What are patients' experiences of discontinuing clozapine and how does this impact their views on subsequent treatment?

BACKGROUND: Discontinuing what is considered the most effective treatment for treatment-resistant schizophrenia may precipitate feelings of failure or a relapse of illness. Clozapine treatment is discontinued for a variety of reasons, including non-adherence, intolerance, or lack of efficacy. Patients' experiences of discontinuing the "best" treatment and the impact on perceptions of subsequent antipsychotic treatment are important in developing an understanding of the factors affecting people's treatment choices. This study is the first of its type, seeking to explore people's perspectives on clozapine discontinuation. METHOD: Semi-structured interviews with sixteen patients who had received clozapine and discontinued treatment-thirteen males and three females, age range: thirty-two to seventy-eight years old-were audio-recorded and transcribed. A modified inductive approach to analysis, based on grounded theory, was taken to identify commonalities and differences in patients' perceptions. RESULTS: The three main themes identified from participants' experiences were: (1) positive and negative effects of treatment; (2) feelings of agency, being the capacity to make decisions about treatment and act independently; (3) choice of treatment in the future. Participants exhibited agency in making choices about medication, including risking relapse, while attempting self-management of medication effects. Different participants perceived the same side effect as beneficial or intolerable. Variation in subsequent treatment choices was reported, with some participants favouring depot (long-acting) injections. A participant was frightened when not told about clozapine's side effects, which led to the participant not being engaged in future treatment decisions. Others, despite suffering serious adverse effects, retained positive perceptions of clozapine; they experienced despair at finding an effective alternative. CONCLUSIONS: Experiences with clozapine discontinuation evoked powerful emotions and resulted in clozapine being the benchmark for other treatments. Knowledge, agency, and being in control were important to participants in relation to treatment. Personal perceptions of treatments or beliefs about illness could lead to non-adherence. People value the clinician listening to their experiences to better understand their perspective, enabling concerns about medication to be addressed through true shared decision making. TRIAL REGISTRATION: NHS Health Research Authority and Health and Care Research Wales, IRAS Project ID 225753, Research Ethics Committee (REC) reference: 18/NW/0413, 25/06/2018

BATSE spectroscopy analysis system

The Burst and Transient Source Experiment (BATSE) Spectroscopy Analysis System (BSAS) is the software system which is the primary tool for the analysis of spectral data from BATSE. As such, Guest Investigators and the community as a whole need to know its basic properties and characteristics. Described here are the characteristics of the BATSE spectroscopy detectors and the BSAS

Non-linear Control of a Piezoelectric Two Stage Servovalve

This paper describes an algorithm to control a two stage hydraulic servovalve designed for aerospace applications. The valve has a piezoelectric ring bender actuating a first stage spool with a significant amount of overlap to reduce internal leakage. The piezoelectric ring bender is a less complex and lighter alternative to a conventional torque motor. The second stage has electrical instead of the conventional mechanical feedback. The control algorithm includes compensation for the first stage spool overlap, piezoelectric hysteresis compensation and a feed forward term. The hysteresis compensation is based on a relatively simple Bouc-Wen hysteresis model that is able to significantly reduce the amount of first stage hysteresis. The overlap compensation, increasing the gain in the overlap region, reduces the impact of amplitude change and increases performance. It can also reduce any asymmetry in the system. The controller has a superior performance compared to a PI controller, as demonstrated experimentally using step and frequency responses

Dimensional approaches to experimental psychopathology of schizophrenia: shift learning and report of psychotic-like experiences in college students

Adopting a dimensional approach to experimental psychopathology, and taking into account inconsistencies in the previous literature, we examined whether reports of psychotic-like experiences in undergraduate students were associated with shift-learning deficits, akin to those seen in schizophrenia. The participants (N=72) were tested on a new compound stimulus discrimination task (CSDT) before and after a target shift, and were administered a multi-dimensional schizotypy inventory (O-LIFE). Performance impairment following a target shift was associated with the negative (Introvertive Anhedonia) and the impulsive (Impulsive Non-conformity) dimension of schizotypy, but not with the positive (Unusual Experiences), nor the disorganised (Cognitive Disorganisation) dimension. None of the schizotypy measures were associated with performance on discrimination learning before the target shift. The obtained results are in line with past evidence that shift learning is associated with the severity of the negative symptomatology of schizophrenia. The possibility that psychotic-like features may contribute differentially to performance deficits across successive stages of learning is considered

Molecular differences between two Jeryl Lynn mumps virus vaccine component strains, JL5 and JL2

The Jeryl Lynn (JL) vaccine against mumps virus (MuV) contains two components, MuVJL5 and MuVJL2, which differ by over 400 nt. Due to the occurrence of bias in the direction of mutation, these differences and those found in nucleotide sequences of different isolates of the minor component in the vaccine (MuVJL2) might be due to the effect of ADAR-like deaminases on MuV grown in tissue-cultured cells. A molecular clone of MuVJL2 (pMuVJL2) and MuVJL2-specific helper plasmids were constructed in order to investigate molecular interactions between MuVJL5 and MuVJL2, to augment the existing molecular clone of MuVJL5 (pMuVJL5) and MuVJL5-specific helper plasmids. Genome and mRNA termini of MuVJL2 were characterized, and an unusual oligo-G insertion transcriptional editing event was detected near the F mRNA polyadenylation site of MuVJL2, but not of MuVJL5. Genes encoding glycoproteins of rMuVJL2 and rMuVJL5 have been exchanged to characterize the oligo-G insertion, which associated with the specific sequence of the F gene of MuVJL2 and not with any other genes or the RNA-dependent RNA polymerase of strain MuVJL2. The results indicate that a single G-to-A sequence change obliterates the co-transcriptional editing of the F mRNA and that this oligo-G insertion does not affect the growth of the virus

Ballistic Puncture Self-Healing Polymeric Materials

Space exploration launch costs on the order of $10,000 per pound provide an incentive to seek ways to reduce structural mass while maintaining structural function to assure safety and reliability. Damage-tolerant structural systems provide a route to avoiding weight penalty while enhancing vehicle safety and reliability. Self-healing polymers capable of spontaneous puncture repair show promise to mitigate potentially catastrophic damage from events such as micrometeoroid penetration. Effective self-repair requires these materials to quickly heal following projectile penetration while retaining some structural function during the healing processes. Although there are materials known to possess this capability, they are typically not considered for structural applications. Current efforts use inexpensive experimental methods to inflict damage, after which analytical procedures are identified to verify that function is restored. Two candidate self-healing polymer materials for structural engineering systems are used to test these experimental methods

Exploring self-harm risk vulnerabilities in autism using the ‘thinking patterns profiling model’

From Springer Nature via Jisc Publications RouterHistory: received 2022-11-21, registration 2023-02-23, accepted 2023-02-23, epub 2023-03-20, online 2023-03-20, collection 2023-12Acknowledgements: This project was conducted through the Structured Operational Research and Training Initiative (SORT IT), a global partnership led by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization. The training is based on a course developed jointly by the International Union Against Tuberculosis and Lung Disease (The Union) and Medécins sans Frontières. This specific SORT IT program was run by Cheshire and Wirral Partnership (CWP) NHS Foundation Trust as part of routine work. Mentorship and the coordination/facilitation of these SORT IT workshops were provided through the CWP NHS Foundation Trust; The Centre for Operational Research, The Union, Paris, France; The Institute of Medicine, University of Chester, UK; and College of Life and Environmental Science, University of Exeter. The authors would like to acknowledge the families who attended the autism diagnostic assessment profiling service, and to thank the experts by experience who shared their insight, contributed to interpretation of the study findings, and reviewed final versions of the manuscript. Experts by experience included Josef de la Moitie and Kevin Carrell who were happy to be named. The authors would also like to thank Professor Taj Nathan (Director of Research and Effectiveness), Dr Fiona Pender (Strategic Director), Anne Casey (Head of Clinical Services), Dr Ian Davidson (Consultant Psychiatrist and Royal College of Psychiatrists Autism Champion), and Heather Pearce (Advanced Specialist Speech and Language Therapist) all at Cheshire and Wirral Partnership NHS Foundation Trust. Finally, thank you to David Tollerfield for permission to use the ‘Thinking Patterns Profiling Model’ digital innovations as part of the diagnostic assessment profiling service.Publication status: PublishedBackground: Autism has been linked to higher rates of self-harm. Research is yet to establish the reason for the association between autism and self-harm as a distress response. Methods: Using the ‘thinking patterns profiling model’, this study explored characteristics associated with self-harm risk in 100 autistic young people. Secondary analysis of routinely collected clinical data was conducted using odds ratios and t-tests. Results: We found the prevalence of reported self-harm risk was 48%. Young people with reported self-harm risks had significantly lower regulation skills (p ≤ 0.01) and lower social flexibility skills (p ≤ 0.01) compared to those without reported self-harm risk. For those described as impulsive, mean scores on the following skills were significantly lower: perspective-taking skills (p ≤ 0.01), flexible thinking for creative problem-solving (p ≤ 0.05) and sensory tolerating (p ≤ 0.05). There was no relationship between reported self-harm risk and adverse childhood experiences. Conclusions: These findings suggest that profiling tools such as ‘Thinking Patterns Profiling Model’ can be used to explore unique patterns of vulnerability and resilience related to self-harm risk in autism. The findings suggest that autistic thinking patterns might interplay with other factors (e.g. impulsivity). Patterns are based on each person’s profile across four core skill-sets: regulation, flexible thinking, sensory coherence, and social perspective-taking. These findings motivate a person-centred and profile-informed approach to planning support and adjustments. Further studies are needed to confirm the ways in which mechanisms typically involved in self-harm risk, may interact with core cognitive and affective differences found in autism