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Monoclonal antibody therapeutics to treat COVID-19 have been authorized by the U.S. 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 three sites at medical centers in the U.S. 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 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.
To determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infection (HAI) incidence in US hospitals, national- and state-level standardized infection ratios (SIRs) were calculated for each quarter in 2020 and compared to those from 2019.
Central–line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), select surgical site infections, and Clostridioides difficile and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia laboratory-identified events reported to the National Healthcare Safety Network for 2019 and 2020 by acute-care hospitals were analyzed. SIRs were calculated for each HAI and quarter by dividing the number of reported infections by the number of predicted infections, calculated using 2015 national baseline data. Percentage changes between 2019 and 2020 SIRs were calculated. Supporting analyses, such as an assessment of device utilization in 2020 compared to 2019, were also performed.
Significant increases in the national SIRs for CLABSI, CAUTI, VAE, and MRSA bacteremia were observed in 2020. Changes in the SIR varied by quarter and state. The largest increase was observed for CLABSI, and significant increases in VAE incidence and ventilator utilization were seen across all 4 quarters of 2020.
This report provides a national view of the increases in HAI incidence in 2020. These data highlight the need to return to conventional infection prevention and control practices and build resiliency in these programs to withstand future pandemics.
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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
A high dose of whey protein hydrolysate fed with milk minerals rich in calcium (Capolac®) results in enhanced glucagon-like peptide-1 (GLP-1) concentrations in lean individuals; however, the effect of different calcium doses ingested alongside protein is unknown. The present study assessed the dose response of calcium fed alongside 25 g whey protein hydrolysate on GLP-1 concentrations in individuals with overweight/obesity. Eighteen adults (mean ± sd: 8M/10F, 34 ± 18 years, 28·2 ± 2·9 kgm−2) completed four trials in a randomised, double-blind, crossover design. Participants consumed test solutions consisting of 25 g whey protein hydrolysate (CON), supplemented with 3179 mg (LOW), 6363 mg (MED) or 9547 mg (HIGH) Capolac® on different occasions, separated by at least 48 h. The calcium content of test solutions equated to 65, 892, 1719 and 2547 mg, respectively. Arterialised-venous blood was sampled over 180 min to determine plasma concentrations of GLP-1TOTAL, GLP-17–36amide, insulin, glucose, NEFA, and serum concentrations of calcium and albumin. Ad libitum energy intake was measured at 180 min. Time–averaged incremental AUC (iAUC) for GLP-1TOTAL (pmol·l−1·min−1) did not differ between CON (23 ± 4), LOW (25 ± 6), MED (24 ± 5) and HIGH (24 ± 6). Energy intake (kcal) did not differ between CON (940 ± 387), LOW (884 ± 345), MED (920 ± 334) and HIGH (973 ± 390). Co-ingestion of whey protein hydrolysate with Capolac® does not potentiate GLP-1 release in comparison with whey protein hydrolysate alone. The study was registered at clinical trials (NCT03819972).
A number of community based surveys have identified an increase in psychological symptoms and distress but there has been no examination of symptoms at the more severe end of the mental health spectrum.
We aimed to analyse numbers and types of psychiatric presentations to inform planning for future demand on mental health services in light of the COVID-19 pandemic.
We analysed electronic data between January and April 2020 for 2534 patients referred to acute psychiatric services, and tested for differences in patient demographics, symptom severity and use of the Mental Health Act 1983 (MHA), before and after lockdown. We used interrupted time-series analyses to compare trends in emergency department and psychiatric presentations until December 2020.
There were 22% fewer psychiatric presentations the first week and 48% fewer emergency department presentations in the first month after lockdown initiated. A higher proportion of patients were detained under the MHA (22.2 v. 16.1%) and Mental Capacity Act 2005 (2.2 v. 1.1%) (χ2(2) = 16.3, P < 0.0001), and they experienced a longer duration of symptoms before seeking help from mental health services (χ2(3) = 18.6, P < 0.0001). A higher proportion of patients presented with psychotic symptoms (23.3 v. 17.0%) or delirium (7.0 v. 3.6%), and fewer had self-harm behaviour (43.8 v. 52.0%, χ2(7) = 28.7, P < 0.0001). A higher proportion were admitted to psychiatric in-patient units (22.2 v. 18.3%) (χ2(6) = 42.8, P < 0.0001) after lockdown.
UK lockdown resulted in fewer psychiatric presentations, but those who presented were more likely to have severe symptoms, be detained under the MHA and be admitted to hospital. Psychiatric services should ensure provision of care for these patients as well as planning for those affected by future COVID-19 waves.
Childhood acute arterial ischemic stroke (AIS) is diagnosed at a median of 23 hours post-symptom onset, delaying treatment. Pediatric stroke pathways can expedite diagnosis. Our goal was to understand the similarities and differences between Canadian pediatric stroke protocols with the aim of optimizing AIS management.
We contacted neurologists at all 16 Canadian pediatric hospitals regarding AIS management. Established protocols were analyzed for similarities and differences in eight domains.
Response rate was 100%. Seven (44%) centers have an established AIS protocol and two (13%) have a protocol under development. Seven centers do not have a protocol; two redirect patients to adult neurology, five rely on a case-by-case approach for management. Analysis of the seven protocols revealed differences in: 1) IV-tPA dosage: age-dependent 0.75–0.9 mg/kg (N = 1) versus age-independent 0.9 mg/kg (N = 6), with maximum doses of 75 mg (N = 1) or 90 mg (N = 6); 2) IV-tPA lower age cut-off: 2 years (N = 5) versus 3 or 10 years (each N = 1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (N = 3), <5 (N = 1), <6 (N = 3); 4) first choice of pre-treatment neuroimaging: computed tomography (CT) (N = 3), magnetic resonance imaging (MRI) (N = 2) or either (N = 2); 5) intra-arterial tPA use (N = 3) and; 6) mechanical thrombectomy timeframe: <6 hour (N = 3), <24 hour (N = 2), unspecified (N = 2).
Although 44% of Canadian pediatric hospitals have established AIS management pathways, several differences remain among centers. Some criteria (dosage, imaging) reflect adult AIS literature. Canadian expert consensus regarding IV-tPA and endovascular treatment should be established to standardize and implement AIS protocols across Canada.
Recent drilling successes on Rutford Ice Stream in West Antarctica demonstrate the viability of hot water drilling subglacial access holes to depths >2000 m. Having techniques to access deep subglacial environments reliably paves the way for subglacial lake exploration beneath the thick central West Antarctic Ice Sheet. An ideal candidate lake, overlain by ~2650 m of ice, identified by Centro de Estudios Científicos (CECs), Chile, has led to collaboration with British Antarctic Survey to access Subglacial Lake CECs (SLCECs). To conform with the Scientific Committee on Antarctic Research code of conduct, which provides a guide to responsible scientific exploration and stewardship of these pristine systems, any access drilling must minimise all aspects of contamination and disturbance of the subglacial environment. To meet these challenges, along with thicker ice and 2000 m elevation, pumping and water treatment systems developed for the Subglacial Lake Ellsworth project, together with new diesel generators, additional water heating and longer drill hose, are currently being integrated with the BEAMISH hot water drill. A dedicated test season near SLCECs will commission the new clean hot water drill, with testing and validation of all clean operating procedures. A subsequent season will then access SLCECs cleanly.
Head impact exposure (HIE) in youth football is a public health concern. The objective of this study was to determine if one season of HIE in youth football was related to cognitive changes.
Over 200 participants (ages 9–13) wore instrumented helmets for practices and games to measure the amount of HIE sustained over one season. Pre- and post-season neuropsychological tests were completed. Test score changes were calculated adjusting for practice effects and regression to the mean and used as the dependent variables. Regression models were calculated with HIE variables predicting neuropsychological test score changes.
For the full sample, a small effect was found with season average rotational values predicting changes in list-learning such that HIE was related to negative score change: standardized beta (β) = -.147, t(205) = -2.12, and p = .035. When analyzed by age clusters (9–10, 11–13) and adding participant weight to models, the R2 values increased. Splitting groups by weight (median split), found heavier members of the 9–10 cohort with significantly greater change than lighter members. Additionaly, significantly more participants had clinically meaningful negative changes: X2 = 10.343, p = .001.
These findings suggest that in the 9–10 age cluster, the average seasonal level of HIE had inverse, negative relationships with cognitive change over one season that was not found in the older group. The mediation effects of age and weight have not been explored previously and appear to contribute to the effects of HIE on cognition in youth football players.
Turbulent fluxes make a substantial and growing contribution to the energy balance of ice surfaces globally, but are poorly constrained owing to challenges in estimating the aerodynamic roughness length (z0). Here, we used structure from motion (SfM) photogrammetry and terrestrial laser scanning (TLS) surveys to make plot-scale 2-D and 3-D microtopographic estimations of z0 and upscale these to map z0 across an ablating mountain glacier. At plot scales, we found spatial variability in z0 estimates of over two orders of magnitude with unpredictable z0 trajectories, even when classified into ice surface types. TLS-derived surface roughness exhibited strong relationships with plot-scale SfM z0 estimates. At the glacier scale, a consistent increase in z0 of ~0.1 mm d−1 was observed. Space-for-time substitution based on time since surface ice was exposed by snow melt confirmed this gradual increase in z0 over 60 d. These measurements permit us to propose a scale-dependent temporal z0 evolution model where unpredictable variability at the plot scale gives way to more predictable changes of z0 at the glacier scale. This model provides a critical step towards deriving spatially and temporally distributed representations of z0 that are currently lacking in the parameterisation of distributed glacier surface energy balance models.
OBJECTIVES/GOALS: Epilepsy with myoclonic-atonic seizures (EMAS) is a childhood onset epilepsy disorder characterized by seizures with sudden loss of posture, or drop seizures. Our objective was to use short-read genome sequencing in 40 EMAS trios to better understand variants contributing to the development of EMAS. METHODS/STUDY POPULATION: Eligibility for the cohort included a potential diagnosis of EMAS by child neurology faculty at Children’s Hospital Colorado. Exclusion criteria included lack of drop seizures upon chart review or structural abnormality on MRI. Some individuals had prior genetic testing and priority for genome sequencing was given to individuals without clear genetic diagnosis based on previous testing. We analyzed single nucleotide variants (SNVs), small insertions and deletions (INDELs), and larger structural variants (SVs) from trio genomes and determined those that were likely contributory based on standardized American College of Medical Genetics (ACMG) criteria. RESULTS/ANTICIPATED RESULTS: Our initial analysis focused on variants in coding regions of known epilepsy-associated genes. We identified pathogenic or likely pathogenic variants in 6 different individuals involving 6 unique genes. Of these, 5 are de novo SNVs or INDELs and 1 is a de novo SV. One of these involve a de novo heterozygous variant in an X-linked gene (ARHGEF9) in a female individual. We hypothesize the skewed X-inactivation may result in primarily expression of the pathogenic variant. We anticipate identifying additional candidate variants in coding regions of genes previously not associated with EMAS or pediatric epilepsies as well as in noncoding regions of the genome. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite the genetic heterogeneity of EMAS, our initial analysis identified de novo pathogenic or likely pathogenic variants in 15% (6/40) of our cohort. As the cost continues to decline, short read genome sequencing represents a promising diagnostic tool for EMAS and other pediatric onset epilepsy syndromes. CONFLICT OF INTEREST DESCRIPTION: The authors have no conflicts of interest to disclose. SD has consulted for Upsher-Smith, Biomarin and Neurogene on an unrelated subject matter. GLC holds a research collaborative grant with Stoke therapeutics on unrelated subject matter.
Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
Surgical site infections (SSIs) are among the most common healthcare-associated infections in low- and middle-income countries. To encourage establishment of actionable and standardized SSI surveillance in these countries, we propose simplified surveillance case definitions. Here, we use NHSN reports to explore concordance of these simplified definitions to NHSN as ‘reference standard.’
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Palmer amaranth is the most common and troublesome weed in North Carolina sweetpotato. Field studies were conducted in Clinton, NC, in 2016 and 2017 to determine the critical timing of Palmer amaranth removal in ‘Covington’ sweetpotato. Palmer amaranth was grown with sweetpotato from transplanting to 2, 3, 4, 5, 6, 7, 8, and 9 wk after transplanting (WAP) and maintained weed-free for the remainder of the season. Palmer amaranth height and shoot dry biomass increased as Palmer amaranth removal was delayed. Season-long competition by Palmer amaranth interference reduced marketable yields by 85% and 95% in 2016 and 2017, respectively. Sweetpotato yield loss displayed a strong inverse linear relationship with Palmer amaranth height. A 0.6% and 0.4% decrease in yield was observed for every centimeter of Palmer amaranth growth in 2016 and 2017, respectively. The critical timing for Palmer amaranth removal, based on 5% loss of marketable yield, was determined by fitting a log-logistic model to the relative yield data and was determined to be 2 WAP. These results show that Palmer amaranth is highly competitive with sweetpotato and should be managed as early as possible in the season. The requirement of an early critical timing of weed removal to prevent yield loss emphasizes the importance of early-season scouting and Palmer amaranth removal in sweetpotato fields. Any delay in removal can result in substantial yield reductions and fewer premium quality roots.
We report on the successful demonstration of a 150 J nanosecond pulsed cryogenic gas cooled, diode-pumped multi-slab Yb:YAG laser operating at 1 Hz. To the best of our knowledge, this is the highest energy ever recorded for a diode-pumped laser system.
Depression and chronic inflammatory medical conditions have been linked to impaired cognitive ability. However despite frequent comorbidity, their combined association with cognitive ability has rarely been examined.
This study examined associations between self-reported depression and chronic inflammatory diseases and their interaction with cognitive performance in 456,748 participants of the UK Biobank, adjusting for sociodemographic and lifestyle factors. Numbers with available data ranged from 94,899 to 453,208 depending on the cognitive test.
Self-reported depression was associated with poorer performance compared to controls in several cognitive tests (fully adjusted models, reaction time: B = 6.08, 95% CI = 5.09, 7.07; pairs matching: incidence rate ratio = 1.02, 95% CI = 1.02, 1.03; Trail Making Test B: B = 1.37, 95% CI = 0.88, 1.87; Digit Symbol Substitution Test (DSST): B = −0.35, 95% CI = −0.44, −0.27). Self-reported chronic inflammatory conditions were associated with slower reaction time (B = 3.79, 95% CI = 2.81, 4.78) and lower DSST scores (B = −0.21, 95% CI = −0.30, −0.13). No interaction effects were observed.
In this large, population-based study we provide evidence of lower cognitive performance in both depression and a comprehensive category of chronic inflammatory conditions. Results are consistent with additive effects of both types of disorder on cognitive ability. Clinicians should be aware of such effects, particularly as cognitive impairment is linked to poorer disease outcomes and quality of life.
Propagating inhomogeneous electromagnetic waves called surface plasmon polaritons (SPPs) can be excited by free-space beams on corrugated conducting surfaces at resonance angles determined by corrugation period, permittivity, and optical frequency. SPPs are coupled to and co-propagate with surface charge displacements. Complete electrical isolation of individual conducting corrugations prevents the charge displacement necessary to sustain an SPP, such that excitation resonances of traveling SPPs are absent. However, SPPs can be excited via electric induction if a smooth conducting surface exists below and nearby the isolated conducting corrugations. The dependence of SPP excitation resonances on that separation is experimentally investigated here at long-wave infrared wavelengths. We find that excitation resonances for traveling SPPs broaden and disappear as the dielectric’s physical thickness is increased beyond ~1% of the free-space wavelength. The resonance line width increases with refractive index and optical thickness of the dielectric.
Sulfur-bearing monazite-(Ce) occurs in silicified carbonatite at Eureka, Namibia, forming rims up to ~0.5 mm thick on earlier-formed monazite-(Ce) megacrysts. We present X-ray photoelectron spectroscopy data demonstrating that sulfur is accommodated predominantly in monazite-(Ce) as sulfate, via a clino-anhydrite-type coupled substitution mechanism. Minor sulfide and sulfite peaks in the X-ray photoelectron spectra, however, also indicate that more complex substitution mechanisms incorporating S2– and S4+ are possible. Incorporation of S6+ through clino-anhydrite-type substitution results in an excess of M2+ cations, which previous workers have suggested is accommodated by auxiliary substitution of OH– for O2–. However, Raman data show no indication of OH–, and instead we suggest charge imbalance is accommodated through F– substituting for O2–. The accommodation of S in the monazite-(Ce) results in considerable structural distortion that may account for relatively high contents of ions with radii beyond those normally found in monazite-(Ce), such as the heavy rare earth elements, Mo, Zr and V. In contrast to S-bearing monazite-(Ce) in other carbonatites, S-bearing monazite-(Ce) at Eureka formed via a dissolution–precipitation mechanism during prolonged weathering, with S derived from an aeolian source. While large S-bearing monazite-(Ce) grains are likely to be rare in the geological record, formation of secondary S-bearing monazite-(Ce) in these conditions may be a feasible mineral for dating palaeo-weathering horizons.
In patients with β-lactam allergies, administration of non–β-lactam surgical prophylaxis is associated with increased risk of infection. Although many patients self-report β-lactam allergies, most are unconfirmed or mislabeled. A quality improvement process, utilizing a structured β-lactam allergy tool, was implemented to improve the utilization of preferred β-lactam surgical prophylaxis.
Cognitive impairment is strongly linked with persistent disability in people with mood disorders, but the factors that explain cognitive impairment in this population are unclear.
To estimate the total effect of (a) bipolar disorder and (b) major depression on cognitive function, and the magnitude of the effect that is explained by potentially modifiable intermediate factors.
Cross-sectional study using baseline data from the UK Biobank cohort. Participants were categorised as having bipolar disorder (n = 2709), major depression (n = 50 975) or no mood disorder (n = 102 931 and n = 105 284). The outcomes were computerised tests of reasoning, reaction time and memory. The potential mediators were cardiometabolic disease and psychotropic medication. Analyses were informed by graphical methods and controlled for confounding using regression, propensity score-based methods and G-computation.
Group differences of small magnitude were found on a visuospatial memory test. Z-score differences for the bipolar disorder group were in the range −0.23 to −0.17 (95% CI −0.39 to −0.03) across different estimation methods, and for the major depression group they were approximately −0.07 (95% CI −0.10 to −0.03). One-quarter of the effect was mediated via psychotropic medication in the bipolar disorder group (−0.05; 95% CI −0.09 to −0.01). No evidence was found for mediation via cardiometabolic disease.
In a large community-based sample in middle to early old age, bipolar disorder and depression were associated with lower visuospatial memory performance, in part potentially due to psychotropic medication use. Mood disorders and their treatments will have increasing importance for population cognitive health as the proportion of older adults continues to grow.
Declaration of interest
I.J.D. is a UK Biobank participant. J.P.P. is a member of the UK Biobank Steering Committee.