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Search Results: 1 - 10 of 195556 matches for " Glenn D Francis "
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Androgen receptor expression predicts breast cancer survival: the role of genetic and epigenetic events
Kate M Peters, Stacey L Edwards, Shalima S Nair, Juliet D French, Peter J Bailey, Kathryn Salkield, Sandra Stein, Sarah Wagner, Glenn D Francis, Susan J Clark, Melissa A Brown
BMC Cancer , 2012, DOI: 10.1186/1471-2407-12-132
Abstract: The levels of Androgen receptor protein in a cohort of breast tumour samples was determined by immunohistochemistry and the results were compared with clinical characteristics, including survival. The role of defects in the regulation of Androgen receptor gene expression were examined by mutation and methylation screening of the 5' end of the gene, reporter assays of the 5' and 3' end of the AR gene, and searching for miRNAs that may regulate AR gene expression.AR was expressed in 56% of tumours and expression was significantly inversely associated with 10-year survival (P = 0.004). An investigation into the mechanisms responsible for the loss of AR expression revealed that hypermethylation of the AR promoter is associated with loss of AR expression in breast cancer cells but not in primary breast tumours. In AR negative breast tumours, mutation screening identified the same mutation (T105A) in the 5'UTR of two AR negative breast cancer patients but not reported in the normal human population. Reporter assay analysis of this mutation however found no evidence for a negative impact on AR 5'UTR activity. The role of miR-124 in regulating AR expression was also investigated, however no evidence for this was found.This study highlights the potential for AR expression to be an informative biomarker for breast cancer survival and sets the scene for a more comprehensive investigation of the molecular basis of this phenomenon.Breast cancer is a heterogeneous disease comprising tumour subtypes associated with variable clinical characteristics [1]. Variables including tumour size, histological subtype and grade, lymph node status and the expression of estrogen receptor alpha (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) currently assist routine clinical management [2]. However, these factors are limited in their ability to predict individual survival and response to therapy [2]. This is particularly apparent for patients with advanced b
“They should know where they stand”: attitudes to HIV Voluntary Counselling and Testing amongst a group of out-of-school youth
D Francis
South African Journal of Education , 2010,
Abstract: This article draws on a larger study that examined the ways in which out-ofschool youth responded to a context of HIV/AIDS and how they themselves can be active participants in HIV/AIDS prevention. In addition, four out-of-school youths, trained as fieldworkers, interviewed 32 other out-of-school youths in the Shongweni area of KwaZulu-Natal about their attitudes towards VCT. The out-of-school youth displayed a very positive attitude towards VCT and 91% stated their intentions of getting tested. However this attitude was contradicted by the facts that only nine (28%) had been for testing and that participants evidenced high levels of fear and stigma surrounding VCT. Of the participants, 43% stated a preference for a VCT site or hospital far from home, or, if they could afford it, a private doctor, to minimise the likelihood of being seen by someone they knew. This factor made it more difficult and costlier for outof- school youth to access VCT. For some, the fear of HIV infection is caught up with their existing social exclusion. In contrast, one reason for wanting to test amongst girls was the health of future children. While out-of-school youth understood the role of VCT in maintaining a healthy lifestyle, the obstacles to acting on those intentions included the context of poverty, gender inequalities, stigma and the fear of gossip. Campaigns have succeeded in raising awareness, but translating awareness into action remains a central problem.
Empirically Based Psychosocial Therapies for Schizophrenia: The Disconnection between Science and Practice
Glenn D. Shean
Schizophrenia Research and Treatment , 2013, DOI: 10.1155/2013/792769
Abstract: Empirically validated psychosocial therapies for individuals diagnosed with schizophrenia were described in the report of the Schizophrenia Patient Outcomes Research Team (PORT, 2009). The PORT team identified eight psychosocial treatments: assertive community treatment, supported employment, cognitive behavioral therapy, family-based services, token economy, skills training, psychosocial interventions for alcohol and substance use disorders, and psychosocial interventions for weight management. PORT listings of empirically validated psychosocial therapies provide a useful template for the design of effective recovery-oriented mental health care systems. Unfortunately, surveys indicate that PORT listings have not been implemented in clinical settings. Obstacles to the implementation of PORT psychosocial therapy listings and suggestions for changes needed to foster implementation are discussed. Limitations of PORT therapy listings that are based on therapy outcome efficacy studies are discussed, and cross-cultural and course and outcome studies of correlates of recovery are summarized. 1. Introduction Schizophrenia is a group of disorders in which biological, psychological, and sociocultural factors interact synergistically during all phases of the disorder to result in impairments in interpersonal, practical life skills, and vocational functioning. In order to ameliorate the range of symptoms and functional impairments associated with this diagnosis, comprehensive treatment programs are necessary that provide an array of continuing services, including medication management, access to appropriate psychosocial therapies, and assistance with housing, employment, and sources of financial sustenance. Antipsychotic medications can be effective in reducing symptoms and risk of relapse; however, many individuals continue to evidence significant functional and social deficits after acute symptoms have been ameliorated. Growing concerns about the recurring nature of the disorder as well as the severity of functional psychosocial deficits have contributed to an increased emphasis on the importance of empirically validated psychosocial therapies that foster recovery, beyond symptom remission [1]. Recovery-oriented psychosocial treatment programs ideally are designed to provide services designed to help participants learn how to more effectively live with vulnerabilities, reduce interpersonal and social deficits, and promote improved social adaptation and general life functioning [2]. Progress in achieving recovery is fostered by access to comprehensive mental
Genetic, Morphometric, and Behavioral Factors Linked to the Midsagittal Area of the Corpus Callosum
Glenn D. Rosen
Frontiers in Genetics , 2012, DOI: 10.3389/fgene.2012.00091
Abstract: The corpus callosum is the main commissure connecting left and right cerebral hemispheres, and varies widely in size. Differences in the midsagittal area of the corpus callosum (MSACC) have been associated with a number of cognitive and behavioral phenotypes, including obsessive-compulsive disorders, psychopathy, suicidal tendencies, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. Although there is evidence to suggest that MSACC is heritable in normal human populations, there is surprisingly little evidence concerning the genetic modulation of this variation. Mice provide a potentially ideal tool to dissect the genetic modulation of MSACC. Here, we use a large genetic reference panel – the BXD recombinant inbred line – to dissect the natural variation of the MSACC. We estimated the MSACC in over 300 individuals from nearly 80 strains. We found a 4-fold difference in MSACC between individual mice, and a 2.5-fold difference among strains. MSACC is a highly heritable trait (h2 = 0.60), and we mapped a suggestive QTL to the distal portion of Chr 14. Using sequence data and neocortical expression databases, we were able to identify eight positional and plausible biological candidate genes within this interval. Finally, we found that MSACC correlated with behavioral traits associated with anxiety and attention.
Modifying Gravity: You Can't Always Get What You Want
Glenn D. Starkman
Physics , 2012, DOI: 10.1098/rsta.2011.0292
Abstract: The combination of GR and the Standard Model disagrees with numerous observations on scales from our Solar System up. In the concordance model of cosmology, these contradictions are removed or alleviated by the introduction of three completely independent new components of stress-energy -- the inflaton, dark matter, and dark energy. Each of these in its turn is meant to have (or to currently) dominate the dynamics of the universe. There is still no non-gravitational evidence for any of these dark sectors; nor for the required extensions of the standard model. An alternative is to imagine that GR itself must be modified. Certain coincidences of scale even suggest that one might expect not to have to make three independent. Because they must address the most different types of data, attempts to replace dark matter with modified gravity are the most controversial. A phenomenological model (or family of models), Modified Newtonian Dynamics, has, over the last few years seen several covariant realizations. We discuss a number of challenges that any model that seeks to replace dark matter with modified gravity must face: the loss of Birkhoff's Theorem, and the calculational simplifications it implies; the failure to explain clusters, whether static or interacting, and the consequent need to introduce dark matter of some form, whether hot dark matter neutrinos, or dark fields that arise in new sectors of the modified gravity theory; the intrusion of cosmological expansion into the modified force law, that arises precisely because of the coincidence in scale between the centripetal acceleration at which Newtonian gravity fails in galaxies, and the cosmic acceleration. We conclude with the observation that, although modified gravity may indeed manage to replace dark matter, it is likely to do so by becoming or incorporating, a dark matter theory itself.
Systems Genetics of the Lateral Septal Nucleus in Mouse: Heritability, Genetic Control, and Covariation with Behavioral and Morphological Traits
Alexander Talishinsky, Glenn D. Rosen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0044236
Abstract: The lateral septum has strong efferent projections to hypothalamic and midbrain regions, and has been associated with modulation of social behavior, anxiety, fear conditioning, memory-related behaviors, and the mesolimbic reward pathways. Understanding natural variation of lateral septal anatomy and function, as well as its genetic modulation, may provide important insights into individual differences in these evolutionarily important functions. Here we address these issues by using efficient and unbiased stereological probes to estimate the volume of the lateral septum in the BXD line of recombinant inbred mice. Lateral septum volume is a highly variable trait, with a 2.5-fold difference among animals. We find that this trait covaries with a number of behavioral and physiological phenotypes, many of which have already been associated with behaviors modulated by the lateral septum, such as spatial learning, anxiety, and reward-seeking. Heritability of lateral septal volume is moderate (h2 = 0.52), and much of the heritable variation is caused by a locus on the distal portion of chromosome (Chr) 1. Composite interval analysis identified a secondary interval on Chr 2 that works additively with the Chr 1 locus to increase lateral septum volume. Using bioinformatic resources, we identified plausible candidate genes in both intervals that may influence the volume of this key nucleus, as well as associated behaviors.
Galactic Cosmic Strings as Sources of Primary Antiprotons
Glenn D. Starkman,Tanmay Vachaspati
Physics , 1996, DOI: 10.1103/PhysRevD.53.R6711
Abstract: A possible signature of a class of superconducting cosmic strings trapped in the Milky Way plasma is the emission of low energy antiprotons due to baryon number violating processes on the string. We find the terrestrial flux and the energy spectrum of such antiprotons. Current observational bounds on the flux of low energy antiprotons place a {\it lower} bound on the string tension which is comparable to that given by the electroweak scale.
Squeezing MOND into a Cosmological Scenario
Arthur Lue,Glenn D. Starkman
Physics , 2003, DOI: 10.1103/PhysRevLett.92.131102
Abstract: Explaining the effects of dark matter using modified gravitational dynamics (MOND) has for decades been both an intriguing and controversial possibility. By insisting that the gravitational interaction that accounts for the Newtonian force also drives cosmic expansion, one may kinematically identify which cosmologies are compatible with MOND, without explicit reference to the underlying theory so long as the theory obeys Birkhoff's law. Using this technique, we are able to self-consistently compute a number of quantities of cosmological interest. We find that the critical acceleration a_0 must have a slight source-mass dependence (a_0 ~ M^(1/3)) and that MOND cosmologies are naturally compatible with observed late-time expansion history and the contemporary cosmic acceleration. However, cosmologies that can produce enough density perturbations to account for structure formation are contrived and fine-tuned. Even then, they may be marginally ruled out by evidence of early (z \~ 20) reionization.
Neutrino Masses and Mixing with General Mass Matrices
Glenn D. Starkman,Dejan Stojkovic
Physics , 1999, DOI: 10.1016/S0370-2693(00)00397-X
Abstract: We consider the most general neutrino masses and mixings including Dirac mass terms, M_D, as well as Majorana masses, M_R and M_L. Neither the Majorana nor the Dirac mass matrices are expected to be diagonal in the eigenbasis of weak interactions, and so the resulting eigenstates of the Hamiltonian are admixtures of $\SU(2)_L$ singlet and doublet fields of different ``generations.'' We show that for three generations each of doublet and singlet neutrinos, diagonalization of the Hamiltonian to obtain the propagating eigenstates in the general case requires diagonalization of a $12\times12$ Hermitian matrix, rather than the traditional $6\times6$ symmetric mass matrix. The symmetries of the $12\times12$ matrix {\em are} such that it has 6 pairs of real eigenvalues. Although the standard "see-saw" mechanism remains valid, and indeed the eigenvalues obtained are identical to the standard ones, the correct description of diagonalization and mixing is more complicated. The analogs of the CKM matrix for the light and the heavy neutrinos are nonunitary, enriching the opportunities for CP violation in the full neutrino sector.
The Angular Scale of Topologically-Induced Flat Spots in the Cosmic Microwave Background Radiation
David Olson,Glenn D. Starkman
Physics , 2000, DOI: 10.1088/0264-9381/17/16/301
Abstract: The notion that the topology of the universe need not be that of the universal covering space of its geometry has recently received renewed attention. Generic signatures of cosmological topology have been sought, both in the distribution of objects in the universe, and especially in the temperature fluctuations of the cosmic microwave background radiation (CMBR). One signature identified in the horn topology but hypothesized to be generic is featureless regions or flat spots in the CMBR sky. We show that typical observation points within the cusped 3-manifold m003 from the Snappea census have flat spots with an angular scale of about five degrees for $\Omega_0$=0.3. We expect that this holds for other small volume cusped manifolds with this $\Omega_0$ value.
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