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In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors.
In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models.
A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (β = −0.09, t = −3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (β = 0.09, t = 3.04, p = 0.002).
In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.
Antibody-mediated encephalitis has been discussed as one possible cause for isolated psychotic syndromes. Mostly based on serum samples, findings have been controversial. We present the results of a retrospective study of 124 clinically diagnosed psychotic patients without documented relevant neurological symptoms. All were tested for different antineuronal antibodies in cerebrospinal fluid (CSF) while 81 received serum testing. Antineuronal antibodies in CSF were negative across the sample. 3.7% showed low positive serum antibodies. Our findings highlight the importance of a deeper discussion about the relevance of low positive serum antibodies without concurrent findings in CSF or clinical signs for autoimmune encephalitis.
We present an analytical model of SNR evolution in a cloudy interstellar medium for a single progenitor star of spectral type 05 V. The model begins with the progenitor on the zero-age main sequence, includes the effects of the star’s wind and ionizing photons, and ends with the SNR’s assimilation by the ISM. We assume that the ISM consists of atomic clouds, molecular clouds, and a hot intercloud phase. The type of SNR that results bears a strong resemblance to N63A in the Large Magellanic Cloud.
Bipolar disorder is a highly heritable polygenic disorder. Recent
enrichment analyses suggest that there may be true risk variants for
bipolar disorder in the expression quantitative trait loci (eQTL) in the
We sought to assess the impact of eQTL variants on bipolar disorder risk
by combining data from both bipolar disorder genome-wide association
studies (GWAS) and brain eQTL.
To detect single nucleotide polymorphisms (SNPs) that influence
expression levels of genes associated with bipolar disorder, we jointly
analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls)
and a genome-wide brain (cortical) eQTL (193 healthy controls) using a
Bayesian statistical method, with independent follow-up replications. The
identified risk SNP was then further tested for association with
hippocampal volume (n = 5775) and cognitive performance
(n = 342) among healthy individuals.
Integrative analysis revealed a significant association between a brain
eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes
factor = 5.48; bipolar disorder P =
5.85×10–5). Follow-up studies across multiple independent
samples confirmed the association of the risk SNP (rs6088662) with gene
expression and bipolar disorder susceptibility (P =
3.54×10–8). Further exploratory analysis revealed that
rs6088662 is also associated with hippocampal volume and cognitive
performance in healthy individuals.
Our findings suggest that 20q11.22 is likely a risk region for bipolar
disorder; they also highlight the informative value of integrating
functional annotation of genetic variants for gene expression in
advancing our understanding of the biological basis underlying complex
disorders, such as bipolar disorder.
This chapter reviews the current status of assisted reproduction techniques in the light of the best evidence available. In order to optimize the results of assisted reproduction, various laboratory modifications have been suggested. These include performing Intracytoplasmic sperm injection (ICSI) rather than in vitro fertilization (IVF) for all oocytes, using co-culturing techniques, assisted hatching techniques, as well as selecting the embryos with the best potential for implantation based on their morphology, their metabolism, or by prolonging their culture in vitro to the blastocyst stage. Embryo transfer (ET) is arguably the most critical step in assisted reproduction and the least successful. Various attempts have been made to improve endometrial receptivity in order to increase the clinical outcome of IVF and ICSI. These include various regimens of luteal support, the use of corticosteroids, the removal of hydrosalpinges, diminishing uterine contractions as well as enhancing the endometrial blood flow.
This research focuses on the design and experimental characterization of two types of asym- metrical MEMS electrothermal microactuators. Both MEMS polysilicon electrothermal microac- tuator designs use resistive (Joule) heating to generate thermal expansion and movement. Deflection and force measurements as a function of applied electrical power are presented.
According to market surveys automotive microsensors will evolve into a multi-billion dollar business by 2005. Key roles are attributed to inertial sensors for passenger safety systems, and mass flow and pressure sensors for engine management systems. Thin film techniques together with silicon bulk or surface micromachining have been established as preferential processes to achieve reduction of sensor size, weight and cost along with improvements of sensor functionality and reliability. Enhanced sensor performance often pushes the limits of process technology and therefore the need arises very early in the MEMS design process to identify materials and geometry related parameters which are critical with respect to their tolerance band specifications. In order to control these critical parameters, automated wafer level test procedures need to be developed (based preferentially on electrical quantities) and additionally considered for in the sensor design phase (design for test). In analogy to microelectronics 2D wafer maps of critical parameters may give hints on how to improve process stability and how to adapt the sensor design in order to optimize yield. Examples of critical model parameter variations include thermal conductivity, thickness, and shear modulus of thin films.
A new polysilicon surface micromachining technique for fabricating and assembling three- dimensional structures has been developed. Single-layer polysilicon elements and laminated polysilicon panels incorporating trapped-glass reinforcement ribs have been successfully fabri- cated on a silicon substrate with robust and continuous hinges that facilitate out-of-plane rotation and assembly. To realize a stable three-dimensional structure, one of the device's elevatable panel components is terminated with an array of open windows, and the mating rotatable element has a matched set of protruding arrowheads/microrivets with flexible barbs that readily flex to facilitate their joining and assembly. Because the arrowhead/microrivet barb tip-to-barb tip sepa- ration is larger than the opening in the mating window, the barbs flex inward as they pass through the open window and then expand to their original shape upon exiting the window, re- sulting in a permanently latched joint and a three-dimensional structure. Three novel arrow- head/microrivet designs have been micromachined to facilitate the latching process, including a simple arrowhead, a high-aspect ratio arrowhead, and a rivet-like structure with a hemispherical shaped cap and a flexible split shank.
We tested the hypothesis that the increased incidence of schizophrenia among Surinamese immigrants to The Netherlands could be explained by a similarly high incidence in Surinam. We conducted a 1-year first-contact incidence study in Surinam and compared the findings with data from a similar study conducted in The Netherlands using the same inclusion criteria and instruments. The risk of developing a schizophrenic disorder was 2.4 times higher (95% CI 1.3–4.2) in Surinamese immigrants than in residents of Surinam. The increased risk is probably due to environmental factors in The Netherlands.
Lawrence F. Brass, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA,
Marina Molino, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy,
Peter J. O'Brien, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA,
Mark Kahn, Departments of Medicine and Pharmacology, and the Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, USA
Thrombin is one of the most potent agonists that platelets will encounter in vivo, but unlike most of the others it is a protease. For years after thrombin was shown to be a platelet activator as well as an effector in the clotting cascade, the precise mechanism by which it activates platelets remained obscure. Binding studies demonstrated high affinity interactions with several sites on the platelet surface, including glycoprotein (GP) Ibα, but efforts to establish that any of these constituted a receptor in the signalling sense were not entirely successful. Substrates on the platelet surface for proteolytic cleavage by thrombin were also identified, including GP V, but cleavage of these sites did not appear to be required for platelet activation by thrombin. Before discussing the receptors that have been identified, it is worth considering what some of the criteria might be for establishing a protein as a true signalling receptor for thrombin. Such criteria would include (i) demonstrating its presence on the platelet surface, (ii) showing that it was a substrate for thrombin or closely associated with a substrate for thrombin, (iii) demonstrating an association of the candidate receptor with mediators or effectors for intracellular signalling cascades, (iv) showing that expression of the candidate receptor could render a cell that was otherwise unresponsive to thrombin capable of responding, and (v) showing that blocking, dismantling or otherwise removing the candidate receptor would reduce platelet responses to thrombin.