Challenges and Success Factors in Nonprofit Arts Organization Mergers

Negative repercussions of the COVID-19 pandemic have prompted a heightened surge of interest in mergers in recent years. Despite the interest, one finds a longstanding paucity of analytical attention on mergers between arts organizations ("arts mergers"). This study presents a comparative case study of two arts mergers involving a total of five performing arts organizations in the United States. By employing grounded theory, this study identified an array of challenges involved in the implementation of arts mergers and the factors that assist a successful implementation. Findings of this study inform a new set of critical considerations for arts mergers and suggest applicable implications for arts and nonprofit management at large. In essence, this study testifies the significance of retaining the artistic identities and assets of all organizations involved in an arts merger and the necessity of merger-related support from outside sources in actualizing merger implementation. Findings testify merits of mergers in increasing artistic and financial capacity of arts organizations also.

SARS-CoV-2 Nsp13 Catalytic Efficiency is Regulated by ATP: Mg2+ Stoichiometry and Functional Cooperativity Among Nsp13 Molecules

Coronavirus disease 19 (COVID-19) is a highly contagious and lethal disease caused by the SARS-CoV-2 positive-strand RNA virus. Nonstructural protein 13 (Nsp13) is the highly conserved ATPase/helicase required for replication of the SARS-CoV-2 genome which allows for the infection and transmission of COVID-19. We biochemically characterized the purified recombinant SARS-CoV-2 Nsp13 helicase protein expressed using a eukaryotic cell-based system and characterized its catalytic functions, focusing on optimization of its reaction conditions and assessment of functional cooperativity among Nsp13 molecules during unwinding of duplex RNA substrates. These studies allowed us to carefully determine the optimal reaction conditions for binding and unwinding various nucleic acid substrates. Previously, ATP concentration was suggested to be an important factor for optimal helicase activity by recombinant SARS-CoV-1 Nsp13. Apart from a single study conducted using fixed concentrations of ATP, the importance of the essential divalent cation for Nsp13 helicase activity had not been examined. Given the importance of the divalent metal ion cofactor for ATP hydrolysis and helicase activity, we assessed if the molar ratio of ATP to Mg2+ was important for optimal SARS-CoV-2 Nsp13 RNA helicase activity. We determined that Nsp13 RNA helicase activity was dependent on ATP and Mg2+ concentrations with an optimum of 1 mM Mg2+ and 2 mM ATP. Next, we examined Nsp13 helicase activity as a function of equimolar ATP:Mg2+ ratio and determined that helicase activity decreased as the equimolar concentration increased, especially above 5 mM. We determined that Nsp13 catalytic functions are sensitive to Mg2+ concentration suggesting a regulatory mechanism for ATP hydrolysis, duplex unwinding, and protein remodeling, processes that are implicated in SARS-CoV-2 replication and proofreading to ensure RNA synthesis fidelity. Evidence is presented that excess Mg2+ impairs Nsp13 helicase activity by dual mechanisms involving both allostery and ionic strength. In addition, using single-turnover reaction conditions, Nsp13 unwound partial duplex RNA substrates of increasing doublestranded regions (16-30 base pairs) with similar kinetic efficiency, suggesting the enzyme unwinds processively in this range under optimal reaction conditions. Furthermore, we determined that Nsp13 displayed sigmoidal behavior for helicase activity as a function of enzyme concentration, suggesting that functional cooperativity and oligomerization are important for optimal activity. The observed functional cooperativity of Nsp13 protomers suggests the essential coronavirus RNA helicase has roles in RNA processing events beyond its currently understood involvement in the SARS-CoV-2 replication-transcription complex (RTC), in which it was suggested that only one of the two Nsp13 subunits has a catalytic function, whereas the other has only a structural role in complex stability. Altogether, the intimate regulation of Nsp13 RNA helicase by divalent cation and protein oligomerization suggests drug targets for modulation of enzymatic activity that may prove useful for the development of novel anti-coronavirus therapeutic strategies. This work was supported by the Intramural Training Program, National Institute on Aging (NIA), NIH, and a Special COVID-19 Grant from the Office of the Scientific Director, NIA, NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

The SARS-CoV-2 Nsp13 Helicase Required for Coronavirus Replication Interacts with Structured Nucleic Acids in a Strand-Specific Manner and Catalyzes a Novel Protein-RNA Remodeling Activity Implicated in the Proofreading Mechanism of the Replication-Transc

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded, positive-sense RNA virus responsible for COVID-19, requires a set of virally encoded nonstructural proteins that compose a replication-transcription complex (RTC) to replicate its 30 kilobase genome. One such nonstructural protein within the RTC is Nsp13, a highly conserved molecular motor ATPase/helicase. Upon purification of the recombinant SARS-CoV-2 Nsp13 protein expressed using a eukaryotic cell-based system, we biochemically characterized the enzyme by examining its catalytic functions, nucleic acid substrate specificity, and putative protein-nucleic acid remodeling activity. We determined that Nsp13 preferentially interacts with single-stranded (ss) DNA compared to ssRNA during loading to unwind with greater efficiency a partial duplex helicase substrate. The binding affinity of Nsp13 to nucleic acid was confirmed through electrophoretic mobility shift assays (EMSA) by determining that Nsp13 binds to DNA substrates with significantly greater efficiency than RNA. These results demonstrate strand-specific interactions of SARS-CoV-2 Nsp13 that dictate its ability to load and unwind structured nucleic acid substrates. We next determined that Nsp13 catalyzed unwinding of double-stranded (ds) RNA forked duplexes on substrates containing a backbone disruption (neutrally charged polyglycol linker (PGL)) was strongly inhibited when the PGL was positioned in the 5' ssRNA overhang, suggesting an unwinding mechanism in which Nsp13 is strictly sensitive to perturbation of the translocating strand sugar-phosphate backbone integrity. Furthermore, we demonstrated for the first time the ability of the coronavirus Nsp13 helicase to disrupt a high-affinity nucleic acid-protein interaction, i.e., a streptavidin tetramer bound to biotinylated RNA or DNA substrate, in a uni-directional manner and with a preferential displacement of the streptavidin complex from biotinylated ssDNA versus ssRNA. In contrast to the poorly hydrolysable ATP-gamma-S or non-hydrolysable AMP-PNP, ATP supports Nsp13-catalyzed disruption of the nucleic acidprotein complex, suggesting that nucleotide binding by Nsp13 is not sufficient for protein-RNA disruption and the chemical energy of nucleoside triphosphate hydrolysis is required to fuel remodeling of protein bound to RNA or DNA. Our results build upon structural studies of the SARS-CoV-2 RTC in which it was suggested that Nsp13 pushes the RNA polymerase (Nsp12) backward on the template RNA strand. Experimental evidence from our studies demonstrate that Nsp13 helicase efficiently remodels a large high affinity protein-RNA complex in a manner dependent on its intrinsic ATP hydrolysis function. We proposed that this novel biochemical activity of Nsp13 is relevant to its role in SARS-CoV-2 RNA processing functions and replication. It was proposed that Nsp13 facilitates proofreading during coronavirus replication when a mismatched base is inadvertently incorporated into the SARS-CoV-2 genome during replication to reposition the RTC so that the proofreading nuclease complex (Nsp14-Nsp10) can gain access and remove the nascently synthesized nucleotide to ensure polymerase fidelity. Our findings implicate a direct catalytic role of Nsp13 in protein-RNA remodeling during coronavirus genome replication beyond its duplex strand separation or structural stabilization of the RTC, yielding new insight into the proofreading mechanism. This work was supported by the Intramural Training Program, National Institute on Aging (NIA), NIH, and a Special COVID-19 Grant from the Office of the Scientific Director, NIA, NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Mpox Awareness, Risk Reduction, and Vaccine Acceptance among Pwh in Washington, Dc

Background: PWH are disproportionally affected by mpox and at high risk for severe complications. The recent mpox outbreak response included increasing awareness, encouraging behavioral changes and pre- and post-exposure vaccination. We assessed knowledge and perceptions of mpox, adoption of preventive behaviors, and attitudes towards vaccination among PWH in Washington, DC. Method(s): Data from a cross-sectional mpox survey were collected between August and December 2022 from PWH enrolled in a longitudinal HIV cohort, the DC Cohort. We conducted uni- and bivariable analyses comparing participants by vaccination status (vaccinated, plan to vaccinate, no plan to vaccinate) and by HIV risk group (MSM vs. non-MSM). We conducted multinomial regression to identify factors associated with vaccine acceptance. Result(s): Among 178 PWH completing the survey (median age 55;71% male, 81% non-Hispanic Black, 37% MSM), 162 (91%) had heard of mpox. Among 159 PWH who had heard of mpox and answered vaccination questions, 21% (n=33) were vaccinated, 43% (n=69) planned to vaccinate and 36% (n=57) did not plan to vaccinate. Comparing the 3 groups, significant differences were observed by age, gender, education, income, HIV risk group, and level of worry about mpox (all p< 0.01). Viral suppression, prior COVID and influenza vaccination, access to STI services, and STI diagnoses in the last year were not associated with vaccine status. Behaviorally, a higher proportion of vaccinated participants reported limiting their number of sexual partners (p< 0.001) and using more preventive behaviors (e.g., limiting gatherings, increased condom use, avoiding skin-to-skin contact;p=0.034) in response to mpox. A higher proportion of MSM reported limiting their number of sexual partners compared to non-MSM (33% vs 7%, p< 0.0001) and were more likely to be vaccinated or plan to vaccinate vs non-MSM (p< 0.001). In adjusted multinomial regression models comparing vaccinated PWH and those planning to vaccinate to those not planning to vaccinate, age (p= 0.0231) and HIV risk factor/gender (p< 0.0001) were significantly associated with vaccination status with younger PWH and MSM more likely to vaccinate (Figure). Conclusion(s): High levels of mpox awareness were observed among this cohort of PWH in Washington, DC with more MSM employing risk reduction behaviors and vaccination as mpox prevention strategies. Ensuring that all PWH, regardless of gender, sexual orientation, or age, understand the risks of mpox may improve vaccination uptake.

COVID-19 in cancer patients: update from the joint analysis of the ESMO-CoCARE, BSMO, and PSMO international databases.

BACKGROUND: COVID-19 has significantly affected patients with cancer and revealed unanticipated challenges in securing optimal cancer care across different disciplines. The European Society for Medical Oncology COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international, real-world database, collecting data on the natural history, management, and outcomes of patients with cancer and SARS-CoV-2 infection. METHODS: This is the 2nd CoCARE analysis, jointly with Belgian (Belgian Society of Medical Oncology, BSMO) and Portuguese (Portuguese Society of Medical Oncology, PSMO) registries, with data from January 2020 to December 2021. The aim is to identify significant prognostic factors for COVID-19 hospitalization and mortality (primary outcomes), as well as intensive care unit admission and overall survival (OS) (secondary outcomes). Subgroup analyses by pandemic phase and vaccination status were carried out. RESULTS: The cohort includes 3294 patients (CoCARE: 2049; BSMO: 928, all hospitalized by eligibility criteria; PSMO: 317), diagnosed in four distinct pandemic phases (January to May 2020: 36%; June to September 2020: 9%; October 2020 to February 2021: 41%; March to December 2021: 12%). COVID-19 hospitalization rate was 54% (CoCARE/PSMO), ICU admission 14%, and COVID-19 mortality 22% (all data). At a 6-month median follow-up, 1013 deaths were recorded with 73% 3-month OS rate. No significant change was observed in COVID-19 mortality among hospitalized patients across the four pandemic phases (30%-33%). Hospitalizations and ICU admission decreased significantly (from 78% to 34% and 16% to 10%, respectively). Among 1522 patients with known vaccination status at COVID-19 diagnosis, 70% were non-vaccinated, 24% had incomplete vaccination, and 7% complete vaccination. Complete vaccination had a protective effect on hospitalization (odds ratio = 0.24; 95% confidence interval [0.14-0.38]), ICU admission (odds ratio = 0.29 [0.09-0.94]), and OS (hazard ratio = 0.39 [0.20-0.76]). In multivariable analyses, COVID-19 hospitalization was associated with patient/cancer characteristics, the first pandemic phase, the presence of COVID-19-related symptoms or inflammatory biomarkers, whereas COVID-19 mortality was significantly higher in symptomatic patients, males, older age, ethnicity other than Asian/Caucasian, Eastern Cooperative Oncology Group performance status ≥2, body mass index <25, hematological malignancy, progressive disease versus no evident disease, and advanced cancer stage. CONCLUSIONS: The updated CoCARE analysis, jointly with BSMO and PSMO, highlights factors that significantly affect COVID-19 outcomes, providing actionable clues for further reducing mortality.

The Impact of COVID-19 on the Mental-Emotional Wellbeing of Primary Healthcare Professionals: A Descriptive Correlational Study

The present study aimed to examine work environment related factors and frontline primary healthcare profes-sionals' mental-emotional wellbeing during the COVID-19 pandemic in school communities of Hong Kong. A total of 61 (20%) school health nurses (frontline primary healthcare professionals) participated in a cross-sec-tional online survey from March to June 2020. Outcomes of mental-emotional health were measured using the Mental Health Continuum-Short Form (14-item scale with three subscales related to emotional, social and psychological wellbeing);the Perceived Stress Scale (10-item scale with two subscales related to perceived help-lessness and lack of self-efficacy;and the Coping Orientation to Problems Experienced Inventory (Brief COPE), a 28-item inventory with two subscales related to adaptive and maladaptive strategies. Almost half (42.6%) of participants experienced mental health problems. Those employed in government subsidized schools had significantly lower scores in mental health wellbeing than those who worked in private schools. Factors relating to increased mental health problems included lack of emotional support, inadequate training relating to infection prevention and control measures, disengagement and self-blame. A variety of factors influencing school health nurses' social, emotional and psychological wellbeing in their work environment during the COVID-19 pandemic were also reported. The mental-emotional wellbeing of school nurses may relate to their subjective feeling of loneliness as participants were the sole frontline primary healthcare professional working in the school community during the COVID-19 pandemic. Study findings provide relevant evidence for management teams to build a culture of psychological and social support into workplace policies and procedures. Continuous staff development and adequate social support are important to promote the mental-emotional wellbeing of primary healthcare professionals in school communities as they play a significant role in safeguarding resources during pandemics. © 2023, Tech Science Press. All rights reserved.

Tixagevimab and Cilgavimab Reduced the Likelihood of Covid after Heart Transplant in the Age of Omicron

SARS-CoV-2 infection (COVID) is associated with high morbidity and mortality in solid organ transplants and vaccine efficacy is suboptimal. Tixagevimab and cilgavimab (T/C) are neutralizing antibodies used in the U.S. under emergency use authorization for COVID pre-exposure prophylaxis. However, T/C were developed when the Alpha and Omega variants were dominant. The purpose of this study is to look at real-world efficacy of T/C during the Omicron phase of the pandemic in heart transplants (HT). This was a retrospective study of adult HT recipients at a single center comparing those who received at least 3 doses of a COVID vaccine plus T/C versus those who only received the vaccine series (control) without prior infections. The primary outcome was development of COVID infection. Secondary outcomes included time from last vaccine to start of Omicron phase of pandemic, time from last vaccine to infection, and time from HT to infection. The Omicron phase was defined from 1/2022 to 2/2022. Chi-square and t-tests were used to assess for differences. Of the 244 patients identified, 44 received vaccination + T/C and 200 had vaccines only (Table 1). In the T/C group, patients were younger and more female (Table 1). In the control and T/C groups, 23% and 9.1% of patients, respectively, had documented COVID infections during the Omicron phase (p=0.039, Table 2). Months from last vaccine to start of Omicron phase, months from last vaccine to infection, and time from date of transplant to infection were similar between the two groups. Characteristics of the T/C patients who had breakthrough infections are shown in Table 3, none of whom required hospitalization or died. Patients who received vaccination + T/C had a significantly lower incidence of COVID infection compared to those who received vaccination alone in the Omicron era. T/C appeared to be protective in both recent and remote HT recipients, underscoring the utility of administering protective monoclonal antibodies in this population. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Differences in D-Dimer Levels in Covid-19 Patients with Versus without Venous Thromboembolisms (Vte)

INTRODUCTION: Coronavirus disease 2019 (COVID19) is known to cause coagulopathy as multiple systemic coagulation and inflammatory responses are activated during infectious complications. In COVID19 patients, hypercoagulopathy usually presents with an elevated D-dimer level. METHOD(S): All patients >= 18 years old who were admitted to NYU Langone Hospital-Long Island with a primary diagnosis of COVID-19 or with a flagged admission of COVID19 during April 1, 2020 to June 30, 2020 were included. IRB approval was acquired prior to data collection and upon permission, the clinical pharmacy IT department ran a report to identify patients. Most patients had a positive reverse-transcription polymerase chain reaction (RT-PCR) test during their admission, while a small number of patients were diagnosed before admission. Admissions included ICU patients or general ward patients. Series of D dimers were recorded. RESULT(S): There were 350 patients enrolled in the study, 331 had no VTE, 19 had VTE. Peak D dimer was 4876 (range 1509 to 15,872) in VTE group vs. 680 in non VTE group (range: 257 to 2723). 47.4% of VTE group had peak D dimer greater than 5000 vs. 16% of non VTE group. Surprisingly, there was no difference in mortality between the two groups: 26.3% for VTE group;19.9% in non VTE group, (p=0.556). However, VTE group had higher ICU admission rate 42.1% vs. 20.2% of non VTE group, p=0.039. Length of intubation was also significantly higher in VTE group (27 days) comparing to non VTE group (6 days), p=0.007. CONCLUSION(S): Covid 19 patients with VTE have much higher D dimer than non VTE Covid 19 patients. Although there is no difference in mortality in the two groups in our study, VTE group is associated with higher ICU admission as well as longer length of intubation days.

The COVID-19 Pandemic: Effects on Pediatric Fracture Patterns in the Emergency Department and Subspecialty Follow-up Care.

PURPOSE: The COVID-19 pandemic affected pediatric fracture injury patterns and volume. There is a paucity of research evaluating this trend throughout the pandemic and also follow-up to orthopaedic subspecialty care after emergency fracture management. METHODS: This retrospective cohort study reviewed patients 2 to 18 years of age presenting for fracture care to an urban pediatric emergency department. We assessed patient demographics, clinical care, and follow-up to surgical subspecialist. Time periods investigated included March 30 to September 4, 2020 (pandemic), March 30 to September 4, 2019, and March 30 to September 4, 2018 (prepandemic). Subanalysis within the pandemic was during the "stay-at-home order" verses the phased re-opening of the state. Descriptive statistical analysis, Pearson's χ 2 or Fisher exact tests, and Mann-Whitney U tests were performed. RESULTS: In this population, fractures overall declined by 40% (n=211) during the pandemic compared with 2019 (n=349) and 28% compared with 2018 (n=292). Lower extremity fractures accounted for a greater percentage of injuries during the pandemic compared with prepandemic. Time to surgical subspecialty follow-up was shortest during the 2020 pandemic peak at 9 days and was significantly longer during phased reopening (phase 1: 18 d, P =0.001; phase 2: 14 d, P =0.005). These patterns were also consistent for days to repeat imaging. CONCLUSIONS: We found differences in fracture prevalence, mechanisms, and follow-up care during the pandemic. Time to subspecialty follow-up care was longer during pandemic phased reopening despite overall fewer fractures. Plans to absorb postponed visits and efficiently engage redeployed staff may be necessary to address difficulties in follow-up orthopaedic management during public health crises. LEVEL OF EVIDENCE: Level II.

Implementation and characterisation of a sterilisation module consisting of novel 265 nm UVC LED packages

To efficiently fight against the COVID-19 pandemic, a sterilisation module using 265 nm UVC LED packages was developed. In this paper, the performance of the sterilisation module in terms of irradiance uniformity, junction temperature increase and sterilisation efficiency were characterised. The irradiance uniformity fluctuation across the four corners and the centre point in a 130 mm × 130 mm area was below 10%, exhibiting good uniformity. Uniform irradiance was important to achieve consistent sterilisation, which was the primary difference between the UVC LED package developed and commercial UVC LED packages. Key to achieving uniform irradiance was the structure, consisting of a stacked silicon reflector and a secondary optical lens designed by ray tracing simulation. The junction temperature increase of the 265 nm UVC LED package driving at 200 mA was only 28°C, sufficiently low to exhibit better reliability and performance. A 99.99% sterilisation efficiency on E. coli bacteria was achieved within one minute with UV dosage of 2.7 mJ/cm2 at 200 mA driving current. From the results, the novel 265 nm UVC LED package was a time-efficient solution for disinfection purposes. © 2021 The Hong Kong Institution of Engineers.

Corpus Callosum Lesion Associated With COVID-19-Psychosis

This case report presents a patient with acute onset psychosis in the setting of a COVID-19 infection. Magnetic resonance imaging of the brain was ordered to evaluate for organic etiologies which revealed cytotoxic lesions of the corpus callosum. These lesions can be associated with infectious diseases which cause inflammation. She was treated with an antipsychotic and later also with an antiepileptic. This case demonstrates that COVID-19 can affect multiple systems. Neuropsychiatric symptoms are possible and neuroimaging may be helpful, especially if symptoms are acute in onset. Copyright © 2022 Cliggott Publishing Co.. All rights reserved.

Cashierless Checkout Vision System for Smart Retail using Deep Learning

As Corona Virus Disease (COVID-19) pandemic strikes the world, retail industry has been severely impacted by staff shortage and high risk of virus outbreak. However, most of existing smart retail solutions is associated with high deployment and maintenance cost that are infeasible for small retail stores. As an effort to mitigate the issue, a computer vision-powered smart cashierless checkout system is proposed based on You Only Look Once (YOLO) v5 and MobileNet V3 for product recognition along with 3-stage image synthesis framework that includes crop and paste algorithm, GAN-based shadow synthesis and light variation algorithm. By using 3000 images generated from the framework, proposed model was trained and optimized with TensorRT. Experimental result shows that the lightweight model can be deployed on affordable edge devices like Jetson Nano while achieving high Mean Average Precision (mAP) of 98.2%, Checkout Accuracy (cAcc) of 89.17% with only 0.142s of inference time. © 2022, Success Culture Press. All rights reserved.

NHS England's National Targeted Lung Health Check: preliminary findings

Introduction: The NHS England Targeted Lung Health Check (TLHC) programme is now live in 23 sites. Expansion to 20 further projects planned in early 2022 will enable every Cancer Alliance the opportunity to participate and scope requirements for a potential national programme. Combined, these cover a population of ~1.35m of an estimated 6.25m ever-smokers aged 55 to 75 nationally (ONS 2019). We present our preliminary findings. Methods: Data returns are collected from sites by the NHS Strategy Unit and collated by Ipsos MORI for independent evaluation. Data management summaries are available to the national team on a quarterly basis to review where improvements might be necessary. A ‘Shiny app’ dashboard summarises site level data returns on a monthly basis. Diagnosis data typically lag behind invitation, LHC and low dose CT (LDCT) completion data due to time taken to confirm diagnosis. Onboarded site data includes retrospective historical activity since inception. Results: 172,684 participants have been invited for TLHC (at 30th September 2021), with 57,409 TLHCs completed approximately equally split across 23 original and ‘onboarded’ sites (phase 2). 33,593 LDCT scans have been undertaken (22,986 baseline). 402 lung cancers are presently reported (1.75% of participants referred for LDCT), but can under-estimate most recent/earliest onboarded cancer diagnoses and require continuous quality assurance. Early data suggests ~80% of cancers found are stage 1 or 2. 95% of responders to the TLHC attendee survey rated their experience as ‘very good’ or ‘good’. The COVID-19 protocol addendum including virtual LHCs and pause on spirometry allowed the programme to continue to grow throughout the pandemic. Conclusions: TLHC teams have made impressive progress in engaging participants with their programmes despite a respiratory pandemic. Preliminary results are as expected and encouraging. Careful adherence to quality assurance and mitigation of potential barriers, particularly workforce is crucial to optimise further expansion

CURRENT GAPS IN MEDICAL EDUCATION AS ILLUSTRATED BY THE COVID-19 PANDEMIC: INTERVIEWS WITH PHYSICIANS ACROSS VARIOUS MEDICAL SPECIALTIES

BACKGROUND: The COVID-19 pandemic brought unforeseen challenges and had many unfortunate consequences. The unprecedented uncertainty and other drastic changes that were driven by the pandemic illuminated some of the existing flaws in our healthcare system and in medical education. Numerous articles have been published discussing the impact of COVID-19;however, relatively few focus on its relation to medical education, specifically regarding communication, health equity, and uncertainty in medicine. We aim to explore these challenges as opportunities to guide improvements in medical education curriculum in these areas. METHODS: Physicians across Colorado from various medical specialties and unique practice environments were interviewed. We developed a standard set of interview questions that focused on the impact of the pandemic in the context of physicians' practices, the effect on patient care, adaptations, and the impact on trainees' education. Audio files of the interviews were transcribed, analyzed, and tallied according to a list of systematically established themes. The final data was reviewed to identify common and critical themes that could be used as an opportunity to create a positive transformation to medical education. RESULTS: Thirty-one physicians across 20 different medical specialties and sub-specialties were interviewed within the month of April 2020. Analysis of the interviews identified a number of common themes including significant mental health impact, a lack of data to drive clinical decisions, challenges in communication with patients and their families, and a disproportionate impact of the pandemic on underserved communities. Next steps include the administration and analysis of a follow-up survey of proposed innovative solutions for all interviewed physicians. CONCLUSIONS: The pandemic illuminated gaps in our healthcare system that were already present but not readily apparent. These identified themes impact all specialties, demonstrating that many of these gaps are universal in the field of medicine, and we believe that the best way to effect change is to incorporate these topics into medical education. Challenging trainees to navigate complex cases that may lack absolute answers would emphasize critical thinking and better prepare physicians for the uncertainties and complexities of medicine. As telehealth has transformed healthcare delivery, students must learn to navigate the nuances of virtual care without sacrificing the quality of care. Also, the increased prevalence of anxiety has highlighted the importance of being adequately trained to identify and address mental health disorders regardless of medical specialty. Lastly, the pandemic's disproportionate impact on underserved populations emphasizes the importance for students to be well-versed on topics such as health equity, policy reform and advocacy, and economics in ways that allow for actionable change.

Viral Nucleases from Herpesviruses and Coronavirus in Recombination and Proofreading: Potential Targets for Antiviral Drug Discovery.

In this review, we explore recombination in two very different virus families that have become major threats to human health. The Herpesviridae are a large family of pathogenic double-stranded DNA viruses involved in a range of diseases affecting both people and animals. Coronaviridae are positive-strand RNA viruses (CoVs) that have also become major threats to global health and economic stability, especially in the last two decades. Despite many differences, such as the make-up of their genetic material (DNA vs. RNA) and overall mechanisms of genome replication, both human herpes viruses (HHVs) and CoVs have evolved to rely heavily on recombination for viral genome replication, adaptation to new hosts and evasion of host immune regulation. In this review, we will focus on the roles of three viral exonucleases: two HHV exonucleases (alkaline nuclease and PolExo) and one CoV exonuclease (ExoN). We will review the roles of these three nucleases in their respective life cycles and discuss the state of drug discovery efforts against these targets.

OUTCOMES OF NEPHRECTOMY FOR RENAL CELL CARCINOMA WITH VENOUS THROMBUS FOLLOWING IMMUNE CHECKPOINT INHIBITOR THERAPY: A MULTICENTER COLLABORATIVE STUDY

INTRODUCTION AND OBJECTIVE: Nephrectomy and venous thrombectomy is a challenging procedure with potential morbidity and mortality. Despite the increasing use of immune checkpoint inhibitors (ICI) in the management of advanced renal cell carcinoma (RCC), data regarding the outcomes of venous thrombectomy following ICI is limited. We evaluated the feasibility and perioperative outcomes of nephrectomy and venous thrombectomy following ICIs. METHODS: Patients with locally advanced or metastatic RCC with venous thrombus undergoing nephrectomy following ICI therapy were evaluated in four high-volume US academic centers between June 2017 and June 2021. Clinical data, perioperative outcomes, and 90-day complications were recorded. RESULTS: Out of 79 patients who received post-ICI nephrectomy, 27 had venous thrombus. Median (IQR) age was 64 (55-71) years. ICI regimens were Nivolumab ± Ipilimumab (n=19), and Pembrolizumab± Axitinib (n=8). Nephrectomy was indicated following either a good clinical response to ICI (n=24) or as a palliative surgery (n=3). Venous thrombi levels are shown in Table-1. Among all patients, 26 (96%) underwent radical and 1 (4%) partial nephrectomy;12 (44.5%) open, 12 (44.5%) robotic and 3 (11%) laparoscopic. One robotic case converted electively to open. Vascular procedures included renal vein thrombectomy (n=6), IVC thrombectomy and primary repair (n=19), IVC patch repair (n=1), and suprarenal cavectomy (n=1). No intraoperative complications were reported. Nine patients showed no viable tumor in the thrombus, of whom 2 had complete response in the primary tumor as well (ypT0N0). 90-day complication rate was 33% (n=9), with 8 patients (30%) requiring readmission (Table-2). One death was reported within 90 days due to COVID-19 infection. CONCLUSIONS: Nephrectomy and venous thrombectomy following systemic immune checkpoint inhibitor therapy is feasible. One third of patients show no viable tumor in the thrombus. Larger studies are needed to predict pathological response.

RECOVERY and SURVIVAL in COVID-19 RESPIRATORY FAILURE, WHEN TREATED with AVIPTADIL

Background: COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vasoactive Intestinal Peptide (VIP) blocks replication of the SARS-CoV-2 virus in alveolar type II cells, inhibits cytokine synthesis, prevents cytopathy, and up regulates surfactant production. Synthetic VIP-aviptadil is a novel strategy to treat patients with COVID-19 and respiratory failure. Methods: This was a prospective, multicenter, randomized, placebo-controlled trial with 196 patients, nasal swab PCR+ for COVID-19 receiving intensive care at 10 U.S. hospitals (6 tertiary care and 4 regional hospitals) to determine if intravenous aviptadil is superior to placebo in achieving recovery from respiratory failure and survival at 60 days post treatment. The analysis was by modified intent to treat (ITT) using a pre-specified logistic regression model. The primary pre-specified endpoint was being alive with no respiratory failure at day 60. Results: There were 213 subjects screened, with 203 eligible and 196 randomized and treated. Baseline characteristics were comparable except for worse NIAID severity for aviptadil (Table 1). All subjects were followed up to 60 days. A favorable trend (OR 1.63;P=.14) was seen for the primary endpoint at 60 days with significance achieved after adjusting for hospital setting. Overall, there was 2.0-fold increased odds of survival (95% CI 1.05-3.88;P<.035) for aviptadil at Day 60 controlling for baseline NIAID score. Odds of survival increased to over 4-fold after adjusting for site of care (Tertiary care vs regional hospital, OR 4.35 (95% CI 1.91, 9.90;P<.035). Logistic regression indicated aviptadil treated patients were also significantly more likely to be discharged earlier than placebo-treated patients (p=0.01). The most common adverse events noted were diarrhea (32.8% vs. 1.5%) and hypotension (26% vs.21.5%) for aviptadil vs. placebo. Additional adverse events occurring more frequently in aviptadil treated patients included acute kidney injury (23.7% vs 20%), hyperkalemia (12.2% vs 6.2%), and atrial fibrillation (11.5% vs 4.6%). Multiple organ dysfunction syndrome (6.9% vs 13.8%) and respiratory failure (12.2% vs 13.8%) occurred more commonly in placebo-treated patients. Conclusion: Treatment with aviptadil demonstrates efficacy in improving the likelihood of recovering from respiratory failure, surviving to 60 days, and reducing hospital stay in critically ill patients with respiratory failure caused by COVID-19.

The Social Practices of Food Bank Volunteer Work

The on-going rise in demand experienced by voluntary and community organisations (VCOs) providing emergency food aid has been described as a sign of a social and public health crisis in the UK (Loopstra, 2018;Lambie-Mumford, 2019), compounded since 2020 by the impact of (and responses to) Covid 19 (Power et al., 2020). In this article we adopted a social practice approach to understanding the work of food bank volunteering. We identify how 'helping others', 'deploying coping strategies' and 'creating atmospheres' are key specific (and connected) forms of shared social practice. Further, these practices are sometimes suffused by faith-based practice. The analysis offers insights into how such spaces of care and encounter (Williams et al., 2016;Cloke et al., 2017) function, considers the implications for these distinctive organisational forms (the growth of which has been subject to justified critique) and suggests avenues for future research.