Cooled Infrared Dichroic Beamsplitters and Filters for the MIRI Spectrometer and Imager (5-29µm)

The spectral design and fabrication of cooled (7K) mid-infrared dichroic beamsplitters and bandpass filter coatings for the MIRI spectrometer and imager are described. Design methods to achieve the spectral performance and coating materials are discussed

Metabolomic systems biology of trypanosomes

Metabolomics analysis, which aims at the systematic identification and quantification of all metabolites in biological systems, is emerging as a powerful new tool to identify biomarkers of disease, report on cellular responses to environmental perturbation, and to identify the targets of drugs. Here we discuss recent developments in metabolomic analysis, from the perspective of trypanosome research, highlighting remaining challenges and the most promising areas for future research

The silicon trypanosome

African trypanosomes have emerged as promising unicellular model organisms for the next generation of systems biology. They offer unique advantages, due to their relative simplicity, the availability of all standard genomics techniques and a long history of quantitative research. Reproducible cultivation methods exist for morphologically and physiologically distinct life-cycle stages. The genome has been sequenced, and microarrays, RNA-interference and high-accuracy metabolomics are available. Furthermore, the availability of extensive kinetic data on all glycolytic enzymes has led to the early development of a complete, experiment-based dynamic model of an important biochemical pathway. Here we describe the achievements of trypanosome systems biology so far and outline the necessary steps towards the ambitious aim of creating a , a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology. We expect that, in the long run, the quantitative modelling enabled by the Silicon Trypanosome will play a key role in selecting the most suitable targets for developing new anti-parasite drugs

Deinstitutionalized patients, homelessness and imprisonment: A systematic review

BackgroundReports linking the deinstitutionalisation of psychiatric care with homelessness and imprisonment have been published widely.AimsTo identify cohort studies that followed up or traced back long-term psychiatric hospital residents who had been discharged as a consequence of deinstitutionalisation.MethodA broad search strategy was used and 9435 titles and abstracts were screened, 416 full articles reviewed and 171 articles from cohort studies of deinstitutionalised patients were examined in detail.ResultsTwenty-three studies of unique populations assessed homelessness and imprisonment among patients discharged from long-term care. Homelessness and imprisonment occurred sporadically; in the majority of studies no single case of homelessness or imprisonment was reported.ConclusionsOur results contradict the findings of ecological studies which indicated a strong correlation between the decreasing number of psychiatric beds and an increasing number of people with mental health problems who were homeless or in prison.</jats:sec

Evaluation of Restaurant Menus to Determine the Availability of Healthy Food Options and Guide Community Transformation Grant Activities in Massachusetts

INTRODUCTION. The availability of healthy menu options in restaurants is an important factor in the prevention of obesity. The Mass in Motion Initiative and two Community Transformation Grant (CTG) projects are conducting statewide longitudinal surveys to determine the availability of healthy food in restaurants in the state of Massachusetts. METHODS. The Community Nutrition Environment Evaluation Data System-Restaurant (C-NEEDS-R) was developed for food environment surveillance. C-NEEDS-R takes into account seasonal and geographic variations in food supplies, cultural relevance, and USDA dietary recommendations. Between summer 2012 and winter 2013, 506 restaurants in 36 Massachusetts towns and cities were surveyed and analyzed. Through menu and site evaluation, the availability of healthy entrees was examined for each restaurant, and the total number of healthy entrees as well as the percent of healthy entrees was calculated for each restaurant. For each municipality, the average number and average percentage of healthy entrees for restaurants within the community was also calculated. RESULTS. The surveyed restaurants had average 3.2 healthy entrees on the menu, accounting for 13.4% of the total number of entrees available. The percentage of healthy options varied widely by restaurant and restaurant type, ranging from 0 to 84%, and only 15 of the 506 surveyed restaurants ( DISCUSSION. As noted, menu evaluation demonstrated that the large majority of the surveyed restaurants had few healthy entrees, indicating a need to increase availability of healthy options. Analysis of restaurant- and community-level variations in availability is useful for CTG programs to formulate and prioritize interventions. Future longitudinal surveys of food stores in the intervention and control communities will help evaluate the effectiveness of CTG interventions

Feasibility randomised controlled trial of online group Acceptance and Commitment Therapy for Functional Cognitive Disorder (ACT4FCD)

INTRODUCTION: Functional cognitive disorder (FCD) is seen increasingly in clinics commissioned to assess cognitive disorders. Patients report frequent cognitive, especially memory, failures. The diagnosis can be made clinically, and unnecessary investigations avoided. While there is some evidence that psychological treatments can be helpful, they are not routinely available. Therefore, we have developed a brief psychological intervention using the principles of acceptance and commitment therapy (ACT) that can be delivered in groups and online. We are conducting a feasibility study to assess whether the intervention can be delivered within a randomised controlled trial. We aim to study the feasibility of recruitment, willingness to be randomised to intervention or control condition, adherence to the intervention, completion of outcome measures and acceptability of treatment. METHODS AND ANALYSIS: We aim to recruit 48 participants randomised 50:50 to either the ACT intervention and treatment as usual (TAU), or TAU alone. ACT will be provided to participants in the treatment arm following completion of baseline outcome measures. Completion of these outcome measures will be repeated at 8, 16 and 26 weeks. The measures will assess several domains including psychological flexibility, subjective cognitive symptoms, mood and anxiety, health-related quality of life and functioning, healthcare utilisation, and satisfaction with care and participant-rated improvement. Fifteen participants will be selected for in-depth qualitative interviews about their experiences of living with FCD and of the ACT intervention. ETHICS AND DISSEMINATION: The study received a favourable opinion from the South East Scotland Research Ethics Committee 02 on 30 September 2022 (REC reference: 22/SS/0059). HRA approval was received on 1 November 2022 (IRAS 313730). The results will be published in full in an open-access journal. TRIAL REGISTRATION NUMBER: ISRCTN12939037

Cognitive behavioural therapy and short-term psychoanalytical psychotherapy versus a brief psychosocial intervention in adolescents with unipolar major depressive disorder (IMPACT): a multicentre, pragmatic, observer-blind, randomised controlled superiority trial.

BACKGROUND: Psychological treatments for adolescents with unipolar major depressive disorder are associated with diagnostic remission within 28 weeks in 65-70% of patients. We aimed to assess the medium-term effects and costs of psychological therapies on maintenance of reduced depression symptoms 12 months after treatment. METHODS: We did this multicentre, pragmatic, observer-blind, randomised controlled superiority trial (IMPACT) at 15 National Health Service child and adolescent mental health service (CAMHS) clinics in three regions in England. Adolescent patients (aged 11-17 years) with a diagnosis of DSM IV major depressive disorder were randomly assigned (1:1:1), via a web-based randomisation service, to receive cognitive behavioural therapy (CBT) or short-term psychoanalytical therapy versus a reference brief psychological intervention. Randomisation was stochastically minimised by age, sex, self-reported depression sum score, and region. Patients and clinicians were aware of group allocation, but allocation was concealed from outcome assessors. Patients were followed up and reassessed at weeks 6, 12, 36, 52, and 86 post-randomisation. The primary outcome was self-reported depression symptoms at weeks 36, 52, and 86, as measured with the self-reported Mood and Feelings Questionnaire (MFQ). Because our aim was to compare the two psychological therapies with the brief psychosocial intervention, we first established whether CBT was inferior to short-term psychoanalytical psychotherapy for the same outcome. Primary analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN83033550. FINDINGS: Between June 29, 2010, and Jan 17, 2013, we randomly assigned 470 patients to receive the brief psychosocial intervention (n=158), CBT (n=155), or short-term psychoanalytical therapy (n=157); 465 patients comprised the intention-to-treat population. 392 (84%) patients had available data for primary analysis by the end of follow-up. Treatment fidelity and differentiation were established between the three interventions. The median number of treatment sessions differed significantly between patients in the brief psychosocial intervention group (n=6 [IQR 4-11]), CBT group (n=9 [5-14]), and short-term psychoanalytical therapy group (n=11 [5-23]; p<0·0001), but there was no difference between groups in the average duration of treatment (27·5 [SD 21·5], 24·9 [17·7], 27·9 [16·8] weeks, respectively; Kruskal-Wallis p=0·238). Self-reported depression symptoms did not differ significantly between patients given CBT and those given short-term psychoanalytical therapy at weeks 36 (treatment effect 0·179, 95% CI -3·731 to 4·088; p=0·929), 52 (0·307, -3·161 to 3·774; p=0·862), or 86 (0·578, -2·948 to 4·104; p=0·748). These two psychological treatments had no superiority effect compared with brief psychosocial intervention at weeks 36 (treatment effect -3·234, 95% CI -6·611 to 0·143; p=0·061), 52 (-2·806, -5·790 to 0·177; p=0·065), or 86 (-1·898, -4·922 to 1·126; p=0·219). Physical adverse events (self-reported breathing problems, sleep disturbances, drowsiness or tiredness, nausea, sweating, and being restless or overactive) did not differ between the groups. Total costs of the trial interventions did not differ significantly between treatment groups. INTERPRETATION: We found no evidence for the superiority of CBT or short-term psychoanalytical therapy compared with a brief psychosocial intervention in maintenance of reduced depression symptoms 12 months after treatment. Short-term psychoanalytical therapy was as effective as CBT and, together with brief psychosocial intervention, offers additional patient choice for psychological therapy, alongside CBT, for adolescents with moderate to severe depression who are attending routine specialist CAMHS clinics. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and the Department of Health.National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and the Department of Health

Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines

The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers

In Context: Lessons About Adolescent Unipolar Depression From the Improving Mood With Psychoanalytic and Cognitive Therapies Trial

This review paper summarizes the results of the Improving Mood with Psychoanalytic and Cognitive Therapies (IMPACT) study and its implications for psychological treatment of adolescents with moderate to severe unipolar major depression. IMPACT was a pragmatic, superiority, randomized controlled trial conducted in the United Kingdom, which compared the clinical and cost-effectiveness of short-term psychoanalytic therapy (STPP), cognitive−behavioral therapy (CBT), and a brief psychosocial intervention (BPI) in reducing depression symptoms in 465 adolescents with unipolar major depression, aged 11 to 17 years. Although this was a clinically heterogeneous group of adolescents, some symptoms (eg, sleep and concentration difficulties, irritability/anger) were common and disabling. The trial reported no significant difference among the 3 treatments in reducing depression symptoms. One year after treatment, 84% of participants showed improvement in depressive symptoms (<50% of baseline symptoms) and improved psychosocial functioning, achieving this through different symptom reduction trajectories. Although participants attended fewer treatment sessions than planned, the 3 treatments were delivered with fidelity to their respective models. Ending treatment without therapist agreement occurred in 37% of cases. This was not associated with outcomes by treatment group. Adolescents emphasized the importance of the therapeutic relationship in all 3 treatments. Results suggest that although most adolescents respond to time-limited, structured psychological therapy, subgroups of depressed adolescents are likely to need additional treatment or support. These include adolescents who live in complex circumstances and/or who believe that their needs are not met in therapy, some who stop treatment early, and the 16% to 18% of adolescents who do not respond to treatment