Gender role orientation, thinking style preference and facets of adult paranormality: A mediation analysis

This study examines the extent to which masculine and feminine gender role orientations predict self-reported anomalous experiences, belief, ability and fear once relevant correlates including biological sex are controlled for. The extent to which rational versus intuitive thinking style preference mediates these relationships is also examined. Path analysis (n=332) found heightened femininity directly predicts stronger intuitive preference plus more anomalous experiences, belief and fear with, additionally, intuitive preference mediating several gender role-paranormality relationships. By comparison, heightened masculinity directly predicts both thinking styles plus lower anomalous fear. The latter relationship is also shaped by the nature of mediators with (a) more anomalous experiences and belief leading to more anomalous fear and (b) either heightened rationality else more anomalous ability leading to, conversely, less anomalous fear. The extent to which findings support a gender (or social) role account of adult paranormality, together with methodological limitations and ideas for future research, is discussed

Abaloparatide, a PTH receptor agonist with homology to PTHrP, enhances callus bridging and biomechanical properties in rats with femoral fracture

Fractures typically heal via endochondral and intramembranous bone formation, which together form a callus that achieves union and biomechanical recovery. PTHrP, a PTH receptor agonist, plays an important physiological role in fracture healing as an endogenous stimulator of endochondral and intramembranous bone formation. Abaloparatide, a novel systemically‐administered osteoanabolic PTH receptor agonist that reduces fracture risk in women with postmenopausal osteoporosis, has 76% homology to PTHrP, suggesting it may have potential to improve fracture healing. To test this hypothesis, ninety‐six 12‐week‐old male rats underwent unilateral internally‐stabilized closed mid‐diaphyseal femoral fractures and were treated starting the next day with daily s.c. saline (Vehicle) or abaloparatide at 5 or 20 µg/kg/d for 4 or 6 weeks (16 rats/group/time point). Histomorphometry and histology analyses indicated that fracture calluses from the abaloparatide groups exhibited significantly greater total area, higher fluorescence scores indicating more newly‐formed bone, and higher fracture bridging scores versus Vehicle controls. Callus bridging score best correlated with callus cartilage score (r = 0.64) and fluorescence score (r = 0.67) at week 4, and callus area correlated with cartilage score (r = 0.60) and fluorescence score (r = 0.89) at Week 6. By micro‐CT, calluses from one or both abaloparatide groups had greater bone volume, bone volume fraction, bone mineral content, bone mineral density, and cross‐sectional area at both time points versus Vehicle controls. Destructive bending tests indicated greater callus maximum load and stiffness in one or both abaloparatide groups at both time points versus Vehicle controls. These results provide preliminary preclinical evidence for improved fracture healing with systemically‐administered abaloparatide. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop ResPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149317/1/jor24254_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149317/2/jor24254.pd

Effects of resistance exercise and whey protein supplementation on cognitive function in older men:secondary analysis of a randomised, double-blind, placebo-controlled trial

Purpose: Ageing is associated with cognitive decline. This study investigated the individual and combined effects of resistance exercise (RE) and whey protein supplementation (PRO) on cognitive function in older men. Methods: In a pooled-groups analysis, 36 older men (age: 67 ± 4 years) were randomised to either RE (2 x/week; n = 18) or no exercise (NE; n = 18), and either PRO (2 × 25 g/d whey protein isolate; n = 18) or control (CON, 2 × 23.75 g maltodextrin/d; n = 18). A sub-analysis was also conducted between RE + CON (n = 9) and RE + PRO (n = 9). At baseline and 12 weeks, participants completed a battery of neuropsychological tests (CANTAB; Cambridge Cognition, UK) and neurobiological, inflammatory, salivary cortisol and insulin sensitivity biomarkers were quantified. Results: PRO improved executive function z-score (+0.31 ± 0.08) greater than CON (+0.06 ± 0.08, P = 0.03) and there was a trend towards improved global cognitive function (P = 0.053). RE and RE + PRO did not improve any cognitive function domains (p ≥ 0.07). RE decreased tumor necrosis factor-alpha (P = 0.02) and interleukin-6 (P = 0.048) concentrations compared to NE, but changes in biomarkers did not correlate with changes in cognitive domains. Muscle strength (r = 0.34, P = 0.045) and physical function (ρ = 0.35–0.51, P &lt; 0.05) outcomes positively correlated with cognitive function domains at baseline, but only Δskeletal muscle index correlated with Δepisodic memory (r = 0.34, P = 0.046) following the intervention. Conclusion: In older men, PRO improved cognitive function, most notably executive functioning. RE did not improve any cognitive function domains but did decrease biomarkers of systemic inflammation. No synergistic effects were observed.</p

Preferences for descriptiveness and co-explanation in evaluating explanations

Good explanations can be distinguished from bad ones in different ways, for instance by how much of the available information they can explain (i.e., maximise the likelihood of) the available data. Here, we consider two different components of likelihood: descriptiveness (the likelihood of the individual data points) and co-explanation (the likelihood of the specific subset of data under consideration). We consider whether people prefer explanations that are high in descriptiveness vs. coexplanation. Moreover, we consider whether people who endorse conspiracy theories prefer explanations for either quality. In a medical diagnosis task, participants make binary choices between two fictional disease variants: one higher in descriptiveness versus another higher in co-explanation. Overall, participants displayed a weak preference for descriptiveness. This preference, however, did not vary across increasing levels of descriptiveness. Moreover, such preferences were unrelated to conspiracy mentality. Thus, both explanatory virtues may play a role in the appeal of likely explanations

SUMO chain-induced dimerization activates RNF4

Dimeric RING E3 ligases interact with protein substrates and conformationally restrain the ubiquitin-E2-conjugating enzyme thioester complex such that it is primed for catalysis. RNF4 is an E3 ligase containing an N-terminal domain that binds its polySUMO substrates and a C-terminal RING domain responsible for dimerization. To investigate how RNF4 activity is controlled, we increased polySUMO substrate concentration by ablating expression of SUMO protease SENP6. Accumulation of SUMO chains in vivo leads to ubiquitin-mediated proteolysis of RNF4. In vitro we demonstrate that at concentrations equivalent to those found in vivo RNF4 is predominantly monomeric and inactive as an ubiquitin E3 ligase. However, in the presence of SUMO chains, RNF4 is activated by dimerization, leading to both substrate ubiquitylation and autoubiquitylation, responsible for degradation of RNF4. Thus the ubiquitin E3 ligase activity of RNF4 is directly linked to the availability of its polySUMO substrates

Age-related Degeneration of Lumbar Muscle Morphology in Healthy Younger versus Older Men

This is an author's accepted manuscript of an article published by Taylor & Francis in The Aging Male, available online: https://doi.org/10.1080/13685538.2021.1878130 The accepted manuscript may differ from the final published version.Aim: The aim of this study was to evaluate age-related changes in lumbar paravertebral muscle (LPM) morphology in healthy younger and older adult men. Methods: T2-weighted axial MRI of the lumbar spine were obtained for 12 healthy older (67.3 ± 6.0 years) and younger (24.7 ± 3.1 years) men. Normalised muscle volume (NMV) and muscle fat infiltrate (MFI) were determined bilaterally for the psoas (PS), quadratus lumborum (QL), erector spinae (ES) and multifidus (MF). MANOVA was used to compare NMV and MFI between age groups. Follow-up ANOVA compared NMV and MFI for each muscle between age groups, with physical activity (PA) as a covariate. Stepwise regression was used to explore the association between muscle morphology. Results: NMV of the ES and QL were significantly lower in the older group (OG) (p = 0.040 and p < 0.001, respectively). MFI across all muscles was significantly greater in the OG (p < 0.001). PA did not moderate the relationship between aging and muscle degeneration. Non-dominant handgrip strength was associated with NMV (p = 0.003). Conclusions: Age-related atrophy is muscle specific in the lumbar spine; changes in lumbar musculature is independent of PA, handgrip strength may reflect morphological changes in the postural muscles with age. This study supports establishing effective targeted exercise interventions in the lumbar musculature.This publication presents independent research funded by Coventry University/University Hospitals Coventry and Warwickshire NHS Trust and carried out with the support of the National Institute of Health Research (NIHR) Coventry and Warwickshire Clinical Research Facility.Published versio

Development and validation of multivariable clinical diagnostic models to identify type 1 diabetes requiring rapid insulin therapy in adults aged 18-50 years

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordObjective: To develop and validate multivariable clinical diagnostic models to assist distinguishing between type 1 and type 2 diabetes in adults aged 18 to 50. Design: Multivariable logistic regression analysis was used to develop classification models integrating five pre-specified predictor variables, including clinical features (age of diagnosis, BMI) and clinical biomarkers (GADA and Islet Antigen 2 islet autoantibodies, Type 1 Diabetes Genetic Risk Score), to identify type 1 diabetes with rapid insulin requirement using data from existing cohorts. Setting: United Kingdom cohorts recruited from primary and secondary care. Participants: 1,352 (model development) and 582 (external validation) participants diagnosed with diabetes between the age of 18 and 50 years of white European origin. Main outcome measures: Type 1 diabetes was defined by rapid insulin requirement (within 3 years of diagnosis) and severe endogenous insulin deficiency (C-peptide <200pmol/L). Type 2 diabetes was defined by either a lack of rapid insulin requirement or, where insulin treated within 3 years, retained endogenous insulin secretion (C-peptide >600pmol/L at ≥5 years diabetes duration). Model performance was assessed using area under the receiver operating characteristic curve (ROC AUC), and internal and external validation. 4 Results: Type 1 diabetes was present in 13% of participants in the development cohort. All five predictor variables were discriminative and independent predictors of type 1 diabetes (p<0.001 for all) with individual ROC AUC ranging from 0.82 to 0.85. Model performance was high: ROC AUC range 0.90 [95%CI 0.88, 0.93] (clinical features only) to 0.97 [0.96, 0.98] (all predictors) with low prediction error. Results were consistent in external validation (clinical features and GADA ROC AUC 0.93 [0.90, 0.96]). Conclusions: Clinical diagnostic models integrating clinical features with biomarkers have high accuracy for identifying type 1 diabetes with rapid insulin requirement, and could assist clinicians and researchers in accurately identifying patients with type 1 diabetes.National Institute for Health Research (NIHR)European Community FP7Oxford Hospitals Charitable FundWellcome TrustMedical Research Council (MRC

Age-related changes in concentric and eccentric isokinetic peak torque of the trunk muscles in healthy older versus younger men

Accepted author manuscript version reprinted, by permission, from Journal of Aging and Physical Activity, 2021, volume 29, issue 6, pp. 941–951, https://doi.org/10.1123/japa.2020-0421 © Human Kinetics, Inc. The accepted manuscript may differ from the final published version.This study investigated age-related changes in trunk muscle function in healthy men and the moderating effect of physical activity. Twelve older (67.3 ± 6.0 years) and 12 younger (24.7 ± 3.1 years) men performed isokinetic trunk flexion and extension tests across a range of angular velocities (15°/s–180°/s) and contractile modes (concentric and eccentric). For concentric trunk extension, mixed-effects analysis of covariance revealed a significant interaction between Angular velocity × Age group (p = .026) controlling for physical activity. Follow-up univariate analysis of covariance revealed that the younger group produced significantly greater peak torque for all concentric extension conditions. Eccentric trunk strength was somewhat preserved in the older group. Age-related changes in trunk strength were independent of physical activity. The normal loss of trunk muscle strength in older age is muscle- and contractile-mode specific. These findings provide guidance for effective intervention strategies to offset adverse health outcomes related to trunk strength loss in older adults.Published versio

Sequencing PDX1 (insulin promoter factor 1) in 1788 UK individuals found 5% had a low frequency coding variant, but these variants are not associated with Type 2 diabetes

OnlineOpen Article. This is a copy of an article published in Diabetic Medicine. This journal is available online at: http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1464-5491Genome-wide association studies have identified >30 common variants associated with Type 2 diabetes (>5% minor allele frequency). These variants have small effects on individual risk and do not account for a large proportion of the heritable component of the disease. Monogenic forms of diabetes are caused by mutations that occur in <1:2000 individuals and follow strict patterns of inheritance. In contrast, the role of low frequency genetic variants (minor allele frequency 0.1-5%) in Type 2 diabetes is not known. The aim of this study was to assess the role of low frequency PDX1 (also called IPF1) variants in Type 2 diabetes

A common genetic variant in the 15q24 nicotinic acetylcholine receptor gene cluster (CHRNA5–CHRNA3–CHRNB4) is associated with a reduced ability of women to quit smoking in pregnancy

Maternal smoking during pregnancy is associated with low birth weight and adverse pregnancy outcomes. Women are more likely to quit smoking during pregnancy than at any other time in their lives, but some pregnant women continue to smoke. A recent genome-wide association study demonstrated an association between a common polymorphism (rs1051730) in the nicotinic acetylcholine receptor gene cluster (CHRNA5–CHRNA3–CHRNB4) and both smoking quantity and nicotine dependence. We aimed to test whether the same polymorphism that predisposes to greater cigarette consumption would also reduce the likelihood of smoking cessation in pregnancy. We studied 7845 pregnant women of European descent from the South-West of England. Using 2474 women who smoked regularly immediately pre-pregnancy, we analysed the association between the rs1051730 risk allele and both smoking cessation during pregnancy and smoking quantity. Each additional copy of the risk allele was associated with a 1.27-fold higher odds (95% CI 1.11–1.45) of continued smoking during pregnancy (P = 0.0006). Adjustment for pre-pregnancy smoking quantity weakened, but did not remove this association [odds ratio (OR) 1.20 (95% CI 1.03–1.39); P = 0.018]. The same risk allele was also associated with heavier smoking before pregnancy and in the first, but not the last, trimester [OR for smoking 10+ cigarettes/day versus 1–9/day in first trimester = 1.30 (95% CI 1.13–1.50); P = 0.0003]. To conclude, we have found strong evidence of association between the rs1051730 variant and an increased likelihood of continued smoking in pregnancy and have confirmed the previously observed association with smoking quantity. Our data support the role of genetic factors in influencing smoking cessation during pregnancy