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IntroductionAvailable evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown.MethodsElectronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission.ResultsCurrent (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97).ConclusionsFormer but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers.ImplicationsPrior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

BackgroundThere is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics.MethodsElectronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined.Results6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aOR) for mortality were 1.58 [95% confidence interval (CI), 1.46-1.70] and 1.04 (95% CI, 0.96-1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and among those with current cancer (aOR, 0.69; 95% CI, 0.53-0.90).ConclusionsCurrent cancer, especially among younger patients, posed a substantially increased risk for death and ICU admission among patients with COVID-19; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types.ImpactThis study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic. See related commentary by Egan et al., p. 3.

Main objectiveThere is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic.Study design and methodsUniversity of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission.Results and significanceThe 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months.ConclusionsMortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes.Trial registrationClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528).

The use of antiretroviral therapy for people with HIV (PWH) has improved life expectancy. However, PWH now lose more life-years to tobacco use than to HIV infection. Unfortunately, PWH smoke at higher rates and have more difficulty maintaining abstinence than the general population, compounding their risk for chronic disease. In this Commentary, we describe a United States National Cancer Institute-led initiative to address the relative lack of research focused on developing, testing, and implementing smoking cessation interventions for PWH. This initiative supports seven clinical trials designed to systematically test and/or develop and test adaptations of evidence-based smoking cessation interventions for PWH (eg, combination of behavioral and pharmacological). We summarize each project, including setting/recruitment sites, inclusion/exclusion criteria, interventions being tested, and outcomes. This initiative provides critical opportunities for collaboration and data harmonization across projects. The knowledge gained will inform strategies to assist PWH to promote and maintain abstinence, and ensure that these efforts are adaptable and scalable, thereby addressing one of the major threats to the health of PWH. Reducing smoking behavior may be particularly important during the COVID-19 pandemic given that smokers who become infected with SARS-CoV-2 may be at risk for more severe disease.ImplicationsThis Commentary describes a National Cancer Institute-led initiative to advance the science and practice of treating tobacco use among PWH, which is now responsible for more life years lost than HIV. We describe the scope of the problem, the objectives of the initiative, and a summary of the seven funded studies. Harmonization of data across projects will provide information related to treatment mediators and moderators that was not previously possible. Stakeholders interested in tobacco cessation, including researchers, clinicians and public health officials, should be aware of this initiative and the evidence-base it will generate to advance tobacco treatment among this high-risk population.

Undergraduate research has proven to be a high-impact practice for students. We discuss the challenges inherent in creating a culture where undergraduate research can thrive. Without a doubt this imposes some costs, but we argue that even relatively modest expenditures can have positive effects on individual student success and on campus culture. We conclude with an aspirational model for what undergraduate research might mean for students during uncertain days within higher education.

A broad consensus exists that the use of appropriate methods are important in the Scholarship of Teaching and Learning. However, methodological controversies arise around what constitutes acceptable evidence, if one needs a control group, how generalizable results must be, and other similar issues. Much SoTL work, I argue, asks questions about how much a particular treatment (innovation) caused an effect (student learning), and how the results found in one particular context can be extended outside that context (generalizability). These concepts, known as internal validity and external validity, respectively, provide a common point of departure for much scholarship on teaching and learning. This paper addresses these concepts and demonstrates how they can unite much of what divides us within the methodological realm of SoTL.

I argue for the value of high-impact educational practices as tools to minimize the commoditization of higher education. As a vehicle for doing so, I discuss a travel course to Washington, D.C., that which I have led. This course is a significant and meaningful learning experience for the students who participate. In reflecting upon the value of this course, I suggest that scholars of teaching and learning have a particular responsibility to resist the increasing commoditization of higher education. Instead, we must think about embedding significant and transformative elements into the curriculum. Scholars of teaching and learning must help to demonstrate, in our research and in our advocacy work, the value of this work for the learning and transformation of our students. We must work, almost as lobbyists and campaigners, to enhance the perceived value of these experiences in the higher education marketplace.

Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have

Identifying the genetic mechanisms of adaptation requires the elucidation of links between the evolution of DNA sequence, phenotype, and fitness1. Convergent evolution can be used as a guide to identify candidate mutations that underlie adaptive traits2-4, and new genome editing technology is facilitating functional validation of these mutations in whole organisms1,5. We combined these approaches to study a classic case of convergence in insects from six orders, including the monarch butterfly (Danaus plexippus), that have independently evolved to colonize plants that produce cardiac glycoside toxins6-11. Many of these insects evolved parallel amino acid substitutions in the α-subunit (ATPα) of the sodium pump (Na+/K+-ATPase)7-11, the physiological target of cardiac glycosides12. Here we describe mutational paths involving three repeatedly changing amino acid sites (111, 119 and 122) in ATPα that are associated with cardiac glycoside specialization13,14. We then performed CRISPR-Cas9 base editing on the native Atpα gene in Drosophila melanogaster flies and retraced the mutational path taken across the monarch lineage11,15. We show in vivo, in vitro and in silico that the path conferred resistance and target-site insensitivity to cardiac glycosides16, culminating in triple mutant 'monarch flies' that were as insensitive to cardiac glycosides as monarch butterflies. 'Monarch flies' retained small amounts of cardiac glycosides through metamorphosis, a trait that has been optimized in monarch butterflies to deter predators17-19. The order in which the substitutions evolved was explained by amelioration of antagonistic pleiotropy through epistasis13,14,20-22. Our study illuminates how the monarch butterfly evolved resistance to a class of plant toxins, eventually becoming unpalatable, and changing the nature of species interactions within ecological communities2,6-11,15,17-19.

Background: The Agency for Healthcare Research and Quality recommends the use of safety huddles, in which clinicians are briefly gathered to review a patient's condition, including new or developing changes in acuity or stability. The Joint Commission describes huddles as a "hallmark" of high-reliability organizations. Previous reviews have confirmed the general utility of huddles, including positive regard by clinicians, but there has not been work specifically looking at huddle use in hospital maternity care settings. Our objective was to identify the ways that huddles have been studied or reported in inpatient maternity settings and synthesize this information with recommendations from professional organizations to identify gaps in the literature published in the United States since 1999. Methods: We used Arksey and O'Malley's framework to guide our scoping review. Using the time frame from 1999 to 2024, we searched the following databases: PubMed, CINAHL, SCOPUS, Embase, as well as gray literature and the reference lists and citing articles of the included manuscripts. Results: We found 160 documents, of which 47 met inclusion criteria, including 11 care bundles, 10 quality improvement projects, and 4 research studies. The remaining 22 were a variety of editorials, position papers, and other gray literature. Discussion: There is scant research on the use of huddles in hospital maternity care settings, and most literature does not define the participants, timing, or agenda of the huddle. Further research is needed to understand how huddles affect outcomes in maternity settings. Researchers should explicitly define the huddles they are studying. The review protocol was registered at Open Science Framework Registries. Huddles are frequently recommended as a patient safety strategy due to their interdisciplinary collaboration feature, however integration of huddles into the hospital maternity care setting has not been well studied. In this scoping review of huddles in the inpatient maternity setting, gaps in the evidence are identified and recommendations for future research are offered. [ABSTRACT FROM AUTHOR]

Objective: To test the feasibility of a university health center-delivered smoking cessation intervention that adds a 6-week course of text messaging to brief advice and nicotine patch therapy. Participants: Young adult cigarette smokers (n = 40) from 2 universities from January 2015 to May 2016. Methods: Randomized controlled trial comparing brief advice, nicotine patch therapy and: (1) a 6-week text messaging intervention (n = 20); or (2) no text messaging (n = 20). Primary outcomes included enrollment, retention and satisfaction. Results: Forty participants enrolled (38% of those screened). Retention rates were 98% and 92.5% at 6 and 12 weeks. Of those who completed the text intervention (n = 16), 64.3% felt the texts were "helpful", however they reported desire for tailoring and concern that texts triggered smoking. Biochemically confirmed abstinence rates did not significantly differ between text and control arms. Conclusions: These feasibility data suggest that text messaging may need to be modified to better engage and motivate college-age smokers.

Evidence shows that college attainment gaps continue to persist in U.S. higher education across historically marginalized communities. Critical consciousness theory posits an antidotal framework for understanding marginalized students' experiences and educational outcomes. Researchers have identified critical reflection and action among core constructs of critical consciousness, and they have articulated the need for more scholarship seeking to understand the action dimension. Responding to this gap with curiosity about the role that leadership plays in sociopolitical action, we conducted 2 studies in the development of an instrument measuring college students' leadership engagement in advocacy. In Study 1, we developed a 10-item measure and tested its initial reliability and validity through exploratory factor analysis with 203 college students. In Study 2, we provided further validity evidence with a different, more diverse sample of 164 students using confirmatory factor analysis. Results suggest that the college students' leadership engagement in advocacy measure has a 1-dimensional structure and high internal reliability. We also provide evidence of convergent and discriminant validity in relation to measures of academic self-efficacy and advocacy outcome expectations. We discuss the utility of this measure for critical consciousness research and higher education practice aiming to close attainment gaps.

Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18-53, 54-64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p54-63 = 1.50x10-9 , OR54-63 = 1.28, 95%CI54-63 = 1.18-1.39; p64+ = 2.14x10-11 , OR64+ = 1.32, 95%CI64+ = 1.21-1.43] and rs11979158 [p54-63 = 6.13x10-8 , OR54-63 = 1.35, 95%CI54-63 = 1.21-1.50; p64+ = 2.18x10-10 , OR64+ = 1.42, 95%CI64+ = 1.27-1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18-53 (p18-53 = 9.30 × 10-11 , OR18-53 = 1.76, 95%CI18-53 = 1.49-2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of 'LGG'-like tumor characteristics in GBM samples in those 18-53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54-63] and 0.8% [64+] (p = 0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18-53 suggests that more younger individuals may present initially with 'secondary glioblastoma.'

BackgroundPhysicians "purchase" many health care services on behalf of patients yet remain largely unaware of the costs of these services. Electronic health record (EHR) cost displays may facilitate cost-conscious ordering of health services.ObjectiveTo determine whether displaying hospital lab and imaging order costs is associated with changes in the number and costs of orders placed.DesignQuasi-experimental study.ParticipantsAll patients with inpatient or observation encounters across a multi-site health system from April 2013 to October 2015.InterventionDisplay of order costs, based on Medicare fee schedules, in the EHR for 1032 lab tests and 1329 imaging tests.Main measuresOutcomes for both lab and imaging orders were (1) whether an order was placed during a hospital encounter, (2) whether an order was placed on a given patient-day, (3) number of orders placed per patient-day, and (4) cost of orders placed per patient-day.Key resultsDuring the lab and imaging study periods, there were 248,214 and 258,267 encounters, respectively. Cost display implementation was associated with a decreased odds of any lab or imaging being ordered during the encounter (lab adjusted odds ratio [AOR] = 0.97, p = .01; imaging AOR = 0.97, p

Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.

To examine for a causal relationship between vitamin D and glioma risk we performed an analysis of genetic variants associated with serum 25-hydroxyvitamin D (25(OH)D) levels using Mendelian randomisation (MR), an approach unaffected by biases from confounding. Two-sample MR was undertaken using genome-wide association study data. Single nucleotide polymorphisms (SNPs) associated with 25(OH)D levels were used as instrumental variables (IVs). We calculated MR estimates for the odds ratio (OR) for 25(OH)D levels with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighted (IVW) and maximum likelihood estimation (MLE) methods. A non-significant association between 25(OH)D levels and glioma risk was shown using both the IVW (OR = 1.21, 95% confidence interval [CI] = 0.90-1.62, P = 0.201) and MLE (OR = 1.20, 95% CI = 0.98-1.48, P = 0.083) methods. In an exploratory analysis of tumour subtype, an inverse relationship between 25(OH)D levels and glioblastoma (GBM) risk was identified using the MLE method (OR = 0.62, 95% CI = 0.43-0.89, P = 0.010), but not the IVW method (OR = 0.62, 95% CI = 0.37-1.04, P = 0.070). No statistically significant association was shown between 25(OH)D levels and non-GBM glioma. Our results do not provide evidence for a causal relationship between 25(OH)D levels and all forms of glioma risk. More evidence is required to explore the relationship between 25(OH)D levels and risk of GBM.

IntroductionA 2012 systematic review and meta-analysis of randomized controlled trials on emergency department-initiated tobacco control (ETC) showed only short-term efficacy. The aim of this study was to update data through May 2015.MethodsAfter registering the study protocol on the international prospective register of systematic reviews (PROSPERO) in May 2015, we searched 7 databases and the gray literature. Our outcome of interest was the point prevalence of tobacco-use abstinence at 1-month, 3-month, 6-month, or 12-month follow-up. We calculated the relative risk (RR) of tobacco-use abstinence after ETC at each follow-up time separately for each study and then pooled Mantel-Haenszel RRs by follow-up time. These results were pooled with results of the 7 studies included in the previous review. We calculated the effect of ETC on the combined point prevalence of tobacco-use abstinence across all follow-up times by using generalized linear mixed models.ResultsWe retrieved 4 additional studies, one published as an abstract, comprising 1,392 participants overall. The 1-month follow-up point prevalence of tobacco-use abstinence after ETC resulted in an RR of 1.49 (95% confidence interval [CI], 1.08-2.05) across 3 studies; 3-month follow-up, an RR of 1.38 (95% CI, 1.12-1.71) across 9 studies; 6-month follow-up, an RR of 1.09 (95% CI, 0.84-1.41) across 6 studies; and 12-month follow-up, an RR of 1.26 (95% CI, 1.00-1.59) across 3 studies. The effect on the combined point prevalence of abstinence was an RR of 1.40 (95% CI, 1.06-1.86) (P = .02).ConclusionETC is effective in promoting continual tobacco-use abstinence up to 12 months after intervention. ETC may be a critically important public health strategy for engaging hard-to-reach smokers in tobacco-use cessation.

Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10-9, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10-10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10-11, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10-10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10-9, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10-10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10-10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10-9, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10-10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10-11, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10-9, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.

The COVID-19 pandemic was managed in part by the rapid development of vaccines, diagnostics, and therapeutics including antiviral agents and advances in emergency airway and ventilatory management. The impact of these therapeutic advances on clinically pertinent metrics of emergency care have not been well-studied. We abstracted data from emergency department (ED) visits made to 21 US health systems during the first two years of the pandemic, from February 1, 2020 to January 31, 2022. These health systems were participants in the NIH-supported COVID EHR Cohort, in which the University of Wisconsin served as the coordinating site. Limited patient-level data files were submitted monthly. Data elements included demographic and clinical variables, as well as standard measures of ED outcomes including 72-h returns, 72-h returns leading to readmission, and in-hospital mortality. Multivariable models were fitted to identify correlates of each of the dependent variables. A test for trend was used to detect changes in outcomes over time. During the two-year period, 150,357 individuals aged 18 years or older visited the ED. The median age was 45.4 years (IQR 27), 58.1 % were female, 49 % were White, 18.3 % Hispanic/Latino, and 45 % were publicly insured or uninsured. The prevalence of 72-h ED returns, readmissions, and in-hospital mortality significantly declined across the two-year period. SARS-CoV-2 vaccination was associated with reduced ED returns and mortality. Therapeutic agents were associated with increased mortality risk but were likely confounded by unmeasured covariates. Operational and clinical outcomes of ED-based treatment of individuals with COVID-19 improved in the first two years of the pandemic. This improvement is likely multifactorial and includes the development and deployment of SARS-CoV-2-specific vaccines, therapeutic agents, and improved healthcare delivery in the ED and elsewhere addressing management of airway and ventilatory status, as well as increased innate immunity in the general population. [ABSTRACT FROM AUTHOR]

BackgroundThe choice of a local control (LC) modality for Ewing sarcoma (EWS) of the femur is controversial. This study aimed to determine the effect of LC modality on tumor LC and patient outcomes.MethodsThe study reviewed the treatment and outcomes for 115 patients who had EWS of the femur treated with similar chemotherapy in three cooperative group trials. Patient outcomes were analyzed according to the LC modality using the log-rank test and the cumulative incidence of local or distant failure using competing risks regression.ResultsThe median age of the patients was 13 years. The most common tumor location was the proximal femur followed by the mid femur. For 55 patients with available data, the tumor was larger than 8 cm in 29 patients and 8 cm or smaller in 26 patients. For 84 patients (73 %), surgery only was performed, whereas 17 patients (15 %) had surgery plus radiation, and 14 patients (12 %) had radiation only. The 5-year event-free survival (EFS) rate was 65 % (95 % confidence interval [CI], 55-73 %), and the 5-year overall survival (OS) rate was 70 % (95 % CI, 61-78 %). Patient outcomes did not differ significantly according to tumor location within the femur (proximal, mid or distal) or tumor size (

Effectively grouping learners in an online environment is a highly useful task. However, datasets used in this task often have large numbers of attributes of disparate types and different scales, which traditional clustering approaches cannot handle effectively. Here, a unique dissimilarity measure based on the random forest, which handles the stated drawbacks of more traditional clustering approaches, is presented. Additionally, a rule-based method is proposed for interpreting the resulting learner segmentations. The approach was implemented on a real dataset of users of the "Career"WISE online educational environment, designed to provide resilience training for women STEM doctoral students, and was shown to find stable and meaningful groups of users.

The scholarship of teaching and learning represents an important movement within higher education. Through this work, the profession of teaching is able to build upon itself through sustained inquiry and an evidence-based culture. However, for the scholarship of teaching and learning to take hold on a campus, a culture shift often needs to occur, during which time actions by campus leaders, change agents and facilitators lay the groundwork for, and effect, institutional change. This paper uses an organizational theory approach to sketch out a model by which this culture change can occur. It then uses our experiences at a regional comprehensive university in the Midwestern United States to elaborate on culture change models. Our experiences teach valuable lessons about how the scholarship of teaching and learning can become an important element within a campus culture. (Contains 7 footnotes and 2 tables.)

BackgroundComplete surgical resection of primary tumors is critical for long-term control of high-grade osteosarcoma. Uniform assessment of the extent of surgical resection is important in clinical trials, though the accuracy of this reporting has been poorly studied.MethodsWe conducted a retrospective cohort study of patients 5-40 years of age with newly diagnosed high-grade resectable osteosarcoma treated as part of the AOST0331 clinical trial at Children's Oncology Group institutions. The extent of surgical resection of the primary tumor was graded as wide or radical by the treating institution. Central assessment of the extent of resection by two orthopedic oncologists was compared with institutional assessment by reviewing pathology and operative reports.ResultsWe included 956 patients who had data available for central review. The extent of resection reported by treating institutions was 536/956 (56%) radical and 420/956 (44%) wide. The extent of resection assessed by central review was 162/956 (17%) radical and 794/956 (83%) wide. The overall discordance rate for the cohort was 43%.ConclusionsInstitutional reports of radical resection in high-grade osteosarcoma significantly over-estimate the proportion of patients undergoing radical resection. This highlights the need for centralized review and improved accuracy of reporting of the extent of resection. J. Surg. Oncol. 2016;113:351-354. © 2016 Wiley Periodicals, Inc.

Spatial segregation of metabolism, such as cellular-localized CO2 fixation in C4 plants or in the cyanobacterial carboxysome, enhances the activity of inefficient enzymes by selectively concentrating them with their substrates. The carboxysome and other bacterial microcompartments (BMCs) have drawn particular attention for bioengineering of nanoreactors because they are self-assembling proteinaceous organelles. All BMCs share an architecturally similar, selectively permeable shell that encapsulates enzymes. Fundamental to engineering carboxysomes and other BMCs for applications in plant synthetic biology and metabolic engineering is understanding the structural determinants of cargo packaging and shell permeability. Here we describe the expression of a synthetic operon in Escherichia coli that produces carboxysome shells. Protein domains native to the carboxysome core were used to encapsulate foreign cargo into the synthetic shells. These synthetic shells can be purified to homogeneity with or without luminal proteins. Our results not only further the understanding of protein-protein interactions governing carboxysome assembly, but also establish a platform to study shell permeability and the structural basis of the function of intact BMC shells both in vivo and in vitro. This system will be especially useful for developing synthetic carboxysomes for plant engineering.

Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions.

When studying the political development of young people, level of education matters. However, instead of concentrating on the amount of education and how it affects one's political attributes (vertical effects of education), we consider the effects of characteristics of one's education, specifically one's college major, among people with similar levels of education (horizontal effects). Our study demonstrates that the discipline in which one majors affects one's political development, over and above the expected self-selection effects. While our results are modest, they suggest that there is much to be gained from exploring horizontal variations in education and its effects on political attributes.

Human islet amyloid polypeptide (hIAPP or Amylin) is a 37 residue hormone that is cosecreted with insulin from the pancreatic islets. The aggregation of hIAPP plays a role in the progression of type 2 diabetes and contributes to the failure of islet cell grafts. Despite considerable effort, little is known about the mode of action of IAPP amyloid inhibitors, and this has limited rational drug design. Insulin is one of the most potent inhibitors of hIAPP fibril formation, but its inhibition mechanism is not understood. In this study, the aggregation of mixtures of hIAPP with insulin, as well as with the separate A and B chains of insulin, were characterized using ion mobility spectrometry-based mass spectrometry and atomic force microscopy. Insulin and the insulin B chain target the hIAPP monomer in its compact isoform and shift the equilibrium away from its extended isoform, an aggregation-prone conformation, and thus inhibit hIAPP from forming β-sheets and subsequently amyloid fibrils. All-atom molecular modeling supports these conclusions.

Introduction: Tobacco contributes to the leading causes of morbidity and mortality among persons with human immunodeficiency virus (PWHs). Nonetheless, medications for tobacco use disorder are widely underused, particularly among PWHs. We sought to characterize the extent to which insurance barriers impacted access to medications for tobacco use disorder and, in comparison, to access to antiretroviral therapy (ART). Methods: This is a secondary analysis of data on individuals enrolled in a randomized clinical trial to address tobacco use involving nicotine replacement therapy and, for some, additionally, varenicline or bupropion. Medication prescriptions are transmitted electronically from the clinic to neighborhood pharmacies. Data sources included participant assessments and intervention visit tracking forms. Results: Of 93 participants enrolled from September 2020 to July 2021, 20 (22%) were unable to fill or had difficulty filling their nicotine replacement therapy (NRT) prescriptions because of insurance barriers. These fell into 2 broad categories: enrollment in a publicly insured managed care plan in which the pharmacy benefit manager excluded nonprescription NRT and lack of understanding by the pharmacy of the scope of coverage. Of these 20 participants, 5 (25%) were unable to obtain medications at all, and 3 of these participants dropped out of the study. One additional participant paid out-of-pocket to obtain NRT. No participant was denied coverage of ART, bupropion, or varenicline. Conclusions: Gaps in insurance coverage may result in PWHs receiving ART without simultaneous medical management of their tobacco use. This may undermine the efficacy of antivirals. Mandated insurance coverage of nonprescription NRT may improve the health of PWHs who smoke. [ABSTRACT FROM AUTHOR]

The ability to integrate learning--to make connections across classes or even within a single class--is integral to students becoming better learners, and to growing their capacity to perform as civic actors. We discuss an upper-level Campaigns and Elections class in which the course structure and assignments were set up to encourage students to integrate their learning. As part of the class, students played the role of state party committees during the 2016 presidential election, at first making arguments to devote more national party resources to their state campaign and then reporting back to the national party on how the election went in their state, and what the party must do to maximize its future success. Through coding of student final exam essay questions, we explore the degree to which students were able to achieve the integrative learning goals we had set for them, and examine factors that might help predict which students achieved these learning goals. We conclude by generalizing from our experience to discuss best practices for achieving integrative learning in our courses.