Prediction of progression in pTa and pT1 bladder carcinomas with p53, p16 and pRb

Currently available prognostic tools appear unable to adequately predict recurrence and progression in non muscle-invasive bladder carcinomas. We aimed to assess the prognostic value of immunohistochemical evaluation of the cell cycle markers p53, p16 and pRb. Paraffin blocks were obtained from 78 cases of pTa and pT1 transitional cell carcinomas, for which long-term follow-up was available. Representative sections were stained using antibodies against p53, p16 and pRb. Altered marker expression was found in 45, 17 and 30% of cases, respectively. Concurrent alteration of two or three markers occurred in 19% of cases, and was significantly associated with grade and stage. In univariate survival analysis, the concurrent alteration of any two markers was significantly associated with progression. The greatest risk was produced by alteration of both p53 and p16, which increased the risk of progression by 14.45 times (95% confidence interval (CI) 3.10-67.35). After adjusting for grade and stage, this risk was 7.73 (CI 1.13-52.70). The markers did not generally predict tumour recurrence, except in the 25 pT1 tumours. In these, p16 alteration was associated with a univariate risk of 2.83 (CI 1.01-7.91), and concurrent p53 and p16 alteration with a risk of 9.29 (CI 1.24-69.50). Overall, we conclude that the immunohistochemical evaluation of p53 and p16 may have independent prognostic value for disease progression, and may help guide management decisions in these tumours

Development of a universal psycho-educational intervention to prevent common postpartum mental disorders in primiparous women: a multiple method approach

<p>Abstract</p> <p>Background</p> <p>Prevention of postnatal mental disorders in women is an important component of comprehensive health service delivery because of the substantial potential benefits for population health. However, diverse approaches to prevention of postnatal depression have had limited success, possibly because anxiety and adjustment disorders are also problematic, mental health problems are multifactorially determined, and because relationships amongst psychosocial risk factors are complex and difficult to modify. The aim of this paper is to describe the development of a novel psycho-educational intervention to prevent postnatal mental disorders in mothers of firstborn infants.</p> <p>Methods</p> <p>Data from a variety of sources were synthesised: a literature review summarised epidemiological evidence about neglected modifiable risk factors; clinical research evidence identified successful psychosocial treatments for postnatal mental health problems; consultations with clinicians, health professionals, policy makers and consumers informed the proposed program and psychological and health promotion theories underpinned the proposed mechanisms of effect. The intervention was pilot-tested with small groups of mothers and fathers and their first newborn infants.</p> <p>Results</p> <p><it>What Were We Thinking! </it>is a psycho-educational intervention, designed for universal implementation, that addresses heightened learning needs of parents of first newborns. It re-conceptualises mental health problems in mothers of infants as reflecting unmet needs for adaptations in the intimate partner relationship after the birth of a baby, and skills to promote settled infant behaviour. It addresses these two risk factors in half-day seminars, facilitated by trained maternal and child health nurses using non-psychiatric language, in groups of up to five couples and their four-week old infants in primary care. It is designed to promote confidence and reduce mental disorders by providing skills in sustainable sleep and settling strategies, and the re-negotiation of the unpaid household workload in non-confrontational ways. Materials include a Facilitators' Handbook, creatively designed worksheets for use in seminars, and a book for couples to take home for reference. A website provides an alternative means of access to the intervention.</p> <p>Conclusions</p> <p><it>What Were We Thinking! </it>is a postnatal mental health intervention which has the potential to contribute to psychologically-informed routine primary postnatal health care and prevent common mental disorders in women.</p

Modelling the Genetic Risk in Age-Related Macular Degeneration

Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69–2.05) than patients aged 75 and above (1.45, 95% CI: 1.36–1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11–1131.96) for individuals in the highest category (GRS 3.44–5.18, 0.5% of the general population) compared to subjects with the most common genetic background (GRS −0.05–1.70, 40.2% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available

Morphometrical malignancy grading is a valuable prognostic factor in invasive ductal breast cancer

The aim of the present study is to augment the prognostic power of breast cancer grading by elaboration of quantitative histopathological methods. We focus on the recently introduced morphometrical grading system in which the three grading sub-features of the WHO grading system are evaluated with the help of computerised nuclear morphometry, and quantitative methods for assessing mitotic activity and tubular differentiation. The prognostic value of the morphometrical grading system is now confirmed in a material of 159 cases of invasive ductal breast cancer. In the current material the morphometrical grading system very efficiently predicted the prognosis of breast cancer by dividing the patients into favourable (grade I), intermediate (grade II), and unfavourable (grade III) outcome (P<0.0001). The morphometrical grading system was especially efficient in identifying patients with the most unfavourable outcome. In our material the morphometrical grade III was associated with a 5.4-fold risk of breast cancer death. In light of the present results, the morphometrical grading can be applied to clinical use as an aid in treatment decisions of patients with invasive ductal breast cancer

Genetic analysis of typical wet-type age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese population

Age-related macular degeneration (AMD) is a common cause of blindness in the elderly. Caucasian patients are predominantly affected by the dry form of AMD, whereas Japanese patients have predominantly the wet form of AMD and/or polypoidal choroidal vasculopathy (PCV). Although genetic association in the 10q26 (ARMS2/HTRA1) region has been established in many ethnic groups for dry-type AMD, typical wet-type AMD, and PCV, the contribution of the 1q32 (CFH) region seem to differ among these groups. Here we show a single nucleotide polymorphism (SNP) in the ARMS2/HTRA1 locus is associated in the whole genome for Japanese typical wet-type AMD (rs10490924: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 4.1 \times 10 ^{ - 4}$$\end{document}, OR = 4.16) and PCV (rs10490924: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 3.7 \times 10 ^{ -8}$$\end{document}, OR = 2.72) followed by CFH (rs800292: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 7.4 \times 10 ^{ -5}$$\end{document}, OR = 2.08; \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 2.6 \times {10^{ - 4}}$$\end{document}, OR = 2.00), which differs from previous studies in Caucasian populations. Moreover, a SNP (rs2241394) in complement component C3 gene showed significant association with PCV (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 2.5 \times {10^{ - 3}}$$\end{document}, OR = 3.47). We conclude that dry-type AMD, typical wet-type AMD, and PCV have both common and distinct genetic risks that become apparent when comparing Japanese versus Caucasian populations

Convergent recombination suppression suggests role of sexual selection in guppy sex chromosome formation.

Sex chromosomes evolve once recombination is halted between a homologous pair of chromosomes. The dominant model of sex chromosome evolution posits that recombination is suppressed between emerging X and Y chromosomes in order to resolve sexual conflict. Here we test this model using whole genome and transcriptome resequencing data in the guppy, a model for sexual selection with many Y-linked colour traits. We show that although the nascent Y chromosome encompasses nearly half of the linkage group, there has been no perceptible degradation of Y chromosome gene content or activity. Using replicate wild populations with differing levels of sexually antagonistic selection for colour, we also show that sexual selection leads to greater expansion of the non-recombining region and increased Y chromosome divergence. These results provide empirical support for longstanding models of sex chromosome catalysis, and suggest an important role for sexual selection and sexual conflict in genome evolution

Probability of Major Depression Classification Based on the SCID, CIDI and MINI Diagnostic Interviews : A Synthesis of Three Individual Participant Data Meta-Analyses

Three previous individual participant data meta-analyses (IPDMAs) reported that, compared to the Structured Clinical Interview for the DSM (SCID), alternative reference standards, primarily the Composite International Diagnostic Interview (CIDI) and the Mini International Neuropsychiatric Interview (MINI), tended to misclassify major depression status, when controlling for depression symptom severity. However, there was an important lack of precision in the results.To compare the odds of the major depression classification based on the SCID, CIDI, and MINI.We included and standardized data from 3 IPDMA databases. For each IPDMA, separately, we fitted binomial generalized linear mixed models to compare the adjusted odds ratios (aORs) of major depression classification, controlling for symptom severity and characteristics of participants, and the interaction between interview and symptom severity. Next, we synthesized results using a DerSimonian-Laird random-effects meta-analysis.In total, 69,405 participants (7,574 [11%] with major depression) from 212 studies were included. Controlling for symptom severity and participant characteristics, the MINI (74 studies; 25,749 participants) classified major depression more often than the SCID (108 studies; 21,953 participants; aOR 1.46; 95% confidence interval [CI] 1.11-1.92]). Classification odds for the CIDI (30 studies; 21,703 participants) and the SCID did not differ overall (aOR 1.19; 95% CI 0.79-1.75); however, as screening scores increased, the aOR increased less for the CIDI than the SCID (interaction aOR 0.64; 95% CI 0.52-0.80).Compared to the SCID, the MINI classified major depression more often. The odds of the depression classification with the CIDI increased less as symptom levels increased. Interpretation of research that uses diagnostic interviews to classify depression should consider the interview characteristics