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COVID-19 vaccination effectiveness in healthcare personnel (HCP) has been established, however, questions remain about its performance in high-risk healthcare occupations and work locations. We describe the effect of a COVID-19 HCP vaccination campaign on SARS-CoV-2 infection by timing of vaccination, job type, and work location.
A retrospective review of COVID-19 vaccination acceptance, incidence of post-vaccination COVID-19 infection, hospitalization, and mortality among 16,156 faculty, students, and staff at a large academic medical center was conducted. Data were collected 8 weeks prior to the start of Phase 1a vaccination of frontline employees and ended 11 weeks after campaign completion.
COVID-19 employee incidence rate at our institution decreased from 3.2% during the 8 weeks prior to the start of vaccinations to 0.38% by four weeks after campaign initiation. SARS-CoV-2 infection risk was reduced among individuals receiving a single vaccination (HR = 0.52 [0.40, 0.68], p<0.0001) and further reduced with 2 doses of vaccine (HR = 0.17 [0.09, 0.32], p<0.0001). By two weeks after the second dose, the observed case positivity rate was 0.04%. Among Phase 1a HCP, we observed a lower risk of SARS-CoV-2 infection among physicians and a trend toward higher risk for respiratory therapists independent of vaccination status. Rates of infection were similar in a sub-group of nurses when examined by work location.
Our findings show the real-world effectiveness of COVID-19 vaccination in HCP. Despite these encouraging results, unvaccinated HCP remain at an elevated risk of infection highlighting the need for targeted outreach to combat vaccine hesitancy.
Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.
ABSTRACT IMPACT: The key to advancing precision medicine is to deepen our understanding of drug modes-of-action (MOA). This project aims to develop a novel method for predicting MOA of potential drug compounds, providing an experimental and computational platform for more efficient drug discovery. OBJECTIVES/GOALS: To develop (1) a targeted CRISPR-Cas9 chemical-genetic screen approach, and (2) a computational method to predict drug mode-of-action from chemical-genetic interaction profiles. METHODS/STUDY POPULATION: Screening drugs against a gene deletion library can identify knockouts that modulate drug sensitivity. These chemical-genetic interaction (CGI) screens can be performed in human cell lines using a pooled lentiviral CRISPR-Cas9 approach to assess drug sensitivity/resistance of single-gene knockouts across the human genome. A targeted, rather than genome-wide, library can enable scaling these screens across many drugs.
CGI profiles can be derived from phenotypic screen readouts. These profiles are analogous to genetic interaction (GI) profiles, which represent sensitivity/resistance of gene knockouts to a second gene knockout rather than a drug. To computationally predict a drug’s genetic target, we leverage the property that a drug’s CGI profile will be similar to its target’s GI profile. RESULTS/ANTICIPATED RESULTS: Five proof-of-principle screens will be conducted with compounds that have existing genome-wide profiles and well-characterized MOA. I will generate CGI profiles for these five compounds and identify genes that are drug-sensitizers or drug-suppressors. I will then evaluate whether targeted library screens can recapitulate the CGIs found in genome-wide screens. Finally, I will develop a computational tool to integrate these CGI profiles with GI profiles (derived from another project) to predict gene-level and bioprocess-level drug targets. These predictions (from both targeted and genome-wide profiles) will be benchmarked against a drug-target and drug-bioprocess standard. DISCUSSION/SIGNIFICANCE OF FINDINGS: This work will develop a scalable, targeted chemical-genetic screen approach to discovering how putative therapeutics work. The targeted screen workflow provides a method for higher-throughput drug screening. The computational pipeline provides a powerful tool for exploring the MOA of uncharacterized drugs or repurposing FDA-approved drugs.
In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a “wet” person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.
This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.
Chronic non-cancer pain (CNCP) involves one-third of the US population, and prescription opioids contribute to the opioid epidemic. The Centers for Disease Control and Prevention emphasizes maximizing non-opioid treatment, but many rural populations cannot access alternative therapies. Clinical and Translational Science Award hubs across four rural states performed a multi-site, single-arm intervention feasibility study testing methods and procedures of implementing a behavioral intervention, acceptance and commitment therapy, in primary care CNCP patients on chronic opioids. Using the CONSORT extension for feasibility studies, we describe lessons learned in recruiting/retaining participants, intervention implementation, data measurement, and multi-site procedures. Results inform a future definitive trial and potentially others conducting rural trials.
Most older adults perceive themselves as good drivers; however, their perception may not be accurate, and could negatively affect their driving safety. This study examined the accuracy of older drivers’ self-awareness of driving ability in their everyday driving environment by determining the concordance between the perceived (assessed by the Perceived Driving Ability [PDA] questionnaire) and actual (assessed by electronic Driving Observation Schedule [eDOS]) driving performance. One hundred and eight older drivers (male: 67.6%; age: mean = 80.6 years, standard deviation [SD] = 4.9 years) who participated in the study were classified into three groups: underestimation (19%), accurate estimation (29%), and overestimation (53%). Using the demographic and clinical functioning information collected in the Candrive annual assessments, an ordinal regression showed that two factors were related to the accuracy of self-awareness: older drivers with better visuo-motor processing speed measured by the Trail Making Test (TMT)-A and fewer self-reported comorbid conditions tended to overestimate their driving ability, and vice versa.
Project management expertise is employed across many professional sectors, including clinical research organizations, to ensure that efforts undertaken by the organization are completed on time and according to specifications and are capable of achieving the needed impact. Increasingly, project leaders (PLs) who possess this expertise are being employed in academic settings to support clinical and preclinical translational research team science. Duke University’s clinical and translational science enterprise has been an early adopter of project management to support clinical and preclinical programs. We review the history and evolution of project management and the PL role at Duke, examine case studies that illustrate their growing value to our academic research environment, and address challenges and solutions to employing project management in academia. Furthermore, we describe the critical role project leadership plays in accelerating and increasing the success of translational team science and team approaches frequently required for systems biology and “big data” scientific studies. Finally, we discuss perspectives from Duke project leadership professionals regarding the training needs and requirements for PLs working in academic clinical and translational science research settings.
We assessed whether paternal demographic, anthropometric and clinical factors influence the risk of an infant being born large-for-gestational-age (LGA). We examined the data on 3659 fathers of term offspring (including 662 LGA infants) born to primiparous women from Screening for Pregnancy Endpoints (SCOPE). LGA was defined as birth weight >90th centile as per INTERGROWTH 21st standards, with reference group being infants ⩽90th centile. Associations between paternal factors and likelihood of an LGA infant were examined using univariable and multivariable models. Men who fathered LGA babies were 180 g heavier at birth (P<0.001) and were more likely to have been born macrosomic (P<0.001) than those whose infants were not LGA. Fathers of LGA infants were 2.1 cm taller (P<0.001), 2.8 kg heavier (P<0.001) and had similar body mass index (BMI). In multivariable models, increasing paternal birth weight and height were independently associated with greater odds of having an LGA infant, irrespective of maternal factors. One unit increase in paternal BMI was associated with 2.9% greater odds of having an LGA boy but not girl; however, this association disappeared after adjustment for maternal BMI. There were no associations between paternal demographic factors or clinical history and infant LGA. In conclusion, fathers who were heavier at birth and were taller were more likely to have an LGA infant, but maternal BMI had a dominant influence on LGA.
We sought to define the prevalence of echocardiographic abnormalities in long-term survivors of paediatric hematopoietic stem cell transplantation and determine the utility of screening in asymptomatic patients. We analysed echocardiograms performed on survivors who underwent hematopoietic stem cell transplantation from 1982 to 2006. A total of 389 patients were alive in 2017, with 114 having an echocardiogram obtained ⩾5 years post-infusion. A total of 95 patients had echocardiogram performed for routine surveillance. The mean time post-hematopoietic stem cell transplantation was 13 years. Of 95 patients, 77 (82.1%) had ejection fraction measured, and 10/77 (13.0%) had ejection fraction z-scores ⩽−2.0, which is abnormally low. Those patients with abnormal ejection fraction were significantly more likely to have been exposed to anthracyclines or total body irradiation. Among individuals who received neither anthracyclines nor total body irradiation, only 1/31 (3.2%) was found to have an abnormal ejection fraction of 51.4%, z-score −2.73. In the cohort of 77 patients, the negative predictive value of having a normal ejection fraction given no exposure to total body irradiation or anthracyclines was 96.7% at 95% confidence interval (83.3–99.8%). Systolic dysfunction is relatively common in long-term survivors of paediatric hematopoietic stem cell transplantation who have received anthracyclines or total body irradiation. Survivors who are asymptomatic and did not receive radiation or anthracyclines likely do not require surveillance echocardiograms, unless otherwise indicated.
A principal mode of corrosion in combustion or fuel cell environments is the formation of volatile hydroxides and oxyhydroxides from metal or oxide surfaces at high temperatures. It is important to determine the degree of volatility and accurate thermodynamic properties for these hydroxides. Significant gaseous metal hydroxides/oxyhydroxides are discussed, along with available experimental and theoretical methods of characterizing species and determining their thermodynamic properties.
The burden of common perinatal mental disorders (CPMD) in low-and-middle-income countries is substantially higher than high-income countries, with low levels of detection, service provision and treatment in resource-constrained settings. We describe the development of an ultra-short screening tool to detect antenatal depression, anxiety disorders and maternal suicidal ideation.
A sample of 376 women was recruited at a primary-level obstetric clinic. Five depression and anxiety symptom-screening questionnaires, demographics and psychosocial risk questionnaires were administered. All participants were assessed with the Mini-International Neuropsychiatric Interview (MINI), a structured, diagnostic interview. Screening tool items were analysed against diagnostic data using multiple logistic regression and receiver operating curve (ROC) analysis.
The prevalence of MINI-defined major depressive episode (MDE) and/or anxiety disorders was 33%. Overall, 18% of participants expressed suicidal ideation and behaviour, 54% of these had no depression or anxiety diagnosis. Multiple logistic regression identified four screening items that were independently predictive of MDE and anxiety disorders, investigating depressed mood, anhedonia, anxiety symptoms and suicidal ideation. ROC analysis of these combined items yielded an area under the curve of 0.83 (95% CI 0.78–0.88). A cut-off score of 2 or more offered a sensitivity of 78% and specificity of 82%.
This novel screening tool is the first measure of CPMD developed in South Africa to include depressed mood, anxiety symptoms and suicidal ideation. While the tool requires further investigation, it may be useful for the early identification of mental health symptoms and morbidity in the perinatal period.
Female family headship has strong implications for endemic poverty in the United States. Consequently, it is imperative to explore the chief factors that contribute to this problem. Departing from prior literature that places significant weight on welfare-incentive effects, our study highlights the role of male marriageability in explaining the prevalence of never-married female family headship for blacks and whites. Specifically, we examine racial differences in the effect of male marriageability on never-married female headship from 1980 to 2010. By exploiting data from IPUMS-USA (N = 4,958,722) and exogenous variation from state-level sentencing reforms, the study finds that the decline in the relative supply of marriageable males significantly increases the incidence of never-married female family headship for blacks but not for whites.
Low-mass stars form from the gravitational collapse of dense molecular cloud cores. While a general consensus picture of this collapse process has emerged, many details on how mass is transferred from cores to stars remain poorly understood. MASSES (Mass Assembly of Stellar Systems and their Evolution with the SMA), an SMA large project, has just finished surveying all 74 Class 0 and Class I protostars in the nearby Perseus molecular cloud to reveal the interplay between fragmentation, angular momentum, and outflows in regulating accretion and setting the final masses of stars. Scientific highlights are presented in this proceedings, covering the topics of episodic accretion, hierarchical thermal Jeans fragmentation, angular momentum transfer, envelope grain sizes, and disk evolution.
Emotional awareness is the ability to recognize, describe, and attend to emotions. A known correlate is emotional processing, the ability to orient to and use inner experiences for information. The goal was to examine emotional awareness during therapy among gynecologic cancer patients, identify baseline predictors, and explore the relationship between in-session emotional awareness and processing.
Psychotherapy and baseline data from a randomized controlled trial comparing a supportive counseling (SC) intervention and a cognitive-behavioral coping and communication (CCI) intervention were used. The sample was patients with gynecologic cancers randomized to either therapy (N = 246). Emotion episode transcripts from the first, middle, and sixth of seven in-person sessions were coded for emotional awareness using the Program for Open-Ended Scoring and emotional processing using the Experiencing Scale. Descriptive and regression analyses were conducted.
Participants had moderate in-session emotional awareness. SC participants exhibited higher levels of awareness in the first (p < 0.001) and sixth (p = 0.002) sessions than CCI participants. Awareness was positively correlated with emotional processing in the first and sixth SC sessions (r = 0.25 and 0.24, respectively) and all CCI sessions (r = 0.29–0.31). Baseline negative emotion expression was associated with awareness during the sixth SC session. Baseline cancer-specific distress was associated with awareness during the sixth CCI session.
Significance of results
SC may facilitate emotional awareness. Greater emotional awareness in therapy may facilitate emotional processing, which is an important component of most psychotherapies. Patients who are psychologically distressed may exhibit more awareness than others. Similarly, greater emotional awareness may signal greater patient distress.
Except for the addition of modern material remains, the archaeological record is a finite resource, which means that, at some point in the future, there will be nothing left to find. In this paper, we model trends in archaeological discovery based on the growth of the field and the probability of site discovery. We compare this model to seven diverse datasets of archaeological discovery trends: (1) all sites from the state of Wyoming, USA; (2) high-altitude archaeological sites from the state of Colorado, USA; (3) mostly complete Neandertal crania; (4) monumental sites of the Maya Classic period; (5) proboscidean kill/scavenge sites globally; (6) Upper Paleolithic sites from Europe; and (7) a compilation of shipwreck discoveries. We forecast discovery trends over the current century. We show that, for all datasets, rates of discovery are in decline, and some segments of the record are near depletion.
Our aim was to compare changes in emotional processing by women newly diagnosed with gynecological cancer enrolled in either a coping and communication skills intervention (CCI) or a supportive counseling (SC) intervention. We examined the association between in-session emotional processing and patient-rated therapeutic progress.
Three therapy sessions with 201 patients were rated for the depth of emotional processing (peak and mode) during emotion episodes (EEs) using the Experiencing Rating Scale (EXP). Participants completed measures of dispositional emotional expressivity, depressive symptoms, and cancer-related distress before treatment began, as well as ratings of perceived progress in therapy after each session.
Peak EXP ratings averaged between 2.7 and 3.1, indicating that women discussed events, their emotional reactions, and their private experiences in sessions. A small proportion of patients had high levels of processing, indicating deeper exploration of the meaning of their feelings and experiences. Women in SC were able to achieve a higher level of emotional processing during the middle and later sessions, and during cancer-related EEs in the later session. However, emotional processing was not significantly associated with a patient's perceived therapeutic progress with SC. In the CCI group, higher levels of emotional processing were associated with greater session progress, suggesting that it may play an important role in patient-rated treatment outcomes.
Significance of results:
Newly diagnosed gynecological cancer patients are able to attend to their emotions and personal experiences, particularly when discussing cancer-related issues during both short-term SC and prescriptive coping skills interventions.