Formation of Supermassive Black Holes

Evidence shows that massive black holes reside in most local galaxies. Studies have also established a number of relations between the MBH mass and properties of the host galaxy such as bulge mass and velocity dispersion. These results suggest that central MBHs, while much less massive than the host (~ 0.1%), are linked to the evolution of galactic structure. In hierarchical cosmologies, a single big galaxy today can be traced back to the stage when it was split up in hundreds of smaller components. Did MBH seeds form with the same efficiency in small proto-galaxies, or did their formation had to await the buildup of substantial galaxies with deeper potential wells? I briefly review here some of the physical processes that are conducive to the evolution of the massive black hole population. I will discuss black hole formation processes for `seed' black holes that are likely to place at early cosmic epochs, and possible observational tests of these scenarios.Comment: To appear in The Astronomy and Astrophysics Review. The final publication is available at http://www.springerlink.co

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Distances and ages of globular clusters using Hipparcos parallaxes of local subdwarfs

We discuss the impact of Population II and Globular Cluster (GCs) stars on the derivation of the age of the Universe, and on the study of the formation and early evolution of galaxies, our own in particular. The long-standing problem of the actual distance scale to Population II stars and GCs is addressed, and a variety of different methods commonly used to derive distances to Population II stars are briefly reviewed. Emphasis is given to the discussion of distances and ages for GCs derived using Hipparcos parallaxes of local subdwarfs. Results obtained by different authors are slightly different, depending on different assumptions about metallicity scale, reddenings, and corrections for undetected binaries. These and other uncertainties present in the method are discussed. Finally, we outline progress expected in the near future.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 22 pages including 3 tables and 2 postscript figures, uses Kluwer's crckapb.sty LaTeX style file, enclose

Supporting mental health, wellbeing and study skills in Higher Education:an online intervention system

Abstract Background Dealing with psychological and study skill difficulties can present a challenge for both Higher Education (HE) students, who suffer from them, but also for HE Institutions and their support services. Alternative means of support, such as online interventions, have been identified as cost-effective and efficient ways to provide inclusive support to HE students, removing many of the barriers to help-seeking as well as promoting mental health and wellbeing. Case presentation The current case study initially outlines the rigorous approach in the development of one such online intervention system, MePlusMe. It further highlights key features that constitute innovative delivery of evidence-based psychological and educational practice in the areas of mental health, promotion of wellbeing, support of mood and everyday functioning, and study-skills enhancement. Conclusions This case study aims to present the innovative features of MePlusMe in relation to current needs and evidence-basis. Finally, it presents future directions in the evaluation, assessment, and evidence of the fitness-for-purpose process

Sigma-2 receptor ligand as a novel method for delivering a SMAC mimetic drug for treating ovarian cancer

BACKGROUND: The sigma-2 receptor has been validated as a biomarker for proliferating tumours. Second mitochondria-derived activator of caspase (Smac) is a protein released from mitochondria into the cytosol, leading to apoptosis. In this study, we investigated a sigma-2 ligand as a tumour-targeting drug delivery agent for treating ovarian cancer. METHODS: A sigma-2 ligand, SW 43, was conjugated with a Smac mimetic compound (SMC), SW IV-52s, to form SW III-123. The delivery function of the sigma-2 moiety and cell killing mechanisms of SW III-123 were examined in human ovarian cancer cell lines. RESULTS: SW III-123 internalisation into ovarian cancer cells was mediated by sigma-2 receptors. SW III-123, but not SW IV-52s or SW 43, exhibited potent cytotoxicity in human ovarian cancer cell lines SKOV-3, CaOV-3 and BG-1 after 24-h treatment, suggesting that the sigma-2 ligand successfully delivered SMC into ovarian cancer cells. SW III-123 induced rapid degradation of inhibitor of apoptosis proteins (cIAP1 and cIAP2), accumulation of NF-κB-inducing kinase (NIK) and phosphorylation of NF-κB p65, suggesting that SW III-123 activated both canonical and noncanonical NF-κB pathways in SKOV-3 cells. SW III-123 cleaved caspase-8, -9 and -3. Tumour necrosis factor alpha (TNFα) antibody markedly blocked SW III-123-induced cell death and caspase-3 activity in SKOV-3 cells, indicating that SW III-123 activated both intrinsic and extrinsic apoptotic pathways and induced TNFα-dependent cell death in SKOV-3 cells. CONCLUSION: Sigma-2 ligands are a promising tumour-targeting drug delivery agent. Sigma-2-conjugated SMC exemplifies a novel class of therapeutic drugs for treating ovarian cancer

The Relationship Between Therapist Effects and Therapy Delivery Factors: Therapy Modality, Dosage, and Non-completion.

To consider the relationships between, therapist variability, therapy modality, therapeutic dose and therapy ending type and assess their effects on the variability of patient outcomes. Multilevel modeling was used to analyse a large sample of routinely collected data. Model residuals identified more and less effective therapists, controlling for case-mix. After controlling for case mix, 5.8 % of the variance in outcome was due to therapists. More sessions generally improved outcomes, by about half a point on the PHQ-9 for each additional session, while non-completion of therapy reduced the amount of pre-post change by six points. Therapy modality had little effect on outcome. Patient and service outcomes may be improved by greater focus on the variability between therapists and in keeping patients in therapy to completion

The molecular hallmarks of primary and secondary vitreoretinal lymphoma

Vitreoretinal lymphoma (VRL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) considered a variant of primary central nervous system lymphoma (PCNSL). Diagnosis of VRL requires examination of vitreous fluid, but cytologic differentiation from uveitis remains difficult. Due to its rarity and difficulty in obtaining diagnostic material, little is known about the genetic profile of VRL. The aim of our study was to investigate the mutational profile of a large series of primary and secondary VRL. Targeted next generation sequencing using a custom panel containing the most frequent mutations in PCNSL was performed on 34 vitrectomy samples of 31 patients with VRL and negative controls with uveitis. In a subset of cases, genome-wide copy number alterations (CNA) were assessed using the Oncoscan platform. Mutations in MYD88 (74%), PIM1 (71%), CD79B (55%), IGLL5 (52%), TBL1XR1 (48%), ETV6 (45%) and 9p21/CDKN2A deletions (85%) were the most common alterations, with similar frequencies in primary (15), synchronous (3) or secondary (13) VRL. This mutational spectrum is similar to MYD88mut/CD79Bmut (MCD or cluster 5) DLBCL with activation of Toll-like and B-cell receptor pathways and CDKN2A loss, confirming their close relationship. Oncoscan analysis demonstrated a high number of CNAs (mean 18.6/case). Negative controls lacked mutations or CNAs. Using cell free DNA of vitreous fluid supernatant, mutations present in cellular DNA were reliably detected in all examined cases. Mutational analysis is a highly sensitive and specific tool for the diagnosis of VRL and can also be applied successfully to cell free DNA derived from the vitreous.Copyright © 2021 American Society of Hematology

Biological predictors of suicidality in schizophrenia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65166/1/j.1600-0447.1996.tb09883.x.pd

Computer-aided DSM-IV-diagnostics – acceptance, use and perceived usefulness in relation to users' learning styles

BACKGROUND: CDSS (computerized decision support system) for medical diagnostics have been studied for long. This study was undertaken to investigate how different preferences of Learning Styles (LS) of psychiatrists might affect acceptance, use and perceived usefulness of a CDSS for diagnostics in psychiatry. METHODS: 49 psychiatrists (specialists and non-specialists) from 3 different clinics volunteered to participate in this study and to use the CDSS to diagnose a paper-based case (based on a real patient). LS, attitudes to CDSS and complementary data were obtained via questionnaires and interviews. To facilitate the study, a special version of the CDSS was created, which automatically could log interaction details. RESULTS: The LS preferences (according to Kolb) of the 49 physicians turned out as follows: 37% were Assimilating, 31% Converging, 27% Accommodating and 6% Diverging. The CDSS under study seemed to favor psychiatrists with abstract conceptualization information perceiving mode (Assimilating and Converging learning styles). A correlation between learning styles preferences and computer skill was found. Positive attitude to computer-aided diagnostics and learning styles preferences was also found to correlate. Using the CDSS, the specialists produced only 1 correct diagnosis and the non-specialists 2 correct diagnoses (median values) as compared to the three predetermined correct diagnoses of the actual case. Only 10% had all three diagnoses correct, 41 % two correct, 47 % one correct and 2 % had no correct diagnose at all. CONCLUSION: Our results indicate that the use of CDSS does not guarantee correct diagnosis and that LS might influence the results. Future research should focus on the possibility to create systems open to individuals with different LS preferences and possibility to create CDSS adapted to the level of expertise of the user

Disordered semantic representation in schizophrenic temporal cortex revealed by neuromagnetic response patterns

BACKGROUND: Loosening of associations and thought disruption are key features of schizophrenic psychopathology. Alterations in neural networks underlying this basic abnormality have not yet been sufficiently identified. Previously, we demonstrated that spatio-temporal clustering of magnetic brain responses to pictorial stimuli map categorical representations in temporal cortex. This result has opened the possibility to quantify associative strength within and across semantic categories in schizophrenic patients. We hypothesized that in contrast to controls, schizophrenic patients exhibit disordered representations of semantic categories. METHODS: The spatio-temporal clusters of brain magnetic activities elicited by object pictures related to super-ordinate (flowers, animals, furniture, clothes) and base-level (e.g. tulip, rose, orchid, sunflower) categories were analysed in the source space for the time epochs 170–210 and 210–450 ms following stimulus onset and were compared between 10 schizophrenic patients and 10 control subjects. RESULTS: Spatio-temporal correlations of responses elicited by base-level concepts and the difference of within vs. across super-ordinate categories were distinctly lower in patients than in controls. Additionally, in contrast to the well-defined categorical representation in control subjects, unsupervised clustering indicated poorly defined representation of semantic categories in patients. Within the patient group, distinctiveness of categorical representation in the temporal cortex was positively related to negative symptoms and tended to be inversely related to positive symptoms. CONCLUSION: Schizophrenic patients show a less organized representation of semantic categories in clusters of magnetic brain responses than healthy adults. This atypical neural network architecture may be a correlate of loosening of associations, promoting positive symptoms