Single-grain and multi-grain OSL dating of river terrace sediments in the Tabernas Basin, SE Spain

River terraces represent important records of landscape response to e.g. base-level change and tectonic movement. Both these driving forces are important in the southern Iberian Peninsula. In this study, Optically Stimulated Luminescence (OSL) dating was used to date two principal river terraces in the Tabernas Basin, SE Spain. A total of 23 samples was collected from the fluvial terraces for dating using quartz OSL. Sixteen of the samples could not be dated because of low saturation levels (e.g. typical 2xD0 < 50 Gy). The remaining seven samples (5 fossil and 2 modern analogues) were investigated using both multi-grain and single-grain analysis. Single grain results show that: (i) measurements from multi-grain aliquots overestimate ages by up to ∼ 4 ka for modern analogues and young samples (<5 ka), presumably because (ii) the presence of many saturated grains has biased the multi-grain results to older ages. Despite the unfavourable luminescence characteristics we are able to present the first numerical ages for two terrace aggradation stages in the Tabernas Basin, one at ∼16 ka and the other within the last 2 ka

The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study

Background: There are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months. Methods: In a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM. Results: Of 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51–70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06–13.77]; p < 0.001). Thirteen (11.4%) survivors had not returned to work due to poor health. There was a decrease in the EQ-5D-5LTM utility score (MD, − 0.19 [− 0.28 to − 0.10]; p < 0.001). At 6 months, 82 of 115 (71.3%) patients reported persistent symptoms. The independent predictors of death or new disability were higher severity of illness and increased frailty. Conclusions: At six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning.Carol L. Hodgson, Alisa M. Higgins, Michael J. Bailey, Anne M. Mather, Lisa Beach, Rinaldo Bellomo, Bernie Bissett, Ianthe J. Boden, Scott Bradley, Aidan Burrell, D. James Cooper, Bentley J. Fulcher, Kimberley J. Haines, Jack Hopkins, Alice Y. M. Jones, Stuart Lane, Drew Lawrence, Lisa van der Lee, Jennifer Liacos, Natalie J. Linke, Lonni Marques Gomes, Marc Nickels, George Ntoumenopoulos, Paul S. Myles, Shane Patman, Michelle Paton, Gemma Pound, Sumeet Rai, Alana Rix, Thomas C. Rollinson, Janani Sivasuthan, Claire J. Tipping, Peter Thomas, Tony Trapani, Andrew A. Udy, Christina Whitehead, Isabelle T. Hodgson, Shannah Anderson, Ary Serpa Neto, and The COVID-Recovery Study Investigators and the ANZICS Clinical Trials Grou

Regions of the genome that affect agronomic performance in two-row barley

Quantitative trait locus (QTL) main effects and QTL by environment (QTL × E) interactions for seven agronomic traits (grain yield, days to heading, days to maturity, plant height, lodging severity, kernel weight, and test weight) were investigated in a two-row barley (Hordeum vulgare L.) cross, Harrington/TR306. A 127-point base map was constructed from markers (mostly RFLP) scored in 146 random double-haploid (DH) lines from the Harrington/TR306 cross. Field experiments involving the two parents and 145 random DH lines were grown in 1992 and/or 1993 at 17 locations in North America. Analysis of QTL was based on simple and composite interval mapping. Primary QTL were declared at positions where both methods gave evidence for QTL. The number of primary QTL ranged from three to six per trait, collectively explaining 34 to 52% of the genetic variance. None of these primary QTL showed major effects, but many showed effects that were consistent across environments. The addition of secondary QTL gave models that explained 39 to 80% of the genetic variance. The QTL were dispersed throughout the barley genome and some were detected in regions where QTL have been found in previous studies. Eight chromosome regions contained pleiotropic loci and/or linked clusters of loci that affected multiple traits. One region on chromosome 7 affected all traits except days to heading. This study was an intensive effort to evaluate QTL in a narrow-base population grown in a large set of environments. The results reveal the types and distributions of QTL effects manipulated by plant breeders and provide opportunities for future testing of marker-assisted selection

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

A locus on barley chromosome 5H affects adult plant resistance to powdery mildew

Adult plant resistance against plant pathogens is of interest as a means to achieve durable resistance. Prior to this research, the barley lines CLE210 (from Uruguay) and Denar (from the Czech Republic) had been reported to exhibit adult-plant resistance against powdery mildew. Here, populations of doubled haploid lines from crosses of these lines with the susceptible cultivar Baudin were evaluated for powdery mildew resistance in field experiments. Using linkage maps constructed from genotyping-by-sequencing (GBS) data, it was determined that differences in resistance were largely attributable to a region on the long arm of chromosome 5H (5HL). Therefore, KASP™ assays were developed based on GBS tag sequences mapped on that chromosome, providing more reliable genetic maps. In each population, a large-effect QTL was mapped on 5HL. As no sequence variation was detected between CLE210 and Denar in this region of 5HL, the two sources of resistance may be identical by descent in the QTL region and carry the same resistance gene. Marker assays from the QTL region were evaluated on a panel of barley lines, providing information that breeders could use to select assays for use in marker-assisted selection