Hyperactive-Impulsive Symptom Scores and Oppositional Behaviours Reflect Alternate Manifestations of a Single Liability

Attention deficit hyperactivity disorder (ADHD) and oppositional behaviours frequently co-occur, We aimed to study the etiology of this overlap in a general population–based twin sample, assessing the symptom domains of hyperactivity-impulsivity and inattentiveness separately for their overlap with oppositionality. We further aimed to investigate whether rater bias may contribute to the overlap in previous data which used one rater only. Using parent and teacher ratings on hyperactivity-impulsivity, inattentiveness and oppositionality, and actigraph measurements of activity level, for 668 7-9-year-old twin pairs, oppositionality showed a higher overlap with hyperactivity-impulsivity (r=.95) than with inattentiveness (r=.52) and all etiological influences on hyperactivity-impulsivity were shared with those on oppositionality, indicated by a genetic correlation of .95 and a child-specific environmental correlation of .94. Actigraph data did not show an overlap with ratings of oppositionality. In middle childhood, symptoms of hyperactivity-impulsivity and oppositional behaviour may represent the same underlying liability, whereas the inattentive domain is more distinct

Identification of genetic loci simultaneously associated with multiple cardiometabolic traits

Background and aims: Cardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits. Methods and results: We conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574–456,823). Multiple loci reached genome-wide levels of significance (N = 145–333) for each trait, but only four loci (in/near VEGFA, GRB14-COBLL1, KLF14, and RGS19-OPRL1) were associated with risk across all seven traits (P < 5 × 10−8). We sought replication of these four loci in an independent set of seven trait-specific GWAS meta-analyses. GRB14-COBLL1 showed the most consistent replication, revealing nominally significant associations (P < 0.05) with all traits except DBP. Conclusions: Our analyses suggest that very few loci are associated in the same direction of risk with traits representing the full spectrum of CMD features. We identified four such loci, and an understanding of the pathways between these loci and CMD risk may eventually identify factors that can be used to identify pathologic disturbances that represent broadly beneficial therapeutic targets.National Institutes of Health12 month embargo; published: 07 January 2022This 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]

High strain rate effect on tensile ductility and fracture of AM fabricated Inconel 718 with voided microstructures

The paper describes Electromagnetic Ring Expansion Tests (ERET) performed on Laser Melting Powder Bed Fusion (LPBF) Inconel 718 stress relieved test pieces, to establish the effect of a randomly dispersed spherically voided microstructure on tensile ductility, fracture, and fragmentation at high strain rate (10-3 < e < 104 s-1). An empirical model to predict porosity type and growth rates as a function of laser energy density was established, to select the LPBF process parameters to fabricate test pieces under stable conduction and keyhole melting. The size, shape, distribution of macro and keyhole pores in the test pieces obtained for ERET testing were characterised. At high strain rate the number of ring fragments for the highest porosity doubled, accompanied by a reduction in true strain at maximum uniform elongation and fracture strain. The trend for reducing fracture strain with increasing porosity at high strain rate was described by a decaying power law. Overall, there was a significant positive strain rate effect on tensile ductility at lower porosities attributed strain rate hardening (Hart, 1967) [1]. Fracture surfaces containing the highest porosity identified four different void coalescence mechanisms that helped explain the influence of larger pores on the stress state in the alloy.The AM of IN718 and tensile testing was funded by the UoD, College of Science and Engineering Research Excellence Framework (REF) funding for the Director of IISE (P. Wood) and AM Researcher (U. Gunputh). The support of G. Williams for IN718 sample preparation and M. Pawlik for tensile testing is acknowledged. A. Rusinek acknowledges the program UC3M-Santander Chair of Excellence in additive manufacturing. The expanding ring tests investigations were funded by the Polish Ministry of Science and Higher Education, Centre for Research and Development under research grant No. TECHMATSTRATEG2/410049/12/NCBR/2019

Evaluation of diet pattern and weight gain in postmenopausal women enrolled in the Women’s Health Initiative Observational Study

Abstract It is unclear which of four popular contemporary diet patterns is best for weight maintenance among postmenopausal women. Four dietary patterns were characterised among postmenopausal women aged 49–81 years (mean 63·6 ( sd 7·4) years) from the Women’s Health Initiative Observational Study: (1) a low-fat diet; (2) a reduced-carbohydrate diet; (3) a Mediterranean-style (Med) diet; and (4) a diet consistent with the US Department of Agriculture’s Dietary Guidelines for Americans (DGA). Discrete-time hazards models were used to compare the risk of weight gain (≥10 %) among high adherers of each diet pattern. In adjusted models, the reduced-carbohydrate diet was inversely related to weight gain (OR 0·71; 95 % CI 0·66, 0·76), whereas the low-fat (OR 1·43; 95 % CI 1·33, 1·54) and DGA (OR 1·24; 95 % CI 1·15, 1·33) diets were associated with increased risk of weight gain. By baseline weight status, the reduced-carbohydrate diet was inversely related to weight gain among women who were normal weight (OR 0·72; 95 % CI 0·63, 0·81), overweight (OR 0·67; 95 % CI 0·59, 0·76) or obese class I (OR 0·63; 95 % CI 0·53, 0·76) at baseline. The low-fat diet was associated with increased risk of weight gain in women who were normal weight (OR 1·28; 95 % CI 1·13, 1·46), overweight (OR 1·60; 95 % CI 1·40, 1·83), obese class I (OR 1·73; 95 % CI 1·43, 2·09) or obese class II (OR 1·44; 95 % CI 1·08, 1·92) at baseline. These findings suggest that a low-fat diet may promote weight gain, whereas a reduced-carbohydrate diet may decrease risk of postmenopausal weight gain

Lipoprotein Lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS

<p>Abstract</p> <p>Background</p> <p>Previous analysis clustered 1,238 individuals from the general population Genetics of Lipid Lowering Drugs Network (GOLDN) study by the size of their fasting very low-density, low-density and high-density lipoproteins (VLDL, LDL, HDL) using latent class analysis. From two of the eight identified groups (N = 251), ~75% of individuals met Adult Treatment Panel III criteria for the metabolic syndrome (MetS). Both showed small LDL diameter (mean = 19.9 nm); however, group 1 (N = 200) had medium VLDL diameter (mean = 53.1 nm) while group 2 had very large VLDL diameter (mean = 65.74 nm). Group 2 additionally showed significantly more insulin resistance (IR), and accompanying higher waist circumference and fasting glucose and triglycerides (all <it>P </it>< .01). Since lipoprotein lipase hydrolyzes triglyceride in the VLDL-LDL cascade, we examined whether these two patterns of lipoprotein diameter were associated with differences across two lipoprotein lipase (<it>LPL</it>) gene variants: D9N (rs1801177) and S447X (rs328).</p> <p>Findings</p> <p>Mixed linear models that controlled for age, sex, center of data collection, and family pedigree revealed no differences between the two groups for the D9N polymorphism (<it>P </it>= .36). However, group 2 contained significantly more carriers (25%) of the 447X variant than group 1 (14%; <it>P </it>= .04).</p> <p>Conclusions</p> <p>This was the first study this kind to show an association between <it>LPL </it>and large VLDL particle size within the MetS, a pattern associated with higher IR. Future work should extend this to larger samples to confirm these findings, and examine the long term outcomes of those with this lipoprotein diameter pattern.</p

Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate

Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association study (GWAS) associated several single nucleotide polymorphisms (SNPs) with lipoprotein measures, and validated these associations in two independent populations. We used this information to construct genetic risk scores (GRSs) for fasting lipoprotein measures at baseline (pre-fenofibrate), and aimed to examine whether these GRSs also associated with the responses of lipoproteins to fenofibrate. Fourteen lipoprotein subclass measures were assayed in 817 men and women before and after a three week fenofibrate trial. We set significance at a Bonferroni corrected alpha &lt;0.05 (p &lt; 0.004). Twelve subclass measures changed with fenofibrate administration (each p = 0.003 to &lt;0.0001). Mixed linear models which controlled for age, sex, body mass index (BMI), smoking status, pedigree and study-center, revealed that GRSs were associated with eight baseline lipoprotein measures (p &lt; 0.004), however no GRS was associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoprotein subclass concentrations with fenofibrate treatment are not mediated by the genetic risk for fasting levels

A clustering analysis of lipoprotein diameters in the metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle diameters with components of the metabolic syndrome (MetS), although this has been the focus of less research. We aimed to explore the relationship of VLDL, LDL and HDL diameters to MetS and its features, and by clustering individuals by their diameters of VLDL, LDL and HDL particles, to capture information across all three fractions of lipoprotein into a unified phenotype.</p> <p>Methods</p> <p>We used nuclear magnetic resonance spectroscopy measurements on fasting plasma samples from a general population sample of 1,036 adults (mean ± SD, 48.8 ± 16.2 y of age). Using latent class analysis, the sample was grouped by the diameter of their fasting lipoproteins, and mixed effects models tested whether the distribution of MetS components varied across the groups.</p> <p>Results</p> <p>Eight discrete groups were identified. Two groups (N = 251) were enriched with individuals meeting criteria for the MetS, and were characterized by the smallest LDL/HDL diameters. One of those two groups, one was additionally distinguished by large VLDL, and had significantly higher blood pressure, fasting glucose, triglycerides, and waist circumference (WC; <it>P </it>< .001). However, large VLDL, in the absence of small LDL and HDL particles, did not associate with MetS features. These associations held after additionally controlling for VLDL, LDL and HDL particle concentrations.</p> <p>Conclusions</p> <p>While small LDL diameters remain associated with IR and the MetS, the occurrence of these in conjunction with a shift to overall larger VLDL diameter may identify those with the highest fasting glucose, TG and WC within the MetS. If replicated, the association of this phenotype with more severe IR-features indicated that it may contribute to identifying of those most at risk for incident type II diabetes and cardiometabolic disease.</p

Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves

peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. Results There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups. Conclusion Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak