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Additional file 2. REC Favourable Opinion.

Additional file 5. (The SPIRIT Checklist). Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT): a checklist for a set of scientific, ethical and administrative elements recommended to be listed in a protocol [21] .

Additional file 6. Full Protocol

Additional file 1. A copy of the Process Evaluation Participant Information Sheet (Medic, Manager, CNS) and Informed Consent Form.

Additional file 4. Patient Invitation Pack (including Patient Information Sheet and Informed Consent Form.

Background: Digital interventions offer a potentially cost-effective means to support patient self-management in primary care, but evidence for the feasibility, acceptability and cost-effectiveness of digital interventions remains mixed. This programme focused on the potential for self-management digital interventions to improve outcomes in two common, contrasting conditions (i.e. hypertension and asthma) for which care is currently suboptimal, leading to excess deaths, illness, disability and costs for the NHS. Objectives: The overall purpose was to address the question of how digital interventions can best provide cost-effective support for patient self-management in primary care. Our aims were to develop and trial digital interventions to support patient self-management of hypertension and asthma. Through the process of planning, developing and evaluating these interventions, we also aimed to generate a better understanding of what features and methods for implementing digital interventions could make digital interventions acceptable, feasible, effective and cost-effective to integrate into primary care. Design: For the hypertension strand, we carried out systematic reviews of quantitative and qualitative evidence, intervention planning, development and optimisation, and an unmasked randomised controlled trial comparing digital intervention with usual care, with a health economic analysis and nested process evaluation. For the asthma strand, we carried out a systematic review of quantitative evidence, intervention planning, development and optimisation, and a feasibility randomised controlled trial comparing digital intervention with usual care, with nested process evaluation. Setting: General practices (hypertension, n = 76; asthma, n = 7) across Wessex and Thames Valley regions in Southern England. Participants: For the hypertension strand, people with uncontrolled hypertension taking one, two or three antihypertensive medications. For the asthma strand, adults with asthma and impaired asthma-related quality of life. Interventions: Our hypertension intervention (i.e. HOME BP) was a digital intervention that included motivational training for patients to self-monitor blood pressure, as well as health-care professionals to support self-management; a digital interface to send monthly readings to the health-care professional and to prompt planned medication changes when patients’ readings exceeded recommended targets for 2 consecutive months; and support for optional patient healthy behaviour change (e.g. healthy diet/weight loss, increased physical activity and reduced alcohol and salt consumption). The control group were provided with a Blood Pressure UK (London, UK) leaflet for hypertension and received routine hypertension care. Our asthma intervention (i.e. My Breathing Matters) was a digital intervention to improve the functional quality of life of primary care patients with asthma by supporting illness self-management. Motivational content intended to facilitate use of pharmacological self-management strategies (e.g. medication adherence and appropriate health-care service use) and non-pharmacological self-management strategies (e.g. breathing retraining, stress reduction and healthy behaviour change). The control group were given an Asthma UK (London, UK) information booklet on asthma self-management and received routine asthma care. Main outcome measures: The primary outcome for the hypertension randomised controlled trial was difference between intervention and usual-care groups in mean systolic blood pressure (mmHg) at 12 months, adjusted for baseline blood pressure, blood pressure target (i.e. standard, diabetic or aged > 80 years), age and general practice. The primary outcome for the asthma feasibility study was the feasibility of the trial design, including recruitment, adherence, intervention engagement and retention at follow-up. Health-care utilisation data were collected via notes review. Review methods: The quantitative reviews included a meta-analysis. The qualitative review comprised a meta-ethnography. Results: A total of 622 hypertensive patients were recruited to the randomised controlled trial, and 552 (89%) were followed up at 12 months. Systolic blood pressure was significantly lower in the intervention group at 12 months, with a difference of –3.4 mmHg (95% confidence interval –6.1 to –0.8 mmHg), and this gave an incremental cost per unit of systolic blood pressure reduction of £11 (95% confidence interval £5 to £29). Owing to a cost difference of £402 and a quality-adjusted life-year (QALY) difference of 0.044, long-term modelling puts the incremental cost per QALY at just over £9000. The probability of being cost-effective was 66% at willingness to pay £20,000 per quality-adjusted life-year, and this was higher at higher thresholds. A total of 88 patients were recruited to the asthma feasibility trial (target n = 80; n = 44 in each arm). At 3-month follow-up, two patients withdrew and six patients did not complete outcome measures. At 12 months, two patients withdrew and four patients did not complete outcome measures. A total of 36 out of 44 patients in the intervention group engaged with My Breathing Matters [with a median of four (range 0–25) logins]. Limitations: Although the interventions were designed to be as accessible as was feasible, most trial participants were white and participants of lower socioeconomic status were less likely to take part and complete follow-up measures. Challenges remain in terms of integrating digital interventions with clinical records. Conclusions: A digital intervention using self-monitored blood pressure to inform medication titration led to significantly lower blood pressure in participants than usual care. The observed reduction in blood pressure would be expected to lead to a reduction of 10–15% in patients suffering a stroke. The feasibility trial of My Breathing Matters suggests that a fully powered randomised controlled trial of the intervention is warranted. The theory-, evidence-and person-based approaches to intervention development refined through this programme enabled us to identify and address important contextual barriers to and facilitators of engagement with the interventions. Future work: This research justifies consideration of further implementation of the hypertension intervention, a fully powered randomised controlled trial of the asthma intervention and wide dissemination of our methods for intervention development. Our interventions can also be adapted for a range of other health conditions. Trial and study registration: The trials are registered as ISRCTN13790648 (hypertension) and ISRCTN15698435 (asthma). The studies are registered as PROSPERO CRD42013004773 (hypertension review) and PROSPERO CRD42014013455 (asthma review).

Additional file 3. ACCU data collection tool.

Additional file 2. Participant information sheet and consent form.

A representation theorem is proved for De Morgan monoids that are (i) semilinear, i.e., subdirect products of totally ordered algebras, and (ii) negatively generated, i.e., generated by lower bounds of the neutral element. Using this theorem, we prove that the De Morgan monoids satisfying (i) and (ii) form a locally finite variety. We then prove that epimorphisms are surjective in every variety of negatively generated semilinear De Morgan monoids. In the process, epimorphism-surjectivity is established for several other classes as well, including the variety of all semilinear idempotent commutative residuated lattices and all varieties of negatively generated semilinear Dunn monoids. The results settle natural questions about Beth-style definability for a range of substructural logics.

Additional file 1. Search strategy for Medline.

Additional file 1. ACCU_SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*.

Background\ud Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups.\ud Methods\ud ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298).\ud Findings\ud Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4–11] in the antibiotics group vs 6 days [4–15] in the placebo group; hazard ratio [HR] 1·13 [95% CI 0·90–1·42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis.\ud Interpretation\ud Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections.

The scope for biocatalytic modification of non‐native carvone derivatives for speciality intermediates has hitherto been limited. Additionally, caprolactones are important feedstocks with diverse applications in the polymer industry and new non‐native terpenone‐derived biocatalytic caprolactone syntheses are thus of potential value for industrial biocatalytic materials applications. Biocatalytic reduction of synthetic analogues of R‐(−)‐carvone with additional substituents at C3 or C6, or both C3 and C6, using three types of OYEs (OYE2, PETNR and OYE3) shows significant impact of both regio‐substitution and the substrate diastereomer. Bioreduction of (−)‐carvone derivatives substituted with a Me and/or OH group at C6 is highly dependent on the diastereomer of the substrate. Derivatives bearing C6 substituents larger than methyl moieties are not substrates. Computer docking studies of PETNR with both (6S)‐Me and (6R)‐Me substituted (−)‐carvone provides a model consistent with the outcomes of bioconversion. The products of bioreduction were efficiently biotransformed by the Baeyer–Villiger monooxygenase (BVase) CHMO_Phi1 to afford novel trisubstituted lactones with complete regioselectivity to provide a new biocatalytic entry to these chiral caprolactones. This provides both new non‐native polymerization feedstock chemicals, but also with enhanced efficiency and selectivity over native (+)‐dihydrocarvone Baeyer–Villigerase expansion. Optimum enzymatic reactions were scaled up to 60–100 mg, demonstrating the utility for preparative biocatalytic synthesis of both new synthetic scaffold‐modified dihydrocarvones and efficient biocatalytic entry to new chiral caprolactones, which are potential single‐isomer chiral polymer feedstocks.

Objective: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting: 76 general practices in the United Kingdom. Participants: 622 people with treated but poorly controlled hypertension (>140/90 mm Hg) and access to the internet. Interventions: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of −3.4 mm Hg (95% confidence interval −6.1 to −0.8 mm Hg) and a mean difference in diastolic blood pressure of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration: ISRCTN13790648.

Objective The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting 76 general practices in the United Kingdom. Participants 622 people with treated but poorly controlled hypertension (>140/90 mm Hg) and access to the internet. Interventions Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of −3.4 mm Hg (95% confidence interval −6.1 to −0.8 mm Hg) and a mean difference in diastolic blood pressure of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration ISRCTN13790648 .

Purpose To investigate the effect of Tai Chi exercise on postural balance among people with dementia (PWD) and the feasibility of a definitive trial on falls prevention. Patients and methods Dyads, comprising community-dwelling PWD and their informal carer (N=85), were randomised to usual care (n=43) or usual care plus weekly Tai Chi classes and home practice for 20 weeks (n=42). The primary outcome was the timed up and go test. All outcomes for PWD and their carers were assessed six months post-baseline, except for falls, which were collected prospectively over the six-month follow-up period. Results For PWD, there was no significant difference at follow-up on the timed up and go test (mean difference [MD] = 0.82, 95% confidence interval [CI] = −2.17, 3.81). At follow-up, PWD in the Tai Chi group had significantly higher quality of life (MD = 0.051, 95% CI = 0.002, 0.100, standardised effect size [ES] = 0.51) and a significantly lower rate of falls (rate ratio = 0.35, 95% CI =0.15, 0.81), which was no longer significant when an outlier was removed. Carers in the Tai Chi group at follow-up were significantly worse on the timed up and go test (MD = 1.83, 95% CI = 0.12, 3.53, ES = 0.61). The remaining secondary outcomes were not significant. No serious adverse events were related to participation in Tai Chi. Conclusion With refinement, this Tai Chi intervention has potential to reduce the incidence of falls and improve quality of life among community-dwelling PWD [Trial registration: NCT02864056]., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/4mLW1DbeYVw

Inducing opposite screw senses at the two ends of a helix traps a helix reversal, allowing it to be characterised spectroscopically., Helical oligomers of achiral monomers adopt domains of uniform screw sense, which are occasionally interrupted by screw-sense reversals. These rare, elusive, and fast-moving features have eluded detailed characterization. We now describe the structure and habits of a screw-sense reversal trapped within a fragment of a helical oligoamide foldamer of the achiral quaternary amino acid 2-aminoisobutyric acid (Aib). The reversal was enforced by compelling the amide oligomer to adopt a right-handed screw sense at one end and a left-handed screw sense at the other. The trapped reversal was characterized by X-ray crystallography, and its dynamic properties were monitored by NMR and circular dichroism, and modelled computationally. Raman spectroscopy indicated that a predominantly helical architecture was maintained despite the reversal. NMR and computational results indicated a stepwise shift from one screw sense to another on moving along the helical chain, indicating that in solution the reversal is not localised at a specific location, but is free to migrate across a number of residues. Analogous unconstrained screw-sense reversals that are free to move within a helical structure are likely to provide the mechanism by which comparable helical polymers and foldamers undergo screw-sense inversion.

Aims of the research: We aim to summarise what is known about shock-absorbing flooring in hospitals and care homes, with regards to reducing injuries from falls. We want to help people decide whether or not to invest in using shock-absorbing floors. We will see if shock-absorbing flooring can: (1) reduce injuries from falls; (2) increase the chances of someone falling over; and (3) lead to injuries in staff who may find it harder to move equipment across a softer floor. We will also summarise any research on the economic costs and savings of shock-absorbing floors. Finally, we will look at any practical issues people had when installing the new floors, and explore the experiences and attitudes of people who have used the floors (staff, residents/patients, and visitors). Background to the research: Falls and fall-related injuries are a major problem in hospitals and care homes. Older people are more at risk of falling, and more at risk of injuring themselves if they do fall. Injuries from falls can lead to loss of independence and mobility, shorter lives, and lower quality lives. Shock-absorbing flooring is one potential solution to help reduce the impact of a fall. Researchers from different countries have been studying the use of shock-absorbing floors in hospitals and care homes, but nobody has brought all of these studies together to summarise their findings in a systematic way. Design and methods used: We will carry out a thorough search to identify all the studies we can find that have looked at shock-absorbing flooring use in hospitals and care homes. We will assess these studies for quality, and gather data on what they did, who they involved, and what they found. We will summarise the information we find, to make it more easily understood. Where appropriate, we will combine the data from different studies to produce an overall result. We will explore the differences between studies, to help us understand which factors might influence whether shock-absorbing flooring works, and to determine how trustworthy the findings are. We will use the findings from studies included in the review to produce recommendations that can guide end-users of the review. Patient and public involvement: Our patient and public members will be involved throughout the project. They will help make sure our findings are easy to understand, and include all the important information. They will check the judgements we make about the quality of the research we find, to make sure we are being fair and clear. They will be involved in meetings to help guide us and make decisions. They will help us make a short video, which explains the findings of our research through patient experiences. Dissemination: We will share our findings in different ways to suit different people. We will publish our report in an academic journal, with universal free access. We will present our findings at two conferences (one in England and one abroad), which have a focus on caring for older people, and online in a webinar. We will hold a half-day workshop, to which we will invite people who may find our review useful. We will produce short reports to give to people who make decisions about which flooring to use in hospitals and care homes. Finally we will make a short online video which tells the findings of the review through the views and stories of patients. This is because many people like to make decisions when they hear patients' or residents' views.

BACKGROUND: Concerns about the degree of compassion in health care have become a focus for national and international attention. However, existing research on compassionate care interventions provides scant evidence of effectiveness or the contexts in which effectiveness is achievable.\ud OBJECTIVES: To assess the feasibility of implementing Creating Learning Environments for Compassionate Care programme (CLECC) in acute hospital settings and evaluating its impact on patient care.\ud DESIGN: Pilot cluster randomised controlled trial (CRT) and associated process and economic evaluations.\ud SETTING: Six inpatient ward nursing teams (clusters) in two English NHS hospitals randomised to intervention (n=4) or control (n=2)\ud PARTICIPANTS: 639 patients, 211 staff, 188 visitors.\ud INTERVENTION: CLECC, a workplace educational intervention focused on developing sustainable leadership and work-team practices (dialogue, reflective learning, mutual support) theorised to support the delivery of compassionate care. Control: no planned staff team-based educational activity.\ud MAIN OUTCOME MEASURES: Quality of Interaction Schedule (QuIS) for staff-patient interactions; patient-reported evaluations of emotional care in hospital (PEECH); nurse-reported empathy (Jefferson Scale of Empathy).\ud DATA SOURCES: structured observations of staff-patient interactions; patient, visitor and staff questionnaires and qualitative interviews; qualitative observations of CLECC activities.\ud RESULTS: CRT: Pilot proceeded as planned and randomisation was acceptable to teams. There was evidence of contamination between wards in the same hospital. QuIS performed well achieving a 93% recruitment rate with 25% of patient sample cognitively impaired. At follow-up there were more positive (78% versus 74%) and less negative (8% versus 11%) QuIS ratings for intervention wards versus control wards. 63% of intervention ward patients scored lowest (i.e. more negative) scores on PEECH connection subscale, compared with 79% of control group patients. These differences, while supported by the qualitative findings, are not statistically significant. No statistically significant differences in nursing empathy were observed, although response rates to staff questionnaire were low (36%). Process evaluation: The CLECC intervention is feasible to implement in practice with medical and surgical nursing teams in acute care hospitals. We found strong evidence of good staff participation in some CLECC activities and staff reported benefits throughout its introductory period and beyond. Further impact and sustainability were limited by the focus on changing ward team behaviours rather than wider system restructuring. Economic evaluation: We also identified the costs associated with using CLECC and recommend that an impact inventory be used in any future study.\ud LIMITATIONS: Findings are not generalizable outside of hospital nursing teams and this feasibility work is not powered to detect differences due to CLECC.\ud CONCLUSIONS: Use of experimental methods is feasible. The use of structured observation of staff-patient interaction quality is a promising primary outcome that is inclusive of patient groups often excluded from research but further validation is required. Further development of the CLECC intervention should focus on ensuring it is adequately supported by resources, norms and relationships in the wider system by, for instance, improving the cognitive participation of senior nurse managers.

AIMS: Polypharmacy is increasingly common in older adults, placing them at risk of medication-related harm (MRH). Patients are particularly vulnerable to problems with their medications in the period following hospital discharge due to medication changes, and poor information transfer between hospital and primary care. The aim of this study was to investigate the incidence, severity, preventability and cost of medication-related harm (MRH) in older adults in England post-discharge.METHODS: An observational multicentre prospective cohort study recruited 1280 older adults (median age 82 years) from five teaching hospitals in Southern England, UK. Participants were followed up for eight weeks by senior pharmacists, using 3 data sources (hospital readmission review, participant telephone interview and primary care records), to identify MRH and associated health service utilisation.RESULTS: Four hundred and thirteen participants (37%) experienced MRH (556 MRH events per 1000 discharges). Three hundred and thirty-six (81%) cases were serious, and 214 (52%) potentially preventable. Four participants experienced fatal MRH. The most common MRH events were gastrointestinal (n=158, 25%) and neurological (n=111, 18%). Medicine classes associated with the highest risk of MRH were opiates, antibiotics, and benzodiazepines. Three hundred and twenty-eight (79%) participants with MRH sought healthcare over the eight-week follow-up. The incidence of MRH associated hospital readmission was 78 per 1000 discharges. Post-discharge MRH in older adults is estimated to cost the National Health Service £396 million annually, of which £243 million is potentially preventable.CONCLUSIONS: MRH is common in older adults following hospital discharge, and results in substantial use of healthcare resources.

Selenium and sulfur derivatives of lead(II) acylchalcogourato complexes have been used to deposit PbSxSe1-x thin films by AACVD. By variation of the mole ratio of sulfur and selenium precursors in the aerosol feed solution the full range of compositions of PbSxSe1-x was obtained, i.e. 0 ≥ x ≥ 1. The films showed no contaminant phases demonstrating the potential for acylchalcogourato metal complexes as precursors for metal chalcogenide thin flms. The crystal structure for bis[N,N-diethyl-N`-2-naphthoylthioureato] lead(II) was solved and displayed the expected decreases in Pb-E bond lengths from the previously reported selenium variant.

Model Consent Form. (PDF 111 kb)

In the title compound, the Ir3+ cation is coordinated by two C atoms and four N atoms in a slightly distorted octa­hedral geometry. The asymmetric unit consists of one complex trication, three hexa­fluorido­phosphate anions and three aceto­nitrile solvent mol­ecules., In the title compound, [Ir(C11H8N)2(C28H20N8)](PF6)3·3CH3CN or [IrIII(ppy)2{(2-pym)2qpy2+}](PF6)3·3CH3CN (ppy = deprotonated 2-phenyl­pyridine, pym = pyrimidyl and qpy = 4,4′:2′,2′′:4′′,4′′′-quaterpyrid­yl), the Ir3+ cation is coordinated by two C atoms and four N atoms in a slightly distorted octa­hedral geometry. The asymmetric unit consists of one complex trication, three hexa­fluorido­phosphate anions and three aceto­nitrile solvent mol­ecules. The average Ir—C distance is 2.011 (14) Å, the average Ir—N(ppy) distance is 2.05 (6) Å and the average Ir—N(qpy) distance is longer at 2.132 (10) Å. The dihedral angles within the 4,4′-bipyridyl units are 31.5 (6) and 23.8 (7)°, while those between the 2-pym and attached pyridyl rings are rather smaller, at 11.7 (9) and 7.1 (9)°. The title compound was refined as a two-component inversion twin.

The synthesis of the asymmetric dithiocarbamates of tin(II) with the formula [Sn(S2CNRR׳)2] (where R=Et, R׳=n-Bu (1); R=Me, R׳=n-Bu (2); R=R׳=Et (3)) and their use for the deposition of SnS thin films by aerosol-assisted chemical vapour deposition (AACVD) is described. The effects of temperature and the concentration of the precursors on deposition were investigated. The stoichiometry of SnS was best at higher concentrations of precursors (250mM) and at 450°C. The direct electronic band gap of the SnS produced by this method was estimated from optical absorbance measurements as 1.2eV. The composition of films was confirmed by powder X-ray diffraction (p-XRD) and energy dispersive analysis of X-rays (EDAX) spectroscopy.

The use of Scholl-type reactions on 4,10-di-substituted chrysene derivatives proceeds via variegated, and unexpected oxidation/coupling pathways. These observations serve as a cautionary note when attempting to employ the Scholl reaction in target-oriented, materials, synthesis.

Literature search strategies for the two reviews. (PDF 242 kb)

The reaction between 3,6,9-trithia-1(2,6)-pyridinacyclodecaphane and representative group 10 and 11 metal salts [Cu(NO3)2, NiCl2 or Ag(CF3CO2 )] afforded 1:1 complexes which in the case of Cu(II) and Ag(I) were characterized by single crystal X-ray crystallography. The catalytic activity of these complexes in A3-coupling reactions between aldehydes, terminal alkynes and amines was assessed in both protic (water) and aprotic (toluene) media. These A3-reactions prove to be more efficient, proceed with lower catalyst loadings and with faster reaction rates, when conducted in a focused microwave reactor as compared to the same reactions promoted by standard, thermal, modes of activation

The application of a new benzannulation reaction for the regiocontrolled synthesis of functionalized chrysenes is reported. The initial benzannulation and the subsequent halogen displacement reactions are both highly regiospecific, which thereby enables the regiocontrolled synthesis of a variety of 4,10-disubstituted chrysenes from commercially available 1,5-dihydroxynaphthalene.

2.2]Paracyclophane-1,9-dienes substituted with n-octyl chains have been synthesised from the corresponding dithia[3.3]paracyclophanes using a benzyne induced Stevens rearrangement. The use of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate and tetra-n-butylammonium fluoride as the in situ benzyne source gave significantly improved yields over traditional sources of benzyne and enabled the preparation of n-octyl substituted [2.2]paracyclophane-1,9-dienes on a multi-gram scale.

The synthetic biology toolbox lacks extendable and conformationally controllable yet easy-to-synthesize building blocks that are long enough to span membranes. To meet this need, an iterative synthesis of α-aminoisobutyric acid (Aib) oligomers was used to create a library of homologous rigid-rod 310-helical foldamers, which have incrementally increasing lengths and functionalizable N- and C-termini. This library was used to probe the inter-relationship of foldamer length, self-association strength, and ionophoric ability, which is poorly understood. Although foldamer self-association in nonpolar chloroform increased with length, with a ∼14-fold increase in dimerization constant from Aib6 to Aib11, ionophoric activity in bilayers showed a stronger length dependence, with the observed rate constant for Aib11 ∼70-fold greater than that of Aib6. The strongest ionophoric activity was observed for foldamers with >10 Aib residues, which have end-to-end distances greater than the hydrophobic width of the bilayers used (∼2.8 nm); X-ray crystallography showed that Aib11 is 2.93 nm long. These studies suggest that being long enough to span the membrane is more important for good ionophoric activity than strong self-association in the bilayer. Planar bilayer conductance measurements showed that Aib11 and Aib13, but not Aib7, could form pores. This pore-forming behavior is strong evidence that Aibm (m ≥ 10) building blocks can span bilayers.

The synthetic biology toolbox lacks extendable and conformationally controllable yet easy-to-synthesize building blocks that are long enough to span membranes. To meet this need, an iterative synthesis of α-aminoisobutyric acid (Aib) oligomers was used to create a library of homologous rigid-rod 310-helical foldamers, which have incrementally increasing lengths and functionalizable N- and C-termini. This library was used to probe the inter-relationship of foldamer length, self-association strength, and ionophoric ability, which is poorly understood. Although foldamer self-association in nonpolar chloroform increased with length, with a ∼14-fold increase in dimerization constant from Aib6 to Aib11, ionophoric activity in bilayers showed a stronger length dependence, with the observed rate constant for Aib11 ∼70-fold greater than that of Aib6. The strongest ionophoric activity was observed for foldamers with >10 Aib residues, which have end-to-end distances greater than the hydrophobic width of the bilayers used (∼2.8 nm); X-ray crystallography showed that Aib11 is 2.93 nm long. These studies suggest that being long enough to span the membrane is more important for good ionophoric activity than strong self-association in the bilayer. Planar bilayer conductance measurements showed that Aib11 and Aib13, but not Aib7, could form pores. This pore-forming behavior is strong evidence that Aibm (m ≥ 10) building blocks can span bilayers.

The title copper(II) complex, {(C27H37N2)[Cu4(CH3COO)8Cl]·3CH2Cl2} n , is a one-dimensional coordination polymer. The asymmetric unit is composed of a copper(II) tetra-acetate paddle-wheel complex, a Cl(-) anion situated on a twofold rotation axis, half a 1,3-bis-(2,6-diisoprop-ylphenyl)imidazolium cation (the whole mol-ecule being generated by twofold rotation symmetry) and one and a half of a di-chloro-methane solvent mol-ecule (one being located about a twofold rotation axis). The central metal-organic framework comprises of a tetra-nuclear copper(II) acetate 'paddle-wheel' complex which arises from the dimerization of the copper(II) tetra-acetate core comprising of three μ2-bidentate acetate and one μ3-tridentate acetate ligands per binuclear paddle-wheel complex. Both Cu(II) atoms of the binuclear component adopt a distorted square-pyramidal coordination geometry (τ = 0.04), with a Cu⋯Cu separation of 2.6016 (2) Å. The apical coordination site of one Cu(II) atom is occupied by an O atom of a neighbouring acetate bridge [Cu-O = 2.200 (2) Å], while that of the second Cu(II) atom is occupied by a bridging chloride ligand [Cu⋯Cl = 2.4364 (4) Å]. The chloride bridge is slightly bent with respect to the Cu⋯Cu inter-nuclear axis [Cu-Cl-Cu = 167.06 (6)°] and the tetra-nuclear units are located about a twofold rotation axis, forming the one-dimensional polymer that propagates along [101]. Charge neutrality is maintained by the inclusion of the 1,3-bis-(2,6-diisoprop-ylphenyl)imidazolium cation within the crystal lattice. In the crystal, the cation and di-chloro-methane solvent mol-ecules are linked to the coordin-ation polymer by various C-H⋯O and C-H⋯Cl hydrogen bonds. There are no other significant inter-molecular inter-actions present.

A generic approach to the regiospecific synthesis of halogenated polycyclic aromatics is made possible by the one- or two-directional benzannulation reactions of readily available (ortho-allylaryl)trichloroacetates (the “BHQ” reaction). Palladium-catalysed cross-coupling reactions of the so-formed haloaromatics enable the synthesis of functionalised polycyclic aromatic hydrocarbons (PAHs) with surgical precision. Overall, this new methodology enables the facile mining of chemical space in search of new electronic functional materials.

Lead sulfide has been grown from single molecular precursors within a polymer matrix to form networks of PbS nanocrystals. These materials are model systems for the processing of polymer–nanoparticle layers for flexible hybrid photovoltaic devices. Processing is achieved by spin coating a solution containing the precursor and polymer onto a substrate, followed by heating of the film to decompose the precursor. The effect of precursor chemistry has been explored using lead(II) dithiocarbamates, their 1,10-phen adducts, and lead(II) xanthates with different alkyl chain lengths (butyl, hexyl, and octyl). The xanthates were found to be more promising precursors giving control over nanocrystal size and shape on variation of the alkyl chain length. The lead(II) octyl xanthate complex causes anisotropic growth, forming PbS nanowires within the polymer matrix.

Criteria for use of systematic reviews to inform trial design. (PDF 58 kb)

Reasons for not referencing and using a systematic review. (PDF 201 kb)

Justification for first-in-class trials. (PDF 19 kb)

We review the design, fabrication, and performance of photonic crystal vertical cavity surface emitting lasers (VCSELs). Using a periodic pattern of etched holes in the top facet of the VCSEL, the optical cavity can be designed to support the fundamental mode only. The electrical confinement is independently defined by proton implantation or oxide confinement. By control of the refractive index and loss created by the photonic crystal, operation in the Gaussian mode can be insured, independent of the lasing wavelength.

OBJECTIVE:\ud To assess the cost effectiveness of different management strategies for urinary tract infections.\ud \ud DESIGN:\ud Cost effectiveness analysis alongside a randomised controlled trial with a one month follow-up.\ud \ud SETTING:\ud Primary care.\ud \ud PARTICIPANTS:\ud 309 non-pregnant adult women aged 18-70 presenting with suspected urinary tract infection.\ud \ud INTERVENTIONS:\ud Patients were randomised to five basic management approaches: empirical antibiotics, empirical delayed (by 48 hours) antibiotics, or targeted antibiotics based on either a high symptom score (two or more of urine cloudiness, smell, nocturia, dysuria), dipstick results (nitrite or leucocytes and blood), or receipt of a positive result on midstream urine analysis.\ud \ud MAIN OUTCOME MEASURE:\ud Duration of symptoms and cost of care.\ud \ud RESULTS:\ud Management with targeted antibiotics with midstream urine analysis was more costly over the period of one month. Costs for the midstream urine analysis and dipstick management groups were pound37 and pound35, respectively; these compared with pound31 for immediate antibiotics. Cost effectiveness acceptability curves suggested that if avoiding a day of moderately bad symptoms was valued at less than pound10, then immediate antibiotics is likely to be the most cost effective strategy. For values over pound10, targeted antibiotics with dipstick testing becomes the most cost effective strategy, though because of the uncertainty we can never be more than 70% certain that this strategy truly is the most cost effective.\ud \ud CONCLUSION:\ud Dipstick testing with targeted antibiotics is likely to be cost effective if the value of saving a day of moderately bad symptoms is pound10 or more, but caution is required given the considerable uncertainty surrounding the estimates.

BackgroundAlzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil.MethodDOMINO-AD is a pragmatic, 15 centre, double-blind, randomized, placebo controlled trial. Patients with AD, currently living at home, receiving donepezil 10 mg daily, and with Standardized Mini-Mental State Examination (SMMSE) scores between 5 and 13 are being recruited. Each is randomized to one of four treatment options: continuation of donepezil with memantine placebo added; switch to memantine with donepezil placebo added; donepezil and memantine together; or donepezil placebo with memantine placebo. 800 participants are being recruited and treatment continues for one year. Primary outcome measures are cognition (SMMSE) and activities of daily living (Bristol Activities of Daily Living Scale). Secondary outcomes are non-cognitive dementia symptoms (Neuropsychiatric Inventory), health related quality of life (EQ-5D and DEMQOL-proxy), carer burden (General Health Questionnaire-12), cost effectiveness (using Client Service Receipt Inventory) and institutionalization. These outcomes are assessed at baseline, 6, 18, 30 and 52 weeks. All participants will be subsequently followed for 3 years by telephone interview to record institutionalization.DiscussionThere is considerable debate about the clinical and cost effectiveness of anti-dementia drugs. DOMINO-AD seeks to provide clear evidence on the best treatment strategies for those managing patients at a particularly important clinical transition point.Trial registrationCurrent controlled trials ISRCTN49545035

This study empirically describes the activity and costs associated with the psychiatric services in England & Wales, Scotland & Ireland from 1845 to 1985. Basic economic concepts are employed to structure data. Key hypotheses from the three historical schools (Progressive, Social Control and Epidemiological) are tested, using a neo-Popperian methodology. The literature is reviewed in Chapter 2 (general and socio-economic) and Chapter 3 (epidemiological). Chapter 4 sets the comparative legal and financing context. Chapters 5, 6 and 7 outline activity and financial data for each country. Major points common to each included: - relative stability in admissions and costs up to around 1945, - a major change after 1945 when admission rates (both first and total) rose sharply, - inflows exceeded outflows until around 1955 when the number of resident inpatients began to fall, - despite the fall in resident inpatients, spending, which was predominantly publicly financed and hospital orientated, continued to increase. Chapter 8 suggests that three hypotheses were not obviously falsified by the data: - a pharmacological hypothesis linking new drugs in the mid-1950s to the changes which occurred then, - Wagner's Law, which predicts continued high levels of spending despite reductions in hospital places, and - Hare's epidemiological hypothesis which relied on the increase in first admission rates between 1850 and 1900. Four other hypotheses related to costs were rejected. Three paradoxes are identified for further investigation. Chapter 9 shows that the decline in the stock of inpatients occurred almost entirely in the long-stay (over 5 years) group, due mainly to deaths rather than live discharges. This pattern helps explain the continued high levels of spending. Ireland's outlier status is linked to both demand and supply side factors. Chapter 10 draws some overall conclusions and offers priorities for further research.

The aim of the project was the preparation and structural determination of dehydro-peptides . Queen Mary College, London

A collection of folklore and local history stories from Ganntaigh (Ganty) (school) (Ganty, Co. Galway), collected as part of the Schools' Folklore Scheme, 1937-1938 under the supervision of teacher Sorcha Bean Uí Chlúin., Hidden Treasures / Dempsey, Chrissie -- Local Riddles / Raftery, James -- Weather-Lore / Kennedy, Christie -- Severe Weather / Kennedy, Patrick -- Local Heroes / Kenny, Rosaleen -- Local Marriage Customs / Namara, Maura Mac -- Local Happenings / Kennedy, Christie -- Old Schools -- Old Crafts / Kennedy, Christie -- Local Cures / Kennedy, Christie -- Bird-Lore -- Homemade Toys -- Travelling Folk / Kennedy, Christie -- Fairy Forts -- Local Poets -- Famine Times -- Proverbs -- Potato Crop / Buckley, Paddy -- Herbs -- Old Story -- Old Story -- Another Old Story -- Another Old Story -- Old Story / Gardiner, Robert -- Old Story - The Cat that Wanted the Shoes -- Another Old Story -- Story - Three Like You -- Story About Biddy Earley -- Old Story / Uniacke, Brian -- Story - Poor Seán / Kennedy, Christie -- Old Story - The Two Wishes / Walsh, Paddy -- Old Story - The Well / Martyn, Mary -- Old Story - The Shadow / Martyn, Mary -- Old Story - Regan's Stone / Buckley, May -- Ghost Story / Kenny, Imelda -- Another Ghost Story / Callanan, Brigid -- Story / Namara, Eveleen Mc -- Old Ghost Story / Buckley, Paddy -- Story about a Fairy / Kennedy, Christie -- Story about a Fairy / Callanan, Brigid -- Old Story / Callanan, Brigid -- Old Story - St Peter and the Beggar / Buckley, Bertie -- Emblems - St Brigid's Cross / Kenny, Imelda -- Other Emblems -- Bread -- Old Houses / Dempsey, Michael / Buckley, Paddy -- Local Ruins - Moyode Castle -- Local Ruins - Strongfort Castle -- Local Ruins - See Finn Castle -- Local Ruins - Dunsandle Castle -- Old Graveyards / Dempsey, Michael / Buckley, Paddy -- Festival Customs / Buckley, Paddy / Raftery, James / Dempsey, Michael -- Local Fairs -- Local Roads / Dempsey, Michael -- Landlord -- Lore of Certain Days -- Care of Our Farm Animals / Uniacke, Madge -- Churning / Uniacke, Madge -- Care of the Feet / Walsh, Paddy -- My Home District / Raftery, James -- My Home District / Namara, Maura Mac -- My Home District / Dempsey, Michael -- Games we Play / Uniacke, Madge / Buckley, Paddy, Supported by funding from the Department of Arts, Heritage and the Gaeltacht (Ireland), University College Dublin, and the National Folklore Foundation (Fondúireacht Bhéaloideas Éireann), 2014-2016.

Here, we report the experimental observation of a dynamical quantum phase transition in a strongly interacting open photonic system. The system studied, comprising a Jaynes-Cummings dimer realized on a superconducting circuit platform, exhibits a dissipation-driven localization transition. Signatures of the transition in the homodyne signal and photon number reveal this transition to be from a regime of classical oscillations into a macroscopically self-trapped state manifesting revivals, a fundamentally quantum phenomenon. This experiment also demonstrates a small-scale realization of a new class of quantum simulator, whose well-controlled coherent and dissipative dynamics is suited to the study of quantum many-body phenomena out of equilibrium., Physical Review X, 4 (3), ISSN:2160-3308