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Patients prescribed higher opioid dosages are at increased risk of overdose and death without added pain reduction. Increases in opioid prescribing continue to fuel the epidemic. We hypothesized a comprehensive guideline to standardize opioid prescribing would decrease postdischarge dosages for patients experiencing trauma without requiring additional refills.This quasiexperimental study compared opioid prescribing by trauma providers before and after the implementation of a departmental guideline on April 1, 2019, aimed at aligning opioid prescription patterns with Centers for Disease Control and Prevention recommendations. Patients prescribed opioids before implementation were the control group, whereas patients prescribed opioids after were the intervention group. The primary outcome was the proportion of patients receiving ≥50 morphine milligram equivalents per day.We identified 293 and 280 patients experiencing trauma in the control and intervention groups, respectively. There were no differences between the groups' Injury Severity Score (P = .69) or the frequency of having a procedure performed (P = .80). Total morphine milligram equivalents and maximum morphine milligram equivalents per day were 16% and 25% lower, respectively, in the intervention group compared with the control group (P.001). The proportion of trauma patients prescribed ≥50 morphine milligram equivalents per day at discharge decreased from 57% to 18% after implementation (P.001). The proportion of trauma patients prescribed ≥90 morphine milligram equivalents per day also decreased, from 37% to 14% (P.001). There was no significant increase in the frequency of refill requests (P = .105) or refill prescriptions (P = .099) after discharge.A departmental guideline aimed at optimizing opioid prescription patterns successfully lowers the amount of morphine milligram equivalents prescribed to trauma patients and improves compliance with Centers for Disease Control and Prevention recommendations.

Civilian extremity trauma with vascular injury carries a significant risk of morbidity, limb loss, and mortality. We aim to describe the trends in extremity vascular injury repair and compare outcomes between trauma and vascular surgeons.We performed a single-center retrospective review of patients 18 years or older with extremity vascular injury requiring surgical intervention between January 2009 and December 2019. Demographics, injury characteristics, operative course, and hospital course were analyzed. Descriptive statistics were used to examine management trends, and outcomes were compared for arterial repairs. Multivariate regression was used to evaluate surgeon specialty as a predictor of complications, readmission, vascular outcomes, and mortality.A total of 231 patients met our inclusion criteria; 80% were male with a median age of 29 years. The femoral vessels were most commonly injured (39.4%), followed by the popliteal vessels (26.8%). Trauma surgeons performed the majority of femoral artery repairs (82%), while vascular surgeons repaired the majority of popliteal artery injuries (84%). Both had a similar share of brachial artery repairs (36% vs. 39%, respectively). There were no differences in complications, readmission, vascular outcomes, and mortality. Median time from arrival to operating room was significantly shorter for trauma surgeons. There was a significant downward trend between 2009 and 2017 in the proportion of total and femoral vascular procedures performed by trauma surgeons. On multivariate regression, surgical specialty was not a significant predictor of need for vascular reintervention, prophylactic or delayed fasciotomies, postoperative complications, or readmissions.Traumas surgeons arrived quicker to the operating and had no difference in short-term clinical outcomes of brachial and femoral artery repairs compared with patients treated by vascular surgeons. Over the last decade, there has been a significant decline in the number of open vascular repairs done by trauma surgeons.Therapeutic/Care Management, Level IV.

The coronavirus disease 2019 (COVID -19) pandemic caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected almost every country in the world, resulting in severe morbidity, mortality and economic hardship, and altering the landscape of healthcare forever. Although primarily a pulmonary illness, it can affect multiple organ systems throughout the body, sometimes with devastating complications and long-term sequelae. As we move into the second year of this pandemic, a better understanding of the pathophysiology of the virus and the varied imaging findings of COVID-19 in the involved organs is crucial to better manage this complex multi-organ disease and to help improve overall survival. This manuscript provides a comprehensive overview of the pathophysiology of the virus along with a detailed and systematic imaging review of the extra-thoracic manifestation of COVID-19 with the exception of unique cardiothoracic features associated with multisystem inflammatory syndrome in children (MIS-C). In Part I, extra-thoracic manifestations of COVID-19 in the abdomen in adults and features of MIS-C will be reviewed. In Part II, manifestations of COVID-19 in the musculoskeletal, central nervous and vascular systems will be reviewed.

Noncommutative K\"ahler structures were recently introduced by the second author as a framework for studying noncommutative K\"ahler geometry on quantum homogeneous spaces. It was subsequently observed that the notion of a positive vector bundle directly generalises to this setting, as does the Kodaira vanishing theorem. In this paper, by restricting to covariant K\"ahler structures of irreducible type (those having an irreducible space of holomorphic one-forms) we provide simple cohomological criteria for positivity, offering a means to avoid explicit curvature calculations. These general results are applied to our motivating family of examples, the irreducible quantum flag manifolds $\mathcal{O}_q(G/L_S)$. Building on the recently established noncommutative Borel-Weil theorem, every covariant line bundle over $\mathcal{O}_q(G/L_S)$ can be identified as positive, negative, or flat, and hence we can conclude that each K\"ahler structure is of Fano type. Moreover, it proves possible to extend the Borel-Weil theorem for $\mathcal{O}_q(G/L_S)$ to a direct noncommutative generalisation of the classical Bott-Borel-Weil theorem for positive line bundles., Comment: 30 pages, 2 tables. Minor changes. To appear in Letters in Mathematical Physics

We explicitly construct and investigate a number of examples of $\mathbb{Z}/p^r$-equivariant formal group laws and complex-oriented spectra, including those coming from elliptic curves and $p$-divisible groups, as well as some other related examples., A first version of this article was written in 2018. The current version, which includes some new material, was accepted for publication in the JHRS

The SARS-CoV-2 envelope (E) protein is a viroporin associated with the acute respiratory symptoms of COVID-19. E forms cation-selective ion channels that assemble in the lipid membrane of the endoplasmic reticulum Golgi intermediate compartment. The channel activity of E is linked to the inflammatory response of the host cell to the virus. Like many viroporins, E is thought to oligomerize with a well-defined stoichiometry. However, attempts to determine the E stoichiometry have led to inconclusive results and suggested mixtures of oligomers whose exact nature might vary with the detergent used. Here, we employ

We study how Turing pattern formation on a growing domain is affected by discrete domain discontinuities. We use the Lengyel–Epstein reaction–diffusion model to numerically simulate Turing pattern formation on radially expanding circular domains containing a variety of obstruction geometries, including obstructions spanning the length of the domain, such as walls and slits, and local obstructions, such as small blocks. The pattern formation is significantly affected by the obstructions, leading to novel pattern morphologies. We show that obstructions can induce growth mode switching and disrupt local pattern formation and that these effects depend on the shape and placement of the objects as well as the domain growth rate. This work provides a customizable framework to perform numerical simulations on different types of obstructions and other heterogeneous domains, which may guide future numerical and experimental studies. These results may also provide new insights into biological pattern growth and formation, especially in non-idealized domains containing noise or discontinuities.

BackgroundNonoperative management of adhesive small bowel obstruction (SBO) is successful in up to 80% of patients. Current recommendations advocate for computed tomography (CT) scan in all patients with SBO to supplement surgical decision-making. The hypothesis of this study was that cumulative findings on CT would predict the need for operative intervention in the setting of SBO.MethodsThis is an analysis of a retrospectively and prospectively collected adhesive SBO database over a 6-year period. A Bowel Ischemia Score (BIS) was developed based on the Eastern Association for the Surgery of Trauma guidelines of CT findings suggestive of bowel ischemia. One point was assigned for each of the six variables. Early operation was defined as surgery within 6 hours of CT scan.ResultsOf the 275 patients in the database, 249 (90.5%) underwent CT scan. The operative rate was 28.3% with a median time from CT to operation of 21 hours (Interquartile range 5.2-59.2 hours). Most patients (166/217, 76.4%) with a BIS of 0 or 1 were successfully managed nonoperatively, whereas the majority of those with a BIS of 3 required operative intervention (5/6, 83.3%). The discrimination (area under the receiver operating characteristic curve) of BIS for early surgery, any operative intervention, and small bowel resection were 0.83, 0.72, and 0.61, respectively.ConclusionThe cumulative signs of bowel ischemia on CT scan represented by BIS, rather than the presence or absence of any one finding, correlate with the need for early operative intervention.

Submitted by Thiago de Oliveira Gonzaga (thiago.gonzaga@fjp.mg.gov.br) on 2022-01-27T23:17:47Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Da percepção do mal como privação do bem à percepção do mal como oportunidade de redenção.pdf: 394941 bytes, checksum: a4d58c108059894640989009ef47161f (MD5) Approved for entry into archive by Renato Lourenço (renato.lourenco@fjp.mg.gov.br) on 2022-01-28T16:22:44Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Da percepção do mal como privação do bem à percepção do mal como oportunidade de redenção.pdf: 394941 bytes, checksum: a4d58c108059894640989009ef47161f (MD5) Made available in DSpace on 2022-01-28T16:22:44Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Da percepção do mal como privação do bem à percepção do mal como oportunidade de redenção.pdf: 394941 bytes, checksum: a4d58c108059894640989009ef47161f (MD5) Previous issue date: 2020 Fundação João Pinheiro Este artigo busca discutir, de forma sucinta, como alguns filósofos judeus refletiram sobre o enigma do mal. Permeado de conflitos e contradições, o pensamento judaico sobre o tema tem sido discutido sob as vertentes ética e metafísica, porém, sempre partindo do pressuposto monoteísta característico do judaísmo. No primeiro apartado, o artigo analisa como Maimônides (1135-1204) afirma a ideia do mal como privação do bem. A segunda parte busca refletir sobre a promessa divina de salvação a partir de algumas ideias de Abraão Isaac Kook (1865-1935) e Joseph Dov Soloveichic (1903-1993). A título de reflexões finais, o artigo defende que a resposta do judaísmo à falta de sentido de uma vida de sofrimentos oculta um plano divino de construção de uma nova realidade apontando para a possibilidade da redenção. This article seeks to discuss, in a succinct way, how some Jewish philosophers have reflected on the enigma of evil. Permeated with conflicts and contradictions, Jewish thinking about evil has been discussed under the ethical and metaphysical aspects, however, always starting from the monotheistic assumption characteristic of Judaism. In the first section, the article analyzes how Maimonides (1135-1204) affirms the idea of evil as a deprivation of good. The second section of the text seeks to reflect on the divine promise of salvation based on some ideas of Abraham Isaac Kook (1865-1935) and Joseph Dov Soloveichic (1903-1993). As a final reflection, the article argues that Judaism's response to the meaninglessness of a life of suffering hides a divine plan for building a new reality pointing to the possibility of redemption. Governo e Política

The clinical utility of intravenous sotalol is limited due to an extended half-life combined with the potential to generate life-threatening arrhythmias. The authors developed a novel sotalol analogue, soestalol, with an ester linkage introduced to the molecule to shorten half-life. Their hypothesis was that soestalol, but not the acid metabolite, would inhibit the hERG potassium current. Whole-cell, voltage-clamp experiments were performed on cells expressing hERG. Soestalol inhibited outward IhERG tail current density in a manner similar to conventional sotalol. Additionally, soestalol right shifted the voltage dependence of activation. These results warrant further assessment of soestalol as a short-acting, Class III antiarrhythmic drug.

Objective Acute decompensated heart failure is often treated with a combination of loop and thiazide-like diuretics. Of these thiazide-like diuretics, two common choices are intravenous chlorothiazide or oral metolazone. Metolazone is more potent and has a longer duration of action, but since it is an oral formulation, it has a longer on-set time as compared to chlorothiazide. In addition, metolazone is poorly water-soluble, thereby rendering intravenous formulation more challenging. To address these issues, we proposed the formulation of a solvent-free metolazone emulsion for intravenous administration. Methods An oil-in-water emulsion containing 1 mg/mL of metolazone was formulated by homogenizing soybean oil and l-lecithin in water in the presence of optimized concentrations of glycerin with tween 80 or poloxamer 188 as surfactant. The emulsion was characterized on the basis of particle size, zeta potential, morphology and metolazone release kinetics. The diuretic effect of the metolazone emulsion was evaluated in rats. Results The 1 mg/mL metolazone emulsion prepared with 5% tween 80 displayed the best physical stability. The emulsion exhibited a hydrodynamic diameter of 157.13±1.52 nm. About 93% of metolazone was released from the formulation within 2 h. The 2 mg/kg and 4 mg/kg dose of the metolazone emulsion increased urine output in the rats by 68.9 and 134%, respectively, as compared to control rats. Furthermore, the 4 mg/kg dose exhibited a 168.8%, 25.8%, and 150.9% increase in sodium, potassium, and chloride, respectively. Conclusion This metolazone emulsion was capable of increasing urine volume output and demonstrated both natriuretic and kaliuretic properties.

Summary paragraphSelective proton transport through proteins is essential for forming and utilizing proton gradients in cells. Protons are conducted along hydrogen-bonded “wires” of water molecules and polar sidechains, which, somewhat surprisingly, are often interrupted by dry apolar stretches in the conduction pathways inferred from static protein structures. We hypothesize that protons are conducted through such dry spots by forming transient water wires, often highly correlated with the presence of the excess proton itself in the water wire. To test this hypothesis, we used molecular dynamics simulations to design transmembrane channels with stable water pockets interspersed by apolar segments capable of forming flickering water wires. The minimalist designed channels conduct protons at rates similar to viral proton channels, and they are at least 106-fold more selective for H+over Na+. These studies inform mechanisms of biological proton conduction and principles for engineering proton-conductive materials.

Graphene oxide (GO), chemically expanded graphite (CEG) and graphite were evaluated as solid lubricant for ultrahigh molecular weight polyethylene composites. Under dry conditions, the addition of all solid lubricants increased the coefficient of friction by up to 38%. For the composites corrugated stick–slip features were observed which correlate with a decrease in matrix degree of crystallinity. GO had the lowest effect on the crystallisation, resulting in the lowest relative increase in friction coefficient of only 13%. Under water lubrication, GO, CEG and graphite were equally effective in reducing friction and wear. The highest friction for the neat matrix was found to be due to a transfer film, which was suppressed by the addition of the solid lubricants. Validerad;2023;Nivå 2;2023-06-26 (hanlid)

Purpose: Hardly any other topic is as current as the gender-conscious medical treatment of every individual. Similarly, in sports, there are crucial differences that should be considered in order to treat everyone appropriately, with the aim to prevent injuries according to their needs. The objective of this study is to show that the differences between biological males and females are so significant that they require both specific injury prevention and therapy programs. Methods: This study is a retrospective analysis of letters from a department of orthopedics and trauma surgery between the years 2000 and 2015. Results: The analysis of 20,567 inpatient and outpatient letters of a level 1 trauma center in Germany revealed that 5455 patients suffered 7279 injuries; 1475 of the patients were female and suffered 2035 injuries, and 3890 patients were male and suffered 5244 injuries. Conclusion: The results show the differences between males and females with regard to sport-specific injuries, pointing out the sex differences in the sport-specific area in relation to the body region.

Resumo A partir de reflexões que analisam o racismo como elemento estruturante do Brasil e de algumas teorias criminológicas, buscamos neste artigo analisar de que forma as questões raciais operam no sistema de justiça criminal. Seguimos os rastros de duas decisões jurídicas que, ao sinalizarem que um réu branco “não possui o estereótipo padrão de bandido” (Tribunal de Justiça de São Paulo [TJSP], 2016) e que um réu negro é “seguramente integrante do grupo criminoso, em razão da sua raça” (Tribunal de Justiça do Paraná [TJPR], 2020), apontaram explicitamente o componente racial como critério de diferenciação. A análise desse mecanismo revela um continuum de práticas e equipamentos, como em abordagens policiais e audiências de custódias, que fixam o sujeito negro no lugar de suspeição e perigo.

We identify the equivariant structure of the filtered pieces of the motivic filtration defined by Bhatt, Morrow and Scholze on the topological Hochschild cohomology spectrum of polynomial algebras over $\mathbb{F}_p$., Comment: accepted for publication in the Advances in Mathematics

Background: Sotalol is often employed to prevent recurrence of symptomatic atrial flutter/atrial fibrillation. Because sotalol can prolong the QT interval excessively causing ventricular arrhythmias, a 3-day in-hospital loading or dose escalation period is mandated with oral administration in the product label for patient safety. In patients with normal renal function, 3 days (five oral doses) are required to obtain steady state maximum sotalol concentration, which results in maximum QT prolongation. The aim of this study is to develop an intravenous to oral loading regime for sotalol therapy that reduces the 3-day in-hospital initiation or dose escalation with oral administration to 1 day without compromising patient safety. Methods: Using model-informed drug development techniques, simulations were developed for initiation and dose escalation of sotalol therapy by employing an intravenous loading dose followed by oral sotalol administrations. Results: In patients with normal renal function, an initial 1-h loading dose of intravenous sotalol followed by two oral doses in 24 h has been developed permitting attainment of three maximum serum concentrations reflecting maximum QT prolongation in a 1-day observation period. Dosing regimens for patients with impaired renal function are also developed. Conclusions: In patients with normal renal function, using an intravenous loading dose followed by oral administrations permits safe initiation or dose escalation of sotalol in 1 day instead of the 3-day dosing regimen with oral administration. Cardiol Res. 2020;11(5):294-304 doi: https://doi.org/10.14740/cr1143

Rib fractures are associated with increased mortality, particularly in the elderly. While opiate-based pain regimens remain the cornerstone of rib fracture management, issues related to opioids have driven research into alternative analgesics. Adjunctive ketamine use in lieu of opioids continues to increase but little evidence exists to support its efficacy or safety within the elderly trauma population.A prospective, randomized, double-blind placebo-controlled trial of elderly patients (age, ≥65 years) with three or more rib fractures admitted to a Level I trauma center was conducted. Exclusion criteria included Glasgow Coma Scale score less than 14, and chronic opiate use. Groups were randomized to either low-dose ketamine (LDK) at 2 μg·kg·min or an equivalent rate of 0.9% normal saline. The primary outcome was reduction in numeric pain scores (NPS). Secondary outcomes included oral morphine equivalent (OME) utilization, epidural rates, pulmonary complications, and adverse events.Thirty (50.8%) of 59 were randomized to the experimental arm. Groups were similar in makeup. Low-dose ketamine failed to reduce 24-hour NPS or OME totals. Subgroup analysis of 24 patients with Injury Severity Score greater than 15 demonstrated that LDK was associated with a reduction in OME utilization the first 24-hours (25.6 mg vs. 42.6 mg, p = 0.04) but at no other time points. No difference in other secondary outcomes or adverse events was noted.Low-dose ketamine failed to affect NPS or OME within the overall cohort, but a decrease in OME was observed in those with an Injury Severity Score greater than 15. Additional studies are necessary to confirm whether LDK benefits severely injured elderly patients.Therapeutic, level I.

We give examples of reducible characteristic cycles for irreducible Harish-Chandra modules for U(p, q) by analyzing a four-dimensional singular subvariety of C8. We relate this singularity ...

Objectives To examine pediatricians' perspectives on administrative tasks including electronic health record (EHR) documentation burden and their effect on work–life balance and life and career satisfaction. Methods We analyzed 2018 survey data from the American Academy of Pediatrics (AAP) Pediatrician Life and Career Experience Study (PLACES), a longitudinal cohort study of early and midcareer pediatricians. Cohorts graduated from residency between 2002 and 2004 or 2009 and 2011. Participants were randomly selected from an AAP database (included all pediatricians who completed U.S. pediatric residency programs). Four in 10 pediatricians (1,796 out of 4,677) were enrolled in PLACES in 2012 and considered participants in 2018. Data were weighted to adjust for differences between study participants and the overall population of pediatricians. Chi-square and multivariable logistic regression examined the association of EHR burden on work–life balance (three measures) and satisfaction with work, career, and life (three measures). Responses to an open-ended question on experiences with administrative tasks were reviewed. Results A total of 66% of pediatrician participants completed the 2018 surveys (1,192 of 1,796; analytic sample = 1,069). Three-fourths reported EHR documentation as a major or moderate burden. Half reported such burden for billing and insurance and 42.7% for quality and performance measurement. Most pediatricians reported satisfaction with their jobs (86.7%), careers (84.5%), and lives (66.2%). Many reported work–life balance challenges (52.5% reported stress balancing work and personal responsibilities). In multivariable analysis, higher reported EHR burden was associated with lower scores on career and life satisfaction measures and on all three measures of work–life balance. Open-ended responses (n = 467) revealed several themes. Two predominant themes especially supported the quantitative findings—poor EHR functionality and lack of support for administrative burdens. Conclusion Most early to midcareer pediatricians experience administrative burdens with EHRs. These experiences are associated with worse work–life balance including more stress in balancing responsibilities and less career and life satisfaction.

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected almost every country in the world resulting in severe morbidity, mortality and economic hardship, altering the landscape of healthcare forever. Its devastating and most frequent thoracic and cardiac manifestations have been well reported since the start of the pandemic. Its extra-thoracic manifestations are myriad and understanding them is critical in diagnosis and disease management. The role of radiology is growing in the second wave and second year of the pandemic as the multiorgan manifestations of COVID-19 continue to unfold. Musculoskeletal, neurologic and vascular disease processes account for a significant number of COVID-19 complications and understanding their frequency, clinical sequelae and imaging manifestations is vital in guiding management and improving overall survival. The authors aim to provide a comprehensive overview of the pathophysiology of the virus along with a detailed and systematic imaging review of the extra-thoracic manifestation of COVID-19. In Part I, abdominal manifestations of COVID-19 in adults and multisystem inflammatory syndrome in children will be reviewed. In Part II, manifestations of COVID-19 in the musculoskeletal, central nervous and vascular systems will be reviewed.

Immunogenic cell death (ICD) is a form of apoptosis that kills susceptible populations of cancer cells while teaching the immune system to attack the remaining resistant cells. Chemotherapeutics which induce ICD elicit their immune response by inducing tumor cells to display or release damage-associated molecular patterns (DAMPs). There are two key biomarkers for ICD: 1) during the apoptotic process, tumor cells secrete ATP (extracellular ATP or eATP) and 2) during secondary necrosis, tumor cells release HMGB1 (high mobility group box 1). Because the dying tumor cells display these DAMP molecules, they stimulate the recruitment of dendritic cells (DCs) into the tumor bed and ultimately “teach” cytotoxic T-lymphocytes (CTLs) to respond to these tumor specific antigens. These primed CTLs will then kill additional tumor cells through a direct cytotoxic response. Therefore, therapeutics which provoke an ICD response offer a therapeutically desirable outcome for cancer therapy. Current assay methods such as ELISA assays and flow cytometry for measuring these ICD biomarkers are laborious and involve multiple transfer and wash steps. We have developed homogeneous (no wash), single addition assays for measuring the two principle ICD biomarkers. The eATP assay uses optimized luciferase detection chemistry that is applied directly to live cells to measure ATP release over 24 hours. The HMGB1 assay uses a complementary luciferase fragment-labeled antibody approach to measure protein concentration. We demonstrated the use of these two assays with model systems for inducing Immunogenic Cell Death with human and murine cell lines including U2OS, EL4, and U937 cells. The potency and response magnitude of ICD-inducing compounds including doxorubicin, idarubicin and mitoxantrone differs depending on the model cell line used. Further, the timing of extracellular ATP release and HMGB1 release differs between cell lines and inducers. Improved assays to measure two markers of Immunogenic Cell Death will expedite the discovery and development of inducers of Immunogenic Cell Death, including small molecule therapeutics, oncolytic viruses, radiation therapy and other novel therapeutics, by streamlining the workflow, increasing sample throughput and providing real time live cell data. Citation Format: Richard L. Somberg, Kevin Kupcho, Andrew Niles, James Cali. Detection ofHMGB1 and extracellular ATP for the assessment of immunogenic cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1112.

The publication of this article unfortunately contained a mistake. A grant number in the acknowledgements was not correct, instead of GACR 306 − 33/1906357 it should be GA19-06357S

In the midst of a pandemic, serologic studies are a valuable tool to understand the course of the outbreak and guide public health and general pandemic management. However, given significant safety constraints including social distancing and stay-at-home orders, sample collection becomes more difficult given traditional phlebotomy protocols. For such studies, a representative sample of the underlying population is paramount to elicit meaningful insights that capture the spread of the infection, particularly when different sub-populations face varying disease burden. We aimed to address these challenges by conducting a fully remote study to investigate the seroprevalence of SARS-CoV-2 in the state of Massachusetts. Leveraging electronic study engagement and at-home self-collection of finger-prick samples, we enrolled 2,066 participants representative of the ethnic and racial composition of Massachusetts. SARS-CoV-2 total IgG seropositivity was 3.15%, and follow-up measurements at days 7, 15, 45, and 90 indicate a generally durable antibody response. A higher risk of infection was observed for healthcare workers and their cohabitants and those with comorbidities, as well as lower-income, less educated, Hispanic, and those in the age groups of 18-29 and 50-59-years-old. High engagement and positive feedback from the participants and quality of self-collected specimens point to the usefulness of this design for future population-level serological studies that more effectively and safely reach a broad representative cohort, thus yielding more comprehensive insights into the burden of infection and disease in populations.Key pointsQuestionWe aimed to implement a fully remote seroprevalence study for SARS-CoV-2, leveraging electronic methods and at-home self-collection of specimens to engage a representative study population.FindingsThe population enrolled reflected the ethnic and racial composition of Massachusetts, revealing a SARS-CoV-2 seroprevalence of 3.15% and higher risk of previous infection associated with healthcare workers/their cohabitants, those with comorbidities, lower-income, less educated, Hispanic, and those in age groups 18-29 and 50-59 years old.MeaningHigh engagement and positive feedback from participants as well as quality of self-collected specimens point to the usefulness of this design for future population-level serological studies.

Introduction: Various mathematical equations have been proposed to correct QT interval for heart rate (QTc). However, with most formulas, QTc remains dependent on heart rate (HR) especially at low and high HR values. Hypothesis: A spline correction function would perform better than standard mathematical formulas by allowing the data to determine the form of the relationship. Methods: A series of regression models using the generalized additive models for location, scale, and shape framework was applied to 10,000 completely normal electrocardiogram data from the National Health and Nutrition Examination Surveys II and III. Evaluation of the model’s performance was performed using the R 2 coefficient of determination and the root mean squared of the errors between the predicted and observed QTc. The new regression models were compared to the Bazett’s and Fredericia’s formulas, which are the 2 most widely used formulas in clinical practice. Results: When boxplots of the QTc for each formula are plotted, grouped by HR in intervals of 5 beats/minute, QTc determined by the penalized spline regression was almost heart rate independent for both male and female as the slope of the regression line was almost zero (-0.003 for female and -0.001 for male) (Figure 1 A—B). By contrast, QTc by Bazett had a positive correlation (regression slope of 0.86 for female and 0.89 for male) while Fredericia’s had a negative correlation (regression slope of -0.14 for female and -0.13 for male) with HR (Figure 1C—F). In all 3 formulas, there was no significant difference between male and female. Conclusions: A new QTc formula was developed, which is almost independent of HR thereby providing a more accurate estimate of QTc for clinical management. Automatic QTc calculation and percentiles estimation could easily be incorporated in an online calculator or app for easy integration in everyday clinical practice.

Bretylium is the only drug approved by the FDA specifically to terminate ventricular fibrillation (VF). It has also been approved to treat life threatening ventricular tachycardia (VT) as a second line agent. Due to shortage of drug substance, bretylium became unavailable for clinical use and has been dropped from ACLS guidelines in 2000. Recently, intravenous (IV) bretylium became available again in the U.S. This study evaluated the efficacy of bretylium IV in the termination of treatment resistant VT and VF. In 4 studies, a total of 85 patients with sustained VT and/or VF were administered IV bretylium 5 mg/kg: 23 patients had VT and 62 had VF. Resistant VT/VF was defined as VT or VF that could not be terminated by shock or other anti-arrhythmics or recurred before bretylium was administered. All patients received IV lidocaine; 71 received between 1 to 5 additional antiarrhythmics, and all patients with VF received DC shocks and failed all pharmacologic therapies prior to bretylium administration. Overall, 61 patients (72%) were successfully treated with IV bretylium and 31 survived to discharge from the hospital (36%). A meta-analysis of these studies indicates that the weighted conversion rate across the studies was 70% (see figure). The only study that compared IV bretylium and amiodarone did not find superiority of amiodarone in the suppression of hemodynamically destabilizing VT or VF. In patients with resistant VT or VF bretylium is reported to be effective in acute termination of the VT or VF that otherwise was not responsive to shock or other anti-arrhythmic drugs. These results suggest that bretylium should be employed in the pharmacotherapy of VT and VF when DC shock or other anti-arrhythmic drugs fail. The studies this report is based on are small studies and thus there is a need for a large controlled clinical trial to provide a better understanding of bretyliums effectiveness and if a higher than 30 mg/kg dose of bretylium would be more effective.

Sotalol is frequently employed to prevent the recurrence of highly symptomatic atrial fibrillation or flutter, but recurrence is not unusual and may require dose escalation. Sotalol can cause QTc prolongation proportional to blood concentration and at times may cause Torsade de Pointes ventricular tachycardia (TdP). Because the risk of TdP, dose escalation of oral sotalol therapy is mandated by FDA to be in-hospital for a minimum of 3 days under ECG monitoring with facilities and personnel able to provide cardiac resuscitation. With oral administration (bid), 3 days are needed to reach the new maximal steady-state blood concentrations (Cmax ss) and thus maximal QTc . Three hospital days in a telemetry bed is costly of time and resources. IV sotalol makes it possible to reduce the escalation time from 3 days to 1 day. The IV to oral dose escalation has been developed by model informed drug development. Serum sotalol concentrations and corresponding QTc were obtained from a bioequivalence study in healthy volunteers who received a single dose of oral and IV sotalol. NONMEM software package was used for population pharmacokinetic modeling and simulation. First Order Conditional Estimation method with Interaction (FOCE-INTER) was used for computation. We chose to administer IV sotalol over 1 hour to obtain the new Cmax ss target in a timeframe convenient for medical staff to supervise. Simulation for dose escalation from 80 to 120 mg bid is shown in the Figure; 75 mg IV sotalol is administered over 1 hour followed by 120 mg oral sotalol at 5 hours from start of infusion, then a second oral dose of 120 mg at 12 hours. One can target escalation from 120 to 160 mg by loading 90 mg IV over 1 hr followed by 160 mg oral dosing. Sotalol concentration will peak in 2-4 hours following each oral administration, thus in 21 hour there will be 3 sotalol peak concentrations. This permits evaluation of QTc response and risk of TdP all within a 1 day admission.

We set up foundations of representation theory over S, the sphere spectrum, which is the “initial ring” of stable homotopy theory. In particular, we treat S-Lie algebras and their representations, characters, g l n ( S ) -Verma modules and their duals, Harish-Chandra pairs and Zuckermann functors. As an application, we construct a Khovanov s l k -stable homotopy type with a large prime hypothesis, which is a new link invariant, using a stable homotopy analogue of the method of J. Sussan.

We investigate certain adjunctions in derived categories of equivariant spectra, including a right adjoint to fixed points, a right adjoint to pullback by an isometry of universes, and a chain of two right adjoints to geometric fixed points. This leads to a variety of interesting other adjunctions, including a chain of 6 (sometimes 7) adjoints involving the restriction functor to a subgroup of a finite group on equivariant spectra indexed over the trivial universe., Accepted for publication in Algebraic and Geometric Topology

RESUMOO texto foca os cursos de capacitação oferecidos pela Fundação João Pinheiro do estado Minas Gerais cuja finalidade é aperfeiçoar e atualizar servidores e cidadãos interessados nos temas da administração pública. O trabalho é um estudo teórico relativo às metodologias ativas educacionais e sobre a possibilidade de aplicação de algumas de suas estratégias no âmbito da Gerência de Capacitação e Treinamento (GCT) da referida Instituição. Inicialmente, o texto discute o conceito de metodologias ativas educacionais e sintetiza alguns de seus pressupostos. Na sequência são indicadas técnicas de metodologias ativas aplicáveis aos cursos da GCT. A título de conclusão, o estudo defende os fundamentos das metodologias ativas ressaltando, no entanto, que a escolha da metodologia a ser adotada deve levar em conta as necessidades dos sujeitos envolvidos no processo de ensino-aprendizagem.Metodologias Ativas de Aprendizagem. Cursos de Capacitação. Competências Contemporâneas. ABSTRACTThe text focuses on training courses offered by the João Pinheiro Foundation in the state of Minas Gerais, whose purpose is to improve and update civil servants and citizens interested in administration public issues. The work is a theoretical study about educational methodologies and about the possibility of applying some of its strategies within the scope of the Capacity Building and Training Management (GCT) of that institution. Initially, the text discusses the concept of active educational methodologies and summarizes some of its assumptions. Following, techniques of active methodologies applicable to GCT courses are indicated. As a conclusion, the study defends the foundations of active methodologies, emphasizing, however, that the choise of the methodology to be adopted must take into account the needs of the subjects involved in the teaching-learning process.Active Learning Methodologies. Training courses. Contemporary skills. RESUMENEl texto se centra en los cursos de capacitación ofrecidos por la Fundación João Pinheiro en el estado de Minas Gerais, cuyo propósito es mejorar y actualizar a los funcionarios y ciudadanos interesados en temas de administración pública. El trabajo es un estudio teórico sobre metodologías educativas activas y sobre la posibilidad de aplicar algunas de sus estrategias en el ámbito de la Gestión de Capacitación y Capacitación (GCT) de la mencionada institución. Inicialmente, el texto discute el concepto de metodologías educativas activas y sintetiza algunos de sus supuestos. A continuación, se indican las técnicas de metodología activa aplicables a los cursos de GCT. En conclusión, el estudio defiende los fundamentos de las metodologías activas, enfatizando, sin embargo, que la elección de la metodología a adoptar debe tener en cuenta las necesidades de los sujetos involucrados en el proceso de enseñanza-aprendizaje.Metodologías de aprendizaje activo. Cursos de formación. Habilidades contemporáneas.

To mitigate the effects of downstream lubricant spillage from hydroelectric power plants, environmentally friendly lubricants are required. For the sustainable operation of oil-free bearings, the development of high performance bearing materials is crucial. In this study, the tribological performance of PPS and UHMWPE-based composites, incorporating various reinforcements, such as graphene oxide, is evaluated and compared with five commercial materials. Experiments were performed under different lubricating conditions; Dry, water, and using a glycerol-based environmentally adaptive lubricant (EAL). The use of water inhibited an adequate transfer film, which increased wear for most materials. EAL lubrication showed a significant reduction in friction (up to 98%) when compared to dry conditions. The experimentally developed PPS composite provided superior tribological properties, especially under water-lubricated conditions.

Background Pediatric subspecialty fellowships are common pathways for graduating pediatric residents. While some subspecialties continue to grow, others struggle to fill their spots. Objective Examine factors of importance in residency graduates’ decision to pursue fellowship by resident characteristics. Methods A random sample of 1000 residency graduates across the US via the 2019 AAP Annual Survey of Graduating Residents were surveyed. Residents were asked about their plans after residency and importance of 12 factors in the decision to pursue their specific fellowship. Chi-square examined variations in importance by gender, children, medical school location, debt, location of residency training and program size. Results 504 (51%) responded. 189 (38%) reported they would be starting pediatric subspecialty fellowships following residency. Future job opportunities and interest in specific disease/organ system were the 2 highest rated factors, with most reporting them as essential or very important (90% and 88%, respectively). Other important factors included subspecialty exposure and mentorship during residency. Factors with the lowest ratings were ability to stay at same institution and education debt, with 1/3 reporting essential or very important. No variation in importance was found by gender, region and program size; few were found by medical school location and debt. Most variation was found among residents with children. E.g., residents with children were more likely than those without to report family considerations and control over work hours as essential/very important (86% vs 48%, p Conclusion Four in 10 graduating residents report starting fellowship training after residency. Residents prioritize factors important in choosing their subspecialty similarly across gender, region and program size, with top factors being job opportunities and interest in specific disease/organ systems. Family considerations and control over work hours are particularly important for residents with children. Understanding of these factors is critical in advising and recruiting trainees into fellowship.