An evaluation of subjective experiences, effects and overall satisfaction with clozapine treatment in a UK forensic service

Objectives: Patients prescribed clozapine were surveyed to assess (a) the effects, both positive and adverse, and overall satisfaction with clozapine in comparison to previously prescribed antipsychotics and (b) the relative significance of effects experienced, both positive and adverse, in terms of impact on subjective well-being. Methods: A total of 56 male patients prescribed clozapine at a forensic psychiatric hospital were surveyed using a 27-item questionnaire. All patients had been prescribed clozapine for a minimum of 3 months. Respondents were asked to rate effects and satisfaction with clozapine treatment in comparison with previously prescribed antipsychotic medication on a five-point scale. Respondents were also asked to rate effects experienced with clozapine treatment in terms of impact on subjective well-being on a five-point scale. Results: A total of 89% of respondents reported greater satisfaction with clozapine than with previously prescribed antipsychotic medication. A majority of patients reported positive effects in terms of an improvement in their quality of life (68%) and social abilities (52%) with clozapine in comparison with previously prescribed antipsychotics. Nocturnal hypersalivation (84%) and weight gain (57%) were the most common adverse effects. Hedonic responses were assessed for each effect in order to determine the associated subjective experiences. The most positive hedonic responses were for quality of life, mood and alertness. In terms of adverse impact on subjective well-being, nocturnal hypersalivation ranked highest. Conclusions: Patients in a UK forensic sample are largely satisfied with clozapine treatment. The subjective effects of clozapine treatment should be taken into account by clinicians when assessing response. This may provide an opportunity to highlight the positive changes and prioritize management of the most undesirable adverse effects, which is likely to promote compliance and improve longer term treatment outcomes

Pre-harvest fruit drop, bunch weight and fruit quality of ‘Rothana’ and ‘Ghur’ date palm cultivars as affected by some plant growth regulators

Pre-harvest fruit drop is a serious problem of some date palm cultivars. During 2010 and 2011 seasons, the effect of plant growth regulators 2,4-dichlorophenoxyacetic acid (2,4-D) (50 and 100 ppm), naphthalene acetic acid (NAA) (100 and 150 ppm), gibberellic acid (GA3) (100 and 150 ppm) and benzyladenine (BA) (100 and 150 ppm) applications, at 40 and 70 days after pollination, on pre-harvest fruit drop and quality of ‘Rothana’ and ‘Ghur’ dates were studied. In both cultivars, the application of growth regulators at both rates significantly decreased fruit drop. In this respect, 2,4-D and GA3 were the most effective treatments followed by BA, while NAA was the least effective. The reduction in fruit drop resulted in a higher bunch weight in the treated fruit than the control. The high rate of BA was more effective than the low rate in decreasing fruit drop of ‘Ghur’ cultivar. In ‘Rothana’ cultivar, bunch weight was higher than the control with both 2,4-D rates; whereas, with GA3 and BA, only the high rate was effective; while in ‘Ghur’ cultivar, bunch weight of all growth regulators treatments was higher than the control. The rutab percentage was lower in NAA treatments than for all the other treatments, except for control in ‘Ghur’ cultivar. Fruit and flesh weight of ‘Rothana’ cultivar were higher at the high rate of 2,4-D, the low rate of GA3 and BA treatments than in the control. There were no consistent effects for growth regulators on the physical and chemical quality characteristics of fruit, possibly due to the large variations of the fruit load among the treatments. It was concluded that under hot arid conditions, the application of growth regulators of especially 2,4-D (50 ppm) and GA3 (150 ppm) at both 40 and 70 days from pollination is recommended to reduce pre-harvest drop, and improve fruit quality of both ‘Rothana’ and ‘Ghur’ date palm cultivars.Keywords: Date palm, plant growth regulators, yield, quality, fruit drop, Phoenix dactylifera

Simple Microwave Method for Detecting Water Holdup

A microwave sensor is designed to measure the resonance behavior of the hydrocarbon mixture to determine the water holdup of a near horizontal oil carrying pipeline. This technique is particularly useful for detecting very small water holdup (<5%) as demonstrated by simulated and experimental results

Simple Microwave Method for Detecting Water Holdup

A microwave sensor is designed to measure the resonance behavior of the hydrocarbon mixture to determine the water holdup of a near horizontal oil carrying pipeline. This technique is particularly useful for detecting very small water holdup (<5%) as demonstrated by simulated and experimental results

A HER2 selective theranostic agent for surgical resection guidance and photodynamic therapy

In many cancers early intervention involves surgical resection of small localised tumour masses. Inadequate resection leads to recurrence whereas overzealous treatment can lead to organ damage. This work describes production of a HER2 targeting antibody Fab fragment dual conjugated to achieve both real time near-infrared fluorescent imaging and photodynamic therapy. The use of fluorescence emission from a NIR-dye could be used to guide resection of tumour bulk, for example during endoscopic diagnosis for oesophago-gastric adenocarcinoma, this would then be followed by activation of the photodynamic therapeutic agent to destroy untreated localised areas of cancer infiltration and tumour infiltrated lymph nodes. This theranostic agent was prepared from the Fab fragment of trastuzumab initially by functional disulfide re-bridging and site-specific click reaction of a NIR-dye. This was followed by further reaction with a novel pre-activated form of the photosensitiser chlorin e6 with the exposed fragments' lysine residues. Specific binding of the theranostic agent was observed in vitro with a HER2 positive cell line and cellular near-infrared fluorescence was observed with flow cytometry. Specific photo-activity of the conjugates when exposed to laser light was observed with HER2 positive but not HER2 negative cell lines in vitro, this selectivity was not seen with the unconjugated drug. This theranostic agent demonstrates that two different photo-active functions can be coupled to the same antibody fragment with little interference to their independent activities

Tunable local polariton modes in semiconductors

We study the local states within the polariton bandgap that arise due to deep defect centers with strong electron-phonon coupling. Electron transitions involving deep levels may result in alteration of local elastic constants. In this case, substantial reversible transformations of the impurity polariton density of states occur, which include the appearance/disappearance of the polariton impurity band, its shift and/or the modification of its shape. These changes can be induced by thermo- and photo-excitation of the localized electron states or by trapping of injected charge carriers. We develop a simple model, which is applied to the $O_P$ center in $GaP$. Further possible experimental realizations of the effect are discussed.Comment: 7 pages, 3 figure

The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): A randomised placebo-controlled trial.

Background: Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted. Methods: Multicentre, double-blind, placebo-controlled trial. We aimed to recruit 222 inpatients with severe BPD aged 18 or over, who had failed to respond to other antipsychotic medications. We randomly allocated participants on a 1:1 ratio to receive up to 400mg of clozapine per day or an inert placebo using a remote web-based randomisation service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at six months. Secondary outcomes included self-harm, aggression, resource use and costs, side effects and adverse events. We used a modified intention to treat analysis (mITT) restricted to those who took one or more dose of trial medication, using a general linear model fitted at six months adjusted for baseline score, allocation group and site. Results: The study closed early due to poor recruitment and the impact of the COVID-19 pandemic. Of 29 study participants, 24 (83%) were followed up at six months, of whom 21 (72%) were included in the mITT analysis. At six months, 11 (73%) participants assigned to clozapine and 6 (43%) of those assigned to placebo were still taking trial medication. Adjusted difference in mean total ZAN-BPD score at six months was -3.86 (95% Confidence Intervals = -10.04 to 2.32, p=0.22). There were 14 serious adverse events; six in the clozapine arm and eight in the placebo arm of the trial. There was little difference in the cost of care between groups. Interpretation: We recruited insufficient participants to test the primary hypothesis. The study findings highlight problems in conducting placebo-controlled trials of clozapine and in using clozapine for people with BPD, outside specialist inpatient mental health units. Trial registration ISRCTN18352058. https://doi.org/10.1186/ISRCTN1835205

A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis

NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as used in the treatment of systemic autoimmune disorders would be tolerable and effective in people with schizophrenia in a feasibility study. Ninety-two participants within 5 years of schizophrenia diagnosis were recruited from inpatient and outpatient facilities in Karachi, Pakistan. They were randomised to receive once weekly 10-mg oral methotrexate (n = 45) or matching placebo (n = 47) both with daily 5-mg folic acid, in addition to treatment as usual for 12 weeks. There were eight dropouts per group. Side effects were non-significantly more common in those on methotrexate and were not severe. One person developed leukopenia. Positive symptom scores improved more in those receiving methotrexate than placebo (β = −2.5; [95% CI −4.7 to −0.4]), whereas negative symptoms were unaffected by treatment (β = −0.39; [95% CI −2.01 to 1.23]). There were no immune biomarkers but methotrexate did not affect group mean leucocyte counts or C-reactive protein. We conclude that further studies are feasible but should be focussed on subgroups identified by advances in neuroimmune profiling. Methotrexate is thought to work in autoimmune disorders by resetting systemic regulatory T-cell control of immune signalling; we show that a similar action in the CNS would account for otherwise puzzling features of the immuno-pathogenesis of schizophrenia