“The future is unstable”: Exploring changing fertility intentions in the United Kingdom during the COVID-19 pandemic

Acknowledgement: The Economic and Social Research Council funded data collection as part of the lead author's PhD studentship.Objective: To understand whether reproductive decision-making among United Kingdom (UK) respondents had changed in light of the COVID-19 pandemic and, if so, why COVID-19 had led them to change their intentions. Methods: We conducted a cross-sectional online survey in January 2021. We asked survey participants if their fertility intentions had changed and to rate how aspects of their life had changed during COVID-19. We also included an open-ended question and asked participants to explain in their own words how COVID-19 had influenced their reproductive decision-making. We used descriptive and regression analyses to explore the quantitative data and thematically analyzed written responses. Results: Nine percent (n = 70) of our 789 UK respondents reported a change in fertility intention after the start of the pandemic. Changes in both pro-natal and anti-natal directions made the overall change in intentions small: there was a 2% increase across the sample in not intending a child between the two time points. Only increased financial insecurity was predictive of changing intentions. Responses to the open-ended question (n = 103) listed health concerns, indirect costs of the pandemic, and changing work-life priorities as reasons for changing their intentions. Conclusion: While studies conducted at the beginning of the pandemic found that fertility intentions became more anti-natal, we found little overall change in fertility intentions in January 2021. Our findings of small pro-natal and anti-natal changes in fertility intentions align with emerging UK birth rate data for 2021, which show minimal change in the total fertility rate in response to the pandemic.Economic and Social Research Council National Science Centre (Poland). Grant Number: 2018/30/E/HS4/0044

Constant amplitude and post-overload fatigue crack growth behavior in PM aluminum alloy AA 8009

A recently developed, rapidly solidified, powder metallurgy, dispersion strengthened aluminum alloy, AA 8009, was fatigue tested at room temperature in lab air. Constant amplitude/constant delta kappa and single spike overload conditions were examined. High fatigue crack growth rates and low crack closure levels compared to typical ingot metallurgy aluminum alloys were observed. It was proposed that minimal crack roughness, crack path deflection, and limited slip reversibility, resulting from ultra-fine microstructure, were responsible for the relatively poor da/dN-delta kappa performance of AA 8009 as compared to that of typical IM aluminum alloys

Microscopy techniques for determining water-cement (w/c) ratio in hardened concrete: A round-robin assessment

Water to cement (w/c) ratio is usually the most important parameter specified in concrete design and is sometimes the subject of dispute when a shortfall in concrete strength or durability is an issue. However, determination of w/c ratio in hardened concrete by testing is very difficult once the concrete has set. This paper presents the results from an inter-laboratory round-robin study organised by the Applied Petrography Group to evaluate and compare microscopy methods for measuring w/c ratio in hardened concrete. Five concrete prisms with w/c ratios ranging from 0.35 to 0.55, but otherwise identical in mix design were prepared independently and distributed to 11 participating petrographic laboratories across Europe. Participants used a range of methods routine to their laboratory and these are broadly divided into visual assessment, measurement of fluorescent intensity and quantitative backscattered electron microscopy. Some participants determined w/c ratio using more than one method or operator. Consequently, 100 individual w/c ratio determinations were collected, representing the largest study of its type ever undertaken. The majority (81%) of the results are accurate to within ± 0.1 of the target mix w/c ratios, 58% come to within ± 0.05 and 37% are within ± 0.025. The study shows that microscopy-based methods are more accurate and reliable compared to the BS 1881-124 physicochemical method for determining w/c ratio. The practical significance, potential sources of errors and limitations are discussed with the view to inform future applications

Recommendations for the design of laboratory studies on non-target arthropods for risk assessment of genetically engineered plants

This paper provides recommendations on experimental design for early-tier laboratory studies used in risk assessments to evaluate potential adverse impacts of arthropod-resistant genetically engineered (GE) plants on non-target arthropods (NTAs). While we rely heavily on the currently used proteins from Bacillus thuringiensis (Bt) in this discussion, the concepts apply to other arthropod-active proteins. A risk may exist if the newly acquired trait of the GE plant has adverse effects on NTAs when they are exposed to the arthropod-active protein. Typically, the risk assessment follows a tiered approach that starts with laboratory studies under worst-case exposure conditions; such studies have a high ability to detect adverse effects on non-target species. Clear guidance on how such data are produced in laboratory studies assists the product developers and risk assessors. The studies should be reproducible and test clearly defined risk hypotheses. These properties contribute to the robustness of, and confidence in, environmental risk assessments for GE plants. Data from NTA studies, collected during the analysis phase of an environmental risk assessment, are critical to the outcome of the assessment and ultimately the decision taken by regulatory authorities on the release of a GE plant. Confidence in the results of early-tier laboratory studies is a precondition for the acceptance of data across regulatory jurisdictions and should encourage agencies to share useful information and thus avoid redundant testing

Single-nucleus RNA sequencing identifies new classes of proximal tubular epithelial cells in kidney fibrosis

Background Proximal tubular cells (PTCs) are the most abundant cell type in the kidney. PTCs are central to normal kidney function and to regeneration versus organ fibrosis following injury. This study used single-nucleus RNA sequencing (snRNAseq) to describe the phenotype of PTCs in renal fibrosis. Methods Kidneys were harvested from naïve mice and from mice with renal fibrosis induced by chronic aristolochic acid administration. Nuclei were isolated using Nuclei EZ Lysis buffer. Libraries were prepared on the 10× platform, and snRNAseq was completed using the Illumina NextSeq 550 System. Genome mapping was carried out with high-performance computing. Results A total of 23,885 nuclei were analyzed. PTCs were found in five abundant clusters, mapping to S1, S1–S2, S2, S2-cortical S3, and medullary S3 segments. Additional cell clusters (“new PTC clusters”) were at low abundance in normal kidney and in increased number in kidneys undergoing regeneration/fibrosis following injury. These clusters exhibited clear molecular phenotypes, permitting labeling as proliferating, New-PT1, New-PT2, and (present only following injury) New-PT3. Each cluster exhibited a unique gene expression signature, including multiple genes previously associated with renal injury response and fibrosis progression. Comprehensive pathway analyses revealed metabolic reprogramming, enrichment of cellular communication and cell motility, and various immune activations in new PTC clusters. In ligand-receptor analysis, new PTC clusters promoted fibrotic signaling to fibroblasts and inflammatory activation to macrophages. Conclusions These data identify unrecognized PTC phenotype heterogeneity and reveal novel PTCs associated with kidney fibrosis

Cultural experience tourist motives dimensionality : a cross-cultural study

This empirical research of tourists&rsquo; cultural experiences aims to advance theory by developing a measurement model of tourists&rsquo; motives towards attending cultural experiences for samples of Western and Asian tourists visiting Melbourne, Australia. Drawing upon Iso-Ahola&rsquo;s (1989) seeking/avoiding dichotomy theory for tourist motivation dimensions, the hypothesized dimensions primarily included escape and seeking-related dimensions, and some hedonic dimensions because of their relevance to aesthetic products (Hirschman &amp; Holbrook, 1982; Holbrook &amp; Hirschman, 1982), which are the context for this study. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to crossvalidate the underlying dimensionality structure of cultural experience motives. A four-factor model was extracted from the EFA consistent with some theoretical formulations and was retained in the CFA. Specific cultural language group differences for the motive dimensions were also hypothesized between Western and Asian tourist samples, and within the Chinese- and Japanese-speaking Asian tourist samples, but not within the different cultural groups of English-speaking Western tourists. These cross-cultural hypotheses were tested for the motive dimension measurement model using invariance testing in CFA. The findings for the motive dimensions differing by cultural group were not as expected. Significant cultural differences between Western and Asian tourists were not found, but a new finding of this study was significant differences between English-speaking tourists in their motives for attending cultural experiences. Marketing implications of these findings are also presented.<br /

Meta-analysis of genetic association with diagnosed Alzheimer's disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing

Late-onset Alzheimers disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly, and risk is partially driven by genetics. Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS). To identify additional LOAD risk loci, we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci (IQCK, ACE, ADAM10, and ADAMTS1). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Abeta processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants (P = 1.32 x 10-7) indicating that additional rare variants remain to be identified

Predictors for a dementia gene mutation based on gene-panel next-generation sequencing of a large dementia referral series

Next-generation genetic sequencing (NGS) technologies facilitate the screening of multiple genes linked to neurodegenerative dementia, but there is little guidance available about their use in clinical practice. Guidelines on which patients would most profit from testing, and information on the likelihood of discovery of a causal variant in a clinical syndrome, are conspicuously absent from the literature, mostly for a lack of large-scale studies. We applied a validated NGS dementia panel to 3241 patients with dementia and healthy aged controls; 13,152 variants were classified by likelihood of pathogenicity. We identified 354 deleterious variants (DV, 12.6% of patients); 39 were novel DVs. Age at clinical onset, clinical syndrome and family history each strongly predict the likelihood of finding a DV, but healthcare setting and gender did not. DVs were frequently found in genes not usually associated with the clinical syndrome. Patients recruited from primary referral centres were compared to those seen at higher-level research centres and a national clinical neurogenetic laboratory; rates of discovery were comparable, making selection bias unlikely and the results generalizable to clinical practice. We estimated penetrance of DVs using large-scale online genomic population databases and found 71 with evidence of reduced penetrance. Two DVs in the same patient were found more frequently than expected. These publicly-available data should provide a basis for informed counselling and clinical decision making