Patient Education: Sodium Awareness in Bomoseen, VT

Many patients in the outpatient setting are placed on diets with sodium restrictions by their primary care physician for management of a variety of chronic diseases. Patients often have difficulties adhering to these diets, a primary reason being unawareness of the sodium content of many foods that make up the American diet. This project aims to increase awareness for these patients and to provide education for them to make more informed decisions about their health. A poster was made for providers to display in their practice that illustrates the sodium content of various food groups. The foods were selected based on recommendations and research from the CDC and American Heart Association. Future evaluation of the efficacy of this project would be elicited by a patient and provider questionnaire after the posters have been displayed for 6 months or more. This questionnaire could then be used to modify the posters to better fit this specific population and assist providers in this facet of patient education.https://scholarworks.uvm.edu/fmclerk/1332/thumbnail.jp

Patient Perspectives on Medication Assisted Therapy in Vermont

Introduction. Medication-Assisted Therapy (MAT) for opioid addiction has dramatically increased in Vermont, supported by a novel statewide system that integrates specialty treatment centers ( Hubs ) with primary care office-based opioid therapy ( Spokes ). In 2010, Vermont had the highest per capita buprenorphine use in the US. Previous studies of patient perspectives of MAT have identified social barriers, rigid program rules, and concerns about withdrawal and relapse as common causes of treatment failure. Our goal was to elicit patient perspectives on barriers and enablers of successful MAT to further inform system refinement. Methods. An interview guide was developed based on previous literature as well as discussions with program leadership, staff and clinicians, and community stakeholders. Responses were organized using thematic content analysis with consensus across seven interviewers and two analysts. The interviews were conducted with 44 patients enrolled in MAT at two Hub sites in Burlington, VT in October 2016. Results. The median age of subjects was 34 years, 34% were employed at least part-time, and 72% were female. Half reported a mental health condition and 20% reported chronic pain. Barriers included transportation (25%), lack of stable housing, and stigma (41%). Enablers included feeling supported (82% felt well-supported; 52% felt supported by healthcare professionals). Subjects expressed high confidence in the treatment system and high self-efficacy for sobriety. Conclusions. Patients in MAT have complex medical, mental health, social, personal, and work lives. A comprehensive system that addresses this wide range of domains is critical to achieving optimal outcomes.https://scholarworks.uvm.edu/comphp_gallery/1245/thumbnail.jp

Tumour regression and improved gastrointestinal tolerability from controlled release of SN-38 from novel polyoxazoline-modified dendrimers

Irinotecan is used clinically for the treatment of colorectal cancer; however, its utility is limited by its narrow therapeutic index. We describe the use of a generation 5 l-lysine dendrimer that has been part-modified with a polyoxazoline as a drug delivery vehicle for improving the therapeutic index of SN-38, the active metabolite of irinotecan. By conjugating SN-38 to the dendrimer via different linker technologies we sought to vary the release rate of the drug to generate diverse pharmacokinetic profiles. Three conjugates with plasma release half-lives of 2.5 h, 21 h, and 72 h were tested for efficacy and toxicity using a mouse SW620 xenograft model. In this model, the linker with a plasma release half-life of 21 h achieved sustained SN-38 exposure in blood, above the target concentration. Control over the release rate of the drug from the linker, combined with prolonged circulation of the dendrimer, enabled administration of an efficacious dose of SN-38, achieving significant regression of the SW620 tumours. The conjugates with 2.5 and 72 h release half-lives did not achieve an anti-tumour effect. Intraperitoneal dosing of the clinically used prodrug irinotecan produces high initial and local concentrations of SN-38, which are associated with gastrointestinal toxicity. Administration of the 21 h release dendrimer conjugate did not produce a high initial Cmax of SN-38. Consequently, a marked reduction in gastrointestinal toxicity was observed relative to irinotecan treatment. Additional studies investigating the dose concentrations and dose scheduling showed that a weekly dosing schedule of 4 mg SN-38/kg was the most efficacious regimen. After 4 doses at weekly intervals, the survival period of the mice extended beyond 70 days following the final dose. These extensive studies have allowed us to identify a linker, dose and dosing regimen for SN-38 conjugated to polyoxazoline-modified dendrimer that maximised efficacy and minimised adverse side effects

Appalachian Spring

A large mural that was created by 19 studio art and education students in 2009. Renowned Latina artist Judith Baca worked alongside the students.https://scholarworks.moreheadstate.edu/university_art_collection/1090/thumbnail.jp

Out of Their Depth? Isolated Deep Populations of the Cosmopolitan Coral Desmophyllum dianthus May Be Highly Vulnerable to Environmental Change

Deep sea scleractinian corals will be particularly vulnerable to the effects of climate change, facing loss of up to 70% of their habitat as the Aragonite Saturation Horizon (below which corals are unable to form calcium carbonate skeletons) rises. Persistence of deep sea scleractinian corals will therefore rely on the ability of larvae to disperse to, and colonise, suitable shallow-water habitat. We used DNA sequence data of the internal transcribed spacer (ITS), the mitochondrial ribosomal subunit (16S) and mitochondrial control region (MtC) to determine levels of gene flow both within and among populations of the deep sea coral Desmophyllum dianthus in SE Australia, New Zealand and Chile to assess the ability of corals to disperse into different regions and habitats. We found significant genetic subdivision among the three widely separated geographic regions consistent with isolation and limited contemporary gene flow. Furthermore, corals from different depth strata (shallow <600 m, mid 1000–1500 m, deep >1500 m) even on the same or nearby seamounts were strongly differentiated, indicating limited vertical larval dispersal. Genetic differentiation with depth is consistent with the stratification of the Subantarctic Mode Water, Antarctic Intermediate Water, the Circumpolar Deep and North Pacific Deep Waters in the Southern Ocean, and we propose that coral larvae will be retained within, and rarely migrate among, these water masses. The apparent absence of vertical larval dispersal suggests deep populations of D. dianthus are unlikely to colonise shallow water as the aragonite saturation horizon rises and deep waters become uninhabitable. Similarly, assumptions that deep populations will act as refuges for shallow populations that are impacted by activities such as fishing or mining are also unlikely to hold true. Clearly future environmental management strategies must consider both regional and depth-related isolation of deep-sea coral populations

Tidal Heating: Lessons from Io and the Jovian System - Final Report

Tidal heating is key to the evolution and habitability of many worlds across our solar system and beyond. However, there remain fundamental gaps in our understanding of tidal heating and coupled orbital evolution, which motivated a Keck Institute for Space Studies (KISS) workshop on this topic. The Cassini mission has led to many recent results about ocean worlds and what may become a new paradigm for understanding orbital evolution with tidal heating, the model of resonance locking in the parent planet (Fuller et al., 2016). Resonance locking explains how subsurface oceans may persist over much of geologic time, even in tiny Enceladus. The discovery of the Laplace resonance of Io, Europa, and Ganymede orbiting Jupiter led to the prediction of intense tidal heating of Io (Peale et al., 1979); this system provides the greatest potential for advances in the next few decades. Europa Clipper and JUpiter ICy moons Explorer (JUICE) will provide in-depth studies of Europa and Ganymede in the 2030s. The easily observed heat flow of Io, from hundreds of continually erupting volcanoes, makes it an ideal target for further investigation, and the missing link—along with missions in development—to understand the Laplace system. We identified five key questions to drive future research and exploration: (Q1) What do volcanic eruptions tell us about the interiors of tidally heated bodies (e.g., Io, Enceladus, and perhaps Europa and Triton)? (Q2) How is tidal dissipation partitioned between solid and liquid materials? (Q3) Does Io have a melt-rich layer, or “magma ocean”, that mechanically decouples the lithosphere from the deeper interior? (Q4) Is the Jupiter/Laplace system in equilibrium (i.e., does the satellite’s heat output equal the rate at which energy is generated)? (Q5) Can stable isotope measurements inform long-term evolution of tidally heated bodies? The most promising avenues to address these questions include a new spacecraft mission making close flybys of Io, missions orbiting and landing on key worlds such as Europa and Enceladus, technology developments to enable advanced techniques, closer coupling between laboratory experiments and tidal heating theory, and advances in Earth-based telescopic observations of solar system and extrasolar planets and moons. All of these avenues would benefit from technological developments. An Io mission should: characterize volcanic processes (Q1); test interior models via a set of geophysical measurements coupled with laboratory experiments and theory (Q2 and Q3); measure the rate of Io’s orbital migration (to complement similar measurements expected at Europa and Ganymede) to determine if the Laplace resonance is in equilibrium (Q4); and determine neutral compositions and measure stable isotopes in Io’s atmosphere and plumes (Q5). No new technologies are required for such an Io mission following advances in radiation design and solar power realized for Europa Clipper and JUICE. Seismology is a promising avenue for future exploration, either from landers or remote laser reflectometry, and interferometric synthetic aperture radar (InSAR) could be revolutionary on these active worlds, but advanced power systems plus lower mass and power-active instruments are needed for operation in the outer solar system

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Law Enforcement Response to Crime in Tennessee: Incident Clearance Rates in Rural vs Nonrural Counties

Incident clearance rates are calculated by dividing the total number of crime occurrences by those solved by police in a given area. While these percentages are commonly used as a measure of law enforcement effectiveness, they are largely influenced by geographic size, economy, and cultural factors. For instance, rural police tend to have fewer financial resources and may not have sufficient personnel and technology to investigate certain criminal offenses. Rural communities also tend to be more close-knit, have stronger social ties, and residents often know one another, which can influence reporting rates and police strategies. Improving our understanding of clearance rates across rural and urban counties is necessary to increase the effectiveness of location-specific law enforcement practices. Data for the present study were obtained from the Tennessee Incident Based Reporting System for reported incidents of crimes against persons and subsequent clearance rates in 2015. Whether an incident was cleared by arrest, cleared by exceptional reasons, or not cleared was noted. Exceptional clearances refer to situations where an offender died prior to being arrested, a prosecutor declined a case, extradition was denied, a victim refused to cooperate, or a juvenile was responsible for the incident. Using the 2013 Rural Urban Continuum Codes (RUCC), counties were categorized based on geographic size and proximity to metropolitan areas, Tennessee\u27s 95 counties were grouped into metropolitan counties (RUCC codes 1-3; n = 42), nonmetropolitan counties with an urban population (RUCC codes 4-7; n = 37), and completely rural counties or those with a population of less than 2,500 (RUCC codes 8-9; n = 16). Preliminary ANOVA analyses with post hoc comparisons using the Bonferroni test suggest that rural counties (M=73.0%, SD=18.1) had higher incidence clearance rates [F(2,92) = 4.19, p = .018], compared to both metropolitan counties (M=61.1%, SD=14.3, p =.024) and nonmetropolitan counties with urban populations greater than 2,500 (M=61.2%, SD=14.2, p =.029). Similarly, rural counties (M=71.9%, SD=18.3) had significantly higher rates of clearance by arrest [F(2,92) = 9.29, p = .000] than metropolitan counties (M=51.5%, SD=14.9, p =.000) and nonmetropolitan counties with urban populations greater than 2,500 (M=55.7%, SD=16.6, p =.004). In contrast, a nonparametric Kruskal-Wallis one-way ANOVA test yielded insignificant differences across the three groups with regard to exceptional clearance rates [F(2,74) = 5.79, p = .055]. Thus, initial findings reveal that overall clearance and clearance by arrest rates in rural areas differ from more urban locations. Additional analyses regarding county-level differences in incidence clearance rates across various types of offenses will be explored. Possible factors that may contribute to discrepancies across counties and future directions will be discussed