Alzheimer’s disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology

Introduction: Cerebrospinal fluid (CSF) biomarkers, although of established utility in the diagnostic evaluation of Alzheimer's disease (AD), are known to be sensitive to variation based on pre-analytical sample processing. We assessed whether gravity droplet collection versus syringe aspiration was another factor influencing CSF biomarker analyte concentrations and reproducibility. Methods: Standardized lumbar puncture using small calibre atraumatic spinal needles and CSF collection using gravity fed collection followed by syringe aspirated extraction was performed in a sample of elderly individuals participating in a large long-term observational research trial. Analyte assay concentrations were compared. Results: For the 44 total paired samples of gravity collection and aspiration, reproducibility was high for biomarker CSF analyte assay concentrations (concordance correlation [95%CI]: beta-amyloid1-42 (Aβ42) 0.83 [0.71 - 0.90]), t-tau 0.99 [0.98 - 0.99], and phosphorylated tau (p-tau) 0.82 [95 % CI 0.71 - 0.89]) and Bonferroni corrected paired sample t-tests showed no significant differences (group means (SD): Aβ42 366.5 (86.8) vs 354.3 (82.6), p = 0.10; t-tau 83.9 (46.6) vs 84.7 (47.4) p = 0.49; p-tau 43.5 (22.8) vs 40.0 (17.7), p = 0.05). The mean duration of collection was 10.9 minutes for gravity collection and <1 minute for aspiration. Conclusions: Our results demonstrate that aspiration of CSF is comparable to gravity droplet collection for AD biomarker analyses but could considerably accelerate throughput and improve the procedural tolerability for assessment of CSF biomarkers

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Decision diversion in diverse teams: Findings from inside a corporate boardroom

Using qualitative data from a 5-year participant observation study conducted inside the corporate board of a publicly-held company, we discovered what happened when team composition changed to increase the diversity of perspectives and interests represented on the team. Based on board meeting transcripts over the 5-year period, we observed that a change in team composition was followed by a process we label decision diversion, a dysfunctional process in which the team replaced its goal of effective task performance with negotiating the interests of subgroup members. A key insight of our study is that this process unfolded as team members attempted to engage in effective task-based information analysis and decision-making. Our study suggests that the traditional assumptions underlying the understanding of team composition may be insufficient. We provide alternative explanations for the origins of the dynamics of decision diversion in teams. In their search for the microprocesses through which diverse team members interact with one another, Harvey, Currall, and Hammer discover a process they call decision diversion: the team’s replacement of its goal of effective task performance with negotiating the interests of subgroup members. This discovery emerges from the in-depth, longitudinal study of the meetings of a corporate board. Quoting one of the referees, “the interesting insight is that increases in the diversity of perspectives and interests represented on the board required processing and integrating large amounts of complex information which the board failed to do, resulting in decision diversion.” This finding challenges some established assumptions, and its implications for our understanding of team composition suggest new questions for research on team diversity

A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications

BackgroundThere is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research

Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.

INTRODUCTION: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice. METHODS: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide. ETHICS/DISSEMINATION: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ISRCTN39653756.The OPTIMISE II trial is supported by Edwards Lifesciences (Irvine, CA) and the UK National Institute for Health Research through RMP’s NIHR Professorship

Understanding the ecological validity of relying practice as a basis for risk identification

Understanding the reliability of hazardous organizations and their protective systems is central to understanding the risk they produce. Work on "high reliability organization" has done much to illuminate the conditions in which social organization becomes reliable in highly demanding conditions. But risk depends just as much on how relying entities do their relying as it does on the reliability of the entities they rely on. Patterns of relying are often opaque in sociotechnical systems, and processes of relying and being relied on are mutually influencing in complex ways, so the relationship between relying and risk may not be at all obvious. This study was an attempt to study relying as a social practice, in particular analyzing how it had ecological validity in a social organization-how practice was responsive to the conditions in which it took place. This involved observational fieldwork and inductive, qualitative analysis on an offshore oil and gas production platform that was nearing the end of its design life and undergoing refurbishment. The analysis produced four main categories of ecological validity: responsiveness to formal organization, responsiveness to situational contingency, responsiveness to information asymmetry, and responsiveness to sociomateriality. This ecological validity of relying practice should be a primary focus of risk identification, assessing how relying can become mismatched to reliability in certain ways, both when relying practice is responsive to circumstances and when it is not

朝鮮干潟地利用論

Background: The Standardising Endpoints for Perioperative Medicine group was established to derive an appropriate set of endpoints for use in clinical trials related to anaesthesia and perioperative medicine. Anaesthetic or analgesic technique during cancer surgery with curative intent may influence the risk of recurrence or metastasis. However, given the current equipoise in the existing literature, prospective, randomised, controlled trials are necessary to test this hypothesis. As such, a cancer subgroup was formed to derive endpoints related to research in onco-anaesthesia based on a current evidence base, international consensus and expert guidance. Methods: We undertook a systematic review to identify measures of oncological outcome used in the oncological, surgical, and wider literature. A multiround Delphi consensus process that included up to 89 clinician–researchers was then used to refine a recommended list of endpoints. Results: We identified 90 studies in a literature search, which were the basis for a preliminary list of nine outcome measures and their definitions. A further two were added during the Delphi process. Response rates for Delphi rounds one, two, and three were 88% (n=9), 82% (n=73), and 100% (n=10), respectively. A final list of 10 defined endpoints was refined and developed, of which six secured approval by ≥70% of the group: cancer health related quality of life, days alive and out of hospital at 90 days, time to tumour progression, disease-free survival, cancer-specific survival, and overall survival (and 5-yr overall survival). Conclusion: Standardised endpoints in clinical outcomes studies will support benchmarking and pooling (meta-analysis) of trials. It is therefore recommended that one or more of these consensus-derived endpoints should be considered for inclusion in clinical trials evaluating a causal effect of anaesthesia–analgesia technique on oncological outcomes