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Background Cigarette smoking is related to greater cancer incidence, worse cancer-related clinical outcomes, and worse patient quality of life. Few studies have evaluated the role of smoking in patients’ experiences of cancer-related symptom burden. This study examined relationships between smoking and total symptom burden as well as the incidence of severe symptoms among adult cancer patients. Patients and Methods Patients at Moffitt Cancer Center completed self-report surveys as part of routine cancer care. Symptom burden was evaluated as the sum of individual symptom ratings (total symptom burden) and the number of symptoms rated severe (incidence of severe symptoms). Zero-inflated negative binomial modeling was used to evaluate the relationships between smoking status (ever vs never smoker) and symptom burden outcomes controlling for relevant sociodemographic and clinical covariates and accounting for the proportion of participants reporting no symptom burden. Results This study included 12 571 cancer patients. More than half reported a history of cigarette smoking (n = 6771, 55%). Relative to never smokers, participants with a smoking history had 15% worse expected total symptom burden (ratio = 1.15, 95% confidence interval [CI] 1.11-1.20, P < .001) and 13% more expected severe symptoms (ratio = 1.13, 95% CI 1.05-1.21, P = .001) above and beyond the effects of relevant sociodemographic and clinical characteristics. Conclusion Results provide support that smoking is associated with worse cancer symptom burden. More research is needed to evaluate how smoking history (ie, current vs former smoker) and smoking cessation influence cancer symptom burden.

BACKGROUND AND PURPOSE: The study objective was to determine whether longitudinal changes in patient-reported outcomes (PROs) were associated with survival among early-stage, non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: Data were obtained from January 2015 through March 2020. We ran a joint probability model to assess the relationship between time-to-death, and longitudinal PRO measurements. PROs were measured through the Edmonton Symptom Assessment Scale (ESAS). We controlled for other covariates likely to affect symptom burden and survival including stage, tumor diameter, comorbidities, gender, race/ethnicity, relationship status, age, and smoking status. RESULTS: The sample included 510 early-stage NSCLC patients undergoing SBRT. The median age was 73.8 (range: 46.3–94.6). The survival component of the joint model demonstrates that longitudinal changes in ESAS scores are significantly associated with worse survival (HR: 1.04; 95% CI: 1.02–1.05). This finding suggests a one-unit increase in ESAS score increased probability of death by 4%. Other factors significantly associated with worse survival included older age (HR: 1.04; 95% CI: 1.03–1.05), larger tumor diameter (HR: 1.21; 95% CI: 1.01–1.46), male gender (HR: 1.87; 95% CI: 1.36–2.57), and current smoking status (HR: 2.39; 95% CI: 1.25–4.56). CONCLUSION: PROs are increasingly being collected as a part of routine care delivery to improve symptom management. Healthcare systems can integrate these data with other real-world data to predict patient outcomes, such as survival. Capturing longitudinal PROs—in addition to PROs at diagnosis—may add prognostic value for estimating survival among early-stage NSCLC patients undergoing SBRT.

BackgroundThe COVID-19 pandemic led to reductions in cervical cancer screening and colposcopy. Therefore, in this mixed method study we explored perceived pandemic-related practice changes to cervical cancer screenings in federally qualified health centers.MethodsBetween October 2021 and June 2022, a national sample of 148 clinicians completed surveys; a subset (n=13) clinicians completed qualitative interviews. Most (86%) reported reduced cervical cancer screening early in the pandemic, and 28% reported continued reduction in services at the time of survey completion (October 2021-July 2022). Nearly half (45%) reported staff shortages impacting their ability to screen or track patients.ResultsCompared to clinicians in OBGYN/Women’s health, those in family medicine and other specialties were less likely to report maintaining or increasing screening compared to pre-pandemic. Advanced practice providers (compared to MDs/DOs,) and Hispanic/Latinx/other clinicians (compared to white non-Hispanic) were more likely to report maintaining or increasing screening vs. pre-pandemic. Most (91%) felt that screening using HPV self-sampling would be helpful to address screening backlogs. Qualitative interviews highlighted the impacts of staff shortages and strategies for improvement.ConclusionsIdentifying barriers to screening and instituting solutions in federally qualified health centers is critical to preventing cervical cancers among patients at highest risk.FundingThis study was funded by the American Cancer Society, who had no role in the study’s design, conduct, or reporting.

BackgroundThe COVID-19 pandemic led to reductions in cervical cancer screening and colposcopy. Therefore, in this mixed method study we explored perceived pandemic-related practice changes to cervical cancer screenings and colposcopies.MethodsIn 2021, a national sample of 1,251 clinicians completed surveys, including 675 clinicians who performed colposcopy; a subset (n=55) of clinicians completed qualitative interviews.ResultsNearly half of all clinicians reported they were currently performing fewer cervical cancer screenings (47%) and colposcopies (44% of those who perform the procedure) than before the pandemic. About one-fifth (18.6%) of colposcopists reported performing fewer LEEPs than prior to the pandemic. Binomial regression analyses indicated that older, non-White, internal medicine and family medicine clinicians (compared to OB-GYNs), and those practicing in community health centers (compared to private practice) had higher odds of reporting reduced screening. Among colposcopists, males, internal medicine physicians, those practicing in community health centers, and in the South had higher odds of reporting reduced colposcopies. Qualitative interviews highlighted pandemic-related care disruptions and lack of tracking systems to identify overdue screenings.ConclusionsReductions in cervical cancer screening and colposcopy among nearly half of clinicians more than one year into the pandemic raise concerns that inadequate screening and follow-up will lead to future increases in preventable cancers.FundingThis study was funded by the American Cancer Society, who had no role in the study’s design, conduct, or reporting.

To assess how the COVID-19 pandemic affected catch-up HPV vaccination among age-eligible adults (ages 18-45). The current study leverages a national, cross-sectional sample of US adults ages 18-45 years to assess the prevalence and determinants of COVID-19 pandemic-related disruptions to catch-up HPV vaccination in 2021. The sample was restricted to adults intending to receive the HPV vaccine. Multinomial logistic regression analysis was conducted to assess the probability of 1) pandemic-related HPV vaccination disruption and 2) uncertainty about pandemic-related HPV vaccination disruption. Report of 'no pandemic-related HPV vaccination disruption' served as the reference category. Among adults intending to get the HPV vaccine (n = 1,683), 8.6 % reported pandemic-related HPV vaccination disruption, 14.7 % reported uncertainty about vaccination disruption, and 76.7 % reported no disruption. Factors associated with higher odds of pandemic-related vaccination disruption included non-English language preference (OR: 3.20; 95 % CI: 1.99-5.13), being a parent/guardian (OR: 1.77; 95 % CI: 1.18-2.66), having at least one healthcare visit in the past year (OR: 1.97; 95 % CI: 1.10-3.53), being up-to-date on the tetanus vaccine (OR: 1.81; 95 % CI: 1.19-2.75), and being a cancer survivor (OR: 2.57; 95 % CI: 1.52-4.34). Catch-up HPV vaccination for age-eligible adults is a critical public health strategy for reducing HPV-related cancers. While a small percentage of adults reported pandemic-related disruptions to HPV vaccination, certain adults (e.g., individuals with a non-English language preference and cancer survivors) were more likely to report a disruption. Interventions may be needed that increase accessibility of catch-up HPV vaccination among populations with reduced healthcare access during the pandemic.

Delays in healthcare, including breast cancer screening, were documented during the coronavirus disease 2019 (COVID-19) pandemic. However, no studies have examined the impact of COVID-19 on healthcare among women at high (≥20 % lifetime) risk for breast cancer. This study fills that gap. Between August 2020 and January 2021, high-risk women (N = 225) living in the United States (US) completed an online survey assessing COVID-related healthcare disruptions. Descriptive statistics characterized the frequency of breast cancer screening (mammogram and breast magnetic resonance imaging [MRI]) since the beginning of the COVID-19 pandemic. Multivariable linear regression analysis with backward selection examined demographic characteristics associated with COVID-related healthcare disruptions. Since March 2020, 40 % of participants had received a mammogram and 12 % had received a screening breast MRI. On average, participants reported low levels of COVID-related healthcare disruptions (

Patient-generated health data (PGHD), or health-related data gathered from patients to help address a health concern, are used increasingly in oncology to make regulatory decisions and evaluate quality of care. PGHD include self-reported health and treatment histories, patient-reported outcomes (PROs), and biometric sensor data. Advances in wireless technology, smartphones, and the Internet of Things have facilitated new ways to collect PGHD during clinic visits and in daily life. The goal of the current review was to provide an overview of the current clinical, regulatory, technological, and analytic landscape as it relates to PGHD in oncology research and care. The review begins with a rationale for PGHD as described by the US Food and Drug Administration, the Institute of Medicine, and other regulatory and scientific organizations. The evidence base for clinic-based and remote symptom monitoring using PGHD is described, with an emphasis on PROs. An overview is presented of current approaches to digital phenotyping or device-based, real-time assessment of biometric, behavioral, self-report, and performance data. Analytic opportunities regarding PGHD are envisioned in the context of big data and artificial intelligence in medicine. Finally, challenges and solutions for the integration of PGHD into clinical care are presented. The challenges include electronic medical record integration of PROs and biometric data, analysis of large and complex biometric data sets, and potential clinic workflow redesign. In addition, there is currently more limited evidence for the use of biometric data relative to PROs. Despite these challenges, the potential benefits of PGHD make them increasingly likely to be integrated into oncology research and clinical care.

Elevated cancer-specific mortality in PWH has been demonstrated for non-AIDS-defining malignancies. However, additional clinical endpoints of interest, including patient-reported outcomes (PROs), have not been systematically examined in PWH and cancer. We evaluated differences in patient-reported symptomology between cancer patients with versus without HIV using data from 12,529 patients at the Moffitt Cancer Center, including 55 with HIV. The symptoms were assessed using the Edmonton Symptom Assessment Scale (ESAS), which asks patients to rank 12 symptoms on a scale of 1–10, with scores ≥7 considered severe. The responses across all questions were summed to create a composite score. Vital status through t July 2021 was determined through linkage to the electronic health record. PWH reported a higher composite ESAS score on average (44.4) compared to HIV-uninfected cancer patients (30.7, p-value < 0.01). In zero-inflated negative binomial regression models adjusted for cancer site, sex, and race, the composite ESAS scores and the count of severe symptoms were 1.41 times (95% CI: 1.13–1.77) and 1.45 times (95% CI: 1.09–1.93) higher, respectively, in cancer patients with HIV. Among PWH, higher ESAS scores were associated with mortality (p-value = 0.02). This is the first demonstration of uniquely poor PROs in PWH and cancer and suggests that patient symptom monitoring to improve clinical endpoints deserves further study.

Vaccination for SARS-CoV-2, the virus that causes COVID-19 illness, is an important public health tool to reduce hospitalizations and deaths.This report focuses on intentions and behaviors related to COVID-19 vaccination among United States (U.S.) adults ages 18-45.From February 25-March 24, 2021, we conducted an online survey assessing COVID-19 vaccine intentions and behaviors, health beliefs, vaccine attitudes, and sociodemographic characteristics. Participants were adults aged 18-45, living throughout the U.S. with oversampling in Florida, panelists of a research panel company directly or via verified partners, and able to read, write, and understand English. Associations between COVID-19 vaccination uptake, intentions, and other study variables were examined through multivariable logistic and proportional odds regression analyses.Among participants in the final analytic sample (n = 2722), 18% reported having received at least one dose of a COVID-19 vaccine. Approximately 31% of unvaccinated participants reported strong intentions to receive a COVID-19 vaccine in the next year, whereas 35% reported strong intentions to receive a COVID-19 vaccine if it were strongly recommended by a healthcare provider. All COVID-19 vaccination outcomes were associated with male gender, sexual minority status, higher levels of education, and previous influenza vaccination. All vaccination intention outcomes were associated with vaccine attitudes and geographic region. Vaccination status and intentions were differentially associated with multiple additional sociodemographic, attitudinal, and/or healthcare experience variables.Several demographic variables, vaccine attitudes, and healthcare experiences were found to contribute to COVID-19 vaccine receipt and intentions. Targeted efforts are necessary to increase uptake of the vaccine in the U.S.

Racial and ethnic disparities are well-documented in cancer outcomes such as disease progression and survival, but less is known regarding potential disparities in symptom burden.The goal of this retrospective study was to examine differences in symptom burden by race and ethnicity in a large sample of cancer patients. We hypothesized that racial and ethnic minority patients would report greater symptom burden than non-Hispanic and White patients.A total of 5798 cancer patients completed the Edmonton Symptom Assessment Scale-revised (ESAS-r-CSS) at least once as part of clinical care. Two indicators of symptom burden were evaluated: (1) total ESAS-r-CSS score (i.e., overall symptom burden) and (2) number of severe symptoms (i.e., severe symptomatology). For patients completing the ESAS-r-CSS on multiple occasions, the highest score for each indicator was used. Zero-inflated negative binomial regression analyses were conducted, adjusting for other sociodemographic and clinical characteristics. Symptomology varied across race. Patients who self-identified as Black reported higher symptom burden (p = .016) and were more likely to report severe symptoms (p .001) than self-identified White patients. Patients with "other" race were also more likely to report severe symptoms than White patients (p = .032), but reported similar total symptom burden (p = .315). Asian and Hispanic patients did not differ from White or non-Hispanic patients on symptom burden (ps .05).This study describes racial disparities in patient-reported symptom burden during routine oncology care, primarily observed in Black patients. Clinic-based electronic symptom monitoring may be useful to detect high symptom burden, particularly in patients who self-identify their race as Black or other. Future research is needed to reduce symptom burden in racially diverse cancer populations.

Background The impact of socioeconomic status (SES) has been described for screening and accessing treatment for colon cancer. However, little is known about the “downstream” effect in patients who receive guideline‐concordant treatment. This study assessed the impact of SES on cancer‐specific survival (CSS) and overall survival (OS) for stage III colon cancer patients. Methods The SEER Census Tract‐Level SES Dataset from 2004 to 2015 was used to identify stage III colon adenocarcinoma patients who received curative‐intent surgery and adjuvant chemotherapy. The predictor variable was census tract SES. SES was analyzed as quintiles. The outcome variables were OR and CSS. Statistical analysis included chi square tests for association, Kaplan–Meier, Cox, Fine and Gray regression for survival analysis. Results In total, 27,222 patients met inclusion criteria. Lower SES was associated with younger age, Black or Hispanic race/ethnicity, Medicaid/uninsured, higher T stage, and lower grade tumors. CSS at the 25th percentile was 54 months for the lowest SES quintile and 80 for the highest. Median OS was 113 months for the lowest SES quintile and not reached for highest. The 5‐year CSS rate was 72.4% for the lowest SES quintile compared to 78.9% in the highest (p, This is the first study to evaluate CSS and OS in a national cohort of stage III colon cancer patients using a granular, standardized measure of SES. We showed that despite receipt of guideline‐based treatment, socioeconomic status is associated with disparities in overall and cancer specific survival. These findings suggest opportunities to improve colon cancer outcomes farther down the cancer care continuum.

In some large clinical studies, it may be impractical to perform the physical examination to every subject at his/her last monitoring time in order to diagnose the occurrence of the event of interest. This gives rise to survival data with missing censoring indicators where the probability of missing may depend on time of last monitoring and some covariates. We present a fully Bayesian semi-parametric method for such survival data to estimate regression parameters of the proportional hazards model of Cox (1972). Theoretical investigation and simulation studies show that our method performs better than competing methods. We apply the proposed method to analyze the survival data with missing censoring indicators from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study.

OBJECTIVES Despite the efforts of various leading organizations in medical education, representation of black students in US medical schools has declined since the mid-1990s. The Florida State University College of Medicine (FSUCOM) has undertaken efforts to increase black and other underrepresented minority in medicine (URMM) representation in medical school through the Bridge to Clinical Medicine Program. This program is described and analyzed by the authors. METHODS Demographic information, Medical College Admission Test scores, undergraduate grade point average, US Medical Licensing Examination (USMLE) scores (Steps 1 and 2), residency match information, and current practice location from 2006 to 2015 were collected from the FSUCOM. Data were analyzed using SAS and linear regression analyses were performed, comparing Bridge students with the College of Medicine and national averages. RESULTS Sixty percent of Bridge students were black, 21% were other URMM, and the remainder were non-URMM. Black Bridge students scored 7.4 points lower on their Medical College Admission Test, and other-URMM Bridge students scored 6.0 points lower (P < 0.0001) than their non-URMM non-Bridge classmates. Black Bridge students also started with a grade point average that was 0.28 points lower than their non-URMM non-Bridge counterparts, but there was no statistical difference for other-URMM Bridge students. Black students, regardless of Bridge participation, were less likely to pass USMLE Step 1 when compared with non-URMM classmates (P < 0.0001). For USMLE Step 2, however, there were no significant differences in passing rates for Bridge students compared with non-Bridge students. CONCLUSIONS The FSUCOM Bridge program has not only increased its URMM enrollment but it also has effectively doubled the number of black students in its medical college. Other universities could produce similar results using the program outlined in this article.

96 Background: Prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) targeted to prostate-specific membrane antigen (PSMA) is a new targeted treatment for progressive metastatic castration-resistant prostate cancer (mCRPC). PSMA-RLT conjugates a radionuclide to a small molecule ligand with affinity for PSMA. Recent trials, such as TheraP and VISION, established improvements in progression free survival, overall survival, and patient-reported outcomes (PROs) for PSMA-RLT. Less is known about the impact of PSMA-RLT on symptoms related to bone metastasis (BM), commonly causing significant morbidity in men with mCRPC. The optimal tools for PRO collection with PSMA-RLT are also uncertain. We previously reported improvements in Brief Pain Inventory and now report EORTC QLQ-BM22 data to describe change in symptoms related to bone metastasis among men receiving PSMA-RLT for mCRPC. Methods: From 2015 to 2017, 50 patients received up to 4 cycles of 177Lu-PSMA-617 every 6 weeks (trial registration: ACTRN12615000912583). Patients completed a validated assessment of bone metastasis-related pain (EORTC QLQ-BM22) prior to each cycle and 6 or 12 weeks after the last cycle of 177Lu-PSMA. Change in pain over the course of the study was examined using linear mixed effects models. We also examined whether unadjusted changes in PROs exceeded published cutoffs for minimal clinically important difference scores. Results: Patients reported reduced bone metastasis-related pain at various sites over time ( p =.01). Of 44 patients completing this scale before cycle 2, 22 (50%) reported clinically significant improvement in pain at various sites. At follow-up, of the 37 patients alive, 25 provided evaluable data on bone metastasis-related pain. Of these, 10 (40%) reported clinically significant improvement in pain at various sites. Patients also reported less functional interference from pain over time ( p 177Lu-PSMA RLT resulted in improvements in bone metastasis-related symptoms, supporting prior findings using other PRO measures. At follow-up, 38-42% of patients completing PRO assessment reported clinically meaningful improvements in bone metastasis-related pain, a significant contributor to quality of life. Clinical trial information: ACTRN12615000912583.

Background Health care professionals are continually challenged by the need to provide health information in a way that successfully changes health practices. Research has documented this as a concern in relation to safe infant sleep health campaigns. Often, caregivers' knowledge of recommended practices is not associated with a change in infant sleep choices. Purpose Health campaigns, including most safe infant sleep efforts, often share specific risk factors and steps for avoiding risk, that is, in a verbatim format. Research has shown that caregivers' behavior may be more likely to change when presented with messages based on their general understanding of risk, that is, gist-based format. This research examines caregivers' responses as related to verbatim- and gist-based safe sleep information. Methods Five hundred forty-one caregivers of infants were shown 12 images depicting infants in safe or unsafe sleep spaces. Images varied across three commercially available spaces, infant race, and presence/absence of one policy-based risk factor. Results Differences in caregivers' discernment of safe and unsafe sleep images paralleled reported differences in knowledge of safe sleep recommendations. Discernment of safe/unsafe images was greater for White than Black caregivers, as well as for females in comparison with male caregivers. Gist-based considerations, such as familiarity with the sleeper depicted or infant race, were also associated with caregivers' discernment of safe/unsafe images. Implications for practice Attending to both gist- and verbatim-based knowledge regarding safe infant sleep campaign information may help to effectively facilitate caregivers' ability to always create safe sleep spaces for their infants.

The manuscript describes and visualizes datasets from the datasets package in the R statistical software, focusing on descriptive statistics and visualizations that provide insights into the clusterability of these datasets. These publicly available datasets are contained in the R software system, and can be downloaded at https://www.r-project.org/, with documentation provided at https://stat.ethz.ch/R-manual/R-devel/library/datasets/html/00Index.html. Further information on clusterability is found in the companion to this article, To Cluster or Not to Cluster: An Analysis of Clusterability Methods? (https://doi.org/10.1016/j.patcog.2018.10.026).Brief descriptions and graphs of the variables contained in each dataset are provided in the form of means, extrema, quartiles, standard deviation and standard error. Two-dimensional plots for each pair of variables are provided. Original references to the data sets are included when available. Further, each dataset is reduced to a single dimension by each of two different methods: pairwise distances and principal component analysis. For the latter, only the first component is used. Histograms of the reduced data are included for every dataset using both methods. Keywords: Datasets, Dimension reduction, Histograms, Principal component analysis, Pairwise distances

Rationale Bottom-up tandem mass spectrometry (MS/MS) is regularly used in proteomics to identify proteins from a sequence database. De novo sequencing is also available for sequencing peptides with relatively short sequence lengths. We recently showed that paired Lys-C and Lys-N proteases produce peptides of identical mass and similar retention time, but different tandem mass spectra. Such parallel experiments provide complementary information, and allow for up to 100% MS/MS sequence coverage. Methods Here, we report digestion by paired Lys-C and Lys-N proteases of a seven-protein mixture: human hemoglobin alpha, bovine carbonic anhydrase 2, horse skeletal muscle myoglobin, hen egg white lysozyme, bovine pancreatic ribonuclease, bovine rhodanese, and bovine serum albumin, followed by reversed-phase nanoflow liquid chromatography, collision-induced dissociation, and 14.5 T Fourier transform ion cyclotron resonance mass spectrometry. Results Matched pairs of product peptide ions of equal precursor mass and similar retention times from each digestion are compared, leveraging single-residue transposed information with independent interferences to confidently identify fragment ion types, residues, and peptides. Selected pairs of product ion mass spectra for de novo sequenced protein segments from each member of the mixture are presented. Conclusions Pairs of the transposed product ions as well as complementary information from the parallel experiments allow for both high MS/MS coverage for long peptide sequences and high confidence in the amino acid identification. Moreover, the parallel experiments in the de novo sequencing reduce false-positive matches of product ions from the single-residue transposed peptides from the same segment, and thereby further improve the confidence in protein identification. Copyright © 2016 John Wiley & Sons, Ltd.

Background Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. Methods We conducted a case–control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure ( 90th percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status. Results We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14]). Conclusion Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes. Birth Defects Research (Part A) 106:240–249, 2016. © 2016 Wiley Periodicals, Inc.

Tenure has been used for years to recruit, promote, and retain faculty in higher education and has been associated with job security and academic freedom. Absence of tenure and not being in tenure-earning tracks is grouped with the challenges faced by underrepresented minorities in academic medicine. Those challenges include being found at the assistant professor rank more often, having more clinical responsibilities, and not being in leadership positions as often as compared to non-minority faculty. The role of tenure and tenure tracks is unclear as it relates to the presence of minority faculty. This article presents a look at the status of tenure among black and Latino faculty in academic medicine at US medical schools.

BACKGROUND: African American adolescents appear to be the most at risk for asthma morbidity and mortality even compared with other minority groups, yet there are few successful interventions for this population that are used to target poorly controlled asthma. METHODS: African American adolescents (age 12–16 years) with moderate-to-severe persistent asthma and ≥1 inpatient hospitalization or ≥2 emergency department visits in 12 months were randomly assigned to Multisystemic Therapy–Health Care or an attention control group (N = 167). Multisystemic Therapy–Health Care is a 6-month home- and community-based treatment that has been shown to improve illness management and health outcomes in high-risk adolescents by addressing the unique barriers for each individual family with cognitive behavioral interventions. The attention control condition was weekly family supportive counseling, which was also provided for 6 months in the home. The primary outcome was lung function (forced expiratory volume in 1 second [FEV1]) measured over 12 months of follow-up. RESULTS: Linear mixed-effects models revealed that compared with adolescents in the comparison group, adolescents in the treatment group had significantly greater improvements in FEV1 secondary outcomes of adherence to controller medication, and the frequency of asthma symptoms. Adolescents in the treatment group had greater reductions in hospitalizations, but there were no differences in reductions in emergency department visits. CONCLUSIONS: A comprehensive family- and community-based treatment significantly improved FEV1, medication adherence, asthma symptom frequency, and inpatient hospitalizations in African American adolescents with poorly controlled asthma. Further evaluation in effectiveness and implementation trials is warranted.

This article resulted from our participation in the session on the “role of expert opinion and judgment in statistical inference” at the October 2017 ASA Symposium on Statistical Inference. We present a strong, unified statement on roles of expert judgment in statistics with processes for obtaining input, whether from a Bayesian or frequentist perspective. Topics include the role of subjectivity in the cycle of scientific inference and decisions, followed by a clinical trial and a greenhouse gas emissions case study that illustrate the role of judgments and the importance of basing them on objective information and a comprehensive uncertainty assessment. We close with a call for increased proactivity and involvement of statisticians in study conceptualization, design, conduct, analysis, and communication.

In a prospective cohort study, examining all participants for incidence of the condition of interest may be prohibitively expensive. For example, the "gold standard" for diagnosing temporomandibular disorder (TMD) is a physical examination by a trained clinician. In large studies, examining all participants in this manner is infeasible. Instead, it is common to use questionnaires to screen for incidence of TMD and perform the "gold standard" examination only on participants who screen positively. Unfortunately, some participants may leave the study before receiving the "gold standard" examination. Within the framework of survival analysis, this results in missing failure indicators. Motivated by the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study, a large cohort study of TMD, we propose a method for parameter estimation in survival models with missing failure indicators. We estimate the probability of being an incident case for those lacking a "gold standard" examination using logistic regression. These estimated probabilities are used to generate multiple imputations of case status for each missing examination that are combined with observed data in appropriate regression models. The variance introduced by the procedure is estimated using multiple imputation. The method can be used to estimate both regression coefficients in Cox proportional hazard models as well as incidence rates using Poisson regression. We simulate data with missing failure indicators and show that our method performs as well as or better than competing methods. Finally, we apply the proposed method to data from the OPPERA study.

RATIONALE Paired Lys-N and Lys-C proteases produce peptides of identical mass and similar retention time, but different tandem mass spectra. Data from these parallel experiments provide constraints that are applied before data analysis. With this approach, we can find matched spectra before analysis, distinguish ion type, and determine residue level confidence. METHODS Aliquots are digested separately by Lys-N and Lys-C peptidases, and analyzed by reversed-phase nano-flow liquid chromatography, collision-induced dissociation, and 14.5 T Fourier transform ion cyclotron resonance mass spectrometry. Matched pairs of fragmentation spectra with equal precursor mass and similar retention times from each digestion are compared, leveraging single-residue transposed information with independent interferences to confidently identify fragment ion type, residues, and peptides. The paired spectra are solved together as a single de novo sequencing problem. RESULTS Two pairs of spectra of a de novo sequenced 18-mer are presented. In one example, the 18-mer has coverage of all residues except the N- and C- terminal lysines and their adjacent residues. The confidence level is high due to six pairs of transposed ions. In the other example, the coverage is incomplete. Nonetheless, nine pairs of transposed ions facilitate identification of two trimer sequence tags with high confidence, one with medium confidence, and additional sequence information with residue-by-residue confidence, thus demonstrating the value of residue-by-residue confidence. CONCLUSIONS Sequence identity and variability, such as post-translational modifications (PTMs), are essential to understanding biological function and disease. The present method facilitates discovery of new peptides with multiple levels of confidence, promises potential characterization of PTMs, and validates peptides from databases. Independent validation may be of interest for a number of applications. Copyright © 2015 John Wiley & Sons, Ltd.

The Dip Test of Unimodality and Silverman's Critical Bandwidth Test are two popular tests to determine if an unknown density contains more than one mode. While the tests can be easily run in R, they are not included in SAS software. We provide implementations of the Dip Test and Silverman Test as macros in the SAS software, capitalizing on the capability of SAS to execute R code internally. Descriptions of the macro parameters, installation steps, and sample macro calls are provided, along with an appendix for troubleshooting. We illustrate the use of the macros on data simulated from one or more Gaussian distributions as well as on the famous $\textit{iris}$ dataset., 14 pages plus appendix and references. 3 tables and 3 figures in separate Tables and Figures sections at the end

Clustering is an essential data mining tool that aims to discover inherent cluster structure in data. For most applications, applying clustering is only appropriate when cluster structure is present. As such, the study of clusterability, which evaluates whether data possesses such structure, is an integral part of cluster analysis. However, methods for evaluating clusterability vary radically, making it challenging to select a suitable measure. In this paper, we perform an extensive comparison of measures of clusterability and provide guidelines that clustering users can reference to select suitable measures for their applications., Comment: 30 pages, 3 figures, 10 tables

We evaluate the use of three different exposure metrics to estimate maternal agricultural pesticide exposure during pregnancy. Using a geographic information system-based method of pesticide exposure estimation, we combine data on crop density and specific pesticide application amounts/dates to create the three exposure metrics. For illustration purposes, we create each metric for a North Carolina cohort of pregnant women, 2003-2005, and analyze the risk of congenital anomaly development with a focus on metric comparisons. Based on the results, and the need to balance data collection efforts/computational efficiency with accuracy, the metric which estimates total chemical exposure using application dates based on crop-specific earliest planting and latest harvesting information is preferred. Benefits and drawbacks of each metric are discussed and recommendations for extending the analysis to other states are provided.

Purpose: The purpose of this study was to compare medical residents and practicing physicians in primary care specialties regarding their knowledge and beliefs about electronic cigarettes (e-cigarettes). We wanted to ascertain whether years removed from medical school had an effect on screening practices, recommendations given to patients, and the types of informational sources utilized. Methods: A statewide sample of Florida primary care medical residents (n = 61) and practicing physicians (n = 53) completed either an online or paper survey, measuring patient screening and physician recommendations, beliefs, and knowledge related to e-cigarettes. χ2 tests of association and linear and logistic regression models were used to assess the differences within- and between-participant groups. Results: Practicing physicians were more likely than medical residents to believe e-cigarettes lower cancer risk in patients who use them as an alternative to cigarettes ( P = .0003). Medical residents were more likely to receive information about e-cigarettes from colleagues ( P = .0001). No statistically significant differences were observed related to e-cigarette knowledge or patient recommendations. Conclusions: Practicing primary care physicians are accepting both the benefits and costs associated with e-cigarettes, while medical residents in primary care are more reticent. Targeted education concerning the potential health risks and benefits associated with the use of e-cigarettes needs to be included in the current medical education curriculum and medical provider training to improve provider confidence in discussing issues surrounding the use of this product.

Background : Extracellular vesicles (EVs) are important mediators of cell-to-cell communication in healthy and pathological environments. Because EVs are present in a variety of biological fluids and contain molecular signatures of their cell or tissue of origin, they have great diagnostic and prognostic value. The ability of EVs to deliver biologically active proteins, RNAs and lipids to cells has generated interest in developing novel therapeutics. Despite their potential medical use, many of the mechanisms underlying EV biogenesis and secretion remain unknown. Methods : Here, we characterized vesicle secretion across the NCI-60 panel of human cancer cells by nanoparticle tracking analysis. Using CellMiner, the quantity of EVs secreted by each cell line was compared to reference transcriptomics data to identify gene products associated with vesicle secretion. Results : Gene products positively associated with the quantity of exosomal-sized vesicles included vesicular trafficking classes of proteins with Rab GTPase function and sphingolipid metabolism. Positive correlates of larger microvesicle-sized vesicle secretion included gene products involved in cytoskeletal dynamics and exocytosis, as well as Rab GTPase activation. One of the identified targets, CD63, was further evaluated for its role in vesicle secretion. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 knockout of the CD63 gene in HEK293 cells resulted in a decrease in small vesicle secretion, suggesting the importance of CD63 in exosome biogenesis. Conclusion : These observations reveal new insights into genes involved in exosome and microvesicle formation, and may provide a means to distinguish EV sub-populations. This study offers a foundation for further exploration of targets involved in EV biogenesis and secretion. Keywords: oncosomes; polyethylene glycol; endocytosis; trafficking; bioinformatics; tetraspanin; genome engineering (Published: 13 July 2016) Citation: Journal of Extracellular Vesicles 2016, 5: 31295 - http://dx.doi.org/10.3402/jev.v5.31295

The notion of an unavoidable set of words appears frequently in the fields of mathematics and theoretical computer science, in particular with its connection to the study of combinatorics on words. The theory of unavoidable sets has seen extensive study over the past twenty years. In this paper we extend the definition of unavoidable sets of words to unavoidable sets of partial words. Partial words, or finite sequences that may contain a number of “do not know” symbols or “holes,” appear naturally in several areas of current interest such as molecular biology, data communication, and DNA computing. We demonstrate the utility of the notion of unavoidability of sets of partial words by making use of it to identify several new classes of unavoidable sets of full words. Along the way we begin work on classifying the unavoidable sets of partial words of small cardinality. We pose a conjecture, and show that affirmative proof of this conjecture gives a sufficient condition for classifying all the unavoidable sets of partial words of size two. We give a result which makes the conjecture easy to verify for a significant number of cases. We characterize many forms of unavoidable sets of partial words of size three over a binary alphabet, and completely characterize such sets over a ternary alphabet. Finally, we extend our results to unavoidable sets of partial words of size k over a k-letter alphabet.

Birth defects are responsible for a large proportion of disability and infant mortality. Pesticides have been linked sporadically to increased risk of birth defects. We conducted a case-control stu...

In a prospective cohort study, examining all participants for incidence of the condition of interest may be prohibitively expensive. For example, the “gold standard” for diagnosing temporomandibular disorder (TMD) is a physical examination by a trained clinician. In large studies, examining all participants in this manner is infeasible. Instead, it is common to use questionnaires to screen for incidence of TMD and perform the “gold standard” examination only on participants who screen positively. Unfortunately, some participants may leave the study before receiving the “gold standard” examination. Within the framework of survival analysis, this results in missing failure indicators. Motivated by the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study, a large cohort study of TMD, we propose a method for parameter estimation in survival models with missing failure indicators. We estimate the probability of being an incident case for those lacking a “gold standard” examination using logistic regression. These estimated probabilities are used to generate multiple imputations of case status for each missing examination that are combined with observed data in appropriate regression models. The variance introduced by the procedure is estimated using multiple imputation. The method can be used to estimate both regression coefficients in Cox proportional hazard models as well as incidence rates using Poisson regression. We simulate data with missing failure indicators and show that our method performs as well as or better than competing methods. Finally, we apply the proposed method to data from the OPPERA study.

The course of preclinical pain symptoms sheds light on the etiology and prognosis of chronic pain. We aimed to quantify rates of developing initial and recurrent symptoms of painful temporomandibular disorder (TMD) and to evaluate associations with health behaviors. In the OPPERA prospective cohort study, 2,719 individuals aged 18 to 44years with lifetime absence of TMD when enrolled completed 25,103 quarterly (3-monthly) questionnaires during a median 2.3-year follow-up period. Questionnaires documented TMD symptom episodes, headache, other body pain, health care attendance, and analgesic use, and. Kaplan-Meier methods for clustered data estimated symptom-free survival time. Multivariable models assessed demographic variation in TMD symptom rates and evaluated associations with health care and analgesic use. One-third of the study subjects developed TMD symptoms and for a quarter of symptomatic episodes, pain intensity was severe. Initial TMD symptoms developed at an annual rate of 18.8 episodes per 100 persons. The annual rate more than doubled for first-recurrence and doubled again for second or subsequent recurrence such that, 1year after first recurrence, 71% of study subjects experienced a second recurrence. The overall rate increased with age and was greater in African Americans and lower in Asians relative to those of white race/ethnicity. The probability of TMD symptoms was strongly associated with concurrent episodes of headache and body pain and with past episodes of TMD symptoms. Episodes of TMD symptoms, headache, and body pain were associated with increases of ∼10% in probability of analgesic use and health care attendance. Yet, even when TMD, headache, and body pain occurred concurrently, 27% of study subjects neither attended health care nor used analgesics.

When studying incidence of pain conditions such as temporomandibular disorder (TMD), repeated monitoring is needed in prospective cohort studies. However, monitoring methods usually have limitations and, over a period of years, some loss to follow-up is inevitable. The OPPERA prospective cohort study of first-onset TMD screened for symptoms using quarterly questionnaires and examined symptomatic participants to definitively ascertain TMD incidence. During the median 2.8-year observation period, 16% of the 3,263 enrollees completed no follow-up questionnaires, others provided incomplete follow-up, and examinations were not conducted for one third of symptomatic episodes. Although screening methods and examinations were found to have excellent reliability and validity, they were not perfect. Loss to follow-up varied according to some putative TMD risk factors, although multiple imputation to correct the problem suggested that bias was minimal. A second method of multiple imputation that evaluated bias associated with omitted and dubious examinations revealed a slight underestimate of incidence and some small biases in hazard ratios used to quantify effects of risk factors. Although “bottom line” statistical conclusions were not affected, multiply-imputed estimates should be considered when evaluating the large number of risk factors under investigation in the OPPERA study. Perspective These findings support the validity of the OPPERA prospective cohort study for the purpose of investigating the etiology of first-onset TMD, providing the foundation for other papers investigating risk factors hypothesized in the OPPERA project.

In this paper we present a functional Bayesian method for detecting genes which are temporally differentially expressed between several conditions. We identify the nature of differential expression (e.g., gene is differentially expressed between the first and the second sample but is not differentially expressed between the second and the third) and subsequently we estimate gene expression temporal profiles. The proposed procedure deals successfully with various technical difficulties which arise in microarray time-course experiments such as a small number of observations, non-uniform sampling intervals and presence of missing data or repeated measurements. The procedure allows to account for various types of errors, thus, offering a good compromise between nonparametric and normality assumption based techniques. In addition, all evaluations are carried out using analytic expressions, hence, the entire procedure requires very small computational effort. The performance of the procedure is studied using simulated data.