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The presence of an intraluminal thrombus in acutely symptomatic carotid stenosis is thought to represent a high-risk lesion for short-term stroke reccurrence though evidence on natural history and treatment is lacking, leading to equipoise and much variation in practice. The objective of this study was to map these variations in practice (medical management and timing of revascularization), determine the considerations that influence clinician decision-making in this condition and gather opinions that inform the development and design of future trials in the area.
Methods:
This was a mixed-methods study using both quantitative survey methods and qualitative interview-based methods. International perspectives were gathered by distributing a case-based survey via the “Practice Current” section of Neurology: Clinical Practice and interviewing international experts using established qualitative research methods.
Results:
The presence of an intraluminal thrombus significantly increased the likelihood of using a regimen containing anticoagulation agents (p < 0.001) in acutely symptomatic carotid stenosis in the case-based survey. Themes that emerged from qualitative interview analysis were therapeutic uncertainty regarding anticoagulation, decision to reimage, revascularization choices and future trial design and anticipated challenges.
Conclusion:
Results of this study demonstrate a preference for anticoagulation and delayed revascularization after reimaging to examine for clot resolution, though much equipoise remains. While there is interest from international experts in future trials, further study is needed to understand the natural history of this condition in order to inform trial design.
While political scientists regularly engage in spirited theoretical debates about elections and voting behavior, few have noticed that elected politicians also have theories of elections and voting. Here, we investigate politicians’ positions on eight central theoretical debates in the area of elections and voting behavior and compare politicians’ theories to those held by ordinary citizens. Using data from face-to-face interviews with nearly one thousand politicians in 11 countries, together with corresponding surveys of more than twelve thousand citizens, we show that politicians overwhelmingly hold thin, minimalist, “democratic realist” theories of voting, while citizens’ theories are more optimistic and policy oriented. Politicians’ theoretical tendencies—along with their theoretical misalignment from citizens—are remarkably consistent across countries. These theories are likely to have important consequences for how politicians campaign, communicate with the public, think about public policy, and represent their constituents.
OBJECTIVES/GOALS: Using a natural canine model of kidney stone disease, we previously identified a pathogenic variant in the uromodulin gene (UMOD) that imparts a dramatic risk for calcium oxalate (CaOx) stones. This study was designed to characterize the effects of the pathogenic variant on uromodulin processing, specifically polymerization and peptide excretion. METHODS/STUDY POPULATION: Uromodulin polymerization status and peptides were measured in random urine samples from CaOx stone-forming dogs with the pathogenic UMOD variant and breed-, sex-, and age-matched healthy control dogs. Polymerization status was determined using an ultracentrifugation protocol and Western blotting in 6 CaOx cases and 3 controls; relative abundance of the polymerizing and nonpolymerizing forms was evaluated. Uromodulin peptide abundances were measured by LC-MS/MS with 4 dogs per group; results were summed to determine total uromodulin peptide excretion for each dog, and individual peptide abundances were calculated as a percentage of the total. Polymerization status and peptides were compared between groups. RESULTS/ANTICIPATED RESULTS: Dogs with the pathogenic UMOD variant had abnormalities in both uromodulin polymerization and peptide processing. The polymerization data showed that the polymerizing form of uromodulin was abundant in all healthy controls but absent or severely reduced in most dogs with the variant. In contrast, nonpolymerizing uromodulin was detected in all dogs with no observed difference between those with and without the variant. The peptidomics data showed that stone-forming dogs with the pathogenic UMOD variant lacked a peptide cleavage site, resulting in the loss of two common peptides that terminate at that site and the presence of longer peptides that span the site. DISCUSSION/SIGNIFICANCE: These findings implicate uromodulin polymerization and peptide processing defects in kidney stone risk. Future studies will define the mechanisms through which these defects affect stone formation, ultimately informing development of novel preventative therapies.
This Element offers a framework for exploring the methodological challenges of neuroethics. The aim is to provide a roadmap for the methodological assumptions, and related pitfalls, involved in the interdisciplinary investigation of the ethical and legal implications of neuroscientific research and technology. It illustrates these points via the debate about the ethical and legal responsibility of psychopaths. Argument and the conceptual analysis of normative concepts such as 'personhood' or 'human agency' is central to neuroethics. This Element discusses different approaches to establishing norms and principles that regulate the practices addressed by neuroethics and that involve the use of such concepts. How to characterize the psychological features central to neuroethics, such as autonomy, consent, moral understanding, moral motivation, and control is a methodological challenge. In addition, there are epistemic challenges when determining the validity of neuroscientific evidence.
Background: The FIRST Trial is a 5-year study funded by the Agency for Healthcare Research and Quality. Our investigation is situated within a more extensive study to restrict fluoroquinolone antibiotics by requiring providers to obtain authorization from an infectious disease physician before prescribing fluoroquinolones. Our research team is performing a systematic evaluation to identify organizational characteristics and influencers of the fluoroquinolone preprescription authorization implementation process to understand variables that may facilitate or hinder implementation success. Methods: To address this critical gap, we present a qualitative analysis from our ongoing, multisite research project aimed at systematically assessing the adoption of an antimicrobial stewardship intervention in the form of an EHR-integrated best-practice alert (BPA) at each site to identify work system factors that impact uptake and variability in the implementation of the BPA at each location. The evaluation provides a detailed explanation of activities through the implementation process (eg, before implementation, during implementation, and after implementation) to assess how an organization effectively negotiates the phases and transitions, ultimately influencing the impact of the intervention. We have used a contextual determinant framework (CFIR) that has enabled us to perform a systematic and comprehensive exploration and identification of potential explanatory themes or variables to shed light on the complex social phenomenon of implementation. Results: Participants who will be a part of our poster presentation will learn about implementing a BPA, the potential barriers to implementation, and strategies for overcoming these barriers. Stakeholders within our study include site coordinators, medical doctors, nurses, pharmacists, and clinical informaticists. Our analysis synthesizes their experiences implementing and sustaining this evidence-based antimicrobial stewardship intervention. It includes (1) a detailed description of the process of change, (2) work-system factors (eg, inner setting and outer setting) that they believe influenced the success of the intervention, (3) barriers and facilitators (eg, CFIR constructs) within the implementation process; and (4) description of how these could have influenced the outcomes of interest (eg, implementation and intervention effectiveness). Conclusions: Our research is expected to advance patient safety research and initiatives by providing a more robust approach to performing systematic intervention evaluations. By outlining stakeholders’ experiences within our study, implementation leaders within healthcare systems will utilize our findings to aid them in their design and implementation process when designing and implementing similar types of healthcare interventions.
From the safety inside vehicles, Knowsley Safari offers visitors a close-up encounter with captive olive baboons. As exiting vehicles may be contaminated with baboon stool, a comprehensive coprological inspection was conducted to address public health concerns. Baboon stools were obtained from vehicles, and sleeping areas, inclusive of video analysis of baboon–vehicle interactions. A purposely selected 4-day sampling period enabled comparative inspections of 2662 vehicles, with a total of 669 baboon stools examined (371 from vehicles and 298 from sleeping areas). As informed by our pilot study, front-line diagnostic methods were: QUIK-CHEK rapid diagnostic test (RDT) (Giardia and Cryptosporidium), Kato–Katz coproscopy (Trichuris) and charcoal culture (Strongyloides). Some 13.9% of vehicles were contaminated with baboon stool. Prevalence of giardiasis was 37.4% while cryptosporidiosis was <0.01%, however, an absence of faecal cysts by quality control coproscopy, alongside lower than the expected levels of Giardia-specific DNA, judged RDT results as misleading, grossly overestimating prevalence. Prevalence of trichuriasis was 48.0% and strongyloidiasis was 13.7%, a first report of Strongyloides fuelleborni in UK. We advise regular blanket administration(s) of anthelminthics to the colony, exploring pour-on formulations, thereafter, smaller-scale indicator surveys would be adequate.
The life of enigmatic Wagner conductor, Reginald Goodall, by the author of the acclaimed Thomas Beecham: An Obsession with Music, newly available in paperback.
Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.
Let $F_{\pi }$ be a finite Galois-algebra extension of a number field F, with group G. Suppose that $F_{\pi }/F$ is weakly ramified and that the square root $A_\pi $ of the inverse different $\mathfrak {D}_{\pi }^{-1}$ is defined. (This latter condition holds if, for example, $|G|$ is odd.) Erez has conjectured that the class $(A_\pi )$ of $A_\pi $ in the locally free class group $\operatorname {\mathrm {Cl}}(\mathbf {Z} G)$ of $\mathbf {Z} G$ is equal to the Cassou–Noguès–Fröhlich root number class $W(F_{\pi }/F)$ associated with $F_\pi /F$. This conjecture has been verified in many cases. We establish a precise formula for $(A_\pi )$ in terms of $W(F_{\pi }/F)$ in all cases where $A_\pi $ is defined and $F_\pi /F$ is tame, and are thereby able to deduce that, in general, $(A_\pi )$ is not equal to $W(F_\pi /F)$.
Variation exists in the timing of surgery for balanced complete atrioventricular septal defect repair. We sought to explore associations between timing of repair and resource utilisation and clinical outcomes in the first year of life.
Methods:
In this retrospective single-centre cohort study, we included patients who underwent complete atrioventricular septal defect repair between 2005 and 2019. Patients with left or right ventricular outflow tract obstruction and major non-cardiac comorbidities (except trisomy 21) were excluded. The primary outcome was days alive and out of the hospital in the first year of life.
Results:
Included were 79 infants, divided into tertiles based on age at surgery (1st = 46 to 137 days, 2nd = 140 – 176 days, 3rd = 178 – 316 days). There were no significant differences among age tertiles for days alive and out of the hospital in the first year of life by univariable analysis (tertile 1, median 351 days; tertile 2, 348 days; tertile 3, 354 days; p = 0.22). No patients died. Fewer post-operative ICU days were used in the oldest tertile relative to the youngest, but days of mechanical ventilation and hospitalisation were similar. Clinical outcomes after repair and resource utilisation in the first year of life were similar for unplanned cardiac reinterventions, outpatient cardiology clinic visits, and weight-for-age z-score at 1 year.
Conclusions:
Age at complete atrioventricular septal defect repair is not associated with important differences in clinical outcomes or resource utilisation in the first year of life.
The paper explores the tale of two 'epicentres’ – metropolitan New York and Lombardy – and seeks to depict the socio-demographic patterns that characterise the worst cases of infection, hospitalisation, and death during the first six months of the Covid-19 pandemic in 2020. By drawing upon secondary data concerning sub-territorial units within the two regions – ZIP-code level and counties in New York and municipalities in Italy – the paper compares the characteristics of the two areas in an effort to understand both how they became the original major epicentres and how their experiences of the pandemic differed. We suspected initially that the pandemic in Lombardy was a function of a complex constellation of variables, such as the age of the population, the unexpected emergence of the virus, and features of the local health system. In New York, the pattern seemed to fit a more familiar dynamic, the kind one would expect from the course that most pandemics take: the poor suffer the worst. The paper tries to extend the understanding of the complex and not univocal mix of social variables that can facilitate the spread of a pandemic and make its effects extreme.
There are some distinct methodological challenges, and possible pitfalls, for neuroethics when it evaluates neuroscientific results and links them to issues such as moral or legal responsibility. Some problems emerge in determining the requirements for responsibility. We will show how philosophical proposals in this area need to interact with legal doctrine and practice. Problems can occur when inferring normative implications from neuroscientific results. Other problems arise when it is not recognized that data about brain anatomy or physiology are relevant to the ascription of responsibility only when they are significantly correlated with the psychological capacities contemplated by the legal formulations of responsibility. We will demonstrate this by considering two significant cases concerning psychopathy. Some paradigms that aim at measuring higher-order capacities, such as moral understanding, have limited validity. More robust paradigms for the study of learning in restricted controlled conditions, on the other hand, have limited ecological validity across individuals and context to be of any use for the law.
A chloroacetamide herbicide by application timing factorial experiment was conducted in 2017 and 2018 in Mississippi to investigate chloroacetamide use in a dicamba-based Palmer amaranth management program in cotton production. Herbicides used were S-metolachlor or acetochlor, and application timings were preemergence, preemergence followed by (fb) early postemergence, preemergence fb late postemergence, early postemergence alone, late postemergence alone, and early postemergence fb late postemergence. Dicamba was included in all preemergence applications, and dicamba plus glyphosate was included with all postemergence applications. Differences in cotton and weed response due to chloroacetamide type were minimal, and cotton injury at 14 d after late postemergence application was less than 10% for all application timings. Late-season weed control was reduced up to 30% and 53% if chloroacetamide application occurred preemergence or late postemergence only, respectively. Late-season weed densities were minimized if multiple applications were used instead of a single application. Cotton height was reduced by up to 23% if a single application was made late postemergence relative to other application timings. Chloroacetamide application at any timing except preemergence alone minimized late-season weed biomass. Yield was maximized by any treatment involving multiple applications or early postemergence alone, whereas applications preemergence or late postemergence alone resulted in up to 56% and 27% yield losses, respectively. While no yield loss was reported by delaying the first of sequential applications until early postemergence, forgoing a preemergence application is not advisable given the multiple factors that may delay timely postemergence applications such as inclement weather.
The current COVID-19 pandemic has caused the shortage of personal protective equipment (PPE) where improvised manufacturing in particular 3D printing has addressed many needs. This prospective discusses the current global crisis, then follows the wide interest in addressing the shortage of medical devices and PPEs used for treatment and protection against pathogens. An overview of the 3D printing process with polymer materials is given followed by the different 3D printing projects of PPEs and medical devices that emerged for the pandemic (including validation/testing). The potential for rapid prototyping with different polymer materials and eventual high-throughput production is emphasized.
Classical stewardship efforts have targeted immunocompetent patients; however, appropriate use of antimicrobials in the immunocompromised host has become a target of interest. Cytomegalovirus (CMV) infection is one of the most common and significant complications after solid-organ transplant (SOT). The treatment of CMV requires a dual approach of antiviral drug therapy and reduction of immunosuppression for optimal outcomes. This dual approach to CMV management increases complexity and requires individualization of therapy to balance antiviral efficacy with the risk of allograft rejection. In this review, we focus on the development and implementation of CMV stewardship initiatives, as a component of antimicrobial stewardship in the immunocompromised host, to optimize the management of prevention and treatment of CMV in SOT recipients. These initiatives have the potential not only to improve judicious use of antivirals and prevent resistance but also to improve patient and graft survival given the interconnection between CMV infection and allograft function.