549 research outputs found
Striatal dopamine D2 receptor binding of risperidone in schizophrenic patients as assessed by 123I-iodobenzamide SPECT: a comparative study with olanzapine
The aim of this investigation was to compare the degree of striatal dopamine-(D2) receptor blockade by two atypical antipsychotic drugs, risperidone and olanzapine. The percentage of D2 receptor occupancy during treatment was calculated by comparing the results of 123I-iodobenzamide SPECT with those from healthy control subjects. Twenty inpatients suffering from schizophrenia or schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with clinically recommended doses of risperidone and compared with 13 inpatients treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade correlated strongly for both risperidone (Pearson r = –0.86, p = 0.0001) and olanzapine (Pearson r = –0.77, p = 0.002). There was no significant difference between the D2 receptor occupancy of the two substances when given in the clinically recommended dose range (unpaired t-test, t= –0.112, p=0.911)
Cosmic Swarms: A search for Supermassive Black Holes in the LISA data stream with a Hybrid Evolutionary Algorithm
We describe a hybrid evolutionary algorithm that can simultaneously search
for multiple supermassive black hole binary (SMBHB) inspirals in LISA data. The
algorithm mixes evolutionary computation, Metropolis-Hastings methods and
Nested Sampling. The inspiral of SMBHBs presents an interesting problem for
gravitational wave data analysis since, due to the LISA response function, the
sources have a bi-modal sky solution. We show here that it is possible not only
to detect multiple SMBHBs in the data stream, but also to investigate
simultaneously all the various modes of the global solution. In all cases, the
algorithm returns parameter determinations within (as estimated from
the Fisher Matrix) of the true answer, for both the actual and antipodal sky
solutions.Comment: submitted to Classical & Quantum Gravity. 19 pages, 4 figure
Stripes, Pseudogaps, and Van Hove Nesting in the Three-band tJ Model
Slave boson calculations have been carried out in the three-band tJ model for
the high-T_c cuprates, with the inclusion of coupling to oxygen breathing mode
phonons. Phonon-induced Van Hove nesting leads to a phase separation between a
hole-doped domain and a (magnetic) domain near half filling, with long-range
Coulomb forces limiting the separation to a nanoscopic scale. Strong
correlation effects pin the Fermi level close to, but not precisely at the Van
Hove singularity (VHS), which can enhance the tendency to phase separation. The
resulting dispersions have been calculated, both in the uniform phases and in
the phase separated regime. In the latter case, distinctly different
dispersions are found for large, random domains and for regular (static)
striped arrays, and a hypothetical form is presented for dynamic striped
arrays. The doping dependence of the latter is found to provide an excellent
description of photoemission and thermodynamic experiments on pseudogap
formation in underdoped cuprates. In particular, the multiplicity of observed
gaps is explained as a combination of flux phase plus charge density wave (CDW)
gaps along with a superconducting gap. The largest gap is associated with VHS
nesting. The apparent smooth evolution of this gap with doping masks a
crossover from CDW-like effects near optimal doping to magnetic effects (flux
phase) near half filling. A crossover from large Fermi surface to hole pockets
with increased underdoping is found. In the weakly overdoped regime, the CDW
undergoes a quantum phase transition (), which could be obscured
by phase separation.Comment: 15 pages, Latex, 18 PS figures Corrects a sign error: major changes,
esp. in Sect. 3, Figs 1-4,6 replace
A novel diffuse large B-cell lymphoma-associated cancer testis antigen encoding a PAS domain protein
Here we report that the OX-TES-1 SEREX antigen, which showed immunological reactivity with serum from four out of 10 diffuse large B-cell lymphoma (DLBCL) patients, is encoded by a novel gene, PAS domain containing 1 (PASD1). PASD1_v1 cDNA encodes a 639 amino-acid (aa) protein product, while an alternatively spliced variant (PASD1_v2), lacking intron 14, encodes a 773 aa protein, the first 638 aa of which are common to both proteins. The PASD1-predicted protein contains a PAS domain that, together with a putative leucine zipper and nuclear localisation signal, suggests it encodes a transcription factor. The expression of PASD1_v1 mRNA was confirmed by RT-PCR in seven DLBCL-derived cell lines, while PASD1_v2 mRNA appears to be preferentially expressed in cell lines derived from non-germinal centre DLBCL. Immunophenotyping studies of de novo DLBCL patients' tumours with antibodies to CD10, BCL-6 and MUM1 indicated that two patients mounting an immune response to PASD1 were of a poor prognosis non-germinal centre subtype. Expression of PASD1 mRNA was restricted to normal testis, while frequent expression was observed in solid tumours (25 out of 68), thus fulfilling the criteria for a novel cancer testis antigen. PASD1 has potential for lymphoma vaccine development that may also be widely applicable to other tumour types
Shared Genetic Etiology Between Alcohol Dependence and Major Depressive Disorder
The clinical comorbidity of alcohol dependence (AD) and
major depressive disorder (MDD) is well established,
whereas genetic factors influencing co-occurrence remain
unclear. A recent study using polygenic risk scores (PRS)
calculated based on the first-wave Psychiatric Genomics
Consortium MDD meta-analysis (PGC-MDD1) suggests a
modest shared genetic contribution to MDD and AD. Using a
(∼10 fold) larger discovery sample, we calculated PRS
based on the second wave (PGC-MDD2) of results, in a
severe AD case–control target sample. We found significant associations between AD disease status and MDD-PRS derived from both PGC-MDD2 (most informative
P-threshold=1.0, P=0.00063, R2=0.533%) and PGCMDD1
(P-threshold=0.2, P=0.00014, R2=0.663%) metaanalyses;
the larger discovery sample did not yield
additional predictive power. In contrast, calculating PRS in a MDD target sample yielded increased power when using
PGC-MDD2 (P-threshold=1.0, P=0.000038, R2=1.34%)
versus PGC-MDD1 (P-threshold=1.0, P=0.0013,
R2=0.81%). Furthermore, when calculating PGC-MDD2
PRS in a subsample of patients with AD recruited explicitly excluding comorbid MDD, significant associations were still found (n=331; P-threshold=1.0, P=0.042, R2=0.398%). Meanwhile, in the subset of patients in which MDD was not the explicit exclusion criteria, PRS predicted more variance (n=999; P-threshold=1.0, P=0.0003, R2=0.693%). Our findings replicate the reported genetic overlap between AD and MDD and also suggest the need for improved, rigorous phenotyping to identify true shared cross-disorder genetic factors. Larger target samples are needed to reduce noise and take advantage of increasing discovery sample size
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