Why Aboriginal and Torres Strait Islander Australians fall and fracture: the codesigned Study of Indigenous Muscle and Bone Ageing (SIMBA) protocol

OBJECTIVES: Aboriginal and Torres Strait Islander Australians have a substantially greater fracture risk, where men are 50% and women are 26% more likely to experience a hip fracture compared with non-Indigenous Australians. Fall-related injuries in this population have also increased by 10%/year compared with 4.3%/year in non-Indigenous Australians. This study aims to determine why falls and fracture risk are higher in Aboriginal and Torres Strait Islander Australians. SETTING: All clinical assessments will be performed at one centre in Melbourne, Australia. At baseline, participants will have clinical assessments, including questionnaires, anthropometry, bone structure, body composition and physical performance tests. These assessments will be repeated at follow-up 1 and follow-up 2, with an interval of 12 months between each clinical visit. PARTICIPANTS: This codesigned prospective observational study aims to recruit a total of 298 adults who identify as Aboriginal and Torres Strait Islander and reside within Victoria, Australia. Stratified sampling by age and sex will be used to ensure equitable distribution of men and women across four age-bands (35-44, 45-54, 55-64 and 65+ years). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is within-individual yearly change in areal bone mineral density at the total hip, femoral neck and lumbar spine assessed by dual energy X-ray absorptiometry. Within-individual change in cortical and trabecular volumetric bone mineral density at the radius and tibia using high-resolution peripheral quantitative computed tomography will be determined. Secondary outcomes include yearly differences in physical performance and body composition. ETHICAL APPROVAL: Ethics approval for this study has been granted by the Monash Health Human Research Ethics Committee (project number: RES-19-0000374A). TRIAL REGISTRATION NUMBER: ACTRN12620000161921

Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence.

When adolescents with ADHD enter adulthood, some no longer meet disorder diagnostic criteria but it is unknown if biological and cognitive abnorma lities persist. We tested the hypothesis that people diagnosed with ADHD during adolescence present residual brain abnormalities both in brain structure and in working memory brain function. 83 young adults (aged 20-24 years) from the Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one patient had received medication for ADHD. T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. A sub-sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg working memory task whilst acquiring fMRI data. Areas of structural difference were used as a region of interest to evaluate the implications that structural abnormalities found in the ADHD group might have on working memory function. There was lower grey matter volume bilaterally in adolescence ADHD participants in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20-24. Working memory was poorer in adolescence ADHD participants, with associated failure to show normal load-dependent caudate activation. Young adults diagnosed with ADHD in adolescence have structural and functional deficits in the caudate associated with abnormal working memory function. These findings are not secondary to stimulant treatment, and emphasise the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time.This work was supported by an Academy of Finland Award to Dr Veijola; a Sigrid Juselius Foundation grant to Dr Moilanen; a Medical Research Council fellowship to Dr Murray (G0701911); a NARSAD, the Brain and Behavior Research Fund independent investigator award to Dr Miettunen; an Oon Khye Beng Ch'Hia Tsio Studentships in Preventative Medicine awarded by Downing College, Cambridge to Dr Roman-Urrestarazu together with a Becas Chile Doctoral Grant awarded by CONICYT, an Academy of Finland grant and Finnish Medical Foundation grant to Dr Kiviniemi, and an award from the Signe and Ane Gyllenberg Foundation, Finland, to Dr Mäki.. The work was partially conducted with the University of Cambridge Behavioural and Clinical Neuroscience Centre, supported by a joint award from the Medical Research Council (G1000183) and Wellcome Trust (093875/Z/10Z).This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00787-015-0755-

Distant Cluster Hunting II: A comparison of X-ray and optical cluster detection techniques and catalogs from the ROX Survey

We present and analyze the optical and X-ray catalogs of moderate-redshift cluster candidates from the ROSAT Optical X-ray Survey, or ROXS. The survey covers 4.8 square degrees (23 ROSAT PSPC pointings). The cross-correlated cluster catalogs were constructed by comparing two independent catalogs extracted from the optical and X-ray bandpasses, using a matched filter technique for the optical data and a wavelet technique for the X-ray data. We cross-id cluster candidates in each catalog. In Paper II we present the cluster catalogs and a numerical simulation of ROXS. We also present color-magnitude plots for several cluster candidates, and examine the prominence of the red sequence in each. We find that the X-ray clusters analyzed in this way do not all have a prominent red sequence. We conclude that while the red sequence may be distinct for massive, virialized clusters, it may be less so for lower-mass clusters at even moderate redshifts. Multiple, complementary methods of selecting and defining clusters may be essential, particularly at high redshift where all methods run into completeness limits, incomplete understanding of physical evolution, and projection effects.Comment: 68 pages, 18 figures ApJ, in pres

Friedrich Hayek and his visits to Chile

F. A. Hayek took two trips to Chile, the first in 1977, the second in 1981. The visits were controversial. On the first trip he met with General Augusto Pinochet, who had led a coup that overthrew Salvador Allende in 1973. During his 1981 visit, Hayek gave interviews that were published in the Chilean newspaper El Mercurio and in which he discussed authoritarian regimes and the problem of unlimited democracy. After each trip, he complained that the western press had painted an unfair picture of the economic situation under the Pinochet regime. Drawing on archival material, interviews, and past research, we provide a full account of this controversial episode in Hayek’s life

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

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

Background-Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results-We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]= 1.11; P=4.1 x 10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1 x 10(-3)). Conclusions-Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication.Peer reviewe

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

Background: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results: We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA‐, AAA‐, and TAA‐associated SNPs and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10−5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10−3). Conclusions: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication

Methodenauswahl der geschlechterperspektivischen Naturwissenschaftsanalyse

Ebeling S, Jäckel J, Meßmer R, Nikoleyczik K, Schmitz S. Methodenauswahl der geschlechterperspektivischen Naturwissenschaftsanalyse. In: Ebeling S, Schmitz S, eds. Geschlechterforschung und Naturwissenschaften. Einführung in ein komplexes Wechselspiel. Studien interdisziplinäre Geschlechterforschung. Vol 14. Wiesbaden: VS Verlag für Sozialwissenschaften; 2006: 297-330

Shear Bond Strength of Three Orthodontic Bonding Systems on Enamel and Restorative Materials

Objective. The aim of this in vitro study was to determine the shear bond strength (SBS) and adhesive remnant index (ARI) score of two self-etching no-mix adhesives (iBond™ and Scotchbond™) on different prosthetic surfaces and enamel, in comparison with the commonly used total etch system Transbond XT™. Materials and Methods. A total of 270 surfaces (1 enamel and 8 restorative surfaces, n=30) were randomly divided into three adhesive groups. In group 1 (control) brackets were bonded with Transbond XT primer. In the experimental groups iBond adhesive (group 2) and Scotchbond Universal adhesive (group 3) were used. The SBS was measured using a Zwicki 1120™ testing machine. The ARI and SBS were compared statistically using the Kruskal–Wallis test (P≤0.05). Results. Significant differences in SBS and ARI were found between the control group and experimental groups. Conclusions. Transbond XT showed the highest SBS on human enamel. Scotchbond Universal on average provides the best bonding on all other types of surface (metal, composite, and porcelain), with no need for additional primers. It might therefore be helpful for simplifying bonding in orthodontic procedures on restorative materials in patients. If metal brackets have to be bonded to a metal surface, the use of a dual-curing resin is recommended

Nursing children and young people

Background: Those receiving tenofovir/emtricitabine (TDF-FTC) had greater bone loss compared with abacavir/lamivudine (ABC-3TC) in a randomized simplification trial (STEAL study). Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD) was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors of BMD change in the hip and spine by dual-energy x-ray absorptiometry in virologically suppressed participants through week 96. Methodology/Principal Findings: Bone turnover markers (BTMs) tested were: formation [bone alkaline phosphatase, procollagen type 1 N-terminal propeptide (P1NP)]; resorption (C-terminal cross-linking telopeptide of type 1 collagen [CTx]); and bone cytokine-signalling (osteoprotegerin, RANK ligand). Independent predictors of BMD change were determined using forward, stepwise, linear regression. BTM changes and fracture risk (FRAX®) at week 96 were compared by t-test. Baseline characteristics (n = 301) were: 98% male, mean age 45 years, current protease-inhibitor (PI) 23%, tenofovir/abacavir-naïve 52%. Independent baseline predictors of greater hip and spine bone loss were TDF-FTC randomisation (p≤0.013), lower fat mass (p-trend≤0.009), lower P1NP (p = 0.015), and higher hip T score/spine BMD (p-trend≤0.006). Baseline PI use was associated with greater spine bone loss (p = 0.004). TDF-FTC increased P1NP and CTx through Wk96 (