Introduction
Three generations of antipsychotics, all of which are based on the dopaminergic hypothesis of schizophrenia, are available for clinical use. Still, more than 66% of the patients ...diagnosed with schizophrenia spectrum disorders (SSD) could not achieve remission. Also, the glutamatergic hypothesis of schizophrenia is supported by translational models of this disease, even if the antipsychotics derived from this conceptual framework are not yet available on the market. However, the need for new pathogenesis models for schizophrenia and new generations of antipsychotics is acute, therefore, an exploration of the antipsychotics in the pipeline could be helpful in understanding the current stage of research in schizophrenia.
Objectives
To assess the evidence supporting the potential benefits of new antipsychotics in the pipeline.
Methods
A literature review was performed through the main electronic databases PubMed, Cochrane, Clarivate/Web Of Science, and EMBASE) and clinical trials repositories (US National Library of Medicine and World Health Organization Clinical Trials Registry Platform) using the search paradigm “antipsychotics” AND “schizophrenia” AND “non-dopaminergic” AND “non-glutamatergic”. All papers published between January 2010 and September 2022 were included.
Results
Xanomeline/trospium (xanomeline is a muscarinic M1/M4 receptor agonist at the central nervous system, while trospium limits its peripheral effects) was efficient for schizophrenia in one phase III clinical trial. Pimavanserin (a selective 5HT2A inverse agonist and antagonist) was efficient in improving negative symptoms of schizophrenia in a phase II trial. Roluperidone (a 5HT2A and σ2 receptor antagonist) has been associated with favorable results in phase III clinical trials, mainly on negative symptoms of schizophrenia. SEP-363856 is a TAAR-1 agonist and 5HT1A agonist, currently explored in phase III clinical trials for schizophrenia. MK-8189 is a phosphodiesterase 10A inhibitor, investigated in phase III clinical trials for schizophrenia.
Conclusions
Based on the retrieved data in the literature, multiple mechanisms, other than glutamatergic and dopaminergic pathways, are currently being investigated, and many of the antipsychotics based on these mechanisms are in the advanced stage of research. This is important not only for the clinical need to find more efficient and tolerable drugs for patients with schizophrenia but also because they may shed new light on the pathogenesis of this disease.
Disclosure of Interest
None Declared
In hydropower systems among hydropower plants there are storage pump units. In order to ensure higher flow rate, the pumps have constructive differences besides regular. Consequently, the complex ...shape of the suction-elbow with symmetric inlet generates an unsteady flow which is ingested by impeller. These phenomena also generate stronger unsteady flow conditions, such as stall, wakes, turbulence and pressure fluctuations, which affect the overall mechanical behaviour of the pump with vibration, noise and radial and axial forces on the rotor. Alternatively, an axial rotor can be installed in front of the impeller. In this case, the non-uniformity flow will be decreased, and the static pressure will be increased at the impeller inlet. Consequently, the efficiency behaviour practically remains unchanged while the cavitational behaviour is improved. The paper investigates experimentally a pump system with the axial rotor having variable speed, while the pump impeller has constant speed. First, the paper presents the experimental test rig, the control and acquisition system. Second, is presented the pump system equipped with the clutch in order to have variable speed for the axial rotor. Thirdly, the experimental results concentrate on the axial rotor influence on the efficiency behaviour. The last section draws the conclusions.
In hydropower systems among hydropower plants there are integrated pumping stations (PS). In order to ensure higher flow rate, the pumps have constructive differences besides regular. Consequently, ...the complex shape of the suction-elbow with symmetric inlet generates an unsteady flow which is ingested by impeller. These phenomena's also generate stronger unsteady flow conditions, such as stall, wakes, turbulence and pressure fluctuations, which affect the overall mechanical behaviour of the pump with vibration, noise and radial and axial forces on the rotor. Alternatively, an axial rotor can be installed in front of the impeller. In this case, the flow non-uniformity will be decreased and the static pressure will be increased at the impeller inlet. Consequently, the efficiency behaviour practically remains unchanged while the cavitational behaviour is improved. From the assembly between axial rotor and centrifugal impeller, the axial rotor usually works in cavitation and is often replaced. The paper investigates experimentally and numerically the comparison between pump impeller without and with axial rotor hydrodynamics taking into account the flow given by the symmetrical suction elbow. Full three-dimensional turbulent numerical investigation of the symmetrical suction elbow, with axial rotor and without, pump impeller and volute are performed. The hydrodynamic analysis confirms that once the axial rotor is mounted in front of the pump impeller increase the static pressure and the incidence angle is improved at the inlet of the pump impeller.
A strategy of urban sewage centralized management is implemented in the most cities (e.g. Timisoara). All wastewater is collected and conveyed to a central location for treatment or disposal. In the ...urban area, the rainwater is embedded in the wastewater management. Seven rainwater pumps are installed in a wastewater treatment plant to protect it against flooding. This type of pumps is vertically installed in Timisoara's wastewater treatment plant in order to pump the additional rainwater protecting it. Several catastrophic events have been occurred at the rainwater pumps tacking them out of service after a limited operation time. The fastening bolts of the blades are brittle broken due to the clog of the impeller with waste rag balls. The cumulated operation time is examined for each rainwater pump together with the catastrophic events identified in service. The mechanical properties of the waste fibres are experimentally determined with respect to it area in order to assess the clog/rag conditions corresponding to the clearance between the impeller blades and housing. Next, the inertial torque associated to the rotating parts of the rainwater pump is estimated to check the level when sudden locking occurs due to the impeller clogging. The maximum stress level of the fastening bolts is exceeded when the impeller is partially clogged or ragged. As a result, the root cause of the problem is associated with the ragging level of the impeller. A solution is proposed to avoid these problems.
The storage pumps are equipped with various types of inlet casings. The flow nonuniformity is generated by the suction elbows being ingested by the impeller leading to unsteady phenomena and worse ...cavitational behaviour. A symmetrical suction elbow model corresponding to the double flux storage pump was manufactured and installed on the test rig in order to assess the flow field at the pump inlet. The experimental investigations are performed for 9 discharge values from 0.5 to 1.3 of nominal discharge. LDV measurements are performed on the annular section of the pump inlet in order to quantify the flow non-uniformity generated by the symmetrical suction elbow. Both axial and circumferential velocity components are simultaneously measured on the half plane (180 degree ) of the annular inlet section along to 19 survey axis with 62 points on each. The flow field on the next half plane is determined tacking into account the symmetry. As a result, the flow map on the pump inlet annular section is reconstructed revealing a significant variation of the circumferential velocity component. The absolute flow angle is computed showing a significant variation of plus or minus 38 degree .
The paper investigates the hydrodynamic field generated by the symmetrical suction elbow at the pump impeller inlet. The full three-dimensional turbulent numerical investigation of the flow in the ...symmetrical suction elbow is performed using FLUENT then the flow non-uniformity generated by it is numerically computed. The numerical results on the annular cross section are qualitatively and quantitatively validated against LDV data. A good agreement between numerical results and experimental data is obtained on this cross section located downstream to the suction elbow and upstream to the pump impeller. The hydrodynamic flow structure with four vortices is identified plotting the vorticity field. The largest values of the vorticity magnitude are identified in the center of both vortices located behind the shaft. The vortex core location is plotted on four annular cross sections located along to the cylindrical part between the suction elbow and the pump inlet. Also, the three-dimensional distribution of the vortex core filaments is visualized and extracted. The shapes of vortex core filaments located behind the pump shaft agree well with its visualization performed on the test rig. As a result, the three-dimensional complex geometry of the suction elbow and the pump shaft are identified as the main sources of the flow non-uniformity at the pump inlet.
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