Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

The Hubble Constant

I review the current state of determinations of the Hubble constant, which gives the length scale of the Universe by relating the expansion velocity of objects to their distance. There are two broad categories of measurements. The first uses individual astrophysical objects which have some property that allows their intrinsic luminosity or size to be determined, or allows the determination of their distance by geometric means. The second category comprises the use of all-sky cosmic microwave background, or correlations between large samples of galaxies, to determine information about the geometry of the Universe and hence the Hubble constant, typically in a combination with other cosmological parameters. Many, but not all, object-based measurements give $H_0$ values of around 72-74km/s/Mpc , with typical errors of 2-3km/s/Mpc. This is in mild discrepancy with CMB-based measurements, in particular those from the Planck satellite, which give values of 67-68km/s/Mpc and typical errors of 1-2km/s/Mpc. The size of the remaining systematics indicate that accuracy rather than precision is the remaining problem in a good determination of the Hubble constant. Whether a discrepancy exists, and whether new physics is needed to resolve it, depends on details of the systematics of the object-based methods, and also on the assumptions about other cosmological parameters and which datasets are combined in the case of the all-sky methods.Comment: Extensively revised and updated since the 2007 version: accepted by Living Reviews in Relativity as a major (2014) update of LRR 10, 4, 200

Complex circular subsidence structures in tephra deposited on large blocks of ice: Varða tuff cone, Öræfajökull, Iceland

Several broadly circular structures up to 16 m in diameter, into which higher strata have sagged and locally collapsed, are present in a tephra outcrop on southwest Öræfajökull, southern Iceland. The tephra was sourced in a nearby basaltic tuff cone at Varða. The structures have not previously been described in tuff cones, and they probably formed by the melting out of large buried blocks of ice emplaced during a preceding jökulhlaup that may have been triggered by a subglacial eruption within the Öræfajökull ice cap. They are named ice-melt subsidence structures, and they are analogous to kettle holes that are commonly found in proglacial sandurs and some lahars sourced in ice-clad volcanoes. The internal structure is better exposed in the Varða examples because of an absence of fluvial infilling and reworking, and erosion of the outcrop to reveal the deeper geometry. The ice-melt subsidence structures at Varða are a proxy for buried ice. They are the only known evidence for a subglacial eruption and associated jökulhlaup that created the ice blocks. The recognition of such structures elsewhere will be useful in reconstructing more complete regional volcanic histories as well as for identifying ice-proximal settings during palaeoenvironmental investigations

The contribution of microlensing surveys to the distance scale

In the early nineties several teams started large scale systematic surveys of the Magellanic Clouds and the Galactic Bulge to search for microlensing effects. As a by product, these groups have created enormous time-series databases of photometric measurements of stars with a temporal sampling duration and accuracy which are unprecedented. They provide the opportunity to test the accuracy of primary distance indicators, such as Cepheids, RRLyrae stars, the detached eclipsing binaries, or the luminosity of the red clump. We will review the contribution of the microlensing surveys to the understanding of the physics of the primary distance indicators, recent differential studies and direct distance determinations to the Magellanic Clouds and the Galactic Bulge.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 21 pages; uses Kluwer's crckapb.sty LaTeX style file, enclose

The prevalence of physical, sexual and mental abuse among adolescents and the association with BMI status

<p>Abstract</p> <p>Background</p> <p>Studies among adults show an association between abuse and Body Mass Index (BMI) status. When an aberrant BMI status as a consequence of abuse is already prevalent in adolescence, early detection and treatment of abuse might prevent these adolescents from developing serious weight problems and other long-term social, emotional and physical problems in adulthood. Therefore, this study investigated the prevalence of physical, sexual and mental abuse among adolescents and examined the association of these abuse subtypes with BMI status.</p> <p>Methods</p> <p>In total, data of 51,856 secondary school students aged 13–16 who had completed a questionnaire on health, well-being and lifestyle were used. BMI was classified into four categories, underweight, normal weight, overweight and obesity. Adolescents reported if they had ever been physically, sexually or mentally abused. Crude and adjusted General Estimation Equation (GEE) analyses were performed to investigate the association between abuse subtypes and BMI status. Analyses were adjusted for ethnicity and parental communication, and stratified for gender and educational level.</p> <p>Results</p> <p>Eighteen percent of the adolescents reported mental abuse, 7% reported sexual abuse, and 6% reported physical abuse. For underweight, overweight and obese adolescents these percentages were 17%, 25%, and 44%; 7%, 8%, and 16%; and 6%, 8%, 18% respectively. For the entire population, all these subtypes of abuse were associated with being overweight and obese (OR=3.67, 1.79 and 1.50) and all but sexual abuse were associated with underweight (OR=1.21 and 1.12). Stratified analyses showed that physical and sexual abuse were significantly associated with obesity among boys (OR=1.77 and 2.49) and among vocational school students (OR=1.60 and 1.69), and with underweight among girls (OR=1.26 and 0.83).</p> <p>Conclusion</p> <p>Mental abuse was reported by almost half of the obese adolescents and associated with underweight, overweight and obesity. Longitudinal analyses are recommended to explore the causality of and the mechanisms explaining this association between abuse and overweight.</p

Using metrics and sustainability considerations to evaluate the use of bio-based and non-renewable Brønsted acidic ionic liquids to catalyse Fischer esterification reactions

Background Ionic liquids have found uses in many applications, one of which is the joint solvation and catalysis of chemical transformations. Suitable Brønsted acidic ionic liquids can be formed by combining lactams with sulphonic acids. This work weighs up the relative benefits and disadvantages of applying these Brønsted acidic ionic liquid catalysts in esterifications through a series of comparisons using green chemistry metrics. Results A new bio-based ionic liquid was synthesised from N-methyl pyrrolidinone and p-cymenesulphonic acid, and tested as a catalyst in three Fischer esterifications under different conditions. An evaluation of the performance of this Brønsted acidic ionic liquid was made through the comparison to other ionic liquid catalysts as well as conventional homogeneous Brønsted acids. Conclusion Extending the argument to feedstock security as well as mass utilisation, ultimately in most instances traditional mineral acids appear to be the most sensible option for Brønsted acid esterification catalysts. Ester yields obtained from Brønsted acidic ionic liquid catalysed procedures were modest. This calls into question the diversity of research exploring esterification catalysis and the role of ionic liquids in esterifications

Brain connectivity changes in autosomal recessive Parkinson Disease: a model for the sporadic form

Biallelic genetic mutations in the Park2 and PINK1 genes are frequent causes of autosomal recessive PD. Carriers of single heterozygous mutations may manifest subtle signs of disease, thus providing a unique model of preclinical PD. One emerging hypothesis suggests that non-motor symptom of PD, such as cognitive impairment may be due to a distributed functional disruption of various neuronal circuits. Using resting-state functional MRI (RS-fMRI), we tested the hypothesis that abnormal connectivity within and between brain networks may account for the patients' cognitive status. Eight homozygous and 12 heterozygous carriers of either PINK1 or Park2 mutation and 22 healthy controls underwent RS-fMRI and cognitive assessment. RS-fMRI data underwent independent component analysis to identify five networks of interest: default-mode network, salience network, executive network, right and left fronto-parietal networks. Functional connectivity within and between each network was assessed and compared between groups. All mutation carriers were cognitively impaired, with the homozygous group reporting a more prominent impairment in visuo-spatial working memory. Changes in functional connectivity were evident within all networks between homozygous carriers and controls. Also heterozygotes reported areas of reduced connectivity when compared to controls within two networks. Additionally, increased inter-network connectivity was observed in both groups of mutation carriers, which correlated with their spatial working memory performance, and could thus be interpreted as compensatory. We conclude that both homozygous and heterozygous carriers exhibit pathophysiological changes unveiled by RS-fMRI, which can account for the presence/severity of cognitive symptom

Teaching Mindfulness to Teachers: a Systematic Review and Narrative Synthesis

School teachers report high levels of stress which impact on their engagement with pupils and effectiveness as a teacher. Early intervention or prevention approaches may support teachers to develop positive coping and reduce the experience and impact of stress. This article reviews research on one such approach: mindfulness-based interventions (MBIs) for school teachers. A systematic review and narrative synthesis were conducted for quantitative and qualitative studies that report the effects of MBIs for teachers of children aged 5– 18 years on symptoms of stress and emotion regulation and self-efficacy. Twelve independent publications were identified meeting the inclusion criteria and these gave a total of 13 samples. Quality appraisal of the identified articles was carried out. The effect sizes and proportion of significant findings are reported for relevant outcomes. The quality of the literature varied, with main strengths in reporting study details, and weaknesses including sample size considerations. A range of MBIs were employed across the literature, ranging in contact hours and aims. MBIs showed strongest promise for intermediary effects on teacher emotion regulation. The results of the review are discussed in the context of a model of teacher stress. Teacher social and emotional competence has implications for pupil wellbeing through teacher–pupil relationships and effective management of the classroom. The implications for practice and research are considered

Assessing the adequacy of self-reported alcohol abuse measurement across time and ethnicity: cross-cultural equivalence across Hispanics and Caucasians in 1992, non-equivalence in 2001–2002

<p>Abstract</p> <p>Background</p> <p>Do estimates of alcohol abuse reflect true levels across United States Hispanics and non-Hispanic Caucasians, or does culturally-based, systematic measurement error (i.e., measurement bias) affect estimates? Likewise, given that recent estimates suggest alcohol abuse has increased among US Hispanics, the field should also ask, "Does cross-ethnic change in alcohol abuse across time reflect true change or does measurement bias influence change estimates?"</p> <p>Methods</p> <p>To address these questions, I used confirmatory factor analyses for ordered-categorical measures to probe for measurement bias on two large, standardized, nationally representative, US surveys of alcohol abuse conducted in 1992 and 2001–2002. In 2001–2002, analyses investigated whether 10 items operationalizing DSM-IV alcohol abuse provided equivalent measurement across Hispanic (<it>n </it>= 4,893) and non-Hispanic Caucasians (<it>n </it>= 16,480). In 1992, analyses examined whether a reduced 6 item item-set provided equivalent measurement among 834 Hispanic and 14,8335 non-Hispanic Caucasians.</p> <p>Results</p> <p>In 1992, findings demonstrated statistically significant measurement bias for two items. However, sensitivity analyses showed that item-level bias did not appreciably bias item-set based alcohol abuse estimates among this cohort. For 2001–2002, results demonstrated statistically significant bias for seven items, suggesting caution regarding the cross-ethnic equivalence of alcohol abuse estimates among the current US Hispanic population. Sensitivity analyses indicated that item-level differences <it>did </it>erroneously impact alcohol abuse rates in 2001–2002, underestimating rates among Hispanics relative to Caucasians.</p> <p>Conclusion</p> <p>1992's item-level findings suggest that estimates of drinking related social or legal problems may underestimate these specific problems among Hispanics. However, impact analyses indicated no appreciable effect on alcohol abuse estimates resulting from the item-set. Efforts to monitor change in alcohol abuse diagnoses among the Hispanic community can use 1992 estimates as a valid baseline. In 2001–2002, item-level measurement bias on seven items did affect item-set based estimates. Bias underestimated Hispanics' self-reported alcohol abuse levels relative to non-Hispanic Caucasians. Given the cross-ethnic equivalence of 1992 estimates, bias in 2001–2002 speciously minimizes current increases in drinking behavior evidenced among Hispanics. Findings call for increased public health efforts among the Hispanic community and underscore the necessity for cultural sensitivity when generalizing measures developed in the majority to minorities.</p