A radio-detected type Ia supernova with helium-rich circumstellar material.

Type Ia supernovae (SNe Ia) are thermonuclear explosions of degenerate white dwarf stars destabilized by mass accretion from a companion star1, but the nature of their progenitors remains poorly understood. A way to discriminate between progenitor systems is through radio observations; a non-degenerate companion star is expected to lose material through winds2 or binary interaction3 before explosion, and the supernova ejecta crashing into this nearby circumstellar material should result in radio synchrotron emission. However, despite extensive efforts, no type Ia supernova (SN Ia) has ever been detected at radio wavelengths, which suggests a clean environment and a companion star that is itself a degenerate white dwarf star4,5. Here we report on the study of SN 2020eyj, a SN Ia showing helium-rich circumstellar material, as demonstrated by its spectral features, infrared emission and, for the first time in a SN Ia to our knowledge, a radio counterpart. On the basis of our modelling, we conclude that the circumstellar material probably originates from a single-degenerate binary system in which a white dwarf accretes material from a helium donor star, an often proposed formation channel for SNe Ia (refs. 6,7). We describe how comprehensive radio follow-up of SN 2020eyj-like SNe Ia can improve the constraints on their progenitor systems.

CarboGrove: a resource of glycan-binding specificities through analyzed glycan-array datasets from all platforms.

Glycan arrays continue to be the primary resource for determining the glycan-binding specificity of proteins. The volume and diversity of glycan-array data are increasing, but no common method and resource exist to analyze, integrate, and use the available data. To meet this need, we developed a resource of analyzed glycan-array data called CarboGrove. Using the ability to process and interpret data from any type of glycan array, we populated the database with the results from 35 types of glycan arrays, 13 glycan families, 5 experimental methods, and 19 laboratories or companies. In meta-analyses of glycan-binding proteins, we observed glycan-binding specificities that were not uncovered from single sources. In addition, we confirmed the ability to efficiently optimize selections of glycan-binding proteins to be used in experiments for discriminating between closely related motifs. Through descriptive reports and a programmatically accessible Application Programming Interface, CarboGrove yields unprecedented access to the wealth of glycan-array data being produced and powerful capabilities for both experimentalists and bioinformaticians.

Statins Are Associated With Increased Insulin Resistance and Secretion.

Objective: Statin treatment reduces the risk of atherosclerotic cardiovascular disease but is associated with a modest increased risk of type 2 diabetes, especially in those with insulin resistance or prediabetes. Our objective was to determine the physiological mechanism for the increased type 2 diabetes risk. Approach and Results: We conducted an open-label clinical trial of atorvastatin 40 mg daily in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline. The co-primary outcomes were changes at 10 weeks versus baseline in insulin resistance as assessed by steady-state plasma glucose during the insulin suppression test and insulin secretion as assessed by insulin secretion rate area under the curve (ISRAUC) during the graded-glucose infusion test. Secondary outcomes included glucose and insulin, both fasting and during oral glucose tolerance test. Of 75 participants who enrolled, 71 completed the study (median age 61 years, 37% women, 65% non-Hispanic White, median body mass index, 27.8 kg/m2). Atorvastatin reduced LDL (low-density lipoprotein)-cholesterol (median decrease 53%, P<0.001) but did not change body weight. Compared with baseline, atorvastatin increased insulin resistance (steady-state plasma glucose) by a median of 8% (P=0.01) and insulin secretion (ISRAUC) by a median of 9% (P<0.001). There were small increases in oral glucose tolerance test glucoseAUC (median increase, 0.05%; P=0.03) and fasting insulin (median increase, 7%; P=0.01). Conclusions: In individuals without type 2 diabetes, high-intensity atorvastatin for 10 weeks increases insulin resistance and insulin secretion. Over time, the risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion.

NF-κB mediates lipopolysaccharide-induced alternative pre-mRNA splicing of MyD88 in mouse macrophages.

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled.

Cultural Complications Curriculum: Applicability to Surgical Oncology Programs and Practices.

BACKGROUND: Recognizing the need to raise awareness of core diversity, equity, and inclusion (DEI) issues in the healthcare system, our previously developed Cultural Complications Curriculum aims to support institutions in reducing cultural error. As we continue program deployment, we discuss the opportunity to apply the Cultural Complications Curriculum to multidisciplinary audiences, such as in cancer programs. METHODS: We discuss applicability of the Cultural Complications Curriculum to cancer programs and practices, including how to tailor case discussions to oncology audiences. By emphasizing the unique characteristics of the multidisciplinary care environment and anticipating potential barriers to curriculum implementation, we demonstrate how the Cultural Complications Curriculum may support culture improvement across broad audiences. RESULTS: The successful application of the Cultural Complication Curriculum to multidisciplinary care programs will depend on appreciating differences in background knowledge, tailoring discussions to audience needs, and adapting material by incorporating new data and addressing emerging DEI issues. Multidisciplinary environments may require innovative approaches to education including virtual platforms, increased collaboration across centers and systems, and support from professional societies. In integrated care environments, like oncology, effective DEI discussions call for the engagement of a variety of medical specialties and departments. CONCLUSIONS: To meet the needs of an increasingly diverse patient population and workforce, our approach to DEI education must embrace the interdependent nature of care delivery. In oncology and other multidisciplinary care environments, application of the Cultural Complications Curriculum may be the first step to combating cultural error by engaging a broader demographic within our healthcare system.

Patterns of Community Violence Exposure among African American Adolescents Living in Low-Resourced Urban Neighborhoods.

African American adolescents living in neighborhoods with concentrated economic disadvantage are disproportionately exposed to community violence. This study builds upon previous research and examines patterns, severity, and chronicity of violence exposure, within a sample of African American adolescents living in low-resourced, urban neighborhoods (n = 327). The influence of both individual- and contextual-level factors on community violence exposure (CVE) is examined. Data were collected across four time points at 6-month intervals. Latent transition analysis identified three patterns of CVE at each time point: low witnessing and low victimization (LW-LV), high witnessing and low victimization (HW-LV), and high witnessing and high victimization (HW-HV), as well as transitions between each class. Although a stable LW-LV class membership over time was the most prevalent pattern, most adolescents experienced some change in exposure. Nearly one-third of the participants were classified in the HW-HV group at some point in time. Analyses on individual- and contextual-level factors revealed that more depressive symptoms, community problems (e.g., drugs, graffiti, noise), or community resources (e.g., schools, parks, recreational facilities) were associated with an increased likelihood of experiencing high levels of violent victimization. Implications for intervention and prevention of CVE are discussed.

Sex Disparity in Academic Rank and Industry Payments to Plastic Surgeons.

INTRODUCTION: Despite increasing representation in surgery, women continue to lag behind men in important metrics. Little is known on how industry funding may also contribute to this ongoing disparity. This article seeks to quantify industry payments to academic plastic surgeons (APSs) by sex and examine the relationship between funding and academic achievement. METHODS: We conducted a cross-sectional analysis of industry payments disbursed to APSs in 2017. Faculty were identified using departmental listings of Accreditation Council for Graduate Medical Education plastic surgery residency programs. Payments were identified via the Center for Medicare and Medicaid Services open payment database. Academic achievement was assessed using rank (eg, assistant professor), leadership designation (eg, division head), and Scopus H-index and then controlled for time in practice. RESULTS: Of the 805 APSs, the majority were male (82% male vs 18% female, P < 0.0001). Significant sex differences emerged in average yearly industry contributions (men, US $3202, vs women, US $707; P < 0.0001). Across all academic ranks, men received significantly higher payments than women (P < 0.0500). Men constituted 93% of full professors and were almost twice as likely to hold additional leadership positions compared with women (odds ratio, 1.82; P = 0.0143). After adjustment for time in practice, there was no difference in H-indices between male and female APSs, although payment disparity persisted (P < 0.0001). CONCLUSIONS: Substantial sex-based disparities exist among APSs' academic rank and leadership attainment, which is not attributed to differences in academic qualifications or experience. To better elucidate the sources of this disparity, future studies should assess sexed differences in payment types. Furthermore, we urge for increased transparency in the selection process for industry payments.

Editorial (Spring) Board? Gender Composition in High-impact General Surgery Journals Over 20 Years.

OBJECTIVE: To quantify gender composition of 10 high-impact general surgery journals, delineate how board composition has changed over time, and evaluate qualification metrics by gender. BACKGROUND: Underrepresentation of women on editorial boards may contribute to the gender-based achievement gap in surgery. METHODS: We performed a cross-sectional analysis of the editorial board gender composition among 10 high-impact general surgery journals in 1997, 2007, and 2017. Univariate and multivariate regression analyses were used to assess differences in editors' H-indices, academic rank, and number of advanced degrees. Differences in editor turnover and multiple board positions were evaluated for each time interval. RESULTS: Over 20 years, the proportion of women on editorial boards increased from 5% to 19%. After controlling for time since board certification, no differences between men and women's number of advanced degrees, H-indices, or academic rank remained significant. Women and men were equally likely to hold multiple board positions (1997 P = 0.74; 2007 P = 0.42; 2017 P = 0.69), but men's editorial board tenure was longer across each time interval (1997-2007 P = 0.003; 2007-2017 P < 0.001; 1997-2017 P = 0.01). CONCLUSIONS: Women surgeons have a small but growing presence on surgical editorial boards, and gender-based qualification differences are likely attributable to practice length. Men's longer tenure on editorial boards may drive some of the observed disparity by limiting new appointment opportunities. Strategies such as imposing term limits or instituting merit-based performance reviews may help editorial boards capture the field's changing demographics.

Not Further Specified: Unclassified Orthopedic Injuries in Trauma Registries, Cause for Concern?

BACKGROUND: Data accuracy is essential to obtaining correct results and making appropriate conclusions in outcomes research. Few have examined the quality of data that is used in studies involving orthopedic surgery. A nonspecific data entry has the potential to affect the results of a study or the ability to appropriately risk adjust for treatments and outcomes. This study evaluated the proportion of Not Further Specified (NFS) orthopedic injury codes found into two large trauma registries. MATERIALS: Data from the National Trauma Data Bank (NTDB) from 2011 to 2015 and from the Michigan Trauma Quality Improvement Program (MTQIP) 2011-2017 were used. We selected multiple orthopedic injuries classified via the Abbreviated Injury Scale, version 2005 (AIS2005) and calculated the percentage of NFS entries for each specific injury. RESULTS: There were a substantial proportion of fractures classified as NFS in each registry, 18.5% (range 2.4%-67.9%) in MTQIP and 27% (range 6.0%-68.5%) in the NTDB. There were significantly more NFS entries when the fractures were complex versus simple in both MTQIP (34.5% versus 9.6%, P < 0.001) and the NTDB (41.8% versus 15.7%, P < 0.001). The level of trauma center affected the proportion of NFS codes differently between the registries. CONCLUSIONS: The proportion of nonspecific entries in these two large trauma registries is concerning. These data can affect the results and conclusions from research studies as well as impact our ability to truly risk adjust for treatments and outcomes. Further studies should explore the reasons for these findings.

Leveraging the Medical Context to Increase Upper Extremity Reconstruction Among Patients With Tetraplegia: A Qualitative Analysis.

OBJECTIVES: To (1) characterize patients' medical experiences from initial injury until they become candidates for upper extremity reconstruction (UER); and (2) identify points in this medical context that may be most amenable to interventions designed to increase UER utilization. DESIGN: A qualitative cross-sectional study using grounded theory methodology and constant comparative analysis of data collected through semistructured individual interviews. SETTING: Community. PARTICIPANTS: A sample of individuals with C4 to C8 cervical spinal injuries (N=19) who sustained injuries at least 1 year before interview. Nine patients had undergone reconstruction, and 10 had not. The study sample was predominantly male (79%) and white (89%), and American Spinal Injury Association grades A through D were represented (A, 42%; B, 32%; C, 16%; D, 10%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants' self-report of their medical experiences from the time of injury through the early recovery period. RESULTS: We identified 3 domains that formed patients' medical context before UER candidacy: (1) their ability to achieve and maintain health; (2) their relationship with health care providers; and (3) their expectations regarding clinicians' tetraplegia-specific expertise. Trust emerged as a major theme driving potential intervention targets. Patients transferred to referral centers had higher trust in tertiary providers relative to local physicians. In the outpatient setting, patients' trust correlated with the tetraplegia-specific expertise level they perceived the specialty to have (high for physical medicine and rehabilitation, intermediate for urology, low for primary care). CONCLUSIONS: In appropriate candidates, UER produces substantial functional gains, but reconstruction remains underused in the tetraplegic population. By analyzing how patients achieve health and build trust in early recovery/injury, our study provides strategies to improve UER access. We propose that interventions targeting highly trusted points of care (transfer hospitals) and avoiding low-trust points (primary care physicians, home health) will be most effective. Urology may represent a novel entry point for UER interventions.

Type 1 Diabetes: Management Strategies.

There is considerable benefit of tight glucose control in patients with type 1 diabetes mellitus. Tight blood glucose control dramatically decreases the incidence of microvascular and macrovascular complications. Although glycemic goals should be individualized, most nonpregnant adults should strive for an A1C level less than 7%. Greater frequency of glucose monitoring and continuous glucose monitoring are both associated with lower A1C levels. The choice to monitor glucose levels via multiple daily capillary blood samples or continuous glucose monitoring is based on cost and patient preference. Intensive insulin treatment is recommended with a combination of multiple mealtime bolus and basal injections or with continuous insulin infusion through an insulin pump. The option to administer insulin with multiple daily injections vs. a pump should be individualized. Adjunctive medical therapy is under investigation but is not currently recommended. All patients with type 1 diabetes should participate in diabetes self-management education and develop individualized premeal insulin bolus plans under the guidance of a dietitian, if possible. Blood pressure and lipid control are important to prevent cardiovascular disease events. Patients with type 1 diabetes should have sick-day plans and be able to identify warning signs of hypoglycemia and diabetic ketoacidosis. Advances in diabetes care, including the bionic pancreas and the closed-loop system of glucose monitoring with an automated insulin pump, may have a significant effect on type 1 diabetes care in the years ahead.

Understanding Patient Preferences in Proximal Interphalangeal Joint Surgery for Osteoarthritis: A Conjoint Analysis.

PURPOSE: We sought to compare preferences for arthroplasty versus arthrodesis among patients with proximal interphalangeal (PIP) joint osteoarthritis (OA) by quantifying the patient-assigned utility of each operation's attributes. METHODS: We undertook a multistep process to identify relevant surgical attributes, including a literature review, surgeon survey, and pretest patient pilot test to build a set of discrete choice experiments. Patients with PIP joint osteoarthritis were identified using a single university electronic medical record and were recruited via electronic message or postcard. Participants completed a demographic survey and 11 discrete choice experiments designed using Sawtooth Software's Discover tool. Utility and importance scores were generated for each attribute. RESULTS: Pretest analysis identified out-of-pocket cost, joint stiffness, need for future surgery, change in grip strength, and total recovery time as the most important surgical attributes. Initial response rate to the conjoint survey was 75% and survey completion rate was 61%. The study sample was predominantly white (91%) and female (72%), mean age 64.3 years (range, 34-90 years), and mean daily pain score was 4.32 (range, 0-10). Attribute importance scores demonstrated that joint stiffness (32%) and grip strength (29%) were most important to patients. Cost (17%) and need for future surgery (19%) were intermediate patient-preference drivers. Recovery time was the least important attribute (2%). CONCLUSIONS: In aggregate, patients prefer surgical attributes characteristic of arthroplasty (ability to preserve joint motion and grip strength) relative to those associated with arthrodesis (decreased need for reoperation, lower costs, and shorter reoperation times). TYPE OF STUDY/LEVEL OF EVIDENCE: Economic/Decision Analysis III.

What is in a Pronoun?: Why Gender-fair Language Matters.

MINI: Mounting evidence demonstrates that gender inequity is perpetuated by language. As such, understanding the ways in which linguistic bias reinforces gender and other stereotypes is paramount to creating a culture of inclusivity. This perspective reviews the science detailing the ways language reinforces gender inequality and offers strategies to reduce linguistic bias.

Checkpoints to Progression: Qualitative Analysis of the Personal and Contextual Factors That Influence Selection of Upper Extremity Reconstruction Among Patients With Tetraplegia.

PURPOSE: Patients with tetraplegia consistently rank better use of the upper extremity as their top functional priority. Multiple case series have demonstrated that upper extremity reconstruction (UER) is well-tolerated and can produce substantial functional improvements for appropriate candidates; however, UER remains critically underutilized. The mechanisms that drive differences in provider practice and referral patterns have been studied, but comprehensive examination of the patient factors that influence UER decisions has not been performed for American patients. METHODS: Nineteen patients with C4-8 cervical spinal injuries were selected using purposive sampling: 9 patients had undergone UER, 10 had not undergone UER. Semistructured interviews were conducted and transcripts evaluated using grounded theory methodology. RESULTS: Our study yielded a conceptual model that describes the characteristics common to all patients who undergo UER. Patients who selected reconstruction proceeded stepwise through a shared sequence of steps: (1) functional dissatisfaction, (2) awareness of UER, and (3) acceptance of surgery. Patients' ability to meet these criteria was determined by 3 checkpoints: how well they coped, their access to information, and the acceptability of surgery. Extremely positive or negative coping prevented patients from moving from the Coping to the Information Checkpoint; thus, they remained unaware of UER and did not undergo surgery. A lack of knowledge regarding reconstruction was the strongest barrier to surgery among our participants. CONCLUSIONS: We built a conceptual model that outlines how patients' personal and contextual factors drive their progression to UER. Moving from functional dissatisfaction to understanding that they were candidates for UER was a substantial barrier for participants, particularly those with very high and very low coping skills. CLINICAL RELEVANCE: To improve utilization for all patients, interventions are needed to increase UER awareness. Standardizing introduction to UER during the rehabilitation process or improving e-content may represent key awareness access points.

Over-the-counter anti-oxidant therapies for use in multiple sclerosis: A systematic review.

BACKGROUND: Anti-oxidant compounds that are found in over-the-counter (OTC) supplements and foods are gaining interest as treatments for multiple sclerosis (MS). They are widely used by patients, sometimes without a clear evidence base. OBJECTIVE: We conducted a systematic review of animal and clinical research to determine the evidence for the benefits of OTC anti-oxidants in MS. METHODS: Using predefined criteria, we searched key databases. Two authors scrutinized all studies against inclusion/exclusion criteria, assessed study risk-of-bias and extracted results. RESULTS: Of the 3507 titles, 145 met criteria and included compounds, α(alpha)-lipoic acid (ALA), anti-oxidant vitamins, Ginkgo biloba, quercetin, resveratrol and epigallocatechin-3-gallate (ECGC). The strongest evidence to support OTC anti-oxidants was for compounds EGCG and ALA in animal models; both consistently showed anti-inflammatory/anti-oxidant effects and reduced neurological impairment. Only vitamin E, Ginkgo biloba and ALA were examined for efficacy in pilot clinical trials with either conflicting evidence or evidence of no benefit. CONCLUSION: OTC anti-oxidants EGCG and ALA show the most consistent benefit, however only in preclinical studies. There is no evidence that they alter MS relapses or progression. Future work should focus on testing more of these therapies for clinical efficacy before recommending them to MS patients.

Predictors of chronic cerebrospinal venous insufficiency procedure use among older people with multiple sclerosis: a national case-control study.

BACKGROUND: Following the initial reports of Chronic Cerebrospinal Venous Insufficiency (CCSVI) and the purported curative potential of venoplasty, (coined the 'liberation' procedure) Canadians living with multiple sclerosis (MS) began to travel abroad to receive the unregulated procedure, often placing them at odds with their health providers. The purpose of this study was to determine the factors influencing older MS patients' decision to undergo the procedure in order to develop more specific and targeted health information. METHODS: We performed secondary analysis of data collected as part of the 'Canadian Survey of Health Lifestyle and Aging with MS' from people over the age of 55 years with MS symptoms for 20 or more years. The survey consisted of self-reported information on impairments, disability, participation, demographics, personal and environmental factors. In order to compare respondents who underwent the procedure to those who did not and to develop a predictive model, we created a comparison group using a case-control algorithm, controlling for age, gender and education, and matching procedure cases to controls 1:3. We used multivariate stepwise least likelihood regression of 'a priori' variables to determine predictive factors. RESULTS: The prevalence of the 'liberation' procedure in our sample was 12.8% (95/743), substantially lower than reported in previous studies of complementary/alternative treatments in MS. The predictive model contained five factors; living alone (Odds ratio 0.24, 95%CI 0.09-0.63), diagnosis of anxiety (Odds ratio 0.29, 95%CI 0.10 - 0.84), rating of neurologist's helpfulness (Odds ratio 0.56, 95%CI 0.44 -0 .71), Body Mass Index (Odds ratio 0.93, 95%CI, 0.89 - 0.98) and perceived physical impact of MS (Odds ratio 1.02, 95%CI 1.01 - 1.04). CONCLUSIONS: Predictive factors differed from previous studies of complementary/alternative treatment use likely due to both the invasiveness of the procedure and the advanced age of our study cohort. Our findings suggest that health professionals should target information on the risks and benefits of unregulated procedures to those patients who feel dissatisfied with their neurologist and they should include family members in discussions since they may be providing the logistical support to travel abroad and undergo the 'liberation' procedure. Our findings may be applicable to others with chronic disabling conditions who contemplate the user-pay unregulated invasive procedures available to them.