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A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).
The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8–40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.
When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).
We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.
The Interdisciplinary Network for Dementia Using Current Technology, INDUCT, is a Marie Sklodowska Curie funded International Training Network that aims to develop a multi-disciplinary, inter-sectorial educational research framework for Europe to improve technology and care for people with dementia, and to provide the evidence to show how technology can improve the lives of people with dementia. Within INDUCT (2016-2020) 15 Early Stage Researchers worked on projects in the areas of Technology to support every day life; technology to promote meaningful activities; and health care technology.
Three transversal objectives were adopted by INDUCT: 1) To determine the practical, cognitive and social factors needed to make technology more useable for people with dementia; 2) To evaluate the effectiveness of specific contemporary technology; and 3) To trace facilitators and barriers for implementation of technology in dementia care.
The main recommendations resulting from the research projects are integrated in a web-based digital Best Practice Guidance on Human Interaction with Technology in Dementia which will be presented at the congress. The recommendations are meant to be helpful for different target groups, i.e. people with dementia, their formal and informal carers, policy makers, designers and researchers, who can easily select the for them relevant recommendations in the Best Practice Guidance by means of a selection tool. The main aim of the Best Practice Guidance is to improve the development, usage and implementation of technology for people with dementia in the three mentioned technology areas.
This Best Practice Guidance is the result of the intensive collaborative partnership of INDUCT with academic and non-academic partners as well as the involvement of representatives of the different target groups throughout the INDUCT project.
Acknowledgements: The research presented was carried out within the Marie Sklodowska Curie International Training Network (ITN) action, H2020-MSCA-ITN-2015, grant agreement number 676265.
Antarctica's ice shelves modulate the grounded ice flow, and weakening of ice shelves due to climate forcing will decrease their ‘buttressing’ effect, causing a response in the grounded ice. While the processes governing ice-shelf weakening are complex, uncertainties in the response of the grounded ice sheet are also difficult to assess. The Antarctic BUttressing Model Intercomparison Project (ABUMIP) compares ice-sheet model responses to decrease in buttressing by investigating the ‘end-member’ scenario of total and sustained loss of ice shelves. Although unrealistic, this scenario enables gauging the sensitivity of an ensemble of 15 ice-sheet models to a total loss of buttressing, hence exhibiting the full potential of marine ice-sheet instability. All models predict that this scenario leads to multi-metre (1–12 m) sea-level rise over 500 years from present day. West Antarctic ice sheet collapse alone leads to a 1.91–5.08 m sea-level rise due to the marine ice-sheet instability. Mass loss rates are a strong function of the sliding/friction law, with plastic laws cause a further destabilization of the Aurora and Wilkes Subglacial Basins, East Antarctica. Improvements to marine ice-sheet models have greatly reduced variability between modelled ice-sheet responses to extreme ice-shelf loss, e.g. compared to the SeaRISE assessments.
Considering the dramatically increasing incidence of type 2 diabetes (T2D), decreasing glycemic variability in T2D patients is a key challenge to limit the occurrence of diabetic complications. Diet appears as one potential lever that can be set up above medications. Particularly, the ingestion of foods with a high content in slowly digestible starch (SDS) demonstrated both lower postprandial glycemic and insulin responses in healthy and insulin resistant subjects. This study aimed at designing a full high-SDS diet by selecting high-SDS starchy food products and at studying its impact on glycemic response and variability in T2D.
Materials and methods
This pilot randomized controlled cross-over study included eight T2D patients (HbA1c = 7.0 ± 0.2%, BMI = 31.7 ± 2.1 kg/m2, treated by Metformin & Sitagliptin) who consumed twice, for one week a controlled diet containing starchy food products screened and selected to be either High (High-SDS) or Low (Low-SDS) in SDS, as determined by the SDS in-vitro method developed by Englyst et al. During each diet period, the glycemic profile was monitored for 6 days using a Continuous Glucose Monitoring System (CGMS). Multiple metrics related to variability and glycemic responses were calculated.
222 SDS analyses were realized on commercial food products as consumed. 23 High-SDS and 20 Low-SDS food items with associated specific cooking instructions were selected to design two diets consistent with local T2D recommendations. The High-SDS diet demonstrated a significantly higher SDS content compared to the Low-SDS diet (61.6 vs 11.6 g/day; p < 0.0001), mainly driven by selected pasta, rice and high-SDS biscuits (75.6% of the consumed SDS content). The % of total daily energy intake (TDEI) for all macronutrients remained similar between diets (p > 0.05) and the carbohydrate content specifically represented 49 ± 1 % and 47 ± 2 % of the TDEI for High-SDS and Low-SDS diets, respectively. With the high-SDS diet, the Mean Amplitude of Glycemic Excursion, a key parameter of glycemic variability, was significantly decreased (79.6 for Low-SDS vs 61.6 mg/dL for High-SDS; p = 0.0067). The significant correlation between the meals SDS contents and various glycemic parameters such as postprandial iAUC, tAUC (up to 180 min) or peak value strengthen this finding (p < 0.05 for all).
It was the first demonstration that a diet including selected starchy food items and cooking recommendations designed to favor products’ high SDS content beneficially impacts glycemic profile in T2D subjects. Carefully selecting starchy food may be a simple and valuable tool to improve glycemic control in T2D.
Dietary fibers (DF) have been classified mainly according to their physico-chemical and fermentability properties but it remains unclear whether such classification is relevant when addressing their health effects. Indeed, the nature of physiological effects induced by DF, particularly through their interaction with gut microbiota, remains poorly known due to their diversity, to gut microbiota inter-subjects variability and to the lack of validated non-invasive biomarkers to characterize DF-gut microbiota interaction. The aim of this pilot study was 1) to follow the metabolic fate of 13C-labeled DF through the assessment of 13C-labelled gut-derived metabolites in excreted breath and 2) to evaluate novel non-invasive breath-derived biomarkers of DF-gut microbiota interactions.
Materials and methods
Six healthy women (29.7 ± 1.7 years old, BMI: 23.2 ± 0.9kg/m2, fiber intake: 23 ± 1g/d) consumed in research settings a controlled breakfast containing eight 13C-labelled wheat bran biscuits (50 g of labelled wheat bran, 3.0At%13C). 13C-labelled wheat bran was obtained from wheat cultivated under 13CO2 enriched atmosphere. Samples of expired gases were collected during 24 h after ingestion in order to measure H2 and CH4 by gas chromatography (GC) with piezoelectric detection and 13CO2 and 13CH4 by gas chromatography coupled with an isotope ratio mass spectrometer (GC-IRMS). Apart test breakfast, subjects only consumed standardized meals without fibers.
The analysis of H2 and CH4 24h-kinetic measurements distinguished 2 groups in terms of fermentation related gas excretion: the high-CH4 producers with high baseline CH4 concentrations (42.1 ± 13.7ppm) and low baseline H2 concentrations (7.3 ± 5.8ppm) and the low-CH4 producers with low baseline CH4 concentrations (6.5 ± 3.6ppm) and high baseline H2 concentrations (20.8 ± 16.0ppm). Following the 13C-wheat bran biscuits’ ingestion, postprandial H2 and CH4 concentrations increased more significantly in the high-CH4 producer subjects. 13C enrichment was detectable in expired gases in all subjects. 13CO2 kinetics were similar for all subjects and correspond to the oxidation of the digestible part of the bran. The appearance of 13CH4 was significantly enhanced and prolonged after 180 min in high-CH4 producers compared to low-CH4 producers, suggesting distinct fiber fermentation profile.
This pilot study allowed to consider novel procedures for development of non-invasive breath biomarkers of fiber-gut microbiota interactions. Assessment of expired gas excretion following 13C-labelled fiber ingestion allowed deciphering distinct fermentation profiles: high-CH4 producers vs low-CH4 producers and accordingly provide a related non-invasive breath metabolic signature of the fiber fermentation for each profile. Further gut microbiota and 13C-metabolites analysis will permit to relate the gut bacteria composition with breath gas excretion kinetics according to fiber fermentation profile.
Alterations of the gut microbiome have been associated with obesity and metabolic disorders. The gut microbiota can be influenced by the intake of dietary fibres with prebiotic properties, such as inulin-type fructans. The present study tested the hypothesis that obese individuals subjected for 12 weeks to an inulin-enriched v. inulin-poor diet have differential faecal fermentation patterns. The fermentation of cellulose and inulin hydrolysates of six different inulin-rich and inulin-poor vegetables of both groups was analysed in vitro on faecal inocula. The results showed that the microbiota from obese patients who received a fructan-rich diet for 3 weeks produces more gas and total SCFA compared with the microbiota taken from the same individuals before the treatment. Obese individuals fed with a low-fructan diet produce less gas and less SCFA compared with the treated group. The present study highlighted profound changes in microbiota fermentation capacity obtained by prebiotic intervention in obese individuals, which favours the production of specific bioactive metabolites.
We report on our search for spectroscopic binaries among a sample of AGB stars. Observations were carried out in the framework of the monitoring of radial velocities of (candidate) binary stars performed at the Mercator 1.2m telescope, using the HERMES spectrograph. We found evidence for duplicity in UV Cam, TU Tau, BL Ori, VZ Per, T Dra, and V Hya.
To study zooplankton–phytoplankton relationships in the diatom-dominated plankton communities of the northern Adriatic we performed feeding experiments with diatoms and zoea I larvae of the brachyuran Xantho poressa. We found that zoea I of X. poressa feed on diatoms of different forms (centric, pennate, colony forming, single celled, with or without setae) and size classes. In a laboratory setup, we presented the zoeas with a mix of diatom species similar to communities observed during blooms regularly found in the northern Adriatic. We report that the grazing activity resulted in a decrease of the relative abundance of the toxic diatom Pseudo-nitzschia calliantha. For the colonial, bloom-forming diatom Skeletonema marinoi our results show a chain length reduction in the presence of zoea I. Of particular interest is the observation that the presence of larvae also resulted in an increased growth rate and abundance of S. marinoi, which resembles bloom induction by grazer presence.
The oomycete Aphanomyces astaci, the causative agent of crayfish plague, is listed as one of the 100 worst invasive species in the world, destroying the native crayfish populations throughout Eurasia. The aim of this study was to examine the potential of selected mitochondrial (mt) genes to track the diversity of the crayfish plague pathogen A. astaci. Two sets of primers were developed to amplify the mtDNA of ribosomal rnnS and rnnL subunits. We confirmed two main lineages, with four different haplogroups and five haplotypes among 27 studied A. astaci strains. The haplogroups detected were (1) the A-haplogroup with the a-haplotype strains originating from Orconectes sp., Pacifastacus leniusculus and Astacus astacus; (2) the B-haplogroup with the b-haplotype strains originating from the P. leniusculus; (3) the D-haplogroup with the d1 and d2-haplotypes strains originating from Procambarus clarkii; and (4) the E-haplogroup with the e-haplotype strains originating from the Orconectes limosus. The described markers are stable and reliable and the results are easily repeatable in different laboratories. The present method has high applicability as it allows the detection and characterization of the A. astaci haplotype in acute disease outbreaks in the wild, directly from the infected crayfish tissue samples.
A large body of research has explored opportunities to mitigate climate change in agricultural systems; however, less research has explored opportunities across the food system. Here we expand the existing research with a review of potential mitigation opportunities across the entire food system, including in pre-production, production, processing, transport, consumption and loss and waste. We detail and synthesize recent research on the topic, and explore the applicability of different climate mitigation strategies in varying country contexts with different economic and agricultural systems. Further, we highlight some potential adaptation co-benefits of food system mitigation strategies and explore the potential implications of such strategies on food systems as a whole. We suggest that a food systems research approach is greatly needed to capture such potential synergies, and highlight key areas of additional research including a greater focus on low- and middle-income countries in particular. We conclude by discussing the policy and finance opportunities needed to advance mitigation strategies in food systems.
High quality evidence for test accuracy can be scarce. We assessed the test accuracy of two tests (Actim Partus and PartoSure) for the prediction of preterm birth. Twenty published full-text papers were included whilst conference abstracts were excluded. Since systematic reviews of diagnostic tests on other topics may need to rely on data from conference abstracts, we test whether the findings of our review would change with conference abstracts included.
Conference citations previously excluded (n=108) were re-screened for inclusion using the following criteria: i) the diagnostic test was Actim Partus or PartoSure ii) test accuracy data of preterm delivery within seven days was reported iii) the population was women with signs/symptoms of preterm labor with intact membranes. Relevant test accuracy data were extracted and used to calculate sensitivity and specificity. Pooled sensitivity and specificity for each test were run using data from full-text papers and conference abstracts combined. These values were compared with the pooled sensitivities and specificities produced for the systematic review using full-text papers only.
Preliminary pooled sensitivities of the sixteen full-text Actim Partus studies and sixteen full-texts and two abstracts were 0.77 (95% confidence interval (CI) 0.68, 0.83) and 0.76 (95% CI 0.69, 0.83) respectively whilst pooled specificities were 0.81 (95% CI 0.76, 0.85).and 0.80 (95% CI 0.75, 0.84) respectively. Preliminary, pooled sensitivities of the four full-text PartoSure studies and four full-texts and three abstracts were 0.83 (95% CI 0.61, 0.94) and 0.82 (95% CI 0.65, 0.92), respectively, whilst pooled specificities were 0.95 (95% CI 0.89, 0.98) and 0.96 (95% CI 0.94, 0.97), respectively.
Our findings suggest that the test accuracy results would not alter substantially with the inclusion of conference abstracts. However, work is ongoing to investigate how the assessment of heterogeneity and risk of bias across studies would alter given the difficulties associated with limited methodological reporting from conference abstracts.
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of olaratumab (Lartruvo®), Eli Lilly & Company Limited, to submit evidence for the clinical and cost effectiveness of this drug, in combination with doxorubicin, for advanced soft tissue sarcoma (STS) not amenable to surgery or radiotherapy, as part of the Institute's Single Technology Appraisal. The Peninsula Technology Assessment Group critically reviewed the submitted evidence.
Clinical effectiveness was derived from an open-label, randomized controlled trial, JGDG. The economic analysis was based on a partitioned survival model with a time horizon of 25 years. The perspective was of the UK National Health Service (NHS) and Personal Social Services. Costs and benefits were discounted at 3.5 percent per year. The company's evidence was submitted in anticipation that olaratumab would be considered as an alternative to doxorubicin, which has been used as a first-line treatment for advanced STS. To improve the cost effectiveness of olaratumab, the company offered a discount through a Commercial Access Agreement with the NHS England.
In the company's submission, the mean base-case and probabilistic incremental cost-effectiveness ratios (ICERs) for olaratumab plus doxorubicin versus doxorubicin alone were GBP 46,076 (USD 61,403) and GBP 47,127 (USD 62,804) per quality-adjusted life-year (QALY) gained, respectively; the probability of this treatment being cost effective at the willingness-to-pay threshold of GBP 50,000 (USD 66,632) per QALY gained, applicable to end-of-life treatments, was 0.54. The respective estimates in our analysis were approximately GBP 60,000 (USD 79,959) per QALY gained, and the probability of cost-effectiveness was 0.21. The increase in the ICERs was primarily due to differences in extrapolation of overall survival, and drug administration costs.
Based on the available evidence, olaratumab in combination with doxorubicin improves the survival of patients with advanced STS. However, this treatment is unlikely to be cost-effective. Olaratumab is now recommended for use within the Cancer Drugs Fund.
Fear responses are particularly intense and persistent in post-traumatic stress disorder (PTSD), and can be evoked by unspecific cues that resemble the original traumatic event. Overgeneralisation of fear might be one of the underlying mechanisms. We investigated the generalisation and discrimination of fear in individuals with and without PTSD related to prolonged childhood maltreatment.
Sixty trauma-exposed women with (N = 30) and without (N = 30) PTSD and 30 healthy control participants (HC) underwent a fear conditioning and generalisation paradigm. In a contingency learning procedure, one of two circles of different sizes was associated with an electrical shock (danger cue), while the other circle represented a safety cue. During generalisation testing, online risk ratings, reaction times and fear-potentiated startle were measured in response to safety and danger cues as well as to eight generalisation stimuli, i.e. circles of parametrically varying size creating a continuum of similarity between the danger and safety cue.
The increase in reaction times from the safety cue across the different generalisation classes to the danger cue was less pronounced in PTSD compared with HC. Moreover, PTSD participants expected higher risk of an aversive event independent of stimulus types and task.
Alterations in generalisation constitute one part of fear memory alterations in PTSD. Neither the accuracy of a risk judgement nor the strength of the induced fear was affected. Instead, processing times as an index of uncertainty during risk judgements suggested a reduced differentiation between safety and threat in PTSD.
The concepts of nature, culture and heritage are deeply entwined; their threads run together in some of our finest museums, in accounts of exploration and discovery, in the work of artists, poets andwriters, and in areas that are cherished and protected because of their landscapes and wildlife. The conservation ethic - placing a value on the natural environment - lies at the heart of the notion of "natural heritage", but we need to question how those values originated, were consolidated and ultimately moulded and changed over time. In a contemporary context the connections between nature andculture have sometimes become lost, fragmented, dislocated or misunderstood; where did "natural heritage" begin and how do we engage with the idea of "nature" today? The essays collected here re-evaluate the role of culture in developing the concept of natural heritage, reflecting on the shifts in its interpretation over the last 300 years.
Contributors: Martin Holdgate, Marie Addyman,E. Charles Nelson, Darrell Smith, Andrew Ramsey, Viktor Kouloumpis, Richard Milner, Gina Douglas, Penny Bradshaw, Arthur MacGregor, Chiara Nepi, Hannah Paddon, Stephen Hewitt, Gordon McGregor Reid, Ghillean T Prance, Peter Davis, Christopher Donaldson, Lucy McRobert, Sophie Darlington, Keith Scholey, Paul A. Roncken, Angus Lunn, Juliet Clutton-Brock, Tim Sands, Robert A. Lambert, James Champion,Erwin van Maanen, Heather Prince, Chris Loynes, Julie Taylor, Sarah Elmeligi, Samantha Finn, Owen Nevin, Jared Bowers, Kate Hennessy, Natasha Lyons, Mike Jeffries.