Cariprazine (CAR) is an antipsychotic drug for the treatment of schizophrenia (SCZ) and bipolar disorder (BD), and it acts as a partial agonist on the dopamine receptors (DR), D2, and D3. Although ...many single nucleotide polymorphisms (SNPs) in genes coding for these receptors are known to influence response to antipsychotics, to date, no study on CAR pharmacogenetics exists. In this pilot study, we investigated the relationship between SNPs in DRD2 (rs1800497 and rs6277) and DRD3 (rs6280), and response to CAR treatment, evaluated by the psychometric Brief Psychiatric Rating Scale (BPRS), in a cohort of Caucasian patients. We found a significant association between DRD2 rs1800497 and rs6277 and response to CAR treatment. When genotypes were combined into an arbitrary score, the receiver operating characteristic curve analysis showed that using a cut-off value of -2.5 the response to CAR treatment could be predicted with a positive likelihood ratio of 8.0. Our study report, for the first time, a correlation between SNPs in DRD2 and response to CAR treatment. After confirmation in a larger cohort of patients, our results could open the way for the identification of new tools for the provision of response to CAR treatment.
Fahr's disease (FD) is a rare disorder, characterized by basal ganglia calcification and presenting with movement disorders, speech impairment, cognitive deficits, and neuropsychiatric symptoms. ...Psychotic disorders related to FD are barely described in the literature, and knowledge is missing concerning pathophysiology, course, and management. Here, we report on the long-term follow-up of a patient who had three acute episodes of FD-psychosis characterized by bizarre delusions and behavioral disorganization, without hallucinations. Genetic and metabolic causes of FD were ruled out. In all three episodes, olanzapine monotherapy rapidly and completely resolved psychosis, without inducing metabolic syndrome and extrapyramidal symptoms. In addition to the acute decompensations, the patient presented a tame, introverted, industrious, and perfectionistic personality, which we could interpret as the "
" described for many other basal ganglia disorders. Moreover, bizarre appearance, reduced affectivity, abulia, concrete speech, and stiff motricity in the context of a mild asymmetric extrapyramidal syndrome characterized the mental status. The cognitive profile was initially marked by executive difficulties and partial agnosia, with an IQ of 86. In the course of 10 years, the patient suffered from an ischemic stroke in the left superior temporal gyrus, which provoked a decline in memory and executive functions, without any impact on the psychiatric picture. Antiphospholipid antibody syndrome emerged as the underlying cause; thus, for the first time in the literature, an overlap of FD and antiphospholipid antibody syndrome is described here. This case report stresses once more the need for better integration of psychiatry and neurology and for the investigation of secondary causes of late-onset psychosis.
Metal additive manufacturing, particularly laser powder bed fusion, is increasingly used in the gas turbine industry for the fabrication of channels with small diameters for conformal cooling and ...flow passage applications. A critical challenge in this context lies in evaluating aspects such as the geometrical and hydraulic diameters, the effective area and the roughness on the internal surface of the channel that affects the flow functionality. This paper proposes a new method to evaluate the geometrical and functional equivalent diameters, i.e., the hydraulic diameter of cylindrical channels and the mean surface topography height on the internal channel surface, using X-ray computed tomography. The developed methods were validated with experimental flow tests, considering the mean surface topography height to be equivalent to the hydrodynamic sand grain roughness, thereby determining the hydraulic diameter and the associated effective area. The method is a much faster approach to determining the available hydraulic diameter compared to flow tests and offers the possibility of evaluating the internal surface characteristics, with discrepancies between the two approaches being less than ±3%.
Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response ...to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles.
We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRS
) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRS
and PRS
) were also tested for their association with response to treatment.
PRS
was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03-1.26,
= 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02-1.37,
= 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04-1.47,
= 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04-1.55,
= 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRS
and PRS
were not significantly associated with response to treatment.
PRS
defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice.
Cariprazine is a third-generation antipsychotic, approved for the treatment of schizophrenia and bipolar disorder and used off-label for schizoaffective disorder and treatment-resistant depression. ...Cariprazine is a partial agonist at dopamine receptors D2 and D3 and serotonin receptor 5HT1A and an antagonist at serotonin receptors 5HT2B and 5HT2A. It is metabolized by CYP3A4 in desmetyl-cariprazine and didesmethyl-cariprazine, both active metabolites with a half-life of 1-2 days and 2-3 weeks, respectively.
Here we show the cases of 3 outpatients diagnosed with bipolar I disorder (two patients) and schizoaffective disorder (one patients) and characterized by low adherence to treatment, satisfactory cognitive and personal functioning and average disease severity to whom we administered cariprazine as a monotherapy, on a two-times a week schedule (i.e., every 72-96 h). We evaluated response to treatment and disease remission according to conventional definitions, using rating scales BPRS, PANSS and BDI-II. Two-times a week treatment was set either after a disease relapse (one patient), after a sustained remission obtained with daily administration of cariprazine (one patient) or since our first evaluation (one patient). After 4 weeks of treatment all three patients satisfied criteria for response to treatment and remission, a result that was sustained for 8 (in one patients) and 12 months (in other two patients) and still ongoing.
Reported results support our hypothesis that long half-lives of cariprazine and its metabolites provide an adequate therapeutic response with a two-times a week administration. In selected patients, cariprazine administered as a "oral long-acting" seems effective in treating acute episodes of illness and in sustaining remission, combining advantages of oral and long-acting injectable antipsychotics concerning therapeutic alliance.
The Online Monitoring System (OMS) at the Compact Muon Solenoid experiment (CMS) at CERN aggregates and integrates different sources of information into a central place and allows users to view, ...compare and correlate information. It displays real-time and historical information. The tool is heavily used by run coordinators, trigger experts and shift crews, to ensure the quality and efficiency of data taking. It provides aggregated information for many use cases including data certification. OMS is the successor of Web Based Monitoring (WBM), which was in use during Run 1 and Run 2 of the LHC. WBM started as a small tool and grew substantially over the years so that maintenance became challenging. OMS was developed from scratch following several design ideas: to strictly separate the presentation layer from the data aggregation layer, to use a well-defined standard for the communication between presentation layer and aggregation layer, and to employ widely used frameworks from outside the HEP community. A report on the experience from the operation of OMS for the first year of data taking of Run 3 in 2022 is presented.
The CMS data acquisition (DAQ) is implemented as a service-oriented architecture where DAQ applications, as well as general applications such as monitoring and error reporting, are run as ...self-contained services. The task of deployment and operation of services is achieved by using several heterogeneous facilities, custom configuration data and scripts in several languages. In this work, we restructure the existing system into a homogeneous, scalable cloud architecture adopting a uniform paradigm, where all applications are orchestrated in a uniform environment with standardized facilities. In this new paradigm DAQ applications are organized as groups of containers and the required software is packaged into container images. Automation of all aspects of coordinating and managing containers is provided by the Kubernetes environment, where a set of physical and virtual machines is unified in a single pool of compute resources. We demonstrate that a container-based cloud architecture provides an acrossthe-board solution that can be applied for DAQ in CMS. We show strengths and advantages of running DAQ applications in a container infrastructure as compared to a traditional application model.
The CMS Orbit Builder for the HL-LHC at CERN Amoiridis, Vassileios; Behrens, Ulf; Bocci, Andrea ...
EPJ Web of Conferences,
2024, Letnik:
295
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
The Compact Muon Solenoid (CMS) experiment at CERN incorporates one of the highest throughput data acquisition systems in the world and is expected to increase its throughput by more than a factor of ...ten for High-Luminosity phase of Large Hadron Collider (HL-LHC). To achieve this goal, the system will be upgraded in most of its components. Among them, the event builder software, in charge of assembling all the data read out from the different sub-detectors, is planned to be modified from a single event builder to an orbit builder that assembles multiple events at the same time. The throughput of the event builder will be increased from the current 1.6 Tb/s to 51 Tb/s for the HL-LHC orbit builder. This paper presents preliminary network transfer studies in preparation for the upgrade. The key conceptual characteristics are discussed, concerning differences between the CMS event builder in Run 3 and the CMS Orbit Builder for the HL-LHC. For the feasibility studies, a pipestream benchmark, mimicking event-builder-like traffic has been developed. Preliminary performance tests and results are discussed.
The data acquisition (DAQ) of the Compact Muon Solenoid (CMS) experiment at CERN, collects data for events accepted by the Level-1 Trigger from the different detector systems and assembles them in an ...event builder prior to making them available for further selection in the High Level Trigger, and finally storing the selected events for offline analysis. In addition to the central DAQ providing global acquisition functionality, several separate, so-called “MiniDAQ” setups allow operating independent data acquisition runs using an arbitrary subset of the CMS subdetectors. During Run 2 of the LHC, MiniDAQ setups were running their event builder and High Level Trigger applications on dedicated resources, separate from those used for the central DAQ. This cleanly separated MiniDAQ setups from the central DAQ system, but also meant limited throughput and a fixed number of possible MiniDAQ setups. In Run 3, MiniDAQ-3 setups share production resources with the new central DAQ system, allowing each setup to operate at the maximum Level-1 rate thanks to the reuse of the resources and network bandwidth. Configuration management tools had to be significantly extended to support the synchronization of the DAQ configurations needed for the various setups. We report on the new configuration management features and on the first year of operational experience with the new MiniDAQ-3 system.
