Response to antipsychotic drugs in treatment-resistant schizophrenia : Conclusions based on systematic review

Peer reviewe

Predictors of response to pharmacological treatments in treatment-resistant schizophrenia - A systematic review and meta-analysis

Background: As the burden of treatment-resistant schizophrenia (TRS) on patients and society is high it is important to identify predictors of response to medications in TRS. The aim was to analyse whether baseline patient and study characteristics predict treatment response in TRS in drug trials. Methods: A comprehensive search strategy completed in PubMed, Cochrane and Web of Science helped identify relevant studies. The studies had to meet the following criteria: English language clinical trial of pharmacological treatment of TRS, clear definition of TRS and response, percentage of response reported, at least one baseline characteristic presented, and total sample size of at least 15. Meta-regression techniques served to explore whether baseline characteristics predict response to medication in TRS. Results: 77 articles were included in the systematic review. The overall sample included 7546 patients, of which 41% achieved response. Higher positive symptom score at baseline predicted higher response percentage. None of the other baseline patient or study characteristics achieved statistical significance at predicting response. When analysed in groups divided by antipsychotic drugs, studies of clozapine and other atypical antipsychotics produced the highest response rate. Conclusions: This meta-analytic review identified surprisingly few baseline characteristics that predicted treatment response. However, higher positive symptoms and the use of atypical antipsychotics - particularly clozapine -was associated with the greatest likelihood of response. The difficulty involved in the prediction of medication response in TRS necessitates careful monitoring and personalised medication management. There is a need for more investigations of the predictors of treatment response in TRS.Peer reviewe

Radiation Tolerance of CMOS Monolithic Active Pixel Sensors with Self-Biased Pixels

CMOS Monolithic Active Pixel Sensors (MAPS) are proposed as a technology for various vertex detectors in nuclear and particle physics. We discuss the mechanisms of ionizing radiation damage on MAPS hosting the the dead time free, so-called self bias pixel. Moreover, we discuss radiation hardened sensor designs which allow operating detectors after exposing them to irradiation doses above 1 Mra

Airway obstruction, serum vitamin D and mortality in a 33-year follow-up study

Background and objective: Chronic obstructive pulmonary disease and low vitamin D status predict mortality, but their combined effect on mortality remains inconclusive. We aimed to investigate a joint effect of airway obstruction and vitamin D status on mortality in a nationally representative cohort. Methods: We analysed data of 6676 Finnish adults participating between 1978 and 1980 in a national health examination survey, undergoing spirometry and having all necessary data collected. We followed them up in national registers through record linkage until 31 December 2011. We categorised the subjects with obstruction using the lower limit of normal (LLN) and the measured serum 25-hydroxyvitamin-D (s-25(OH)D) into tertiles. Results: Both obstruction and low s-25(OH) D independently predicted mortality in a multivariate model adjusted also for age, sex, smoking, education, leisure physical activity, body mass index, asthma and serum C-reactive protein. However, a statistically significant (p = 0.007) interaction emerged: the adjusted mortality HRs (95% CI's) for s-25(OH)D in tertiles among the subjects without and with obstruction were 1.00 (lowest), 0.96 (0.87-1.05) and 0.89 (0.81-0.98); and 1.00, 0.96 (0.71-1.31) and 0.57 (0.40-0.80), respectively. Conclusions: In conclusion, obstruction and low s-25(OH)D predict mortality independently of each other. Our findings suggest that low vitamin D status might be particularly detrimental among subjects with obstruction.Peer reviewe

CMOS pixel sensor development: a fast read-out architecture with integrated zero suppression

International audienceCMOS Monolithic Active Pixel Sensors (MAPS) have demonstrated their strong potential for tracking devices, particularly for flavour tagging. They are foreseen to equip several vertex detectors and beam telescopes. Most applications require high read-out speed, which imposes sensors to feature digital output with integrated zero suppression. The most recent development of MAPS at IPHC and IRFU addressing this issue will be reviewed. The design architecture, combining pixel array, column-level discriminators and zero suppression circuits, will be presented. Each pixel features a preamplifier and a correlated double sampling (CDS) micro-circuit reducing the temporal and fixed pattern noises. The sensor is fully programmable and can be monitored. It will equip experimental apparatus starting data taking in 2009/2010

A ten thousand frames per second readout MAPS for the EUDET beam telescope

Designed and manufactured in a commercial CMOS 0.35 μm OPTO process for equipping the EUDET beam telescope, MIMOSA26 is the first reticule size pixel sensor with digital output and integrated zero suppression. It features a matrix of pixels with 576 rows and 1152 columns, covering an active area of ~224 mm2. A single point resolution of about 4 μm was obtained with a pixel pitch of 18.4 μm. Its architecture allows a fast readout frequency of ~10 k frames/s. The paper describes the chip design, test and major characterisation outcome

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

Clinical and radiological features related to the growth potential of meningioma

Clinical and radiological features that help predict the growth potential of meningioma would be beneficial. The purpose of this study is to clarify the characteristics related to proliferating potential using the MIB-1 staining index. We analyzed the relationship of MIB-1 staining indices to characteristics of 342 consecutive patients with meningioma surgically removed between 1995 and 2004 by logistic regression analysis. One hundred and forty-nine of the patients with meningioma were ≥60 in age; 89 male; 48 recurrent; 203 symptomatic; 157 at the skull base; 124 over 20 cm(3); 24 multiple; 136 with edema; 117 with calcification. The MIB-1 staining index in 56 of 296 grade I meningiomas in WHO classification was ≥ 3.0; in 27 of 28 grade II; and in 17 of 18 grade III, respectively. Logistic regression analysis demonstrated that male (odds ratio [OR], 2.374, p=0.003), recurrence (OR, 7.574, p=0.0001), skull base (OR, 0.540, p=0.035), calcification (OR, 0.498, p=0.019) were independent risk factors for a high MIB-1 staining index (≥3.0); age, symptomatic, volume, multiple, edema were not. Male, recurrence, non-skull base, absence of calcification are independent risk factors for a high proliferative potential. These should be taken into consideration when managing meningiomas

Assessment of Epidermal Growth Factor Receptor (EGFR) expression in human meningioma

<p>Abstract</p> <p>Purpose</p> <p>This study explores whether meningioma expresses epidermal growth factor receptor (EGFR) and determines if there is a correlation between the WHO grade of this tumor and the degree of EGFR expression.</p> <p>Methods</p> <p>Following institutional review board approval, 113 meningioma specimens from 89 patients were chosen. Of these, 85 were used for final analysis. After a blinded review, immunohistochemical stains for EGFR were performed. Staining intensity (SI) was scored on a scale 0-3 (from no staining to strong staining). Staining percentage of immunoreactive cells (SP) was scored 1-5 (from the least to the maximum percent of the specimen staining). Immunohistochemical score (IHS) was calculated as the product of SI and SP.</p> <p>Results</p> <p>Eighty-five samples of meningioma were classified in accordance with World Health Organization (WHO) criteria: benign 57/85 (67%), atypical 23/85 (27%), and malignant 5/85 (6%). The majority of samples demonstrated a moderate SI for EGFR. IHS for EGFR demonstrated a significant association between SI and histopathologic subtype. Also, there was a correlation between the SP and histopathologic subtype (p = 0.029). A significant association was determined when the benign and the atypical samples were compared to the malignant with respect to the SP (p = 0.009). While there was a range of the IHS for the benign and the atypical histologic subtypes, malignant tumors exhibited the lowest score and were statistically different from the benign and the atypical specimens (p < 0.001).</p> <p>Conclusions</p> <p>To our knowledge, this represents the largest series of meningioma samples analyzed for EGFR expression reported in the literature. EGFR expression is greatest in benign meningiomas and may serve a potential target for therapeutic intervention with selective EGFR inhibitors.</p