Characterisation and reproducibility of the HumanMethylationEPIC v2.0 BeadChip for DNA methylation profiling.

BACKGROUND: The Illumina family of Infinium Methylation BeadChip microarrays has been widely used over the last 15 years for genome-wide DNA methylation profiling, including large-scale and population-based studies, due to their ease of use and cost effectiveness. Succeeding the popular HumanMethylationEPIC BeadChip (EPICv1), the recently released Infinium MethylationEPIC v2.0 BeadChip (EPICv2) claims to extend genomic coverage to more than 935,000 CpG sites. Here, we comprehensively characterise the reproducibility, reliability and annotation of the EPICv2 array, based on bioinformatic analysis of both manifest data and new EPICv2 data from diverse biological samples. RESULTS: We find a high degree of reproducibility with EPICv1, evidenced by comparable sensitivity and precision from empirical cross-platform comparison incorporating whole genome bisulphite sequencing (WGBS), and high correlation between technical sample replicates, including between samples with DNA input levels below the manufacturer's recommendation. We provide a full assessment of probe content, evaluating genomic distribution and changes from previous array versions. We characterise EPICv2's new feature of replicated probes and provide recommendations as to the superior probes. In silico analysis of probe sequences demonstrates that probe cross-hybridisation remains a significant problem in EPICv2. By mapping the off-target sites at single nucleotide resolution and comparing with WGBS we show empirical evidence for preferential off-target binding. CONCLUSIONS: Overall, we find EPICv2 a worthy successor to the previous Infinium methylation microarrays, however some technical issues remain. To support optimal EPICv2 data analysis we provide an expanded version of the EPICv2 manifest to aid researchers in understanding probe design, data processing, choosing appropriate probes for analysis and for integration with methylation datasets from previous versions of the Infinium Methylation BeadChip.

No longer "non-traditional": Genetic counselors' perceptions towards laboratory and industry roles.

A growing percentage of genetic counselors are employed in roles that do not involve direct patient care, commonly in commercial diagnostic laboratories. This study aimed to assess characteristics of laboratory and industry (LI) roles and perceptions of the genetic counseling community's views towards such roles. Members of NSGC and ABGC were invited to participate in this study. Data analysis included descriptive and inferential statistics and select participant quotes are included to highlight key points identified by statistical analyses. Three hundred twenty-six genetic counselors who self-identified as currently or previously working within an LI role responded to the survey. Over 40% of participants reported feeling that they were not perceived positively by colleagues outside of LI settings, and 54% felt that GC colleagues in non-LI roles provided mostly negative commentary about LI GC roles. Over 90% of individuals felt that their employer was a factor in the way they were perceived by others and that this factor carried a bigger weight than job title, work setting, or even professional responsibilities. Qualitative responses from open-ended text questions suggest that while perceptions toward LI roles have improved over time, commentary regarding the "dark side" of genetic counseling persists. To promote the continued, unified growth of the genetic counseling profession and other healthcare professions, it is necessary to address this source of intra-professional conflict.

Elective genomic testing: Practice resource of the National Society of Genetic Counselors.

Genetic counseling for patients who are pursuing genetic testing in the absence of a medical indication, referred to as elective genomic testing (EGT), is becoming more common. This type of testing has the potential to detect genetic conditions before there is a significant health impact permitting earlier management and/or treatment. Pre- and post-test counseling for EGT is similar to indication-based genetic testing. Both require a complete family and medical history when ordering a test or interpreting a result. However, EGT counseling has some special considerations including greater uncertainties around penetrance and clinical utility and a lack of published guidelines. While certain considerations in the selection of a high-quality genetic testing laboratory are universal, there are some considerations that are unique to the selection of a laboratory performing EGT. This practice resource intends to provide guidance for genetic counselors and other healthcare providers caring for adults seeking pre- or post-test counseling for EGT. Genetic counselors and other genetics trained healthcare providers are the ideal medical professionals to supply accurate information to individuals seeking counseling about EGT enabling them to make informed decisions about testing and follow-up.

Physician Communication Coaching: How Psychologists can Elevate Skills and Support Resident Education, Professionalism, and Well-being.

Many factors influence resident physician communication, including rigorous training demands that can contribute to professionalism issues or burnout. The University of Rochester Physician Communication Coaching program launched for attendings in 2011, and expanded to residency programs within 11 clinical departments of our institution. In this model, psychologists serve as coaches, drawing on their expertise in communication skills, behavior change, and wellness promotion. These coaches conduct real-time observation of patient encounters, coding communication with an expanded Cambridge-Calgary Patient-Centered Observational Checklist. Residents receive a written report with individualized feedback. From 2013 to 2020, 279 residents were coached. Since 2018, residents have been formally surveyed for feedback (n = 70 surveys completed; 61% response rate), with 97% rating the experience Very Helpful or Helpful. Of the 70 completed surveys, 54 (77%) included qualitative feedback that has also been positive. Due to the feasibility and growing demand for communication coaching from other residency and fellowship programs, in 2018 two authors (SM and LD-R) developed a 2-year, part-time program to train communication coaches.

The different faces of mental illness stigma: Systematic variation of stereotypes, prejudice and discrimination by type of illness.

Mental illness (MI) stigma has been characterized as multi-dimensional including problems of knowledge (stereotypes), attitudes (prejudice) and behavior (discrimination); however, most research practice is predominantly applying unidimensional behavioral measures such as social distance scales. Moreover, specific types of MIs and different forms of discriminatory behaviors are not being differentiated. The Stereotype Content Model predicts that group stereotypes (warmth, competence) are linked with different forms of discriminatory behaviors (harm or facilitation) via emotional prejudices (pity, envy, contempt). The present study sought to establish how differential stereotypic perceptions of MI subgroups elicit distinct forms of behavioral discrimination via emotional prejudices. A community sample (N = 60) was randomly assigned to one of three conditions representing MIs across the warmth-competence stereotype space. Patterns of self-completed measures for stereotypes, emotions and behaviors differed significantly between conditions. The association between stereotypes and behaviors were largely mediated by emotions. Systematic patterns of stereotypic perceptions, emotional prejudices and behavioral discrimination are present for individuals with different types of MIs. Hence, generic measures of discrimination, such as social distance scales, may be misleading. Intervention strategies should consider the systematic variation of the factors involved in stigma, differentiating by type of MI and discriminatory behaviors.

Machine learning for automatic identification of thoracoabdominal asynchrony in children.

BACKGROUND: The current methods for assessment of thoracoabdominal asynchrony (TAA) require offline analysis on the part of physicians (respiratory inductance plethysmography (RIP)) or require experts for interpretation of the data (sleep apnea detection). METHODS: To assess synchrony between the thorax and abdomen, the movements of the two compartments during quiet breathing were measured using pneuRIP. Fifty-one recordings were obtained: 20 were used to train a machine-learning (ML) model with elastic-net regularization, and 31 were used to test the model's performance. Two feature sets were explored: (1) phase difference (ɸ) between the thoracic and abdominal signals and (2) inverse cumulative percentage (ICP), which is an alternate measure of data distribution. To compute accuracy of training, the model outcomes were compared with five experts' assessments. RESULTS: Accuracies of 61.3% and 90.3% were obtained using ɸ and ICP features, respectively. The inter-rater reliability (i.r.r.) of the assessments of experts was 0.402 and 0.684 when they used ɸ and ICP to identify TAA, respectively. CONCLUSIONS: With this pilot study, we show the efficacy of the ICP feature and ML in developing an accurate automated approach to identifying TAA that reduces time and effort for diagnosis. ICP also helped improve consensus among experts. IMPACT: Our article presents an automated approach to identifying thoracic abdominal asynchrony using machine learning and the pneuRIP device. It also shows how a modified statistical measure of cumulative frequency can be used to visualize the progression of the pulmonary functionality along time. The pulmonary testing method we developed gives patients and doctors a noninvasive and easy to administer and diagnose approach. It can be administered remotely, and alerts can be transmitted to the physician. Further, the test can also be used to monitor and assess pulmonary function continuously for prolonged periods, if needed.

Analysis of the reported use of practice-based competencies by North American genetic counselors during the COVID-19 pandemic.

Genetic counseling services changed due to the COVID-19 pandemic. Many genetic counselors (GCs) moved from in-person to telehealth services. Others were redeployed by choice or necessity, using their expertise to provide COVID-19 care and education. For some, their employment status changed due to budgetary constraints or decreasing referrals. This study surveyed North American GCs to assess the relative use of genetic counseling Practice-Based Competencies (PBCs) as a proxy for the skills used during the first wave of the pandemic, whether GCs were in their current role or in new or adjusted roles. A secondary aim was to determine whether GCs believe their training should be refocused in view of the workforce shifts posed by the pandemic. The survey comprised closed- and open-ended questions and was completed in full by 97 respondents. The study population was representative of the general genetic counseling workforce in terms of gender, race/ethnicity, age, and practice area when compared to the National Society of Genetic Counselors 2020 Professional Status Survey. Most participants (97.9%) indicated that the COVID-19 pandemic resulted in a change to their work, and 89.7% used at least one PBC at a different frequency than before the pandemic. The most significant change was the adaptation of genetic counseling skills for varied service delivery models: 83.5% of respondents indicated that their roles and responsibilities moved to a remote setting and/or utilized telehealth. The majority of participants felt competent using the PBCs during the pandemic. Major themes that emerged from the qualitative data were as follows: (a) adaptation of service delivery, (b) translation of genetic counseling skills, and (c) provision of psychosocial support. This study highlights practice changes for GCs due to the COVID-19 pandemic as well as the increased use of, and need for focused training in, varied service delivery models.

Results of the Genetic Counselor SARS-CoV-2 Impact Survey from the National Society of Genetic Counselors: Progress and penalty during the COVID-19 pandemic.

The Genetic Counselor SARS-CoV-2 Impact Survey (GCSIS) describes the impact of the pandemic on genetic counselors and genetic counseling services. With this information, the National Society of Genetic Counselors (NSGC) can better: (1) support advocacy and access efforts for genetic counseling services at both federal- and state-level; (2) promote effective billing and reimbursement for genetic counseling services provided via telemedicine; and (3) make decisions about how to best support genetic counselors. The survey was hosted on a novel data collection and analysis platform from LunaDNA and was open to all genetic counselors (n = 5,531 based on professional society membership). Survey response rate was approximately 3.8% (n = 212/5,531), with a demographic distribution broadly representative of the North American genetic counseling field. Genetic counselors remained largely employed, providing genetic counseling services throughout the pandemic, although almost one in five respondents (17%, n = 35/211) reported experiencing some degree of pandemic-related financial hardship. Nearly all respondents (90%, n = 104/115) transitioned, at least in part, to remote work settings, with about half (47%. n = 88/189) reporting restrictions in the care they were able to provide. These shifts came at a cost: existing gaps in Medicare status for genetic counselors and attendant reimbursement concerns led to uncertainty about whether genetic counselors' work will be reimbursed. Outside of work, caregiving responsibilities increased for 34% (n = 74/212) of respondents. The results of the GCSIS amplify the importance of federal- and state-level advocacy efforts for genetic counselors and their employers. They also highlight the impact of broader cultural intransigence on our majority-female profession. During the pandemic, genetic counselors continued to provide care, but without consistent financial support or expectation of reimbursement. The ability to attract and retain talented professionals to the genetic counseling field will hinge on the success of continued advocacy efforts.

Daily physical activity and alcohol use among young adults.

Evidence suggests that physical activity and alcohol use are positively related among young adults. Two studies have examined daily relations, and results have shown conflicting findings. We examined relations between physical activity and alcohol use at both within- and between-individual levels and investigated moderators of the relation at both levels. 269 college students wore accelerometers to collect physical activity data over a 2-week period. At the end of each day, they indicated whether or not they drank alcohol. Multilevel logistic regression indicated neither within- nor between-subject relations were statistically significant. Positive affect, negative affect, and drinking motives moderated these relations at the between-subject level. Contrary to previous research, we did not observe a relation between physical activity and alcohol use at the daily level. Unique features of the current study suggest next steps for future research examining the perplexing PA-alcohol relation in this population.

Age-related ranges of respiratory inductance plethysmography (RIP) reference values for infants and children.

The current noninvasive method for respiratory monitoring is respiratory inductance plethysmography (RIP); two bands are connected, one each to the chest and the abdomen, to measure the breathing pattern. RIP requires post hoc analysis to calculate indices such as respiratory rate, phase angle, labored breathing index, and percent of rib cage contribution to breathing. Clinical studies have provided patient RIP values and age-matched normal values, but they lack global evaluation of normative data for a wide age range of pediatric subjects. Herein, we compiled normative RIP indices from numerous studies for a large range of pediatric ages. From these data, we derived regression equations useful for computing normal RIP parameters as a function of age. The presented review will provide caregivers the ability to compare RIP data of pediatric patients against the regression analysis. This comparison will help identify patients with pulmonary complications and aid in guiding respiratory therapy.

Vaped, Not Stirred: Vaporized Alcohol Knowledge, Use, and Susceptibility.

Background: Vaporized alcohol is an alternative method of ingesting alcohol that has received significant attention in the press. However, research on vaporized alcohol to date is limited. Objectives: The current study sought to assess vaporized alcohol knowledge, use, and future susceptibility in diverse sample of young adults in the Southwest United States. Method: A cross-sectional survey design was used to assess perception and use of vaporized alcohol in a sample of 986 young adults in college gathered in 2015 and 2016. Results: Overall, 26% of participants had heard of vaporized alcohol, 1.7% had used vaporized alcohol, and 33.5% were susceptible to future vaporized alcohol use. Contrary to our hypothesis, heavy drinkers were not more likely to have tried vaporized alcohol. Further, there were no significant differences in vaporized alcohol use across any sociodemographic groups. Conclusions/Importance: Ever use of vaporized alcohol was low, which was generally consistent with prior research, debunking media reports that vaporized alcohol is a widespread problem. However, ongoing monitoring of this method of alcohol ingestions appears warranted, especially with different populations (i.e., adolescents, and young adults not in college) where no empirical research has been published to date.

Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients.

PURPOSE: Many women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 and BRCA2. Among them, a subset has hereditary susceptibility to cancer and requires further testing. We sought to identify specific groups who remain at high risk and evaluate whether they should be offered multi-gene panel testing. METHODS: We tested 300 women on a multi-gene panel who were previously enrolled in a long-term study at UCSF. As part of their long-term care, all previously tested negative for mutations in BRCA1 and BRCA2 either by limited or comprehensive sequencing. Additionally, they met one of the following criteria: (i) personal history of bilateral breast cancer, (ii) personal history of breast cancer and a first or second degree relative with ovarian cancer, and (iii) personal history of ovarian, fallopian tube, or peritoneal carcinoma. RESULTS: Across the three groups, 26 women (9%) had a total of 28 pathogenic mutations associated with hereditary cancer susceptibility, and 23 women (8%) had mutations in genes other than BRCA1 and BRCA2. Ashkenazi Jewish and Hispanic women had elevated pathogenic mutation rates. In addition, two women harbored pathogenic mutations in more than one hereditary predisposition gene. CONCLUSIONS: Among women at high risk of breast and ovarian cancer who have previously tested negative for pathogenic BRCA1 and BRCA2 mutations, we identified three groups of women who should be considered for subsequent multi-gene panel testing. The identification of women with multiple pathogenic mutations has important implications for family testing.

Synthetic scale-up of a novel fluorescent probe and its biological evaluation for surface detection of Staphylococcus aureus.

This paper reports on the LGX fluorometric test for enzymatic MRSA/MSSA detection. It highlights the reasons rhodamines have been overlooked and also strategies to improve the synthesis of rhodamine-peptide conjugates. Evaluation of the LGX test for detection of MRSA/MSSA on surfaces is undertaken in the presence of potentially confounding E. coli and S. epidermidis for the first time.

Genetic Counselors in Startup Companies: Redefining the Genetic Counselor Role.

Genetic counselors (GCs) have recently begun moving into non-clinic based roles in increasing numbers. A relatively new role for GCs is working for startup companies. Startups are newly established companies in the phase of developing and researching new scalable businesses. This article explores the experiences of four GCs working at different startup companies and aims to provide resources for GCs interested in learning more about these types of roles. The article describes startup culture, including a relatively flat organizational structure, quick product iterations, and flexibility, among other unique cultural characteristics. Financial considerations are described, including how to understand and evaluate a company's financial status, along with a brief explanation of alternate forms of compensation including stock options and equity. Specifically, the article details the uncertainties and rewards of working in a fast-paced startup environment that affords opportunities to try new roles and use the genetic counseling skill set in new ways. This article aims to aid GCs in determining whether a startup environment would be a good fit, learning how to evaluate a specific startup, and understanding how to market themselves for positions at startups.

Dementia spousal caregivers and past transgressions: Measuring and understanding forgiveness experiences.

The transition from "wife" to "caregiver" for a cognitively impaired husband can be an overwhelming experience. Communication patterns change and small conflicts can grow, at times bringing angry feelings and new burdens. Engagement with forgiveness processes may benefit wives by lowering resentment over past tensions, restoring trust, and enhancing the overall caregiving experience. This study examined the utility of the Enright Forgiveness Inventory (EFI) within a sample of caregiving wives. Our intent was to better understand this population's experience with forgiveness when other contextual factors were likely to influence this process. Forgiveness scores on the EFI were positively related to the cognitive status of the care recipient, a particularly important finding for clinical intervention, and inversely related to marital distress and state anxiety.

Hospital to home: a geriatric educational program on effective discharge planning.

There has been increased attention on the needs of the burgeoning older adult population, with focus on the limited education and training experiences available in geriatric care. Older adults transitioning between levels of care often require increased attention, and the American Geriatrics Society (AGS) Task Force on the Future of Geriatric Medicine has encouraged greater training opportunities be provided to better understand the needs of this population. The Hospital to Home Program is one model of geriatric training emphasizing many of the AGS recommendations. Through qualitative analyses of 51 internal medicine residents' reflections, the authors report how this educational program is meeting the above need and share how Hospital to Home is enhancing residents' skills in creating a safe discharge for geriatric patients and their families.

The California breast density information group: a collaborative response to the issues of breast density, breast cancer risk, and breast density notification legislation.

In anticipation of breast density notification legislation in the state of California, which would require notification of women with heterogeneously and extremely dense breast tissue, a working group of breast imagers and breast cancer risk specialists was formed to provide a common response framework. The California Breast Density Information Group identified key elements and implications of the law, researching scientific evidence needed to develop a robust response. In particular, issues of risk associated with dense breast tissue, masking of cancers by dense tissue on mammograms, and the efficacy, benefits, and harms of supplementary screening tests were studied and consensus reached. National guidelines and peer-reviewed published literature were used to recommend that women with dense breast tissue at screening mammography follow supplemental screening guidelines based on breast cancer risk assessment. The goal of developing educational materials for referring clinicians and patients was reached with the construction of an easily accessible Web site that contains information about breast density, breast cancer risk assessment, and supplementary imaging. This multi-institutional, multidisciplinary approach may be useful for organizations to frame responses as similar legislation is passed across the United States. Online supplemental material is available for this article.

Learning in a sensory cortical microstimulation task is associated with elevated representational stability.

Sensory cortical representations can be highly dynamic, raising the question of how representational stability impacts learning. We train mice to discriminate the number of photostimulation pulses delivered to opsin-expressing pyramidal neurons in layer 2/3 of primary vibrissal somatosensory cortex. We simultaneously track evoked neural activity across learning using volumetric two-photon calcium imaging. In well-trained animals, trial-to-trial fluctuations in the amount of photostimulus-evoked activity predicted animal choice. Population activity levels declined rapidly across training, with the most active neurons showing the largest declines in responsiveness. Mice learned at varied rates, with some failing to learn the task in the time provided. The photoresponsive population showed greater instability both within and across behavioral sessions among animals that failed to learn. Animals that failed to learn also exhibited a faster deterioration in stimulus decoding. Thus, greater stability in the stimulus response is associated with learning in a sensory cortical microstimulation task.

Cortical circuitry mediating inter-areal touch signal amplification.

Sensory cortical areas are often organized into topographic maps which represent the sensory epithelium1,2. Individual areas are richly interconnected3, in many cases via reciprocal projections that respect the topography of the underlying map4,5. Because topographically matched cortical patches process the same stimulus, their interaction is likely central to many neural computations6-10. Here, we ask how topographically matched subregions of primary and secondary vibrissal somatosensory cortices (vS1 and vS2) interact during whisker touch. In the mouse, whisker touch-responsive neurons are topographically organized in both vS1 and vS2. Both areas receive thalamic touch input and are topographically interconnected4. Volumetric calcium imaging in mice actively palpating an object with two whiskers revealed a sparse population of highly active, broadly tuned touch neurons responsive to both whiskers. These neurons were especially pronounced in superficial layer 2 in both areas. Despite their rarity, these neurons served as the main conduits of touch-evoked activity between vS1 and vS2 and exhibited elevated synchrony. Focal lesions of the whisker touch-responsive region in vS1 or vS2 degraded touch responses in the unlesioned area, with whisker-specific vS1 lesions degrading whisker-specific vS2 touch responses. Thus, a sparse and superficial population of broadly tuned touch neurons recurrently amplifies touch responses across vS1 and vS2.