Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.

Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material. From this resource we have defined variation in mitotic mis-segregation rates across tissue types and genotypes. Analysis of matched genomic and image measurements revealed correlations between cellular morphology and genome ploidy states. Aggregation of cells sharing copy number profiles allowed for calculation of single-nucleotide resolution clonal genotypes and inference of clonal phylogenies and avoided the limitations of bulk deconvolution. Finally, joint analysis over the above features defined clone-specific chromosomal aneuploidy in polyclonal populations.

Satisfaction with diabetes involvement: Exploring parent and adolescent perspectives.

AIMS: Both parent and adolescent involvement in type 1 diabetes management are critical during adolescence. The current study sought to understand the factors associated with parent and adolescent satisfaction with their own and one another's involvement in diabetes management. METHODS: Cross-sectional baseline data from 157 parent-adolescent dyads enrolled in an RCT were used. Adolescent ages ranged from 12 to 19 (Mage = 14.7, SD = 1.89) and were balanced by gender (50.3% male). Paired t-tests examined concordance between parent and adolescent satisfaction, bivariate correlations identified correlates, and regressions examined unique associations. RESULTS: Roughly, 43% of adolescents and 29% of parents were very satisfied with adolescent involvement in diabetes management, whereas 71% of adolescents and 26.1% of parents were very satisfied with parent involvement. Indicators of better glycaemic health (via higher percent time-in-range and lower HbA1c and percent time in hyperglycaemia) and psychosocial functioning (less diabetes distress and depression) were correlated with higher satisfaction. Parent satisfaction with adolescent involvement was higher among older adolescents (R = 0.198, p = 0.013). Non-Hispanic white youth were more satisfied with their own involvement than youth of colour (t(149) = -2.783, p = 0.003). Both percent time-in-range and one's own diabetes distress uniquely related to parent and adolescent satisfaction with adolescent involvement. Conversely, parent satisfaction with their own involvement was only uniquely associated with parent diabetes distress. CONCLUSION: Both adolescent and parents' satisfaction with adolescents' involvement in self-management are indicators of both glycaemic control and psychosocial well-being, whereas parents' self-evaluations are more closely tied to diabetes-specific distress.

'I was ready for it at the beginning': Parent experiences with early introduction of continuous glucose monitoring following their child's Type 1 diabetes diagnosis.

AIM: This study aimed to capture the experience of parents of youth with recent onset Type 1 diabetes who initiated use of continuous glucose monitoring (CGM) technology soon after diagnosis, which is a new practice. METHODS: Focus groups and individual interviews were conducted with parents of youth with Type 1 diabetes who had early initiation of CGM as part of a new clinical protocol. Interviewers used a semi-structured interview guide to elicit feedback and experiences with starting CGM within 30 days of diagnosis, and the benefits and barriers they experienced when adjusting to this technology. Groups and interviews were audio recorded, transcribed and analysed using content analysis. RESULTS: Participants were 16 parents (age 44.13 ± 8.43 years; 75% female; 56.25% non-Hispanic White) of youth (age 12.38 ± 4.15 years; 50% female; 50% non-Hispanic White; diabetes duration 10.35 ± 3.89 months) who initiated CGM 11.31 ± 7.33 days after diabetes diagnosis. Overall, parents reported high levels of satisfaction with starting CGM within a month of diagnosis and described a high level of reliance on the technology to help manage their child's diabetes. All participants recommended early CGM initiation for future families and were committed to continue using the technology for the foreseeable future, provided that insurance covered it. CONCLUSION: Parents experienced CGM initiation shortly after their child's Type 1 diabetes diagnosis as a highly beneficial and essential part of adjusting to living with diabetes.

Human Papillomavirus Vaccination and Human Papillomavirus-Related Cancer Rates.

Importance: To inform the design and implementation of targeted interventions to reduce the future burden of human papillomavirus (HPV)-related cancers in Texas, it is necessary to examine the county and health service region (HSR) levels of (1) the proportion of children and teenagers aged 9 to 17 years who initiated and were up to date for HPV vaccination series and (2) HPV-related cancer incidence rates (IRs). Objective: To evaluate temporal trends and geospatial patterns of HPV vaccination initiation and up-to-date status as well as HPV-related cancer rates at county and HSR levels in Texas. Design, Setting, and Participants: This population-based cross-sectional study used data from the Texas Immunization Registry, the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database, and Texas Department of State Health Services annual population counts from 2006 to 2022. The analysis of HPV vaccination rates was conducted among children and teenagers aged 9 to 17 years; the analysis of HPV-related cancer rates was conducted among adults aged 20 years and older. Data were extracted between June and July 2023 and statistical analysis was performed from February to April 2024. Main Outcomes and Measures: HPV vaccination initiation and up-to-date status rates and HPV-related cancer IR at county and HSR levels. Results: A total of 32 270 243 children and teenagers (65.8% female individuals and 34.2% male individuals) and 22 490 105 individuals aged 20 years and older (50.7% female individuals and 49.3% male individuals) were included. The mean 2021 to 2022 county-level HPV vaccination series initiation estimates ranged from 6.3% to 69.1% for female and from 7.0% to 77.6% for male children and teenagers aged 9 to 17 years. County-level vaccination up-to-date estimates were generally lower compared with those of initiation estimates and ranged from 1.6% to 30.4% for female and from 2.1% to 34.8% for male children and teenagers. The pattern of HPV vaccination rates stratified by sex were similar across counties and HSRs. The age-adjusted annual HPV-related cancer IR by county for years 2016 to 2020 ranged from 0 to 154.2 per 100 000 for female individuals and from 0 to 60.1 per 100 000 for male individuals. The counties located in North Texas, HSRs 2/3 and 4/5N, had lower HPV vaccination rates and higher IRs of HPV-related cancers for both female and male individuals compared with other regions. Conclusions and Relevance: In this study, the incidence of HPV-related cancers varied widely across the counties and HSRs of Texas. More counties in North Texas, HSRs 2/3 and 4/5N, had higher IRs of HPV-related cancers and a lower proportion of HPV vaccination rates than counties in other regions. Designing and implementing targeted interventions to increase uptake and completion of HPV vaccination series across counties with low HPV vaccination rates may help to reduce future the burden of HPV-related cancers.

Simulation-Based Mastery Learning Improves the Performance of Donning and Doffing of Personal Protective Equipment by Medical Students.

INTRODUCTION: Medical students lack adequate training on how to correctly don and doff personal protective equipment (PPE). Simulation-based mastery learning (SBML) is an effective technique for procedural education. The aim of this study was to determine whether SBML improves proper PPE donning and doffing by medical students. METHODS: This was a prospective, pre-test/post-test study of 155 medical students on demonstration of correct PPE use before and after a SBML intervention. Subjects completed standard hospital training by viewing a US Centers for Disease Control and Prevention training video on proper PPE use prior to the intervention. They then participated in a SBML training session that included baseline testing, deliberate practice with expert feedback, and post-testing until mastery was achieved. Students were assessed using a previously developed 21-item checklist on donning and doffing PPE with a minimum passing standard (MPS) of 21/21 items. We analyzed differences between pre-test and post-test scores using paired t-tests. Students at preclinical and clinical levels of training were compared with an independent t-test. RESULTS: Two participants (1.3%) met the MPS on pre-test. Of the remaining 153 subjects who participated in the intervention, 151 (98.7%) reached mastery. Comparison of mean scores from pre-test to final post-test significantly improved from an average raw score of 12.55/21 (standard deviation [SD] = 2.86), to 21/21(SD = 0), t(150) = 36.3, P <0.001. There was no difference between pre-test scores of pre-clinical and clinical students. CONCLUSION: Simulation-based mastery learning improves medical student performance in PPE donning and doffing in a simulated environment. This approach standardizes PPE training for students in advance of clinical experiences.

ONBOARD: A Feasibility Study of a Telehealth-Based Continuous Glucose Monitoring Adoption Intervention for Adults with Type 1 Diabetes.

Background: Continuous glucose monitoring (CGM) can improve glycemic control for adults with type 1 diabetes (T1D) but certain barriers interfere with consistent use including cost, data overload, alarm fatigue, physical discomfort, and unwanted social attention. This pilot study aimed to examine feasibility and acceptability of a behavioral intervention, ONBOARD (Overcoming Barriers and Obstacles to Adopting Diabetes Devices) to support adults with T1D in optimizing CGM use. Methods: Adults (18-50 years) with T1D in their first year of CGM use were invited to participate in a tailored, multicomponent telehealth-based intervention delivered over four 60-min sessions every 2-3 weeks. Participants completed surveys (demographics; diabetes distress, Diabetes Distress Scale for adults with type 1 diabetes; satisfaction with program) and provided CGM data at baseline and postintervention (3 months). Data were analyzed using paired t-tests and Wilcoxon signed-rank tests. Results: Twenty-two participants (age = 30.95 ± 8.32 years; 59% women; 91% non-Hispanic; 86% White, 5% Black, 9% other; 73% pump users) completed the study. ONBOARD demonstrated acceptability and a high rate of retention. Moderate effect sizes were found for reductions in diabetes distress (P = 0.01, r = -0.37) and increases in daytime spent in target range (70-180 mg/dL: P = 0.03, r = -0.35). There were no significant increases in hypoglycemia. Conclusions: Findings show preliminary evidence of feasibility, acceptability, and efficacy of ONBOARD for supporting adults with T1D in optimizing CGM use while alleviating diabetes distress. Further research is needed to examine ONBOARD in a larger sample over a longer period.

Drive-through medicine: a novel proposal for rapid evaluation of patients during an influenza pandemic.

STUDY OBJECTIVE: During a pandemic, emergency departments (EDs) may be overwhelmed by an increase in patient visits and will foster an environment in which cross-infection can occur. We developed and tested a novel drive-through model to rapidly evaluate patients while they remain in or adjacent to their vehicles. The patient's automobile would provide a social distancing strategy to mitigate the person-to-person spread of infectious diseases. METHODS: We conducted a full-scale exercise to test the feasibility of a drive-through influenza clinic and measure throughput times of simulated patients and carbon monoxide levels of staff. We also assessed the disposition decisions of the physicians who participated in the exercise. Charts of 38 patients with influenza-like illness who were treated in the Stanford Hospital ED during the initial H1N1 outbreak in April 2009 were used to create 38 patient scenarios for the drive-through influenza clinic. RESULTS: The total median length of stay was 26 minutes. During the exercise, physicians were able to identify those patients who were admitted and discharged during the real ED visit with 100% accuracy (95% confidence interval 91% to 100%). There were no significant increases of carboxyhemoglobin in participants tested. CONCLUSION: The drive-through model is a feasible alternative to a traditional walk-in ED or clinic and is associated with rapid throughput times. It provides a social distancing strategy, using the patient's vehicle as an isolation compartment to mitigate person-to-person spread of infectious diseases.

Rare Cause of Syncope in a Gravid Female.

CASE PRESENTATION: A 33-year-old gravid female was brought to the emergency department after she collapsed in the street. Point-of-care ultrasound showed free fluid in the abdomen and confirmed an intrauterine pregnancy. Surgical teams were consulted, and cross-sectional imaging revealed a spontaneously ruptured splenic artery aneurysm (SAA). The patient was taken expeditiously to the operating room for splenic artery ligation and subsequent splenectomy. DISCUSSION: Ruptured SAA in pregnant patients is associated with significant mortality for both mother and fetus. Maintaining a high index of suspicion in the correct population is crucial to avoid diagnostic errors and provide definitive care with operative repair.

Improving the Efficiency and the Technique of the Corneal Scrape Procedure via an Evidence Based Instructional Video at a Quaternary Referral Eye Hospital.

Purpose: Corneal culturing requires understanding of aseptic non-touch technique and avoidance of possible contaminants. Currently, there is no formal training in the technique and registrars are typically taught by another registrar in the emergency setting.The aim of the study was to develop an evidence-based instructional video for the corneal scrape procedure in microbial keratitis. The study then aims to assess the effect of the instructional video on clinician performance of the corneal scrape procedure.Method: An instructional video for corneal scraping was developed by identifying key steps for the procedure based on available evidence from a review of the literature and clinical practice. A prospective observational comparative case series that included clinicians at the Sydney Hospital/Sydney Eye Hospital, NSW Australia was conducted. Clinicians performing corneal scrapes had their performance of the procedure assessed prior to and after viewing the instructional video.Results: Sixteen key steps to follow in performing the corneal scrape procedure were found and demonstrated in the instructional video. Fourteen clinicians were observed performing 24 corneal scrapes in 24 patients with a median age of 56 years (IQR 34-65 years) and 45% male. Pre-video 11 scrapes were observed vs 13 scrapes post-video. Descriptive data were summarised and non-parametric categorical data analyzed using IBM SPSS (version 1.0.0.800) to perform chi-square and Wilcoxon signed-rank tests. Statistical significance was defined as p < .05. The steps of the corneal scrape procedure were performed correctly by a greater number of clinicians post-video compared to pre-video (p = .003). There was a significant improvement in inoculation of agar plates with cross-hatched streaks (92% post- vs 55% pre-video) and the maintenance of an intact agar surface (92% post vs 55% pre-video) (p = .033).Conclusion: An instructional video optimized the performance of corneal scraping, by ophthalmology trainees, in patients with microbial keratitis.

Meta-analysis suggests evidence of novel stress-related pathway components in Orsay virus - Caenorhabditis elegans viral model.

The genetic model organism, Caenorhabditis elegans (C. elegans), shares many genes with humans and is the best-annotated of the eukaryotic genome. Therefore, the identification of new genes and pathways is unlikely. Nevertheless, host-pathogen interaction studies from viruses, recently discovered in the environment, has created new opportunity to discover these pathways. For example, the exogenous RNAi response in C. elegans by the Orsay virus as seen in plants and other eukaryotes is not systemic and transgenerational, suggesting different RNAi pathways between these organisms. Using a bioinformatics meta-analysis approach, we show that the top 17 genes differentially-expressed during C. elegans infection by Orsay virus are functionally uncharacterized genes. Furthermore, functional annotation using similarity search and comparative modeling, was able to predict folds correctly, but could not assign easily function to the majority. However, we could identify gene expression studies that showed a similar pattern of gene expression related to toxicity, stress and immune response. Those results were strengthened using protein-protein interaction network analysis. This study shows that novel molecular pathway components, of viral innate immune response, can be identified and provides models that can be further used as a framework for experimental studies. Whether these features are reminiscent of an ancient mechanism evolutionarily conserved, or part of a novel pathway, remain to be established. These results reaffirm the tremendous value of this approach to broaden our understanding of viral immunity in C. elegans.

Regional bone mineral density in male athletes: a comparison of soccer players, runners and controls.

OBJECTIVES: To investigate the association of soccer playing and long-distance running with total and regional bone mineral density (BMD). DESIGN: Cross-sectional study. SETTING: Academic medical centre. PARTICIPANTS: Elite male soccer players (n = 15), elite male long-distance runners (n = 15) and sedentary male controls (n = 15) aged 20-30 years. MAIN OUTCOME MEASUREMENTS: BMD (g/cm2) of the lumbar spine (L1-L4), right hip, right leg and total body were assessed by dual-energy x-ray absorptiometry, and a scan of the right calcaneus was performed with a peripheral instantaneous x-ray imaging bone densitometer. RESULTS: After adjustment for age, weight and percentage body fat, soccer players had significantly higher whole body, spine, right hip, right leg and calcaneal BMD than controls (p = 0.008, p = 0.041, p<0.001, p = 0.019, p<0.001, respectively) and significantly higher right hip and spine BMD than runners (p = 0.012 and p = 0.009, respectively). Runners had higher calcaneal BMD than controls (p = 0.002). Forty percent of the runners had T-scores of the lumbar spine between -1 and -2.5. Controls were similar: 34% had T-scores below -1 (including 7% with T-scores lower than -2.5). CONCLUSIONS: Playing soccer is associated with higher BMD of the skeleton at all sites measured. Running is associated with higher BMD at directly loaded sites (the calcaneus) but not at relatively unloaded sites (the spine). Specific loading conditions, seen in ball sports or in running, play a pivotal role in skeletal adaptation. The importance of including an appropriate control group in clinical studies is underlined.

De qi: Chinese acupuncture patients' experiences and beliefs regarding acupuncture needling sensation--an exploratory survey.

INTRODUCTION: While de qi, the acupuncture needling sensation, has been considered as an important component of acupuncture, little is known of the acupuncture patient's experience and beliefs about de qi in clinical settings. The aim of this study was to describe Chinese acupuncture patients' perceived sensations of, and beliefs about, acupuncture needling. METHODS: We developed a questionnaire and conducted a survey study at two time periods among 200 subjects at six outpatient acupuncture clinics in Beijing, China. RESULTS: Respondents were 55% female and had a mean age of 41 years. The most common types of needling sensations reported by subjects were the terms 'distended' (94%), 'sore' (81%), 'electric' (81%) and 'numb' (78%). Eighty-nine percent of subjects reported that the needling sensation travelled away from the puncturing points or travelled among the needling points. Eighty-two percent of subjects believed that the needling sensation was very important for acupuncture treatment, and 68% further indicated that the stronger the needling sensation, the more effective the therapy. Eighty-one percent of subjects found the acupuncture process to be very comfortable and relaxing. CONCLUSION: Chinese acupuncture patients described the common characteristics of de qi and its migratory nature. The sensations were believed to be important in producing clinical efficacy by most patients. Measuring the sensations described as de qi in future prospective studies will help us understand the degree to which this phenomenon has an effect on the physiological outcome and clinical response to acupuncture. There appears to be a limit to the number of sensations that can be discriminated by each individual patient, and further development of the questionnaire is planned.

Disaster Medicine: A Multi-Modality Curriculum Designed and Implemented for Emergency Medicine Residents.

OBJECTIVE: Few established curricula are available for teaching disaster medicine. We describe a comprehensive, multi-modality approach focused on simulation to teach disaster medicine to emergency medicine residents in a 3-year curriculum. METHODS: Residents underwent a 3-year disaster medicine curriculum incorporating a variety of venues, personnel, and roles. The curriculum included classroom lectures, tabletop exercises, virtual reality simulation, high-fidelity simulation, hospital disaster drills, and journal club discussion. All aspects were supervised by specialty emergency medicine faculty and followed a structured debriefing. Residents rated the high-fidelity simulations by using a 10-point Likert scale. RESULTS: Three classes of emergency medicine residents participated in the 3-year training program. Residents found the exercise to be realistic, educational, and relevant to their practice. After participating in the program, residents felt better prepared for future disasters. CONCLUSIONS: Given the large scope of impact that disasters potentiate, it is understandably difficult to teach these skills effectively. Training programs can utilize this simulation-based curriculum to better prepare the nation's emergency medicine physicians for future disasters. (Disaster Med Public Health Preparedness. 2016;10:611-614).

Effects of ball sports on future risk of stress fracture in runners.

OBJECTIVE: To evaluate whether playing ball sports during childhood and adolescence is associated with the risk of stress fractures in runners later in life. DESIGN: Retrospective cohort study. SETTING: National track and field championships, held at Stanford University. PARTICIPANTS: One hundred fifty-six elite female and 118 elite male distance runners, age 18 to 44 years. INTERVENTIONS: A 1-page questionnaire was used to collect data regarding ages during which athletes played basketball and soccer, as well as other important covariates and outcomes. OUTCOME MEASUREMENTS: Athletes reported the ages when stress fractures occurred. Time to event was defined as the number of years from beginning competitive running to the first stress fracture or to current age, if no fracture had occurred. RESULTS: In both men and women, playing ball sports in youth correlated with reduced stress fracture incidence later in life by almost half, controlling for possible confounders. In men, each additional year of playing ball sports conferred a 13% decreased incidence of stress fracture (adjusted hazard ratio [HR] and 95% confidence interval, 0.87 [0.79-0.95]. Among women with regular menses, the HR for each additional year of playing ball sports was similar: 0.87 (0.75-1.00); however, there was no effect of length of time played among women with irregular menses (HR, 1.03 [0.92-1.16]). In men, younger ages of playing ball sports conferred more protection against stress fractures (HR for each 1-year-older age at first exposure, 1.29 [1.14, 1.45]). CONCLUSIONS: Runners who participate during childhood and adolescence in ball sports may develop bone with greater and more symmetrically distributed bone mass, and with enhanced protection from future stress fractures.

Physicians and lay people are unable to apply pressure immobilization properly in a simulated snakebite scenario.

OBJECTIVE: To determine whether volunteers (with or without prior medical training) can correctly apply pressure immobilization (PI) in a simulated snakebite scenario after receiving standard instructions describing the technique. METHODS: Twenty emergency medicine physicians (residents and attendings) and 20 lay volunteers without prior formal medical training were given standard printed instructions describing the application of PI for field management of snakebite. They were then supplied with appropriate materials and asked to apply the technique five separate times (twice to another individual [one upper and one lower extremity] and three times to themselves [nondominant upper extremity, dominant upper extremity, and one lower extremity]). Successful application was defined a priori by four criteria previously published in the literature: wrap begins at the bite site, entire extremity is wrapped, splint or sling is applied, and pressures under the dressing are between 40 and 70 mm Hg in upper-extremity application and between 55 and 70 mm Hg in lower-extremity use. Pressures were determined using a specially designed skin interface pressure-measuring device placed at the simulated bite site. RESULTS: The technique was correctly applied as judged by the preset criteria in only 13 out of 100 applications by emergency medicine physicians and in only 5 out of 100 applications by lay people. There was no significant difference in success rates between physicians and lay volunteers. Likewise, there was no significant difference in success based on which extremity was being wrapped. More detailed analysis revealed that the major contributor to failure was inability to achieve recommended target pressures. CONCLUSIONS: Volunteers in a simulated snakebite scenario have difficulty applying PI correctly, as defined in the literature. The major source of failure is an inability to achieve recommended pressure levels under the dressing. New methods of instructing people in the proper use of PI or new technologies to guide or automate application are needed if this technique is to be used consistently in an effective manner for field management of bites by venomous snakes not known to cause significant local wound necrosis.