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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.
Skin and soft tissue infections (SSTIs) account for over 2.8 million annual emergency department (ED) visits and often result in suboptimal antibiotic therapy. The objective of this study was to evaluate a set of interventions in minimizing inappropriate prescription of antibiotics for presumed SSTIs in the ED.
Design:
Case vignette survey.
Participants:
A national sample of emergency medicine (EM) physicians.
Methods:
Each vignette described a clinical scenario of a presumed SSTI (cellulitis or abscess) and included a unique combination of zero to five interventions (outpatient follow-up, inappropriate antibiotic request flag, thermal imaging for cellulitis or rapid wound MRSA PCR for abscess, patient education/shared decision-making, and clinical decision support). Out of 64 possible vignettes, we asked participants to respond to eight vignettes. Following each vignette, we asked participants if they would prescribe an antibiotic in their everyday practice (yes/no). We built adjusted hierarchical logistic regression models to estimate the probability of prescribing an antibiotic for each intervention and vignette.
Results:
Surveys were completed by 113 EM physicians. The thermal imaging, rapid wound MRSA PCR, and patient education/shared decision-making interventions showed the largest decrease (15–20%) in antibiotic prescribing probability. Vignettes with a combination of both a diagnostic intervention (thermal imaging or rapid wound MRSA PCR) and a patient education/shared decision-making intervention had the lowest prescribing probabilities.
Conclusion:
We recommend future research focuses on the development and integration of novel diagnostic tools to identify true infection and incorporate shared decision-making to improve diagnosis and management of SSTIs.
Several metrics exist for matching the size of donor to recipient in paediatric cardiac transplantation. Different centres employ different metrics for size-matching to determine the viability of donor hearts. Inconsistent evidence exists, with limited consensus as to the metric for size-matching that is most predictive of outcomes after cardiac transplantation. Furthermore, any metric must function within the tight timeline available for the assessment of the suitability of the donor. At the time of the writing of this paper, the most commonly used metric for size-matching in paediatric cardiac transplantation is the donor-to-recipient body weight ratio. In this article, we review published literature evaluating commonly used metrics for size-matching in paediatric cardiac transplantation, including weight, height, body surface area, and imaging parameters.
The relevance of education and outreach (E&O) activities about the Antarctic Treaty has been recognized at the Antarctic Treaty Consultative Meetings (ATCM) and at the Committee for Environmental Protection (CEP). This study examines the key topics and the target audiences detailed in papers submitted to the ATCM on E&O. Since the Antarctic Treaty entered into force in 1961, a total of 216 ATCM papers on E&O have been produced. The number of papers has increased substantially since the mid-1990s. ‘Science’ (76.9%) and ‘Wildlife/Biodiversity/Environment’ (75.5%) were the most addressed topics in these papers, while the ‘Public’ (81.0%) and those attending ‘Schools’ (69.0%) are the main target audiences. ‘Science’ in ATCM papers increased ~120-fold from 1961–1997 to 2015–2023, while ATCM papers discussing engagement with the ‘Public’ increased ~40-fold during the same period. ‘Climate change’ was first mentioned in 2006, and the number of papers per year increased fourfold by 2015–2023. This study shows the increasing interest in E&O through time, addressing key topics to relevant audiences related to the Antarctic region. From an educational perspective, attention should be paid to emerging topics (e.g. equity, diversity and inclusion), and the engagement of early-career professionals and educators should be made a priority.
Alexandrov’s estimate states that if $\Omega $ is a bounded open convex domain in $\mathbb {R}^n$ and $u:\bar \Omega \to \mathbb {R}$ is a convex solution of the Monge-Ampère equation $\det D^2 u = f$ that vanishes on $\partial \Omega $, then
We establish a variety of improvements of this, depending on the geometry of $\partial \Omega $. For example, we show that if the curvature is bounded away from $0$, then the estimate remains valid if $\omega (\delta )$ is replaced by $C_\Omega \delta ^{\frac 12 + \frac 1{2n}}$. We determine the sharp constant $C_\Omega $ when $n=2$, and when $n\ge 3$ and $\partial \Omega $ is $C^2$, we determine the sharp asymptotics of the optimal modulus of continuity $\omega _\Omega (\delta )$ as $\delta \to 0$. For arbitrary convex domains, we characterize the scaling of the optimal modulus $\omega _\Omega $. Our results imply in particular that unless $\partial \Omega $ has a flat spot, $\omega _\Omega (\delta ) = o(\delta ^{1/n})$ as $\delta \to 0$, and under very mild nondegeneracy conditions, they yield the improved Hölder estimate, $\omega _\Omega (\delta ) \le C \delta ^\alpha $ for some $\alpha>1/n$.
In December 2018, an outbreak of Salmonella Enteritidis infections was identified in Canada by whole-genome sequencing (WGS). An investigation was initiated to identify the source of the illnesses, which proved challenging and complex. Microbiological hypothesis generation methods included comparisons of Salmonella isolate sequence data to historical domestic outbreaks and international repositories. Epidemiological hypothesis generation methods included routine case interviews, open-ended centralized re-interviewing, thematic analysis of open-ended interview data, collection of purchase records, a grocery store site visit, analytic comparison to healthy control groups, and case–case analyses. Food safety hypothesis testing methods included food sample collection and analysis, and traceback investigations. Overall, 83 cases were identified across seven provinces, with onset dates from 6 November 2018 to 7 May 2019. Case ages ranged from 1 to 88 years; 60% (50/83) were female; 39% (22/56) were hospitalized; and three deaths were reported. Brand X profiteroles and eclairs imported from Thailand were identified as the source of the outbreak, and eggs from an unregistered facility were hypothesized as the likely cause of contamination. This study aims to describe the outbreak investigation and highlight the multiple hypothesis generation methods that were employed to identify the source.
Obesity can increase the risk of postoperative complications. Despite increased demand for patients living with obesity to lose weight prior to common surgical procedures, the impact of intentional weight loss on surgical outcomes is largely unknown. We aimed to conduct a pilot study to assess the feasibility of a full-scale randomised controlled trial (RCT) to examine the effect of preoperative dietitian-led Very Low Calorie Diet (VLCD) Clinic on surgical outcomes in gynaecology and general surgeries. Between August 2021 and January 2023, a convenience sample of adults living with obesity (BMI ≥ 30 kg/m2) awaiting gynaecology, laparoscopic cholecystectomy and ventral hernia repair procedures were randomised to dietitian-led VLCD (800–1000 kcal using meal replacements and allowed foods), or control (no dietary intervention), 2–12 weeks preoperatively. Primary outcome was feasibility (recruitment, adherence, safety, attendance, acceptability and quality of life (QoL)). Secondary outcomes were anthropometry and 30-d postoperative outcomes. Outcomes were analysed as intention-to-treat. Fifty-one participants were recruited (n 23 VLCD, n 28 control), mean 48 (sd 13) years, 86 % female, and mean BMI 35·8 (sd 4·6) kg/m2. Recruitment was disrupted by COVID-19, but other thresholds for feasibility were met for VLCD group: high adherence without unfavourable body composition change, high acceptability, improved pre/post QoL (22·1 ± 15 points, < 0·001), with greater reductions in weight (–5·5 kg VLCD v. −0·9 kg control, P < 0·05) waist circumference (–6·6 cm VLCD v. +0·6 control, P < 0·05) and fewer 30-d complications (n 4/21) than controls (n 8/22) (P > 0·05). The RCT study design was deemed feasible in a public hospital setting. The dietitian-led VLCD resulted in significant weight loss and waist circumference reduction compared with a control group, without unfavourable body composition change and improved QoL.
We evaluated diagnostic test and antibiotic utilization among 252 patients from 11 US hospitals who were evaluated for coronavirus disease 2019 (COVID-19) pneumonia during the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) omicron variant pandemic wave. In our cohort, antibiotic use remained high (62%) among SARS-CoV-2–positive patients and even higher among those who underwent procalcitonin testing (68%).
Previous research has found that subjective cognitive decline corresponds with assessed memory impairment and could even be predictive of neurocognitive impairment. The purpose of this study was to investigate whether a single self-report item of subjective cognitive decline corresponds with the results of a performance-based measure of episodic memory.
Participants and Methods:
Older adults (n = 100; age 60-90) were given the single item measure of subjective cognitive decline developed by Verfaille et al. (2018).
Results:
Those who endorsed subjective cognitive decline (n = 68) had lower scores on the CVLT-II long delay free recall than those who did not endorse such a decline (n = 32). Additionally, older adults with a neurocognitive diagnosis believed their memory was becoming worse at a higher proportion than those without.
Conclusions:
While a single item of subjective cognitive decline should not be substituted for a comprehensive evaluation of memory, the results suggest that it may have utility as a screening item.
For infections to be maintained in a population, pathogens must compete to colonize hosts and transmit between them. We use an experimental approach to investigate within-and-between host dynamics using the pathogen Pseudomonas aeruginosa and the animal host Caenorhabditis elegans. Within-host interactions can involve the production of goods that are beneficial to all pathogens in the local environment but susceptible to exploitation by non-producers. We exposed the nematode host to ‘producer’ and two ‘non-producer’ bacterial strains (specifically for siderophore production and quorum sensing), in single infections and coinfections, to investigate within-host colonization. Subsequently, we introduced infected nematodes to pathogen-naive populations to allow natural transmission between hosts. We find that producer pathogens are consistently better at colonizing hosts and transmitting between them than non-producers during coinfection and single infection. Non-producers were poor at colonizing hosts and between-host transmission, even when coinfecting with producers. Understanding pathogen dynamics across these multiple levels will ultimately help us predict and control the spread of infections, as well as contribute to explanations for the persistence of cooperative genotypes in natural populations.
In the past decade, scholars of the here-and-now have (re)discovered the concept of enclosure, applying it with considerable zeal and in a bewildering variety of situations: from the securitisation of the Internet, and patenting genes, to attempts to privatise urban ‘public’ spaces, the English ‘enclosure story’ is presented as a given, a narrative that is set in stone. One critical aspect of this account is that enclosure was exported to Britain's overseas colonies in a one-way process. This paper shows, however, that from the early sixteenth century – and insistently so from the late eighteenth century – arguments for the enclosure of English commons and wastes were framed using techniques and discourses deployed overseas: the languages and practices of colonialism. Commons and wastes, so the paper argues, were not just increasingly seen as empty spaces, but the peoples that inhabited them were written as if they were uncivilised and unable to manage the land. Further, arguments for the enclosure of wastes were made as an alternative to Britain's overseas imperialism. The paper traces a variety of debates and proposals that collectively constitute a coherent body of ‘internal colonial’ thought.
Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and a severe threat to pregnant people and offspring health. The molecular origins of GDM, and in particular the placental responses, are not fully known. The present study aimed to perform a comprehensive characterisation of the lipid species in placentas from pregnancies complicated with GDM using high-resolution MS lipidomics, with a particular focus on sphingolipids and acylcarnitines in a semi-targeted approach. The results indicated that despite no major disruption in lipid metabolism, placentas from GDM pregnancies showed significant alterations in sphingolipids, mostly lower abundance of total ceramides. Additionally, very long-chain ceramides and sphingomyelins with twenty-four carbons were lower, and glucosylceramides with sixteen carbons were higher in placentas from GDM pregnancies. Semi-targeted lipidomics revealed the strong impact of GDM on the placental acylcarnitine profile, particularly lower contents of medium and long-chain fatty-acyl carnitine species. The lower contents of sphingolipids may affect the secretory function of the placenta, and lower contents of long-chain fatty acylcarnitines is suggestive of mitochondrial dysfunction. These alterations in placental lipid metabolism may have consequences for fetal growth and development.
In porcine in vitro production (IVP) systems, the use of oocytes derived from prepubertal gilts, whilst being commercially attractive, remains challenging due to their poor developmental competence following in vitro maturation (IVM). Follicular fluid contains important growth factors and plays a key role during oocyte maturation; therefore, it is a common supplementation for porcine IVM medium. However, follicular fluid contains many poorly characterized components, is batch variable, and its use raises biosecurity concerns. In an effort to design a defined IVM system, growth factors such as cytokines have been previously tested. These include leukaemia inhibitory factor (LIF), fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 (IGF1), the combination of which is termed ‘FLI’. Here, using abattoir-derived oocytes in a well established porcine IVP system, we compared follicular fluid and FLI supplementation during both IVM and embryo culture to test the hypothesis that FLI can substitute for follicular fluid without compromising oocyte nuclear and cytoplasmic maturation. We demonstrate that in oocytes derived from prepubertal gilts, FLI supplementation enhances oocyte meiotic maturation and has a positive effect on the quality and developmental competence of embryos. Moreover, for the first time, we studied the effects of follicular fluid and FLI combined showing no synergistic effects.
An enduring interest in categories (katēgoriai),1 and in Aristotle’s Categories in particular, has led readers since antiquity to study the treatise which Porphyry entitled On the Genera of Being (6.1–3).2 Ancient and modern readers broadly agree that: (1) Plotinus understands his own subject matter to be ‘the kinds of things that exist’ (peri tōn genōn tou ontos); (2) the treatise displays the result of a deep and substantial engagement with Aristotle’s Categories; and (3) Plotinus raises important and substantive puzzles (aporiai) about what is said in the Categories.3 Beyond this, plausible interpretations diverge. On one view, Plotinus deploys the resources of earlier Platonist critics to challenge the Categories’ ontological prioritization of particular substance, especially as it is treated by earlier Aristotelian commentators.4 On an alternative reading, Plotinus ‘purifies’ Aristotelian ontology in order to sketch a new taxonomy of the sensible world, complementing his own account of the intelligible world and clearing a trail for Porphyry’s integration of Aristotle into a new Platonist curriculum.5
OBJECTIVES/GOALS: Decongestion, or fluid removal, is an important goal in the management of acute heart failure (AHF) among patients with heart failure with reduced ejection fraction (HFrEF). We sought to examine whether the rate of decongestion is associated with mortality and cardiovascular (CV) outcomes. METHODS/STUDY POPULATION: Using data from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial (n=4133), we evaluated the rate of decongestion by using linear mixed models to derive the in-hospital slope of b-type natriuretic peptide (BNP) and hematocrit as proxies of volume overload and hemoconcentration, respectively. A propensity score was developed to match patients from the quartile with most rapid rates of decongestion to the three quartiles with slower rates. Cox proportional hazards regression models were fitted to assess the association between rate of decongestion with risk of all-cause mortality and a composite of CV mortality or AHF hospitalization. RESULTS/ANTICIPATED RESULTS: Slower rates of in-hospital decongestion were associated with increased risk of both outcomes over a median 10-month follow-up. Those with slower rates of BNP decline, in comparison to the propensity-score matched patients with the most rapid rates of BNP decline, had higher hazards of mortality (HR=1.73 [1.23, 2.42]) and the composite outcome (HR=1.48 [1.18, 1.86]). Those with slower rates of hematocrit increase, in comparison to the propensity-score matched patients with the most rapid rates of hematocrit increase, showed a trend toward higher hazard of mortality (HR=1.17 [0.95, 1.43]) and an increased risk of the composite outcome (HR=1.26 [1.08, 1.47]). DISCUSSION/SIGNIFICANCE: Among patients with HFrEF admitted for AHF, slower rates of decongestion are associated with increased risk of mortality, CV mortality and AHF hospitalization. It remains unknown whether more rapid decongestion provides cardiovascular benefit or if it serves as a proxy for less treatment resistant heart failure.
The Centers for Medicare and Medicaid mandated that nursing homes implement antibiotic stewardship programs (ASPs) by November 2017. We conducted surveys of Wisconsin nursing-home stewardship practices before and after this mandate. Our comparison of these surveys shows an overall increase in ASP implementation efforts, but it also highlights areas for further improvement.
Our goal was to examine the association between moral injury, mental health, and suicide attempts during military service and after separation by gender in post-9/11 veterans.
Methods
A nationally representative sample of 14057 veterans completed a cross-sectional survey. To examine associations of exposure to potentially morally injurious events (PMIEs; witnessing, perpetrating, and betrayal) and suicidal self-directed violence, we estimated two series of multivariable logistic regressions stratified by gender, with peri- and post-military suicide attempt as the dependent variables.
Results
PMIE exposure accounted for additional risk of suicide attempt during and after military service after controlling for demographic and military characteristics, current mental health status, and pre-military history of suicidal ideation and attempt. Men who endorsed PMIE exposure by perpetration were 50% more likely to attempt suicide during service and twice as likely to attempt suicide after separating from service. Men who endorsed betrayal were nearly twice as likely to attempt suicide during service; however, this association attenuated to non-significance after separation in the fully adjusted models. In contrast, women who endorsed betrayal were over 50% more likely to attempt suicide during service and after separation; PMIE exposure by perpetration did not significantly predict suicide attempts before or after service among women in the fully adjusted models.
Conclusions
Our findings indicate that suicide assessment and prevention programs should consider the impact of moral injury and attend to gender differences in this risk factor in order to provide the most comprehensive care.