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To describe the evolution of respiratory antibiotic prescribing during the coronavirus disease 2019 (COVID-19) pandemic across 3 large hospitals that maintained antimicrobial stewardship services throughout the pandemic.
Design:
Retrospective interrupted time-series analysis.
Setting:
A multicenter study was conducted including medical and intensive care units (ICUs) from 3 hospitals within a Canadian epicenter for COVID-19.
Methods:
Interrupted time-series analysis was used to analyze rates of respiratory antibiotic utilization measured in days of therapy per 1,000 patient days (DOT/1,000 PD) in medical units and ICUs. Each of the first 3 waves of the pandemic were compared to the baseline.
Results:
Within the medical units, use of respiratory antibiotics increased during the first wave of the pandemic (rate ratio [RR], 1.76; 95% CI, 1.38–2.25) but returned to the baseline in waves 2 and 3 despite more COVID-19 admissions. In ICU, the use of respiratory antibiotics increased in wave 1 (RR, 1.30; 95% CI, 1.16–1.46) and wave 2 of the pandemic (RR, 1.21; 95% CI, 1.11–1.33) and returned to the baseline in the third wave, which had the most COVID-19 admissions.
Conclusions:
After an initial surge in respiratory antibiotic prescribing, we observed the normalization of prescribing trends at 3 large hospitals throughout the COVID-19 pandemic. This trend may have been due to the timely generation of new research and guidelines developed with frontline clinicians, allowing for the active application of new research to clinical practice.
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.
Two works against the Council of Chalcedon are attributed to Timothy Aelurus. The first survives fully in Armenian and as a synopsis in a Syriac epitome; its title in Armenian is very long, so today scholars call it Against the Dyophysites or On the Unity of Christ. Timothy includes over three hundred quotations not only from authors whose views he opposed but also from works cited in support of his understanding of Christology. He also refutes the Definition of Faith promulgated by the Council of Chalcedon and Leo of Rome’s Tome to Flavian of Constantinople in this work, which was endorsed by the Definition. The second work survives in a single Syriac manuscript, which dates to before 562. It consists of four parts: (1) a section-by-section refutation of the Chalcedonian Definition, (2) a section-by-section refutation of the Tome of Leo, (3) a florilegium of quotations from the acts of Ephesus II chosen to demonstrate the bishops’ stunning change of mind at Chalcedon, and (4) a eulogy for Dioscorus of Alexandria along with an exhortation to persevere in the faith.
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.
In April 2019, the U.S. Fish and Wildlife Service (USFWS) released its recovery plan for the jaguar Panthera onca after several decades of discussion, litigation and controversy about the status of the species in the USA. The USFWS estimated that potential habitat, south of the Interstate-10 highway in Arizona and New Mexico, had a carrying capacity of c. six jaguars, and so focused its recovery programme on areas south of the USA–Mexico border. Here we present a systematic review of the modelling and assessment efforts over the last 25 years, with a focus on areas north of Interstate-10 in Arizona and New Mexico, outside the recovery unit considered by the USFWS. Despite differences in data inputs, methods, and analytical extent, the nine previous studies found support for potential suitable jaguar habitat in the central mountain ranges of Arizona and New Mexico. Applying slightly modified versions of the USFWS model and recalculating an Arizona-focused model over both states provided additional confirmation. Extending the area of consideration also substantially raised the carrying capacity of habitats in Arizona and New Mexico, from six to 90 or 151 adult jaguars, using the modified USFWS models. This review demonstrates the crucial ways in which choosing the extent of analysis influences the conclusions of a conservation plan. More importantly, it opens a new opportunity for jaguar conservation in North America that could help address threats from habitat losses, climate change and border infrastructure.
The global community needs to be aware of the potential psychosocial consequences that may be experienced by health care workers who are actively managing patients with coronavirus disease (COVID-19). These health care workers are at increased risk for experiencing mood and trauma-related disorders, including posttraumatic stress disorder (PTSD). In this concept article, strategies are recommended for individual health care workers and hospital leadership to aid in mitigating the risk of PTSD, as well as to build resilience in light of a potential second surge of COVID-19.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
${\sim}60\%$
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
Posttraumatic stress disorder (PTSD) is often complicated by the after-effects of mild traumatic brain injury (mTBI). The mixture of brain conditions results in abnormal affective and cognitive functioning, as well as maladaptive behavior. To better understand how brain activity explains cognitive and emotional processes in these conditions, we used an emotional N-back task and functional magnetic resonance imaging (fMRI) to study neural responses in US military veterans after deployments to Iraq and Afghanistan. Additionally, we sought to examine whether hierarchical dimensional models of maladaptive personality could account for the relationship between combat-related brain conditions and fMRI responses under cognitive and affective challenge. FMRI data, measures of PTSD symptomatology (PTSS), blast-induced mTBI (bmTBI) severity, and maladaptive personality (MMPI-2-RF) were gathered from 93 veterans. Brain regions central to emotion regulation were selected for analysis, and consisted of bilateral amygdala, bilateral dorsolateral prefrontal (dlPFC), and ventromedial prefrontal/subgenual anterior cingulate (vmPFC-sgACC). Cognitive load increased activity in dlPFC and reduced activity in emotional responding brain regions. However, individuals with greater PTSS showed blunted deactivations in bilateral amygdala and vmPFC-sgACC, and weaker responses in right dlPFC. Additionally, we found that elevated emotional/internalizing dysfunction (EID), specifically low positive emotionality (RC2), accounted for PTSS-related changes in bilateral amygdala under increased cognitive load. Findings suggest that PTSS might result in amygdala and vmPFC-sgACC activity resistant to moderation by cognitive demands, reflecting emotion dysregulation despite a need to marshal cognitive resources. Anhedonia may be an important target for interventions that improve the affective and cognitive functioning of individuals with PTSD.
Use latent class analysis (LCA) to identify patterns of cognitive functioning in a sample of older adults with clinical depression and without dementia and assess demographic, psychiatric, and neurobiological predictors of class membership.
Method:
Neuropsychological assessment data from 121 participants in the Alzheimer’s Disease Neuroimaging Initiative-Depression project (ADNI-D) were analyzed, including measures of executive functioning, verbal and visual memory, visuospatial and language functioning, and processing speed. These data were analyzed using LCA, with predictors of class membership such as depression severity, depression and treatment history, amyloid burden, and APOE e4 allele also assessed.
Results:
A two-class model of cognitive functioning best fit the data, with the Lower Cognitive Class (46.1% of the sample) performing approximately one standard deviation below the Higher Cognitive Class (53.9%) on most tests. When predictors of class membership were assessed, carrying an APOE e4 allele was significantly associated with membership in the Lower Cognitive Class. Demographic characteristics, age of depression onset, depression severity, history of psychopharmacological treatment for depression, and amyloid positivity did not predict class membership.
Conclusion:
LCA allows for identification of subgroups of cognitive functioning in a mostly cognitively intact late life depression (LLD) population. One subgroup, the Lower Cognitive Class, more likely to carry an APOE e4 allele, may be at a greater risk for subsequent cognitive decline, even though current performance on neuropsychological testing is within normal limits. These findings have implications for early identification of those at greatest risk, risk factors, and avenues for preventive intervention.
Internal gravity wave energy contributes significantly to the energy budget of the oceans, affecting mixing and the thermohaline circulation. Hence it is important to determine the internal wave energy flux $\boldsymbol{J}=p\,\boldsymbol{v}$, where $p$ is the pressure perturbation field and $\boldsymbol{v}$ is the velocity perturbation field. However, the pressure perturbation field is not directly accessible in laboratory or field observations. Previously, a Green’s function based method was developed to calculate the instantaneous energy flux field from a measured density perturbation field $\unicode[STIX]{x1D70C}(x,z,t)$, given a constant buoyancy frequency $N$. Here we present methods for computing the instantaneous energy flux $\boldsymbol{J}(x,z,t)$ for an internal wave field with vertically varying background $N(z)$, as in the oceans where $N(z)$ typically decreases by two orders of magnitude from the pycnocline to the deep ocean. Analytic methods are presented for computing $\boldsymbol{J}(x,z,t)$ from a density perturbation field for $N(z)$ varying linearly with $z$ and for $N^{2}(z)$ varying as $\tanh (z)$. To generalize this approach to arbitrary $N(z)$, we present a computational method for obtaining $\boldsymbol{J}(x,z,t)$. The results for $\boldsymbol{J}(x,z,t)$ for the different cases agree well with results from direct numerical simulations of the Navier–Stokes equations. Our computational method can be applied to any density perturbation data using the MATLAB graphical user interface ‘EnergyFlux’.
Timing of weed emergence and seed persistence in the soil influence the ability to implement timely and effective control practices. Emergence patterns and seed persistence of kochia populations were monitored in 2010 and 2011 at sites in Kansas, Colorado, Wyoming, Nebraska, and South Dakota. Weekly observations of emergence were initiated in March and continued until no new emergence occurred. Seed was harvested from each site, placed into 100-seed mesh packets, and buried at depths of 0, 2.5, and 10 cm in fall of 2010 and 2011. Packets were exhumed at 6-mo intervals over 2 yr. Viability of exhumed seeds was evaluated. Nonlinear mixed-effects Weibull models were fit to cumulative emergence (%) across growing degree days (GDD) and to viable seed (%) across burial time to describe their fixed and random effects across site-years. Final emergence densities varied among site-years and ranged from as few as 4 to almost 380,000 seedlings m−2. Across 11 site-years in Kansas, cumulative GDD needed for 10% emergence were 168, while across 6 site-years in Wyoming and Nebraska, only 90 GDD were needed; on the calendar, this date shifted from early to late March. The majority (>95%) of kochia seed did not persist for more than 2 yr. Remaining seed viability was generally >80% when seeds were exhumed within 6 mo after burial in March, and declined to <5% by October of the first year after burial. Burial did not appear to increase or decrease seed viability over time but placed seed in a position from which seedling emergence would not be possible. High seedling emergence that occurs very early in the spring emphasizes the need for fall or early spring PRE weed control such as tillage, herbicides, and cover crops, while continued emergence into midsummer emphasizes the need for extended periods of kochia management.
The functional properties of the high-temperature superconductor Y1Ba2Cu3O7−δ (Y-123) are closely correlated to the exact stoichiometry and oxygen content. Exceeding the critical value of 1 oxygen vacancy for every five unit cells (δ>0.2, which translates to a 1.5 at% deviation from the nominal oxygen stoichiometry of Y7.7Ba15.3Cu23O54−δ) is sufficient to alter the superconducting properties. Stoichiometry at the nanometer scale, particularly of oxygen and other lighter elements, is extremely difficult to quantify in complex functional ceramics by most currently available analytical techniques. The present study is an analysis and optimization of the experimental conditions required to quantify the local nanoscale stoichiometry of single crystal yttrium barium copper oxide (YBCO) samples in three dimensions by atom probe tomography (APT). APT analysis required systematic exploration of a wide range of data acquisition and processing conditions to calibrate the measurements. Laser pulse energy, ion identification, and the choice of range widths were all found to influence composition measurements. The final composition obtained from melt-grown crystals with optimized superconducting properties was Y7.9Ba10.4Cu24.4O57.2.
The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled ‘Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies’. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation–health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation–health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.
Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013–2014 influenza season. Little is known about the epidemiology of severe influenza during this season.
METHODS
A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes.
RESULTS
A total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4–6.9], P=.006 and 50–64 years, 2.5 [1.3–4.9], P=.007; reference age 18–49 years), male sex (1.9 [1.1–3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9–37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2–1.4], P<.001).
CONCLUSION
Risk factors for death among US patients with severe influenza during the 2013–2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.
Infect. Control Hosp. Epidemiol. 2015;36(11):1251–1260
Voters and political candidates increasingly use social networking sites (SNSs) such as Facebook. This study uses data from an online posttest-only experiment (N = 183) in analyzing how exposure to supportive or challenging user comments on a fictional candidate's Facebook page influenced participants’ perceptions of and willingness to vote for the candidate, as well as whether candidate replies to each type of user comments affected these outcomes. Participants who viewed a page with supportive comments and “likes” reported more favorable perceptions of and greater support for the candidate, relative to participants who viewed a page with challenging comments. Thus, the appearance of interactivity between a candidate and other users on the candidate's Facebook page can shape the responses of those viewing the page. However, exposure to candidate replies to either supportive or challenging comments did not lead to significantly more favorable perceptions or a greater likelihood of voting for the candidate.