Communicating Personal Melanoma Polygenic Risk Information: Participants' Experiences of Genetic Counseling in a Community-Based Study.

Personalized polygenic risk information may be used to guide risk-based melanoma prevention and early detection at a population scale, but research on communicating this information is limited. This mixed-methods study aimed to assess the acceptability of a genetic counselor (GC) phone call in communicating polygenic risk information in the Melanoma Genomics Managing Your Risk randomized controlled trial. Participants (n = 509) received personalized melanoma polygenic risk information, an educational booklet on melanoma prevention, and a GC phone call, which was audio-recorded. Participants completed the Genetic Counseling Satisfaction Survey 1-month after receiving their risk information (n = 346). A subgroup took part in a qualitative interview post-study completion (n = 20). Survey data were analyzed descriptively using SPSS, and thematic analysis of the qualitative data was conducted using NVivo 12.0 software. The survey showed a high level of acceptability for the GC phone call (mean satisfaction score overall: 4.3 out of 5, standard deviation (SD): 0.6) with differences according to gender (mean score for women: 4.4, SD: 0.6 vs. men: 4.2, SD: 0.7; p = 0.005), health literacy (lower literacy: 4.1, SD: 0.8; average: 4.3, SD: 0.6; higher: 4.4, SD: 0.6: p = 0.02) and polygenic risk group (low risk: 4.5, SD: 0.5, SD: average: 4.3, SD: 0.7, high: 4.3, SD: 0.7; p = 0.03). During the GC phone calls, the discussion predominately related to the impact of past sun exposure on personal melanoma risk. Together our findings point to the importance of further exploring educational and support needs and preferences for communicating personalized melanoma risk among population subgroups, including diverse literacy levels.

Electrophysiology and the magnetic sense: a guide to best practice.

Magnetoreception, sensing the Earth's magnetic field, is used by many species in orientation and navigation. While this is established on the behavioural level, there is a severe lack in knowledge on the underlying neuronal mechanisms of this sense. A powerful technique to study the neuronal processing of magnetic cues is electrophysiology but, thus far, few studies have adopted this technique. Why is this the case? A fundamental problem is the introduction of electromagnetic noise (induction) caused by the magnetic stimuli, within electrophysiological recordings which, if too large, prevents feasible separation of neuronal signals from the induction artefacts. Here, we address the concerns surrounding the use of electromagnetic coils within electrophysiology experiments and assess whether these would prevent viable electrophysiological recordings within a generated magnetic field. We present calculations of the induced voltages in typical experimental situations and compare them against the neuronal signals measured with different electrophysiological techniques. Finally, we provide guidelines that should help limit and account for possible induction artefacts. In conclusion, if great care is taken, viable electrophysiological recordings from magnetoreceptive cells are achievable and promise to provide new insights on the neuronal basis of the magnetic sense.

Impact of personal genomic risk information on melanoma prevention behaviors and psychological outcomes: a randomized controlled trial.

PURPOSE: We evaluated the impact of personal melanoma genomic risk information on sun-related behaviors and psychological outcomes. METHODS: In this parallel group, open, randomized controlled trial, 1,025 Australians of European ancestry without melanoma and aged 18-69 years were recruited via the Medicare database (3% consent). Participants were randomized to the intervention (n = 513; saliva sample for genetic testing, personalized melanoma risk booklet based on a 40-variant polygenic risk score, telephone-based genetic counseling, educational booklet) or control (n = 512; educational booklet). Wrist-worn ultraviolet (UV) radiation dosimeters (10-day wear) and questionnaires were administered at baseline, 1 month postintervention, and 12 months postbaseline. RESULTS: At 12 months, 948 (92%) participants completed dosimetry and 973 (95%) the questionnaire. For the primary outcome, there was no effect of the genomic risk intervention on objectively measured UV exposure at 12 months, irrespective of traditional risk factors. For secondary outcomes at 12 months, the intervention reduced sunburns (risk ratio: 0.72, 95% confidence interval: 0.54-0.96), and increased skin examinations among women. Melanoma-related worry was reduced. There was no overall impact on general psychological distress. CONCLUSION: Personalized genomic risk information did not influence sun exposure patterns but did improve some skin cancer prevention and early detection behaviors, suggesting it may be useful for precision prevention. There was no evidence of psychological harm.

Physiological Basis of Noise-Induced Hearing Loss in a Tympanal Ear.

Acoustic overexposure, such as listening to loud music too often, results in noise-induced hearing loss. The pathologies of this prevalent sensory disorder begin within the ear at synapses of the primary auditory receptors, their postsynaptic partners and their supporting cells. The extent of noise-induced damage, however, is determined by overstimulation of primary auditory receptors, upstream of where the pathologies manifest. A systematic characterization of the electrophysiological function of the upstream primary auditory receptors is warranted to understand how noise exposure impacts on downstream targets, where the pathologies of hearing loss begin. Here, we used the experimentally-accessible locust ear (male, Schistocerca gregaria) to characterize a decrease in the auditory receptor's ability to respond to sound after noise exposure. Surprisingly, after noise exposure, the electrophysiological properties of the auditory receptors remain unchanged, despite a decrease in the ability to transduce sound. This auditory deficit stems from changes in a specialized receptor lymph that bathes the auditory receptors, revealing striking parallels with the mammalian auditory system.SIGNIFICANCE STATEMENT Noise exposure is the largest preventable cause of hearing loss. It is the auditory receptors that bear the initial brunt of excessive acoustic stimulation, because they must convert excessive sound-induced movements into electrical signals, but remain functional afterward. Here we use the accessible ear of an invertebrate to, for the first time in any animal, characterize changes in auditory receptors after noise overexposure. We find that their decreased ability to transduce sound into electrical signals is, most probably, due to changes in supporting (scolopale) cells that maintain the ionic composition of the ear. An emerging doctrine in hearing research is that vertebrate primary auditory receptors are surprisingly robust, something that we show rings true for invertebrate ears too.

The melanoma genomics managing your risk study: A protocol for a randomized controlled trial evaluating the impact of personal genomic risk information on skin cancer prevention behaviors.

BACKGROUND: Reducing ultraviolet radiation (UV) exposure and improving early detection may reduce melanoma incidence, mortality and health system costs. This study aims to evaluate the efficacy and cost-effectiveness of providing information on personal genomic risk of melanoma in reducing UV exposure at 12 months, according to low and high traditional risk. METHODS: In this randomized controlled trial, participants (target sample = 892) will be recruited from the general population, and randomized (1:1 ratio, intervention versus control). Intervention arm participants provide a saliva sample, receive personalized melanoma genomic risk information, a genetic counselor phone call, and an educational booklet on melanoma prevention. Control arm participants receive only the educational booklet. Eligible participants are aged 18-69 years, have European ancestry and no personal history of melanoma. All participants will complete a questionnaire and wear a UV dosimeter to objectively measure their sun exposure at baseline, 1- and 12-month time-points, except 1-month UV dosimetry will be limited to ~250 participants. The primary outcome is total daily Standard Erythemal Doses at 12 months. Secondary outcomes include objectively measured UV exposure for specific time periods (e.g. midday hours), self-reported sun protection and skin-examination behaviors, psycho-social outcomes, and ethical considerations surrounding offering genomic testing at a population level. A within-trial and modelled economic evaluation will be undertaken from an Australian health system perspective to assess the intervention costs and outcomes. DISCUSSION: This trial will inform the clinical and personal utility of introducing genomic testing into the health system for melanoma prevention and early detection at a population-level. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12617000691347.

Distress, uncertainty, and positive experiences associated with receiving information on personal genomic risk of melanoma.

The aim of this research was to understand how genomics-based personal melanoma risk information impacts psychological and emotional health outcomes in the general population. In a pilot randomized controlled trial, participants (n = 103) completed the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire, 3 months after receiving personal melanoma genomic risk information. Mean scores for MICRA items and subscales were stratified by genomic risk group (low, average, high), gender, education, age, and family history of melanoma. P values were obtained from t-tests and analysis of variance tests. We found that overall, participants (mean age: 53 years, range: 21-69; 52% female) had a total MICRA mean score of 18.6 (standard deviation: 11.1, range: 1-70; possible range: 0-105). The high genomic risk group had higher mean scores for the total (24.2, F2,100 = 6.7, P = 0.0019), distress (3.3, F2,100 = 9.4, P = 0.0002) and uncertainty (8.5, F2,100 = 6.5, P = 0.0021) subscales compared with average (17.6, 1.1, and 4.5, respectively) and low-risk groups (14.1, 0.5, and 2.5, respectively). Positive experiences scores were consistent across risk groups. In conclusion, MICRA scores for the total, distress and uncertainty subscales in our study were relatively low overall, but people who receive a high genomic risk result may benefit from increased support following testing.

Validation of Questionnaire and Diary Measures of Time Outdoors Against an Objective Measure of Personal Ultraviolet Radiation Exposure.

Self-reported sun exposure is commonly measured using questionnaires or diaries, but there are limited data on their validity, particularly for population subgroups. This research aimed to compare self-reported sun exposure, measured as (1) habitual time outdoors over the past month on weekends and weekdays and (2) a 4-day diary measure, against objective measurement of personal ultraviolet radiation using polysulfone film dosimeters. From November 2015 to January 2016, 94 people (22-69 years and living in New South Wales, Australia) completed a questionnaire, 4-day diary and 4-day dosimeter measures of overall, weekday and weekend sun exposure. Spearman correlations and Bland-Altman plots were used to measure agreement. The overall weekly correlation was 0.57 (95% confidence interval [CI] 0.44, 0.68) between standard erythemal doses (SEDs) measured by dosimeter and time spent outdoors measured by questionnaire, 0.74 (95% CI 0.66-0.81) between dosimeter and diary, and 0.59 (95% CI 0.48-0.68) between questionnaire and diary measures. Validity was lower for younger people and weekend sun exposure. There was strong correlation between dosimeter and sun diary measures and moderate correlation between dosimeter and questionnaire measures. Daily measurement over a longer period may be required to accurately capture weeklong sun exposure in all population subgroups.

Development and Evaluation of a Telephone Communication Protocol for the Delivery of Personalized Melanoma Genomic Risk to the General Population.

Communicating personalized genomic risk results for common diseases to the general population as a form of tailored prevention is novel and may require alternative genetic counseling service delivery models. We describe the development and evaluation of a communication protocol for disclosing melanoma genomic risk information to the asymptomatic general population and assess participants' satisfaction and acceptability. Participants (n = 117) were aged 22-69 years, living in New South Wales, Australia and unselected for family history. They provided a saliva sample and had genomic testing for melanoma for low to moderate penetrant melanoma susceptibility variants in 21 genes. Participants could choose to receive their results from a genetic counselor via telephone, followed by a mailed booklet or to receive their risk result via mailed booklet only with a follow-up call for those at high risk. A follow-up questionnaire was completed by 85% of participants 3-months later. Most participants (80%) elected to receive their result via telephone. Participants were highly satisfied with the delivery of results (mean 3.4 out of 4, standard deviation 0.5), and this did not differ by delivery mode, risk category, age or sex. On follow-up, 75% accurately recalled their risk category, 6% indicated a preference for a different delivery mode, either electronic or face-to-face. The process of disclosing genomic risk results to the general population over the telephone with accompanying written material was feasible and acceptable, and may be useful for communicating polygenic risk for common diseases in the context of increasing demands for genomic testing.

A Pilot Randomized Controlled Trial of the Feasibility, Acceptability, and Impact of Giving Information on Personalized Genomic Risk of Melanoma to the Public.

BACKGROUND: Communication of personalized melanoma genomic risk information may improve melanoma prevention behaviors. METHODS: We evaluated the feasibility and acceptability of communicating personalized genomic risk of melanoma to the public and its preliminary impact on behaviors and psychosocial outcomes. One hundred eighteen people aged 22 to 69 years provided a saliva sample and were randomized to the control (nonpersonalized educational materials) or intervention (personalized booklet presenting melanoma genomic risk as absolute and relative risks and a risk category based on variants in 21 genes, telephone-based genetic counseling, and nonpersonalized educational materials). Intention-to-treat analyses overall and by-risk category were conducted using ANCOVA adjusted for baseline values. RESULTS: Consent to participate was 41%, 99% were successfully genotyped, and 92% completed 3-month follow-up. Intervention participants reported high satisfaction with the personalized booklet (mean = 8.6, SD = 1.6; on a 0-10 scale) and genetic counseling (mean = 8.1, SD = 2.2). No significant behavioral effects at 3-month follow-up were identified between intervention and control groups overall: objectively measured standard erythemal doses per day [-16%; 95% confidence interval (CI), -43% to 24%] and sun protection index (0.05; 95% CI, -0.07 to 0.18). There was increased confidence identifying melanoma at 3 months (0.40; 95% CI, 0.10-0.69). Stratified by risk category, effect sizes for intentional tanning and some individual sun protection items appeared stronger for the average-risk group. There were no appreciable group differences in skin cancer-related worry or psychologic distress. CONCLUSIONS: Our results demonstrate feasibility and acceptability of providing personalized genomic risk of melanoma to the public. IMPACT: Genomic risk information has potential as a melanoma prevention strategy. Cancer Epidemiol Biomarkers Prev; 26(2); 212-21. ©2016 AACR.

Sex differences in learned fear expression and extinction involve altered gamma oscillations in medial prefrontal cortex.

Sex differences in learned fear expression and extinction involve the medial prefrontal cortex (mPFC). We recently demonstrated that enhanced learned fear expression during auditory fear extinction and its recall is linked to persistent theta activation in the prelimbic (PL) but not infralimbic (IL) cortex of female rats. Emerging evidence indicates that gamma oscillations in mPFC are also implicated in the expression and extinction of learned fear. Therefore we re-examined our in vivo electrophysiology data and found that females showed persistent PL gamma activation during extinction and a failure of IL gamma activation during extinction recall. Altered prefrontal gamma oscillations thus accompany sex differences in learned fear expression and its extinction. These findings are relevant for understanding the neural basis of post-traumatic stress disorder, which is more prevalent in women and involves impaired extinction and mPFC dysfunction.

Persistent prelimbic cortex activity contributes to enhanced learned fear expression in females.

Anxiety disorders, such as post-traumatic stress, are more prevalent in women and are characterized by impaired inhibition of learned fear and medial prefrontal cortex (mPFC) dysfunction. Here we examined sex differences in fear extinction and mPFC activity in rats. Females showed more learned fear expression during extinction and its recall, but not fear conditioning. They also showed more spontaneous fear recovery and more contextual fear before extinction and its recall. Moreover, enhanced learned fear expression in females was associated with sustained prelimbic (PL) cortex activity. These results suggest that sex differences in learned fear expression may involve persistent PL activation.