-invasive upper airway sampling is an alternative method for monitoring airway microbiota; however, there are limited data describing the relationship of such results with lung microbiota in young children. In this study, we compared the upper and lower airway microbiota in young children to determine whether non-invasive upper airway sampling procedures provide a reliable measure of either lung microbiota or clinically defined differences.
The microbiota in oropharyngeal (OP) swabs, nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) from 78 children (median age 2.2 years) with and without lung disease were characterised using 16S rRNA gene sequencing. Permutational multivariate analysis of variance (PERMANOVA) detected significant differences between the microbiota in BAL and those in both OP swabs (p = 0.0001, Pseudo-F = 12.2, df = 1) and NP swabs (p = 0.0001; Pseudo-F = 21.9, df = 1) with the NP and BAL microbiota more different than the OP and BAL, as indicated by a higher Pseudo-F value. The microbiota in combined OP and NP data (upper airways) provided a more comprehensive representation of BAL microbiota, but significant differences between the upper airway and BAL microbiota remained, albeit with a considerably smaller Pseudo-F (PERMANOVA p = 0.0001; Pseudo-F = 4.9, df = 1). Despite this overall difference, paired BAL and upper airway (OP and NP) microbiota were >50 % similar among 69 % of children. Furthermore, canonical analysis of principal coordinates (CAP analysis) detected significant differences between the microbiota from clinically defined groups when analysing either BAL (eigenvalues >0.8; misclassification rate 26.5 %) or the combined OP and NP data (eigenvalues >0.8; misclassification rate 12.2 %).
Upper airway sampling provided an imperfect, but reliable, representation of the BAL microbiota for most children in this study. We recommend inclusion of both OP and NP specimens when non-invasive upper airway sampling is needed to assess airway microbiota in young children who do not expectorate. The results of the CAP analysis suggest lower and upper airway microbiota profiles may differentiate children with chronic suppurative lung disease from those with persistent bacterial bronchitis; however, further research is needed to confirm this observation.
Visual-verbal serial recall is disrupted when task-irrelevant background speech has to be ignored. Contrary to previous suggestion, it has recently been shown that the magnitude of disruption may be ...accentuated by the semantic properties of the irrelevant speech. Sentences ending with unexpected words that did not match the preceding semantic context were more disruptive than sentences ending with expected words. This particular instantiation of a deviation effect has been termed the semantic mismatch effect. To establish a new phenomenon, it is necessary to show that the effect can be independently replicated and does not depend on specific boundary conditions such as the language of the stimulus material. Here we report a preregistered replication of the semantic mismatch effect in which we examined the effect of unexpected words in 4 different languages (English, French, German, and Swedish) across 4 different laboratories. Participants performed a serial recall task while ignoring sentences with expected or unexpected words that were recorded using text-to-speech software. Independent of language, sentences ending with unexpected words were more disruptive than sentences ending with expected words. In line with previous results, there was no evidence of habituation of the semantic mismatch effect in the form of a decrease in disruption with repeated exposure to the occurrence of unexpected words. The successful replication and extension of the effect to different languages indicates the expression of a general and robust mechanism that reacts to violations of expectancies based on the semantic content of the irrelevant speech.
The atomic nucleus and its electrons are often thought of as independent systems that are held together in the atom by their mutual attraction. Their interaction, however, leads to other important ...effects, such as providing an additional decay mode for excited nuclear states, whereby the nucleus releases energy by ejecting an atomic electron instead of by emitting a γ-ray. This 'internal conversion' has been known for about a hundred years and can be used to study nuclei and their interaction with their electrons. In the inverse process-nuclear excitation by electron capture (NEEC)-a free electron is captured into an atomic vacancy and can excite the nucleus to a higher-energy state, provided that the kinetic energy of the free electron plus the magnitude of its binding energy once captured matches the nuclear energy difference between the two states. NEEC was predicted in 1976 and has not hitherto been observed. Here we report evidence of NEEC in molybdenum-93 and determine the probability and cross-section for the process in a beam-based experimental scenario. Our results provide a standard for the assessment of theoretical models relevant to NEEC, which predict cross-sections that span many orders of magnitude. The greatest practical effect of the NEEC process may be on the survival of nuclei in stellar environments, in which it could excite isomers (that is, long-lived nuclear states) to shorter-lived states. Such excitations may reduce the abundance of the isotope after its production. This is an example of 'isomer depletion', which has been investigated previously through other reactions, but is used here to obtain evidence for NEEC.
Background
The US physician workforce does not represent the racial or ethnic diversity of the population it serves.
Objectives
To assess whether the proportion of US physician trainees of Black race ...and Hispanic ethnicity has changed over time and then provide a conceptual projection of future trends.
Design
Cross-sectional, retrospective, analysis based on 11 years of publicly available data paired with recent US census population estimates.
Participants
A total of 86,303 (2007–2008) to 103,539 (2017–2018) resident physicians in the 20 largest US Accreditation Council for Graduate Medical Education resident specialties.
Main Measures
Changes in proportion of physician trainees of Black race and Hispanic ethnicity per academic year. Projected number of years it will then take, for specialties with positive changes, to reach proportions of Black race and Hispanic ethnicity comparable to that of the US population.
Key Results
Among the 20 largest specialty training programs, Radiology was the only specialty with a statistically significant increase in the proportion of Black trainees, but it could take Radiology 77 years to reach levels of Black representation comparable to that of the US population. Obstetrics/Gynecology, Emergency Medicine, Internal Medicine/Pediatrics, and Orthopedic Surgery demonstrated a statistically significant increase in the proportion of Hispanic trainees, but it could take these specialties 35, 54, 61, and 93 years respectively to achieve Hispanic representation comparable to that of the US population.
Conclusions
Among US residents in the 20 largest specialties, no specialty represented either the Black or Hispanic populations in proportions comparable to the overall US population. Only a small number of specialties demonstrated statistically significant increases. This conceptual projection suggests that current efforts to promote diversity are insufficient.
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