Second to fourth digit ratio (2D:4D) and concentrations of circulating sex hormones in adulthood

BACKGROUND: The second to fourth digit ratio (2D:4D) is used as a marker of prenatal sex hormone exposure. The objective of this study was to examine whether circulating concentrations of sex hormones and SHBG measured in adulthood was associated with 2D:4D. METHODS: This analysis was based on a random sample from the Melbourne Collaborative Cohort Study. The sample consisted of of 1036 men and 620 post-menopausal women aged between 39 and 70 at the time of blood draw. Concentrations of circulating sex hormones were measured from plasma collected at baseline (1990-1994), while digit length was measured from hand photocopies taken during a recent follow-up (2003-2009). The outcome measures were circulating concentrations of testosterone, oestradiol, dehydroepiandrosterone sulphate, androstenedione, Sex Hormone Binding Globulin, androstenediol glucoronide for men only and oestrone sulphate for women only. Free testosterone and oestradiol were estimated using standard formulae derived empirically. Predicted geometric mean hormone concentrations (for tertiles of 2D:4D) and conditional correlation coefficients (for continuous 2D:4D) were obtained using mixed effects linear regression models. RESULTS: No strong associations were observed between 2D:4D measures and circulating concentrations of hormones for men or women. For males, right 2D:4D was weakly inversely associated with circulating testosterone (predicted geometric mean testosterone was 15.9 and 15.0 nmol/L for the lowest and highest tertiles of male right 2D:4D respectively (P-trend = 0.04). There was a similar weak association between male right 2D:4D and the ratio of testosterone to oestradiol. These associations were not evident in analyses of continuous 2D:4D. CONCLUSIONS: There were no strong associations between any adult circulating concentration of sex hormone or SHGB and 2D:4D. These results contribute to the growing body of evidence indicating that 2D:4D is unrelated to adult sex hormone concentrations

A three-protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease

Only a minority of prostate cancers lead to death. Because no tissue biomarkers of aggressiveness other than Gleason score are available at diagnosis, many nonlethal cancers are treated aggressively. We evaluated whether a panel of biomarkers, associated with a range of disease outcomes in previous studies, could predict death from prostate cancer for men with localized disease. Using a case-only design, subjects were identified from three Australian epidemiological studies. Men who had died of their disease, cases (N = 83), were matched to referents (N = 232), those who had not died of prostate cancer, using incidence density sampling. Diagnostic tissue was retrieved to assess expression of AZGP1, MUC1, NKX3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC). Poisson regression was used to estimate mortality rate ratios (MRRs) adjusted for age, Gleason score, and stage and to estimate survival probabilities. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51, 95% CI 1.14-5.54, P = 0.02 and 3.08, 95% CI 1.41-6.95, P = 0.005, respectively), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, 95% CI 0.20-0.96, P = 0.04). Analyzing all markers under a combined model indicated that the three markers were independent predictors of prostate cancer death and survival. For men with localized disease at diagnosis, assessment of AZGP1, MUC1, and p53 expression in diagnostic tissue by IHC could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)

The future of medical diagnostics: Review paper

While histopathology of excised tissue remains the gold standard for diagnosis, several new, non-invasive diagnostic techniques are being developed. They rely on physical and biochemical changes that precede and mirror malignant change within tissue. The basic principle involves simple optical techniques of tissue interrogation. Their accuracy, expressed as sensitivity and specificity, are reported in a number of studies suggests that they have a potential for cost effective, real-time, in situ diagnosis. We review the Third Scientific Meeting of the Head and Neck Optical Diagnostics Society held in Congress Innsbruck, Innsbruck, Austria on the 11th May 2011. For the first time the HNODS Annual Scientific Meeting was held in association with the International Photodynamic Association (IPA) and the European Platform for Photodynamic Medicine (EPPM). The aim was to enhance the interdisciplinary aspects of optical diagnostics and other photodynamic applications. The meeting included 2 sections: oral communication sessions running in parallel to the IPA programme and poster presentation sessions combined with the IPA and EPPM posters sessions. © 2011 Jerjes et al; licensee BioMed Central Ltd

Wikipedia Information Flow Analysis Reveals the Scale-Free Architecture of the Semantic Space

In this paper we extract the topology of the semantic space in its encyclopedic acception, measuring the semantic flow between the different entries of the largest modern encyclopedia, Wikipedia, and thus creating a directed complex network of semantic flows. Notably at the percolation threshold the semantic space is characterised by scale-free behaviour at different levels of complexity and this relates the semantic space to a wide range of biological, social and linguistics phenomena. In particular we find that the cluster size distribution, representing the size of different semantic areas, is scale-free. Moreover the topology of the resulting semantic space is scale-free in the connectivity distribution and displays small-world properties. However its statistical properties do not allow a classical interpretation via a generative model based on a simple multiplicative process. After giving a detailed description and interpretation of the topological properties of the semantic space, we introduce a stochastic model of content-based network, based on a copy and mutation algorithm and on the Heaps' law, that is able to capture the main statistical properties of the analysed semantic space, including the Zipf's law for the word frequency distribution

Regulation of proteasome assembly and activity in health and disease

The proteasome degrades most cellular proteins in a controlled and tightly regulated manner and thereby controls many processes, including cell cycle, transcription, signalling, trafficking and protein quality control. Proteasomal degradation is vital in all cells and organisms, and dysfunction or failure of proteasomal degradation is associated with diverse human diseases, including cancer and neurodegeneration. Target selection is an important and well-established way to control protein degradation. In addition, mounting evidence indicates that cells adjust proteasome-mediated degradation to their needs by regulating proteasome abundance through the coordinated expression of proteasome subunits and assembly chaperones. Central to the regulation of proteasome assembly is TOR complex 1 (TORC1), which is the master regulator of cell growth and stress. This Review discusses how proteasome assembly and the regulation of proteasomal degradation are integrated with cellular physiology, including the interplay between the proteasome and autophagy pathways. Understanding these mechanisms has potential implications for disease therapy, as the misregulation of proteasome function contributes to human diseases such as cancer and neurodegeneration.</p

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Teaching appropriate interactions with pharmaceutical company representatives: The impact of an innovative workshop on student attitudes

BACKGROUND: Pharmaceutical company representatives (PCRs) influence the prescribing habits and professional behaviour of physicians. However, the skills for interacting with PCRs are not taught in the traditional medical school curriculum. We examined whether an innovative, mandatory workshop for third year medical students had immediate effects on knowledge and attitudes regarding interactions with PCRs. METHODS: Surveys issued before and after the workshop intervention solicited opinions (five point Likert scales) from third year students (n = 75) about the degree of bias in PCR information, the influence of PCRs on prescribing habits, the acceptability of specific gifts, and the educational value of PCR information for both practicing physicians and students. Two faculty members and one PCR led the workshop, which highlighted typical physician-PCR interactions, the use of samples and gifts, the validity and legal boundaries of PCR information, and associated ethical issues. Role plays with the PCR demonstrated appropriate and inappropriate strategies for interacting with PCRs. RESULTS: The majority of third year students (56%, 42/75) had experienced more than three personal conversations with a PCR about a drug product since starting medical school. Five percent (4/75) claimed no previous personal experience with PCRs. Most students (57.3%, 43/75) were not aware of available guidelines regarding PCR interactions. Twenty-eight percent of students (21/75) thought that none of the named activities/gifts (lunch access, free stethoscope, textbooks, educational CD-ROMS, sporting events) should be restricted, while 24.0% (8/75) thought that students should be restricted only from sporting events. The perceived educational value of PCR information to both practicing physicians and students increased after the workshop intervention from 17.7% to 43.2% (chi square, p = .0001), and 22.1% to 40.5% (p = .0007), respectively. Student perceptions of the degree of bias of PCR information decreased from 84.1% to 72.9% (p = .065), but the perceived degree of influence on prescribing increased (44.2% to 62.1% (p = .02)). CONCLUSIONS: Students have exposure to PCRs early in their medical training. A single workshop intervention may influence student attitudes toward interactions with PCRs. Students were more likely to acknowledge the educational value of PCR interactions and their impact on prescribing after the workshop intervention

Psycho-education programme for temporomandibular disorders: a pilot study

BACKGROUND: Temporomandibular disorders (TMDs) are by far the most predominant condition affecting the temporomandibular joint (TMJ), however many patients have mild self-limiting symptoms and should not be referred for specialist care. The aim of this pilot study was to develop a simple, cost-effective management programme for TMDs using CD-ROM. 41 patients (age 18–70) participated in this study, patients were divided into three groups: the 1st group were involved in an attention placebo CD-ROM (contain anatomical information about the temporomandibular system), the 2nd group received information on CD-ROM designed to increase their control and self efficacy, while the 3rd group received the same programme of the 2nd group added to it an introduction to self-relaxing techniques followed by audio tape of progressive muscle relaxation exercises. Each of the groups was asked to complete a number of questionnaires on the day of initial consultation and six weeks afterwards. RESULTS: The two experimental groups (2nd & 3rd) were equally effective in reducing pain, disability and distress, and both were more effective than the attention placebo group (1st), however the experimental groups appeared to have improved at follow-up relative to the placebo-group in terms of disability, pain and depressed mood. CONCLUSION: This pilot study demonstrates the feasibility and acceptability of the design. A full, randomized, controlled trial is required to confirm the efficacy of the interventions developed here