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

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

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

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

Predictors of nursing home admission of individuals without a dementia diagnosis before admission - results from the Leipzig Longitudinal Study of the Aged (LEILA 75+)

<p>Abstract</p> <p>Background</p> <p>In previous decades a substantial number of community-based studies mostly including dementia cases examined predictors of nursing home admission (NHA) among elderly people. However, no one study has analysed predictors of NHA for individuals without developing dementia before NHA.</p> <p>Methods</p> <p>Data were derived from the Leipzig Longitudinal Study of the Aged, a population-based study of individuals aged 75 years and older. 1,024 dementia-free older adults were interviewed six times on average every 1.4 years. Socio-demographic, clinical, and psychometric variables were obtained. Kaplan-Meier estimates were used to determine mean time to NHA. Cox proportional hazards regression was used to examine predictors of long-term NHA.</p> <p>Results</p> <p>Of the overall sample, 7.8 percent of the non-demented elderly (n = 59) were admitted to nursing home (NH) during the study period. The mean time to NHA in the dementia-free sample was 7.6 years. Characteristics associated with a shorter time to NHA were increased age, living alone, functional and cognitive impairment, major depression, stroke, myocardial infarction, a low number of specialist visits and paid home helper use.</p> <p>Conclusions</p> <p>Severe physical or psychiatric diseases and living alone have a significant effect on NHA for dementia-free individuals. The findings offer potentialities of secondary prevention to avoid or delay NHA for these elderly individuals. Further investigation of predictors of institutionalization is warranted to advance understanding of the process leading to NHA for this important group.</p

Effect of different protein sources on satiation and short-term satiety when consumed as a starter

<p>Abstract</p> <p>Background</p> <p>Because the source of protein may play a role in its satiating effect, we investigated the effect of different proteins on satiation and short-term satiety.</p> <p>Methods</p> <p>Two randomized single-blind cross-over studies were completed. In the first study, we investigated the effect of a preload containing 20 g of casein, whey, pea protein, egg albumin or maltodextrin vs. water control on food intake 30 min later in 32 male volunteers (25 ± 4 yrs, BMI 24 ± 0.4 kg/m²). Subjective appetite was assessed using visual analogue scales at 10 min intervals after the preload. Capillary blood glucose was measured every 30 min during 2 hrs before and after the ad libitum meal. In the second study, we compared the effect of 20 g of casein, pea protein or whey vs. water control on satiation in 32 male volunteers (25 ± 0.6 yrs, BMI 24 ± 0.5 kg/m²). The preload was consumed as a starter during an ad libitum meal and food intake was measured. The preloads in both studies were in the form of a beverage.</p> <p>Results</p> <p>In the first study, food intake was significantly lower only after casein and pea protein compared to water control (P = 0.02; 0.04 respectively). Caloric compensation was 110, 103, 62, 56 and 51% after casein, pea protein, whey, albumin and maltodextrin, respectively. Feelings of satiety were significantly higher after casein and pea protein compared to other preloads (P < 0.05). Blood glucose response to the meal was significantly lower when whey protein was consumed as a preload compared to other groups (P < 0.001). In the second study, results showed no difference between preloads on ad libitum intake. Total intake was significantly higher after caloric preloads compared to water control (P < 0.05).</p> <p>Conclusion</p> <p>Casein and pea protein showed a stronger effect on food intake compared to whey when consumed as a preload. However, consuming the protein preload as a starter of a meal decreased its impact on food intake as opposed to consuming it 30 min before the meal.</p

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

The formation of massive black holes through collision runaway in dense young star clusters

A luminous X-ray source is associated with a cluster (MGG-11) of young stars \~200pc from the center of the starburst galaxy M82. The properties of the X-ray source are best explained by a black hole with a mass of at least 350Msun, which is intermediate between stellar-mass and supermassive black holes. A nearby but somewhat more massive star cluster (MGG-9) shows no evidence of such an intermediate mass black hole, raising the issue of just what physical characteristics of the clusters can account for this difference. Here we report numerical simulations of the evolution and the motions of stars within the clusters, where stars are allowed to mergers with each other. We find that for MGG-11 dynamical friction leads to the massive stars sinking rapidly to the center of the cluster to participate in a runaway collision, thereby producing a star of 800-3000Msun, which ultimately collapses to an black hole of intermediate mass. No such runaway occurs in the cluster MGG-9 because the larger cluster radius leads to a mass-segregation timescale a factor of five longer than for MGG-11.Comment: Accepted for publication in Nature (Including supplementary information