Preliminary study on the use of near infrared hyperspectral imaging for quantitation and localisation of total glucosinolates in freeze-dried broccoli

peer-reviewedThe use of hyperspectral imaging to (a) quantify and (b) localise total glucosinolates in florets of a single broccoli species has been examined. Two different spectral regions (vis–NIR and NIR), a number of spectral pre-treatments and different mask development strategies were studied to develop the quantitative models. These models were then applied to freeze-dried slices of broccoli to identify regions within individual florets which were rich in glucosinolates. The procedure demonstrates potential for the quantitative screening and localisation of total glucosinolates in broccoli using the 950–1650 nm wavelength range. These compounds were mainly located in the external part of florets.Universidad de SevillaJ.M. Hernández-Hierro thanks the Spanish MICINN for the Juan de la Cierva contract (JCI-2011-09201) and Universidad de Sevilla for the mobility Grant (Universidad de Sevilla Research Plan). Spanish MICINN Project AGL2011-30254-C02 and Junta de Andalucia PGC Project AGR 6331

Validation of a deep neural network-based algorithm supporting clinical management of adnexal mass

BackgroundConservative management of adnexal mass is warranted when there is imaging-based and clinical evidence of benign characteristics. Malignancy risk is, however, a concern due to the mortality rate of ovarian cancer. Malignancy occurs in 10–15% of adnexal masses that go to surgery, whereas the rate of malignancy is much lower in masses clinically characterized as benign or indeterminate. Additional diagnostic tests could assist conservative management of these patients. Here we report the clinical validation of OvaWatch, a multivariate index assay, with real-world evidence of performance that supports conservative management of adnexal masses.MethodsOvaWatch utilizes a previously characterized neural network-based algorithm combining serum biomarkers and clinical covariates and was used to examine malignancy risk in prospective and retrospective samples of patients with an adnexal mass. Retrospective data sets were assembled from previous studies using patients who had adnexal mass and were scheduled for surgery. The prospective study was a multi-center trial of women with adnexal mass as identified on clinical examination and indeterminate or asymptomatic by imaging. The performance to detect ovarian malignancy was evaluated at a previously validated score threshold.ResultsIn retrospective, low prevalence (N = 1,453, 1.5% malignancy rate) data from patients that received an independent physician assessment of benign, OvaWatch has a sensitivity of 81.8% [95% confidence interval (CI) 65.1–92.7] for identifying a histologically confirmed malignancy, and a negative predictive value (NPV) of 99.7%. OvaWatch identified 18/22 malignancies missed by physician assessment. A prospective data set had 501 patients where 106 patients with adnexal mass went for surgery. The prevalence was 2% (10 malignancies). The sensitivity of OvaWatch for malignancy was 40% (95% CI: 16.8–68.7%), and the specificity was 87% (95% CI: 83.7–89.7) when patients were included in the analysis who did not go to surgery and were evaluated as benign. The NPV remained 98.6% (95% CI: 97.0–99.4%). An independent analysis set with a high prevalence (45.8%) the NPV value was 87.8% (95% CI: 95% CI: 75.8–94.3%).ConclusionOvaWatch demonstrated high NPV across diverse data sets and promises utility as an effective diagnostic test supporting management of suspected benign or indeterminate mass to safely decrease or delay unnecessary surgeries

Longitudinal change in the BODE index predicts mortality in severe emphysema

Rationale: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients. Objectives: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival. Methods: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components. Measurements and Main Results: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91943/1/2008 AJRCCM Longitudinal change in the BODE index predicts mortality in severe emphysema.pd

BMI Development of Normal Weight and Overweight Children in the PIAMA Study

Background: There is evidence that rapid weight gain during the first year of life is associated with overweight later in life. However, results from studies exploring other critical periods for the development of overweight are inconsistent. Objective: The objective was to investigate BMI development to assess at what ages essential differences between normal weight and overweight children occur, and to assess which age intervals the most strongly influence the risk of overweight at 8 years of age. Methods: Longitudinal weight and height data

Primary Care and Youth Mental Health in Ireland: Qualitative Study in Deprived Urban Areas

BACKGROUND: Mental disorders account for six of the 20 leading causes of disability worldwide with a very high prevalence of psychiatric morbidity in youth aged 15-24 years. However, healthcare professionals are faced with many challenges in the identification and treatment of mental and substance use disorders in young people (e.g. young people\u27s unwillingness to seek help from healthcare professionals, lack of training, limited resources etc.) The challenge of youth mental health for primary care is especially evident in urban deprived areas, where rates of and risk factors for mental health problems are especially common. There is an emerging consensus that primary care is well placed to address mental and substance use disorders in young people especially in deprived urban areas. This study aims to describe healthcare professionals\u27 experience and attitudes towards screening and early intervention for mental and substance use disorders among young people (16-25 years) in primary care in deprived urban settings in Ireland. METHODS: The chosen method for this qualitative study was inductive thematic analysis which involved semi-structured interviews with 37 healthcare professionals from primary care, secondary care and community agencies at two deprived urban centres. RESULTS: We identified three themes in respect of interventions to increase screening and treatment: (1) Identification is optimised by a range of strategies, including raising awareness, training, more systematic and formalised assessment, and youth-friendly practices (e.g. communication skills, ensuring confidentiality); (2) Treatment is enhanced by closer inter-agency collaboration and training for all healthcare professionals working in primary care; (3) Ongoing engagement is enhanced by motivational work with young people, setting achievable treatment goals, supporting transition between child and adult mental health services and recognising primary care\u27s longitudinal nature as a key asset in promoting treatment engagement. CONCLUSIONS: Especially in deprived areas, primary care is central to early intervention for youth mental health. Identification, treatment and continuing engagement are likely to be enhanced by a range of strategies with young people, healthcare professionals and systems. Further research on youth mental health and primary care, including qualitative accounts of young people\u27s experience and developing complex interventions that promote early intervention are priorities

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk