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Monoclonal antibody therapeutics to treat coronavirus disease (COVID-19) have been authorized by the US Food and Drug Administration under Emergency Use Authorization (EUA). Many barriers exist when deploying a novel therapeutic during an ongoing pandemic, and it is critical to assess the needs of incorporating monoclonal antibody infusions into pandemic response activities. We examined the monoclonal antibody infusion site process during the COVID-19 pandemic and conducted a descriptive analysis using data from 3 sites at medical centers in the United States supported by the National Disaster Medical System. Monoclonal antibody implementation success factors included engagement with local medical providers, therapy batch preparation, placing the infusion center in proximity to emergency services, and creating procedures resilient to EUA changes. Infusion process challenges included confirming patient severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, strained staff, scheduling, and pharmacy coordination. Infusion sites are effective when integrated into pre-existing pandemic response ecosystems and can be implemented with limited staff and physical resources.
This chapter outlines some of the ways in which cognitive behavior therapy (CBT) for anxiety disorders and depression has been modified and adapted to the ageing older population. Aspects that are outlined include modifications to the process of conceptualization, which has been expanded to include relevant gerontological factors. The areas that should be incorporated into the assessment of older adults with anxiety and depression prior to starting therapy are delineated, with a focus on the characteristic features that color the presentation in the case of older adults. The changes that must be made in carrying out CBT for older adults with depression and anxiety disorders so that it is effective are described. This includes accommodations for cognitive changes and health-related difficulties as well as taking into consideration factors that are specific to the older population.
Racial disparities in colorectal cancer (CRC) can be addressed through increased adherence to screening guidelines. In real-life encounters, patients may be more willing to follow screening recommendations delivered by a race concordant clinician. The growth of telehealth to deliver care provides an opportunity to explore whether these effects translate to a virtual setting. The primary purpose of this pilot study is to explore the relationships between virtual clinician (VC) characteristics and CRC screening intentions after engagement with a telehealth intervention leveraging technology to deliver tailored CRC prevention messaging.
Methods:
Using a posttest-only design with three factors (VC race-matching, VC gender, intervention type), participants (N = 2267) were randomised to one of eight intervention treatments. Participants self-reported perceptions and behavioral intentions.
Results:
The benefits of matching participants with a racially similar VC trended positive but did not reach statistical significance. Specifically, race-matching positively influenced screening intentions for Black participants but not for Whites (b = 0.29, p = 0.10). Importantly, perceptions of credibility, attractiveness, and message relevance significantly influenced screening intentions and the relationship with race-matching.
Conclusions:
To reduce racial CRC screening disparities, investments are needed to identify patient-focused interventions to address structural barriers to screening. This study suggests that telehealth interventions that match Black patients with a Black VC can enhance perceptions of credibility and message relevance, which may then improve screening intentions. Future research is needed to examine how to increase VC credibility and attractiveness, as well as message relevance without race-matching.
While there have been numerous applications of large eddy simulations (LES) to complex flows, their application to practical engineering configurations, such as full aircraft models, have been limited to date. Recently, however, advances in rapid, high quality mesh generation, low-dissipation numerical schemes and physics-based subgrid-scale and wall models have led to, for the first time, accurate simulations of a realistic aircraft in landing configuration (the Japanese Aerospace Exploration Agency Standard Model) in less than a day of turnaround time with modest resource requirements. In this paper, a systematic study of the predictive capability of LES across a range of angles of attack (including maximum lift and post-stall regimes), the robustness of the predictions to grid resolution and the incorporation of wind tunnel effects is carried out. Integrated engineering quantities of interest, such as lift, drag and pitching moment will be compared with experimental data, while sectional pressure forces will be used to corroborate the accuracy of the integrated quantities. Good agreement with experimental $C_L$ data is obtained across the lift curve with the coefficient of lift at maximum lift, $C_{L,max}$, consistently being predicted to within five lift counts of the experimental value. The grid point requirements to achieve this level of accuracy are reduced compared with recent estimates (even for wall modelled LES), with the solutions showing systematic improvement upon grid refinement, with the exception of the solution at the lowest angles of attack, which will be discussed later in the text. Simulations that include the wind tunnel walls and aircraft body mounting system are able to replicate important features of the flow field noted in the experiment that are absent from free air calculations of the same geometry, namely, the onset of inboard flow separation in the post-stall regime. Turnaround times of the order of a day are made possible in part by algorithmic advances made to leverage graphical processing units. The results presented herein suggest that this combined approach (meshing, numerical algorithms, modelling, efficient computer implementation) is on the threshold of readiness for industrial use in aeronautical design.
The present study aimed to clarify the neuropsychological profile of the emergent diagnostic category of Mild Cognitive Impairment with Lewy bodies (MCI-LB) and determine whether domain-specific impairments such as in memory were related to deficits in domain-general cognitive processes (executive function or processing speed).
Method:
Patients (n = 83) and healthy age- and sex-matched controls (n = 34) underwent clinical and imaging assessments. Probable MCI-LB (n = 44) and MCI-Alzheimer’s disease (AD) (n = 39) were diagnosed following National Institute on Aging-Alzheimer’s Association (NIA-AA) and dementia with Lewy bodies (DLB) consortium criteria. Neuropsychological measures included cognitive and psychomotor speed, executive function, working memory, and verbal and visuospatial recall.
Results:
MCI-LB scored significantly lower than MCI-AD on processing speed [Trail Making Test B: p = .03, g = .45; Digit Symbol Substitution Test (DSST): p = .04, g = .47; DSST Error Check: p < .001, g = .68] and executive function [Trail Making Test Ratio (A/B): p = .04, g = .52] tasks. MCI-AD performed worse than MCI-LB on memory tasks, specifically visuospatial (Modified Taylor Complex Figure: p = .01, g = .46) and verbal (Rey Auditory Verbal Learning Test: p = .04, g = .42) delayed recall measures. Stepwise discriminant analysis correctly classified the subtype in 65.1% of MCI patients (72.7% specificity, 56.4% sensitivity). Processing speed accounted for more group-associated variance in visuospatial and verbal memory in both MCI subtypes than executive function, while no significant relationships between measures were observed in controls (all ps > .05)
Conclusions:
MCI-LB was characterized by executive dysfunction and slowed processing speed but did not show the visuospatial dysfunction expected, while MCI-AD displayed an amnestic profile. However, there was considerable neuropsychological profile overlap and processing speed mediated performance in both MCI subtypes.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with its impact on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behaviour and, therefore, the risk of contracting the virus.
Aims
We examined overlapping genetic underpinnings between major psychiatric disorders, personality traits and susceptibility to SARS-CoV-2 infection.
Method
Linkage disequilibrium score regression was used to explore the genetic correlations of coronavirus disease 2019 (COVID-19) susceptibility with psychiatric disorders and personality traits based on data from the largest available respective genome-wide association studies (GWAS). In two cohorts (the PsyCourse (n = 1346) and the HeiDE (n = 3266) study), polygenic risk scores were used to analyse if a genetic association between, psychiatric disorders, personality traits and COVID-19 susceptibility exists in individual-level data.
Results
We observed no significant genetic correlations of COVID-19 susceptibility with psychiatric disorders. For personality traits, there was a significant genetic correlation for COVID-19 susceptibility with extraversion (P = 1.47 × 10−5; genetic correlation 0.284). Yet, this was not reflected in individual-level data from the PsyCourse and HeiDE studies.
Conclusions
We identified no significant correlation between genetic risk factors for severe psychiatric disorders and genetic risk for COVID-19 susceptibility. Among the personality traits, extraversion showed evidence for a positive genetic association with COVID-19 susceptibility, in one but not in another setting. Overall, these findings highlight a complex contribution of genetic and non-genetic components in the interaction between COVID-19 susceptibility and personality traits or mental disorders.
The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.
Methods
Face-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.
Results
3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.
Conclusion
ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.
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.
The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia.
Methods
Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects.
Results
There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness.
Discussion
Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.
Dairy goat farming is an important sector of the agricultural industry in Greece, with an annual total milk production exceeding 450 000 l and accounting for over 25% of all goat milk produced in the European Union; this milk is used mainly for cheese production. Despite the importance of goat milk for the agricultural sector in Greece, no systematic countrywide investigations in the bulk-tank milk of goats in Greece have been reported. Objectives were to investigate somatic cell counts (SCC) and total bacterial counts (TBC) in raw bulk-tank milk of goat herds in Greece, study factors influencing SCC and TBC therein and evaluate their possible associations with milk content. Throughout Greece, 119 dairy goat herds were visited for milk sampling for somatic cell counting, microbiological examination and composition measurement. Geometric mean SCC and TBC were 0.838 × 106 cells ml−1 and 581 × 103 cfu ml−1, respectively. Multivariable analyses revealed annual frequency of check-ups of milking system and total milk quantity per goat (among 53 variables) to be significant for increased SCC; no factor emerged (among 58 variables) to be significant for increased TBC. Negative correlation of SCC with total protein was found; mean total protein content in the bulk-tank milk in herds with SCC >0.75 × 106 cells ml−1 was 5.1% lower and in herds with SCC >1.5 × 106 cells ml−1, it was 7.8% lower.
Urine cultures have poor specificity for catheter-associated urinary tract infections (CAUTIs). We evaluated the effect of a urine-culture stewardship program on urine culture utilization and CAUTI in adult intensive care units (ICUs).
Design:
A quasi-interventional study was performed from 2015 to 2017.
Setting and patients:
The study cohort comprised 21,367 patients admitted to the ICU at a teaching hospital.
Intervention:
The urine culture stewardship program included monthly 1-hour discussions with ICU house staff emphasizing avoidance of “pan-culture” for sepsis workup and obtaining urine culture only if a urinary source of sepsis is suspected. The urine culture utilization rate metric (UCUR; ie, no. urine cultueres/catheter days ×100) was utilized to measure the effect. Monthly UCUR, catheter utilization ratio (CUR), and CAUTI rate were reported on an interactive quality dashboard. To ensure safety, catheterized ICU patients (2015–2016) were evaluated for 30-day readmission for UTI. Time-series data and relationships were analyzed using Spearman correlation coefficients and regression analysis.
Results:
Urine culture utilization decreased from 3,081 in 2015 to 2,158 in 2016 to 1,218 in 2017. CAUTIs decreased from 78 in 2015 to 60 in 2016 and 28 in 2017. Regression analysis over time showed significant decreases in UCUR (r, 0.917; P < .0001) and CAUTI rate (r, 0.657; P < .0001). The co-correlation between UCUR and CAUTI rate was (r, 0.625; P < .0001) compared to CUR and CAUTI rate (r, 0.523; P = .004). None of these patients was readmitted with a CAUTI.
Conclusions:
Urine culture stewardship program was effective and safe in reducing UC overutilization and was correlated with a decrease in CAUTIs. Addition of urine-culture stewardship to standard best practices could reduce CAUTI in ICUs.
Multicentre research databases can provide insights into healthcare processes to improve outcomes and make practice recommendations for novel approaches. Effective audits can establish a framework for reporting research efforts, ensuring accurate reporting, and spearheading quality improvement. Although a variety of data auditing models and standards exist, barriers to effective auditing including costs, regulatory requirements, travel, and design complexity must be considered.
Materials and methods:
The Congenital Cardiac Research Collaborative conducted a virtual data training initiative and remote source data verification audit on a retrospective multicentre dataset. CCRC investigators across nine institutions were trained to extract and enter data into a robust dataset on patients with tetralogy of Fallot who required neonatal intervention. Centres provided de-identified source files for a randomised 10% patient sample audit. Key auditing variables, discrepancy types, and severity levels were analysed across two study groups, primary repair and staged repair.
Results:
Of the total 572 study patients, data from 58 patients (31 staged repairs and 27 primary repairs) were source data verified. Amongst the 1790 variables audited, 45 discrepancies were discovered, resulting in an overall accuracy rate of 97.5%. High accuracy rates were consistent across all CCRC institutions ranging from 94.6% to 99.4% and were reported for both minor (1.5%) and major discrepancies type classifications (1.1%).
Conclusion:
Findings indicate that implementing a virtual multicentre training initiative and remote source data verification audit can identify data quality concerns and produce a reliable, high-quality dataset. Remote auditing capacity is especially important during the current COVID-19 pandemic.
In this paper, we describe the system design and capabilities of the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope at the conclusion of its construction project and commencement of science operations. ASKAP is one of the first radio telescopes to deploy phased array feed (PAF) technology on a large scale, giving it an instantaneous field of view that covers $31\,\textrm{deg}^{2}$ at $800\,\textrm{MHz}$. As a two-dimensional array of 36$\times$12 m antennas, with baselines ranging from 22 m to 6 km, ASKAP also has excellent snapshot imaging capability and 10 arcsec resolution. This, combined with 288 MHz of instantaneous bandwidth and a unique third axis of rotation on each antenna, gives ASKAP the capability to create high dynamic range images of large sky areas very quickly. It is an excellent telescope for surveys between 700 and $1800\,\textrm{MHz}$ and is expected to facilitate great advances in our understanding of galaxy formation, cosmology, and radio transients while opening new parameter space for discovery of the unknown.
Circular milling, a stunning manifestation of collective motion, is found across the natural world, from fish shoals to army ants. It has been observed recently that the plant-animal worm Symsagittifera roscoffensis exhibits circular milling behaviour, both in shallow pools at the beach and in Petri dishes in the laboratory. Here we investigate this phenomenon experimentally and theoretically, from a fluid dynamical viewpoint, focusing on the effect that an established circular mill has on the surrounding fluid. Unlike systems such as confined bacterial suspensions and collections of molecular motors and filaments that exhibit spontaneous circulatory behaviour, and which are modelled as force dipoles, the front–back symmetry of individual worms precludes a stresslet contribution. Instead, singularities such as source dipoles and Stokes quadrupoles are expected to dominate. We analyse a series of models to understand the contributions of these singularities to the azimuthal flow fields generated by a mill, in light of the particular boundary conditions that hold for flow in a Petri dish. A model that treats a circular mill as a rigid rotating disc that generates a Stokes flow is shown to capture basic experimental results well, and gives insights into the emergence and stability of multiple mill systems.
Identify risk factors that could increase progression to severe disease and mortality in hospitalized SARS-CoV-2 patients in the Southeast region of the United States.
Design, setting, and participants:
Multicenter, retrospective cohort including 502 adults hospitalized with laboratory-confirmed COVID-19 between March 1, 2020, and May 8, 2020 within 1 of 15 participating hospitals in 5 health systems across 5 states in the Southeast United States.
Methods:
The study objectives were to identify risk factors that could increase progression to hospital mortality and severe disease (defined as a composite of intensive care unit admission or requirement of mechanical ventilation) in hospitalized SARS-CoV-2 patients in the Southeast United States.
Results:
In total, 502 patients were included, and 476 of 502 (95%) had clinically evaluable outcomes. The hospital mortality rate was 16% (76 of 476); 35% (177 of 502) required ICU admission and 18% (91 of 502) required mechanical ventilation. By both univariate and adjusted multivariate analyses, hospital mortality was independently associated with age (adjusted odds ratio [aOR], 2.03 for each decade increase; 95% confidence interval [CI], 1.56-–2.69), male sex (aOR, 2.44; 95% CI, 1.34–4.59), and cardiovascular disease (aOR, 2.16; 95% CI, 1.15–4.09). As with mortality, risk of severe disease was independently associated with age (aOR, 1.17 for each decade increase; 95% CI, 1.00–1.37), male sex (aOR, 2.34; 95% CI, 1.54–3.60), and cardiovascular disease (aOR, 1.77; 95% CI, 1.09–2.85).
Conclusions:
In an adjusted multivariate analysis, advanced age, male sex, and cardiovascular disease increased risk of severe disease and mortality in patients with COVID-19 in the Southeast United States. In-hospital mortality risk doubled with each subsequent decade of life.
The resistance of Plasmodium falciparum to antimalarial drugs remains a major impairment in the treatment and eradication of malaria globally. Following the introduction of artemisinin-based combination therapy (ACT), there have been reports of delayed parasite clearance. In Kenya, artemether–lumefantrine (AL) is the recommended first-line treatment of uncomplicated malaria. This study sought to assess the efficacy of AL after a decade of use as the preferred method of managing malarial infections in Kenya. We assessed clinical and parasitological responses of children under 5 years between May and November 2015 in Chulaimbo sub-County, Kisumu, Kenya. Patients aged between 6 and 60 months with uncomplicated P. falciparum mono-infection, confirmed through microscopy, were enrolled in the study. The patients were admitted at the facility for 3 days, treated with a standard dose of AL, and then put under observation for the next 28 days for the assessment of clinical and parasitological responses. Of the 90 patients enrolled, 14 were lost to follow-up while 76 were followed through to the end of the study period. Seventy-five patients (98.7%) cleared the parasitaemia within a period of 48 h while one patient (1.3%) cleared on day 3. There was 100% adequate clinical and parasitological response. All the patients cleared the parasites on day 3 and there were no re-infections observed during the stated follow-up period. This study, therefore, concludes that AL is highly efficacious in clearing P. falciparum parasites in children aged ≥6 and ≤60 months. The study, however, underscores the need for continued monitoring of the drug to forestall both gradual ineffectiveness and possible resistance to the drug in all target users.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with
$\sim$
15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination
$+41^\circ$
made over a 288-MHz band centred at 887.5 MHz.
Animal-derived dietary protein ingestion and physical activity stimulate myofibrillar protein synthesis rates in older adults. We determined whether a non-animal-derived diet can support daily myofibrillar protein synthesis rates to the same extent as an omnivorous diet. Nineteen healthy older adults (aged 66 (sem 1) years; BMI 24 (sem 1) kg/m2; twelve males, seven females) participated in a randomised, parallel-group, controlled trial during which they consumed a 3-d isoenergetic high-protein (1·8 g/kg body mass per d) diet, where the protein was provided from predominantly (71 %) animal (OMNI; n 9; six males, three females) or exclusively vegan (VEG; n 10; six males, four females; mycoprotein providing 57 % of daily protein intake) sources. During the dietary control period, participants conducted a daily bout of unilateral resistance-type leg extension exercise. Before the dietary control period, participants ingested 400 ml of deuterated water, with 50-ml doses consumed daily thereafter. Saliva samples were collected throughout to determine body water 2H enrichments, and muscle samples were collected from rested and exercised muscle to determine daily myofibrillar protein synthesis rates. Deuterated water dosing resulted in body water 2H enrichments of approximately 0·78 (sem 0·03) %. Daily myofibrillar protein synthesis rates were 13 (sem 8) (P = 0·169) and 12 (sem 4) % (P = 0·016) greater in the exercised compared with rested leg (1·59 (sem 0·12) v. 1·77 (sem 0·12) and 1·76 (sem 0·14) v. 1·93 (sem 0·12) %/d) in OMNI and VEG groups, respectively. Daily myofibrillar protein synthesis rates did not differ between OMNI and VEG in either rested or exercised muscle (P > 0·05). Over the course of a 3-d intervention, omnivorous- or vegan-derived dietary protein sources can support equivalent rested and exercised daily myofibrillar protein synthesis rates in healthy older adults consuming a high-protein diet.