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To quantify the impact of patient- and unit-level risk adjustment on infant hospital-onset bacteremia (HOB) standardized infection ratio (SIR) ranking.
Design:
A retrospective, multicenter cohort study.
Setting and participants:
Infants admitted to 284 neonatal intensive care units (NICUs) in the United States between 2016 and 2021.
Methods:
Expected HOB rates and SIRs were calculated using four adjustment strategies: birthweight (model 1), birthweight and postnatal age (model 2), birthweight and NICU complexity (model 3), and birthweight, postnatal age, and NICU complexity (model 4). Sites were ranked according to the unadjusted HOB rate, and these rankings were compared to rankings based on the four adjusted SIR models.
Results:
Compared to unadjusted HOB rate ranking (smallest to largest), the number and proportion of NICUs that left the fourth quartile (worst-performing) following adjustments were as follows: adjusted for birthweight (16, 22.5%), birthweight and postnatal age (19, 26.8%), birthweight and NICU complexity (22, 31.0%), birthweight, postnatal age and NICU complexity (23, 32.4%). Comparing NICUs that moved into the better-performing quartiles after birthweight adjustment to those that remained in the better-performing quartiles regardless of adjustment, the median percentage of low birthweight infants was 17.1% (Interquartile Range (IQR): 15.8, 19.2) vs 8.7% (IQR: 4.8, 12.6); and the median percentage of infants who died was 2.2% (IQR: 1.8, 3.1) vs 0.5% (IQR: 0.01, 12.0), respectively.
Conclusion:
Adjusting for patient and unit-level complexity moved one-third of NICUs in the worst-performing quartile into a better-performing quartile. Risk adjustment may allow for a more accurate comparison across units with varying levels of patient acuity and complexity.
This study documents several correlations observed during the first run of the plasma wakefield acceleration experiment E300 conducted at FACET-II, using a single drive electron bunch. The established correlations include those between the measured maximum energy loss of the drive electron beam and the integrated betatron X-ray signal, the calculated total beam energy deposited in the plasma and the integrated X-ray signal, among three visible light emission measuring cameras and between the visible plasma light and X-ray signal. The integrated X-ray signal correlates almost linearly with both the maximum energy loss of the drive beam and the energy deposited into the plasma, demonstrating its usability as a measure of energy transfer from the drive beam to the plasma. Visible plasma light is found to be a useful indicator of the presence of a wake at three locations that overall are two metres apart. Despite the complex dynamics and vastly different time scales, the X-ray radiation from the drive bunch and visible light emission from the plasma may prove to be effective non-invasive diagnostics for monitoring the energy transfer from the beam to the plasma in future high-repetition-rate experiments.
NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.
We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
Until recently, the influence of basal liquid water on the evolution of buried glaciers in Mars' mid latitudes was assumed to be negligible because the latter stages of Mars' Amazonian period (3 Ga to present) have long been thought to have been similarly cold and dry to today. Recent identifications of several landforms interpreted as eskers associated with these young (100s Ma) glaciers calls this assumption into doubt. They indicate basal melting (at least locally and transiently) of their parent glaciers. Although rare, they demonstrate a more complex mid-to-late Amazonian environment than was previously understood. Here, we discuss several open questions posed by the existence of glacier-linked eskers on Mars, including on their global-scale abundance and distribution, the drivers and dynamics of melting and drainage, and the fate of meltwater upon reaching the ice margin. Such questions provide rich opportunities for collaboration between the Mars and Earth cryosphere research communities.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Patients presenting to hospital with suspected coronavirus disease 2019 (COVID-19), based on clinical symptoms, are routinely placed in a cohort together until polymerase chain reaction (PCR) test results are available. This procedure leads to delays in transfers to definitive areas and high nosocomial transmission rates. FebriDx is a finger-prick point-of-care test (PoCT) that detects an antiviral host response and has a high negative predictive value for COVID-19. We sought to determine the clinical impact of using FebriDx for COVID-19 triage in the emergency department (ED).
Design:
We undertook a retrospective observational study evaluating the real-world clinical impact of FebriDx as part of an ED COVID-19 triage algorithm.
Setting:
Emergency department of a university teaching hospital.
Patients:
Patients presenting with symptoms suggestive of COVID-19, placed in a cohort in a ‘high-risk’ area, were tested using FebriDx. Patients without a detectable antiviral host response were then moved to a lower-risk area.
Results:
Between September 22, 2020, and January 7, 2021, 1,321 patients were tested using FebriDx, and 1,104 (84%) did not have a detectable antiviral host response. Among 1,104 patients, 865 (78%) were moved to a lower-risk area within the ED. The median times spent in a high-risk area were 52 minutes (interquartile range [IQR], 34–92) for FebriDx-negative patients and 203 minutes (IQR, 142–255) for FebriDx-positive patients (difference of −134 minutes; 95% CI, −144 to −122; P < .0001). The negative predictive value of FebriDx for the identification of COVID-19 was 96% (661 of 690; 95% CI, 94%–97%).
Conclusions:
FebriDx improved the triage of patients with suspected COVID-19 and reduced the time that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR-negative patients spent in a high-risk area alongside SARS-CoV-2–positive patients.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care.
Methods
We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted.
Results
Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3–4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3–4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions.
Conclusions
When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments.
Technical summary
A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost–benefit ratio and new perspectives on the potential for green growth in the short- and long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations.
Social media summary
Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
This essay argues that social theory, and social science per se, must be reconstructed to address a rapidly emergent planetary crisis characterized by exceptional ecological degradation and extreme economic inequality. The task requires re-envisioning society as part of the interdependent “web of nature,” acknowledging that humans face ecological constraints like all other living things with which we share the planet, grasping the growth imperative for capital accumulation as the primary driver of the socioecological crisis, and coming to terms with the need to radically transform capitalism as we have known it to escape catastrophe.
Robert J. Antonio teaches sociology at the University of Kansas.He specializes in social theory, but also works on globalization, political economy, and the environment.Currently he is working on projects related to capitalism’s crisis tendencies, especially concerning the intersection of increased economic inequality, ecological risk, and democratic and authoritarian responses.
Brett Clark is Professor of Sociology, Environmental Humanities, and Environmental and Sustainability Studies at the University of Utah. His research interests include social theory, political economy, and ecology.
Optical tracking systems typically trade off between astrometric precision and field of view. In this work, we showcase a networked approach to optical tracking using very wide field-of-view imagers that have relatively low astrometric precision on the scheduled OSIRIS-REx slingshot manoeuvre around Earth on 22 Sep 2017. As part of a trajectory designed to get OSIRIS-REx to NEO 101955 Bennu, this flyby event was viewed from 13 remote sensors spread across Australia and New Zealand to promote triangulatable observations. Each observatory in this portable network was constructed to be as lightweight and portable as possible, with hardware based off the successful design of the Desert Fireball Network. Over a 4-h collection window, we gathered 15 439 images of the night sky in the predicted direction of the OSIRIS-REx spacecraft. Using a specially developed streak detection and orbit determination data pipeline, we detected 2 090 line-of-sight observations. Our fitted orbit was determined to be within about 10 km of orbital telemetry along the observed 109 262 km length of OSIRIS-REx trajectory, and thus demonstrating the impressive capability of a networked approach to Space Surveillance and Tracking.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
This paper provides an up-to-date review of the problems related to the generation, detection and mitigation of strong electromagnetic pulses created in the interaction of high-power, high-energy laser pulses with different types of solid targets. It includes new experimental data obtained independently at several international laboratories. The mechanisms of electromagnetic field generation are analyzed and considered as a function of the intensity and the spectral range of emissions they produce. The major emphasis is put on the GHz frequency domain, which is the most damaging for electronics and may have important applications. The physics of electromagnetic emissions in other spectral domains, in particular THz and MHz, is also discussed. The theoretical models and numerical simulations are compared with the results of experimental measurements, with special attention to the methodology of measurements and complementary diagnostics. Understanding the underlying physical processes is the basis for developing techniques to mitigate the electromagnetic threat and to harness electromagnetic emissions, which may have promising applications.
The uncertainty surrounding high intakes of folic acid and associations with cognitive decline in older adults with low vitamin B12 status has been an obstacle to mandatory folic acid fortification for many years. We estimated the prevalence of combinations of low/normal/high vitamin B12 and folate status and compared associations with global cognitive function using two approaches, of individuals in a population-based study of those aged ≥50 years in the Republic of Ireland. Cross-sectional data from 3781 men and women from Wave 1 of The Irish Longitudinal Study on Ageing were analysed. Global cognitive function was assessed by the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Prevalence estimates for combinations of vitamin B12 (plasma vitamin B12 < or ≥258 pmol/l) and folate (plasma folate ≤ or >45·3 nmol/l) concentrations were generated. Negative binomial regression models were used to investigate the associations of vitamin B12 and folate status with global cognitive function. Of the participants, 1·5 % (n 51) had low vitamin B12 (<258 pmol/l) and high folate (>45·3 nmol/l) status. Global cognitive performance was not significantly reduced in these individuals when compared with those with normal status for both B-vitamins (n 2433). Those with normal vitamin B12/high folate status (7·6 %) had better cognitive performance (MMSE: incidence rate ratio (IRR) 0·82, 95 % CI 0·68, 0·99; P = 0·043, MoCA: IRR 0·89, 95 % CI 0·80, 0·99; P = 0·025). We demonstrated that high folate status was not associated with lower cognitive scores in older adults with low vitamin B12 status. These findings provide important safety information that could guide fortification policy recommendations in Europe.
We propose the nasal administration of calcium-enriched physiological salts as a new hygienic intervention with possible therapeutic application as a response to the rapid and tenacious spread of COVID-19. We test the effectiveness of these salts against viral and bacterial pathogens in animals and humans. We find that aerosol administration of these salts to the airways diminishes the exhalation of the small particles that face masks fail to filter and, in the case of an influenza swine model, completely block airborne transmission of disease. In a study of 10 human volunteers (5 less than 65 years and 5 older than 65 years), we show that delivery of a nasal saline comprising calcium and sodium salts quickly (within 15 min) and durably (up to at least 6 h) diminishes exhaled particles from the human airways. Being predominantly smaller than 1 μm, these particles are below the size effectively filtered by conventional masks. The suppression of exhaled droplets by the nasal delivery of calcium-rich saline with aerosol droplet size of around 10 μm suggests the upper airways as a primary source of bioaerosol generation. The suppression effect is especially pronounced (99%) among those who exhale large numbers of particles. In our study, we found this high-particle exhalation group to correlate with advanced age. We argue for a new hygienic practice of nasal cleansing by a calcium-rich saline aerosol, to complement the washing of hands with ordinary soap, use of a face mask, and social distancing.
The Cassini Visual Infrared Mapping Spectrometer (VIMS) spans a wavelength range of 0.34 to 5.2 µm. Executing numerous close targeted flybys of the major moons of Saturn, as well as serendipitous flybys of the smaller moons, VIMS gathered millions of spectra of these bodies during its 13-year mission, some at spatial resolutions of a few hundred meters. The surfaces of the inner moons are dominated by water ice, while Iapetus, Hyperion, and Titan have substantial amounts of dark materials, including hydrocarbons, on their surfaces. Phoebe is grayer in color in the visible than Saturn’s other low-albedo moons. The surfaces of the inner small moons are also dominated by water ice, and they share compositional similarities to the main rings. The optical properties of the main moons are affected by particles from Saturn’s rings: the inner moons are coated by the E-ring, which originates from cryoactivity on Enceladus, while Iapetus and Hyperion are coated by particles from the Phoebe ring. Cassini VIMS detected previously unknown volatiles and organics on these moons, including CO2, H2, organic molecules as complex as aromatic hydrocarbons, nano-iron, and nano-iron oxides.
To detect modest associations of dietary intake with disease risk, observational studies need to be large and control for moderate measurement errors. The reproducibility of dietary intakes of macronutrients, food groups and dietary patterns (vegetarian and Mediterranean) was assessed in adults in the UK Biobank study on up to five occasions using a web-based 24-h dietary assessment (n 211 050), and using short FFQ recorded at baseline (n 502 655) and after 4 years (n 20 346). When the means of two 24-h assessments were used, the intra-class correlation coefficients (ICC) for macronutrients varied from 0·63 for alcohol to 0·36 for polyunsaturated fat. The ICC for food groups also varied from 0·68 for fruit to 0·18 for fish. The ICC for the FFQ varied from 0·66 for meat and fruit to 0·48 for bread and cereals. The reproducibility was higher for vegetarian status (κ > 0·80) than for the Mediterranean dietary pattern (ICC = 0·45). Overall, the reproducibility of pairs of 24-h dietary assessments and single FFQ used in the UK Biobank were comparable with results of previous prospective studies using conventional methods. Analyses of diet–disease relationships need to correct for both measurement error and within-person variability in dietary intake in order to reliably assess any such associations with disease in the UK Biobank.