Search

We examined whether practice activities adopted by professional youth soccer coaches are modulated through the implementation of and engagement with cocreative evidence-based programs. Across two experiments, we used systematic observation to identify the practice activities of seven coaches across 134 sessions. In Experiment A, drill-based and games-based activities were recorded and quantified. To encourage behaviour change across the study, the systematic observation data were compared with skill acquisition literature to provide coaches with quantitative feedback and recommendations during workshops. Postworkshop systematic observation data indicated that practice activities used by coaches changed in accordance with the evidenced-based information (increase in games-based activities) delivered within the workshop. Interview data indicated that coaches typically stated that the workshop was a key reason for behaviour change. In a follow-up Experiment B, feedback and recommendations were delivered using an interactive video-based workshop. The systematic observation data indicated that coaches increased the use of soccer activities that contained active decision making with coaches citing the workshop as a key reason for behaviour change. These findings indicate that coaching practice activities can be supported and shaped through the implementation of cocreated workshops wherein coaches collaborate with sport scientists and researchers to bridge the gap between science and application.

Effects of fluid dynamics on cells are often studied by growing the cells on the base of cylindrical wells or dishes that are swirled on the horizontal platform of an orbital shaker. The swirling culture medium applies a shear stress to the cells that varies in magnitude and directionality from the center to the edge of the vessel. Computational fluid dynamics methods are used to simulate the flow and hence calculate shear stresses at the base of the well. The shear characteristics at each radial location are then compared with cell behavior at the same position. Previous simulations have generally ignored effects of surface tension and wetting, and results have only occasionally been experimentally validated. We investigated whether such idealized simulations are sufficiently accurate, examining a commonly-used swirling well configuration. The breaking wave predicted by earlier simulations was not seen, and the edge-to-center difference in shear magnitude (but not directionality) almost disappeared, when surface tension and wetting were included. Optical measurements of fluid height and velocity agreed well only with the computational model that incorporated surface tension and wetting. These results demonstrate the importance of including accurate fluid properties in computational models of the swirling well method.

Course-based undergraduate research experiences (CUREs) are high-impact practices that allow students to conduct research during class time. Benefits of a CURE can be maximized when integrated into a faculty member’s ongoing research. However, this can be particularly challenging for field biologists, especially when field sites are not situated near their university. Indeed, few existing CUREs are field based. One solution is to partner with a collaborator near the field site. We describe a semester-long CURE in an animal behavior class that involved collaboration among three institutions: researchers from two “distant” institutions have ongoing research at the “local” institution where the CURE took place. This model uses remote conferencing and strategic collaboration to meet all stakeholders’ needs. Undergraduate students engaged as active participants in collaborative inquiry-based work, learned in a cooperative context, and even participated in the publication process. The local principal investigator and their institution generated a high-impact course that integrated research and teaching. Likewise, the distant principal investigators were able to collect more extensive and longer-term field-based data than otherwise possible, and they gained valuable input from the local researchers that contributed to future projects. Remote collaborations open the door to international collaboration with smaller institutions, promoting greater inclusion in science.

Community mitigation strategies to combat COVID-19, ranging from healthy hygiene to shelter-in-place orders, exact substantial socioeconomic costs. Judicious implementation and relaxation of restrictions amplify their public health benefits while reducing costs. We derive optimal strategies for toggling between mitigation stages using daily COVID-19 hospital admissions. With public compliance, the policy triggers ensure adequate intensive care unit capacity with high probability while minimizing the duration of strict mitigation measures. In comparison, we show that other sensible COVID-19 staging policies, including France’s ICU-based thresholds and a widely adopted indicator for reopening schools and businesses, require overly restrictive measures or trigger strict stages too late to avert catastrophic surges. As proof-of-concept, we describe the optimization and maintenance of the staged alert system that has guided COVID-19 policy in a large US city (Austin, Texas) since May 2020. As cities worldwide face future pandemic waves, our findings provide a robust strategy for tracking COVID-19 hospital admissions as an early indicator of hospital surges and enacting staged measures to ensure integrity of the health system, safety of the health workforce, and public confidence., Selection of COVID-19 mitigation measures requires balancing health outcomes with economic impacts. Here, the authors derive a system to set triggers for increasing mitigation measures to preserve healthcare capacity, and describe how it has been used to support public health decision making in Austin, Texas.

We used the incidence of spike gene target failures identified during PCR testing to provide an early projection of the prevalence of severe acute respiratory syndrome coronavirus 2 variant B.1.1.7 in a university setting in Texas, USA, before sequencing results were available. Findings from a more recent evaluation validated those early projections.

The integration of advanced analytics and artificial intelligence (AI) technologies into the practice of medicine holds much promise. Yet, the opportunity to leverage these tools carries with it an equal responsibility to ensure that principles of equity are incorporated into their implementation and use. Without such efforts, tools will potentially reflect the myriad of ways in which data, algorithmic, and analytic biases can be produced, with the potential to widen inequities by race, ethnicity, gender, and other sociodemographic factors implicated in disparate health outcomes. We propose a set of strategic assertions to examine before, during, and after adoption of these technologies in order to facilitate healthcare equity across all patient population groups. The purpose is to enable generalists to promote engagement with technology companies and co-create, promote, or support innovation and insights that can potentially inform decision-making and health care equity.

Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery, and is associated with increased morbidity and mortality. Inflammation has been implicated as an etiology of POAF. Mitochondrial DNA (mtDNA) has been shown to initiate inflammation. This study analyzed inflammatory mechanisms of POAF by evaluating mtDNA, neutrophils, and cytokines/chemokines in the pericardial fluid and blood after cardiac surgery.Blood and pericardial fluid from patients who underwent coronary artery bypass or heart valve surgery, or both, were collected intraoperatively and at 4, 12, 24, and 48 hours postoperatively. Real-time polymerase chain reaction was used to quantify mtDNA in the pericardial fluid and blood. A Luminex (Luminex Corp, Austin, TX) assay was used to study cytokine and chemokine levels. Flow cytometry was used to analyze neutrophil infiltration and activation in the pericardial fluid.Samples from 100 patients were available for analysis. Postoperatively, mtDNA and multiple cytokine levels were higher in the pericardial fluid versus blood. Patients who had POAF had significantly higher levels of mtDNA in the pericardial fluid compared with patients who did not (P.001, area under the curve 0.74). There was no difference in the mtDNA concentration in the blood between the POAF group and non-POAF group (P = .897). Neutrophil concentration increased in the pericardial fluid over time from a baseline of 0.8% to 56% at 48 hours (P.01).The pericardial space has a high concentration of inflammatory mediators postoperatively. Mitochondrial DNA in the pericardial fluid was strongly associated with the development of POAF. This finding provides insight into a possible mechanism of inflammation that may contribute to POAF, and may offer novel therapeutic targets.

Background Previous research from our center has shown that 27% of the pediatric trauma transfers from referring facilities are potentially preventable. Our hospital is the only level 1 pediatric trauma center (PTC) in our state, and we are developing a pediatric trauma telehealth network to help keep certain injured children closer to home. We instituted a pediatric trauma telehealth program with a partnering community-based hospital in our state and aim to report our experience over the first year. Methods All pediatric trauma patients that presented to our partnering hospital from January 2019 to February 2020 were reviewed. Disposition was: a) telehealth consultation, b) admission to the children's unit without a telehealth consultation per our head trauma protocol, or c) transfer without telehealth consultation. Data on demographics, hospital course, and disposition were collected via chart review. Results Eight patients underwent telehealth consults and another 8 patients were admitted to the partnering hospital's children's unit based on the head trauma protocol without a telehealth consult. Patient's ages ranged from 7 months to 15 years. Of the patients that underwent telehealth consult, 7 presented with a head injury and 1 presented with a rib fracture/small pneumothorax. The patient with a pneumothorax was observed for 6 h and discharged home after a repeat chest x-ray was stable. All 15 patients with head injuries were observed and discharged from either the emergency department or children's unit after passing concussion testing. No patients required transfer to our PTC after observation, and none were readmitted. Fifty-six patients were transferred without telehealth consultation, and 3 of these patients could potentially have avoided transfer with a telehealth consultation. Conclusions Telehealth in pediatric trauma can be a safe mechanism for preventing the transfer of patients that can be safely observed at a partnering hospital. From a facility that transfers an average of 30 trauma patients per year to our hospital, this program prevented 16 such transfers. Development of a head trauma protocol in collaboration with a pediatric neurosurgeon leads to an unexpected number of patients being admitted to the partnering hospital for observation without utilization of a telehealth consultation. Type of study Retrospective study. Level of evidence III

The novel coronavirus (SARS-CoV-2) emerged in late 2019 and spread globally in early 2020. Initial reports suggested the associated disease, COVID-19, produced rapid epidemic growth and caused high mortality. As the virus sparked local epidemics in new communities, health systems and policy makers were forced to make decisions with limited information about the spread of the disease. We developed a compartmental model to project COVID-19 healthcare demands that combined information regarding SARS-CoV-2 transmission dynamics from international reports with local COVID-19 hospital census data to support response efforts in three Metropolitan Statistical Areas (MSAs) in Texas, USA: Austin-Round Rock, Houston-The Woodlands-Sugar Land, and Beaumont-Port Arthur. Our model projects that strict stay-home orders and other social distancing measures could suppress the spread of the pandemic. Our capacity to provide rapid decision-support in response to emerging threats depends on access to data, validated modeling approaches, careful uncertainty quantification, and adequate computational resources.

During rollout of coronavirus disease vaccination, policymakers have faced critical trade-offs. Using a mathematical model of transmission, we found that timing of vaccination rollout would be expected to have a substantially greater effect on mortality rate than risk-based prioritization and uptake and that prioritizing first doses over second doses may be lifesaving.

Background Learning curves and skill attrition with aging have been reported to impair outcomes in select surgical subspecialties, but their role in complex cardiac surgery remains unknown. Methods From 1986 to 2019, 2314 patients underwent reoperative cardiac surgery: coronary artery bypass grafting (n = 543), valve (n = 1527), or combined coronary artery bypass grafting and valve (n = 244). Thirty-four different surgeons in practice between 1 and 39 years were included. Standardized mortality ratio (observed-to-expected) was determined for all surgeons in each post-training year of experience. Results Risk-adjusted cumulative sum change-point analysis was used to define five distinct career phases: 0 to 4 years, 5 to 8 years, 9 to 17 years, 18 to 28 years, and 29 to 39 years. With 5 to 8 years and 18 to 28 years of experience, standardized mortality ratio was near unity (0.95 and 1.05, respectively) and lowest with 9 to 17 years of experience (0.78, P = .03). In the youngest experience group (0 to 4 years), observed and expected mortality were both highest, and standardized mortality ratio was elevated at 1.29, which approached statistical significance (P = .059). In the oldest experience group (29 to 39 years), expected mortality was low compared with most other groups but observed mortality increased, yielding a significantly elevated standardized mortality ratio at 1.53 (P = .032). Conclusions Standardized mortality ratios with reoperative cardiac surgery were highest early and late in a surgeon’s career and lowest in mid career. As surgeons gain experience, outcomes improve through the first two career decades, then stabilize in the third decade before declining in the fourth decade.

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)—an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles—to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1–3 V/cm), intermediate-frequency (100–300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.

Social distancing orders have been enacted worldwide to slow the coronavirus disease (COVID-19) pandemic, reduce strain on healthcare systems, and prevent deaths. To estimate the impact of the timing and intensity of such measures, we built a mathematical model of COVID-19 transmission that incorporates age-stratified risks and contact patterns and projects numbers of hospitalizations, patients in intensive care units, ventilator needs, and deaths within US cities. Focusing on the Austin metropolitan area of Texas, we found that immediate and extensive social distancing measures were required to ensure that COVID-19 cases did not exceed local hospital capacity by early May 2020. School closures alone hardly changed the epidemic curve. A 2-week delay in implementation was projected to accelerate the timing of peak healthcare needs by 4 weeks and cause a bed shortage in intensive care units. This analysis informed the Stay Home-Work Safe order enacted by Austin on March 24, 2020.

Pressure–velocity-based analysis of arterial wave intensity gives clinically relevant information about the performance of the heart and vessels, but its utility is limited because accurate pressure measurements can only be obtained invasively. Diameter–velocity-based wave intensity can be obtained noninvasively using ultrasound; however, due to the nonlinear relationship between blood pressure and arterial diameter, the two wave intensities might give disparate clinical indications. To test the magnitude of the disagreement, we have generated an age-stratified virtual population to investigate how the two dominant nonlinearities, viscoelasticity and strain-stiffening, cause the two formulations to differ. We found strong agreement between the pressure–velocity and diameter–velocity methods, particularly for the systolic wave energy, the ratio between systolic and diastolic wave heights, and older subjects. The results are promising regarding the introduction of noninvasive wave intensities in the clinic.

Aortic valve replacement is recommended in symptomatic patients with severe aortic stenosis (AS) or asymptomatic with reduced left ventricular ejection fraction (LVEF). The treatment algorithm of p...

The purpose of this review is to summarize and evaluate relevant literature on combination antifungal therapy for invasive fungal infections (IFIs). Cryptococcal meningitis has the largest body and highest quality in support of combination therapy with amphotericin B and flucytosine. More recent data in treatment of invasive aspergillosis suggest combination therapy with voriconazole and echinocandins may be effective in select patients. Quality studies are needed to define combination therapy in rare mold infections. Multiple strategies have been employed to optimize treatment of the growing incidence of IFIs. With exceptions as noted above, justification for the use of combination antifungal therapy is most often based on uncontrolled and/or underpowered studies, in vitro data, and case reports.

Neurosyphilis is a disease caused by systemic infection with Treponema pallidum, which infiltrates the central nervous system and preganglionic dorsal roots. This process presents as neurological deficits and can occur any time during the infection course, but usually takes many years. Neurosyphilis is rare in the developed world where antibiotics are readily available to treat the early stages of syphilis. This report describes a case of neurosyphilis in a 71-year-old woman who presented with ataxia and vision changes and was ultimately found to have a positive rapid plasma reagin test and protein in the cerebrospinal fluid. She was treated with intravenous penicillin for two weeks with a good response.

Background: Total ankle arthroplasty (TAA) is a surgical procedure commonly reserved for patients suffering from symptomatic end-stage ankle arthritis. As the number of TAAs increases, so does the associated economic burden. Given these economic constraints, there has been interest in the feasibility of outpatient TAA. The purpose of this study is to evaluate the safety, efficacy, and satisfaction of patients undergoing outpatient TAA. Methods: This is a retrospective case series of consecutive patients who underwent outpatient TAA from July 2018 to June 2019. Inclusion criteria included any patient undergoing a primary TAA in the outpatient setting. This was defined as discharge on the same day of surgery or within 12 hours of surgery. All surgeries were completed by a single experienced surgeon through an anterior approach using the Cadence Total Ankle System. Prior to surgery, all patients received a popliteal nerve block. Patients were then discharged home with oral analgesic and a popliteal nerve catheter, which they removed after 48 hours. The primary outcome of interest was postoperative pain control, which was measured using a numeric scale. Secondary outcomes included complication rate, readmission rate, and patient satisfaction. A review of the current literature was then completed to supplement our results. Results: In total, 41 patients were included in our analysis. In terms of the primary outcome, the average numeric scale score was 1.98, indicating excellent pain control. Additionally, nearly all 41 patients stated they were very satisfied with their postoperative pain control regimen. In terms of secondary outcomes, the majority of patients stated they were satisfied with discharge on the same day as surgery. There were no readmissions or major complications in our outpatient TAA cohort. When asked if they would recommend the care they experienced to a friend with the same condition, 95% of patients said that they would recommend this care pathway. Our literature review included 5 original studies, which were all retrospective level IV studies. These studies uniformly demonstrated the safety and efficacy of outpatient TAA. Conclusions: The results of our study demonstrate the outpatient TAA is associated with excellent pain control using a multidisciplinary pain approach. The use of standardized outpatient postoperative pathways was effective in preventing readmissions and complications, while still resulting in high patient satisfaction scores. A review of the literature complemented our results, as there are largely no significant differences between outpatient and inpatient TAA. Level of Evidence: Level IV, case series.

As coronavirus disease spreads throughout the United States, policymakers are contemplating reinstatement and relaxation of shelter-in-place orders. By using a model capturing high-risk populations and transmission rates estimated from hospitalization data, we found that postponing relaxation will only delay future disease waves. Cocooning vulnerable populations can prevent overwhelming medical surges.

Objective Obesity is a strong and independent factor for the development of atrial fibrillation (AF), and adversely impacts the success of catheter ablation procedures for AF. This study evaluated the impact of body mass index (BMI) on the outcomes following surgical ablation of AF. Methods Between 2003 and 2019, 236 patients underwent a stand-alone biatrial Cox maze IV procedure (CMP-IV) for refractory AF. Obesity was defined as BMI ≥30 kg/m2. Patients were divided into two groups: BMI 2 ( n = 100) and BMI ≥30 kg/m2 ( n = 136). Freedom from atrial tachyarrhythmia (ATA) was determined using electrocardiography, Holter, or pacemaker interrogation at 1 year and annually thereafter. Recurrence was defined as any documented ATA lasting ≥30 s. Predictors of recurrence were determined using multivariable logistic regression. Preoperative and procedural outcomes were compared between groups. Results Obese patients had a higher rate of diabetes (16% vs 7%, P = 0.044) and larger left atrial diameter (4.9 ± 1.1 cm vs 4.6 ± 1.0 cm, P = 0.021) when compared to non-obese patients. There was no difference in major complication rate between the groups (4% vs 7%, P = 0.389). There was no operative mortality in either group. During 4.1 ± 2.4 years of follow-up, there was no significant difference in freedom from ATA with or without antiarrhythmic drugs in obese patients when compared to the non-obese group ( P > 0.05). Absence of sinus rhythm at discharge predicted AF recurrence up to 7 years postoperatively. Conclusions As opposed to catheter ablation, obesity did not adversely impact the short and long-term outcomes of stand-alone surgical ablation with CMP-IV, and BMI was not a predictor of AF recurrence. Additionally, there was no significant increase in major complications in obese patients.

The surgical treatment of atrial fibrillation has evolved over the past 2 decades due to the advent of ablation technology, and the introduction of less invasive surgical approaches. Current devices produce ablation lines that aim to replace the incisions of traditional surgical ablation strategies, such as the Cox-Maze procedure. This has helped to simplify and shorten surgical ablation procedures and has allowed for the development of minimally invasive surgical techniques. This review discusses surgical ablation energy sources and devices, providing background on device characteristics, mechanism of tissue injury, and success in creating transmural lesions.

Background Inappropriate sinus tachycardia (IST) is a rare clinical disorder characterized by an elevated resting heart rate and an exaggerated rate response to exercise or autonomic stress. Pharmacologic therapy and catheter ablation are considered first-line treatments for IST but can yield suboptimal relief of symptoms. The results of surgical ablation at our center were reviewed for patients with refractory IST. Methods Between 1987 and 2018, 18 patients underwent surgical sinoatrial (SA) node isolation for treatment-refractory IST. All 18 patients had previously failed pharmacologic therapy, and 15 patients had failed catheter ablation of the SA node. Results Ten patients underwent a median sternotomy, and 8 patients underwent a minimally invasive right thoracotomy. The SA node was isolated with the use of surgical incisions, cryoablation, or bipolar radiofrequency ablations. Sinus tachycardia was eliminated in 100% of patients in the immediate postoperative period. Long-term follow-up data were available for 17 patients, with a mean follow-up of 11.4 ± 7.9 years. At last follow-up, 100% of patients were free from recurrent symptomatic IST. More than 80% of patients were completely asymptomatic, whereas 3 patients reported occasional palpitations. Four patients were on β-blockers, and 5 patients required subsequent pacemaker implantation. All 8 patients who underwent minimally invasive isolation were in normal sinus rhythm at last follow-up, and only 1 patient complained of palpitations. Conclusions Surgical isolation of the SA node is a feasible treatment for IST refractory to pharmacologic therapy and catheter ablation. A minimally invasive surgical approach offers a less morbid alternative to traditional median sternotomy.

Management of chronic isolated scapholunate interosseous ligament (SLIL) injuries has generated a substantial volume of low-quality literature with descriptions of multiple new surgical techniques, and the impact of instability pattern and the optimal surgical technique remain unclear. The primary goal of this review was to compare clinical, radiographic and patient-rated outcomes between current surgical techniques.We performed a systematic literature search using multiple databases. We analyzed clinical, radiographic and patient-reported outcomes. We used a fixed-effects model weighted by sample size with combined outcomes estimated via least squares means with 95% confidence intervals. We also performed a subgroup analysis of static versus dynamic instability.We assessed 805 procedures from 37 study groups, with 429 procedures used in subgroup analysis. There were no statistically significant differences in outcomes between surgical techniques or in subgroup analysis. Overall, postoperative wrist flexion and pain scores decreased, and grip strength and patient-rated outcomes improved.Compared to overall preoperative values, modest improvements in pain score, grip strength and functional outcome scores were obtained from a range of reconstructive procedures performed for chronic isolated SLIL injuries. No significant differences could be ascertained between surgical techniques, potentially owing to the low quality of evidence and procedure heterogeneity. This study provides accurate preoperative reference values for future studies, highlights the controversial clinical impact of instability classification, and the need for higher-quality multicentre or collaborative trials to improve our understanding and management of this common injury.La prise en charge des blessures chroniques du ligament interosseux scapho-lunaire (LISL) a généré un volume substantiel d’articles de faible qualité où sont décrites plusieurs nouvelles techniques chirurgicales, mais l’impact du modèle d’instabilité et la technique chirurgicale optimale restent à clarifier. Le principal objectif de cette revue était de comparer les résultats cliniques, radiographiques et autodéclarés par les patients entre les diverses techniques chirurgicales actuelles.Nous avons procédé à une interrogation systématique de la littérature dans plusieurs bases de données. Nous avons analysé les résultats cliniques, radiographiques et autodéclarés par les patients. Nous avons utilisé un modèle à effets fixes pondéré par la taille de l’échantillon, avec paramètres mixtes estimés par les moyennes des moindres carrés et des intervalles de confiance à 95 %. Nous avons aussi effectué une analyse de sous-groupes (instabilité radiographique dynamique c. statique).Nous avons évalué 805 interventions dans 37 groupes étudiés, et 429 interventions ont été utilisées dans les analyses de sous-groupes. On n’a noté aucune différence statistiquement significative pour ce qui est des résultats entre les techniques chirurgicales ni dans les analyses de sous-groupes. Globalement, la flexion du poignet et la douleur ont diminué, et la force préhensile et autres paramètres autodéclarés par les patients se sont améliorés.Comparativement aux valeurs préopératoires globales, de modestes améliorations du score de douleur, de la force préhensile et des paramètres fonctionnels ont été obtenues au moyen de diverses interventions de reconstruction effectuées pour des blessures chroniques isolées du LISL. Aucune différence significative n’a pu être confirmée entre les techniques chirurgicales, probablement en raison de la faible qualité des données et de l’hétérogénéité des interventions. Cette étude fournit des valeurs de référence préopératoires précises pour de futures études et souligne l’impact clinique controversé de la classification de l’instabilité, ainsi que la nécessité de procéder à des essais multicentriques ou collaboratifs de meilleure qualité pour mieux comprendre et prendre en charge ce type fréquent de blessure.

Intracerebral hemorrhage (ICH) accounts for only 10 to 15% of all strokes but remains a significant cause of morbidity and mortality. Despite lengthy stays in critical care units, only one-half of those experiencing an ICH survive after 30 days, and those who do are often left with considerable disability. Treatment has traditionally focused on minimizing the hemorrhage expansion and reducing clot volume through both medical and surgical means. Management of ICH is a complex and multidisciplinary process. This review will discuss a few common etiologies, explore the pathophysiology of secondary neuronal injury after ICH, review the basics of ICH imaging with computed tomography and magnetic resonance imaging, and highlight latest practices in medical and surgical management. Secondary injury mechanisms such as perihematomal edema and disordered cerebral autoregulation are discussed as potential targets for new treatment modalities. Emergent treatment in the “golden hour” after ictus provides a template of measures to adopt from initial contact with emergency medical services, to the emergency department, and thereafter, triage to the intensive care unit. Medical management including blood pressure control, hemostasis, and coagulopathy reversal are discussed and evidence from trials such as INTERACT 2, ATACH 2, and ANNEXA-4 are given a clinical context. Surgical management including intracranial pressure monitoring, surgical evacuation with open craniotomy, and minimally invasive approaches such as stereotactic-guided aspiration and thrombolysis, ultrasound-induced thrombolysis, image-guided stereotactic endoscopic aspiration, and stereotactic ICH underwater blood aspiration are enumerated. The outcomes and relevance of STICH, MISTIE, and CLEAR trials to present surgical care are elaborated. The review summarizes the current guidelines for the treatment of ICH and the latest literature in the field they are based upon. It aims to provide a concise article beneficial to the emergency physicians and neurointensivists/neuroanesthesiologists.

Background Travellers’ diarrhoea (TD) is the most common clinical syndrome affecting travellers. This narrative review summarizes key discoveries reported in the last two years related to TD and suggests areas for future research. Methods A PubMed literature search was conducted for novel data in TD research published between 12 January 2018 and 12 January 2020. Inclusion was based on contribution to epidemiology, aetiology, diagnostics, management and long-term consequences and relevance to public health, discovery and clinical practice. Results The initial literature search yielded 118 articles. We retrieved 72 and reviewed 31 articles for inclusion. The findings support our understanding that TD incidence varies by traveller group and environment with students and military-travel remaining moderately high risk, and control of food and water in mass gathering events remain an important goal. The growth of culture-independent testing has led to a continued detection of previously known pathogens, but also an increased detection frequency of norovirus. Another consequence is the increase in multi-pathogen infections, which require consideration of clinical, epidemiological and diagnostic data. Fluoroquinolone resistant rates continue to rise. New data on non-absorbable antibiotics continue to emerge, offering a potential alternative to current recommendations (azithromycin and fluoroquinolones), but are not recommended for febrile diarrhoea or dysentery or regions/itineraries where invasive pathogens are likely to cause illness. Recent studies investigated the interaction of the microbiome in TD prevention and consequences, and while discriminating features were identified, much uncertainty remains. The prevalence of extended-spectrum beta-lactamase–producing Enterobacteriaceae (ESBL-PE) acquisition and carriage is increasing. Finally, continued research documents the post-infectious consequences, whereas mechanisms of reactive arthritis and post-infectious IBS necessitate further investigation. Conclusions Globally, TD remains an important travel health issue and advances in our understanding continue. More research is needed to mitigate risk factors where possible and develop risk-based management strategies to reduce antibiotic usage and its attendant consequences.

INTRODUCTION: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and results in significant morbidity and mortality. The Cox-Maze IV procedure (CMP-IV) has been shown to have excellent efficacy in returning patients to sinus rhythm, but there have been few reports of late follow-up in sizable cohorts of patients with longstanding persistent AF, the most difficult type of AF to treat. METHODS AND RESULTS: Between May 2003 and March 2020, 174 consecutive patients underwent a stand-alone CMP-IV for longstanding persistent AF. Rhythm outcome was assessed postoperatively for up to 10 years, primarily via prolonged monitoring (Holter monitor, pacemaker interrogation, or implantable loop recorder). Fine-Gray regression was used to investigate factors associated with atrial tachyarrhythmia (ATA) recurrence, with death as a competing risk. Median duration of preoperative AF was 7.8 years (interquartile range: 4.0–12.0 years), with 71% (124/174) having failed at least one prior catheter-based ablation. There were no 30-day mortalities. Freedom from ATAs was 94% (120/128), 83% (53/64), and 88% (35/40) at 1, 5, and 7 years, respectively. On regression analysis, preoperative AF duration and early postoperative ATAs were associated with late ATAs recurrence. CONCLUSION: Despite the majority of patients having a long-duration of preoperative AF and having failed at least one catheter-based ablation, the stand-alone CMP-IV had excellent late efficacy in patients with longstanding persistent AF, with low morbidity and no mortality. We recommend consideration of stand-alone CMP-IV for patients with longstanding persistent AF who have failed or are poor candidates for catheter ablation.

SummaryDuring most of 2020, the COVID-19 pandemic gave rise to considerable and growing numbers of hospitalizations across most of the U.S. Typical COVID-19 hospitalization data, including length of stay, intensive care unit (ICU) use, mechanical ventilation (Vent), and in-hospital mortality provide clearly interpretable health care endpoints that can be compared across population strata. They capture the resources consumed for the care of COVID-19 patients, and analysis of these endpoints can be used for resource planning at the local level. Yet, hospitalization data embody novel features that require careful statistical treatment to be useful in this context. Specifically, statistical models must meet three goals: (i) They should mesh with and inform mathematical epidemiologic or agent-based models of the COVID-19 experience in the population. (ii) They need to handle administrative censoring of hospitalization experience when data are extracted and downloaded for a given patient before that patient’s hospitalization experience has terminated. And, (iii) models need to handle risks for competing events, the occurrence of one blocking the possibility of the other(s). For example, live discharge from the hospital “competes with” (i.e., blocks) in-hospital mortality. We have adapted approaches from the survival analysis literature to address these challenges in order to better understand and quantify the population experience in hospital with respect to length of stay, ICU, Vent use and so on. Using hospitalization data from a large U.S. metropolitan region, in this report, we show how standard techniques from survival analysis can be brought to bear to address these challenges and yield interpretable results. In the breakout/discussion, we will discuss formulation, estimation and inference, and interpretation of competing risks models.

Nearly two months after a near-death car accident, I am in the passenger seat of my younger brother’s car. Two of our friends sit in the back. A crisp December day, we are heading to the local mall...

In patients with hypertrophic obstructive cardiomyopathy, atrial fibrillation is associated with heart failure and increased late mortality. However, the role of surgical ablation in these patients is not well defined. The aim of this study was to evaluate the efficacy of the concomitant Cox-Maze IV procedure in patients undergoing septal myectomy for hypertrophic obstructive cardiomyopathy.Between 2005 and 2019, 347 patients who underwent septal myectomy at a single institution (Washington University School of Medicine, Barnes-Jewish Hospital, St Louis, MO) were retrospectively reviewed. For patients with hypertrophic obstructive cardiomyopathy and atrial fibrillation who underwent a concomitant Cox-Maze IV procedure, freedom from atrial tachyarrhythmias (ATAs) on or off antiarrhythmic drugs (AADs) was evaluated annually. Predictors of ATA recurrence were identified using Fine-Gray regression, with death as a competing risk.A total of 42 patients underwent concomitant septal myectomy and Cox-Maze IV procedures. The majority of patients, 69% (29 of 42), had paroxysmal atrial fibrillation with a 2.5-year median duration. Operative mortality was 7% (3 of 42). New York Heart Association functional class was reduced after surgery (P.01). Rates of freedom from recurrent ATAs at 1- and 5-year intervals were 93% (27 of 29) and 100% (14 of 14), respectively. Rates of freedom from ATAs and AADs were 83% (24 of 29) and 100% (14 of 14) at the same time points, respectively. Increased left atrial diameter predicted first ATA recurrence (P.01). Cerebrovascular accident risk was lower in patients with atrial fibrillation who underwent concomitant Cox-Maze IV and septal myectomy relative to myectomy only (P = .02).Late freedom from ATAs on or off AADs was excellent after Cox-Maze IV and septal myectomy. Although there was a higher than expected rate of perioperative complications, the study results suggest that concomitant surgical ablation should be considered in selected patients with hypertrophic obstructive cardiomyopathy and atrial fibrillation.

Introduction Glioblastoma is the most common cancer arising within the brain. Despite surgery, followed by DNA-damaging chemoradiotherapy, average survival remains between 12-15 months. Unacceptable survival rates underline the need to develop preclinical research models which recapitulate features underpinning therapeutic resistance in patients, such as intratumoural heterogeneity and treatment resistant glioblastoma stem cell (GSC) subpopulations which demonstrate elevated DNA damage response (DDR) activity. Method Tumour specimens from patients were used to generate 2D and 3D scaffold-based GSC models, with a range of preclinical survival and molecular assays used to interrogate cancer biology and assess therapeutic responses. Result We have developed a ‘living biobank’ of 20+ ex-vivo GSC models which reflect key clinicopathological diversity. These models include residual disease models based on careful macrodissection of rare en-blocpartial lobectomy specimens to liberate parallel GSC lines from the tumour core and adjacent infiltrated brain, to represent cells typically left behind after surgery. Therapeutic strategies targeting fundamental DDR processes demonstrate preclinical efficacy, for example dual inhibition of ATR and the FA DNA damage repair pathways elicits profound radiosensitisation (sensitiser enhancement ratio of 3.23 (3.03-3.49, 95%-CI)) with evidence of delayed DNA damage repair on single-cell gel electrophoresis. Finally, characterisation of our surgically-relevant resected and residual models reveals numerous divergent properties including elevated stem cell marker expression in residual models (p=0.0021), which may partially explain treatment resistance in disease left behind after surgery. Conclusion Our living biobank represents a useful resource for preclinical glioblastoma research and demonstrates the value of partnership between surgeons and laboratory-based scientists. Take-home message Our living biobank represents a useful resource for preclinical glioblastoma research and demonstrates the value of partnership between surgeons and laboratory-based scientists.

Abstract The performance in heterogeneous catalysis is an example of a complex materials function, governed by an intricate interplay of several processes (e.g., the different surface chemical reactions, and the dynamic restructuring of the catalyst material at reaction conditions). Modeling the full catalytic progression via first-principles statistical mechanics is impractical, if not impossible. Instead, we show here how a tailored artificial-intelligence approach can be applied, even to a small number of materials, to model catalysis and determine the key descriptive parameters (“materials genes”) reflecting the processes that trigger, facilitate, or hinder catalyst performance. We start from a consistent experimental set of “clean data,” containing nine vanadium-based oxidation catalysts. These materials were synthesized, fully characterized, and tested according to standardized protocols. By applying the symbolic-regression SISSO approach, we identify correlations between the few most relevant materials properties and their reactivity. This approach highlights the underlying physicochemical processes, and accelerates catalyst design. Impact statement Artificial intelligence (AI) accepts that there are relationships or correlations that cannot be expressed in terms of a closed mathematical form or an easy-to-do numerical simulation. For the function of materials, for example, catalysis, AI may well capture the behavior better than the theory of the past. However, currently the flexibility of AI comes together with a lack of interpretability, and AI can only predict aspects that were included in the training. The approach proposed and demonstrated in this IMPACT article is interpretable. It combines detailed experimental data (called "clean data") and symbolic regression for the identification of the key descriptive parameters (called "materials genes") that are correlated with the materials function. The approach demonstrated here for the catalytic oxidation of propane will accelerate the discovery of improved or novel materials while also enhancing physical understanding.

BackgroundPeriprosthetic infection is a major cause of failure after segmental endoprosthetic reconstruction. The purpose of this study is to determine whether certain aspects of drain output affect infection risk, particularly the 30 mL/day criterion for removal.MethodsTwo hundred and ninety-five patients underwent segmental bone resection and lower limb endoprosthetic reconstruction at one institution. Data on surgical drain management and occurrence of infection were obtained from a retrospective review of patients’ charts and radiographs. Univariate and multivariate Cox regression analyses were performed to identify factors associated with infection.ResultsThirty-one of 295 patients (10.5%) developed infection at a median time of 13 months (range 1–108 months).Staphylococcus aureuswas the most common organism and was responsible for the majority of cases developing within 1 year of surgery. Mean output at the time of drain removal was 72 mL/day. Ten of 88 patients (11.3%) with ≤ 30 mL/day drainage and 21 of 207 patients (10.1%) with > 30 mL/day drainage developed infection (p= 0.84). In multivariate analysis, independent predictive factors for infection included sarcoma diagnosis (HR 4.13, 95% CI 1.4–12.2,p= 0.01) and preoperative chemotherapy (HR 3.29, 95% CI 1.1–9.6,p= 0.03).ConclusionWaiting until drain output is < 30 mL/day before drain removal is not associated with decreased risk of infection for segmental endoprostheses of the lower limb after tumor resection. Sarcoma diagnosis and preoperative chemotherapy were independent predictors of infection.

Simple Summary Glioblastomas are high-grade brain tumours and are the most common form of malignancy arising in the brain. Patient survival has improved little over the last 40 years, highlighting an urgent unmet need for more effective treatments for these tumours. Current standard-of-care treatment involves surgical removal of as much of the tumour as possible followed by a course of chemo-/radiotherapy. The main chemotherapeutic drug used is called temozolomide, however even with this treatment regimen, the average patient survival following diagnosis is around 15 months. We have identified a protein called ERK5 which is present at higher levels in these high-grade brain tumours compared to normal brain tissue, and which is also associated with resistance to temozolomide and poor patient survival. Additionally, we show that targeting ERK5 in brain tumour cells can improve the effectiveness of temozolomide in killing these tumour cells and offers potential much-needed future clinical benefit to patients diagnosed with glioblastoma. Abstract Brain tumours kill more children and adults under 40 than any other cancer, with approximately half of primary brain tumours being diagnosed as high-grade malignancies known as glioblastomas. Despite de-bulking surgery combined with chemo-/radiotherapy regimens, the mean survival for these patients is only around 15 months, with less than 10% surviving over 5 years. This dismal prognosis highlights the urgent need to develop novel agents to improve the treatment of these tumours. To address this need, we carried out a human kinome siRNA screen to identify potential drug targets that augment the effectiveness of temozolomide (TMZ)—the standard-of-care chemotherapeutic agent used to treat glioblastoma. From this we identified ERK5/MAPK7, which we subsequently validated using a range of siRNA and small molecule inhibitors within a panel of glioma cells. Mechanistically, we find that ERK5 promotes efficient repair of TMZ-induced DNA lesions to confer cell survival and clonogenic capacity. Finally, using several glioblastoma patient cohorts we provide target validation data for ERK5 as a novel drug target, revealing that heightened ERK5 expression at both the mRNA and protein level is associated with increased tumour grade and poorer patient survival. Collectively, these findings provide a foundation to develop clinically effective ERK5 targeting strategies in glioblastomas and establish much-needed enhancement of the therapeutic repertoire used to treat this currently incurable disease.

An efficient computational method is presented based on the thick strip method for Large-Eddy simulation of flexible wings in stall. Fluid domain is break down into series of smaller 3k strips which one independently solved using implicit LES method. Force and moments are obtained from each strips and used to evolved the nonlinear dynamics of the structure. High deformation response of high-altitude long-endurance wing under several angle of attacks leading to the stall regions are presented to show the capability of proposed FSI method.

As COVID-19 vaccination begins worldwide, policymakers face critical trade-offs. Using a mathematical model of COVID-19 transmission, we find that timing of the rollout is expected to have a substantially greater impact on mortality than risk-based prioritization and uptake and that prioritizing first doses over second doses may be life saving.

The overlapping 2020-2021 influenza season and COVID-19 pandemic may overwhelm hospitals throughout the Northern Hemisphere. Using a mathematical model, we project that COVID-19 burden will dwarf that of influenza. If non-pharmacological mitigation efforts fail, increasing influenza vaccination coverage by 30% points would avert 54 hospitalizations per 100,000 people.

IntroductionDelirium is a potentially preventable disorder characterised by acute disturbances in attention and cognition with fluctuating severity. Postoperative delirium is associated with prolonged intensive care unit and hospital stay, cognitive decline and mortality. The development of biomarkers for tracking delirium could potentially aid in the early detection, mitigation and assessment of response to interventions. Because sleep disruption has been posited as a contributor to the development of this syndrome, expression of abnormal electroencephalography (EEG) patterns during sleep and wakefulness may be informative. Here we hypothesise that abnormal EEG patterns of sleep and wakefulness may serve as predictive and diagnostic markers for postoperative delirium. Such abnormal EEG patterns would mechanistically link disrupted thalamocortical connectivity to this important clinical syndrome.Methods and analysisP-DROWS-E (Prognosticating Delirium Recovery Outcomes Using Wakefulness and Sleep Electroencephalography) is a 220-patient prospective observational study. Patient eligibility criteria include those who are English-speaking, age 60 years or older and undergoing elective cardiac surgery requiring cardiopulmonary bypass. EEG acquisition will occur 1–2 nights preoperatively, intraoperatively, and up to 7 days postoperatively. Concurrent with EEG recordings, two times per day postoperative Confusion Assessment Method (CAM) evaluations will quantify the presence and severity of delirium. EEG slow wave activity, sleep spindle density and peak frequency of the posterior dominant rhythm will be quantified. Linear mixed-effects models will be used to evaluate the relationships between delirium severity/duration and EEG measures as a function of time.Ethics and disseminationP-DROWS-E is approved by the ethics board at Washington University in St. Louis. Recruitment began in October 2018. Dissemination plans include presentations at scientific conferences, scientific publications and mass media.Trial registration numberNCT03291626.

Although many studies on the frequency of endoparasites in dogs and cats in Canada have been reported, seasonal and/or annual patterns are often not evaluated. The frequency and risk factors of endoparasite infections from fecal samples of cats and dogs submitted to the Veterinary Teaching Hospital of the Atlantic Veterinary College, University of Prince Edward Island-Canada were determined, using univariable and multivariable logistic regression analyses. Investigated predictors of endoparasitism available in the 2000–2017 database included sex, age, geographic origin and seasonality. A total of 15,016 dogs and 2,391 cats were evaluated for endoparasite status using specific diagnostic tests: direct smear, Baermann, and/or 33 % zinc sulfate solution in a standardized centrifugal flotation method. Overall, twelve and eight parasite genera were detected in dogs and cats, respectively. The overall proportional infection was 14.6 %, and the cat population showed a higher frequency of positivity to parasites compared to the dog population (P < 0.001). The most frequent genera recovered in the whole population (dogs and cats), were Giardia duodenalis (5.2 %), Cystoisospora spp. (3.3 %) and Toxocara spp. (3.2 %). Endoparasitism levels were diagnosed more in feces submitted from young, female intact dogs from PEI compared to the baselines of mature, sterilized male dogs from other provinces, respectively, and diagnoses occurred more often in autumn months than in winter months. There was no significant diagnostic trend across the years for the individual parasites models. The frequency of detected potentially zoonotic parasites in this study highlights the veterinary public health and One Health context of parasitic infections in pets. Although the presented results are not from a random sample and therefore frequency results should be interpreted with caution, the model relationship results may still be relevant. In addition, results are of value to estimate parasite impact and to assist researchers, veterinarians and pet-owners with suitable information to control parasites.

OBJECTIVE: Patients with severe mitral regurgitation commonly develop atrial fibrillation. The precise mechanisms of this relationship remain unknown. The objective of this study was to apply noninvasive electrocardiographic imaging of the atria during sinus rhythm to identify changes in atrial electrophysiology that may contribute to development of atrial fibrillation in patients with severe mitral regurgitation referred for mitral valve surgery. METHODS: Twenty subjects (9 atrial fibrillation and mitral regurgitation, 11 mitral regurgitation alone) underwent electrocardiographic imaging. Biatrial electrophysiology was imaged with activation maps in sinus rhythm. The reconstructed unipolar electrograms were analyzed for voltage amplitude, number of deflections and conduction heterogeneity. In subjects with mitral regurgitation, left atrial biopsies were obtained at the time of surgery. Results: Subjects with history of atrial fibrillation demonstrated prolonged left atrial conduction times (110±25 ms vs. mitral regurgitation alone (85±21), p=0.025); right atrial conduction times were unaffected. Variable patterns of conduction slowing were imaged in the left atria of most subjects, but those with prior history of atrial fibrillation had more complex patterns of conduction slowing or unidirectional block. The presence of atrial fibrillation was not associated with the extent of fibrosis in atrial biopsies. CONCLUSIONS: Detailed changes in sinus rhythm atrial electrophysiology can be imaged noninvasively and can be used to assess the impact and evolution of atrial fibrillation on atrial conduction properties in patients with mitral regurgitation. If replicated in larger studies, electrocardiographic imaging may identify patients with mitral regurgitation at risk for atrial fibrillation and could be used to guide treatment strategies.

Key Points Question Is construction work associated with increased community transmission of coronavirus disease 2019 (COVID-19) and disproportionate morbidity among construction workers in US cities? Findings This decision analytical model of COVID-19 found that resuming construction work during shelter-in-place orders was associated with increased hospitalization risks in the construction workforce and increase transmission in the surrounding community. Based on COVID-19 hospitalization data through August 20, 2020, construction workers had a nearly 5-fold increased risk of hospitalization in central Texas compared with other occupational categories. Meaning The findings of this study suggest that enacting workplace safety policies and providing paid sick leave could protect essential workers in high-contact industries and prevent further widening of disparities in COVID-19 morbidity and mortality., This decision analytical model assesses the association between construction work during the coronavirus disease 2019 (COVID-19) pandemic and hospitalization rates for construction workers and the surrounding community., Importance Policy makers have relaxed restrictions for certain nonessential industries, including construction, jeopardizing the effectiveness of social distancing measures and putting already at-risk populations at greater risk of coronavirus disease 2019 (COVID-19) infection. In Texas, Latinx populations are overly represented among construction workers, and thus have elevated rates of exposure that are compounded by prevalent high-risk comorbidities and lack of access to health care. Objective To assess the association between construction work during the COVID-19 pandemic and hospitalization rates for construction workers and the surrounding community. Design, Setting, and Participants This decision analytical model used a mathematical model of COVID-19 transmission, stratified by age and risk group, with construction workers modeled explicitly. The model was based on residents of the Austin–Round Rock metropolitan statistical area, with a population of 2.17 million. Based on 500 stochastic simulations for each of 15 scenarios that varied the size of the construction workforce and level of worksite transmission risk, the association between continued construction work and hospitalizations was estimated and then compared with anonymized line-list hospitalization data from central Texas through August 20, 2020. Exposures Social distancing interventions, size of construction workforce, and level of disease transmission at construction worksites. Main Outcomes and Measures For each scenario, the total number of COVID-19 hospitalizations and the relative risk of hospitalization among construction workers was projected and then compared with relative risks estimated from reported hospitalization data. Results Allowing unrestricted construction work was associated with an increase of COVID-19 hospitalization rates through mid-August 2020 from 0.38 per 1000 residents to 1.5 per 1000 residents and from 0.22 per 1000 construction workers to 9.3 per 1000 construction workers. This increased risk was estimated to be offset by safety measures (such as thorough cleaning of equipment between uses, wearing of protective equipment, limits on the number of workers at a worksite, and increased health surveillance) that were associated with a 50% decrease in transmission. The observed relative risk of hospitalization among construction workers compared with other occupational categories among adults aged 18 to 64 years was 4.9 (95% CI, 3.8-6.2). Conclusions and Relevance The findings of this study suggest that unrestricted work in high-contact industries, such as construction, is associated with a higher level of community transmission, increased risks to at-risk workers, and larger health disparities among members of racial and ethnic minority groups.

Central blood pressure (cBP) is a highly prognostic cardiovascular (CV) risk factor whose accurate, invasive assessment is costly and carries risks to patients. We developed and assessed novel algorithms for estimating cBP from noninvasive aortic hemodynamic data and a peripheral blood pressure measurement. These algorithms were created using three blood flow models: the two- and three-element Windkessel (0-D) models and a one-dimensional (1-D) model of the thoracic aorta. We tested new and existing methods for estimating CV parameters (left ventricular ejection time, outflow BP, arterial resistance and compliance, pulse wave velocity, and characteristic impedance) required for the cBP algorithms, using virtual (simulated) subjects (n = 19,646) for which reference CV parameters were known exactly. We then tested the cBP algorithms using virtual subjects (n = 4,064), for which reference cBP were available free of measurement error, and clinical datasets containing invasive (n = 10) and noninvasive (n = 171) reference cBP waves across a wide range of CV conditions. The 1-D algorithm outperformed the 0-D algorithms when the aortic vascular geometry was available, achieving central systolic blood pressure (cSBP) errors ≤ 2.1 ± 9.7 mmHg and root-mean-square errors (RMSEs) ≤ 6.4 ± 2.8 mmHg against invasive reference cBP waves (n = 10). When the aortic geometry was unavailable, the three-element 0-D algorithm achieved cSBP errors ≤ 6.0 ± 4.7 mmHg and RMSEs ≤ 5.9 ± 2.4 mmHg against noninvasive reference cBP waves (n = 171), outperforming the two-element 0-D algorithm. All CV parameters were estimated with mean percentage errors ≤ 8.2%, except for the aortic characteristic impedance (≤13.4%), which affected the three-element 0-D algorithm’s performance. The freely available algorithms developed in this work enable fast and accurate calculation of the cBP wave and CV parameters in datasets containing noninvasive ultrasound or magnetic resonance imaging data. NEW & NOTEWORTHY First, our proposed methods for CV parameter estimation and a comprehensive set of methods from the literature were tested using in silico and clinical datasets. Second, optimized algorithms for estimating cBP from aortic flow were developed and tested for a wide range of cBP morphologies, including catheter cBP data. Third, a dataset of simulated cBP waves was created using a three-element Windkessel model. Fourth, the Windkessel model dataset and optimized algorithms are freely available., This work was supported by a PhD Fellowship awarded by the King’s College London and Imperial College London EPSRC Centre for Doctoral Training in Medical Imaging [EP/L015226/1], the British Heart Foundation (BHF) [PG/15/104/31913], and the Wellcome EPSRC Centre for Medical Engineering at King’s College London [WT 203148/Z/16/Z]. The authors acknowledge financial support from the Department of Health through the National Institute for Health Research (NIHR) Cardiovascular MedTech Co-operative at Guy’s and St Thomas’ NHS Foundation Trust (GSTT).

Letter textThe prevalence of asymptomatic COVID-19 infections is largely unknown and may determine the course of future pandemic waves and the effectiveness of interventions. Using an epidemiological model fit to COVID-19 hospitalization counts from New York City, New York and Austin, Texas, we found that the undocumented attack rate in the first pandemic wave depends on the proportion of asymptomatic infections but not on the infectiousness of such individuals. Based on a recent report that 22.7% of New Yorkers are seropositive for SARS-CoV-2, we estimate that 56% (95% CI: 53-59%) of COVID-19 infections are asymptomatic. Given uncertainty in the case hospitalization rate, however, the asymptomatic proportion could be as low as 20% or as high as 80%. We find that at most 1.26% of the Austin population was infected by April 27, 2020 and conclude that immunity from undetected infections is unlikely to slow future pandemic spread in most US cities in the summer of 2020.

BACKGROUND: Bipolar radiofrequency (RF) clamps have been shown to be capable of reproducibly creating transmural lesions with a single ablation in animal models. Unfortunately, in clinical experience, the bipolar clamps have not been as effective, and often require multiple ablations to create conduction block. This study created a new experimental model using fresh, cardioplegically-arrested human hearts turned down for transplantation to evaluate the performance of a non-irrigated bipolar RF clamp. METHODS: Nine human hearts turned down for transplantation were harvested and the Cox-Maze IV lesion set was performed with a non-irrigated bipolar RF clamp. In the first seven hearts, a single ablation was performed for each lesion. In the last two hearts, a set of two successive ablations without unclamping were performed. The heart tissue was stained with 2,3,5-triphenyl-tetrazolium chloride. Each ablation lesion was cross-sectioned to assess lesion depth and transmurality. RESULTS: A single ablation with the bipolar RF clamp resulted in 89% (469/529) of the histologic sections and 65% (42/65) of the lesions being transmural. Of the non-transmural sections, 92% occurred in areas with epicardial fat. Performing two successive ablations without unclamping resulted in 100% of the cross-sections (201/201) and lesions (25/25) being transmural. CONCLUSIONS: A single ablation failed to create a transmural lesion 35% of the time, and this was associated with the presence of epicardial fat. Two successive ablations without unclamping resulted in 100% lesion transmurality using the bipolar RF clamp.

Objectives Stand-alone surgical ablation of atrial fibrillation is indicated in patients with refractory atrial fibrillation who have failed medical or catheter-based ablation. Few reports of late outcomes after stand-alone surgical ablation exist using comprehensive follow-up with strict definitions of success. This study examined our late outcomes of the stand-alone Cox-Maze IV procedure. Methods Between January 2003 and December 2019, 236 patients underwent a stand-alone Cox-Maze IV for refractory atrial fibrillation. Freedom from atrial tachyarrhythmias was assessed by electrocardiography, Holter, or pacemaker interrogation for up to 10 years, with a mean follow-up of 4.8 ± 3.5 years. Rhythm outcomes were compared in multiple subgroups. Factors associated with recurrence were determined using Fine-Gray regression, allowing for death as the competing risk. Results The majority of patients (176/236, 75%) had nonparoxysmal atrial fibrillation. Median duration of preoperative atrial fibrillation was 6.2 years (interquartile range, 3-11). Fifty-nine percent of patients (140/236) failed 1 or more prior catheter-based ablation. Thirteen patients (6%) experienced a major complication. There was no 30-day mortality. Freedom from atrial tachyarrhythmias was 94% (187/199), 89% (81/91), and 77% (24/31) at 1, 5, and 10 years, respectively. There was no difference in freedom from atrial tachyarrhythmias between patients with paroxysmal atrial fibrillation versus nonparoxysmal atrial fibrillation (P > .05) or those undergoing sternotomy versus a minimally invasive approach (P > .05). Increased left atrial size and number of catheter ablations were associated with late atrial fibrillation recurrence. For patients who experienced any atrial tachyarrhythmia recurrence, the median number of recurrences was 1.5 (1.0-3.0). Conclusions The stand-alone Cox-Maze IV had excellent late efficacy at maintaining sinus rhythm in patients with symptomatic, refractory atrial fibrillation, with low morbidity and no mortality. The Cox-Maze IV, in contrast to catheter-based ablation, was equally effective in patients with paroxysmal and nonparoxysmal atrial fibrillation.

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, has pushed the health systems of many countries to breaking point and precipitated social distancing measures that have crippled economic activities across the globe. A return to normality is unlikely until effective therapeutics and a vaccine are available. The immediacy of this problem suggests that drug strategies should focus on repurposing approved drugs or late-stage clinical candidates, as these have the shortest path to use in the clinic. Here, we review and discuss the role of host cell N-glycosylation pathways to virus replication and the drugs available to disrupt these pathways. In particular, we make a case for evaluation of the well-tolerated drugs miglitol, celgosivir and especially miglustat for the treatment of COVID-19.

BackgroundA novel coronavirus (SARS-CoV-2) emerged in Wuhan, China in late 2019 and rapidly spread worldwide. In the absence of effective antiviral drugs and vaccines, well-targeted social distancing measures are essential for mitigating the COVID-19 pandemic, reducing strain on local health systems, and preventing mortality. Here, we provide a quantitative assessment of the efficacy of social distancing to slow COVID-19 transmission and reduce hospital surge, depending on the timing and extent of the measures imposed for a metropolitan region and its health care systems.Methods and FindingsWe built a granular mathematical model of COVID-19 transmission that incorporated age-specific and risk-stratified heterogeneity, estimates for the transmission, and severity of COVID-19 using current best evidence. We performed thousands of stochastic simulations of COVID-19 transmission in the Austin-Round Rock Metropolitan Area to project the impact of school closures coupled with social distancing measures that were estimated to reduce non-household contacts by 0%, 25%, 50%, 75% or 90%. We compare early versus late implementation and estimate the number of COVID-19 hospitalizations, ICU patients, ventilator needs and deaths through mid-August, 2020. We queried local emergency services and hospital systems to estimate total hospital bed, ICU, and ventilator capacity for the region. We expected COVID-19 hospital beds and ICU requirements would surpass local capacity by mid-May if no intervention was taken.Assuming a four-day epidemic doubling time, school closures alone would be expected to reduce peak hospitalizations by only 18% and cumulative deaths by less than 3%. Immediate social distancing measures that reduced non-household contacts by over 75%, such as stay-at-home orders and closing of non-essential businesses, would be required to ensure that COVID-19 cases do not overwhelm local hospital surge capacity. Peak ICU bed demand prior to mid August 2020 would be expected to be reduced from 2,121 (95% CI: 2,018-2,208) with no intervention to 698 (95% CI: 204-1,100) with 75% social distancing and 136 (95% CI: 38-308) with 90% social distancing; current ICU bed capacity was estimated at 680. A two-week delay in implementation of such measures is projected to accelerate a local ICU bed shortage by four weeks.ConclusionsSchool closures alone hardly impact the epidemic curve. Immediate social distancing measures that reduce non-household contacts by over 75% were required to ensure that COVID-19 cases do not overwhelm local hospital surge capacity. These findings helped inform the Stay Home-Work Safe order enacted by the city of Austin, Texas on March 24, 2020 as a means of mitigating the emerging COVID-19 epidemic.

We investigated characteristics of patients with colon cancer that predicted nonreceipt of posttreatment surveillance testing and the subsequent associations between surveillance status and survival outcomes. This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Patients diagnosed between 2002 and 2009 with disease stages II and III and who were between 66 and 84 years of age were eligible. A minimum of 3 years’ follow-up was required, and patients were categorized as having received any surveillance testing (any testing) versus none (no testing). Poisson regression was used to obtain risk ratios with 95% confidence intervals for the relative likelihood of No Testing. Cox models were used to obtain subdistribution hazard ratios with 95% confidence intervals for 5- and 10-year cancer-specific and noncancer deaths. There were 16,009 colon cancer cases analyzed. Patient characteristics that predicted No Testing included older age, Black race, stage III disease, and chemotherapy. Patients in the No Testing group had an increased rate of 10-year cancer death that was greater for patients with stage III disease (subdistribution hazard ratio = 1.79, 95% confidence interval: 1.48, 2.17) than those with stage II disease (subdistribution hazard ratio = 1.41, 95% confidence interval: 1.19, 1.66). Greater efforts are needed to ensure all patients receive the highest quality medical care after diagnosis of colon cancer.

Background: Advances in the health sciences rely on sharing research and data through publication. As information professionals are often asked to contribute their knowledge to assist clinicians and researchers in selecting journals for publication, the authors recognized an opportunity to build a decision support tool, SPI-Hub: Scholarly Publishing Information Hub™, to capture the team’s collective publishing industry knowledge, while carefully retaining the quality of service.Case Presentation: SPI-Hub’s decision support functionality relies on a data framework that describes journal publication policies and practices through a newly designed metadata structure, the Knowledge Management Journal Record™. Metadata fields are populated through a semi-automated process that uses custom programming to access content from multiple sources. Each record includes 25 metadata fields representing best publishing practices. Currently, the database includes more than 24,000 health sciences journal records. To correctly capture the resources needed for both completion and future maintenance of the project, the team conducted an internal study to assess time requirements for completing records through different stages of automation.Conclusions: The journal decision support tool, SPI-Hub, provides an opportunity to assess publication practices by compiling data from a variety of sources in a single location. Automated and semi-automated approaches have effectively reduced the time needed for data collection. Through a comprehensive knowledge management framework and the incorporation of multiple quality points specific to each journal, SPI-Hub provides prospective users with both recommendations for publication and holistic assessment of the trustworthiness of journals in which to publish research and acquire trusted knowledge.