DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease.

DAX-1 (NR0B1) and SF-1 (NR5A1) are two nuclear receptor transcription factors that play a key role in human adrenal and reproductive development. Loss of DAX-1 function is classically associated with X-linked adrenal hypoplasia congenita. This condition typically affects boys and presents as primary adrenal insufficiency in early infancy or childhood, hypogonadotropic hypogonadism at puberty and impaired spermatogenesis. Late onset forms of this condition and variant phenotypes are increasingly recognized. In contrast, disruption of SF-1 only rarely causes adrenal insufficiency, usually in combination with testicular dysgenesis. Variants in SF-1/NR5A1 more commonly cause a spectrum of reproductive phenotypes ranging from 46,XY DSD (partial testicular dysgenesis or reduced androgen production) and hypospadias to male factor infertility or primary ovarian insufficiency. Making a specific diagnosis of DAX-1 or SF-1 associated conditions is important for long-term monitoring of endocrine and reproductive function, appropriate genetic counselling for family members, and for providing appropriate informed support for young people

Cognitive impairment in Parkinson's disease: impact on quality of life of carers.

BACKGROUND: The quality of life (QoL) of informal caregivers of people with Parkinson's disease (PD) (PwP) can be affected by the caring role. Because of cognitive symptoms and diminished activities of daily living, in addition to the management of motor symptoms, carers of PwP and cognitive impairment may experience increased levels of burden and poorer QoL compared with carers of PwP without cognitive impairment. This study aimed to investigate the impact of cognitive impairment in PD upon QoL of carers. METHODS: Approximately 36 months after diagnosis, 66 dyadic couples of PwP and carers completed assessments. PwP completed a schedule of neuropsychological assessments and QoL measures; carers of PwP completed demographic questionnaires and assessments of QoL. Factor scores of attention, memory/executive function and global cognition, as derived by principal component analysis, were used to evaluate cognitive domains. RESULTS: Hierarchical regression analysis found lower Montreal Cognitive Assessment was a significant independent predictor of poorer carer QoL, in addition to number of hours spent caregiving, carer depression and PD motor severity. Attentional deficits accounted for the largest proportion of variance of carer QoL. Carers of PwP and dementia (n = 9) had significantly poorer QoL scores compared with PwP and mild cognitive impairment (n = 18) or normal cognition (n = 39) carers (p < 0.01). CONCLUSIONS: Attentional deficits were the strongest predictor of carer QoL compared with other cognitive predictors. Carers for those with PD dementia reported the poorest QoL. Interventions such as respite or cognitive behavioural therapy to improve mood and self-efficacy in carers may improve carer QoL. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd

Kahler Moduli Inflation Revisited

We perform a detailed numerical analysis of inflationary solutions in Kahler moduli of type IIB flux compactifications. We show that there are inflationary solutions even when all the fields play an important role in the overall shape of the scalar potential. Moreover, there exists a direction of attraction for the inflationary trajectories that correspond to the constant volume direction. This basin of attraction enables the system to have an island of stability in the set of initial conditions. We provide explicit examples of these trajectories, compute the corresponding tilt of the density perturbations power spectrum and show that they provide a robust prediction of n_s approximately 0.96 for 60 e-folds of inflation.Comment: 27 pages, 9 figure

Restoration of diaphragmatic function after diaphragm reinnervation by inferior laryngeal nerve; experimental study in rabbits

OBJECTIVES: To assess the possibilities of reinnervation in a paralyzed hemidiaphragm via an anastomosis between phrenic nerve and inferior laryngeal nerve in rabbits. Reinnervation of a paralyzed diaphragm could be an alternative to treat patients with ventilatory insufficiency due to upper cervical spine injuries. MATERIAL AND METHOD: Rabbits were divided into five groups of seven rabbits each. Groups I and II were respectively the healthy and the denervated control groups. The 3 other groups were all reinnervated using three different surgical procedures. In groups III and IV, phrenic nerve was respectively anastomosed with the abductor branch of the inferior laryngeal nerve and with the trunk of the inferior laryngeal nerve. In group V, the fifth and fourth cervical roots were respectively anastomosed with the abductor branch of the inferior laryngeal nerve and with the nerve of the sternothyroid muscle (originating from the hypoglossal nerve). Animals were evaluated 4 months later using electromyography, transdiaphragmatic pressure measurements, sonomicrometry and histological examination. RESULTS: A poor inspiratory activity was found in quiet breathing in the reinnervated groups, with an increasing pattern of activity during effort. In the reinnervated groups, transdiaphragmatic pressure measurements and sonomicrometry were higher in group III with no significant differencewith groups IV and V. CONCLUSION: Inspiratory contractility of an hemidiaphragm could be restored with immediate anastomosis after phrenic nerve section between phrenic nerve and inferior laryngeal nerve

Maxwell-Chern-Simons Vortices and Holographic Superconductors

We investigate probe limit vortex solutions of a charged scalar field in Einstein-Maxwell theory in 3+1 dimensions, for an asymptotically AdS Schwarzschild black hole metric with the addition of an axionic coupling to the Maxwell field. We show that the inclusion of such a term, together with a suitable potential for the axion field, can induce an effective Chern-Simons term on the 2+1 dimensional boundary. We obtain numerical solutions of the equations of motion and find Maxwell-Chern-Simons like magnetic vortex configurations, where the magnetic field profile varies with the size of the effective Chern-Simons coupling. The axion field has a non-trivial profile inside the AdS bulk but does not condense at spatial infinity.Comment: 17 pages, 5 figures, version accepted for publication in JHE

Young neutron stars with soft gamma ray emission and anomalous X-ray pulsar

The observational properties of Soft Gamma Repeaters and Ano\-malous X-ray Pulsars (SGR/AXP) indicate to necessity of the energy source different from a rotational energy of a neutron star. The model, where the source of the energy is connected with a magnetic field dissipation in a highly magnetized neutron star (magnetar) is analyzed. Some observational inconsistencies are indicated for this interpretation. The alternative energy source, connected with the nuclear energy of superheavy nuclei stored in the nonequilibrium layer of low mass neutron star is discussed.Comment: 29 pages, 13 figures, Springer International Publishing Switzerland 2016 A.W. Alsabti, P. Murdin (eds.), Handbook of Supernova

Has education lost sight of children?

The reflections presented in this chapter are informed by clinical and personal experiences of school education in the UK. There are many challenges for children and young people in the modern education system and for the professionals who support them. In the UK, there are significant gaps between the highly selective education provided to those who pay privately for it and to the majority of those educated in the state-funded system. Though literacy rates have improved around the world, many children, particularly boys, do not finish their education for reasons such as boredom, behavioural difficulties or because education does not ‘pay’. Violence, bullying, and sexual harassment are issues faced by many children in schools and there are disturbing trends of excluding children who present with behavioural problems at school whose origins are not explored. Excluded children are then educated with other children who may also have multiple problems which often just make the situation worse. The experience of clinicians suggests that school-related mental health problems are increasing in severity. Are mental health services dealing with the consequences of an education system that is not meeting children’s needs? An education system that is testing- and performance-based may not be serving many children well if it is driving important decisions about them at increasingly younger ages. Labelling of children and setting them on educational career paths can occur well before they reach secondary schools, limiting potential very early on in their developmental trajectory. Furthermore, the emphasis at school on testing may come at the expense of creativity and other forms of intelligence, which are also valuable and important. Meanwhile the employment marketplace requires people with widely different skills, with an emphasis on innovation, creativity, and problem solving. Is education losing sight of the children it is educating

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function

Planar projections of graphs

We introduce and study a new graph representation where vertices are embedded in three or more dimensions, and in which the edges are drawn on the projections onto the axis-parallel planes. We show that the complete graph on $n$ vertices has a representation in $\lceil \sqrt{n/2}+1 \rceil$ planes. In 3 dimensions, we show that there exist graphs with $6n-15$ edges that can be projected onto two orthogonal planes, and that this is best possible. Finally, we obtain bounds in terms of parameters such as geometric thickness and linear arboricity. Using such a bound, we show that every graph of maximum degree 5 has a plane-projectable representation in 3 dimensions.Comment: Accepted at CALDAM 202

Measures for assessing practice change in medical practitioners

BACKGROUND: There are increasing numbers of randomised trials and systematic reviews examining the efficacy of interventions designed to bring about a change in clinical practice. The findings of this research are being used to guide strategies to increase the uptake of evidence into clinical practice. Knowledge of the outcomes measured by these trials is vital not only for the interpretation and application of the work done to date, but also to inform future research in this expanding area of endeavour and to assist in collation of results in systematic reviews and meta-analyses. METHODS: The objective of this review was to identify methods used to measure change in the clinical practices of health professionals following an intervention aimed at increasing the uptake of evidence into practice. All published trials included in a recent, comprehensive Health Technology Assessment of interventions to implement clinical practice guidelines and change clinical practice (n = 228) formed the sample for this study. Using a standardised data extraction form, one reviewer (SH), extracted the relevant information from the methods and/or results sections of the trials. RESULTS: Measures of a change of health practitioner behaviour were the most common, with 88.8% of trials using these as outcome measures. Measures that assessed change at a patient level, either actual measures of change or surrogate measures of change, were used in 28.8% and 36.7% of studies (respectively). Health practitioners' knowledge and attitudes were assessed in 22.8% of the studies and changes at an organisational level were assessed in 17.6%. CONCLUSION: Most trials of interventions aimed at changing clinical practice measured the effect of the intervention at the level of the practitioner, i.e. did the practitioner change what they do, or has their knowledge of and/or attitude toward that practice changed? Less than one-third of the trials measured, whether or not any change in practice, resulted in a change in the ultimate end-point of patient health status