Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials

BACKGROUND: Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo. METHODS: We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated. RESULTS: Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth. CONCLUSION: It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations

Functional Sensory-Motor Performance Following Long Term Space Flight: The First Results of "Field Test" Experiment

The effect that extended-duration space flights may have on human space travelers, including exploration missions, is widely discussed at the present time. Specifically, there is an increasing amount of evidence showing that the physical capacity of cosmonauts is significantly reduced after long-duration space flights. It is evident that the most impaired functions are those that rely on gravity, particularly up right posture and gait. Because of the sensorimotor disturbances manifested in the neurology of the posture and gait space flight and postflight changes may also be observed in debilitating motion sickness. While the severity of particular symptoms varies, disturbances in spatial orientation and alterations in the accuracy of voluntary movements are persistently observed after long-duration space flights. At this time most of the currently available data are primarily descriptive and not yet suitable for predicting operational impacts of most sensorimotor decrements observed upon landing on planetary surfaces or asteroids. In particular there are no existing data on the recovery dynamics or functionality of neurological, cardiovascular or muscle performance making it difficult to model or simulate the cosmonauts' activity after landing and develop the appropriate countermeasure that will ensure the rapid and safe recovery of crewmembers immediately after landing in what could be hostile environments. However and as a starting position, the videos we have acquired during recent data collection following the long duration flights of cosmonauts and astronauts walking and performing other tasks shortly after return from space flight speak volumes about their level of deconditioning. A joint Russian-American team has developed a new study specifically to address the changes in crewmembers performance and the recovery of performance with the intent of filling the missing data gaps. The first (pilot) phase of this study includes recording body kinematics and quantifying the coordination and timing of relatively simple basic movements - transition from seated and prone positions to standing, walking, stepping over obstacles, tandem walking, muscle compliance, as well as characteristics of postural sway and orthostatic tolerance. Testing for changes in these parameters have been initiated in the medical tent at the landing site. The first set of experiments showed that during the first hour after landing, cosmonauts and astronauts were able to execute (although slower and with more effort than preflight) simple movements such as egress from a seated or prone position and also to remain standing for 3.5 minutes without exhibiting pronounced cardiovascular changes. More challenging tests, however, demonstrated a prominent reduction in coordination - the obstacle task, for example, was performed at much slower speed and with a marked overestimation of the obstacle height and tandem walking was greatly degraded suggesting significant changes in proprioception, brainstem and vestibular function. There is some speculation that the neural changes, either from the bottom-up or top down may be long lasting; requiring compensatory responses that will modify or mask the adverse responses we have observed. Furthermore, these compensatory responses may actually be beneficial, helping achieve a more rapid adaptation to both weightlessness and a return to earth

Model for initiation of quality factor degradation at high accelerating fields in superconducting radio-frequency cavities

A model for the onset of the reduction in SRF cavity quality factor, the so-called Q-drop, at high accelerating electric fields is presented. Breakdown of the surface barrier against magnetic flux penetration at the cavity equator is considered to be the critical event that determines the onset of Q-drop. The worst case of triangular grooves with low field of first flux penetration Hp, as analyzed previously by Buzdin and Daumens, [1998 Physica C 294: 257], was adapted. This approach incorporates both the geometry of the groove and local contamination via the Ginzburg-Landau parameter kappa, so the proposed model allows new comparisons of one effect in relation to the other. The model predicts equivalent reduction of Hp when either roughness or contamination were varied alone, so smooth but dirty surfaces limit cavity performance about as much as rough but clean surfaces do. When in combination, contamination exacerbates the negative effects of roughness and vice-versa. To test the model with actual data, coupons were prepared by buffered chemical polishing and electropolishing, and stylus profilometry was used to obtain distributions of angles. From these data, curves for surface resistance generated by simple flux flow as a function of magnetic field were generated by integrating over the distribution of angles for reasonable values of kappa. This showed that combined effects of roughness and contamination indeed reduce the Q-drop onset field by ~30%, and that that contamination contributes to Q-drop as much as roughness. The latter point may be overlooked by SRF cavity research, since access to the cavity interior by spectroscopy tools is very difficult, whereas optical images have become commonplace. The model was extended to fit cavity test data, which indicated that reduction of the superconducting gap by contaminants may also play a role in Q-drop.Comment: 15 pages with 7 figure

First Observation of Self-Amplified Spontaneous Emission in a Free-Electron Laser at 109 nm Wavelength

We present the first observation of Self-Amplified Spontaneous Emission (SASE) in a free-electron laser (FEL) in the Vacuum Ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approx. 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width and intensity fluctuations all corroborate the existing models for SASE FELs.Comment: 6 pages including 6 figures; e-mail: [email protected]

The Superconducting TESLA Cavities

The conceptional design of the proposed linear electron-positron collider TESLA is based on 9-cell 1.3 GHz superconducting niobium cavities with an accelerating gradient of Eacc >= 25 MV/m at a quality factor Q0 > 5E+9. The design goal for the cavities of the TESLA Test Facility (TTF) linac was set to the more moderate value of Eacc >= 15 MV/m. In a first series of 27 industrially produced TTF cavities the average gradient at Q0 = 5E+9 was measured to be 20.1 +- 6.2 MV/m, excluding a few cavities suffering from serious fabrication or material defects. In the second production of 24 TTF cavities additional quality control measures were introduced, in particular an eddy-current scan to eliminate niobium sheets with foreign material inclusions and stringent prescriptions for carrying out the electron-beam welds. The average gradient of these cavities at Q0 = 5E+9 amounts to 25.0 +- 3.2 MV/m with the exception of one cavity suffering from a weld defect. Hence only a moderate improvement in production and preparation techniques will be needed to meet the ambitious TESLA goal with an adequate safety margin. In this paper we present a detailed description of the design, fabrication and preparation of the TESLA Test Facility cavities and their associated components and report on cavity performance in test cryostats and with electron beam in the TTF linac. The ongoing R&D towards higher gradients is briefly addressed.Comment: 45 pages (Latex), 39 figures (Encapsulated Postscript), 53 Author

Physiological Observations and Omics to Develop Personalized Sensormotor Adaptability Countermeasures Using Bed Rest and Space Flight Data

Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the re-adapation phase following a return to an earth-gravitational environment. These alterations may disrupt the ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from space flight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual space flight, which crewmembers are likely to experience the greatest challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures that include: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; 3) genotype markers for genetic polymorphisms in Catechol-O-Methyl Transferase, Dopamine Receptor D2, Brain-derived neurotrophic factor and genetic polymorphism of alpha2-adrenergic receptor that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration space flight and an analog bed rest environment. We will be conducting a retrospective study leveraging data already collected from relevant ongoing/completed bed rest and space flight studies. These data will be combined with predictor metrics that will be collected prospectively - behavioral, brain imaging and genomic measures; from these returning subjects to build models for predicting post-mission (bed rest - non-astronauts or space flight - astronauts) adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions against decrements in post-mission adaptive capability. This ability will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes

Recovery of Functional Sensorimotor Performance Following Long Duration Space Flight (Field Test)

No abstract availabl

Postflight Quiet Stance Stability of Astronauts Following Recovery From a Simulated Fall

INTRODUCTION: Astronauts returning from space flight universally present with postural ataxia. Throughout the Space Shuttle Program, measurement of ataxia has concentrated on sway in the anterior-posterior plane. Implementation of an interdisciplinary pre- and postflight study (Functional Task Test, FTT) designed to evaluate both astronaut postflight functional performance and related physiological changes has allowed the investigation of postural instability by characterizing dynamic stabilographic sway patterns. METHODS: Six astronauts from short-duration (Shuttle) and three from long-duration (ISS) flights were required to recover from a simulated fall. Subjects with eyes open, wearing running shoes lay prone on the floor for 2 minutes and then quickly stood up, maintained a quiet stance for 3 minutes, arms relaxed along the side of the body, and feet comfortably placed on the force plate. Crewmembers were tested twice before flight, on landing day (Shuttle only), and 1, 6, and 30 days after flight. Anterior-posterior (AP) and medial-lateral (ML) center-of-pressure (COP) coordinates were calculated from the ground reaction forces collected at 500 Hz. The 3-minute quiet stance trial was broken into three 1-minute segments for stabilogram diffusion analysis. A mean sway speed (rate of change of COP displacement) was also calculated as an additional postural stability parameter. RESULTS/CONCLUSION: While there was considerable variation, most of crewmembers tested exhibited increased stochastic activity evidenced by larger short-term COP diffusion coefficients postflight in both the AP and ML planes, suggesting significant changes in postural control mechanisms, particularly control of lower limb muscle function. As expected, postural instability of ISS astronauts on the first day postflight was similar to that of Shuttle crewmembers on landing day. Recoveries of stochastic activity and mean sway speed to baseline levels were typically observed by the 30th day postflight for both long-duration and short-duration crewmembers. Dynamic postural stability characteristics obtained in this low-impact study complement the data measured with computerized dynamic posturography

Action anticipation based on an agent's epistemic state in toddlers and adults

Do toddlers and adults engage in spontaneous Theory of Mind (ToM)? Evidence from anticipatory looking (AL) studies suggests that they do. But a growing body of failed replication studies raised questions about the paradigm’s suitability. In this multi-lab collaboration, we test the robustness of spontaneous ToM measures. We examine whether 18- to 27-month-olds’ and adults’ anticipatory looks distinguish between two basic forms of an agent’s epistemic states: knowledge and ignorance. In toddlers [ANTICIPATED n = 520 50% FEMALE] and adults [ANTICIPATED n = 408, 50% FEMALE] from diverse ethnic backgrounds, we found [SUPPORT/NO SUPPORT] for epistemic state-based action anticipation. Future research can probe whether this conclusion extends to more complex kinds of epistemic states, such as true and false beliefs