CTNNB1, AXIN1 and APC expression analysis of different medulloblastoma variants

OBJECTIVES: We investigated four components of the Wnt signaling pathway in medulloblastomas. Medulloblastoma is the most common type of malignant pediatric brain tumor, and the Wnt signaling pathway has been shown to be activated in this type of tumor. METHODS: Sixty-one medulloblastoma cases were analyzed for β-catenin gene (CTNNB1) mutations, β-catenin protein expression via immunostaining and Wnt signaling pathway-related gene expression. All data were correlated with histological subtypes and patient clinical information. RESULTS: CTNNB1 sequencing analysis revealed that 11 out of 61 medulloblastomas harbored missense mutations in residues 32, 33, 34 and 37, which are located in exon 3. These mutations alter the glycogen synthase kinase-3β phosphorylation sites, which participate in β-catenin degradation. No significant differences were observed between mutation status and histological medulloblastoma type, patient age and overall or progression-free survival times. Nuclear β-catenin accumulation, which was observed in 27.9% of the cases, was not associated with the histological type, CTNNB1 mutation status or tumor cell dissemination. The relative expression levels of genes that code for proteins involved in the Wnt signaling pathway (CTNNB1, APC, AXIN1 and WNT1) were also analyzed, but no significant correlations were found. In addition, large-cell variant medulloblastomas presented lower relative CTNNB1 expression as compared to the other tumor variants. CONCLUSIONS: A small subset of medulloblastomas carry CTNNB1 mutations with consequent nuclear accumulation of β-catenin. The Wnt signaling pathway plays a role in classic, desmoplastic and extensive nodularity medulloblastoma variants but not in large-cell medulloblastomas

ASPiH 2021 Conference – Moving upstream: using simulation to improve systems

Editorial - No abstract

Quantum-classical transition in Scale Relativity

The theory of scale relativity provides a new insight into the origin of fundamental laws in physics. Its application to microphysics allows us to recover quantum mechanics as mechanics on a non-differentiable (fractal) spacetime. The Schrodinger and Klein-Gordon equations are demonstrated as geodesic equations in this framework. A development of the intrinsic properties of this theory, using the mathematical tool of Hamilton's bi-quaternions, leads us to a derivation of the Dirac equation within the scale-relativity paradigm. The complex form of the wavefunction in the Schrodinger and Klein-Gordon equations follows from the non-differentiability of the geometry, since it involves a breaking of the invariance under the reflection symmetry on the (proper) time differential element (ds - ds). This mechanism is generalized for obtaining the bi-quaternionic nature of the Dirac spinor by adding a further symmetry breaking due to non-differentiability, namely the differential coordinate reflection symmetry (dx^mu - dx^mu) and by requiring invariance under parity and time inversion. The Pauli equation is recovered as a non-relativistic-motion approximation of the Dirac equation.Comment: 28 pages, no figur

Identication-robust moment-based tests for Markov switching in autoregressive models

This paper develops tests of the null hypothesis of linearity in the context of autoregressive models with Markov-switching means and variances. These tests are robust to the identification failures that plague conventional likelihood-based inference methods. The approach exploits the moments of normal mixtures implied by the regime-switching process and uses Monte Carlo test techniques to deal with the presence of an autoregressive component in the model specification. The proposed tests have very respectable power in comparison with the optimal tests for Markov-switching parameters of Carrasco et al. (2014), and they are also quite attractive owing to their computational simplicity. The new tests are illustrated with an empirical application to an autoregressive model of USA output growth

Variation in the initial assessment and investigation for ovarian cancer in symptomatic women: a systematic review of international guidelines

Abstract: Background: Women with ovarian cancer can present with a variety of symptoms and signs, and an increasing range of tests are available for their investigation. A number of international guidelines provide advice for the initial assessment of possible ovarian cancer in symptomatic women. We systematically identified and reviewed the consistency and quality of these documents. Methods: MEDLINE, Embase, guideline-specific databases and professional organisation websites were searched in March 2018 for relevant clinical guidelines, consensus statements and clinical pathways, produced by professional or governmental bodies. Two reviewers independently extracted data and appraised documents using the Appraisal for Guidelines and Research Evaluation 2 (AGREEII) tool. Results: Eighteen documents from 11 countries in six languages met selection criteria. Methodological quality varied with two guidance documents achieving an AGREEII score ≥ 50% in all six domains and 10 documents scoring ≥50% for “Rigour of development” (range: 7–96%). All guidance documents provided advice on possible symptoms of ovarian cancer, although the number of symptoms included in documents ranged from four to 14 with only one symptom (bloating/abdominal distension/increased abdominal size) appearing in all documents. Fourteen documents provided advice on physical examinations but varied in both the examinations they recommended and the physical signs they included. Fifteen documents provided recommendations on initial investigations. Transabdominal/transvaginal ultrasound and the serum biomarker CA125 were the most widely advocated initial tests. Five distinct testing strategies were identified based on the number of tests and the order of testing advocated: ‘single test’, ‘dual testing’, ‘sequential testing’, ‘multiple testing options’ and ‘no testing’. Conclusions: Recommendations on the initial assessment and investigation for ovarian cancer in symptomatic women vary considerably between international guidance documents. This variation could contribute to differences in the way symptomatic women are assessed and investigated between countries. Greater research is needed to evaluate the assessment and testing approaches advocated by different guidelines and their impact on ovarian cancer detection

Animal or Plant: Which Is the Better Fog Water Collector?

Occasional fog is a critical water source utilised by plants and animals in the Namib Desert. Fog basking beetles (Onymacris unguicularis, Tenebrionidae) and Namib dune bushman grass (Stipagrostris sabulicola, Poaceae) collect water directly from the fog. While the beetles position themselves optimally for fog water collection on dune ridges, the grass occurs predominantly at the dune base where less fog water is available. Differences in the fog-water collecting abilities in animals and plants have never been addressed. Here we place beetles and grass side-by-side in a fog chamber and measure the amount of water they collect over time. Based on the accumulated amount of water over a two hour period, grass is the better fog collector. However, in contrast to the episodic cascading water run-off from the grass, the beetles obtain water in a steady flow from their elytra. This steady trickle from the beetles' elytra to their mouth could ensure that even short periods of fog basking – while exposed to predators – will yield water. Up to now there is no indication of specialised surface properties on the grass leafs, but the steady run-off from the beetles could point to specific property adaptations of their elytra surface

Cultural Competency in Peer-Run Programs: Results of a Web Survey and Implications for Future Practice

Objective: The study explored perceptions of adults with psychiatric disabilities regarding cultural competency of peer-run mental health support groups and programs. Methods: Web survey respondents were recruited via mental health listservs, web sites, newsletters, emails, and word of mouth. A total of 527 peers were surveyed about cultural competency barriers facing peer-run programs; common reasons for not using peer services; and strategies to engage diverse communities. Results: Both multicultural and Caucasian respondents agreed that lack of funding and staff education about diversity were barriers to cultural competency in peer programs. Multicultural respondents were more likely than whites to feel that both the recognition of the need for and interest in attending cultural competency training is lacking in peer programs, as well as information about the diverse composition of peer program memberships. Among those who had never participated in peer support, people of color were more likely than whites to endorse feeling they would not belong and believing their languages would not be spoken in peer programs. Whites, on the other hand, were more likely to cite a preference for professional over peer support, while nearly half of both groups indicated that the main reason for non-attendance is a lack of knowledge about peer programs. Qualitative results highlighted successful outreach and engagement strategies. Conclusions: Study findings informed development of a cultural competency tool that was pilot-tested among peer-run programs. Given the importance of peer support in recovery, these findings suggest the need for additional research on cultural competency in peer programs

Permanence of the information given during oncogenetic counseling to persons at familial risk of breast/ovarian and/or colon cancer

How long counselees retain the information given during their genetic consultation is of major importance. To address this issue, we conducted a survey among the 3500 families that have been offered genetic counseling at our Center since 1988. In August 2007, we mailed a questionnaire to a representative subset of 579 persons belonging to breast/ovarian or colon cancer families seen in the last 10 years, either carrying an identified mutation or not. Targeted topics included the meaning of hereditary predisposition, the medical prevention related to the familial risk, the steps to undertake for a new family member to enter the genetic testing program and general knowledge of hereditary predisposition to cancer. A total of 91 randomized non-respondents were sent a second, more inciting letter, in order to assess any non-response bias. Overall, 337 questionnaires were collected: response rate was 58%. Standardized average knowledge was 7.28±1.52 of 10. Scores were lowest concerning medical prevention. The level of knowledge decreased with age (P<10−6), but increased with educational level (P<10−5) and mutation status (P=0.01). Surprisingly, no erosion of patients' knowledge over the time was observed (P=0.41). Among persons at hereditary risk of colon cancer, the level of knowledge tended to improve with time, in contrast to the breast/ovarian group (P=0.017). Among persons with a familial risk of breast/ovarian or colon cancer, a renewal of oncogenetic counseling does not seem necessary to maintain the level of specific knowledge. Measures to help patients follow their medical prevention, as organizing or checking their medical examinations, seem indicated

An investigation of factors associated with the health and well-being of HIV-infected or HIV-affected older people in rural South Africa

BackgroundDespite the severe impact of HIV in sub-Saharan Africa, the health of older people aged 50+ is often overlooked owing to the dearth of data on the direct and indirect effects of HIV on older people's health status and well-being. The aim of this study was to examine correlates of health and well-being of HIV-infected older people relative to HIV-affected people in rural South Africa, defined as participants with an HIV-infected or death of an adult child due to HIV-related cause. MethodsData were collected within the Africa Centre surveillance area using instruments adapted from the World Health Organization (WHO) Study on global AGEing and adult health (SAGE). A stratified random sample of 422 people aged 50+ participated. We compared the health correlates of HIV-infected to HIV-affected participants using ordered logistic regressions. Health status was measured using three instruments: disability index, quality of life and composite health score. ResultsMedian age of the sample was 60 years (range 50-94). Women HIV-infected (aOR 0.15, 95% confidence interval (CI) 0.08-0.29) and HIV-affected (aOR 0.20, 95% CI 0.08-0.50), were significantly less likely than men to be in good functional ability. Women's adjusted odds of being in good overall health state were similarly lower than men's; while income and household wealth status were stronger correlates of quality of life. HIV-infected participants reported better functional ability, quality of life and overall health state than HIV-affected participants. Discussion and Conclusions The enhanced healthcare received as part of anti-retroviral treatment as well as the considerable resources devoted to HIV care appear to benefit the overall well-being of HIV-infected older people; whereas similar resources have not been devoted to the general health needs of HIV uninfected older people. Given increasing numbers of older people, policy and programme interventions are urgently needed to holistically meet the health and well-being needs of older people beyond the HIV-related care system. <br/