Utilizing rarely used source materials and identifying points of bias among more commonly used sources, this critical review provides a more complete representation of wartime Los Alamos computing ...operations and personnel, including the Laboratory's typically underrepresented human computers and how they contributed to the success of the Trinity test. This paper also identifies how the Laboratory's unusual wartime computing demands served as a formative experience among many Los Alamos personnel and consultants who contributed significantly to the development and use of mechanized computing at and beyond Los Alamos after the war.
Abstract
Highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage (GsGd), which threaten the health of poultry, wildlife and humans, are spreading across Asia, Europe, ...Africa and North America but are currently absent from South America and Oceania. In December 2021, H5N1 HPAI viruses were detected in poultry and a free-living gull in St. John’s, Newfoundland and Labrador, Canada. Our phylogenetic analysis showed that these viruses were most closely related to HPAI GsGd viruses circulating in northwestern Europe in spring 2021. Our analysis of wild bird migration suggested that these viruses may have been carried across the Atlantic via Iceland, Greenland/Arctic or pelagic routes. The here documented incursion of HPAI GsGd viruses into North America raises concern for further virus spread across the Americas by wild bird migration.
Several studies have identified clinical, psychosocial, patient characteristic, and perioperative variables that are associated with persistent postsurgical pain; however, the relative effect of ...these variables has yet to be quantified. The aim of the study was to provide a systematic review and meta-analysis of predictor variables associated with persistent pain after total knee arthroplasty (TKA).
Included studies were required to measure predictor variables prior to or at the time of surgery, include a pain outcome measure at least 3 months post-TKA, and include a statistical analysis of the effect of the predictor variable(s) on the outcome measure. Counts were undertaken of the number of times each predictor was analysed and the number of times it was found to have a significant relationship with persistent pain. Separate meta-analyses were performed to determine the effect size of each predictor on persistent pain. Outcomes from studies implementing uni- and multivariable statistical models were analysed separately.
Thirty-two studies involving almost 30 000 patients were included in the review. Preoperative pain was the predictor that most commonly demonstrated a significant relationship with persistent pain across uni- and multivariable analyses. In the meta-analyses of data from univariate models, the largest effect sizes were found for: other pain sites, catastrophizing, and depression. For data from multivariate models, significant effects were evident for: catastrophizing, preoperative pain, mental health, and comorbidities.
Catastrophizing, mental health, preoperative knee pain, and pain at other sites are the strongest independent predictors of persistent pain after TKA.
The preternaturally long-lived naked mole-rat, like other long-lived species and experimental models of extended longevity, is resistant to both endogenous (e.g., reactive oxygen species) and ...environmental stressors and also resists age-related diseases such as cancer, cardiovascular disease, and neurodegeneration. The mechanisms behind the universal resilience of longer-lived organisms to stress, however, remain elusive. We hypothesize that this resilience is linked to the activity of a highly conserved transcription factor, nuclear factor erythroid 2-related factor (Nrf2). Nrf2 regulates the transcription of several hundred cytoprotective molecules, including antioxidants, detoxicants, and molecular chaperones (heat shock proteins). Nrf2 itself is tightly regulated by mechanisms that either promote its activity or increase its degradation. We used a comparative approach and examined Nrf2-signaling activity in naked mole-rats and nine other rodent species with varying maximum lifespan potential (MLSP). We found that constitutive Nrf2-signaling activity was positively correlated ( P = 0.0285) with MLSP and that this activity was also manifested in high levels of downstream gene expression and activity. Surprisingly, we found that species longevity was not linked to the protein levels of Nrf2 itself, but rather showed a significant ( P < 0.01) negative relationship with the regulators Kelch-like ECH-Associated Protein 1 (Keap1) and β-transducin repeat-containing protein (βTrCP), which target Nrf2 for degradation. These findings highlight the use of a comparative biology approach for the identification of evolved mechanisms that contribute to health span, aging, and longevity.
Significance Both genetically altered and naturally long-lived mammals are more resistant to toxic compounds that may cause cancer and age-associated diseases than their shorter-lived counterparts. The mechanisms by which this stress resistance occurs remain elusive. We found that longer-lived rodent species had markedly higher levels of signaling activity of the multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) and that this increase in cytoprotective signaling appeared to be due to species differences in Kelch-like ECH-Associated Protein 1 (Keap1) and β-transducin repeat-containing protein (βTrCP) regulation of Nrf2 activity. Both of these negative regulators of Nrf2-signaling activity are significantly lower in longer-lived species. By targeting the proteins that regulate Nrf2 rather than Nrf2 itself, we may be able to identify new therapies that impact aging and age-associated diseases such as cancer.
Summary
Background Following the appreciation of the importance of gliadin deamidation in the immunopathogenesis of coeliac disease, diagnostic tests based on antibodies to deamidated gliadin ...peptides have been developed and shown to have high sensitivity and specificity.
Aim To compare the performance of the deamidated gliadin peptides antibody test with the current standard, the tissue transglutaminase antibody test, through a meta‐analysis of published studies.
Methods Databases from 1998 to 2008 were searched for relevant studies. These were assessed for methodological quality and standard statistical tests were applied to compare particularly the sensitivity and specificity of the two tests for the diagnosis of coeliac disease.
Results Most studies had methodological flaws, especially ascertainment bias. The pooled sensitivities for the deamidated gliadin peptides antibody and tissue transglutaminase antibody tests were 87.8% (95% CI, 85.6–89.9) and 93.0% (95% CI, 91.2–94.5) respectively and the pooled specificities were 94.1% (95% CI, 92.5–95.5) and 96.5% (95% CI, 95.2–97.5) respectively.
Conclusion Although both tests perform well, the tissue transglutaminase antibody test outperforms the deamidated gliadin peptides antibody test and remains the preferred serological test for the diagnosis and/or exclusion of coeliac disease.
The interindividual variation in ventilatory acclimatization to high altitude is likely reflected in variability in the cerebrovascular responses to high altitude, particularly between brain regions ...displaying disparate hypoxic sensitivity. We assessed regional differences in cerebral blood flow (CBF) measured with Duplex ultrasound of the left internal carotid and vertebral arteries. End-tidal Pco2, oxyhemoglobin saturation (SpO2), blood pressure, and heart rate were measured during a trekking ascent to, and during the first 2 wk at, 5,050 m. Transcranial color-coded Duplex ultrasound (TCCD) was employed to measure flow and diameter of the middle cerebral artery (MCA). Measures were collected at 344 m (TCCD-baseline), 1,338 m (CBF-baseline), 3,440 m, and 4,371 m. Following arrival to 5,050 m, regional CBF was measured every 12 h during the first 3 days, once at 5-9 days, and once at 12-16 days. Total CBF was calculated as twice the sum of internal carotid and vertebral flow and increased steadily with ascent, reaching a maximum of 842 ± 110 ml/min (+53 ± 7.6% vs. 1,338 m; mean ± SE) at ∼ 60 h after arrival at 5,050 m. These changes returned to +15 ± 12% after 12-16 days at 5,050 m and were related to changes in SpO2 (R(2) = 0.36; P < 0.0001). TCCD-measured MCA flow paralleled the temporal changes in total CBF. Dilation of the MCA was sustained on days 2 (+12.6 ± 4.6%) and 8 (+12.9 ± 2.9%) after arrival at 5,050 m. We observed no significant differences in regional CBF at any time point. In conclusion, the variability in CBF during ascent and acclimatization is related to ventilatory acclimatization, as reflected in changes in SpO2.
GJ 3470b is a warm Neptune transiting an M-dwarf star at the edge of the evaporation desert. It offers the possibility of investigating how low-mass, close-in exoplanets evolve under the irradiation ...from their host stars. We observed three transits of GJ 3470b in the Lyman-α line with the Hubble Space Telescope (HST) as part of the Panchromatic Comparative Exoplanet Treasury (PanCET) program. Absorption signatures are detected with similar properties in all three independent epochs, with absorption depths of 35 ± 7% in the blue wing of the line, and 23 ± 5% in the red wing. The repeatability of these signatures, their phasing with the planet transit, and the radial velocity of the absorbing gas allow us to conclude that there is an extended upper atmosphere of neutral hydrogen around GJ 3470b. We determine from our observations the stellar radiation pressure and XUV irradiation from GJ 3470 and use them to perform numerical simulations of the upper atmosphere of GJ 3470b with the EVaporating Exoplanets (EVE) code. The unusual redshifted signature can be explained by the damping wings of dense layers of neutral hydrogen that extend beyond the Roche lobe and are elongated in the direction of the planet motion. This structure could correspond to a shocked layer of planetary material formed by the collision of the expanding thermosphere with the wind of the star. The blueshifted signature is well explained by neutral hydrogen atoms escaping at rates of about 1010 g s−1 that are blown away from the star by its strong radiation pressure and are quickly photoionized, resulting in a smaller exosphere than that of the warm Neptune GJ 436b. The stronger escape from GJ 3470b, however, may have led to the loss of about 4–35% of its current mass over its ~2 Gyr lifetime.
The atmospheres of late M stars represent a significant challenge in the characterization of any transiting exoplanets because of the presence of strong molecular features in the stellar atmosphere. ...TRAPPIST-1 is an ultracool dwarf, host to seven transiting planets, and contains its own molecular signatures that can potentially be imprinted on planetary transit lightcurves as a result of inhomogeneities in the occulted stellar photosphere. We present a case study on TRAPPIST-1g, the largest planet in the system, using a new observation together with previous data, to disentangle the atmospheric transmission of the planet from that of the star. We use the out-of-transit stellar spectra to reconstruct the stellar flux on the basis of one, two, and three temperature components. We find that TRAPPIST-1 is a 0.08 M*, 0.117 R*, M8V star with a photospheric effective temperature of 2400 K, with ∼35% 3000 K spot coverage and a very small fraction, <3%, of ∼5800 K hot spot. We calculate a planetary radius for TRAPPIST-1g to be Rp = 1.124 R⊕with a planetary density of p = 0.8214 ⊕. On the basis of the stellar reconstruction, there are 11 plausible scenarios for the combined stellar photosphere and planet transit geometry; in our analysis, we are able to rule out eight of the 11 scenarios. Using planetary models, we evaluate the remaining scenarios with respect to the transmission spectrum of TRAPPIST-1g. We conclude that the planetary transmission spectrum is likely not contaminated by any stellar spectral features and are able to rule out a clear solar H2/He-dominated atmosphere at greater than 3 .
Abstract
We present a thermal emission spectrum of the bloated hot Jupiter HAT-P-32Ab from a single eclipse observation made in spatial scan mode with the Wide Field Camera 3 (WFC3) aboard the Hubble ...Space Telescope (HST). The spectrum covers the wavelength regime from 1.123 to 1.644 μm which is binned into 14 eclipse depths measured to an averaged precision of 104 parts-per million. The spectrum is unaffected by a dilution from the close M-dwarf companion HAT-P-32B, which was fully resolved. We complemented our spectrum with literature results and performed a comparative forward and retrieval analysis with the 1D radiative-convective ATMO model. Assuming solar abundance of the planet atmosphere, we find that the measured spectrum can best be explained by the spectrum of a blackbody isothermal atmosphere with Tp = 1995 ± 17 K, but can equally well be described by a spectrum with modest thermal inversion. The retrieved spectrum suggests emission from VO at the WFC3 wavelengths and no evidence of the 1.4 μm water feature. The emission models with temperature profiles decreasing with height are rejected at a high confidence. An isothermal or inverted spectrum can imply a clear atmosphere with an absorber, a dusty cloud deck or a combination of both. We find that the planet can have continuum of values for the albedo and recirculation, ranging from high albedo and poor recirculation to low albedo and efficient recirculation. Optical spectroscopy of the planet's day-side or thermal emission phase curves can potentially resolve the current albedo with recirculation degeneracy.
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