Torus fibrations and localization of index II

We give a framework of localization for the index of a Dirac-type operator on an open manifold. Suppose the open manifold has a compact subset whose complement is covered by a family of finitely many open subsets, each of which has a structure of the total space of a torus bundle. Under an acyclic condition we define the index of the Dirac-type operator by using the Witten-type deformation, and show that the index has several properties, such as excision property and a product formula. In particular, we show that the index is localized on the compact set.Comment: 47 pages, 2 figures. To appear in Communications in Mathematical Physic

Actinobacillus pleuropneumoniae serovar 8 predominates in England and Wales

This work was supported by a Longer and Larger (LoLa) grant from the Biotechnology and Biological Sciences Research Council (BBSRC grant numbers BB/G020744/1, BB/G019177/1, BB/G019274/1 and BB/G018553/1) and Zoetis (formerly Pfizer Animal Health) awarded to the Bacterial Respiratory Diseases of Pigs-1 Technology (BRaDP1T) Consortium

A multistate model of health transitions in older people: a secondary analysis of ASPREE clinical trial data

Background: Understanding the nature of transitions from a healthy state to chronic diseases and death is important for planning health-care system requirements and interventions. We aimed to quantify the trajectories of disease and disability in a population of healthy older people. Methods: We conducted a secondary analysis of data from the ASPREE trial, which was done in 50 sites in Australia and the USA and recruited community-dwelling, healthy individuals who were aged 70 years or older (≥65 years for Black and Hispanic people in the USA) between March 10, 2010, and Dec 24, 2014. Participants were followed up with annual face-to-face visits, biennial assessments of cognitive function, and biannual visits for physical function until death or June 12, 2017, whichever occurred first. We used multistate models to examine transitions from a healthy state to first intermediate disease events (ie, cancer events, stroke events, cardiac events, and physical disability or dementia) and, ultimately, to death. We also examined the effects of age and sex on transition rates using Cox proportional hazards regression models. Findings: 19 114 participants with a median age of 74·0 years (IQR 71·6–77·7) were included in our analyses. During a median follow-up of 4·7 years (IQR 3·6–5·7), 1933 (10·1%) of 19 114 participants had an incident cancer event, 487 (2·5%) had an incident cardiac event, 398 (2·1%) had an incident stroke event, 924 (4·8%) developed persistent physical disability or dementia, and 1052 (5·5%) died. 15 398 (80·6%) individuals did not have any of these events during follow-up. The highest proportion of deaths followed incident cancer (501 [47·6%] of 1052) and 129 (12·3%) participants transitioned from disability or dementia to death. Among 12 postulated transitions, transitions from the intermediate states to death had much higher rates than transitions from a healthy state to death. The progression rates to death were 158 events per 1000 person-years (95% CI 144–172) from cancer, 112 events per 1000 person-years (86–145) from stroke, 88 events per 1000 person-years (68–111) from cardiac disease, 69 events per 1000 person-years (58–82) from disability or dementia, and four events per 1000 person-years (4–5) from a healthy state. Age was significantly associated with an accelerated rate for most transitions. Male sex (vs female sex) was significantly associated with an accelerate rate for five of 12 transitions. Interpretation: We describe a multistate model in a healthy older population in whom the most common transition was from a healthy state to cancer. Our findings provide unique insights into the frequency of events, their transition rates, and the impact of age and sex. These results have implications for preventive health interventions and planning for appropriate levels of residential care in healthy ageing populations. Funding: The National Institutes of Health

A core outcome set for nonpharmacological community-based interventions for people living with dementia at home: A systematic review of outcome measurement instruments

YesIt is questionable whether existing outcome measurement instruments (OMIs) in dementia research reflect what key stakeholders' value. We attained consensus from over 300 key stakeholders, including people living with dementia, and identified 13 core outcome items for use in nonpharmacological and community-based interventions for people with dementia living at home. In this systematic review we review OMIs that have previously been used in dementia care research to determine how, or even if, the 13 core outcome items can be measured. We extracted self-reported OMIs from trials, reviews and reports of instrument development. Searches were undertaken in the ALOIS database, Medline, PsycINFO, CINAHL, socINDEX and COSMIN database. We aimed to assess the psychometric properties of OMI items for face validity with the core outcome items, content validity, internal consistency and responsiveness. We held a co-research workshop involving people living with dementia and care partners in order to ratify the findings. In total 347 OMIs were located from 354 sources. Of these 76 OMIs met the inclusion criteria. No OMIs were deemed to have sufficient face validity for the COS items, and no OMIs proceeded to further assessment. The 'best' available OMI is the Engagement and Independence in Dementia Questionnaire (EID-Q). This study provides a practical resource for those designing dementia research trials. Being able to measure the COS items would herald a paradigm shift for dementia research, be responsive to what key stakeholders value and enhance the ability to make comparisons.This study was funded jointly by the Economic and Social Research Council (ESRC) and the National Institute for Health Research (NIHR). ESRC is part of UK Research and Innovation (UKRI)

What is important to people with dementia living at home? A set of core outcome items for use in the evaluation of non-pharmacological community-based health and social care interventions

YesObjectives: Inconsistency in outcome measurement in dementia care trials impedes the comparisons of effectiveness between trials. The key aim of this study is to establish an agreed standardised core outcome set (COS) for use when evaluating non-pharmacological health and social care interventions for people with dementia living at home. Method: We used a mixed-methods research design, including substantive qualitative research with five key stakeholders groups. We consulted with people living with dementia for many aspects of this research. We applied a modified two-round 54 item Delphi approach to attain consensus on core outcomes. The COS was finalised in a face-to-face consensus meeting in 2018. Results: Of the 288 who completed round 1 (21 people living with dementia, 58 care partners, 137 relevant health and social care professionals, 60 researchers, 12 policy makers), 246 completed round 2 (85% response rate). Twenty participants attended the consensus meeting. We reached consensus for the inclusion of 13 outcome items. Conclusion: We identified 13 outcome items which are considered core; many relate to social health. Providing there are adequate measures, measuring these core outcome items will enhance comparisons for effectiveness making trial evidence more useful. The items will provide commissioners and service planners with information on what types of interventions are most likely to be valued highly by people living with dementia.This study was funded jointly by the Economic and Social Research Council (ESRC) and the National Institute for Health Research (NIHR). ESRC is part of UK Research and Innovation

Performance Issues in U.S.–China Joint Ventures

Based on an in-depth study of U.S.-China joint ventures, this article offers some insights into the performance of such international business relationships. While the conventional literature treats government as an amorphous aspea of the political-legal environment, in this case government is an active participant and influence in the performance of international joint ventures (UVs). It has both a constraining and enabling effect on LJV structure, strategy, and performance. For example, limits can be placed on ownership shares of joint ventures and on prices of the output. At the same time, government can cooperate with LJVs and foreign parent companies by creating partners for foreign parent companies, acting as major customers, and improving financial performance by lowering taxes

A web-based, peer-supported self-management intervention to reduce distress in relatives of people with psychosis or bipolar disorder:the REACT RCT

BACKGROUND: Relatives caring for people with severe mental health problems find information and emotional support hard to access. Online support for self-management offers a potential solution. OBJECTIVE: The objective was to determine the clinical effectiveness and cost-effectiveness of an online supported self-management tool for relatives: the Relatives' Education And Coping Toolkit (REACT). DESIGN AND SETTING: This was a primarily online (UK), single-blind, randomised controlled trial, comparing REACT plus a resource directory and treatment as usual with the resource directory and treatment as usual only, by measuring user distress and other well-being measures at baseline and at 12 and 24 weeks. PARTICIPANTS: A total of 800 relatives of people with severe mental health problems across the UK took part; relatives who were aged ≥ 16 years, were experiencing high levels of distress, had access to the internet and were actively seeking help were recruited. INTERVENTION: REACT comprised 12 psychoeducation modules, peer support through a group forum, confidential messaging and a comprehensive resource directory of national support. Trained relatives moderated the forum and responded to messages. MAIN OUTCOME MEASURE: The main outcome was the level of participants' distress, as measured by the General Health Questionnaire-28 items. RESULTS: Various online and offline strategies, including social media, directed potential participants to the website. Participants were randomised to one of two arms: REACT plus the resource directory (n = 399) or the resource directory only (n = 401). Retention at 24 weeks was 75% (REACT arm, n = 292; resource directory-only arm, n = 307). The mean scores for the General Health Questionnaire-28 items reduced substantially across both arms over 24 weeks, from 40.2 (standard deviation 14.3) to 30.5 (standard deviation 15.6), with no significant difference between arms (mean difference -1.39, 95% confidence interval -3.60 to 0.83; p = 0.22). At 12 weeks, the General Health Questionnaire-28 items scores were lower in the REACT arm than in the resource directory-only arm (-2.08, 95% confidence interval -4.14 to -0.03; p = 0.027), but this finding is likely to be of limited clinical significance. Accounting for missing data, which were associated with higher distress in the REACT arm (0.33, 95% confidence interval -0.27 to 0.93; p = 0.279), in a longitudinal model, there was no significant difference between arms over 24 weeks (-0.56, 95% confidence interval -2.34 to 1.22; p = 0.51). REACT cost £142.95 per participant to design and deliver (£62.27 for delivery only), compared with £0.84 for the resource directory only. A health economic analysis of NHS, health and Personal Social Services outcomes found that REACT has higher costs (£286.77), slightly better General Health Questionnaire-28 items scores (incremental General Health Questionnaire-28 items score adjusted for baseline, age and gender: -1.152, 95% confidence interval -3.370 to 1.065) and slightly lower quality-adjusted life-year gains than the resource directory only; none of these differences was statistically significant. The median time spent online was 50.8 minutes (interquartile range 12.4-172.1 minutes) for REACT, with no significant association with outcome. Participants reported finding REACT a safe, confidential environment (96%) and reported feeling supported by the forum (89%) and the REACT supporters (86%). No serious adverse events were reported. LIMITATIONS: The sample comprised predominantly white British females, 25% of participants were lost to follow-up and dropout in the REACT arm was not random. CONCLUSIONS: An online self-management support toolkit with a moderated group forum is acceptable to relatives and, compared with face-to-face programmes, offers inexpensive, safe delivery of National Institute for Health and Care Excellence-recommended support to engage relatives as peers in care delivery. However, currently, REACT plus the resource directory is no more effective at reducing relatives' distress than the resource directory only. FUTURE WORK: Further research in improving the effectiveness of online carer support interventions is required. TRIAL REGISTRATION: Current Controlled Trials ISRCTN72019945. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 32. See the NIHR Journals Library website for further project information. Relatives of people with severe mental health problems need better access to information and emotional support. The Relatives’ Education And Coping Toolkit (REACT) is a website designed to do this. It includes lots of information presented in text and video, an online forum for relatives to share knowledge and experience, a messaging system where they can ask questions in confidence and a comprehensive directory of contact details for national organisations offering relevant support. Trained relatives support the forum and messaging. In the UK, we recruited 800 relatives of people with severe mental health problems: all were aged ≥ 16 years, had high levels of distress, had access to the internet and wanted help. We divided them into two equal groups: one group received REACT (including the resource directory), whereas the other group received the resource directory only. To ensure that there were no differences between groups at the start, relatives were allocated to the two groups randomly, so they had an equal chance of being in either group. We followed up with both groups at 12 and 24 weeks, and received data from approximately three-quarters of the participants. This trial found that REACT was acceptable, safe and inexpensive to deliver (£62.27 per relative), compared with face-to-face interventions, and that relatives using it felt well supported. However, once we accounted for missing data (relatives who dropped out of the trial or did not complete the follow-up questionnaires), there were no significant differences between the groups. There was no evidence that REACT increased relatives’ quality of life or saved money for the NHS

Guidelines for Reporting Outcomes in Trial Protocols: The SPIRIT-Outcomes 2022 Extension

Importance: Complete information in a trial protocol regarding study outcomes is crucial for obtaining regulatory approvals, ensuring standardized trial conduct, reducing research waste, and providing transparency of methods to facilitate trial replication, critical appraisal, accurate reporting and interpretation of trial results, and knowledge synthesis. However, recommendations on what outcome-specific information should be included are diverse and inconsistent. To improve reporting practices promoting transparent and reproducible outcome selection, assessment, and analysis, a need for specific and harmonized guidance as to what outcome-specific information should be addressed in clinical trial protocols exists. Objective: To develop harmonized, evidence- and consensus-based standards for describing outcomes in clinical trial protocols through integration with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement. Evidence Review: Using the Enhancing the Quality and Transparency of Health Research (EQUATOR) methodological framework, the SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement was developed by (1) generation and evaluation of candidate outcome reporting items via consultation with experts and a scoping review of existing guidance for reporting trial outcomes (published within the 10 years prior to March 19, 2018) identified through expert solicitation, electronic database searches of MEDLINE and the Cochrane Methodology Register, gray literature searches, and reference list searches; (2) a 3-round international Delphi voting process (November 2018-February 2019) completed by 124 panelists from 22 countries to rate and identify additional items; and (3) an in-person consensus meeting (April 9-10, 2019) attended by 25 panelists to identify essential items for outcome-specific reporting to be addressed in clinical trial protocols. Findings: The scoping review and consultation with experts identified 108 recommendations relevant to outcome-specific reporting to be addressed in trial protocols, the majority (72%) of which were not included in the SPIRIT 2013 statement. All recommendations were consolidated into 56 items for Delphi voting; after the Delphi survey process, 19 items met criteria for further evaluation at the consensus meeting and possible inclusion in the SPIRIT-Outcomes 2022 extension. The discussions during and after the consensus meeting yielded 9 items that elaborate on the SPIRIT 2013 statement checklist items and are related to completely defining and justifying the choice of primary, secondary, and other outcomes (SPIRIT 2013 statement checklist item 12) prospectively in the trial protocol, defining and justifying the target difference between treatment groups for the primary outcome used in the sample size calculations (SPIRIT 2013 statement checklist item 14), describing the responsiveness of the study instruments used to assess the outcome and providing details on the outcome assessors (SPIRIT 2013 statement checklist item 18a), and describing any planned methods to account for multiplicity relating to the analyses or interpretation of the results (SPIRIT 2013 statement checklist item 20a). Conclusions and Relevance: This SPIRIT-Outcomes 2022 extension of the SPIRIT 2013 statement provides 9 outcome-specific items that should be addressed in all trial protocols and may help increase trial utility, replicability, and transparency and may minimize the risk of selective nonreporting of trial results

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe