A Naturalistic Study of the Associations between Changes in Alcohol Problems, Spiritual Functioning and Psychiatric Symptoms

The study evaluated how spiritual and religious functioning (SRF), alcohol-related problems, and psychiatric symptoms change over the course of treatment and follow-up. Problem drinkers (n = 55, including 39 males and 16 females) in outpatient treatment were administered questionnaires at pretreatment, posttreatment, and follow up, which assessed two aspects of SRF (religious well-being and existential well-being), two aspects of alcohol misuse (severity and consequences), and two aspects of psychiatric symptoms (depression and anxiety). Significant improvements in SRF, psychiatric symptoms and alcohol misuse were observed from pretreatment to follow-up. Although SRF scores were significantly correlated with psychiatric symptoms at all three time points, improvement in the former did not predict improvement in the latter. When measured at the same time points, SRF scores were not correlated with the measures of alcohol misuse. However, improvement in SRF (specifically in existential well-being) over the course of treatment was predictive of improvement in the alcohol misuse measures at follow-up. These results suggest that the association between SRF, emotional problems, and alcohol misuse is complex. They further suggest that patients who improve spiritual functioning over the course of treatment are more likely to experience improvement in drinking behavior and alcohol-related problems after treatment has ended. (PsycINFO Database Record (c) 2011 APA, all rights reserved

Equal Protection, Class Legislation, and Colorblindness

Scholars and judges have long assumed that the Equal Protection Clause is concerned only with state action that has the effect of singling out certain persons or groups of persons for special benefits or burdens. Under the traditional doctrinal framework, state action that has this purpose and effect bears a certain burden of justification under the clause, a burden whose stringency varies, depending on the criteria used to define the class being singled out for special treatment and the importance of the interest affected. But state action that lacks such a discriminatory effect is not, on the traditional understanding, subject to equal protection challenge at all; if its rationality is to be challenged, it must be under the Due Process Clause instead. Over the years, the United States Supreme Court has often had difficulty deciding whether certain kinds of state action actually single out certain persons or groups of persons for special benefits or burdens. But all of its great equal protection battles - over racial segregation, state legislative reapportionment, gender discrimination, and affirmative action - have been fought on the assumption that such a discriminatory effect is a necessary element of an equal protection claim. On this fundamental aspect of its equal protection jurisprudence, the Court has long displayed remarkable unanimity - that is, until the racial gerrymandering cases of the last few years

Psychology Doctoral Students’ Perspectives on Addressing Spirituality and Religion with Clients: Associations with Personal Preferences and Training

Students (n = 543) in doctoral clinical and counseling psychology programs were surveyed about training experiences with regard to addressing the spiritual and religious beliefs and practices (SRBP) of their patients. About one fourth of the respondents indicated they had received no training related to patients’ SRBP. Another half had only read material on their own or discussed such issues with a supervisor. Nonetheless, respondents almost universally endorsed the idea that patients should be asked about spirituality and religiousness. Participants also rated the appropriateness of spiritual and religious queries that might be asked of patients. As expected, queries about the relevance of SRBP were rated as the most appropriate, whereas queries that implied a disrespectful or challenging tone were rated as the least appropriate. Participants’ personal SRBP and training that was specific to patients’ SRBP were weakly but significantly associated with appropriateness ratings. The results suggest that students are formulating ideas about how to ask patients about their spiritual and religious issues despite potentially inadequate formal instruction

A protocol for whole-exome sequencing in newborns with congenital deafness: a prospective population-based cohort

Introduction: The aetiology of congenital hearing loss is heterogeneous, and in many infants a genetic cause is suspected. Parents face a diagnostic odyssey when searching for a cause of their infant’s hearing loss. Through the Melbourne Genomics Health Alliance, a prospective cohort of infants will be offered whole-exome sequencing (WES) with targeted analysis in conjunction with chromosome microarray to determine the genetic causes of congenital hearing loss. Parents will also be offered the opportunity to receive additional results from their infant’s WES. Methods: Eligible infants will be identified through the Victorian Infant Hearing Screening Program and offered an appointment in a paediatrician-run clinic, a genetics assessment and enrolment in the Victorian Childhood Hearing Impairment Longitudinal Databank. If parents consent to WES, genes causing deafness will be analysed and they can choose to obtain additional findings. For the additional results component, a modified laboratory protocol has been designed for reporting of results in the absence of a relevant phenotype. Parents’ experience of being offered WES will be evaluated using surveys. Discussion This project will provide descriptive analysis of the genetic aetiology of congenital hearing loss in this cohort and may provide data on genotype–phenotype correlations. Additionally, choices regarding additional findings will be analysed. Participants will represent a diverse cross section of the population, increasing the ability to generalise results beyond the study group. Evaluation surveys will allow analysis of preferences around counselling, usefulness of a decision aid and adequacy of information provision

A panel of genes methylated with high frequency in colorectal cancer

Background: The development of colorectal cancer (CRC) is accompanied by extensive epigenetic changes, including frequent regional hypermethylation particularly of gene promoter regions. Specific genes, including SEPT9, VIM1 and TMEFF2 become methylated in a high fraction of cancers and diagnostic assays for detection of cancer-derived methylated DNA sequences in blood and/or fecal samples are being developed. There is considerable potential for the development of new DNA methylation biomarkers or panels to improve the sensitivity and specificity of current cancer detection tests. Methods: Combined epigenomic methods - activation of gene expression in CRC cell lines following DNA demethylating treatment, and two novel methods of genome-wide methylation assessment - were used to identify candidate genes methylated in a high fraction of CRCs. Multiplexed amplicon sequencing of PCR products from bisulfite-treated DNA of matched CRC and non-neoplastic tissue as well as healthy donor peripheral blood was performed using Roche 454 sequencing. Levels of DNA methylation in colorectal tissues and blood were determined by quantitative methylation specific PCR (qMSP). Results: Combined analyses identified 42 candidate genes for evaluation as DNA methylation biomarkers. DNA methylation profiles of 24 of these genes were characterised by multiplexed bisulfite-sequencing in ten matched tumor/normal tissue samples; differential methylation in CRC was confirmed for 23 of these genes. qMSP assays were developed for 32 genes, including 15 of the sequenced genes, and used to quantify methylation in tumor, adenoma and non-neoplastic colorectal tissue and from healthy donor peripheral blood. 24 of the 32 genes were methylated in \u3e50% of neoplastic samples, including 11 genes that were methylated in 80% or more CRCs and a similar fraction of adenomas. Conclusions: This study has characterised a panel of 23 genes that show elevated DNA methylation in \u3e50% of CRC tissue relative to non-neoplastic tissue. Six of these genes (SOX21, SLC6A15, NPY, GRASP, ST8SIA1 and ZSCAN18) show very low methylation in non-neoplastic colorectal tissue and are candidate biomarkers for stool-based assays, while 11 genes (BCAT1, COL4A2, DLX5, FGF5, FOXF1, FOXI2, GRASP, IKZF1, IRF4, SDC2 and SOX21) have very low methylation in peripheral blood DNA and are suitable for further evaluation as blood-based diagnostic markers

Preclinical data do not support the use of amiodarone or dronedarone as antiparasitic drugs for Chagas disease at the approved human dosing regimen

The repurposing of approved drugs is an appealing method to fast-track the development of novel therapies for neglected diseases. Amiodarone and dronedarone, two approved antiarrhythmic agents, have been reported to have potential for the management of Chagas disease patients displaying symptomatic heart pathology. More recently, it has been suggested that both molecules not only have an antiarrhythmic effect, but also have trypanocidal activity against Trypanosoma cruzi, the causative agent of Chagas disease. In this work, we assessed the in vitro activity of these compounds against T. cruzi, the in vivo pharmacokinetics, and pharmacodynamics, to determine the potential for repurposing these drugs as therapies for Chagas disease. Based on these results, we were unable to reproduce the in vitro potencies of amiodarone and dronedarone described in the literature, and both drugs were found to be inactive or cytotoxic against a variety of different mammalian cell lines. The evaluation of in vivo efficacy in a bioluminescent murine model of T. cruzi did not show antiparasitic activity at the highest tolerated dose tested. While the potential of amiodarone and dronedarone as antiarrhythmic agents in Chagas cardiomyopathic patients cannot be completely excluded, a trypanocidal effect in patients treated with these two drugs appears unlikely

Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. RESULTS: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). CONCLUSIONS: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. IMPACT: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.D F. Easton was recipient of the CR-UK grant C1287/A10118. R A. Eeles was recipient of the CR-UK grant C5047/A10692 and B E. Henderson was recipient of the NIH grant 1U19CA148537-01This is the author accepted manuscript. The final version is available via AACR at http://cebp.aacrjournals.org/content/early/2015/04/02/1055-9965.EPI-14-0317.long