The intra-rater reliability of the supraspinatus cross-sectional area measurement using diagnostic ultrasound

The purpose of this study was to determine the intra-rater reliability between-scans and betweendays on measurements of the supraspinatus cross-sectional area of using diagnostic ultrasound. The subjects were five male volunteers(age range:19-23 years old). The diagnostic ultrasound images were acquired using the same 7.5MHz real time probe with an Aloka Echo Camera SSD-1000 system to all subjects. The section through the midpoint of the scapular spine was observed. Right shoulders were measured three times on the same day for between scan reliability and one time on the next day for between days reliability. The reliability of measuring the CSA of the supraspinatus using diagnostic ultrasound was high in this study. The intraclass correlation coefficients of this study were 0.83 for between three scans and 0.81 for between days. These findings support that the CSA of the supraspinatus can be used as a reliable clinical parameter if the examiner has experience in using diagnostic ultrasound.肩の様々な病態や、老化による棘上筋の萎縮が報告されている。棘上筋は肩関節の動的安定性に寄与する筋であり、この筋萎縮を検討することは臨床的に重要な指標となる。一般に筋の萎縮を測定するためにはMRI、CT、超音波画像を用いる方法がある。超音波画像はMRIやCTと比較して簡便に安全にくり返し検査を行うことができるが、画像を導出するプロ?べの大きさや、対象となる組織の音響抵抗などに影響を受けて、鮮明な画像をくり返し導出することが難しいとされている。本研究の目的は、超音波画像を用いた棘上筋断面積計測の再現性を同一検査者がくり返して測定することにより検討することにある。健常成人男性５名の右肩棘上筋の断面像計測を同一日に３回、異なる日に１回行い、同一日の３回の測定における級内相関係数および異なる日のそれぞれ１回目の測定における級内相関係数を検討した。同一日の３回の測定間の級内相関係数は0.83、異なる日の測定間のそれは0.81であった

Oxygen isotopic heterogeneity in the Temora-2 reference zircon

For the past decade and a half, Geoscience Australia has distributed zircon from a portion of the Middledale Gabbroic Diorite under the label “Temora-2”. This reference zircon was originally developed as a reference material for use in ion microprobe U-Th-Pb geochronological analyses. As ion probe capability has increased to allow the measurements of other isotopic systems at geologically useful precision and accuracy, the Temora-2 zircon has remained a convenient reference material to use for those systems. However, the suitability of this material for non-geochronological applications must be continuously reassessed. This study demonstrates that some (but not all) aliquots of the Temora-2 zircon, distributed by Geoscience Australia to analytical laboratories worldwide, have δ18O values up to 1‰ lower than the reference laser fluorination δ18O value quoted in Black et al. (2004). Although the long and complex collection history of this material makes it difficult to pinpoint the cause of this discrepancy, we suspect it relates to material from two or more boulders from the Temora-2 site, with different δ18O values, being sampled and mixed together in the field prior to storage at Geoscience Australia. Therefore, oxygen isotope measurements on SIMS mounts where Temora is the only reference zircon may be biased towards heavier values by up to 1‰, unless there are additional constrains on the actual δ18O value of the specific aliquot of Temora-2 zircons placed on that particular ion probe mount. We recommend that future oxygen isotope work should use a reference zircon other than Temora-2, until Geoscience Australia can replace the current stock of heterogeneous Temora-2 material with zircon which has a uniform δ18O value

DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle

peer-reviewedBackground: Studies in mice and humans have shown that imprinted genes, whereby expression from one of the two parentally inherited alleles is attenuated or completely silenced, have a major effect on mammalian growth, metabolism and physiology. More recently, investigations in livestock species indicate that genes subject to this type of epigenetic regulation contribute to, or are associated with, several performance traits, most notably muscle mass and fat deposition. In the present study, a candidate gene approach was adopted to assess 17 validated single nucleotide polymorphisms (SNPs) and their association with a range of performance traits in 848 progeny-tested Irish Holstein-Friesian artificial insemination sires. These SNPs are located proximal to, or within, the bovine orthologs of eight genes (CALCR, GRB10, PEG3, PHLDA2, RASGRF1, TSPAN32, ZIM2 and ZNF215) that have been shown to be imprinted in cattle or in at least one other mammalian species (i.e. human/mouse/pig/sheep). Results: Heterozygosities for all SNPs analysed ranged from 0.09 to 0.46 and significant deviations from Hardy-Weinberg proportions (P ≤ 0.01) were observed at four loci. Phenotypic associations (P ≤ 0.05) were observed between nine SNPs proximal to, or within, six of the eight analysed genes and a number of performance traits evaluated, including milk protein percentage, somatic cell count, culled cow and progeny carcass weight, angularity, body conditioning score, progeny carcass conformation, body depth, rump angle, rump width, animal stature, calving difficulty, gestation length and calf perinatal mortality. Notably, SNPs within the imprinted paternally expressed gene 3 (PEG3) gene cluster were associated (P ≤ 0.05) with calving, calf performance and fertility traits, while a single SNP in the zinc finger protein 215 gene (ZNF215) was associated with milk protein percentage (P ≤ 0.05), progeny carcass weight (P ≤ 0.05), culled cow carcass weight (P ≤ 0.01), angularity (P ≤ 0.01), body depth (P ≤ 0.01), rump width (P ≤ 0.01) and animal stature (P ≤ 0.01). Conclusions: Of the eight candidate bovine imprinted genes assessed, DNA sequence polymorphisms in six of these genes (CALCR, GRB10, PEG3, RASGRF1, ZIM2 and ZNF215) displayed associations with several of the phenotypes included for analyses. The genotype-phenotype associations detected here are further supported by the biological function of these six genes, each of which plays important roles in mammalian growth, development and physiology. The associations between SNPs within the imprinted PEG3 gene cluster and traits related to calving, calf performance and gestation length suggest that this domain on chromosome 18 may play a role regulating pre-natal growth and development and fertility. SNPs within the bovine ZNF215 gene were associated with bovine growth and body conformation traits and studies in humans have revealed that the human ZNF215 ortholog belongs to the imprinted gene cluster associated with Beckwith-Wiedemann syndrome--a genetic disorder characterised by growth abnormalities. Similarly, the data presented here suggest that the ZNF215 gene may have an important role in regulating bovine growth. Collectively, our results support previous work showing that (candidate) imprinted genes/loci contribute to heritable variation in bovine performance traits and suggest that DNA sequence polymorphisms within these genes/loci represents an important reservoir of genomic markers for future genetic improvement of dairy and beef cattle populations.Department of Agriculture, Fisheries and Food Ireland - Research Stimulus Fund (project numbers: RSF-06-406, RSF-06-0353 and RSF-06-0409); Science Foundation Ireland - Investigator Programme Grants(SFI/01/F.1/B028; SFI/08/IN.1/B1931, 07/SRC/B1156 (MPM)

Aspherical Supernova Shock Breakout and the Observations of Supernova 2008D

Shock breakout is the earliest, readily-observable emission from a core-collapse supernova explosion. Observing supernova shock breakout may yield information about the nature of the supernova shock prior to exiting the progenitor and, in turn, about the core-collapse supernova mechanism itself. X-ray Outburst 080109, later associated with SN 2008D, is a very well-observed example of shock breakout from a core-collapse supernova. Despite excellent observational coverage and detailed modeling, fundamental information about the shock breakout, such as the radius of breakout and driver of the light curve time scale, is still uncertain. The models constructed for explaining the shock breakout emission from SN 2008D all assume spherical symmetry. We present a study of the observational characteristics of {\it aspherical} shock breakout from stripped-envelope core-collapse supernovae. We conduct two-dimensional, jet-driven supernova simulations from stripped-envelope progenitors and calculate the resulting shock breakout X-ray spectra and light curves. The X-ray spectra evolve significantly in time as the shocks expand outward and are not well-fit by single-temperature and radius black bodies. The time scale of the X-ray burst light curve of the shock breakout is related to the shock crossing time of the progenitor, not the much shorter light crossing time that sets the light curve time scale in spherical breakouts. This could explain the long shock breakout light curve time scale observed for XRO 080109/SN 2008D.Comment: 16 pages, 29 figures. Accepted to Ap

MicroRNA profiling of the bovine alveolar macrophage response to Mycobacterium bovis infection suggests pathogen survival is enhanced by microRNA regulation of endocytosis and lysosome trafficking

peer-reviewedMycobacterium bovis, the causative agent of bovine tuberculosis, a major problem for global agriculture, spreads via an airborne route and is taken up by alveolar macrophages (AM) in the lung. Here, we describe the first next-generation sequencing (RNA-seq) approach to temporally profile miRNA expression in primary bovine AMs post-infection with M. bovis. One, six, and forty miRNAs were identified as significantly differentially expressed at 2, 24 and 48 h post-infection, respectively. The differential expression of three miRNAs (bta-miR-142-5p, bta-miR-146a, and bta-miR-423-3p) was confirmed by RT-qPCR. Pathway analysis of the predicted mRNA targets of differentially expressed miRNAs suggests that these miRNAs preferentially target several pathways that are functionally relevant for mycobacterial pathogenesis, including endocytosis and lysosome trafficking, IL-1 signalling and the TGF-β pathway. Over-expression studies using a bovine macrophage cell-line (Bomac) reveal the targeting of two key genes in the innate immune response to M. bovis, IL-1 receptor-associated kinase 1 (IRAK1) and TGF-β receptor 2 (TGFBR2), by miR-146. Taken together, our study suggests that miRNAs play a key role in tuning the complex interplay between M. bovis survival strategies and the host immune response

A prospective, randomized trial of complete avoidance of steroids in liver transplantation with follow‐up of over 7 years

Objectives Steroids are a mainstay of treatment in orthotopic liver transplantation ( OLT ) and are associated with significant morbidity. This trial was conducted to assess the efficacy of steroids avoidance. Methods Patients undergoing OLT between June 2002 and April 2005 were entered into a prospective, randomized trial of complete steroids avoidance and followed until November 2011. Recipients received either standard therapy ( n = 50) or complete steroids avoidance ( n = 50). Analyses were performed on an intention‐to‐treat basis. The mean follow‐up of all recipients was 2095 ± 117 days. Sixteen (32%) recipients randomized to the steroids avoidance group ultimately received steroids for clinical indications. Results Incidences of diabetes and hypertension prior to or after OLT were similar in both groups, as was the incidence of rejection. Patient and graft survival rates at 1, 3 and 5 years were lower in the steroids avoidance group than in the standard therapy group (patient survival: 1‐year, 80% versus 86%; 3‐year, 68% versus 76%; 5‐year, 60% versus 72%; graft survival: 1‐year, 76% versus 76%; 3‐year, 64% versus 74%; 5‐year, 56% versus 72%), but the differences were not statistically different. Conclusions Complete steroids avoidance provides liver transplant recipients with minimal benefit and appears to result in a concerning trend towards decreased graft and recipient survival. The present data support the use of at least a short course of steroids after liver transplantation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97180/1/hpb576.pd

Identification of PKD1L1 Gene Variants in Children with the Biliary Atresia Splenic Malformation Syndrome

Biliary atresia (BA) is the most common cause of end‐stage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations — a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patient‐parent trios, from the NIDDK‐supported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a pre‐specified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious bi‐allelic variants in polycystin 1‐like 1, PKD1L1, a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other non‐cholestatic diseases. Conclusion WES identified bi‐allelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN dataset. The dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a new, biologically plausible, cholangiocyte‐expressed candidate gene for the BASM syndrome

Associations of long chain polyunsaturated fatty acids with bone mineral density and bone turnover in postmenopausal women

PURPOSE: The immunomodulatory properties of n-3 long chain polyunsaturated fatty acids (LCPUFA) are reported to reduce bone loss through alteration of bone remodelling and n-3 LCPUFA, therefore, may benefit bone health in post-menopausal women, a vulnerable group at high risk of osteoporosis. METHODS: Measures of bone mineral density (BMD) were determined using dual energy X-ray absorptiometry (DEXA) in 300 post-menopausal women. The bone turnover markers osteocalcin (OC), C-terminal telopeptides of type 1 collagen (CTX) and total alkaline phosphatase were quantified in serum along with urinary creatinine corrected deoxypyridinoline (DPD/Cr) and CTX/Cr and the CTX:OC ratio calculated. Total serum n-6 PUFA (LA + AA) and n − 3 LCPUFA (ALA + EPA + DPA + DHA) were measured and the n − 6:n − 3 ratio was calculated. RESULTS: Mean (SD) age and body mass index (BMI) were 61 (6.4) years and 27.4 (4.8) kg/m(2), respectively with participants being 12.6 (7.6) years post-menopause. Multiple regression analysis identified no association between n-3 LCPUFA and any of the measures of T-score or BMD albeit a significant positive association between total n − 3 LCPUFA and femur BMD (β = 0.287; p = 0.043) was observed within those women with a low n − 6:n − 3 ratio. There was a significant inverse association between ALA and urinary DPD/Cr (β = − 0.141; p = 0.016). CONCLUSION: A favourable low n − 6:n − 3 ratio was associated with higher femur BMD and a higher n − 3 LCPUFA (ALA) was associated with lower bone resorption. These results support a beneficial role for n − 3 LCPUFA in reducing postmenopausal bone resorption and favourably influencing BMD. TRIAL NUMBER & DATE OF REGISTRATION: ISRCTN63118444, 2nd October 2009, “Retrospectively registered”

Global Gene Expression and Systems Biology Analysis of Bovine Monocyte-Derived Macrophages in Response to In Vitro Challenge with Mycobacterium bovis

peer-reviewedBackground Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. Results Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis. Conclusions The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.Science Foundation Ireland (www.sfi.ie) Investigator grants (Nos: SFI/01/F.1/B028 and SFI/08/IN.1/B2038); Department of Agriculture, Fisheries and Food (www.agriculture.ie) Research Stimulus Grant (No: RSF 06 405); European Union Framework 7 (http://cordis.europa.eu/fp7) Project Grant (No: KBBE-211602-MACROSYS); Irish Research Council for Science, Engineering and Technology (IRCSET) funded Bioinformatics and Systems Biology PhD Programme (http://bioinfo-casl.ucd.ie/PhD)