Integrative clinical genomics of advanced prostate cancer.

Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, ß-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals.

Genetic variants regulating immune cell levels in health and disease.

The complex network of specialized cells and molecules in the immune system has evolved to defend against pathogens, but inadvertent immune system attacks on "self" result in autoimmune disease. Both genetic regulation of immune cell levels and their relationships with autoimmunity are largely undetermined. Here, we report genetic contributions to quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages. We first estimated trait heritability, showing that it can be substantial, accounting for up to 87% of the variance (mean 41%). Next, by assessing ∼8.2 million variants that we identified and confirmed in an extended set of 2,870 individuals, 23 independent variants at 13 loci associated with at least one trait. Notably, variants at three loci (HLA, IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease associations. These results connect specific cellular phenotypes to specific genetic variants, helping to explicate their involvement in disease.

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

Distinct Benefits Given Large Versus Small Grain Orthographic Instruction for English-Speaking Adults Learning to Read Russian Cyrillic.

Initial instruction emphasizing large grain units (i.e., words) showed distinct advantages over small grain instruction for English-speaking adults learning to read an artificial orthography (Brennan and Booth in Read Writ 28(7):917-938, 2015. https://doi.org/10.1007/s11145-015-9555-2 ). The current study extends this research by training 34 English-speaking adults to read Russian Cyrillic given initial instruction emphasizing either large or small units (words or letters). Results reveal no differences on word learning, but higher accuracy on letter-phoneme matching given letter-based instruction and higher accuracy on rime-rhyme matching given word-based instruction. Differences in phonological awareness (PA) skill showed that higher PA skill resulted in higher accuracy and slower reaction times only for the adults given the instruction with the word emphasis, suggesting that adults with high PA skill given word-based instruction may engage in time intensive small grain analyses (e.g., grapheme-phoneme correspondence) even when their attention is directed to larger grain units. Overall, these results extend previous findings and reveal that word and letter-based instruction each have distinct advantages for facilitating increased sensitivity to either letters/phonemes or rimes/rhymes when adults are learning a natural second (L2) consistent alphabetic orthography.

Breastfeeding Rates and Programs in Europe: A Survey of 11 National Breastfeeding Committees and Representatives.

INTRODUCTION: Among the world's regions, the WHO European Region has the lowest rates of exclusive breastfeeding at the age of 6 months with approximately 25%. Low rates and early cessation of breastfeeding have important adverse health consequences for women, infants, and young children. Protecting, promoting, and supporting breastfeeding are a public health priority. OBJECTIVES: National breastfeeding data and monitoring systems among selected European countries and the WHO European Region are compared. Mechanisms for the support, protection, and promotion of breastfeeding are reviewed and successes and challenges in implementation of national programs are presented. METHODS: National representatives of national breastfeeding committees and initiatives in 11 European countries, including Belgium, Croatia, Denmark, Germany, Ireland, Italy, The Netherlands, Norway, Spain, Sweden, and Switzerland, participated in a standardized survey. Results are evaluated and compared in a narrative review. RESULTS: Variation exists in Europe on breastfeeding rates; methodology for data collection; and mechanisms for support, protection, and promotion of breastfeeding. Directly after birth, between 56% and 98% of infants in all countries were reported to receive any human milk, and at 6 months 38% to 71% and 13% to 39% of infants to be breastfed or exclusively breastfed, respectively. National plans addressing breastfeeding promotion, protection, and support exist in 6 of the 11 countries. CONCLUSIONS: National governments should commit to evidence-based breastfeeding monitoring and promotion activities, including financial and political support, to improve breastfeeding rates in the Europe. Renewed efforts for collaboration between countries in Europe, including a sustainable platform for information exchange, are needed.

The use of exome capture RNA-seq for highly degraded RNA with application to clinical cancer sequencing.

RNA-seq by poly(A) selection is currently the most common protocol for whole transcriptome sequencing as it provides a broad, detailed, and accurate view of the RNA landscape. Unfortunately, the utility of poly(A) libraries is greatly limited when the input RNA is degraded, which is the norm for research tissues and clinical samples, especially when specimens are formalin-fixed. To facilitate the use of RNA sequencing beyond cell lines and in the clinical setting, we developed an exome-capture transcriptome protocol with greatly improved performance on degraded RNA. Capture transcriptome libraries enable measuring absolute and differential gene expression, calling genetic variants, and detecting gene fusions. Through validation against gold-standard poly(A) and Ribo-Zero libraries from intact RNA, we show that capture RNA-seq provides accurate and unbiased estimates of RNA abundance, uniform transcript coverage, and broad dynamic range. Unlike poly(A) selection and Ribo-Zero depletion, capture libraries retain these qualities regardless of RNA quality and provide excellent data from clinical specimens including formalin-fixed paraffin-embedded (FFPE) blocks. Systematic improvements across key applications of RNA-seq are shown on a cohort of prostate cancer patients and a set of clinical FFPE samples. Further, we demonstrate the utility of capture RNA-seq libraries in a patient with a highly malignant solitary fibrous tumor (SFT) enrolled in our clinical sequencing program called MI-ONCOSEQ. Capture transcriptome profiling from FFPE revealed two oncogenic fusions: the pathognomonic NAB2-STAT6 inversion and a therapeutically actionable BRAF fusion, which may drive this specific cancer's aggressive phenotype.

Characterizing reduced coverage regions through comparison of exome and genome sequencing data across 10 centers.

PURPOSE: As massively parallel sequencing is increasingly being used for clinical decision making, it has become critical to understand parameters that affect sequencing quality and to establish methods for measuring and reporting clinical sequencing standards. In this report, we propose a definition for reduced coverage regions and describe a set of standards for variant calling in clinical sequencing applications. METHODS: To enable sequencing centers to assess the regions of poor sequencing quality in their own data, we optimized and used a tool (ExCID) to identify reduced coverage loci within genes or regions of particular interest. We used this framework to examine sequencing data from 500 patients generated in 10 projects at sequencing centers in the National Human Genome Research Institute/National Cancer Institute Clinical Sequencing Exploratory Research Consortium. RESULTS: This approach identified reduced coverage regions in clinically relevant genes, including known clinically relevant loci that were uniquely missed at individual centers, in multiple centers, and in all centers. CONCLUSION: This report provides a process road map for clinical sequencing centers looking to perform similar analyses on their data.

Modelling attrition and nonparticipation in a longitudinal study of prostate cancer.

BACKGROUND: Attrition occurs when a participant fails to respond to one or more study waves. The accumulation of attrition over several waves can lower the sample size and power and create a final sample that could differ in characteristics than those who drop out. The main reason to conduct a longitudinal study is to analyze repeated measures; research subjects who drop out cannot be replaced easily. Our group recently investigated factors affecting nonparticipation (refusal) in the first wave of a population-based study of prostate cancer. In this study we assess factors affecting attrition in the second wave of the same study. We compare factors affecting nonparticipation in the second wave to the ones affecting nonparticipation in the first wave. METHODS: Information available on participants in the first wave was used to model attrition. Different sources of attrition were investigated separately. The overall and race-stratified factors affecting attrition were assessed. Kaplan-Meier survival curve estimates were calculated to assess the impact of follow-up time on participation. RESULTS: High cancer aggressiveness was the main predictor of attrition due to death or frailty. Higher Charlson Comorbidity Index increased the odds of attrition due to death or frailty only in African Americans (AAs). Young age at diagnosis for AAs and low income for European Americans (EAs) were predictors for attrition due to lost to follow-up. High cancer aggressiveness for AAs, low income for EAs, and lower patient provider communication scores for EAs were predictors for attrition due to refusal. These predictors of nonparticipation were not the same as those in wave 1. For short follow-up time, the participation probability of EAs was higher than that of AAs. CONCLUSIONS: Predictors of attrition can vary depending on the attrition source. Examining overall attrition (combining all sources of attrition under one category) instead of distinguishing among its different sources should be avoided. The factors affecting attrition in one wave can be different in a later wave and should be studied separately.

Non-Dipping and Cardiometabolic Profile: A Study on Normotensive Overweight Middle-Aged Men.

BACKGROUND: We aimed to assess insulin sensitivity and other metabolic features of dippers and non-dippers among overweight middle-aged men. METHODS: We studied 73 men (45.8 ± 5.3 years) who were overweight but normotensive. Participants were separated into dippers and non-dippers based on the magnitude of the nocturnal decline of blood pressure, with dippers experiencing an overnight decline ≥10% as per standard definition. Our study included 51 dippers and 22 non-dippers. All participants underwent 24-hour ambulatory blood pressure monitoring. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test; other assessments included carotid artery intima-media thickness (CIMT), body composition derived from dual-energy X-ray absorptiometry, lipid profiles, and a physical activity questionnaire. RESULTS: Non-dippers had lower daytime systolic (-5.0mmHg; p=0.022) and diastolic (-3.3mmHg; p=0.035) blood pressure than dippers. Conversely, during sleep, non-dippers had higher systolic (+6.5mmHg; p=0.003) and diastolic (+5.6mmHg; p=0.001) blood pressure. In continuous associations, increasing CIMT was associated with decreasing systolic (p=0.012) and diastolic (p=0.042) dipping. Thus, non-dippers had CIMT that was 9% greater than that of dippers (749 vs 820µm; p=0.036). Importantly, there was no association between non-dipping status or the magnitude of the nocturnal dip with insulin sensitivity. CONCLUSIONS: Non-dippers had lower blood pressure in the daytime, but higher blood pressure in the night time compared to dippers. Non-dippers had increased CIMT, which suggests that normotensive men with a non-dipping ambulatory blood pressure profile may be at increased cardiovascular risk. However, it appears that the non-dipping profile is unrelated to dysfunction of glucose homeostasis in overweight normotensive men.

The brain adapts to orthography with experience: evidence from English and Chinese.

Using functional magnetic resonance imaging (fMRI), we examined the process of language specialization in the brain by comparing developmental changes in two contrastive orthographies: Chinese and English. In a visual word rhyming judgment task, we found a significant interaction between age and language in left inferior parietal lobule and left superior temporal gyrus, which was due to greater developmental increases in English than in Chinese. Moreover, we found that higher skill only in English children was correlated with greater activation in left inferior parietal lobule. These findings suggest that the regions associated with phonological processing are essential in English reading development. We also found greater developmental increases in English than in Chinese in left inferior temporal gyrus, suggesting refinement of this region for fine-grained word form recognition. In contrast, greater developmental increases in Chinese than in English were found in right middle occipital gyrus, suggesting the importance of holistic visual-orthographic analysis in Chinese reading acquisition. Our results suggest that the brain adapts to the special features of the orthography by engaging relevant brain regions to a greater degree over development.

Increasing parental age at childbirth is associated with greater insulin sensitivity and more favorable metabolic profile in overweight adult male offspring.

OBJECTIVE: To assess the effect of parental age at childbirth on insulin sensitivity and other metabolic outcomes in overweight middle-aged males. METHODS: We studied 73 men aged 46.0±5.4 years, who were overweight (body mass index, BMI 25-30 kg/m(2) ) but otherwise healthy. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test. Other assessments included dual-energy X-ray absorptiometry-derived body composition, lipid profile, 24-hour ambulatory blood pressure, and carotid intima-media thickness. Maternal and paternal ages were highly correlated (r = 0.71; P < 0.0001), and the main parameter of interest in this study was the mean parental age at childbirth (MPAC), calculated as the average of maternal and paternal ages. RESULTS: Increasing MPAC was associated with a continuous increase in insulin sensitivity (ß = 0.193; P = 0.008), as well as reductions in insulin resistance (HOMA-IR; ß = -0.064; P = 0.011), fasting insulin (ß = -0.221; P = 0.018) and fasting glucose (ß = -0.030; P = 0.033) concentrations. Increasing MPAC was also associated with reductions in night time systolic (ß = -0.500; P = 0.020) and diastolic (ß = -0.325; P = 0.047) blood pressure, as well as with improved (greater) nocturnal diastolic blood pressure dipping (ß = 0.413; P = 0.046). Subgroup analyses on participants of European descent (n = 64) showed that increasing MPAC was associated with reduced carotid intima-media thickness (ß = -0.008; P = 0.018) and lower low-density lipoprotein cholesterol concentrations (ß = -0.042; P = 0.028). CONCLUSIONS: Increasing parental age at childbirth was associated with a more favorable metabolic phenotype in overweight middle-aged males. However, it is unknown whether the effect was maternal, paternal, or both. Future studies on the effects of parental age at childbirth on the metabolism of males and females across the BMI range are required.

Metabolomic profiling identifies biochemical pathways associated with castration-resistant prostate cancer.

Despite recent developments in treatment strategies, castration-resistant prostate cancer (CRPC) is still the second leading cause of cancer-associated mortality among American men, the biological underpinnings of which are not well understood. To this end, we measured levels of 150 metabolites and examined the rate of utilization of 184 metabolites in metastatic androgen-dependent prostate cancer (AD) and CRPC cell lines using a combination of targeted mass spectrometry and metabolic phenotyping. Metabolic data were used to derive biochemical pathways that were enriched in CRPC, using Oncomine concept maps (OCM). The enriched pathways were then examined in-silico for their association with treatment failure (i.e., prostate specific antigen (PSA) recurrence or biochemical recurrence) using published clinically annotated gene expression data sets. Our results indicate that a total of 19 metabolites were altered in CRPC compared to AD cell lines. These altered metabolites mapped to a highly interconnected network of biochemical pathways that describe UDP glucuronosyltransferase (UGT) activity. We observed an association with time to treatment failure in an analysis employing genes restricted to this pathway in three independent gene expression data sets. In summary, our studies highlight the value of employing metabolomic strategies in cell lines to derive potentially clinically useful predictive tools.

Overlapping hearing and communication profiles for the deletion and the RAI1 variant form of Smith-Magenis Syndrome (SMS).

Smith-Magenis syndrome (SMS), a rare, genetically linked complex developmental disorder is associated with hearing loss and delays in speech-language development. Approximately 70 % of those with SMS have a genetic deletion within chromosome 17p11.2 and 10 % have a single gene mutation in the same area, known as the RAI1 variant form of SMS. Previous studies presented preliminary comparisons of the phenotype of those with deletion versus the mutation form of SMS, but none focused on hearing, speech-language, and communication profiles. The current study examined patient registry data and compared two groups of individuals with SMS to determine if genetic differences influence the communication phenotype and to determine the importance of the RAI1 gene in hearing, speech, and language abilities in children. Speech-language and hearing data from the international SMS Patient Registry for 33 subjects with SMS were analyzed: 23 with a genetic deletion (SMS (del)) and 10 with an RAI1 mutation (SMS (RAI1)). Hearing status, otopathology findings, early speech-language milestones, mode of communication, intelligibility, vocal quality, language abilities, and literacy skills were analyzed. There were small differences between the groups for hearing status, otopathological findings, mode of communication, voice quality, intelligibility, speech-language abilities, and literacy. Overlap in the speech-language phenotype between groups confirms previous hypotheses that suggest haploinsufficiency of the RAI1 gene is responsible for the SMS phenotype and that the RAI1 gene is critical for speech-language development. Future studies should include direct testing of receptive and expressive language abilities, including analyses of language samples, with larger groups of individuals to replicate and extend the current findings.

Successful use of an eye gaze AAC communication board by a young adult with advanced Sanfilippo Syndrome (MPS IIIA): Case report.

Sanfilippo syndrome (Mucopolysaccharidosis Type III or MPS III) is a family of rare, lysosomal disorders characterized by progressive cognitive and motor deterioration. Even though individuals with MPS III present with complex communication needs, research regarding augmentative and alternative communication (AAC) in this population is scarce. While life expectancy for individuals with MPS IIIA typically does not exceed 20 years of age, this case report involves a 22-year-old adult with postregression MPS IIIA. Prior to this study, the participant could not communicate using speech and only responded to yes/no questions using eye blink responses. The participant was given a low-tech AAC system utilizing eye gaze so that she could respond to a variety of caregiver questions and take conversational turns. The following communication outcomes were measured during each session in which caregivers used the AAC system: number of eye gaze responses, total number of responses (using any means), the percent of responses to questions asked, and the total count of expressive vocabulary words available to the participant with the AAC system. Increases were observed in the number of eye gaze responses per session and in the expressive vocabulary accessible via the eye gaze board. A higher percentage of responses given caregiver questions was noted for the intervention sessions (71%) compared to the baseline sessions (55%). There were also qualitative changes characterized by the types of questions the participant could respond to during conversational exchanges. Despite the progression of MPS IIIA, the results suggest that use of the eye gaze board resulted in quantitative and qualitative changes in functional communication. This case report provides preliminary evidence that AAC can improve communication in a young adult with postregression MPS IIIA.

Successful use of an eye gaze AAC communication board by a young adult with advanced Sanfilippo Syndrome (MPS IIIA): Case Report This article reports a case of a 22-year-old woman who was diagnosed with mucopolysaccharidosis type III (MPS III) or Sanfilippo Syndrome. MPS III is a rare lysosomal disorder characterized by progressive cognitive and motor deterioration. Children with MPS III experience regression in speech and communication skills and speech is typically lost by age eight years. AAC (Augmentative and Alternative Communication) are systems or devices that can be used by individuals with limited to no speech to aid or supplement communication. Even though individuals with MPS III have significant impairment in communication and could potentially benefit from AAC, research regarding the use of AAC (Augmentative and Alternative Communication) by this population is scarce. In this case, an eye-gaze AAC system was introduced to a young adult with postregression MPS IIIA who is well beyond average life expectancy for this disease. Despite the progression of MPS IIIA and complicating medical issues, there were quantitative and qualitative changes and improvement in this woman's functional communication after the eye gaze board was introduced. This case study provides preliminary evidence that AAC use can potentially improve communication in individuals with postregression MPS IIIA.

Hearing loss and psychosocial outcomes: Influences of social emotional aspects and personality.

The aim of this study was to examine the effects of social isolation, loneliness, anxiety, depression, higher stress, and memory complaints interacting with personality traits as a function of hearing loss. Personality traits have previously been shown to correlate with anxiety and depression, as well as hearing loss, suggesting an effect of personality on the relationship between social emotional outcomes and hearing loss. A cross-sectional survey including validated screening measures was anonymously administered. Measures included personality (Big Five Index-2 Extra-Short Form), stress (Perceived Stress Scale), anxiety and depression (Patient Health Questionnaire for Depression and Anxiety), loneliness (Three-Item Loneliness Scale), social engagement (Lubben Social Network Scale-6), and self-perceived memory complaints (Subjective Cognitive Function). Eight hundred and ninety-one responses were obtained from adults between the ages of 18 and 90 years old (M = 50 years old). Hearing loss was positively correlated with subjective memory complaints only when not accounting for demographic variables, personality traits, psychosocial outcomes, and social emotional outcomes. There were additive effects of hearing loss and negative emotionality on increases in memory complaints in those who self-identified as maybe having hearing loss. Higher degrees of hearing loss also increased loneliness, with greater hearing loss negating the positive correlation between extraversion and social engagement. Overall, our results suggest that hearing loss significantly interacts with personality traits and other social emotional measures. Our results suggest that the impact of hearing loss on memory complaints, social isolation, and loneliness may differ across patients with hearing loss in comparison with those who think they maybe have hearing loss. Information from this study may provide insights for hearing healthcare and mental healthcare professionals to better serve persons with hearing loss who may require additional support or interventions.

Speech, Language, Hearing, and Otopathology Results From the International Smith-Magenis Syndrome Patient Registry.

PURPOSE: Smith-Magenis syndrome (SMS), a rare, genetically linked complex developmental disorder caused by a deletion or mutation within chromosome 17p11.2, is associated with delays in speech-language development, otopathology, and hearing loss, yet previous studies lack comprehensive descriptions of hearing and communication profiles. Here, analyses of patient registry data expand what is known about speech, language, hearing, and otopathology in SMS. METHOD: International speech-language and hearing registry survey data for 82 individuals with SMS were analyzed using descriptive and inferential statistics. Hearing loss, history of otitis media and pressure equalization (PE) tubes, communication mode, expressive/receptive language, and vocal quality were analyzed for all subjects and subjects grouped by age. Statistical methods included descriptive statistics and Pearson's chi-square tests of independence to test for differences between age groups for each variable of interest. Association analyses included Pearson's correlations. RESULTS: Hearing and otological analyses revealed that 35% of subjects had hearing loss, 66% had a history of otitis media, and 62% had received PE tubes. Speech-language analyses revealed that 60% of subjects communicated using speech, 79% began speaking words at/after 24 months of age, 92% combined words at/after 36 months, and 41% used sign language before speech. There was a significant association between the age that first words were spoken and the age that PE tubes were first placed. Communication strengths noted in more than 40% of subjects included social interest, humor, and memory for people, past events, and/or facts. CONCLUSIONS: Significant delays and impairment in speech-language were common, but the majority of those with SMS communicated using speech by age 6 years. Age was a significant factor for some aspects of hearing loss and communication. Neither hearing loss nor otitis media exacerbated language impairment. These results confirm and extend previous findings about the nature of speech, language, hearing, and otopathology in those with SMS.

Person-centered aural rehabilitation program improved mood, cognition, and auditory processing in a professional musician who uses a hearing aid and cochlear implant: Case Report.

Introduction: Aural rehabilitation focused on music for individuals with cochlear implants (CIs) and/or hearing aids (HAs) typically emphasizes perceptual skills rather than enjoyment of music. Yet, those with CIs and/or HAs often struggle to enjoy music, complaining that it sounds distorted with the implant or HAs. Typically, aural rehabilitation programs require a significant time commitment, but this may not be feasible or preferable for many patients. This study aimed to evaluate the efficacy of two individualized intensive 3-week home practice programs focused on enjoyment of music, a personal goal for this subject. Methods: The subject was a professional musician who used a CI and HA. Cognitive measures of global cognitive function, executive function, processing speed, auditory working memory, visual-spatial abilities, verbal fluency, and auditory-verbal memory, as well as auditory electrophysiology (EEG) measures were conducted pre-post experiment 2. Two experiments were undertaken to evaluate responses to two practice programs that incorporated different variations in listening dosage and intervention activities. Results: Experiment 1 resulted in minimal measurable improvements related to music likability ratings, with the highest dosage condition showing a small increase in average likability rating from baseline to week 3. The results of experiment 2 revealed an improvement in likability ratings only when dosage steadily increased each week. The subject also reported improved mood and decreased frustration during weeks two and three of experiment 2. Finally, we found improvement pre-post experiment 2 on several cognitive and EEG measures. Discussion: The results of these experiments are encouraging and support the use of an individualized, person-centered, and semi-structured home practice program to increase music enjoyment and improve quality of life and auditory processing for individuals with hearing loss. Future studies should aim to increase sample size and explore pairing person-centered home practice programs with concurrent clinician-lead aural rehabilitation.

Reading acquisition reorganizes the phonological awareness network only in alphabetic writing systems.

It is unknown how experience with different types of orthographies influences the neural basis of oral language processing. In order to determine the effects of alphabetic and nonalphabetic writing systems, the current study examined the influence of learning to read on oral language in English and Chinese speakers. Children (8-12 years olds) and adults made rhyming judgments to pairs of spoken words during functional magnetic resonance imaging (fMRI). Developmental increases were seen only for English speakers in the left hemisphere phonological network (superior temporal gyrus (STG), inferior parietal lobule, and inferior frontal gyrus). The increase in the STG was more pronounced for words with conflicting orthography (e.g. pint-mint; jazz-has) even though access to orthography was irrelevant to the task. Moreover, higher reading skill was correlated with greater activation in the STG only for English speaking children. The effects suggest that learning to read reorganizes the phonological awareness network only for alphabetic and not logographic writing systems because of differences in the principles for mapping between orthographic and phonological representations. The reorganization of the auditory cortex may result in better phonological awareness skills in alphabetic readers.

How does health literacy affect quality of life among men with newly diagnosed clinically localized prostate cancer? Findings from the North Carolina-Louisiana Prostate Cancer Project (PCaP).

BACKGROUND: Health literacy deficits affect half of the US overall patient population, especially the elderly, and are linked to poor health outcomes among noncancer patients. Yet little is known about how health literacy affects cancer populations. The authors examined the relation between health-related quality of life (HRQOL) and health literacy among men with prostate cancer. METHODS: Data analysis included 1581 men with newly diagnosed clinically localized prostate cancer from a population-based study, the North Carolina-Louisiana Prostate Cancer Project (PCaP). Participants completed assessment of health literacy using Rapid Estimate of Adult Literacy in Medicine (REALM) and HRQOL using the Short Form-12 General Health Survey (SF12). Bivariate and multivariate regression was used to determine the potential association between REALM and HRQOL, while controlling for sociodemographic and illness-related variables. RESULTS: Higher health literacy level was significantly associated with better mental well-being (SF12-Mental Component Summary [MCS]; P < .001) and physical well-being (SF12-Physical Component Summary [PCS]; P < .001) in bivariate analyses. After controlling for sociodemographic (age, marital status, race, income, and education) and illness-related factors (types of cancer treatment, tumor aggressiveness, and comorbidities), health literacy remained significantly associated with SF12-MCS scores (P < .05) but not with SF12-PCS scores. CONCLUSIONS: Among patients with newly diagnosed localized prostate cancer, those with low health literacy levels were more vulnerable to mental distress than those with higher health literacy levels, but physical well-being was no different. These findings suggest that health literacy may be important in patients managing prostate cancer and the effects of treatment, and provide the hypothesis that supportive interventions targeting patients with lower health literacy may improve their HRQOL.