Biochemical Analysis of Fossil and Living Plants

Lignin oxidation products from a variety of living and fossil plants were obtained using the alkaline cupric oxide method. The aldehydes and ketones obtained were separated by gas chromatography and gas chromatography/mass spectroscopy was used to verify the structures of the lignin oxidation products. Vanillin remained the major ligning oxidation product obtained from the lignin of gymnosperms. However small amounts of p-hydroxybenzaldehyde and syringic aldehyde were obtained from all the symnospermous ligning examined. Immature dicotyledons and the woodmeal of the monocotyledons examined gave varying emounts of p-hydroxybenzaldehyde when oxidized. No phydoxybenzaldehyde was detected from the lignin of the monoxotyledon fibres examined. Syringic aldehyde remained the major lignin oxidation product obtained from the angiosperms. All three types of lignin nuclei were obtained in small amounts from several lower plants including the mosses and liverworts. No correlation between the presence of syringic aldehyde and the occurrence of vessels was found. The suggestion that it is the fibres in plants which contribute to the presence of syringic aldehyde is made. All three types of lignin nuclei were observed from certain fossil wood, fossil compressions and coals. Syringic aldehyde remained as a lignin oxidation product in bituminous coals of 3OO million years old. Lignin derivatives can be used as supporting evidence for anatomical and morphological studies. However lignin derivatives cannot be used as characteristics for fossil compressions and coals because chemical changes which occur alter the original phenolic aldehyde ratios. Only speculations can be made

Multifactorial falls prevention programme compared with usual care in UK care homes for older people: Multicentre cluster randomised controlled trial with economic evaluation

Objectives: To determine the clinical and cost effectiveness of a multifactorial fall prevention programme compared with usual care in long term care homes. Design: Multicentre, parallel, cluster randomised controlled trial. Setting: Long term care homes in the UK, registered to care for older people or those with dementia. Participants: 1657 consenting residents and 84 care homes. 39 were randomised to the intervention group and 45 were randomised to usual care. Interventions: Guide to Action for Care Homes (GtACH): a multifactorial fall prevention programme or usual care. Main outcome measures: Primary outcome measure was fall rate at 91-180 days after randomisation. The economic evaluation measured health related quality of life using quality adjusted life years (QALYs) derived from the five domain five level version of the EuroQoL index (EQ-5D-5L) or proxy version (EQ-5D-5L-P) and the Dementia Quality of Life utility measure (DEMQOL-U), which were self-completed by competent residents and by a care home staff member proxy (DEMQOL-P-U) for all residents (in case the ability to complete changed during the study) until 12 months after randomisation. Secondary outcome measures were falls at 1-90, 181-270, and 271-360 days after randomisation, Barthel index score, and the Physical Activity Measure-Residential Care Homes (PAM-RC) score at 91, 180, 270, and 360 days after randomisation. Results: Mean age of residents was 85 years. 32% were men. GtACH training was delivered to 1051/1480 staff (71%). Primary outcome data were available for 630 participants in the GtACH group and 712 in the usual care group. The unadjusted incidence rate ratio for falls between 91 and 180 days was 0.57 (95% confidence interval 0.45 to 0.71, P<0.001) in favour of the GtACH programme (GtACH: six falls/1000 residents v usual care: 10 falls/1000). Barthel activities of daily living indices and PAM-RC scores were similar between groups at all time points. The incremental cost was £108 (95% confidence interval −£271.06 to 487.58), incremental QALYs gained for EQ-5D-5L-P was 0.024 (95% confidence interval 0.004 to 0.044) and for DEMQOL-P-U was 0.005 (−0.019 to 0.03). The incremental costs per EQ-5D-5L-P and DEMQOL-P-U based QALY were £4544 and £20 889, respectively. Conclusions: The GtACH programme was associated with a reduction in fall rate and cost effectiveness, without a decrease in activity or increase in dependency. Trial registration: ISRCTN34353836

A multidomain decision support tool to prevent falls in older people: the FinCH cluster RCT

BackgroundFalls in care home residents are common, unpleasant, costly and difficult to prevent.ObjectivesThe objectives were to evaluate the clinical effectiveness and cost-effectiveness of the Guide to Action for falls prevention in Care Homes (GtACH) programme.DesignA multicentre, cluster, parallel, 1 : 1 randomised controlled trial with embedded process evaluation and economic evaluation. Care homes were randomised on a 1 : 1 basis to the GtACH programme or usual care using a secure web-based randomisation service. Research assistants, participating residents and staff informants were blind to allocation at recruitment; research assistants were blind to allocation at follow-up. NHS Digital data were extracted blindly.SettingOlder people’s care homes from 10 UK sites.ParticipantsOlder care home residents.InterventionThe GtACH programme, which includes care home staff training, systematic use of a multidomain decision support tool and implementation of falls prevention actions, compared to usual falls prevention care.OutcomesThe primary trial outcome was the rate of falls per participating resident occurring during the 90-day period between 91 and 180 days post randomisation. The primary outcome for the cost-effectiveness analysis was the cost per fall averted, and the primary outcome for the cost–utility analysis was the incremental cost per quality adjusted life-year. Secondary outcomes included the rate of falls over days 0–90 and 181–360 post randomisation, activity levels, dependency and fractures. The number of falls per resident was compared between arms using a negative binomial regression model (generalised estimating equation).ResultsA total of 84 care homes were randomised: 39 to the GtACH arm and 45 to the control arm. A total of 1657 residents consented and provided baseline measures (mean age 85 years, 32% men). GtACH programme training was delivered to 1051 staff (71% of eligible staff) over 146 group sessions. Primary outcome data were available for 630 GtACH participants and 712 control participants. The primary outcome result showed an unadjusted incidence rate ratio of 0.57 (95% CI 0.45 to 0.71; p < 0.01) in favour of the GtACH programme. Falls rates were lower in the GtACH arm in the period 0–90 days. There were no other differences between arms in the secondary outcomes. Care home staff valued the training, systematic strategies and specialist peer support, but the incorporation of the GtACH programme documentation into routine care home practice was limited. No adverse events were recorded. The incremental cost was £20,889.42 per Dementia Specific Quality of Life-based quality-adjusted life-year and £4543.69 per quality-adjusted life-year based on the EuroQol-5 dimensions, five-level version. The mean number of falls was 1.889 (standard deviation 3.662) in the GtACH arm and 2.747 (standard deviation 7.414) in the control arm. Therefore, 0.858 falls were averted. The base-case incremental cost per fall averted was £190.62.ConclusionThe GtACH programme significantly reduced the falls rate in the study care homes without restricting residents’ activity levels or increasing their dependency, and was cost-effective at current thresholds in the NHS.Future workFuture work should include a broad implementation programme, focusing on scale and sustainability of the GtACH programme.LimitationsA key limitation was the fact that care home staff were not blinded, although risk was small because of the UK statutory requirement to record falls in care homes.Trial registrationThis trial is registered as ISRCTN34353836.FundingThis 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. 26, No. 9. See the NIHR Journals Library website for further project information

Medical Crises in Older People: cohort study of older people attending acute medical units, developmental work and randomised controlled trial of a specialist geriatric medical intervention for high-risk older people; cohort study of older people with mental health problems admitted to hospital, developmental work and randomised controlled trial of a specialist medical and mental health unit for general hospital patients with delirium and dementia; and cohort study of residents of care homes and interview study of health-care provision to residents of care homes

BackgroundThis programme of research addressed shortcomings in the care of three groups of older patients: patients discharged from acute medical units (AMUs), patients with dementia and delirium admitted to general hospitals, and care home residents.MethodsIn the AMU workstream we undertook literature reviews, performed a cohort study of older people discharged from AMU (Acute Medical Unit Outcome Study; AMOS), developed an intervention (interface geriatricians) and evaluated the intervention in a randomised controlled trial (Acute Medical Unit Comprehensive Geriatric Assessment Intervention Study; AMIGOS). In the second workstream we undertook a cohort study of older people with mental health problems in a general hospital, developed a specialist unit to care for them and tested the unit in a randomised controlled trial (Trial of an Elderly Acute care Medical and mental health unit; TEAM). In the third workstream we undertook a literature review, a cohort study of a representative sample of care home residents and a qualitative study of the delivery of health care to care home residents.ResultsAlthough 222 of the 433 (51%) patients recruited to the AMIGOS study were vulnerable enough to be readmitted within 3 months, the trial showed no clinical benefit of interface geriatricians over usual care and they were not cost-effective. The TEAM study recruited 600 patients and there were no significant benefits of the specialist unit over usual care in terms of mortality, institutionalisation, mental or functional outcomes, or length of hospital stay, but there were significant benefits in terms of patient experience and carer satisfaction with care. The medical and mental health unit was cost-effective. The care home workstream found that the organisation of health care for residents in the UK was variable, leaving many residents, whose health needs are complex and unpredictable, at risk of poor health care. The variability of health care was explained by the variability in the types and sizes of homes, the training of care home staff, the relationships between care home staff and the primary care doctors and the organisation of care and training among primary care doctors.DiscussionThe interface geriatrician intervention was not sufficient to alter clinical outcomes and this might be because it was not multidisciplinary and well integrated across the secondary care–primary care interface. The development and evaluation of multidisciplinary and better-integrated models of care is justified. The specialist unit improved the quality of experience of patients with delirium and dementia in general hospitals. Despite the need for investment to develop such a unit, the unit was cost-effective. Such units provide a model of care for patients with dementia and delirium in general hospitals that requires replication. The health status of, and delivery of health care to, care home residents is now well understood. Models of care that follow the principles of comprehensive geriatric assessment would seem to be required, but in the UK these must be sufficient to take account of the current provision of primary health care and must recognise the importance of the care home staff in the identification of health-care needs and the delivery of much of that care.Trial registrationCurrent Controlled Trials ISRCTN21800480 (AMIGOS); ClinicalTrials.gov NCT01136148 (TEAM)

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570