RAFT dispersion polymerization of glycidyl methacrylate for the synthesis of epoxy-functional block copolymer nanoparticles in mineral oil

Epoxy-functional poly(stearyl methacrylate)-poly(glycidyl methacrylate) (PSMA-PGlyMA) diblock copolymer nanoparticles are synthesized via reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of glycidyl methacrylate (GlyMA) in mineral oil at 70 °C. This efficient polymerization-induced self-assembly (PISA) formulation yields well-defined spheres of tunable diameter as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies. 1H NMR spectroscopy and gel permeation chromatography (GPC) studies indicate that such non-polar dispersions exhibit greater stability during their long-term storage at 20 °C compared to related epoxy-functional nanoparticles prepared via RAFT aqueous emulsion polymerization. Model epoxy-amine ring-opening reactions using N-methylaniline demonstrate the potential for post-polymerization functionalization of such spherical nanoparticles

Epoxy-functional diblock copolymer spheres, worms and vesicles via polymerization-induced self-assembly in mineral oil

Epoxy-functional diblock copolymer spheres, worms and vesicles are synthesized at 30% w/w solids via reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of glycidyl methacrylate (GlyMA) in mineral oil at 70 °C. This is achieved by using a relatively short oil-soluble poly(stearyl methacrylate) (PSMA) macromolecular chain transfer agent (macro-CTA) with a mean degree of polymerization of 9. Gel permeation chromatography (GPC) studies indicate that good control over the molecular weight distribution can be obtained and the resulting PSMA9-PGlyMAx nano-objects are characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS). Oscillatory rheology studies of a 30% w/w PSMA9-PGlyMA75 worm gel indicate that thermally-triggered degelation occurs on heating to 100 °C. TEM studies indicate that a partial worm-to-vesicle transition occurs under such conditions

Stakeholder involvement in the development of trial material for a clinical trial

Background: Stakeholder involvement includes not just patients and public, but also those delivering treatment e.g. clinicians and students. Each stakeholder brings unique experiences to the process. The aim of this stakeholder exercise was to explore readability and understanding of the trial material for the future trial to be conducted by the authors: Biomechanical Effects of Manual Therapy – A Feasibility Study. Design: Volunteers from identified stakeholder groups were provided with trial material which included the information sheet, consent form, questionnaires and home management booklet. They provided feedback on content (readability, understanding) and style (font, layout). An additional document was provided with genres of pictures to choose the most appropriate style to be used in the booklet. Readability formulas were used to calculate reading age before and after feedback to objectively measure ease of reading. Results: The public group provided a layperson’s perspective to clarify the information sheet for patients, whereas practitioner and intern groups indicated where information could be clarified. The reading age of all documentation decreased following feedback; however templated sections of the documentation did not. The majority (87%) of volunteers chose coloured classic cartoons for the booklet. Conclusion: This process highlighted the importance of involving different stakeholder groups in the development of research materials as each group made a unique contribution. Readability and understanding of the trial material were improved, feeding back into the consent process contributing towards fully informed consent. Patient or Public Contribution: Public helped develop materials for a future trial but not with manuscript preparation

A public and patient consultation process as an aid to design a person-centred randomized clinical trial.

BACKGROUND: Involving patients and members of the public, together with researchers, in decisions about how studies are designed and conducted can create a study that is more person-centred. The aim of this consultation process was to explore ways of designing a study which takes the person into consideration for the randomized clinical study entitled 'Biomechanical Effects of Manual Therapy-A Feasibility Study' using the novel approach of usability testing. DESIGN: Patient and public volunteers were sought with experience of low back pain. Volunteers were invited to participate in usability testing (a physical walkthrough) of the proposed study method. This was followed by a discussion of areas where usability testing could not be used, such as recruitment strategies, continuity of participant care and dissemination of results. Resulting feedback was considered by the research team and alterations to the original study method were incorporated, provided the research questions could be answered and were practical within the resources available. RESULTS: Additional recruitment strategies were proposed. Alterations to the study included reduction in study time burden; completion of study paperwork in a quieter location; continuity of participant care after the study; and methods of dissemination of overall study results to participants. CONCLUSION: The consultation process used the unique method of usability testing, together with a post-usability discussion, and resulted in alterations to the future study which may facilitate making it more person-centred. PATIENT AND PUBLIC CONTRIBUTION: Patients and public developed the future study design but did not participate in manuscript preparation

A Scalable Home Care System Infrastructure Supporting Domiciliary Care

Technology-mediated home care is attractive for older people living at home and also for their carers. It provides the information necessary to give confidence and assurance to everyone interested in the wellbeing of the older person. From a care delivery perspective, however, widespread deployment of home care technologies presents system developers with a set of challenges. These challenges arise from the issues associated with scaling from individual installations to providing a community-wide service, particularly when each installation is to be fitted to the particular but changing needs of the residents, their in-home carers and the larger healthcare community. This paper presents a home care software architecture and services that seek to address these challenges. The approach aims to generate the information needed in a timely and appropriate form to inform older residents and their carers about changing life style that may indicate a loss of well-being. It unites sensor-based services, home care policy management, resource discovery, multimodal interaction and dynamic configuration services. In this way, the approach offers the integration of a variety of home care services with adaptation to the context of use

Statistical validation of the criteria for symptom remission in schizophrenia: Preliminary findings

<p>Abstract</p> <p>Background</p> <p>Published methods for assessing remission in schizophrenia are variable and none have been definitively validated or standardized. Andreasen et al (2005) suggest systematic operational criteria using eight PANSS items for which patients must score ≤ 3 (mild) for at least six months.</p> <p>Methods</p> <p>Using data from a one year, multi-site clinical trial (n = 675) remission criteria were compared to total PANSS scores and other endpoints and demonstrate excellent agreement with overall clinical status.</p> <p>Results</p> <p>Compared to total PANSS score of 60 points and other criteria, at time points > 6 months (8 and 12 months) the specificity of the remission criteria was 85%, i.e. of the patients who had a total score >60, 85% were classified as "not in remission." Sensitivity was also very high; 75% of patients with scores of <60 were classified as "in remission."Patients who dropped out of the trial were more likely not to be in remission prior to dropping out.</p> <p>Conclusion</p> <p>These findings indicate that the remission criteria are both sensitive and specific indicators of clinical status. Additional analyses are required to determine if remission status predicts other outcomes, such as employment, independent living, and prognosis.</p

Varying spin state composition by the choice of capping ligand in a family of molecular chains: detailed analysis of magnetic properties of chromium(III) horseshoes

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The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK:a prospective multicentre cohort study

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council