Inhibiting the Thermal Gelation of Copolymer Stabilized Nonaqueous Dispersions and the Synthesis of Full Color PMMA Particles

Polymeric particle dispersions have numerous potential applications; currently one of the most relevant is their use as inks in electrophoretic displays. These colloidal particles are synthesized from the appropriate monomer using nonaqueous dispersion (NAD) polymerization in a nonpolar solvent, which requires a stabilizer to control particle size and morphology. We have previously reported the facile synthesis of poly(methyl methacrylate)-block-poly(octadecyl acrylate) (PMMA-b-PODA) by atom transfer radical polymerization (ATRP), and its use in the NAD polymerization of MMA in hexane/dodecane solvent mixtures. Here we report the synthesis of monodisperse PMMA particles in dodecane following a standard “industrial” procedure using these PMMA-b-PODA stabilizers. However, it was observed that the particle suspensions solidified when they were left at temperatures below ?18 °C yet redispersed upon being heated. Differential scanning calorimetry, dynamic light scattering, and rheological studies demonstrated that this thermoresponsive behavior was due to a liquid–gel transition occurring at 17.5 °C as a consequence of the upper critical solution temperature of PODA in dodecane being traversed. Consequently, new copolymers were synthesized by ATRP with an ethylhexyl acrylate (EHA) co-monomer incorporated into the lyophilic (dodecane compatible) block. Dispersions stabilized by these PMMA-b-P(ODA-co-EHA) polymers with high EHA contents exhibited lower gelation temperatures because of the greater solvent compatibility with dodecane. The use of a PMMA65-b-(ODA10-co-EHA45) copolymer stabilizer (with the highest EHA content) gave PMMA dispersions that showed no gelation down to 4 °C and monodisperse cross-linked PMMA particles containing organic dyes (cyan, magenta, red, and black) giving colored particles across the size range of approximately 100–1300 nm

Meta-analysis of regional white matter volume in bipolar disorder with replication in an independent sample using coordinates, T-maps, and individual MRI data

Converging evidence suggests that bipolar disorder (BD) is associated with white matter (WM) abnormalities. Meta-analyses of voxel based morphometry (VBM) data is commonly performed using published coordinates, however this method is limited since it ignores non-significant data. Obtaining statistical maps from studies (T-maps) as well as raw MRI datasets increases accuracy and allows for a comprehensive analysis of clinical variables. We obtained coordinate data (5-studies), T-Maps (12-studies, including unpublished data) and raw MRI datasets (5-studies) and analysed the 24 studies using Seed-based d Mapping (SDM). A VBM analysis was conducted to verify the results in an independent sample. The meta-analysis revealed decreased WM volume in the posterior corpus callosum extending to WM in the posterior cingulate cortex. This region was significantly reduced in volume in BD patients in the independent dataset (p=0.003) but there was no association with clinical variables. We identified a robust WM volume abnormality in BD patients that may represent a trait marker of the disease and used a novel methodology to validate the findings

Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress

A functional genomics study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. Comparative metabolomics and lipidomics demonstrated that acetate is used as a nutritional source by cancer cells in an ACSS2-dependent manner, and supplied a significant fraction of the carbon within the fatty acid and phospholipid pools. ACSS2 expression is upregulated under metabolically stressed conditions and ACSS2 silencing reduced the growth of tumor xenografts. ACSS2 exhibits copy-number gain in human breast tumors, and ACSS2 expression correlates with disease progression. These results signify a critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment

The Relationship between Asthma and Depression in Primary Care Patients: A Historical Cohort and Nested Case Control Study

Asthma and depression are common health problems in primary care. Evidence of a relationship between asthma and depression is conflicting. Objectives: to determine 1. The incidence rate and incidence rate ratio of depression in primary care patients with asthma compared to those without asthma, and 2. The standardized mortality ratio of depressed compared to non-depressed patients with asthma.A historical cohort and nested case control study using data derived from the United Kingdom General Practice Research Database. Participants: 11,275 incident cases of asthma recorded between 1/1/95 and 31/12/96 age, sex and practice matched with non-cases from the database (ratio 1∶1) and followed up through the database for 10 years. 1,660 cases were matched by date of asthma diagnosis with 1,660 controls. Main outcome measures: number of cases diagnosed with depression, the number of deaths over the study period.The rate of depression in patients with asthma was 22.4/1,000 person years and without asthma 13.8 /1,000 person years. The incident rate ratio (adjusted for age, sex, practice, diabetes, cardiovascular disease, cerebrovascular disease, smoking) was 1.59 (95% CI 1.48–1.71). The increased rate of depression was not associated with asthma severity or oral corticosteroid use. It was associated with the number of consultations (odds ratio per visit 1.09; 95% CI 1.07–1.11). The age and sex adjusted standardized mortality ratio for depressed patients with asthma was 1.87 (95% CI: 1.54–2.27).Asthma is associated with depression. This was not related to asthma severity or oral corticosteroid use but was related to service use. This suggests that a diagnosis of depression is related to health seeking behavior in patients with asthma. There is an increased mortality rate in depressed patients with asthma. The cause of this needs further exploration. Consideration should be given to case-finding for depression in this population

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Long Covid in adults discharged from UK hospitals after Covid-19 : a prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol

Funding: This work is supported by grants from: the National Institute for Health Research (NIHR) [award CO-CIN-01], the Medical Research Council [grant MC_PC_19059], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant P45058), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], and the Bill and Melinda Gates Foundation [OPP1209135], and Liverpool Experimental Cancer Medicine Centre (Grant Reference: C18616/A25153), NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013], EU Platform for European Preparedness Against (Re-) emerging Epidemics 1 [FP7 project 602525] and NIHR Clinical Research Network for providing infrastructure support for this research. LT is a Wellcome Trust clinical career development fellow, supported by grant number 205228/Z/16/Z. This research was funded in part, by the Wellcome Trust. PJMO is supported by a NIHR Senior Investigator Award [award 201385].Background : This study sought to establish the long-term effects of Covid-19 following hospitalisation. Methods : 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). Findings : 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Interpretation : Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females.Publisher PDFPeer reviewe

Use of information and communication technologies to support effective work practice innovation in the health sector: a multi-site study

<p>Abstract</p> <p>Background</p> <p>Widespread adoption of information and communication technologies (ICT) is a key strategy to meet the challenges facing health systems internationally of increasing demands, rising costs, limited resources and workforce shortages. Despite the rapid increase in ICT investment, uptake and acceptance has been slow and the benefits fewer than expected. Absent from the research literature has been a multi-site investigation of how ICT can support and drive innovative work practice. This Australian-based project will assess the factors that allow health service organisations to harness ICT, and the extent to which such systems drive the creation of new sustainable models of service delivery which increase capacity and provide rapid, safe, effective, affordable and sustainable health care.</p> <p>Design</p> <p>A multi-method approach will measure current ICT impact on workforce practices and develop and test new models of ICT use which support innovations in work practice. The research will focus on three large-scale commercial ICT systems being adopted in Australia and other countries: computerised ordering systems, ambulatory electronic medical record systems, and emergency medicine information systems. We will measure and analyse each system's role in supporting five key attributes of work practice innovation: changes in professionals' roles and responsibilities; integration of best practice into routine care; safe care practices; team-based care delivery; and active involvement of consumers in care.</p> <p>Discussion</p> <p>A socio-technical approach to the use of ICT will be adopted to examine and interpret the workforce and organisational complexities of the health sector. The project will also focus on ICT as a potentially <it>disruptive innovation </it>that challenges the way in which health care is delivered and consequently leads some health professionals to view it as a threat to traditional roles and responsibilities and a risk to existing models of care delivery. Such views have stifled debate as well as wider explorations of ICT's potential benefits, yet firm evidence of the effects of role changes on health service outcomes is limited. This project will provide important evidence about the role of ICT in supporting new models of care delivery across multiple healthcare organizations and about the ways in which innovative work practice change is diffused.</p

Radical cystectomy (bladder removal) against intravesical BCG immunotherapy for high-risk non-muscle invasive bladder cancer (BRAVO): a protocol for a randomised controlled feasibility study

INTRODUCTION: High-risk non-muscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease that can be difficult to predict. While around 25% of cancers progress to invasion and metastases, the remaining majority of tumours remain within the bladder. It is uncertain whether patients with HRNMIBC are better treated with intravesical maintenance BCG (mBCG) immunotherapy or primary radical cystectomy (RC). A definitive randomised controlled trial (RCT) is needed to compare these two different treatments but may be difficult to recruit to and has not been attempted to date. Before undertaking such an RCT, it is important to understand whether such a comparison is possible and how best to achieve it. METHODS AND ANALYSIS: BRAVO is a multi-centre, parallel-group, mixed-methods, individually randomised, controlled, feasibility study for patients with HRNMIBC. Participants will be randomised to receive either mBCG immunotherapy or RC. The primary objective is to assess the feasibility and acceptability of performing the definitive phase III trial via estimation of eligibility and recruitment rates, assessing uptake of allocated treatment and compliance with mBCG, determining quality-of-life questionnaire completion rates and exploring reasons expressed by patients for declining recruitment into the study. We aim to recruit 60 participants from six centres in the UK. Surgical trials with disparate treatment options find recruitment challenging from both the patient and clinician perspective. By building on the experiences of other similar trials through implementing a comprehensive training package aimed at clinicians to address these challenges (qualitative substudy), we hope that we can demonstrate that a phase III trial is feasible. ETHICS AND DISSEMINATION: The study has ethical approval (16/YH/0268). Findings will be made available to patients, clinicians, the funders and the National Health Service through traditional publishing and social media. TRIAL REGISTRATION NUMBER: ISRCTN12509361; Pre results

Physiotherapy Post Lumbar Discectomy: Prospective Feasibility and Pilot Randomised Controlled Trial

Objectives To evaluate: acceptability and feasibility of trial procedures; distribution of scores on the Roland Morris Disability Questionnaire (RMDQ, planned primary outcome); and efficient working of trial components. Design and Setting A feasibility and external pilot randomised controlled trial (ISRCTN33808269, assigned 10/12/2012) was conducted across 2 UK secondary care outpatient physiotherapy departments associated with regional spinal surgery centres. Participants Consecutive consenting patients aged >18 years; post primary, single level, lumbar discectomy. Interventions Participants were randomised to either 1:1 physiotherapy outpatient management including patient leaflet, or patient leaflet alone. Main Outcome Measures Blinded assessments were made at 4 weeks post surgery (baseline) and 12 weeks post baseline (proposed primary end point). Secondary outcomes included: Global Perceived Effect, back/leg pain, straight leg raise, return to work/function, quality of life, fear avoidance, range of movement, medication, re-operation. Results At discharge, 110 (44%) eligible patients gave consent to be contacted. 59 (54%) patients were recruited. Loss to follow up was 39% at 12 weeks, with one site contributing 83% losses. Mean (SD) RMDQ was 10.07 (5.58) leaflet and 10.52 (5.94) physiotherapy/leaflet at baseline; and 5.37 (4.91) leaflet and 5.53 (4.49) physiotherapy/leaflet at 12 weeks. 5.1% zero scores at 12 weeks illustrated no floor effect. Sensitivity to change was assessed at 12 weeks with mean (SD) change -4.53 (6.41), 95%CI -7.61 to -1.44 for leaflet; and -6.18 (5.59), 95%CI -9.01 to -3.30 for physiotherapy/leaflet. RMDQ mean difference (95%CI) between change from baseline to twelve weeks was 1.65(-2.46 to 5.75). Mean difference (95%CI) between groups at 12 weeks was -0.16 (-3.36 to 3.04). Participant adherence with treatment was good. No adverse events were reported. Conclusions Both interventions were acceptable, and it is promising that they both demonstrated a trend in reducing disability in this population. A randomised controlled trial, using a different trial design, is needed to ascertain the effectiveness of combining the interventions into a stepped care intervention and comparing to a no intervention arm. Findings will guide design changes for an adequately powered randomised controlled trial, using RMDQ as the primary outcome

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences