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Background: Aphids are common crop pests. These insects reproduce by facultative parthenogenesis involving several rounds of clonal reproduction interspersed with an occasional sexual cycle. Furthermore, clonal aphids give birth to live young that are already pregnant. These qualities enable rapid population growth and have facilitated the colonisation of crops globally. In several cases, so-called "super clones" have come to dominate agricultural systems. However, the extent to which the sexual stage of the aphid life cycle has shaped global pest populations has remained unclear, as have the origins of successful lineages. Here, we used chromosome-scale genome assemblies to disentangle the evolution of two global pests of cereals—the English (Sitobion avenae) and Indian (Sitobion miscanthi) grain aphids. Results: Genome-wide divergence between S. avenae and S. miscanthi is low. Moreover, comparison of haplotype-resolved assemblies revealed that the S. miscanthi isolate used for genome sequencing is likely a hybrid, with one of its diploid genome copies closely related to S. avenae (~ 0.5% divergence) and the other substantially more divergent (> 1%). Population genomics analyses of UK and China grain aphids showed that S. avenae and S. miscanthi are part of a cryptic species complex with many highly differentiated lineages that predate the origins of agriculture. The complex consists of hybrid lineages that display a tangled history of hybridisation and genetic introgression. Conclusions: Our analyses reveal that hybridisation has substantially contributed to grain aphid diversity, and hence, to the evolutionary potential of this important pest species. Furthermore, we propose that aphids are particularly well placed to exploit hybridisation events via the rapid propagation of live-born "frozen hybrids" via asexual reproduction, increasing the likelihood of hybrid lineage formation. [ABSTRACT FROM AUTHOR]

In the absence of agreed institutional arrangements for the post-Brexit EU-UK relationship the present contribution explores whether guidance can be found for the institutional dimension of their future relationship in a number of other documents and principles. We will, first of all, examine the institutional framework laid down in the 'Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community, done at Brussels and London on 24 January 2020', and its implementation. Second, we will uncover some aspects of the future institutional relationship based on the 'Political Declaration setting out the framework for the future relationship between the European Union and the United Kingdom' of 17 October 2019, which was adopted by the EU and the UK in parallel with the Withdrawal Agreement. Third, we will explore how the Commission sees that relationship based on its March 2020 draft text. Fourth, we will discuss at a meta level the principles which will in any event govern the institutional side of the future relationship, in particular the principle of good faith. Some brief concluding remarks round up. [ABSTRACT FROM AUTHOR]

Although recently introduced in the pharmacological treatment algorithm of chronic obstructive pulmonary disease (COPD), there is a need for more data supporting the use of blood eosinophil counts as a biomarker to guide inhaled corticosteroids (ICS) therapy. The aim of this study was to evaluate the risk of moderate and/or severe exacerbations and all-cause mortality in a large primary care population after withdrawal of ICS compared to continued users stratified by elevated blood eosinophil counts. In this population based cohort study, we used data from the Clinical Practice Research Datalink (CPRD) in the United Kingdom. We included subjects' aged 40 years or more who had a diagnosis of COPD. We excluded subjects with a history of asthma, pulmonary fibrosis, cardiac arrhythmia and bronchiectasis, COPD exacerbations occurring within 6 weeks prior to index date, or with a myocardial infarction within 3 months prior to index date. Continuous users were subjects who received their most recent ICS prescription within 3 months before the start of an interval. ICS withdrawals were those who discontinued ICS for more than 3 months. We evaluated the risk of moderate and/or severe exacerbations and all-cause mortality among subjects with various blood eosinophil thresholds who withdrew from ICS compared to continuous ICS users with elevated blood eosinophil levels using Cox regression analysis adjusted for potential confounders. We identified 48,157 subjects diagnosed with COPD between 1 January 2005 to 31 January 2014. Withdrawal of ICS was not associated with an increased risk of moderate-to-severe exacerbations among subjects with absolute blood eosinophil counts ≥0.34 × 109 cells/L [adjusted hazard ratio (adj. HR) 0.72; 95% confidence interval (CI) 0.63–0.81] or relative counts ≥ 4.0% (adj. HR 0.72; 95% CI: 0.66–0.78). Similarly, withdrawal of ICS was not associated with an increased risk of severe exacerbations among subjects with absolute blood eosinophil ≥0.34 × 109 cells/L (adj. HR 0.82; 95% CI: 0.61–1.10) or relative blood eosinophil counts ≥4.0% (adj. HR 0.80; 95% CI: 0.61–1.04). No increased risk of all-cause mortality was observed among subjects who withdrew from ICS irrespective of elevated absolute or relative blood eosinophil counts. In a real-world primary care population, we did not observe an increased risk of moderate and/or severe COPD exacerbations or all-cause mortality among subjects with eosinophilia who withdrew their use of ICS. [ABSTRACT FROM AUTHOR]

Flamborough Head chalks are located at the extremities of E-W and N-S trending fault systems along the Yorkshire coast (UK). Rock deformation is expressed in Selwicks Bay where a normal fault is exposed along with a high density of calcite veins. The fault mineralization is tested using geochemistry. Crosscutting relationships are used to differentiate between three vein generations: a network of parallel veins that are oriented perpendicular to stratigraphy (Group I), hydraulic breccia with typical jigsaw puzzle structure (Group II), and a third generation of calcite veins crosscutting the two previous generations (Group III). Geochemical analyses revealed that all three generations possess the same chemical signature and must reflect successive pulses from the same mineralizing fluid source. Strontium isotope analyses showed that the veins have elevated 87Sr/86Sr ratios, that is, up to 7.110, while ratios of the chalk matrix equal 7.707. The latter value is in agreement with the signature of Late Cretaceous seawater. Consequently, the source of the fluid is external, reflecting an open system. The radiogenic Sr-isotope ratios, combined with low iron concentration, suggest that fluids migrated through sandy deposits. Fluid inclusion salinities range from 0 to 12 eq. wt% NaCl equiv. with a dominance of very low salinity inclusions, reflecting a meteoric signal. This leads to a model where meteoric fluids stored in an underlying confined sandstone aquifer were remobilized. The wide range of salinities could result from mixing of the meteoric fluid with some more saline fluids present in the rock sequence or from the dissolution of salts in the subsurface. In addition to the understanding of the local paragenetic evolution of the veining in Flamborough Head chalks, this study offers an insight into the way how fluid flows and mineralizes along fault zones. [ABSTRACT FROM AUTHOR]

Fireproof mill construction had been developed in England at the end of the 18th century. In Brussels, the first large fireproof building was constructed in 1844–1847. All at once, the backlog of 50 years was eliminated. Moreover, for Brussels, the experimental period just started. Not bound by traditions, new techniques and materials were soon adopted. The evolution of the construction history of fireproof building in Brussels is discussed by going more deeply into the construction of six buildings, erected between 1844 and 1870. [ABSTRACT FROM AUTHOR]

Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1 -/- and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the UK Biobank. MSR1 expression was associated with the occurrence of hepatic lipid-laden foamy macrophages and correlated with the degree of steatosis and steatohepatitis in patients with NAFLD. Mice lacking Msr1 were protected against diet-induced metabolic disorder, showing fewer hepatic foamy macrophages, less hepatic inflammation, improved dyslipidaemia and glucose tolerance, and altered hepatic lipid metabolism. Upon induction by saturated fatty acids, MSR1 induced a pro-inflammatory response via the JNK signalling pathway. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a pro-inflammatory phenotype and the release of cytokines such as TNF-ɑ. Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and human liver slices resulted in the prevention of foamy macrophage formation and inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1 , was associated with altered serum triglycerides and aspartate aminotransferase levels in a cohort of over 400,000 patients. Taken together, our data suggest that MSR1 plays a critical role in lipid-induced inflammation and could thus be a potential therapeutic target for the treatment of NAFLD. Non-alcoholic fatty liver disease (NAFLD) is a chronic disease primarily caused by excessive consumption of fat and sugar combined with a lack of exercise or a sedentary lifestyle. Herein, we show that the macrophage scavenger receptor MSR1, an innate immune receptor, mediates lipid uptake and accumulation in Kupffer cells, resulting in liver inflammation and thereby promoting the progression of NAFLD in humans and mice. [Display omitted] • In human NAFLD, MSR1 is expressed in mature Kupffer cells and foamy macrophages. • MSR1 transcript levels are associated with disease activity in patients with NAFLD. • Mice lacking Msr1 are protected from diet-induced metabolic disorder. • Uptake of saturated fatty acids via MSR1 results in a pro-inflammatory response. • The SNP rs41505344 upstream of MSR1 is associated with altered serum triglycerides. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To compare domains of cognitive functioning between persons with and without obstructive lung disease (OLD) and to analyze the relationship between cognitive functioning and the degree of airflow limitation. Design: An observational population-based study. Setting: This research was conducted using the United Kingdom Biobank Resource. Participants: The study population consisted of 43,039 persons with complete data on cognitive functioning and spirometry. Measurements: Cognitive functioning was compared between persons with and without OLD using linear regression analysis. The relationship between impairment in lung function and cognitive impairment was assessed among persons with OLD. Results: Persons with OLD had significantly worse scores than persons without OLD on prospective memory [β = –0.15 (–0.22 to –0.09)], visuospatial memory [β round 1 = 0.06 (0.03‒0.10)]; β round 2 = 0.09 (<0.001‒0.18)), numeric short-term memory [β = ‒0.05 (‒0.10 to <0.001)] and cognitive processing speed [β = 4.62 (1.25‒8.01)] after correction for possible confounders. Impairment in prospective memory [β = 0.004 (<0.001‒0.01)] and numeric short-term memory [β = 0.01 (0.003‒0.01)] were weakly related to FEV1 (adjusted P < .05). Conclusions: Persons with OLD experience cognitive impairment in different domains, which is partially related to airway obstruction. In particular, memory and information processing are affected. Further assessment of the relationship with patient-related outcomes is needed to optimize patient-oriented treatment. [Copyright &y& Elsevier]

Abstract: Background: Low fat-free mass (FFM) is a risk factor for morbidity and mortality in elderly and patient populations. Therefore, measurement of FFM is important in nutritional assessment. Bioelectrical impedance analysis (BIA) is a convenient method to assess FFM and FFM index (FFMI; FFM/height2). Although reference values have been established for individuals with normal body weight, no specific cutoff values are available for overweight and obese populations. Also, limited studies accounted for the age-related decline in FFM. Objective: To determine BMI- and age-specific reference values for abnormal low FFM(I) in white-ethnic men and women free of self-reported disease from the general population. Design: The UK Biobank is a prospective epidemiological study of the general population from the United Kingdom. Individuals in the age category 45 to 69 years were analyzed. In addition to body weight, FFM and FFMI were measured using a Tanita BC-418MA. Also, self-reported chronic conditions and ethnic background were registered, and lung function was assessed using spirometry. Results: After exclusion of all individuals with missing data, nonwhite ethnicity, self-reported disease, body mass index (BMI) less than 14 or 36 kg/m2 or higher, and/or an obstructive lung function, reference values for FFM and FFMI were derived from 186,975 individuals (45.9% men; age: 56.9 ± 6.8 years; BMI: 26.5 ± 3.6 kg/m2; FFMI 18.3 ± 2.4 kg/m2). FFM and FFMI were significantly associated with BMI and decreased with age. Percentiles 5, 10, 25, 50, 75, 90, and 95 were calculated for FFM, FFMI, and fat mass (index), after stratification for gender, age, and BMI. Conclusions: Using the UK Biobank dataset, new reference values for body composition assessed with BIA were determined in white-ethnic men and women aged 45 to 69 years. Because these reference values are BMI specific, they are of broad interest for overweight and obese populations. [Copyright &y& Elsevier]

Abstract: Objectives: To develop normative values for right and left handgrip strength after stratification for confounders like gender, age, and height. Design: Cross-sectional, descriptive. Setting: General population. Participants: A total of 502,713 people living in the United Kingdom. Intervention: None. Measurements: Handgrip strength was measured using a Jamar hydraulic hand dynamometer, which is considered to be an accurate instrument to measure handgrip strength. In addition, self-reported chronic conditions and ethnic background were registered, and lung function was assessed using spirometry. Results: After exclusion of all individuals with missing data, a nonwhite ethnic background, the presence of 1 or more self-reported conditions, and/or an obstructive lung function (defined as FEV1/FVC <0.7), new normative values for right and left handgrip strength were derived from 224,830 and 224,852 individuals (54.2% women; age: 55.0 [8.0] years; height: 169.0 [9.2] cm; body mass index: 26.9 [4.4] kg/m2) with a nonobstructed spirometry (FEV1: 3.0 [0.8] L). Men were stronger than women. Moreover, significant associations were found between handgrip strength and height, and between handgrip strength and age. Finally, percentiles 5, 10, 25, 50, 75, 90, and 95 were calculated for right and left handgrip strength, after stratification for gender, age, and height. Conclusion: The UK Biobank dataset provided the opportunity to determine new normative values for handgrip strength in men and women aged 39 to 73 years. These normative values take into consideration age, height, and measurement side. Therefore, these new normative handgrip strength values are of broad clinical interest. [Copyright &y& Elsevier]