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Unexploded ordnance (UXO), often deployed in WWI and WWII, are still present on the seabed posing a risk to seabed construction. UXO surveys identify potential UXO targets which are then investigated and removed where necessary; however, approximately 96 per cent of targets investigated on projects included in this study were non-UXO (false positives). Here we investigate methods of improving statistical confidence in targets picked through the improved classification of magnetic response, utilizing simulation methods and historic data. A simulation of the induced magnetism of UXO was developed to model the most likely dimensions and orientation of a given source item. Modelling results and measured variables were combined in an optimization algorithm, hereon referred to as 'the classifier'. We document the results of integrating the magnetic responses of 3027 targets from 18 offshore wind projects into the classifier. Five of these projects were performed as tests in which the target results were unknown during classification. Finally, the classifier was deployed on a live project, Hollandse Kust Zuid 3 and 4 Offshore Wind Farm, in which it enabled the removal of 67 targets from the from the 1200-target investigation list. The classifier proved to be a valuable additional tool to assist the target rationalization process, reliably and repeatably distinguishing UXO from other items, thereby reducing false positives and repeatably demonstrating no threshold UXO false negatives. Assumptions and limitations of this methodology were highlighted, which must be understood and considered when integrating this approach on future projects. [ABSTRACT FROM AUTHOR]

Background A growing number of older people provide unpaid care, but contemporary research evidence on this group is limited. Aim This study aims to describe the characteristics of older people who provide unpaid care and how these vary by socioeconomic position. Methods Using recent information from the English Longitudinal Study of Ageing (ELSA wave 9, 2019), we analysed cross-sectional data on 1,282 unpaid carers aged ≥50. Data on sociodemographics, health, social wellbeing, care intensity and caregiver–recipient relationships were extracted. Total net non-pension wealth quintiles were used as a relative measure of socioeconomic position. Differences between the poorest and richest wealth quintiles were examined through logistic regression. Findings Most older carers in ELSA were female and looking after another older person. Poor mental and physical health and social isolation were common, and socially patterned. Compared with carers in the middle wealth group, the poorest group were more likely to be living with the person they cared for (odds ratio (OR) 1.56 [95% confidence interval (CI) 1.03–2.36]) and more likely to experience loneliness (OR 2.29 [95% CI 1.42–3.69]), dependency (i.e. the need for help with activities of daily living) (OR 1.62 [95% CI 1.05–2.51]), chronic pain (OR 1.81 [95% CI 1.23–2.67]), a higher number of diseases (OR 1.75 [95% CI 1.15–2.65]) and fair/poor self-rated health (OR 2.59 [95% CI 1.79–3.76]). The poorest carers were also less likely to have a high quality of life (OR 0.51 [95% CI 0.33–0.80]) or be in work (OR 0.33 [95% CI 0.19–0.59]). Conclusion Our findings suggest that financially disadvantaged unpaid carers (and their households) may have the greatest needs for intervention and support. Focussing resources on this group has potential to address social inequalities. [ABSTRACT FROM AUTHOR]

Context: Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases. Objective: We evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, β-nicotinamide mononucleotide (MIB-626, Metro International Biotech, Worcester, MA), in adults at risk for age-related conditions. Methods: Thirty overweight or obese adults, ≥45 years, were randomized in a 2:1 ratio to 2 MIB-626 tablets each containing 500 mg of microcrystalline β-nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics. Results: Adverse events were similar between groups. MIB-626 treatment substantially increased circulating concentrations of NAD and its metabolites. Body weight (difference −1.9 [−3.3, −0.5] kg, P=.008); diastolic blood pressure (difference −7.01 [−13.44, −0.59] mmHg, P=.034); total cholesterol (difference −26.89 [−44.34, −9.44] mg/dL, P=.004), low-density lipoprotein (LDL) cholesterol (−18.73 [−31.85, −5.60] mg/dL, P=.007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 group than placebo. Changes in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ significantly between groups. Insulin sensitivity and hepatic and intra-abdominal fat did not change in either group. Conclusions: MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure. These data provide the rationale for larger trials to assess the efficacy of NAD augmentation in improving cardiometabolic outcomes in older adults. [ABSTRACT FROM AUTHOR]

Background frailty is a condition of reduced function and health due to ageing processes and is associated with a higher risk of falls, hospitalisation, disability and mortality. Objective to determine the relationship between household wealth and neighbourhood deprivation with frailty status, independently of demographic factors, educational attainment and health behaviours. Design population-based cohort study. Setting communities in England. Subjects in total 17,438 adults aged 50+ from the English Longitudinal Study of Ageing. Methods multilevel mixed-effects ordered logistic regression was used in this study. Frailty was measured using a frailty index. We defined small geographic areas (neighbourhoods) using English Lower layer Super Output Areas. Neighbourhood deprivation was measured by the English Index of Multiple Deprivation, grouped into quintiles. Health behaviours included in this study are smoking and frequency of alcohol consumption. Results the proportion of respondents who were prefrail and frail were 33.8% [95% confidence interval (CI) 33.0–34.6%] and 11.7 (11.1–12.2)%, respectively. Participants in the lowest wealth quintile and living in the most deprived neighbourhood quintile had 1.3 (95% CI = 1.2–1.3) and 2.2 (95% CI = 2.1–2.4) times higher odds of being prefrail and frail, respectively, than the wealthiest participants living in the least deprived neighbourhoods Living in more deprived neighbourhood and poorer wealth was associated with an increased risk of becoming frail. Those inequalities did not change over time. Conclusions in this population-based sample, living in a deprived area or having low wealth was associated with frailty in middle-aged and older adults. This relationship was independent of the effects of individual demographic characteristics and health behaviours. [ABSTRACT FROM AUTHOR]

Sirtuins are a family of proteins that protect against cellular injury and aging; understanding their evolution should reveal fundamental mechanisms governing longevity. "Early-branching" animals such as sea sponges and jellyfish have been understudied in previous analyses of sirtuin diversity. These organisms not only hold important positions at the base of the evolutionary tree, but also have unique aging dynamics that defy convention, such as quasi-immortality and high regenerative capacity. In this study, we survey the evolution of sirtuin proteins in animals, with a focus on the oldest living lineages. We describe previously unrecognized expansions of "Class IV" and "Class I" sirtuins around the origin of animals, raising the number of sirtuin families in the last common ancestor to at least nine. Most of these undescribed sirtuins have been lost in vertebrates and other bilaterian animals. Our work also clarifies the evolution of PNC1 and NAMPT enzymes that carry out the rate-limiting step in sirtuin-related NAD+ biosynthesis. The genes for PNC1 and NAMPT enzymes were both present in the first animals, with the genes being lost a minimum of 11 and 13 times, respectively, over the course of animal evolution. We propose that species with these ancestral gene repertoires are ideal model organisms for studying the genetic regulation of animal longevity and will provide clues to increasing longevity in humans. [ABSTRACT FROM AUTHOR]

The Frailty Inferred Geriatric Health Timeline (FRIGHT) and Analysis of Frailty and Death (AFRAID) clocks were developed to predict biological age and lifespan, respectively, in mice. Their utility within the context of polypharmacy (≥5 medications), which is very common in older adults, is unknown. In male C57BL/6J(B6) mice administered chronic polypharmacy, monotherapy, and undergoing treatment cessation (deprescribing), we aimed to compare these clocks between treatment groups; investigate whether treatment affected correlation of these clocks with mortality; and explore factors that may explain variation in predictive performance. Treatment (control, polypharmacy, or monotherapy) commenced from age 12 months. At age 21 months, each treatment group was subdivided to continue treatment or have it deprescribed. Frailty index was assessed and informed calculation of the clocks. AFRAID, FRIGHT, frailty index, and mortality age did not differ between continued treatment groups and control. Compared to continued treatment, deprescribing some treatments had inconsistent negative impacts on some clocks and mortality. FRIGHT and frailty index, but not AFRAID, were associated with mortality. The bias and precision of AFRAID as a predictor of mortality varied between treatment groups. Effects of deprescribing some drugs on elements of the clocks, particularly on weight loss, contributed to bias. Overall, in this cohort, FRIGHT and AFRAID measures identified no treatment effects and limited deprescribing effects (unsurprising as very few effects on frailty or mortality), with variable prediction of mortality. These clocks have utility, but context is important. Future work should refine them for intervention studies to reduce bias from specific intervention effects. [ABSTRACT FROM AUTHOR]

This article problematises protection for lesbian, gay, bisexual, transgender, and intersex (LGBTI) refugees in contexts of state-condoned persecution against this group. Based on ethnographic evidence from Kampala, Uganda, we draw attention to the homogenising tendencies of centralised protection systems in cities in the global south, which are primarily centred on nationality-based communities. We examine the processes of social exclusion that limit the involvement of LGBTI refugees from the Great Lakes Region in such communities, de facto placing them outside the parameters of institutional refugee protection. We then focus on their relational experiences of protection and safety within the office of an LGBTI support group in Kampala and argue for a micro-level approach that considers how LGBTI refugee protection is grounded in the geopolitics of the everyday. Our findings underscore the limitations of institutional policy and practice, which continues to overlook the protection gap that exists for LGBTI persons within the refugee population in Uganda. In order to remedy this protection gap, we suggest that a critical reconsideration is needed of the participatory spaces and cooperation between LGBTI refugee-led advocates and refugee serving institutions and decision-makers. [ABSTRACT FROM AUTHOR]

SRT1720, a sirtuin1-activator, and metformin (MET), an antidiabetic drug, confer health and life-span benefits when administered individually. It is unclear whether combination of the two compounds could lead to additional benefits. Groups of 56-week-old C57BL/6J male mice were fed a high-fat diet (HFD) alone or supplemented with either SRT1720 (2 g/kg food), a high dose of MET (1% wt/wt food), or a combination of both. Animals were monitored for survival, body weight, food consumption, body composition, and rotarod performance. Mice treated with MET alone did not have improved longevity, and life span was dramatically reduced by combination of MET with SRT1720. Although all groups of animals were consuming similar amounts of food, mice on MET or MET + SRT1720 showed a sharp reduction in body weight. SRT1720 + MET mice also had lower percent body fat combined with better performance on the rotarod compared to controls. These data suggest that co-treatment of SRT1720 with MET is detrimental to survival at the doses used and, therefore, risk-benefits of combining life-span-extending drugs especially in older populations needs to be systematically evaluated. [ABSTRACT FROM AUTHOR]

Background: Resveratrol, a plant-derived polyphenol, has been reported to improve glucose metabolism and vascular function and to extend life span in animal models, but studies in humans have been inconclusive.Methods: In a randomized, double-blind crossover study, we treated older glucose-intolerant adults (n = 30) with resveratrol (2-3 g/daily) or placebo, each for 6 weeks. A standard mixed-meal test was used to assess insulin sensitivity (Matsuda index) and secretion (C-peptide deconvolution) and vascular function by reactive hyperemia peripheral arterial tonometry. Skeletal muscle samples were obtained for gene expression using RNA-Seq analysis and to assess mitochondrial morphology.Results: There were no changes in glucose tolerance, insulin sensitivity, weight, blood pressure, or lipid profile following resveratrol treatment. Fasting reactive hyperemia index improved with resveratrol (2.02 ± 0.2 vs 1.76 ± 0.02, p = .002). RNA-Seq analysis yielded 140 differentially expressed transcripts (corrected p-value ≤ .05), predominantly associated with mitochondrial genes and noncoding RNA. Ingenuity Pathway Analysis confirmed that mitochondrial dysfunction (p = 2.77 × 10-12) and oxidative phosphorylation (p = 1.41 × 10-11) were the most significantly perturbed pathways. Mitochondrial number, but not size, was increased.Conclusions: Resveratrol treatment of older adults with impaired glucose regulation may have beneficial effects on vascular function, but not glucose metabolism or insulin sensitivity. Changes in gene expression suggest effects similar to those observed with caloric restriction, which has been shown to increase life and health span in animal models, although its significance for humans is uncertain. Future human studies should address the appropriate dose range and low bioavailability of resveratrol. [ABSTRACT FROM AUTHOR]

Background: Documents from advocacy and fund-raising organizations for child mass deworming programmes in low- and middle-income countries cite unpublished economic studies claiming long-term effects on health, schooling and economic development.Methods: To summarize and appraise these studies, we searched for and included all long-term follow-up studies based on cluster-randomized trials included in a 2015 Cochrane review on deworming. We used Cochrane methods to assess risk of bias, and appraised the credibility of the main findings. Where necessary we contacted study authors for clarifications.Results: We identified three studies (Baird 2016, Ozier 2016 and Croke 2014) evaluating effects more than 9 years after cluster-randomized trials in Kenya and Uganda. Baird and Croke evaluate short additional exposures to deworming programmes in settings where all children were dewormed multiple times. Ozier evaluates potential spin-off effects to infants living in areas with school-based deworming. None of the studies used pre-planned protocols nor blinded the analysis to treatment allocation.Conclusions: In the context of reliable epidemiological methods, all three studies are at risk of substantial methodological bias. They therefore help in generating hypotheses, but should not be considered to provide reliable evidence of effects. [ABSTRACT FROM AUTHOR]

Sirtuins (Sirt1-Sirt7) comprise a family of nicotinamide adenine dinucleotide (NAD+)-dependent enzymes. While deacetylation reflects their main task, some of them have deacylase, adenosine diphosphate-ribosylase, demalonylase, glutarylase, and desuccinylase properties. Activated upon caloric restriction and exercise, they control critical cellular processes in the nucleus, cytoplasm, and mitochondria to maintain metabolic homeostasis, reduce cellular damage and dampen inflammation-all of which serve to protect against a variety of age-related diseases, including cardiovascular pathologies. This review focuses on the cardiovascular effects of Sirt1, Sirt3, Sirt6, and Sirt7. Most is known about Sirt1. This deacetylase protects from endothelial dysfunction, atherothrombosis, diet-induced obesity, type 2 diabetes, liver steatosis, and myocardial infarction. Sirt3 provides beneficial effects in the context of left ventricular hypertrophy, cardiomyopathy, oxidative stress, metabolic homeostasis, and dyslipidaemia. Sirt6 is implicated in ameliorating dyslipidaemia, cellular senescence, and left ventricular hypertrophy. Sirt7 plays a role in lipid metabolism and cardiomyopathies. Most of these data were derived from experimental findings in genetically modified mice, where NFkB, Pcsk9, low-density lipoprotein-receptor, PPARg, superoxide dismutase 2, poly[adenosine diphosphate-ribose] polymerase 1, and endothelial nitric oxide synthase were identified among others as crucial molecular targets and/or partners of sirtuins. Of note, there is translational evidence for a role of sirtuins in patients with endothelial dysfunction, type 1 or type 2 diabetes and longevity. Given the availability of specific Sirt1 activators or pan-sirtuin activators that boost levels of the sirtuin cofactor NAD+, we anticipate that this field will move quickly from bench to bedside. [ABSTRACT FROM AUTHOR]

Aims The deacetylase sirtuin 1 (Sirt1) exerts beneficial effects on lipid metabolism, but its roles in plasma LDL-cholesterol regulation and atherosclerosis are controversial. Thus, we applied the pharmacological Sirt1 activator SRT3025 in a mouse model of atherosclerosis and in hepatocyte culture. Methods and results Apolipoprotein E-deficient (Apoe−/−) mice were fed a high-cholesterol diet (1.25% w/w) supplemented with SRT3025 (3.18 g kg−1 diet) for 12 weeks. In vitro, the drug activated wild-type Sirt1 protein, but not the activation-resistant Sirt1 mutant; in vivo, it increased deacetylation of hepatic p65 and skeletal muscle Foxo1. SRT3025 treatment decreased plasma levels of LDL-cholesterol and total cholesterol and reduced atherosclerosis. Drug treatment did not change mRNA expression of hepatic LDL receptor (Ldlr) and proprotein convertase subtilisin/kexin type 9 (Pcsk9), but increased their protein expression indicating post-translational effects. Consistent with hepatocyte Ldlr and Pcsk9 accumulation, we found reduced plasma levels of Pcsk9 after pharmacological Sirt1 activation. In vitro administration of SRT3025 to cultured AML12 hepatocytes attenuated Pcsk9 secretion and its binding to Ldlr, thereby reducing Pcsk9-mediated Ldlr degradation and increasing Ldlr expression and LDL uptake. Co-administration of exogenous Pcsk9 with SRT3025 blunted these effects. Sirt1 activation with SRT3025 in Ldlr−/− mice reduced neither plasma Pcsk9, nor LDL-cholesterol levels, nor atherosclerosis. Conclusion We identify reduction in Pcsk9 secretion as a novel effect of Sirt1 activity and uncover Ldlr as a prerequisite for Sirt1-mediated atheroprotection in mice. Pharmacological activation of Sirt1 appears promising to be tested in patients for its effects on plasma Pcsk9, LDL-cholesterol, and atherosclerosis. [ABSTRACT FROM PUBLISHER]

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews. [ABSTRACT FROM AUTHOR]

Aims: The molecular epidemiological studies on the association of the opioid receptor μ-1 (OPRM1) polymorphism Al 18G (Asn40Asp, rs 1799971) and alcohol use disorders have given conflicting results. The aim of this study was to test the possible association of A118G polymorphism and alcohol use disorders and alcohol consumption in three large cohort-based study samples. Methods: The association between the OPRM1 Al 18G (Asn40Asp, rs 1799971) polymorphism and alcohol use disorders and alcohol consumption was analyzed using three different population-based samples: (a) a Finnish cohort study, Health 2000, with 503 partici-pants having a DSM-IV diagnosis for alcohol dependence and/or alcohol abuse and 506 age- and sex-matched controls; (b) a Finnish cohort study, FINRISK (« = 2360) and (c) the Helsinki Birth Cohort Study (n= 1384). The latter two populations lacked diagnosis-based phenotypes, but included detailed information on alcohol consumption. Results: We found no statistically significant differences in genotypic or allelic distribution between controls and subjects with alcohol dependence or abuse diagnoses. Likewise no significant effects were observed between the A118G genotype and alcohol consumption. Conclusion: These results suggest that A118G (Asn40Asp) polymorphism may not have a major effect on the development of alcohol use disorders at least in the Finnish population. [ABSTRACT FROM AUTHOR]

The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only. [ABSTRACT FROM PUBLISHER]

Rapamycin was administered in food to genetically heterogeneous mice from the age of 9 months and produced significant increases in life span, including maximum life span, at each of three test sites. Median survival was extended by an average of 10% in males and 18% in females. Rapamycin attenuated age-associated decline in spontaneous activity in males but not in females. Causes of death were similar in control and rapamycin-treated mice. Resveratrol (at 300 and 1200 ppm food) and simvastatin (12 and 120 ppm) did not have significant effects on survival in male or female mice. Further evaluation of rapamycin’s effects on mice is likely to help delineate the role of the mammalian target of rapamycin complexes in the regulation of aging rate and age-dependent diseases and may help to guide a search for drugs that retard some or all of the diseases of aging. [ABSTRACT FROM PUBLISHER]

The most common approach to automatic summarization and highlight detection in sports video is to train an automatic classifier to detect semantic highlights based on occurrences of low-level features such as action replays, excited commentators or changes in a scoreboard. We propose an alternative approach based on the detection of perception concepts (PCs) and the construction of Petri-Nets, which can be used for both semantic description and event detection within sports videos. Low-level algorithms to detect PCs using visual, aural and motion characteristics are proposed, and a series of Petri-Nets composed of PCs is formally defined to describe video content. We call this a perception concept network–Petri-Net (PCN–PN) model. Using PCN–PNs, personalized high-level semantic descriptions of video highlights can be facilitated and queries on high-level semantics can be achieved. A particular strength of this framework is that we can easily build semantic detectors based on PCN–PNs to search within sports videos and locate interesting events. Experimental results based on recorded sports video data across three types of sports games (soccer, basketball and rugby), and each from multiple broadcasters, are used to illustrate the potential of this framework. [ABSTRACT FROM PUBLISHER]

Focuses on the Labour Party's constitutional revolution in Great Britain in 1997-1998. Devolution and decentralization of the British constitution; British government's pledge to incorporate European Convention on Human Rights into the country's law; Electoral reform.

Discusses the genetics of the synthesis of serine from glycine and the utilization of glycine as sole nitrogen source by Saccharomyces cerevisiae. Lack of decarboxylase multienzyme complex activity; Effects of mutations in lipoamide dehydrogenase; Complementation groups of mutants; Knowledge on the nature of mutations through glycine uptake and decarboxylation.

The authors discuss the development of drug targets to prevent aging. They mention that biological processes associated with aging are not necessarily involved in the pathogenesis of aging. They discuss the study of hormetic and dietary influences on aging. They mention the article in this issue "Dietary interventions to extend lifespan and healthspan based on calorie restriction," by R. K. Minor and others.