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

Nanoscale phase-engineering of thermal transport with a Josephson heat modulator

Macroscopic quantum phase coherence has one of its pivotal expressions in the Josephson effect [1], which manifests itself both in charge [2] and energy transport [3-5]. The ability to master the amount of heat transferred through two tunnel-coupled superconductors by tuning their phase difference is the core of coherent caloritronics [4-6], and is expected to be a key tool in a number of nanoscience fields, including solid state cooling [7], thermal isolation [8, 9], radiation detection [7], quantum information [10, 11] and thermal logic [12]. Here we show the realization of the first balanced Josephson heat modulator [13] designed to offer full control at the nanoscale over the phase-coherent component of thermal currents. Our device provides magnetic-flux-dependent temperature modulations up to 40 mK in amplitude with a maximum of the flux-to-temperature transfer coefficient reaching 200 mK per flux quantum at a bath temperature of 25 mK. Foremost, it demonstrates the exact correspondence in the phase-engineering of charge and heat currents, breaking ground for advanced caloritronic nanodevices such as thermal splitters [14], heat pumps [15] and time-dependent electronic engines [16-19].Comment: 6+ pages, 4 color figure

Quantum critical states and phase transitions in the presence of non equilibrium noise

Quantum critical points are characterized by scale invariant correlations and correspondingly long ranged entanglement. As such, they present fascinating examples of quantum states of matter, the study of which has been an important theme in modern physics. Nevertheless very little is known about the fate of quantum criticality under non equilibrium conditions. In this paper we investigate the effect of external noise sources on quantum critical points. It is natural to expect that noise will have a similar effect to finite temperature, destroying the subtle correlations underlying the quantum critical behavior. Surprisingly we find that in many interesting situations the ubiquitous 1/f noise preserves the critical correlations. The emergent states show intriguing interplay of intrinsic quantum critical and external noise driven fluctuations. We demonstrate this general phenomenon with specific examples in solid state and ultracold atomic systems. Moreover our approach shows that genuine quantum phase transitions can exist even under non equilibrium conditions.Comment: 9 pages, 2 figure

Knowledge and care seeking practices for ear infections among parents of under five children in Kigali, Rwanda : a cross-sectional study

Background: Infections affecting the middle ear are a common childhood occurrence. Some cases may present with ear discharge through a tympanic membrane perforation which may heal spontaneously. However, up to 5% or more cases of those affected have persistent ear discharge. A number of barriers contribute towards delayed presentation at health facilities for treatment of ear infections. We conducted a study to evaluate parents’ and caregivers’ knowledge and care seeking practices for ear infections in children under five in Gasabo district in Kigali, Rwanda. Methods: Parents/guardians (n = 810) were interviewed using a structured questionnaire to elicit their knowledge of ear infections in children under five and their attitude to seeking care for their children. Results: The mean age of the respondents was 31.27 years (SD = 7.88, range 17–83). Considering an average of knowledge parameters which included causes, symptoms, prevention, treatment and consequences of ear infections, we found that 76.6% (622) of respondents were knowledgeable about ear infections. We defined a positive practice as seeking medical treatment (community health workers or health facility) and this was found in 89.1% (722) respondents. Correlating knowledge with choice of seeking treatment, respondents were 33% less likely to practice medical pluralism (OR = 0.33, CI 0.11–0.97, P = 0.043) if they were familiar with infections. Moreover, urban dweller were 1.7 times more likely to know ear infections compared to rural dwellers (OR = 1.70, CI 1.22–2.38, P = 0.002). Conclusion: The majority of respondents had good knowledge and positive attitudes and practices about ear infection. However, medical pluralism was common. There is need to improve the community’s awareness and access to primary health care facilities for the care of ear infections especially in rural areas of Rwanda

The working alliance in a randomized controlled trial comparing online with face-to-face cognitive-behavioral therapy for depression

Background: Although numerous efficacy studies in recent years have found internet-based interventions for depression to be effective, there has been scant consideration of therapeutic process factors in the online setting. In face-to face therapy, the quality of the working alliance explains variance in treatment outcome. However, little is yet known about the impact of the working alliance in internet-based interventions, particularly as compared with face-to-face therapy. Methods: This study explored the working alliance between client and therapist in the middle and at the end of a cognitive-behavioral intervention for depression. The participants were randomized to an internet-based treatment group (n = 25) or face-to-face group (n = 28). Both groups received the same cognitive behavioral therapy over an 8-week timeframe. Participants completed the Beck Depression Inventory (BDI) post-treatment and the Working Alliance Inventory at mid- and post- treatment. Therapists completed the therapist version of the Working Alliance Inventory at post-treatment. Results: With the exception of therapists' ratings of the tasks subscale, which were significantly higher in the online group, the two groups' ratings of the working alliance did not differ significantly. Further, significant correlations were found between clients' ratings of the working alliance and therapy outcome at post-treatment in the online group and at both mid- and post-treatment in the face-to-face group. Correlation analysis revealed that the working alliance ratings did not significantly predict the BDI residual gain score in either group. Conclusions: Contrary to what might have been expected, the working alliance in the online group was comparable to that in the face-to-face group. However, the results showed no significant relations between the BDI residual gain score and the working alliance ratings in either group

Landau-Zener-Stuckelberg interferometry

A transition between energy levels at an avoided crossing is known as a Landau-Zener transition. When a two-level system (TLS) is subject to periodic driving with sufficiently large amplitude, a sequence of transitions occurs. The phase accumulated between transitions (commonly known as the Stuckelberg phase) may result in constructive or destructive interference. Accordingly, the physical observables of the system exhibit periodic dependence on the various system parameters. This phenomenon is often referred to as Landau-Zener-Stuckelberg (LZS) interferometry. Phenomena related to LZS interferometry occur in a variety of physical systems. In particular, recent experiments on LZS interferometry in superconducting TLSs (qubits) have demonstrated the potential for using this kind of interferometry as an effective tool for obtaining the parameters characterizing the TLS as well as its interaction with the control fields and with the environment. Furthermore, strong driving could allow for fast and reliable control of the quantum system. Here we review recent experimental results on LZS interferometry, and we present related theory.Comment: 34 single-column pages, 11 figure

Can Jupiters be found by monitoring Galactic Bulge microlensing events from northern sites?

In 1998 the EXPORT team monitored microlensing event lightcurves using a CCD camera on the IAC 0.8m telescope on Tenerife to evaluate the prospect of using northern telescopes to find microlens anomalies that reveal planets orbiting the lens stars. The high airmass and more limited time available for observations of Galactic Bulge sources makes a northern site less favourable for microlensing planet searches. However, there are potentially a large number of northern 1m class telescopes that could devote a few hours per night to monitor ongoing microlensing events. Our IAC observations indicate that accuracies sufficient to detect planets can be achieved despite the higher airmass.Comment: 8 pages, 14 figures, 1 bbl file, based on EXPORT observations, accepted by MNRA

Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses

Plant plasma membrane localized pattern recognition receptors (PRRs) detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo)-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistance to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24), two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components