Anatomy, Age and Origin of an Intramontane Top Basin Surface (Sorbas Basin, Betic Cordillera, SE Spain)

Collisional mountain belts commonly develop intramontane basins from mechanical and isostatic subsidence during orogenic development. These frequently display a relict top surface, evidencing a change interval from basin infilling to erosion often via capture or overspill. Such surfaces provide markers that inform on orogenic growth patterns via climate and base level interplay. Here, we describe the top surface from the Sorbas Basin, a key intramontane basin within the Betic Cordillera (SE Spain). The surface is fragmentary comprising high elevation hilltops and discontinuous ridges developed onto the variably deformed final basin infill outcrop (Gochar Formation). We reconstruct surface configuration using DEM interpolation and apply 10Be/26Al cosmonuclides to assess surface formation timing. The surface is a degraded Early Pleistocene erosional pediment developed via autogenic switching of alluvial fan streams under stable dryland climate and base level conditions. Base-level lowering since the Middle Pleistocene focused headwards incision up interfan drainages, culminating in fan head capture and fan morphological preservation within the abandoned surface. Post abandonment erosion has lowered the basin surface by 31 m (average) and removed ~5.95 km3 of fill. Regional basin comparisons reveal a phase of Early Pleistocene surface formation, marking landscape stability following the most recent Pliocene-Early Pleistocene mountain building. Post-surface erosion rate quantification is low and in accordance with 10Be denudation rates typical of the low uplift Betic Cordillera.</jats:p

Controls on modern tributary-junction alluvial fan occurrence and morphology: High Atlas Mountains, Morocco

Modern tributary-junction alluvial fans (cone-shaped depositional landforms formed in confined valley settings) were analysed from a 20-km-long reach of the Dades River in the distal part of the fold-thrust belt region in the south-central High Atlas Mountains of Morocco. Here, a deeply dissected network of ephemeral tributary streams and a perennial trunk drainage characterised by an arid mountain desert climate are configured onto a folded and thrust faulted Mesozoic sedimentary sequence. Out of 186 tributary streams, only 29 (16%) generated alluvial fans at their tributary junctions. The fan-generating catchments possess higher relief, longer lengths, lower gradients, and larger areas than nonfan-generating catchments. Whilst geologically, fan-generating catchments are underlain by folded / steeply dipping weak bedrock conducive to high sediment yield. Tributary-junction fans are built from debris flow or fluvial processes into open or confined canyon trunk valley settings. The proximity of the perennial trunk drainage combined with the valley morphology produces lobate or foreshortened trimmed fan forms. Analysis of fan (area, gradient, process), catchment (area, relief, length, gradient), and tributary valley (width) variables reveals weak morphometric relationships, highlighted by residual plots that show dominance of smaller and lower gradient than expected fan forms. These morphometric relationships can be explained by interplay between the catchment and trunk drainage geology, morphology, climate, and flood regime that are combined into a conceptual ‘build and reset’ model. Ephemeral tributary-junction fans develop progressively during annual localised winter-spring storm events, attempting to build toward a morphological equilibrium. However, the fans never reach an equilibrium morphological form as they are reset by rare (>10 year) large floods along the River Dades that are linked to regional incursions of Atlantic low pressure troughs. The model highlights the spatial and temporal variability of tributary-junction fan building and illustrates the connectivity / coupling importance of such features in dryland mountainous terrains

Erythropoietic protoporphyria without skin symptoms-you do not always see what they feel

Erythropoietic protoporphyria (EPP) is an inherited disorder of the porphyrin metabolism that often remains undiagnosed in children. We report on a 4-year-old girl who had been suffering for 1 year from recurrent painful crises affecting her hands, feet, and nose following sun exposure. Objective skin lesions were absent until the age of 6. Porphyrin analysis revealed elevated free erythrocyte protoporphyrin (FEP) levels confirming the diagnosis of EPP. This illustrates that skin lesions might be completely absent in children affected with EPP, a fact that has only been reported once previously. Because EPP can manifest with few and unspecific cutaneous symptoms or no skin lesions at all, like in this patient, the diagnosis of EPP might be delayed or missed. EPP should be excluded in all photosensitive children, especially when discomfort is disproportionate to the extent of the cutaneous lesions. The clinic, pathophysiology, diagnosis, complications, and therapy of EPP are discussed

Dynamics of Salmonella enterica and antimicrobial resistance in the Brazilian poultry industry and global impacts on public health

Non-typhoidal Salmonella enterica is a common cause of diarrhoeal disease; in humans, consumption of contaminated poultry meat is believed to be a major source. Brazil is the world’s largest exporter of chicken meat globally, and previous studies have indicated the introduction of Salmonella serovars through imported food products from Brazil. Here we provide an in-depth genomic characterisation and evolutionary analysis to investigate the most prevalent serovars and antimicrobial resistance (AMR) in Brazilian chickens and assess the impact to public health of products contaminated with S. enterica imported into the United Kingdom from Brazil. To do so, we examine 183 Salmonella genomes from chickens in Brazil and 357 genomes from humans, domestic poultry and imported Brazilian poultry products isolated in the United Kingdom. S. enterica serovars Heidelberg and Minnesota were the most prevalent serovars in Brazil and in meat products imported from Brazil into the UK. We extended our analysis to include 1,259 publicly available Salmonella Heidelberg and Salmonella Minnesota genomes for context. The Brazil genomes form clades distinct from global isolates, with temporal analysis suggesting emergence of these Salmonella Heidelberg and Salmonella Minnesota clades in the early 2000s, around the time of the 2003 introduction of the Enteritidis vaccine in Brazilian poultry. Analysis showed genomes within the Salmonella Heidelberg and Salmonella Minnesota clades shared resistance to sulphonamides, tetracyclines and beta-lactams conferred by sul2, tetA and blaCMY-2 genes, not widely observed in other co-circulating serovars despite similar selection pressures. The sul2 and tetA genes were concomitantly carried on IncC plasmids, whereas blaCMY-2 was either co-located with the sul2 and tetA genes on IncC plasmids or independently on IncI1 plasmids. Long-term surveillance data collected in the UK showed no increase in the incidence of Salmonella Heidelberg or Salmonella Minnesota in human cases of clinical disease in the UK following the increase of these two serovars in Brazilian poultry. In addition, almost all of the small number of UK-derived genomes which cluster with the Brazilian poultry-derived sequences could either be attributed to human cases with a recent history of foreign travel or were from imported Brazilian food products. These findings indicate that even should Salmonella from imported Brazilian poultry products reach UK consumers, they are very unlikely to be causing disease. No evidence of the Brazilian strains of Salmonella Heidelberg or Salmonella Minnesota were observed in UK domestic chickens. These findings suggest that introduction of the Salmonella Enteritidis vaccine, in addition to increasing antimicrobial use, could have resulted in replacement of salmonellae in Brazilian poultry flocks with serovars that are more drug resistant, but less associated with disease in humans in the UK. The plasmids conferring resistance to beta-lactams, sulphonamides and tetracyclines likely conferred a competitive advantage to the Salmonella Minnesota and Salmonella Heidelberg serovars in this setting of high antimicrobial use, but the apparent lack of transfer to other serovars present in the same setting suggests barriers to horizontal gene transfer that could be exploited in intervention strategies to reduce AMR. The insights obtained reinforce the importance of One Health genomic surveillance

Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases.

Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer's disease, atypical neurodegenerative dementias and Parkinson's disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.Includes MRC, NIHR, Wellcome Trust, H2020 and FP7

Cardiovascular disease by diabetes status in five ethnic minority groups compared to ethnic Norwegians

<p>Abstract</p> <p>Background</p> <p>The population in Norway has become multi-ethnic due to migration from Asia and Africa over the recent decades. The aim of the present study was to explore differences in the self-reported prevalence of cardiovascular disease (CVD) and associated risk factors by diabetes status in five ethnic minority groups compared to ethnic Norwegians.</p> <p>Methods</p> <p>Pooled data from three population-based cross-sectional studies conducted in Oslo between 2000 and 2002 was used. Of 54,473 invited individuals 24,749 (45.4%) participated. The participants self-reported health status, underwent a clinical examination and blood samples were drawn. A total of 17,854 individuals aged 30 to 61 years born in Norway, Sri-Lanka, Pakistan, Iran, Vietnam or Turkey were included in the study. Chi-square tests, one-way ANOVAs, ANCOVAs, multiple and logistic regression were used.</p> <p>Results</p> <p>Age- and gender-standardized prevalence of self-reported CVD varied between 5.8% and 8.2% for the ethnic minority groups, compared to 2.9% among ethnic Norwegians (p < 0.001). Prevalence of self-reported diabetes varied from 3.0% to 15.0% for the ethnic minority groups versus 1.8% for ethnic Norwegians (p < 0.001). Among individuals without diabetes, the CVD prevalence was 6.0% versus 2.6% for ethnic minorities and Norwegians, respectively (p < 0.001). Corresponding CVD prevalence rates among individuals with diabetes were 15.3% vs. 12.6% (p = 0.364). For individuals without diabetes, the odds ratio (OR) for CVD in the ethnic minority groups remained significantly higher (range 1.5-2.6) than ethnic Norwegians (p < 0.05), after adjustment for age, gender, education, employment, and body height, except for Turkish individuals. Regardless of diabetes status, obesity and physical inactivity were prevalent in the majority of ethnic minority groups, whereas systolic- and diastolic- blood pressures were higher in Norwegians. In nearly all ethnic groups, individuals with diabetes had higher triglycerides, waist-to-hip ratio (WHR), and body mass index compared to individuals without diabetes. Age, diabetes, hypertension, hypercholesterolemia, and WHR were significant predictors of CVD in both ethnic Norwegians and ethnic minorities, but significant ethnic differences were found for age, diabetes, and hypercholesterolemia.</p> <p>Conclusions</p> <p>Ethnic differences in the prevalence of CVD were prominent for individuals without diabetes. Primary CVD prevention including identification of undiagnosed diabetes should be prioritized for ethnic minorities without known diabetes.</p

A One Health Perspective on Salmonella enterica Serovar Infantis, an Emerging Human Multidrug-Resistant Pathogen

Salmonella enterica serovar Infantis presents an ever-increasing threat to public health because of its spread throughout many countries and association with high levels of antimicrobial resistance (AMR). We analyzed whole-genome sequences of 5,284 Salmonella Infantis strains from 74 countries, isolated during 1989-2020 from a wide variety of human, animal, and food sources, to compare genetic phylogeny, AMR determinants, and plasmid presence. The global Salmonella Infantis population structure diverged into 3 clusters: a North American cluster, a European cluster, and a global cluster. The levels of AMR varied by Salmonella Infantis cluster and by isolation source; 73% of poultry isolates were multidrug resistant, compared with 35% of human isolates. This finding correlated with the presence of the pESI megaplasmid; 71% of poultry isolates contained pESI, compared with 32% of human isolates. This study provides key information for public health teams engaged in reducing the spread of this pathogen

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

<div><h3>Objectives</h3><p>Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort.</p> <h3>Methods</h3><p>664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique.</p> <h3>Results</h3><p>At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years.</p> <h3>Conclusions</h3><p>Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.</p> </div

Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease

Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.Etude de cohorte sur la santé des étudiantsStopping cognitive decline and dementia by fighting covert cerebral small vessel diseaseStudy on Environmental and GenomeWide predictors of early structural brain Alterations in Young student