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Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25–26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs. Prominent themes surfaced, including competing research priorities and incentives, inadequate representation of patient population in clinical trials, opportunities to better leverage existing technology and infrastructure in trial design, and a need for heightened transparency and accountability in research practices. The group determined that together these elements contribute to an inefficient and costly clinical research enterprise, amplifying disparities in population health and sustaining gaps in evidence that impede advancements in equitable healthcare delivery and outcomes. The goal of addressing the identified challenges is to ultimately make clinical trials faster, more inclusive, and more efficient across diverse communities and settings.
Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.
To examine the relationships between baseline gray matter volumes, diagnostic status, and executive function performance at 24-month follow-up, and the relative importance of predictors of executive function in a cohort of non-demented older adults.
Participants and Methods:
The study sample included 147 participants from the Alzheimer’s Disease Neuroimaging Initiative (mean age = 70.6, SD = 6.4; mean education = 17 years, SD = 2.4). At baseline, 49 participants were diagnosed as cognitively normal (CN), 60 as early mild cognitive impairment (EMCI), and 38 as late mild cognitive impairment (LMCI). Magnetic resonance imaging (MRI) data were collected at baseline. A composite score of executive function and FreeSurfer-derived gray matter regions-of-interest (ROI; whole brain, superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, orbitofrontal cortex, anterior cingulate cortex, superior parietal lobule, inferior parietal lobule, hippocampus) were examined. Hierarchical linear regression models were employed to assess whether brain volume predicted executive function at 24-month follow-up and interaction effects between baseline ROI volume and diagnostic status. Age, gender, education, Mini-Mental State Examination scores, and APOE-e4 allele status were included as control variables in each model. Relative importance metrics, which quantifies an individual regressor’s contribution to a multiple regression model, were computed using the Lindemen, Merenda, and Gold (lmg) method to assess the relative contribution of each variable in predicting executive function performance.
Results:
Across all participants, baseline gray matter ROI volume accounted for a significant amount of variance in executive function at 24-months after accounting for control variables. Specifically, anterior cingulate cortex and superior parietal lobule accounted for an additional 7% and 6% of variance in executive function at 24-months. Significant brain region X diagnostic status interaction effects were observed in executive function performance at 24-months. Relative importance metrics within each group indicated that age is the most important predictor of executive function at 24-months for CN, anterior cingulate cortex is most important for EMCI, and Mini-Mental Examination score is most important for LMCI.
Conclusions:
Our findings implicate frontoparietal gray matter regions as significant predictors of executive function performance at 24-months, and that this relationship is moderated by diagnostic status. Our results indicate that the value of specific variables to predict executive function performance varies based on diagnostic status. Specifically, anterior cingulate cortex was a significant predictor of executive function performance across all participants and was the most important variable in predicting performance in the earliest stage of mild cognitive impairment. These results support previous studies examining gray matter correlates of executive function and extend the literature by exploring predictors of executive function in early and late stages of mild cognitive impairment.
Emergency departments are high-risk settings for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) surface contamination. Environmental surface samples were obtained in rooms with patients suspected of having COVID-19 who did or did not undergo aerosol-generating procedures (AGPs). SARS-CoV-2 RNA surface contamination was most frequent in rooms occupied by coronavirus disease 2019 (COVID-19) patients who received no AGPs.
Mitotic-inhibiting herbicides, like prodiamine and dithiopyr, are used to control annual bluegrass (Poa annua L.) preemergence in managed turfgrass; however, resistance to mitotic-inhibiting herbicides has evolved due to repeated applications of herbicide from a single mechanism of action. Three suspected resistant populations (R1, R2, and R3) were collected in Alabama and Florida and screened for resistance to prodiamine. Part of the α-tubulin gene was sequenced for known target-site mutations. Target-site mutations were reported in all three R populations, with each containing an amino acid substitution at position 239 from threonine to isoleucine (Thr-239-Ile). Previous research has indicated that the Thr-239-Ile mutation confers resistance to dinitroaniline herbicides in other species. Dose–response screens using prodiamine and dithiopyr were conducted and I50 values were calculated for R1, R2, and R3 using regression models based on seedling emergence. For prodiamine, I50 values for R1, R2, and R3 were 35.3, 502.7, and 91.5 g ai ha−1, respectively, resulting in 2.9-, 41.9-, and 7.6-fold resistance, respectively, when compared with a susceptible (S) population. For dithiopyr, I50 values for R1, R2, and R3 were 154.0, 114.2, and 190.1 g ai ha−1, respectively, resulting in 3.6-, 2.7-, and 4.5-fold resistance, respectively, when compared with an S population. When comparing I90 values with the highest labeled use rates, R2 had a 2.9-fold level of resistance to prodiamine, and R1, R2, and R3 had a 2.4-, 2.0-, and 3.2-fold levels of resistance to dithiopyr, respectively. This is the first report of a variable response in P. annua to prodiamine despite each R population possessing the same mutation.
To review and study implementation of an automated hand hygiene reminder system (AHHRS).
Design:
Prospective, nonrandomized, before-after quality improvement pilot study conducted over 6 months.
Setting:
Medical-surgical unit (MSU) and medical intensive care unit (MICU) at a public hospital in New York City.
Participants:
There were 2,642 healthcare worker observations in the direct observation (DO) period versus 265,505 in the AHHRS period, excluding AHHRS observations collected during the 1-month crossover period when simultaneous DO occurred.
Intervention:
We compared hand hygiene adherence (HHA) measured by DO prior to the pilot and after AHHRS implementation. We compared changes in HHA and potential cross-contamination events (CCEs) (room exit and subsequent entry without HHA) from baseline for each biweekly period during the pilot.
Results:
Engagement, education/training, data transparency, and optimization period resulted in successful implementation and adoption of the AHHRS. Observations were greater utilizing AHHRS than DO (265,505 vs 2,642, P < .01). Due to the expected Hawthorne effect, HHA was significantly less for AHHRS than DO in MSU (90.99% vs 97.21%, P < .01) and MICU (91.21% vs 98.65%, P < .01). HHA significantly improved from 86.47% to 89.68% in MSU (P < .001) and 85.93% to 91.24% in the MICU (P < .001) from the first biweekly period of AHHRS utilization to the last. CCE decreased from 73.42% to 65.11% in the MSU and significantly decreased from 81.22% to 53.19% in the MICU (P < .05).
Conclusions:
We describe how an AHHRS approach was successfully implemented at our facility. With ongoing feedback and system optimization, AHHRS improved HHA and reduced CCE over time.
The mitotic-inhibiting herbicide pronamide controls susceptible annual bluegrass (Poa annua L.) pre- and postemergence, but in some resistant populations, postemergence activity is compromised, hypothetically due to a target-site mutation, lack of root uptake, or an unknown resistance mechanism. Three suspected pronamide-resistant (LH-R, SC-R, and SL-R) and two pronamide-susceptible (BS-S and HH-S) populations were collected from Mississippi golf courses. Dose–response experiments were conducted to confirm and quantify pronamide resistance, as well as resistance to flazasulfuron and simazine. Target sites known to confer resistance to mitotic-inhibiting herbicides were sequenced, as were target sites for herbicides inhibiting acetolactate synthase (ALS) and photosystem II (PSII). Pronamide absorption and translocation were investigated following foliar and soil applications. Dose–response experiments confirmed pronamide resistance of LH-R, SC-R, and SL-R populations, as well as instances of multiple resistance to ALS- and PSII-inhibiting herbicides. Sequencing of the α-tubulin gene confirmed the presence of a mutation that substituted isoleucine for threonine at position 239 (Thr-239-Ile) in LH-R, SC-R, SL-R, and BS-S populations. Foliar application experiments failed to identify differences in pronamide absorption and translocation between the five populations, regardless of harvest time. All populations had limited basipetal translocation—only 3% to 13% of the absorbed pronamide—across harvest times. Soil application experiments revealed that pronamide translocation was similar between SC-R, SL-R, and both susceptible populations across harvest times. The LH-R population translocated less soil-applied pronamide than susceptible populations at 24, 72, and 168 h after treatment, suggesting that reduced acropetal translocation may contribute to pronamide resistance. This study reports three new pronamide-resistant populations, two of which are resistant to two modes of action (MOAs), and one of which is resistant to three MOAs. Results suggest that both target site– and translocation-based mechanisms may be associated with pronamide resistance. Further research is needed to confirm the link between pronamide resistance and the Thr-239-Ile mutation of the α-tubulin gene.
Considerable progress continues to be made with regards to the value and use of disease associated polygenic scores (PGS). PGS aim to capture a person’s genetic liability to a condition, disease, or a trait, combining information across many risk variants and incorporating their effect sizes. They are already available for clinicians and consumers to order in Australasia. However, debate is ongoing over the readiness of this information for integration into clinical practice and population health. This position statement provides the viewpoint of the Human Genetics Society of Australasia (HGSA) regarding the clinical application of disease-associated PGS in both individual patients and population health. The statement details how PGS are calculated, highlights their breadth of possible application, and examines their current challenges and limitations. We consider fundamental lessons from Mendelian genetics and their continuing relevance to PGS, while also acknowledging the distinct elements of PGS. Use of PGS in practice should be evidence based, and the evidence for the associated benefit, while rapidly emerging, remains limited. Given that clinicians and consumers can already order PGS, their current limitations and key issues warrant consideration. PGS can be developed for most complex conditions and traits and can be used across multiple clinical settings and for population health. The HGSA’s view is that further evaluation, including regulatory, implementation and health system evaluation are required before PGS can be routinely implemented in the Australasian healthcare system.
Bustards comprise a highly threatened family of birds and, being relatively fast, heavy fliers with very limited frontal visual fields, are particularly susceptible to mortality at powerlines. These infrastructures can also displace them from immediately adjacent habitat and act as barriers, fragmenting their ranges. With geographically ever wider energy transmission and distribution grids, the powerline threat to bustards is constantly growing. Reviewing the published and unpublished literature up to January 2021, we found 2,774 records of bustard collision with powerlines, involving 14 species. Some studies associate powerline collisions with population declines. To avoid mortalities, the most effective solution is to bury the lines; otherwise they should be either routed away from bustard-frequented areas, or made redundant by local energy generation. When possible, new lines should run parallel to existing structures and wires should preferably be as low and thick as possible, with minimal conductor obstruction of vertical airspace, although it should be noted that these measures require additional testing. A review of studies finds limited evidence that ‘bird flight diverters’ (BFDs; devices fitted to wires to induce evasive action) achieve significant reductions in mortality for some bustard species. Nevertheless, dynamic BFDs are preferable to static ones as they are thought to perform more effectively. Rigorous evaluation of powerline mortalities, and effectiveness of mitigation measures, need systematic carcass surveys and bias corrections. Whenever feasible, assessments of displacement and barrier effects should be undertaken. Following best practice guidelines proposed with this review paper to monitor impacts and mitigation could help build a reliable body of evidence on best ways to prevent bustard mortality at powerlines. Research should focus on validating mitigation measures and quantifying, particularly for threatened bustards, the population effects of powerline grids at the national scale, to account for cumulative impacts on bustards and establish an equitable basis for compensation measures.
The transition to open data practices is straightforward albeit surprisingly challenging to implement largely due to cultural and policy issues. A general data sharing framework is presented along with two case studies that highlight these challenges and offer practical solutions that can be adjusted depending on the type of data collected, the country in which the study is initiated, and the prevailing research culture. Embracing the constraints imposed by data privacy considerations, especially for biomedical data, must be emphasized for data outside of the United States until data privacy law(s) are established at the Federal and/or State level.
People with age-related macular degeneration (AMD) can report reduced mental health. There is also evidence that they struggle with daily tasks because of vision loss.
Aims
The purpose of this study was to assess the psychological impact of instrumental activities of daily living on people with simulated AMD.
Method
Twenty-four normally sighted participants completed 12 household tasks, in a simulated home environment, under a moderate-to-severe AMD simulation. Participants’ psychological state was measured through self-report questionnaires and physiological measurements related to anxiety and stress. Tasks were completed twice, under counterbalanced vision conditions (normal and simulated AMD).
Results
Linear mixed models on vision condition (normal versus simulated AMD) and trial order (trial 1 versus trial 2) revealed a significant large negative effect of the AMD simulation on time to complete tasks, and the anxiety, task engagement and distress self-reports (all P < 0.024, all ω2 > 0.177). There were also significant medium-large effects of trial order on time, task incompletion, task errors, and the anxiety and task engagement self-reports (all P < 0.047, all ω2 > 0.130), whereby the results improved during the second attempt at the tasks. No physiological measures were significant (all P > 0.05).
Conclusions
Completing instrumental activities of daily living under an AMD simulation had a negative impact on participants’ self-reported mental state. The observed trial order effects also illuminated how practice with tasks could ease anxiety and stress over time.
To examine Hb level and anaemia status among infants under 6 months of age in rural China.
Design:
A cross-sectional survey collected data among infants under 6 months and their primary caregivers in Sichuan, China. Anaemia was defined using both the WHO and China Pediatrics Association thresholds. Multivariable linear regression was used to identify relevant factors among two age groups (<4 months; 4–5 months).
Setting:
Eighty townships were selected in Sichuan, China from November to December 2019.
Participants:
Nine hundred and forty-two infants under 6 months, while Hb level was tested for 577 infants.
Results:
The overall mean (±sd) Hb level was 106·03 (± 12·04) g/l. About 62·6 % (95 % CI 58·5, 66·6) of sample infants were anaemic using the WHO threshold, and 20·5 % (95 % CI 17·3, 24·1) were anaemic using the China Pediatrics Association thresholds. Anaemia rates rose with increasing age in months. Multivariable linear regressions revealed that lower Hb levels were significantly associated with lower birth weight (<4 months: β = 4·14, 95 % CI 0·19, 8·08; 4–5 months: β = 6·60, 95 % CI 2·94, 10·27) and delivery by caesarean section (<4 months: β = −4·64, 95 % CI −7·79, −1·49; 4–5 months: β = −4·58, 95 % CI −7·45, −1·71).
Conclusion:
A large share of infants under 6 months in rural western China are anaemic. Infants with low birth weight and caesarean delivered should be prioritised for anaemia testing. Future studies should move the point of focus forward to at least 4 months of age and examine the link between caesarean section and anaemia to promote health and development in infancy.
Repeated serosurveys are an important tool for understanding trends in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination. During 1 September 2020–20 March 2021, the NYC Health Department conducted a population-based SARS-CoV-2 antibody prevalence survey of 2096 NYC adults who either provided a blood specimen or self-reported the results of a previous antibody test. The serosurvey, the second in a series of surveys conducted by the NYC Health Department, aimed to estimate SARS-CoV-2 antibody prevalence across the city and for different groups at higher risk for adverse health outcomes. Weighted citywide prevalence was 23.5% overall (95% confidence interval (CI) 20.1–27.4) and increased from 19.2% (95% CI 14.7–24.6) before coronavirus disease 2019 vaccines were available to 31.3% (95% CI 24.5–39.0) during the early phases of vaccine roll-out. We found no differences in antibody prevalence by age, race/ethnicity, borough, education, marital status, sex, health insurance coverage, self-reported general health or neighbourhood poverty. These results show an overall increase in population-level seropositivity in NYC following the introduction of SARS-CoV-2 vaccines and highlight the importance of repeated serosurveys in understanding the pandemic's progression.
Background: Aerosol-generating procedures (AGPs) performed on COVID-19–positive patients raise concerns about the dissemination of SARS-CoV-2 via aerosols and droplets. Infectious aerosols and droplets generated by SARS-CoV-2–positive patient AGPs or through direct COVID-19 patient coughing or exhalation could potentially contaminate surfaces, leading to the indirect spread of SARS-CoV-2 via fomites within the emergency department (ED). We sampled surfaces of ED patient rooms occupied by known SARS-CoV-2–positive patients or patients under investigation for COVID-19 and undergoing an AGP to determine the frequency of room contamination with SARS-CoV-2 RNA. Methods: Swabs were collected from 5 room surfaces in the ED following AGPs performed on patients under investigation for COVID-19 or positive for SARS-CoV-2. High- and low-touch surfaces 6 feet (2 m) from the patient (door handle and return vent, respectively) and reusable medical equipment were swabbed. Swabs were tested for SARS-CoV-2 RNA by RT-qPCR; positive samples were cultured in Vero E6 cells. Patient COVID-19 results were confirmed through the electronic medical record. Results: In total, 203 rooms were sampled: 43 SARS-CoV-2–positive patients with an AGP, 44 SARS-CoV-2–positive patients who did not have an AGP, and 116 SARS-CoV-2–negative patients with an AGP, for a total of 1,015 swabs. Overall, SARS-CoV-2 RNA was detected on 36 (3.5%) surfaces from 29 rooms (14.3%) (Table 1). RNA contamination was detected more frequently in rooms occupied by SARS-CoV-2–positive patients who did not have an AGP than rooms occupied by COVID-19 patients (30% vs 14%). SARS-CoV-2 RNA was also detected in rooms occupied by SARS-CoV-2–negative patients undergoing an AGP (9%). SARS-CoV-2 RNA was most frequently detected on air vents (n = 15), bedrails (n = 10), equipment and vital signs monitors (n = 4 each), and door handles (n = 3). One bedrail was positive by culture and confirmed by an RT-qPCR cycle threshold reduction from >40 to 13. Conclusions: We detected SARS-CoV-2 RNA contamination on room surfaces in the ED, regardless of patient AGP or COVID-19 status; however, RNA contamination of room surfaces was most common in rooms occupied by SARS-CoV-2–positive patients who did not have an AGP, which may be attributable to stage of disease and viral shedding. SARS-CoV-2 RNA contamination was also present in rooms where APGs were performed on SARS-CoV-2–negative patients, suggesting carryover from previous patients. SARS-CoV-2 RNA was found most often on room air-return vents, further emphasizing the importance of aerosols in the spread of SARS-CoV-2.
Empirical studies have the potential to both inform and transform cyber peace research. Empirical research can shed light on opaque phenomena, summarize and synthesize diverse stakeholder perspectives, and allow causal inferences about the impact of policymaking efforts. However, researchers embarking on empirical projects in the area of cyber peace generally, and cybersecurity specifically, face significant challenges – particularly related to data collection. In this chapter, we identify some of the key impediments to empirical cyber research and suggest how researchers and other interested stakeholders can overcome these barriers.
Sexual orientation is considered from Savin-Williams’ continuum perspective, and gender and sexual orientation are both conceptualized from a fluid, rather than a categorical viewpoint. A Minority Stress Model is applied to the experience of LGBTQ+ communities, whereby stress reactions relate to concerns about one’s safety, discrimination, oppression, and internalized oppression, among many other negative mental and physical health outcomes. Proximal and distal stressors are presented in conjunction with the Minority Stress Model and applied to several domains illustrating community gaps and interventions in academic, legislative, religious, economic, medical, social, and social-environmental realms. Key policies are presented supporting greater rights for LGBTQ+ communities. Despite these advances, significant gaps remain with regard to responsiveness to the needs of LGBTQ+ communities. A case study highlights adverse effects and policy regarding conversion therapy.
Dithiopyr and dinitroanilines are preemergence-applied, mitotic-inhibiting herbicides used to control goosegrass [Eleusine indica (L.) Gaertn.] in turfgrass. A suspected resistant E. indica population was collected from a golf course putting green and was evaluated for possible resistance to dithiopyr and prodiamine. After dose–response evaluation, the α-tubulin gene was sequenced for known target-site mutations that have been reported to confer resistance to mitotic-inhibiting herbicides. A mutation was discovered that resulted in an amino acid substitution at position 136 from leucine to phenylalanine (Leu-136-Phe). Previous research has indicated that Leu-136-Phe does confer resistance to dinitroaniline herbicides. The level of resistance indicated by regression models and I50 values indicates that there is 54.1-, 4.7-, >100-, and >100-fold resistance to dithiopyr, prodiamine, pendimethalin, and oryzalin, respectively, when compared with the susceptible population based on seedling emergence response and 88.4-, 7.8-, >100-, and >100-fold resistance to dithiopyr, prodiamine, pendimethalin, and oryzalin, respectively, when compared with the susceptible population based on biomass reduction response. This is the first report of less resistance to prodiamine compared with pendimethalin or oryzalin due to a target-site α-tubulin mutation and the first report of a target-site α-tubulin mutation associated with dithiopyr resistance.
The papers in this forum offer an interdisciplinary assessment of the state of the field of Anglican Studies and perspectives on future trajectories. The first three papers, on liturgy, history, and world Anglicanism, offer an assessment of the respective state of these areas of Anglican Studies. The second set, on theology, sociology of religion, and biblical studies, stake out positions on how these disciplines inform the work of Anglican Studies. A concluding essay offers a synthesis of these papers, focusing on the themes of local contexts for Anglicanism, a further complexification of decolonizing processes in Anglicanism, and the critical role of conversation in Anglican Studies regarding disciplines, languages, and power dynamics.