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Background: We tested the hypothesis that delivering remote ischemic conditioning (RIC) with an adjunct tissue reflectance sensor (TRS) device may be feasible in patients with acute ischemic stroke (AIS) and cerebral small vessel disease (cSVD). Methods: AIS patients with neurological deficits within 7 days of symptom onset were screened for moderate to severe cSVD. Eligible patients were randomized 2:1 to receive intervention RIC or sham RIC (7 days). The primary outcome measure was intervention feasibility. It was assessed as an intervention-related comfort by a 5-point Likert scale during each session (1-very uncomfortable, 5-very comfortable). The secondary outcome measure was assessment of TRS derived dermal blood concentration and blood oxygenation changes during RIC. Results: Forty-seven (32 intervention, 15 sham) patients were enrolled at a median (IQR) 39.7 (25-64) hours after symptom onset, with mean±SD age of 75±12 years, 22 (46.8%) were females and median baseline NIHSS of 5(3-7). The Likert scale was 3.5 (3-4) in the intervention group and 4 (4-5) in the sham group. The TRS derived blood concentration and blood oxygenation changes were proportionate in the intervention arm and absent in the sham arm. Conclusions: RIC treatment with TRS is feasible in patients with AIS+cSVD. The efficacy of RIC needs further assessment.
We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.
Technical summary
The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.
Social media summary
We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.
Intimate partner violence (IPV) is a public health challenge negatively affecting victims’ health. Telomere length (TL), a marker for biological ageing, might be reflective of the mechanisms through which IPV leads to adverse health outcomes. The objective of the current study was to explore the association between IPV and leucocyte TL.
Methods
We conducted an analysis using a subset of the UK Biobank (N = 144 049). Physical, sexual and emotional IPV were reported by the participants. DNA was extracted from peripheral blood leukocytes. TL was assayed by quantitative polymerase chain reaction. We used multivariable linear regressions to test the associations between IPV and TL adjusted for age, sex, ethnicity, deprivation, education, as well as symptoms of depression and post-traumatic stress disorder in a sensitivity analysis.
Results
After adjusting for sociodemographic factors, any IPV was associated with 0.02-s.d. shorter TL (β = −0.02, 95% CI −0.04 to −0.01). Of the three types of IPV, physical violence had a marginally stronger association (β = −0.05, 95% CI −0.07 to −0.02) than the other two types. The associations of numbers of IPV and TL showed a dose–response pattern whereby those who experienced all three types of IPV types had the shortest TL (β = −0.07, 95% CI −0.12 to −0.03), followed by those who experienced two types (β = −0.04, 95% CI −0.07 to −0.01). Following additional adjustment for symptoms of depression and PTSD, the associations were slightly attenuated but the general trend by number of IPVs remained.
Conclusions
Victims of IPV, particularly those exposed to multiple types of IPVs, had shorter TL indicative of accelerated biological ageing. Given that all three types of IPV are linked to TL, clinical practitioners need to comprehensively identify all types of IPV and those who received multiple types. Further studies should explore the association of violence with changes in TL over time, as well as to which extent biological ageing is a mechanistic factor.
There is evidence that child maltreatment is associated with shorter telomere length in early life.
Aims
This study aims to examine if child maltreatment is associated with telomere length in middle- and older-age adults.
Method
This was a retrospective cohort study of 141 748 UK Biobank participants aged 37–73 years at recruitment. Leukocyte telomere length was measured with quantitative polymerase chain reaction, and log-transformed and scaled to have unit standard deviation. Child maltreatment was recalled by participants. Linear regression was used to analyse the association.
Results
After adjusting for sociodemographic characteristics, participants with three or more types of maltreatment presented with the shortest telomere lengths (β = −0.05, 95% CI −0.07 to −0.03; P < 0.0001), followed by those with two types of maltreatment (β = −0.02, 95% CI −0.04 to 0.00; P = 0.02), referent to those who had none. When adjusted for depression and post-traumatic stress disorder, the telomere lengths of participants with three or more types of maltreatment were still shorter (β = −0.04, 95% CI −0.07 to −0.02; P = 0.0008). The telomere lengths of those with one type of maltreatment were not significantly different from those who had none. When mutually adjusted, physical abuse (β = −0.05, 95% CI −0.07 to −0.03; P < 0.0001) and sexual abuse (β = −0.02, 95% CI −0.04 to 0.00; P = 0.02) were independently associated with shorter telomere length.
Conclusions
Our findings showed that child maltreatment is associated with shorter telomere length in middle- and older-aged adults, independent of sociodemographic and mental health factors.
Cognitive impairment is strongly linked with persistent disability in people with mood disorders, but the factors that explain cognitive impairment in this population are unclear.
Aims
To estimate the total effect of (a) bipolar disorder and (b) major depression on cognitive function, and the magnitude of the effect that is explained by potentially modifiable intermediate factors.
Method
Cross-sectional study using baseline data from the UK Biobank cohort. Participants were categorised as having bipolar disorder (n = 2709), major depression (n = 50 975) or no mood disorder (n = 102 931 and n = 105 284). The outcomes were computerised tests of reasoning, reaction time and memory. The potential mediators were cardiometabolic disease and psychotropic medication. Analyses were informed by graphical methods and controlled for confounding using regression, propensity score-based methods and G-computation.
Results
Group differences of small magnitude were found on a visuospatial memory test. Z-score differences for the bipolar disorder group were in the range −0.23 to −0.17 (95% CI −0.39 to −0.03) across different estimation methods, and for the major depression group they were approximately −0.07 (95% CI −0.10 to −0.03). One-quarter of the effect was mediated via psychotropic medication in the bipolar disorder group (−0.05; 95% CI −0.09 to −0.01). No evidence was found for mediation via cardiometabolic disease.
Conclusions
In a large community-based sample in middle to early old age, bipolar disorder and depression were associated with lower visuospatial memory performance, in part potentially due to psychotropic medication use. Mood disorders and their treatments will have increasing importance for population cognitive health as the proportion of older adults continues to grow.
Declaration of interest
I.J.D. is a UK Biobank participant. J.P.P. is a member of the UK Biobank Steering Committee.
Low birth weight has been inconsistently associated with risk of developing affective disorders, including major depressive disorder (MDD). To date, studies investigating possible associations between birth weight and bipolar disorder (BD), or personality traits known to predispose to affective disorders such as neuroticism, have not been conducted in large cohorts.
Aims
To assess whether very low birth weight (<1500 g) and low birth weight (1500–2490 g) were associated with higher neuroticism scores assessed in middle age, and lifetime history of either MDD or BD. We controlled for possible confounding factors.
Method
Retrospective cohort study using baseline data on the 83 545 UK Biobank participants with detailed mental health and birth weight data. Main outcomes were prevalent MDD and BD, and neuroticism assessed using the Eysenck Personality Inventory Neuroticism scale - Revised (EPIN-R)
Results
Referent to normal birth weight, very low/low birth weight were associated with higher neuroticism scores, increased MDD and BD. The associations between birth weight category and MDD were partially mediated by higher neuroticism.
Conclusions
These findings suggest that intrauterine programming may play a role in lifetime vulnerability to affective disorders.
The relative contribution of demographic, lifestyle and medication factors to the association between affective disorders and cardiometabolic diseases is poorly understood.
Aims
To assess the relationship between cardiometabolic disease and features of depresion and bipolar disorder within a large population sample.
Method
Cross-sectional study of 145 991 UK Biobank participants: multivariate analyses of associations between features of depression or bipolar disorder and five cardiometabolic outcomes, adjusting for confounding factors.
Results
There were significant associations between mood disorder features and ‘any cardiovascular disease’ (depression odds ratio (OR) = 1.15, 95% CI 1.12–1.19; bipolar OR = 1.28, 95% CI 1.14–1.43) and with hypertension (depression OR = 1.15, 95% CI 1.13–1.18; bipolar OR = 1.26, 95% CI 1.12–1.42). Individuals with features of mood disorder taking psychotropic medication were significantly more likely than controls not on psychotropics to report myocardial infarction (depression OR = 1.47, 95% CI 1.24–1.73; bipolar OR = 2.23, 95% CI 1.53–3.57) and stroke (depression OR = 2.46, 95% CI 2.10–2.80; bipolar OR = 2.31, 95% CI 1.39–3.85).
Conclusions
Associations between features of depression or bipolar disorder and cardiovascular disease outcomes were statistically independent of demographic, lifestyle and medication confounders. Psychotropic medication may also be a risk factor for cardiometabolic disease in individuals without a clear history of mood disorder.
The current paper describes Diet In Nutrients Out (DINO), an integrated dietary assessment system incorporating dietary data entry and nutritional analysis within one platform for use in dietary assessment in small-scale intervention studies to national surveys.
Design
DINO contains >6000 food items, mostly aggregated composites of branded foods, across thirty-one main food groups divided into 151 subsidiary groups for detailed reporting requirements, with fifty-three core nutrient fields.
Setting
MRC Human Nutrition Research (HNR), Cambridge, UK and MRC Keneba, Gambia.
Subjects
DINO is used across dietary assessment projects at HNR and MRC Keneba.
Results
DINO contains macro- and micronutrients as well as additional variables of current research and policy interest, such as caffeine, whole grains, vitamin K and added sugars. Disaggregated data are available for fruit, vegetables, meat, fish and cheese in composite foods, enabling greater accuracy when reporting food consumption or assessing adherence to dietary recommendations. Portion sizes are categorised in metric and imperial weights, with standardised portion sizes for each age group. Regular reviews are undertaken for portion sizes and food composition to ensure contemporary relevance. A training programme and a checking schedule are adhered to for quality assurance purposes, covering users and data. Eating context questions are integrated to record where and with whom the respondent is eating, allowing examination between these factors and the foods consumed.
Conclusions
An up-to-date quality-assured system for dietary assessment is crucial for nutritional surveillance and research, but needs to have the flexibility to be tailored to address specific research questions.
In order to investigate further the interest of using the Chilean gene pool in potato breeding programmes, the genetic diversity and population structure of a collection of Solanum tuberosum L. genotypes including 350 worldwide varieties or breeders' lines (referred to as the modern group) and 30 Chiloé Island landraces were examined using simple sequence repeat markers. The close genetic proximity of the Chiloé Island landraces to the modern group was confirmed using several structure analysis methods: principal coordinate analysis; hierarchical clustering analysis; analysis of molecular variance; Bayesian model-based clustering analysis. The latter analysis, in particular, revealed no clear genetic structure between the modern group and the Chiloé Island landraces. The Chiloé Island germplasm appears to represent an interesting gene pool that could be exploited in potato breeding programmes using an association mapping approach.
An 8-year-long field experiment (1998–2006) was established in Sweden with the aim of evaluating the effects of applying organic wastes in combination with mineral nitrogen (N) to agricultural soil. Sewage sludge (SS), biogas residues (BR) and municipal compost (CO) were applied annually at rates corresponding to 50 kg N/ha and supplementary mineral N fertilizer also applied at rates corresponding to 50 kg N/ha. The effects were evaluated by analysing crop yield and soil chemical and microbiological properties. The results showed that none of the fertilizers produced significantly higher yield of barley over the 8-year period compared to any other. Biogas residue proved to be particularly beneficial for the substrate-induced respiration (SIR) in soil and increased the proportion of active to dormant micro-organisms. Treatment with SS increased plant-available phosphorus (P-AL) and N mineralization (N-min), whereas CO increased the basal respiration (B-resp). Changes in the microbial community structure were assayed by terminal restriction fragment length polymorphism (T-RFLP); the T-RFLP signatures of the soil bacterial community were largely unaffected by the addition of organic waste. Of the chemical properties assayed, the largest increases were seen in P-AL, where SS produced the highest value. Treatments with the organic wastes showed no negative effects other than a slight decrease in B-resp induced by SS and BR. In conclusion, the microbiological activity in the soil responded more rapidly than the changes in the community structure and the chemical properties to changes in the soil environment.
The aim of this paper is to explain the process of diversification of normative economics by presenting the work of two authors—Tibor Scitovsky (1910–2002) and Amartya Sen (1933–). While these two authors first contributed to traditional welfare analysis from within, they were subsequently involved in the development of two different, and even opposed, programs: the economics of happiness; and the capability approach. They focused on different concepts of well-being: the “joy” of satisfied consumers for Scitovsky; and the “capabilities” of deprived individuals for Sen. In imposing new theoretical frameworks and applications, as well as new concepts of well-being, which are measureable, the capability approach and the economics of happiness represent two major attempts to renew normative economic analysis.
The potential of antibodies raised against insulin-like growth factor-1 (IGF-1) as a treatment to enhance the anabolic actions of IGF-1 has been demonstrated in both rodent and ruminant models. We investigated whether treatment of genetically normal rats with anti-IGF-1 immunoglobulin (Ig, raised in cattle) would enhance growth and if anti-IGF-1 Ig treatment would ameliorate live-weight loss in genetically normal rats offered a severely protein-restricted diet. Scatchard analysis was used to characterise ammonium sulphate precipitated bovine anti-IGF-1 Ig. Anti-IGF-1 Ig binding to 125I-IGF-1 yielded an almost linear Scatchard plot, with a Hill co-efficient of 0.951 ± 0.012, indicating a single class of IGF-1 binding sites. The affinity of anti-IGF-1 Ig for IGF-1 was 2.14 ± 0.66 × 109 l/mol. The non-immune Ig preparation did not bind IGF-1. Rats were offered either a diet with a normal protein level (20%) or protein restricted (4% protein), and each dietary group was further treated with twice-daily i.p. injections of either diluent phosphate buffered saline, non-immune Ig or anti-IGF-1 Ig. Dietary protein level had a significant effect on live-weight gain, but there was no effect of non-immune Ig or anti-IGF-1 Ig on live-weight gain. Treatment with anti-IGF-1 Ig prevented the significant depression of cumulative dietary intake observed in diluent, and non-immune Ig treated groups offered the 4% protein diet. The cumulative dietary intake of the anti-IGF-1 Ig treated, 4% dietary protein group did not differ significantly from those of the groups offered the 20% protein diet. In addition, within the 4% dietary protein group, rats treated with non-immune Ig exhibited a cumulative feed intake that was intermediate between that of the diluent treated and anti-IGF-1 Ig treated groups (P < 0.05). Size exclusion chromatography was used to characterise in vitro125I-IGF-1 binding in end-point plasma from each treatment group. In comparison to control groups, anti-IGF-1 Ig treatment resulted in substantially increased 125I-IGF-1 binding in the 30 to 40 kDa region and a concomitant reduction in elution of free 125I-IGF-1. Protein restriction markedly depressed IGF-1 binding at ∼150 kDa in the plasma of diluent and non-immune Ig treated groups. Anti-IGF-1 Ig treatment was effective in preventing this decrease in ∼150 kDa binding. Thus, anti-IGF-1 Ig appears to have a beneficial effect on dietary intake in protein-restricted rats, which is associated with induced changes in IGF-1 binding profiles in plasma.
How do hormones and growth factors regulate animal growth in the developing embryo and after injury? What processes at the molecular level determine the growth patterns of different tissues? In this diverse synthesis of recent research the regulation of growth in response to environmental and genetic stimuli is discussed at the level of the animal, tissues and cells. Contrasts are drawn between regulation in foetal and adult tissues, and in different tissues such as the CNS, bone and muscle. Functional chapters focus on the molecular links between mechanical tension and muscle growth, for example, while other chapters review the roles of specific molecules such as growth hormone. This state-of-the-art review will be of significant interest to graduate students and research scientists in the fields of animal growth, endocrinology and cell biology.
A laboratory colony of Glossina morsitans morsitans Westw. which originated from puparia collected near Kariba, Rhodesia was more productive than another colony which originated from Handeni, northern Tanzania; during 1975, the former produced an average of 5–9 puparia per female and the latter 3–6. Although mortality in the Tanzanian colony was somewhat higher than in the Rhodesian colony, the main reason for the lower productivity of the Tanzanian colony was the much poorer fecundity of the females. This was associated with abnormalities of the reproductive system. The differences in laboratory performance between the two stocks were probably a reflection of their genetic diversity. Thus the Tanzanian Y chromosome is metacentric compared with the almost acrocentric Y chromosome of Rhodesian males, and some individuals carry small metacentric supernumerary chromosomes which are not present in Rhodesian flies. Giemsa C-banding showed band differences between the chromosome complements of the two stocks. Probably the most important difference, revealed by polytene chromosome analysis, is a large inversion in the X chromosome of Tanzanian flies, which, together with at least one band difference, is fixed in the homozygous condition. The possible evolutionary pathways of these mutations are outlined and their significance is discussed in terms of their distribution in nature and of the performance of the two strains in the laboratory.
Two assemblages of organic-walled microfossils have been recognized in drillcore samples from the late Proterozoic Rodda Beds in theeastern Officer Basin, South Australia. The fossils include tube-like remains and large, simple and sculptured acritarchs. Lithostratigraphic studies and seismic information, in conjunction with previous (albeit limited) acritarch finds, allow local correlation of the Rodda Beds with Ediacaran or terminal Proterozoic sequences in the northern Adelaide Fold Belt (site of the nominated Ediacaran stratotype). The new palynofloras are comparable withacritarch assemblages in the Amadeus Basin of central Australia, and suggest tentative correlations with sequences in China and the U.S.S.R. The presence of isotopically heavy marine carbonate in the lower fossiliferous horizons of the Rodda Beds (σ13CPDB = +3 to +6%0) is consistent with isotopic data from the equivalent interval in China. In contrast, the upper fossiliferous strata occur higher in the Rodda Beds where carbonate is significantly lighter (σ13CPDB = -1 to + 3%0).