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Objectives/Goals: Mayo Clinic Florida’s Clinical Research Units develop over 200 clinical studies on average annually. Almost 30% of these projects are developed and then are unable to activate due to a variety of operational factors. To increase the success rate, a scoring tool was created to assess the risk associated with the development of these research projects. Methods/Study Population: A project team comprised of members of research administration and physician leadership developed a rapid project management (RPM) scoring tool to assess operational risk factors. The scoring algorithm was embedded into an existing REDCap database, using a combination of identified variables and calculated fields. All noncancer industry sponsor-initiated clinical studies were scored at intake. According to the following categories: enrollment timelines, study team capacity, and previous experience with the Sponsor. Studies with a score greater than the established threshold were referred to physician leadership for transparent discussions with the principal investigator regarding the identified study development-related risks. Results/Anticipated Results: The RPM tool has assessed close to 200 projects since implementation in June 2022. An interim analysis is being conducted of all projects assessed by the RPM tool dating from implementation to May 2024 to compare the outcomes of these studies with the given RPM score. We anticipate based on anecdotal evidence gathered during the course of this pilot project that the RPM tool will show a correlation between risks identified and study outcomes as defined as successful activation of trials, or rationale of project development failures. We anticipate a reduction in the amount of time elapsed and effort expended developing projects with scores reflecting identified project development-related risk factors. Discussion/Significance of Impact: The RPM tool provides an opportunity to allocate resources to studies with the greatest potential for successful activation. In the future, the RPM tool may be used to identify risk factors associated with enrollment and accrual of participants.
Clostridioides difficile infection (CDI) may be misdiagnosed if testing is performed in the absence of signs or symptoms of disease. This study sought to support appropriate testing by estimating the impact of signs, symptoms, and healthcare exposures on pre-test likelihood of CDI.
Methods:
A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI. Consensus, defined as agreement by >70% of panelists, was assessed via a REDCap survey. Items without consensus were discussed in a virtual meeting followed by a second survey.
Results:
All fifteen panelists completed both surveys (100% response rate). In the initial survey, consensus was present on 6 of 15 (40%) items related to risk of CDI. After panel discussion and clarification of questions, consensus (>70% agreement) was reached on all remaining items in the second survey. Antibiotics were identified as the primary risk factor for CDI and grouped into three categories: high-risk (likelihood ratio [LR] 7, 93% agreement among panelists in first survey), low-risk (LR 3, 87% agreement in first survey), and minimal-risk (LR 1, 71% agreement in first survey). Other major factors included new or unexplained severe diarrhea (e.g., ≥ 10 liquid bowel movements per day; LR 5, 100% agreement in second survey) and severe immunosuppression (LR 5, 87% agreement in second survey).
Conclusion:
Infectious disease experts concurred on the importance of signs, symptoms, and healthcare exposures for diagnosing CDI. The resulting risk estimates can be used by clinicians to optimize CDI testing and treatment.
We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.
Methods
We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.
Results
The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).
Conclusions
The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.
While unobscured and radio-quiet active galactic nuclei are regularly being found at redshifts
$z > 6$
, their obscured and radio-loud counterparts remain elusive. We build upon our successful pilot study, presenting a new sample of low-frequency-selected candidate high-redshift radio galaxies (HzRGs) over a sky area 20 times larger. We have refined our selection technique, in which we select sources with curved radio spectra between 72–231 MHz from the GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) survey. In combination with the requirements that our GLEAM-selected HzRG candidates have compact radio morphologies and be undetected in near-infrared
$K_{\rm s}$
-band imaging from the Visible and Infrared Survey Telescope for Astronomy Kilo-degree Infrared Galaxy (VIKING) survey, we find 51 new candidate HzRGs over a sky area of approximately
$1200\ \mathrm{deg}^2$
. Our sample also includes two sources from the pilot study: the second-most distant radio galaxy currently known, at
$z=5.55$
, with another source potentially at
$z \sim 8$
. We present our refined selection technique and analyse the properties of the sample. We model the broadband radio spectra between 74 MHz and 9 GHz by supplementing the GLEAM data with both publicly available data and new observations from the Australia Telescope Compact Array at 5.5 and 9 GHz. In addition, deep
$K_{\rm s}$
-band imaging from the High-Acuity Widefield K-band Imager (HAWK-I) on the Very Large Telescope and from the Southern Herschel Astrophysical Terahertz Large Area Survey Regions
$K_{\rm s}$
-band Survey (SHARKS) is presented for five sources. We discuss the prospects of finding very distant radio galaxies in our sample, potentially within the epoch of reionisation at
$z \gtrsim 6.5$
.
Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample.
Methods
Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of ‘Genetic’ models (solely fitted with PRS-SZ), ‘Environmental’ models (solely fitted with each environmental stressor), ‘Independent’ models (with PRS-SZ and each environmental factor), and ‘Interaction’ models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models.
Results
There were no genes-environment associations. PRS-SZ was associated with positive dimensions (β = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension.
Conclusions
This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.
Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmissions among healthcare workers and hospitalized patients are challenging to confirm. Investigation of infected persons often reveals multiple potential risk factors for viral acquisition. We combined exposure investigation with genomic analysis confirming 2 hospital-based clusters. Prolonged close contact with unmasked, unrecognized infectious, individuals was a common risk.
Understanding the cognitive determinants of healthcare worker (HCW) behavior is important for improving the use of infection prevention and control (IPC) practices. Given a patient requiring only standard precautions, we examined the dimensions along which different populations of HCWs cognitively organize patient care tasks (ie, their mental models).
Design:
HCWs read a description of a patient and then rated the similarities of 25 patient care tasks from an infection prevention perspective. Using multidimensional scaling, we identified the dimensions (ie, characteristics of tasks) underlying these ratings and the salience of each dimension to HCWs.
Setting:
Adult inpatient hospitals across an academic hospital network.
Participants:
In total, 40 HCWs, comprising infection preventionists and nurses from intensive care units, emergency departments, and medical-surgical floors rated the similarity of tasks. To identify the meaning of each dimension, another 6 nurses rated each task in terms of specific characteristics of tasks.
Results:
Each HCW population perceived patient care tasks to vary along 3 common dimensions; most salient was the perceived magnitude of infection risk to the patient in a task, followed by the perceived dirtiness and risk of HCW exposure to body fluids, and lastly, the relative importance of a task for preventing versus controlling an infection in a patient.
Conclusions:
For a patient requiring only standard precautions, different populations of HCWs have similar mental models of how various patient care tasks relate to IPC. Techniques for eliciting mental models open new avenues for understanding and ultimately modifying the cognitive determinants of IPC behaviors.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
This study examined the separate relationships between socio-economic disadvantage and the density of multiple types of food outlets, and relationships between socio-economic disadvantage and composite food environment indices.
Design:
Cross-sectional data were analysed using geospatial kernel density techniques. Food outlet data included convenience stores, discount stores, fast-food and fast casual restaurants, and grocery stores. Controlling for urbanicity and race/ethnicity, multivariate linear regression was used to examine the relationships between socio-economic disadvantage and density of food outlets.
Setting:
This study occurred in a large Southeastern US county containing 255 census block groups with a total population of 474 266, of which 77·1 % was Non-Hispanic White, the median household income was $48 886 and 15·0 % of residents lived below 125 % of the federal poverty line.
Participants:
The unit of analysis was block groups; all data about neighbourhood socio-economic disadvantage and food outlets were publicly available.
Results:
As block group socio-economic disadvantage increased, so too did access to all types of food outlets. The total food environment index, calculated as the ratio of unhealthy food outlets to all food outlets, decreased as block group disadvantage increased.
Conclusions:
Those who reside in more disadvantaged block groups have greater access to both healthy and unhealthy food outlets. The density of unhealthy establishments was greater in more disadvantaged areas; however, because of having greater access to grocery stores, disadvantaged populations have less obesogenic total food environments. Structural changes are needed to reduce access to unhealthy food outlets to ensure environmental injustice and reduce obesity risk.
Multi-attribute utility instruments (MAUIs) are generic health-related quality of life (HRQoL) measures that enable valuation of health states relative to death (0.0) and full health (1.0). The usefulness of MAUIs in people with psychosis has been questioned, with the EQ-5D considered “insensitive”, the 15D “problematic” and the SF-6D “unsuitable”.
Objectives
Confirm the Assessment of Quality of Life (AQoL)-4D MAUI is useful and meaningful in people with psychosis.
Aims
Assess utility values across demographic, general and disease-specific health categorisations for a large nationally-representative sample with psychosis (n = 1825).
Methods
Participants underwent a comprehensive 32 module interview encompassing psychopathology to service use. Utility values were calculated by applying a standard algorithm to responses to each of 12 items of the AQoL-4D.
Results
Utility values were assessed for 1793 participants (98.2%). No ceiling effect was observed and only 6.6% of participants scored in the top decile of HRQoL [0.9–10.0]. In contrast, 10.8% scored in the lowest decile [−0.04–0.10], a floor effect observed in 0.4%. The mean utility value was 0.49 (95% CI: 0.48–0.51), significantly lower than the Australian population norm of 0.81 (95% CI: 0.81–0.82). Greatest impacts on HRQoL were for diminishing global independent functioning as measured by the MSIF (ESMSIF: 0.68–2.24), self-rated current mental health (ESMH: 0.15–1.65) and physical health status (ESPH: 0.11–1.21). Strong effects also observed for course of disorder (ESCoD: 0.08–1.13), current suicidal ideation (ESCSI1: 0.76–1.08), and labor force participation (ESLFP: 0.11–0.97).
Conclusions
The AQoL-4D had good lower end sensitivity in a large sample of people with a psychotic illness, and demonstrated responsiveness across subjective, objective and symptom measures.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together $60+$ programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
OBJECTIVES/SPECIFIC AIMS: To build a multisite de-identified database of female adolescents, aged 12–21 years (January 2011–December 2012), and their subsequent offspring through 24 months of age from electronic health records (EHRs) provided by participating Community Health. METHODS/STUDY POPULATION: We created a community-academic partnership that included New York City Community Health Centers (n=4) and Hospitals (n=4), The Rockefeller University, The Sackler Institute for Nutrition Science and Clinical Directors Network (CDN). We used the Community-Engaged Research Navigation model to establish a multisite de-identified database extracted from EHRs of female adolescents aged 12–21 years (January 2011–December 2012) and their offspring through 24 months of age. These patients received their primary care between 2011 and 2015. Clinical data were used to explore possible associations among specific measures. We focused on the preconception, prenatal, postnatal periods, including pediatric visits up to 24 months of age. RESULTS/ANTICIPATED RESULTS: The analysis included all female adolescents (n=122,556) and a subset of pregnant adolescents with offspring data available (n=2917). Patients were mostly from the Bronx; 43% of all adolescent females were overweight (22%) or obese (21%) and showed higher systolic and diastolic blood pressure, blood glucose levels, hemoglobin A1c, total cholesterol, and triglycerides levels compared with normal-weight adolescent females (p<0.05). This analysis was also performed looking at the nonpregnant females and the pregnant females separately. Overall, the pregnant females were older (mean age=18.3) compared with the nonpregnant females (mean age=16.5), there was a higher percentage of Hispanics among the pregnant females (58%) compared with the nonpregnant females (43.9%). There was a statistically significant association between the BMI status of mothers and infants’ birth weight, with underweight/normal-weight mothers having more low birth weight (LBW) babies and overweight/obese mothers having more large babies. The odds of having a LBW baby was 0.61 (95% CI: 0.41, 0.89) lower in obese compared with normal-weight adolescent mothers. The risk of having a preterm birth before 37 weeks was found to be neutral in obese compared with normal-weight adolescent mothers (OR=0.81, 95% CI: 0.53, 1.25). Preliminary associations are similar to those reported in the published literature. DISCUSSION/SIGNIFICANCE OF IMPACT: This EHR database uses available measures from routine clinical care as a “rapid assay” to explore potential associations, and may be more useful to detect the presence and direction of associations than the magnitude of effects. This partnership has engaged community clinicians, laboratory, and clinical investigators, and funders in study design and analysis, as demonstrated by the collaborative development and testing of hypotheses relevant to service delivery. Furthermore, this research and learning collaborative is examining strategies to enhance clinical workflow and data quality as well as underlying biological mechanisms. The feasibility of scaling-up these methods facilitates studying similar populations in different Health Systems, advancing point-of-care studies of natural history and comparative effectiveness research to identify service gaps, evaluate effective interventions, and enhance clinical and data quality improvement.
To examine perspectives on food access among low-income families participating in a cost-offset community-supported agriculture (CO-CSA) programme.
Design
Farm Fresh Foods for Healthy Kids (F3HK) is a multicentre randomized intervention trial assessing the effect of CO-CSA on dietary intake and quality among children from low-income families. Focus groups were conducted at the end of the first CO-CSA season. Participants were interviewed about programme experiences, framed by five dimensions of food access: availability, accessibility, affordability, acceptability and accommodation. Transcribed data were coded on these dimensions plus emergent themes.
Setting
Nine communities in the US states of New York, North Carolina, Washington and Vermont.
Subjects
Fifty-three F3HK adults with children.
Results
CSA models were structured by partner farms. Produce quantity was abundant; however, availability was enhanced for participants who were able to select their own produce items. Flexible CSA pick-up times and locations made produce pick-up more accessible. Despite being affordable to most, payment timing was a barrier for some. Unfamiliar foods and quick spoilage hindered acceptability through challenging meal planning, despite accommodations that included preparation advice.
Conclusions
Although CO-CSA may facilitate increased access to fruits and vegetables for low-income families, perceptions of positive diet change may be limited by the ability to incorporate share pick-up into regular travel patterns and meal planning. Food waste concerns may be particularly acute for families with constrained resources. Future research should examine whether CO-CSA with flexible logistics and produce self-selection are sustainable for low-income families and CSA farms.
The thermal decomposition of caledonite has been examined by simultaneous differential thermal analysis, thermogravimetry and mass spectrometry. Structural H2O and CO2 are liberated endothermically between 300 and 400°C leaving a residue of lead sulphate, oxysulphate, and Cu(I) and Cu(II) oxides. A series of sharp endothermic peaks between 850 and 950°C correspond to phase transition and melting reactions of the PbO-PbSO4 mixture. The sulphate anion breaks down above 880 °C. Mass spectra of the gaseous decomposition products show SO2, SO, and O2, although SO is an artefact arising from ion fragmentation of the SO2 within the mass spectrometer. The residue at 1060 °C is composed predominantly of 2PbO · PbSO4 and Cu(I) and Cu(II) oxides.
We have previously reported an association between childhood abuse and psychotic experiences (PEs) in survey data from South East London. Childhood abuse is related to subsequent adulthood adversity, which could form one pathway to PEs. We aimed to investigate evidence of mediation of the association between childhood abuse and PEs by adverse life events.
Methods.
Data were analysed from the South East London Community Health Study (SELCoH, n = 1698). Estimates of the total effects on PEs of any physical or sexual abuse while growing up were partitioned into direct (i.e. unmediated) and indirect (total and specific) effects, mediated via violent and non-violent life events.
Results.
There was strong statistical evidence for direct (OR 1.58, 95% CI: 1.19–2.1) and indirect (OR 1.51, 95% CI: 1.32–1.72) effects of childhood abuse on PEs after adjustment for potential confounders, indicating partial mediation of this effect via violent and non-violent life events. An estimated 47% of the total effect of abuse on PEs was mediated via adulthood adverse life events, of which violent life events made up 33% and non-violent life events the remaining 14%.
Conclusions.
The association between childhood abuse and PEs is partly mediated through the experience of adverse life events in adulthood. There is some evidence that a larger proportion of this effect was mediated through violent life events than non-violent life events.
Firn temperatures at the Dome Summit South drill site, East Antarctica, are simulated by driving a thermal model of the ice sheet with observed instrumental records over the period 1960-96. The model incorporates firn density and thermal properties to reproduce measured borehole temperatures as shallow as 5 m below the surface, where the seasonal temperature wave is readily apparent. The study shows that ice-sheet temperatures are approximately 0.8°C cooler than mean 4 m air temperatures. It also finds that non-conductive processes such as ventilation and radiation can be simulated at this site by assuming perfect thermal contact between the top ∼1 m of firn and the atmosphere on monthly time-scales.
We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.
The current generation of experiments aiming to detect the neutral hydrogen signal from the Epoch of Reionisation (EoR) is likely to be limited by systematic effects associated with removing foreground sources from target fields. In this paper, we develop a model for the compact foreground sources in one of the target fields of the MWA’s EoR key science experiment: the ‘EoR1’ field. The model is based on both the MWA’s GLEAM survey and GMRT 150 MHz data from the TGSS survey, the latter providing higher angular resolution and better astrometric accuracy for compact sources than is available from the MWA alone. The model contains 5 049 sources, some of which have complicated morphology in MWA data, Fornax A being the most complex. The higher resolution data show that 13% of sources that appear point-like to the MWA have complicated morphology such as double and quad structure, with a typical separation of 33 arcsec. We derive an analytic expression for the error introduced into the EoR two-dimensional power spectrum due to peeling close double sources as single point sources and show that for the measured source properties, the error in the power spectrum is confined to high k⊥ modes that do not affect the overall result for the large-scale cosmological signal of interest. The brightest 10 mis-modelled sources in the field contribute 90% of the power bias in the data, suggesting that it is most critical to improve the models of the brightest sources. With this hybrid model, we reprocess data from the EoR1 field and show a maximum of 8% improved calibration accuracy and a factor of two reduction in residual power in k-space from peeling these sources. Implications for future EoR experiments including the SKA are discussed in relation to the improvements obtained.
Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.
Method
We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.
Results
Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.
Conclusions
Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.