A method for in situ SEM fracture studies of brittle materials using the double torsion technique : application to nuclear graphite

This work concerned the design and development of a miniature double torsion (DT) testing rig, for use inside the chamber of a scanning electron microscope, to perform in situ loading studies of brittle materials using the DT fracture mechanics specimen. The in situ performance of the system inside the SEM was highly satisfactory, while still providing free rotation of the attached stepper motor. Crack growth rates of down to 19nm/s were directly observed in PMMA specimens. It was concluded that the technique displayed merit in its ability to contribute to the knowledge base of slow cracking and damage development in brittle materials, with the advantage being that the gearing ratios of the current device resulted in slower specimen loading rates, which were more controlled, than reported previously

Can genomic research make a useful contribution to social policy?

As genetic research into outcomes beyond health gathers pace, largely through the use of genome-wide association studies, interest from policy-makers has grown. In the last year, two UK reports have explored the policy implications of genomic research, one from the UK Government Office for Science and one from the Early Intervention Foundation. In this article, we explore areas of consensus between these two reports and use them to propose priorities for policy-makers as we prepare for what some have termed a 'genetic revolution'. Both reports agree on two clear recommendations for science and policy communities. One of these relates to public education and engagement, and the other to ensuring that genomic databases are ancestrally diverse. Both reports agree that-even if it is found to be a viable and ethical idea in the medium-term future-DNA data should not be incorporated into social policy before these two issues have been comprehensively addressed. In the article, we argue that scientists are taking the lead on tackling the diversity deficit but that there is a clear role for policy-makers to play in addressing low genetic literacy in society, and that this is a matter of urgency

La Vida Buena (The Good Life) evaluation: a quasi experimental intervention of a community health worker-led family-based childhood obesity program for Latino children 5-8 years of age on the US-Mexico border

Background: Due to multiple and interacting factors, Latino children are disproportionately at risk for overweight and obesity in the United States. Childhood obesity increases the risk for adverse physical and psychosocial outcomes throughout the lifespan. Intensive behavioral interventions recommended in primary care settings may not conform to current practices, and the most vulnerable populations are often unable to access these services. Community Health Workers (CHWs) offer a promising approach to bridging the gap between vulnerable communities and culturally competent services. La Vida Buena (The Good Life) is an 8-week family-focused intervention for Latino children 5-8years old and their parents or caregivers who are patients at a Federally-Qualified Community Health Center (FQHC). It is a culturally and linguistically appropriate curriculum, facilitated by CHWs, that targets family behaviors to foster a healthy lifestyle in order to prevent and mitigate childhood overweight and obesity. Methods: The primary objective is to test the effectiveness of the La Vida Buena (LVB) childhood obesity program among Latino children 5-8years old and their families as compared with a single educational session. This study uses a parallel two-arm quasi-experimental design. The intervention group receives the 8-week La Vida Buena intervention and the comparison group receives a single educational session. The primary outcome is the change in the child's BMI z-score from baseline to 6 months. Discussion: The implementation and evaluation of La Vida Buena may inform research and practice for linking Latino patients in FQHCs to culturally responsive community-based childhood obesity interventions. It will also contribute to the literature about CHWs as facilitators of behavior change for families underserved by health services and preventive programs. La Vida Buena can serve as a culturally and linguistically appropriate early intervention curriculum that will foster a healthy home environment for childhood obesity mitigation and prevention. Trial registration: The trial was retrospectively registered on December 18, 2018. The ClinicalTrials.gov Identifier is NCT03781856.U.S. Department of Health and Human Services Office of Minority Health through the Empowered Communities for a Healthier Nation grant [5-CPIMP171152-02-05]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Preliminary assessment of pre-morbid DNA methylation in individuals at high genetic risk of mood disorders

OBJECTIVES: Accumulating evidence implicates altered DNA methylation in psychiatric disorders, including bipolar disorder (BD) and major depressive disorder (MDD). It is not clear, however, whether these changes are causative or result from illness progression or treatment. To disentangle these possibilities we profiled genome‐wide DNA methylation in well, unrelated individuals at high familial risk of mood disorder. DNA methylation was compared between individuals who subsequently developed BD or MDD [ill later (IL)] and those who remained well [well later (WL)]. METHODS: DNA methylation profiles were obtained from whole‐blood samples from 22 IL and 23 WL individuals using the Infinium HumanMethylation450 BeadChip. Differential methylation was assessed on a single‐locus and regional basis. Pathway analysis was performed to assess enrichment for particular biological processes amongst nominally significantly differentially methylated loci. RESULTS: Although no locus withstood correction for multiple testing, uncorrected P‐values provided suggestive evidence for altered methylation at sites within genes previously implicated in neuropsychiatric conditions, such as Transcription Factor 4 (TCF4) and Interleukin 1 Receptor Accessory Protein‐Like 1 ([IL1RAPL1]; P≤3.11×10(−5)). Pathway analysis revealed significant enrichment for several neurologically relevant pathways and functions, including Nervous System Development and Function and Behavior; these findings withstood multiple testing correction (q≤0.05). Analysis of differentially methylated regions identified several within the major histocompatibility complex (P≤.000 479), a region previously implicated in schizophrenia and BD. CONCLUSIONS: Our data provide provisional evidence for the involvement of altered whole‐blood DNA methylation in neurologically relevant genes in the aetiology of mood disorders. These findings are convergent with the findings of genome‐wide association studies

Assessing and predicting adolescent and early adulthood common mental disorders using electronic primary care data:analysis of a prospective cohort study (ALSPAC) in Southwest England

OBJECTIVES: We aimed to examine agreement between common mental disorders (CMDs) from primary care records and repeated CMD questionnaire data from ALSPAC (the Avon Longitudinal Study of Parents and Children) over adolescence and young adulthood, explore factors affecting CMD identification in primary care records, and construct models predicting ALSPAC-derived CMDs using only primary care data. DESIGN AND SETTING: Prospective cohort study (ALSPAC) in Southwest England with linkage to electronic primary care records. PARTICIPANTS: Primary care records were extracted for 11 807 participants (80% of 14 731 eligible). Between 31% (3633; age 15/16) and 11% (1298; age 21/22) of participants had both primary care and ALSPAC CMD data. OUTCOME MEASURES: ALSPAC outcome measures were diagnoses of suspected depression and/or CMDs. Primary care outcome measure were Read codes for diagnosis, symptoms and treatment of depression/CMDs. For each time point, sensitivities and specificities for primary care CMD diagnoses were calculated for predicting ALSPAC-derived measures of CMDs, and the factors associated with identification of primary care-based CMDs in those with suspected ALSPAC-derived CMDs explored. Lasso (least absolute selection and shrinkage operator) models were used at each time point to predict ALSPAC-derived CMDs using only primary care data, with internal validation by randomly splitting data into 60% training and 40% validation samples. RESULTS: Sensitivities for primary care diagnoses were low for CMDs (range: 3.5%–19.1%) and depression (range: 1.6%–34.0%), while specificities were high (nearly all >95%). The strongest predictors of identification in the primary care data for those with ALSPAC-derived CMDs were symptom severity indices. The lasso models had relatively low prediction rates, especially in the validation sample (deviance ratio range: −1.3 to 12.6%), but improved with age. CONCLUSIONS: Primary care data underestimate CMDs compared to population-based studies. Improving general practitioner identification, and using free-text or secondary care data, is needed to improve the accuracy of models using clinical data

High prevalence of the neonicotinoid clothianidin in liver and plasma samples collected from gamebirds during autumn sowing

Since neonicotinoid insecticides were introduced to the agricultural market, evidence of the negative impacts of these systemic compounds on non-target species has accumulated. Birds are one of the largest groups of species to inhabit farmland, but the extent of neonicotinoid exposure in avian communities is poorly understood and very little is known about how any exposure may affect wild birds. Here, free-living gamebirds were used as a model group to measure the extent of avian exposure to the neonicotinoid clothianidin via seed treatment. During a typical sowing period of winter cereals treated with clothianidin, blood and liver samples were collected simultaneously from individual hunted gamebird carcasses, both pre- (n = 18) and post-sowing (n = 57) and were analysed for clothianidin via LC/MS-MS. Body weight, fat score and faecal parasite load were also quantified in the birds to ascertain whether any of these health parameters were associated with clothianidin exposure under field conditions. Clothianidin was detected in 6% of individuals sampled pre-sowing and 89% of individuals sampled post-sowing. The frequency of clothianidin detection in plasma samples and the concentration of clothianidin in liver and plasma samples decreased significantly between the first week and 2-4 weeks post-sowing. Faecal parasite load was positively associated with concentrations of clothianidin in the liver (but not plasma) of partridge species, but there was no association between clothianidin concentration and fat score or body weight, for either sample type. This study provides clear evidence that treated seed is a source of pesticide exposure for gamebirds following autumn sowing. These findings have implications for gamebirds worldwide where seed treatments are in use, and will aid the design of any future avian biomonitoring studies for agrochemical compounds

From seeds to plasma : confirmed exposure of multiple farmland bird species to clothianidin during sowing of winter cereals

Neonicotinoids are the largest group of systemic insecticides worldwide and are most commonly applied as agricultural seed treatments. However, little is known about the extent to which farmland birds are exposed to these compounds during standard agricultural practices. This study uses winter cereal, treated with the neonicotinoid clothianidin, as a test system to examine patterns of exposure in farmland birds during a typical sowing period. The availability of neonicotinoid-treated seed was recorded post-sowing at 39 fields (25 farms), and camera traps were used to monitor seed consumption by wild birds in situ. The concentration of clothianidin in treated seeds and crop seedlings was measured via liquid chromatography-tandem mass spectrometry, and avian blood samples were collected from 11 species of farmland bird from a further six capture sites to quantify the prevalence and level of clothianidin exposure associated with seed treatments. Neonicotinoid-treated seeds were found on the soil surface at all but one of the fields surveyed at an average density of 2.8 seeds/m2. The concentration of clothianidin in seeds varied around the target application rate, whilst crop seedlings contained on average 5.9% of the clothianidin measured in seeds. Exposure was confirmed in 32% of bird species observed in treated fields and 50% of individual birds post-sowing; the median concentration recorded in positive samples was 12 ng/mL. Results here provide clear evidence that a variety of farmland birds are subject to neonicotinoid exposure following normal agricultural sowing of neonicotinoid-treated cereal seed. Furthermore, the widespread availability of seeds at the soil surface was identified as a primary source of exposure. Overall, these data are likely to have global implications for bird species and current agricultural policies where neonicotinoids are in use, and may be pertinent to any future risk assessments for systemic insecticide seed treatments

Identification of influential probe types in epigenetic predictions of human traits: implications for microarray design

BACKGROUND: CpG methylation levels can help to explain inter-individual differences in phenotypic traits. Few studies have explored whether identifying probe subsets based on their biological and statistical properties can maximise predictions whilst minimising array content. Variance component analyses and penalised regression (epigenetic predictors) were used to test the influence of (i) the number of probes considered, (ii) mean probe variability and (iii) methylation QTL status on the variance captured in eighteen traits by blood DNA methylation. Training and test samples comprised ≤ 4450 and ≤ 2578 unrelated individuals from Generation Scotland, respectively. RESULTS: As the number of probes under consideration decreased, so too did the estimates from variance components and prediction analyses. Methylation QTL status and mean probe variability did not influence variance components. However, relative effect sizes were 15% larger for epigenetic predictors based on probes with known or reported methylation QTLs compared to probes without reported methylation QTLs. Relative effect sizes were 45% larger for predictors based on probes with mean Beta-values between 10 and 90% compared to those based on hypo- or hypermethylated probes (Beta-value ≤ 10% or ≥ 90%). CONCLUSIONS: Arrays with fewer probes could reduce costs, leading to increased sample sizes for analyses. Our results show that reducing array content can restrict prediction metrics and careful attention must be given to the biological and distribution properties of CpG probes in array content selection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01320-9