Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant.

We identified an emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the western United States. Named B.1.427/B.1.429 to denote its two lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6%-24% increased transmissibility relative to wild-type circulating strains. The variant carries three mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 4.0- to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California exhibiting decreased antibody neutralization warrants further investigation.

Expansion of an Australian food composition database to estimate plant and animal intakes.

Despite evidence for favourable health outcomes associated with plant-based diets, a database containing the plant and animal content of all foods eaten is required to undertake a reliable assessment of plant-based diets within a population. This study aimed to expand an existing Australian food database to include the plant and animal content of all whole foods, beverages, multi-ingredient products and mixed dishes. Twenty-three plant- and animal-based food group classifications were first defined. The food servings per 100 g of each product were then systematically calculated using either a recipe-based approach, a food label-based approach, estimates based on similar products or online recipes. Overall, 4687 (83·5 %) foods and beverages were identified as plant or plant-containing products, and 3701 (65·9 %) were animal or animal-containing products. Results highlighted the versatility of plant and animal ingredients as they were found in various foods across many food categories, including savoury and sweet foods, as well as discretionary and core foods. For example, over 97 % of animal fat-containing foods were found in major food groups outside the AUSNUT 2011-2013 'fats and oils' group. Surprisingly, fruits, nuts and seeds were present in a greater percentage of discretionary products than in core foods and beverages. This article describes a systematic approach that is suitable for the development of other novel food databases. This database allows more accurate quantitative estimates of plant and animal intakes, which is significant for future epidemiological and clinical research aiming to investigate plant-based diets and their related health outcomes.

The presence, action, and influence of bystanders who witness sexual harassment against medical students.

PURPOSE: Sexual harassment (SH) is a widespread problem in academia, with a disproportionate impact on female medical students and those who experience marginalization via multiple systems of oppression (e.g. racism, heterosexism). Bystander intervention education is a potential approach which frames violence as a community issue where all members have a role to play in response and prevention. This study assessed the presence and influence of bystanders in SH situations for students at two medical schools. MATERIALS AND METHODS: Data came from a larger U.S. campus climate study administered online in 2019 and 2020. The sample included 584 students who responded to validated survey questions about sexual harassment experiences, bystander behavior, disclosure, perceptions of the university response to SH, and demographics. RESULTS: More than one-third of respondents experienced some form of SH by a faculty/staff member. Bystanders were present for more than half of these incidents, yet they rarely intervened. When bystanders intervened, people were more likely to disclose an incident than not. CONCLUSIONS: The results indicate that there are many missed opportunities for intervention and given the profound impact that SH has on the well-being of medical students, continued work is needed to determine effective intervention and prevention methods.[Box: see text].

Bystander Intervention as a Prevention Strategy for Campus Sexual Violence: Perceptions of Historically Minoritized College Students.

The bystander intervention approach to campus sexual violence has received increased attention as a promising prevention strategy. However, there lacks research on the perspective of historically minoritized students, such as students of color, LGBTQ-spectrum students, and the intersections thereof. As such, the purpose of this paper is to present the findings from an exploratory study regarding bystander intervention that focused exclusively on the perspectives of 101 racialized and/or LGBTQ-spectrum students at three campuses across a large public university. Using concept mapping methodology, the study was conducted in three phases: brainstorming of statements about bystander intervention, sorting and rating of statements, and mapping and interpretation of the results. Using multidimensional scaling and hierarchical cluster analysis, a six-cluster solution was determined, representing key themes related to supporting students' efforts as helpful bystanders. Overall, findings indicate a need for bystander intervention efforts to widen their focus by employing an intersectional, social justice lens. Study participants identified various forms of racism, homophobia, transphobia, and microaggressions as intertwined with their ability to be active bystanders on college campuses.

Views of health professionals on the clinical recognition of orthorexia nervosa: a pilot study.

PURPOSE: We present pilot, cross-sectional online survey data of health professionals in Australia and New Zealand about their attitudes towards orthorexia nervosa (ON), the proposed health food eating disorder. Our primary outcome was whether the professionals believed that ON should be a distinct, clinically recognised eating disorder. METHODS: Fifty-two health professionals, predominantly psychologists and dietitians, completed the survey. RESULTS: Nearly, three-quarters of respondents (71%) believed that ON should be a distinct, clinically recognised eating disorder. CONCLUSIONS: This finding should be extended in a full study to inform future iterations of diagnostic manuals and the recognition and treatment of obsessively healthy eating. LEVEL OF EVIDENCE: Level V, descriptive study of opinions of health professionals.

Impact of Exposure to Sexual Violence Prevention Messages on Students' Bystander Behavior.

Bystander intervention is a prevention strategy commonly used to address campus sexual violence. Increasingly, there are calls for prevention efforts to be multilevel and ongoing. The current study investigated the impact of receiving varied prevention messages throughout adolescence and into early adulthood to determine whether it influences college students' awareness of sexual violence, willingness to intervene as a helpful bystander, and actual prosocial bystander behavior. These questions were tested through administration of an online survey to a racially and ethnically diverse sample of 1,047 undergraduate students at a large, urban university in the mid-Atlantic. Results found that most students received information about sexual violence prior to coming to campus from a variety of sources, and that the sources varied significantly by gender and race. Regression analysis found that greater exposure to prevention messages prior to coming to college was significantly associated with greater bystander intentions and behavior even after accounting for gender and race and exposure since coming to college. The findings provide initial support to expand the scope of prevention efforts and to begin them prior to college.

Campus Sexual Assault: Future Directions for Research.

Campus sexual assault (CSA) has received unprecedented attention over recent years, resulting in an abundance of federal guidance and mandates. In response, efforts to address and prevent CSA at Institutions of Higher Education (IHE) across the country have grown quickly, including the development and implementation of programs and policies. Because the changes on campuses have occurred at such a rapid pace, a number of gaps exist within the field of CSA research. To ensure that changes on IHE are evidence-based, there is a need to review the existing research available and the inquiry still needed, based on key areas outlined in federal guidance, the expressed needs of campus community members, survivors, and students who commit sexual offenses on college campuses. The purpose of this review is to summarize the empirical research related to CSA gained from the past two decades and identify areas in which further work is needed, specifically related to key areas identified in recent guidance provided to IHE. This article concludes with guidance for research moving forward to help strengthen response and prevention efforts.

Integrative transcriptome-wide analyses reveal critical HER2-regulated mRNAs and lincRNAs in HER2+ breast cancer.

Breast cancer is a major health problem affecting millions of women worldwide. Over 200,000 new cases are diagnosed annually in the USA, with approximately 40,000 of these cases resulting in death. HER2-positive (HER2+) breast tumors, representing 20-30 % of early-stage breast cancer diagnoses, are characterized by the amplification of the HER2 gene. However, the critical genes and pathways that become affected by HER2 amplification in humans are yet to be specifically identified. Furthermore, it is yet to be determined if HER2 amplification also affects the expression of long intervening non-coding (linc)RNAs, which are involved in the epigenetic regulation of gene expression. We examined changes in gene expression by next generation RNA sequencing in human tumors pre- and post- HER2 inhibition by trastuzumab in vivo, and changes in gene expression in response to HER2 knock down in cell culture models. We integrated our results with gene expression analysis of HER2+ tumors vs matched normal tissue from The Cancer Genome Atlas. The integrative analyses of these datasets led to the identification of a small set of mRNAs, and the associated biological pathways that become deregulated by HER2 amplification. Furthermore, our analyses identified three lincRNAs that become deregulated in response to HER2 amplification both in vitro and in vivo. Our results should provide the foundation for functional studies of these candidate mRNAs and lincRNAs to further our understanding of how HER2 amplification results in tumorigenesis. Also, the identified lincRNAs could potentially open the door for future RNA-based biomarkers and therapeutics in HER2+ breast cancer.

A randomized controlled trial of a multi-dose bystander intervention program using peer education theater.

This article reports findings from a longitudinal, experimental evaluation of a peer education theater program, Students Challenging Realities and Educating Against Myths (SCREAM) Theater. This study examines the impact of SCREAM Theater on a range of bystander-related outcomes (i.e. bystander intentions, bystander efficacy, perception of friend norms and bystander behaviors) in situations involving sexual violence and whether there was a differential impact of the program by participant sex. First-year college students completed three waves of surveys (pretest, first post-test and second post-test). All participants received one dose of the intervention during summer orientation after the pretest. After the first post-test, participants were randomly assigned to receive two additional doses, or to a control condition, in which they received no additional doses. Students in both one- and three-dose groups reported a number of positive increases. Overall, an intent-to-treat analysis (n = 1390) indicated three doses of the intervention during the first semester of college resulted in better outcomes than the one-time intervention during summer orientation alone. Although both male and female students' scores increased during the study period, female students consistently scored higher than male students on each outcome. The findings suggest that peer education theater holds promise for bystander intervention education on college campuses.

Call for research on bystander intervention to prevent sexual violence: the role of campus environments.

An important next step for the field is to determine what setting-level factors beyond the individual are critical to fostering campus environments that support pro-social, helpful bystander intervention action to prevent sexual violence. Therefore, the purpose of this paper is to provide a research agenda to investigate key areas of the campus environment and their potential influence on bystander intervention. To create the research agenda, a number of steps were followed including: (1) systematically reviewing the larger bystander literature to identify key environmental areas, (2) assessing what research is available specific to college campuses and sexual assault in each of these areas, and (3) outlining future research to address each of these areas on college campuses and determine their applicability to sexual violence situations. Five main groups of factors were found to influence bystander intervention beyond the individual, group and situational levels, including: social norms, sense of community, pro-social modeling, policies, and the physical environment. Certain areas of research on environmental influences on bystander intervention are more developed such as social norms, with little research on areas such as policies and the physical environment. However, further research is needed in each of the identified five areas to help identify how college campuses can support bystander intervention.

Predicting Bystander Behavior to Prevent Sexual Assault on College Campuses: The Role of Self-Efficacy and Intent.

Bystander intervention has been increasingly applied to prevent sexual violence on college campuses. Its underlying theory assumes unidirectional relationships between variables, predicting that bystander behaviors (i.e., actions taken to intervene in sexual violence situations) will be influenced by bystander intentions (BI; i.e., likelihood to intervene in the future), which in turn will be affected by bystander efficacy (BE; i.e., confidence to intervene). One question for theory is whether a reciprocal relationship exists between BI and BE. We used structural equation modeling (SEM) with longitudinal data to test unidirectional and reciprocal causal relations between BI and BE. Participants (n = 1390) were students at a northeastern US university. Four models were examined using SEM: (1) a baseline model with autoregressive paths; (2) a model with autoregressive effects and BI predicting future BE; (3) a model with autoregressive effects and BE predicting future BI; and, (4) a fully cross-lagged model. Results indicated that reciprocal causality was found to occur between BI and BE. In addition, a final model demonstrated indirect effects of a bystander intervention program on bystander behaviors through both BI and BE at different time points. Implications for theory and practice are described, and directions for future research discussed.

Mutational patterns in the breast cancer mitochondrial genome, with clinical correlates.

The presence of mitochondrial DNA (mtDNA) mutations in human cancer has long been recognized, but their functional significance has remained obscure. Debate persists as to whether the mutations help drive the tumor, or are bystander events. Here, we analyze next-generation mtDNA sequence data from 99 breast cancer patients. High depth coverage enables detection of even low-level heteroplasmic variants, and data from matched normal tissue allow us to distinguish between shifts in heteroplasmy and acquired mutations. Somatic mtDNA mutations are found in 73 (73.7%) of patient tumors, and dramatic shifts from the initial germline allele proportions are observed for many heteroplasmies. Clustering of somatic mutations in promoter and replication regions, and also in genes coding for electron transport chain complex I, suggest selection for mutations affecting critical mitochondrial processes. Furthermore, statistical tests for Darwinian selection reveal evidence for positive and relaxed negative selection for somatic missense mutations. We also observe a dramatic decrease in per-cell mtDNA content in tumor tissues, as well as a surprising positive correlation between somatic mtDNA mutational burden and patient survival. Taken together, our results support the view that somatic mtDNA mutations are not solely bystander events, but have significance in cancer from both biological and clinical perspectives. We also anticipate that the catalog of heteroplasmies and somatic mutations presented here will serve as a reference for future studies of cancer mitochondrial genomes.

DB2: a probabilistic approach for accurate detection of tandem duplication breakpoints using paired-end reads.

BACKGROUND: With the advent of paired-end high throughput sequencing, it is now possible to identify various types of structural variation on a genome-wide scale. Although many methods have been proposed for structural variation detection, most do not provide precise boundaries for identified variants. In this paper, we propose a new method, Distribution Based detection of Duplication Boundaries (DB2), for accurate detection of tandem duplication breakpoints, an important class of structural variation, with high precision and recall. RESULTS: Our computational experiments on simulated data show that DB2 outperforms state-of-the-art methods in terms of finding breakpoints of tandem duplications, with a higher positive predictive value (precision) in calling the duplications' presence. In particular, DB2's prediction of tandem duplications is correct 99% of the time even for very noisy data, while narrowing down the space of possible breakpoints within a margin of 15 to 20 bps on the average. Most of the existing methods provide boundaries in ranges that extend to hundreds of bases with lower precision values. Our method is also highly robust to varying properties of the sequencing library and to the sizes of the tandem duplications, as shown by its stable precision, recall and mean boundary mismatch performance. We demonstrate our method's efficacy using both simulated paired-end reads, and those generated from a melanoma sample and two ovarian cancer samples. Newly discovered tandem duplications are validated using PCR and Sanger sequencing. CONCLUSIONS: Our method, DB2, uses discordantly aligned reads, taking into account the distribution of fragment length to predict tandem duplications along with their breakpoints on a donor genome. The proposed method fine tunes the breakpoint calls by applying a novel probabilistic framework that incorporates the empirical fragment length distribution to score each feasible breakpoint. DB2 is implemented in Java programming language and is freely available at http://mendel.gene.cwru.edu/laframboiselab/software.php.

Growth during pubertal induction in girls with Turner Syndrome: a retrospective cohort analysis.

CONTEXT: Patients with Turner Syndrome often present with short stature and ovarian insufficiency. The optimal method of pubertal induction to maximize adult height (AH) is unknown. OBJECTIVE: To identify variables related to pubertal induction that are associated with growth and AH. DESIGN & SETTING: Retrospective cohort analysis of patients attending a specialized Turner Syndrome clinic at a quaternary children's hospital. PATIENTS: Patients with Turner Syndrome (n=107) who attended the clinic between 2015 and 2021. Of these, 51 received estradiol for pubertal induction. MAIN OUTCOME MEASURES: Change in height standard deviation score (ΔHeightSDS) during pubertal induction, and AH. METHODS: Age at pubertal induction, bone age delay, midparental height (MPH), growth hormone treatment, and karyotype were assessed as predictors of AH and ΔHeightSDS. Associations between karyotype and comorbidities were also assessed. RESULTS: AH was predicted by MPH (0.8cm/cm, P=0.0001) and bone age delay (-1.84 cm/year, P= 0.006). ΔHeightSDS was predicted by growth hormone dose (0.09 SDS/mg/m2/week; P=0.017), bone age delay (-1.37 SDS/year; P=0.003), and age at pubertal induction (0.44 SDS/year; P=0.001). There was an interaction between bone age delay and pubertal induction age (P=0.013), with the combination of younger age at pubertal induction and a less-delayed bone age associated with a lower ΔHeightSDS. Karyotype did not influence AH or ΔHeightSDS, but did affect rates of other comorbidities. CONCLUSIONS: Decisions around timing of pubertal induction in patients with Turner Syndrome should be tailored to the individual. The current approach to estrogen supplementation needs to be refined in order to facilitate pubertal induction in a physiological manner without compromising height.

Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes.

Vitamin D is synthesised in the skin through the action of UVB radiation (sunlight), and 25-hydroxy vitamin D (25OHD) measured in serum as a marker of vitamin D status. Several studies, mostly conducted in high latitudes, have shown an association between type 1 diabetes mellitus (T1DM) and low serum 25OHD. We conducted a case-control study to determine whether, in a sub-tropical environment with abundant sunlight (latitude 27.5°S), children with T1DM have lower serum vitamin D than children without diabetes. Fifty-six children with T1DM (14 newly diagnosed) and 46 unrelated control children participated in the study. Serum 25OHD, 1,25-dihydroxy vitamin D (1,25(OH)(2) D) and selected biochemical indices were measured. Vitamin D receptor (VDR) polymorphisms Taq1, Fok1, and Apa1 were genotyped. Fitzpatrick skin classification, self-reported daily hours of outdoor exposure, and mean UV index over the 35 d prior to blood collection were recorded. Serum 25OHD was lower in children with T1DM (n = 56) than in controls (n = 46) [mean (95%CI) = 78.7 (71.8-85.6) nmol/L vs. 91.4 (83.5-98.7) nmol/L, p = 0.02]. T1DM children had lower self-reported outdoor exposure and mean UV exposure, but no significant difference in distribution of VDR polymorphisms. 25OHD remained lower in children with T1DM after covariate adjustment. Children newly diagnosed with T1DM had lower 1,25(OH)(2) D [median (IQR) = 89 (68-122) pmol/L] than controls [121 (108-159) pmol/L, p = 0.03], or children with established diabetes [137 (113-153) pmol/L, p = 0.01]. Children with T1DM have lower 25OHD than controls, even in an environment of abundant sunlight. Whether low vitamin D is a risk factor or consequence of T1DM is unknown.

Engaging Campuses in Meaningful Change Efforts to Address Relationship Violence and Sexual Misconduct: Lessons Learned From the Michigan State University Experience.

Although recent decades have been marked by tremendous strides in addressing relationship violence and sexual misconduct at institutions of higher education across the country, there still exists a range of degree and meaningfulness of these changes. A key question raised by Campbell et al. in the discussion of the model developed at Michigan State University (MSU) is how to align institutional commitment with actions, as well as engage in "meaningful" change. Three aspects of the MSU model that stand out as especially critical for other institutions to consider include working toward culture change, engaging the larger campus community, and conducting an ongoing evaluation.

Sexual violence prevalence and disclosure patterns among college undergraduates: exploring types of sexual violence and incident-specific characteristics.

Objective: Study explores the role of well-documented individual-level correlates of a range of types of sexual violence among undergraduates and examines both individual-level and incident-level correlates of disclosure patterns to formal and informal sources. Participants: The current study involves the analysis of campus climate data collected in 2018 from 2,271 undergraduate participants. Methods: Descriptive and bivariate analyses are conducted to examine correlates of sexual violence, and a logistic regression model is estimated to examine disclosure by both individual and incident-level correlates. Results: 19% of students experience at least one incident of sexual violence since coming to campus, with many reporting multiple victimizations which differs by race, gender, and sexual orientation. Significant differences found in disclosure based on gender and relationship to who committed the sexual violence. Conclusions: Overall, findings from this study highlight the importance of using a nuanced approach to examining college students' experiences of sexual violence.

Development of the Services, Policies and Programs Audit Tool to Address Campus Sexual Violence.

Evidence suggests that resources to address campus sexual violence (CSV) are inconsistently offered across institutions of higher education (IHE), and thus there is a need for campuses to continually assess their provision of resources and services to improve the climate and well-being of students. Conducting a periodical scan of resources provided is one way for IHE to assess their adherence to best practices. The current study describes the development of the Services, Policies and Programs Audit (SPPA) tool, created to help IHE evaluate their adherence with best practices related to the provision of services, policies, and programs on campus. The tool was piloted with 18 individuals from 12 different IHE across the country. Exploratory evaluation of the SPPA indicates that it may be a useful tool for self-examination of campus policies, services, and prevention and education efforts. Participants from the 12 IHE who participated in the pilot generally reported that the SPPA was helpful to their efforts. Interrater reliability results indicated that the position of the person who completes the tool impacts the scoring, with those who are more familiar with CSV services scoring higher. This aligns with other research indicating that it is important not only to have resources on campus to address CSV but also to ensure that the campus community is aware of them. The SPPA can potentially serve as one part of a larger toolkit used by IHE to assess their efforts to address CSV.

Bystander Intervention for the Prevention of Campus Sexual Violence: Opportunity, Frequency of Action, and Consequences for Confronting Those at Risk of Perpetration.

This cross-sectional study examined students' (Campus 1, n = 1,153; Campus 2, n = 1,113) experiences with four situations of direct confrontation of those at risk for sexual assault perpetration. The most reported opportunity was to confront those making false statements about sexual assault; many students reported more than one opportunity to intervene in the past year. Bystanders intervened most of the time across the four situations examined in this study. The most reported consequence of intervening was that no further harm was caused. More nuanced measures can offer practitioners further information to tailor sexual violence prevention programs.

College Students' Engagement in Violence Prevention Discussions with Peers.

The bystander intervention (BI) model recognizes a range of prosocial helping behaviors individuals can perform to support sexual and dating violence (S/DV) prevention efforts. Individuals can demonstrate a commitment to ending violence through proactive BI, such as participating in prevention initiatives or talking with peers about ways to keep safe, which are different than reactive BI behaviors when violence is underway. Given the anchoring of the BI model in Diffusion of Innovation Theory, which articulates the uptake of new behaviors throughout a population or community and the role of change agent aids in that process, investigating demographic, and other individual-level correlates, of proactive behaviors may help identify those students who are particularly positioned to help diffuse and normalize anti-violence behaviors. The purpose of this study was to examine (1) the occurrence of students' engagement in peer discussions about violence prevention in the past year and (2) the correlates of reporting to have those discussions among university students in a cross-sectional study implemented on two campuses in the Mid-Atlantic U.S. Results showed that the most common discussion was talking to friends about being safe in dating relationships and the least common was talking with friends about participating in violence-prevention-related activities, with 66.2% and 22.5% having done so, respectively. Women, younger students, and those reporting to know a survivor of either DV or SV were more likely to report having discussions, compared to men, older students, and those not knowing a survivor. Additional relationships were detected between other individual characteristics, knowledge about violence/victimization, and climate-related variables but differed depending on whether participants participated in the DV or SV-related survey module. Findings suggest the need for BI training initiatives to emphasize proactive engagement and peer discussions, and that gender continues to be a robust indicator of violence-prevention actions.