Rhodium(I) carbonyl complexes of mono selenium functionalized enylphosphino)methane and Bis(di- phenylphosphino)amine chelating ligands and their catalytic carbonylation activity

The chelate complexes of the types [Rh(CO)Cl(Ph2PCH2P(Se)Ph2)] (1) and [Rh(CO)Cl(Ph2PN(CH3)P(Se)Ph2)] (2) have been synthesized and characterized by IR and NMR spectroscopy. The lower shift of the m(P–Se) bands and downfield shift of the 31P– { 1H}NMR signals for both P(III) and P(V) atoms in 1 and 2 compared to the corresponding free ligands indicate chelate formation through selenium donor. 1 and 2 show terminalm(CO) bands at 1977 and 1981cm 1, respectively, suggesting high electron density at themetalcenter.Themolecularstructureof2hasbeendeterminedbysingle-crystalX-raydiffraction.Therhodiumatomisatthecenter ofasquareplanargeometryhavingthephosphorusandseleniumatomsofthechelatingligandatcis-position,onecarbonylgrouptransto selenium and one chlorine atom trans- to phosphorus atom. 1 and 2 undergo oxidative addition (OA) reaction with CH 3I to produce acyl complexes [Rh(COCH3)ClI(Ph2PCH2P(Se)Ph2)] (3) and [Rh(COCH3)ClI(Ph2PN(CH3)P(Se)Ph2)] (4), respectively. The kinetics of the OAreactionsrevealthat1undergoesfasterreactionbyabout4.5timesthan2.Thecatalyticactivityof1and2incarbonylationofmethanol was higher than that of the well known species [Rh(CO) 2I2] and 2 shows higher catalytic activity compared to 1. 2005 Elsevier B.V. All rights reserved. Keywords: Rhodium(I) carbonyl complexes; Bis(diphenylphosphino)methane selenide; Bis(diphenylphosphino)amine selenide; Oxidative addition; Carbonylatio

The antimicrobial activity of a carbon monoxide releasing molecule (EBOR-CORM-1) is shaped by intraspecific variation within3 Pseudomonas aeruginosa populations

Carbon monoxide releasing molecules (CORMs) have been suggested as a new synthetic class of antimicrobials to treat bacterial infections. Here we utilized a novel EBOR-CORM-1 ([NEt4][MnBr2(CO)4]) capable of water-triggered CO-release, and tested its efficacy against a collection of clinical Pseudomonas aeruginosa strains that differ in infection-related virulence traits. We found that while EBOR-CORM-1 was effective in clearing planktonic and biofilm cells of P. aeruginosa strain PAO1 in a concentration dependent manner, this effect was less clear and varied considerably between different P. aeruginosa cystic fibrosis (CF) lung isolates. While a reduction in cell growth was observed after 8 h of CORM application, either no effect or even a slight increase in cell densities and the amount of biofilm was observed after 24 h. This variation could be partly explained by differences in bacterial virulence traits: while CF isolates showed attenuated in vivo virulence and growth compared to strain PAO1, they formed much more biofilm, which could have potentially protected them from the CORM. Even though no clear therapeutic benefits against a subset of isolates was observed in an in vivo wax moth acute infection model, EBOR-CORM-1 was more efficient at reducing the growth of CF isolate co-culture populations harboring intraspecific variation, in comparison with efficacy against more uniform single isolate culture populations. Together these results suggest that CORMs could be effective at controlling genetically diverse P. aeruginosa populations typical for natural chronic CF infections and that the potential benefits of some antibiotics might not be observed if tested only against clonal bacterial populations

Getting the strain under control: Trans-Varestraint tests for hot cracking susceptibility

A new method for conducting Trans-Varestraint tests for assessing hot cracking susceptibility is proposed. Experiments were carried out, to validate the new method, with an industrial scale rig using tungsten inert gas welding. The hot cracking susceptibility of API-5L X65 and EN3B steel was compared. The results indicated that, by using the new method, the strain applied to the welding bead and consequently to the solidification front was controlled in a repeatable and reliable way. The results also indicated that EN3B has a maximum crack length (a parameter in the test) higher than X65 and it is reached at lower augmented strain thus demonstrating it is more susceptible to hot cracking, while also indicating that there is a capability of predicting the initiation position of hot cracks during welding. By using the method proposed, the capability of setting standardized test procedures for Trans-Varestraint tests is improved. It is recommended that future tests for assessing hot cracking susceptibility should employ the proposed method in order for the results to be comparable and to also study the effect of strain rate in hot cracking of materials

The EMPOWER blended digital intervention for relapse prevention in schizophrenia: a feasibility cluster randomised controlled trial in Scotland and Australia

Background: Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia. Methods: This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262). Findings: We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Aug 8, 2018; 73 were randomised (42 [58%] to EMPOWER and 31 [42%] to treatment as usual). There were 37 (51%) men and 36 (49%) women. At 12 months, main outcomes were collected for 32 (76%) of service users in the EMPOWER group and 30 (97%) of service users in the treatment as usual group. Of those randomised to EMPOWER, 30 (71%) met our a priori criterion of more than 33% adherence to daily monitoring that assumed feasibility. Median time to discontinuation of these participants was 31·5 weeks (SD 14·5). There were 29 adverse events in the EMPOWER group and 25 adverse events in the treatment as usual group. There were 13 app-related adverse events, affecting 11 people, one of which was serious. Fear of relapse was lower in the EMPOWER group than in the treatment as usual group at 12 months (mean difference –7·53 (95% CI –14·45 to 0·60; Cohen's d –0·53). Interpretation: A trial of digital technology to monitor early warning signs blended with peer support and clinical triage to detect and prevent relapse appears to be feasible, safe, and acceptable. A further main trial is merited. Funding: UK National Institute for Health Research Health Technology Assessment programme and the Australian National Health and Medical Research Council

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT

Background: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. Objective: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? Design: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. Settings: Glasgow, UK, and Melbourne, Australia. Participants: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. Interventions: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. Main outcome measures: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. Results: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference –4.29, 95% confidence interval –7.29 to –1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. Limitations: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. Conclusions: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible

The Synthesis of [{n-Bu2Sn(S2N2)}2] and its use in the preparation of Organometallic Iridium Sulfur Nitrogen Complexes

The addition of [n-Bu2SnCl2] to a solution of [S4N3][Cl] in liquid ammonia gave after extraction of the dry reaction mixture the new tin disulfur dinitrido compound [{n-Bu2Sn(S2N2)}(2)] (1). Reaction of [{n-Bu2Sn(S2N2)}(2)] (1) with the pentamethylcyclopentadienyl (Cp*) iridium derivatives [{IrCl(mu-Cl)(eta(5)-C5Me5)}(2)] or [(eta(5)-C5Me5)IrCl2(PPh3)] gave different products, which were dependent on the reactant ratios. A 1:1 reaction between 1 and [{IrCl(mu-Cl)(eta(5)-C5Me5)}(2)] gave only [(eta(5)-C5Me5)Ir(S2N2)] (2) in moderate yield; the same product in higher yield was obtained from a 2:1 reaction between 1 and [(eta(5)-C5Me5)IrCl2(PPh3)]. Reaction of 1 and [(eta(5)-C5Me5)(2)IrCl2(PPh3)] (1:1 molar ratio) in the presence of NH4[PF6] gave the unusual bimetallic species [(eta(5)-C5Me5)IrCl(PPh3)(S2N2)Ir(eta(5)-C5Me5)][PF6] (3). The X-ray crystal structures of 1, 2, and 3 are reported.PostprintPeer reviewe

Effect of non-meat, high protein supplementation on quality of life and clinical outcomes for older people living in care homes: systematic review and meta-analysis

CONTEXT: Care home residents are at risk of malnutrition through reduced overall food intake, ‘anabolic resistance’ in ageing muscle and high prevalence of medical morbidity and functional dependency. There has been limited consensus regarding effectiveness of a high protein diet on quality of life or clinical outcomes for care home residents. OBJECTIVE: To evaluate the effectiveness of non-meat, high protein supplementation on Health-Related Quality of Life (HRQOL) and relevant clinical and nutritional outcomes in older people in the care home setting. DATA SOURCES: We searched EMBASE, AMED, CINAHL, MEDLINE, and the Cochrane Registry of Clinical Trials, OpenGrey, clinicaltrials.gov, the WHO clinical trial registry and the ISRCTN and NIHR trial portfolio (to February 2018) for randomised controlled trials. DATA EXTRACTION: We extracted data from included trials if they assessed people aged 65 years and over living in care homes, who received a protein supplementation compared to not. DATA ANALYSIS: We assessed trial quality using Cochrane Risk of Bias tool and meta-analysis was undertaken when appropriate. RESULTS: 17 papers with 1,246 participants fulfilled the inclusion criteria. All studies were low or moderate quality. No evidence of improving HRQOL when the SF-36 was used (Standardised Mean Difference (SMD: -0.10; 95% CI: -0.51 to 0.31; p=0.62), although significant improvement was seen in the single trial using EQ-5D (SMD: 2.58; 95% CI: 2.05 to 3.10; p<0.00001). CONCLUSIONS: Non-meat, high-protein oral supplements can improve markers of nutritional status in care home residents. However, there is insufficient high-quality evidence to determine the effect of such interventions for older adults in care homes with regard to HRQOL

Feasibility study of portable technology for weight loss and HbA1c control in type 2 diabetes

Background The study investigated the feasibility of conducting a future Randomised Controlled Trial (RCT) of a mobile health (mHealth) intervention for weight loss and HbA1c reduction in Type 2 Diabetes Mellitus (T2DM). Methods The intervention was a small wearable mHealth device used over 12 weeks by overweight people with T2DM with the intent to lose weight and reduce their HbA1c level. A 4 week maintenance period using the device followed. The device records physical activity level and information about food consumption, and provides motivational feedback based on energy balance. Twenty-seven participants were randomised to receive no intervention; intervention alone; or intervention plus weekly motivational support. All participants received advice on diet and exercise at the start of the study. Weight and HbA1c levels were recorded at baseline and weeks 6, 12, and 16. Qualitative interviews were conducted with participants who received the intervention to explore their experiences of using the device and involvement in the study including the training received. Results Overall the device was perceived to be well-liked, acceptable, motivational and easy to use by participants. Some logistical changes were required during the feasibility study, including shortening of the study duration and relaxation of participant inclusion criteria. Descriptive statistics of weight and HbA1c data showed promising trends of weight loss and HbA1c reduction in both intervention groups, although this should be interpreted with caution. Conclusions A number of methodological recommendations for a future RCT emerged from the current feasibility study. The mHealth device was acceptable and promising for helping individuals with T2DM to reduce their HbA1c and lose weight. Devices with similar features should be tested further in larger studies which follow these methodological recommendations

Identifying barriers and tailoring interventions to improve the management of urinary tract infections and sore throat: a pragmatic study using qualitative methods

BACKGROUND: Theories of behaviour change indicate that an analysis of factors that facilitate or impede change is helpful when trying to influence professional practice. The aim of this study was to identify barriers to implementing evidence-based guidelines for urinary tract infection and sore throat in general practice in Norway, and to tailor interventions to address these barriers. METHODS: We used a checklist to identify barriers and possible interventions to address these in an iterative process that included a review of the literature, brainstorming, focus groups, a pilot study, small group discussions and interviews. RESULTS: We identified at least one barrier for each category. Both guidelines recommended increased use of telephone consultations and reduced use of laboratory tests, and the barriers and the interventions were similar for the two guidelines. The complexity of changing routines involving patients, general practitioners and general practitioner assistants, loss of income with telephone consultations, fear of overlooking serious disease, perceived patient expectations and lack of knowledge about the evidence for the guidelines were the most prominent barriers. The interventions that were tailored to address these barriers included support for change processes in the practices, increasing the fee for telephone consultations, patient information leaflets and computer-based decision support and reminders. CONCLUSION: A systematic approach using qualitative methods helped identify barriers and generate ideas for tailoring interventions to support the implementation of guidelines for the management of urinary tract infections and sore throat. Lack of resources limited our ability to address all of the barriers adequately

Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis

Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl(4)-induced model of reversible hepatic fibrosis to identify and characterize the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11B(hi) F4/80(int) Ly-6C(lo) macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoter–diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C(hi) monocytes, a common origin with profibrotic Ly-6C(hi) macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C(lo) subset, compared with Ly-6C(hi) macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process