Congenital contractural arachnodactyly (Beals syndrome)

Congenital contractural arachnodactyly (Beals syndrome) is an autosomal dominantly inherited connective tissue disorder characterized by multiple flexion contractures, arachnodactyly, severe kyphoscoliosis, abnormal pinnae and muscular hypoplasia. It is caused by a mutation in FBN2 gene on chromosome 5q23. Although the clinical features can be similar to Marfan syndrome (MFS), multiple joint contractures (especially elbow, knee and finger joints), and crumpled ears in the absence of significant aortic root dilatation are characteristic of Beals syndrome and rarely found in Marfan syndrome. The incidence of CCA is unknown and its prevalence is difficult to estimate considering the overlap in phenotype with MFS; the number of patients reported has increased following the identification of FBN2 mutation. Molecular prenatal diagnosis is possible. Ultrasound imaging may be used to demonstrate joint contractures and hypokinesia in suspected cases. Management of children with CCA is symptomatic. Spontaneous improvement in camptodactyly and contractures is observed but residual camptodactyly always remains. Early intervention for scoliosis can prevent morbidity later in life. Cardiac evaluation and ophthalmologic evaluations are recommended

Long-Time Asymptotics for the Korteweg-de Vries Equation via Nonlinear Steepest Descent

We apply the method of nonlinear steepest descent to compute the long-time asymptotics of the Korteweg-de Vries equation for decaying initial data in the soliton and similarity region. This paper can be viewed as an expository introduction to this method.Comment: 31 page

Physical Properties of Wolf-Rayet Stars

The striking broad emission line spectroscopic appearance of Wolf-Rayet (WR) stars has long defied analysis, due to the extreme physical conditions within their line and continuum forming regions. Recently, model atmosphere studies have advanced sufficiently to enable the determination of stellar temperatures, luminosities, abundances, ionizing fluxes and wind properties. The observed distributions of nitrogen (WN) and carbon (WC) sequence WR stars in the Milky Way and in nearby star forming galaxies are discussed; these imply lower limits to progenitor masses of ~25, 40, 75 Msun for hydrogen-depleted (He-burning) WN, WC, and H-rich (H-burning) WN stars, respectively. WR stars in massive star binaries permit studies of wind-wind interactions and dust formation in WC systems. They also show that WR stars have typical masses of 10-25 Msun, extending up to 80 Msun for H-rich WN stars. Theoretical and observational evidence that WR winds depend on metallicity is presented, with implications for evolutionary models, ionizing fluxes, and the role of WR stars within the context of core-collapse supernovae and long-duration gamma ray bursts.Comment: 76 pages, 8 figures. Minor revision to "Annual Review of Astronomy & Astrophysics" review article Volume 45 (2007) following editors comments. Version with full resolution figures is available from ftp://astro1.shef.ac.uk/pub/pac/AnnRev_revised.pd

Prevalence of mental disorders from adolescence through early adulthood in American Indian and First Nations communities

Indigenous communities lack representation in psychiatric epidemiology despite disproportionate exposure to risk factors. We document the cumulative and 12-month prevalence of psychiatric disorders across the early life course among a sample of Indigenous young adults and compare prospective and retrospective reporting of lifetime mental disorders. This community-based participatory research includes data from 735 Indigenous people from 8 reservations/reserves. Personal interviews were conducted between 2002–2010 and 2017–2018 totaling 9 waves; diagnostic assessments of DSM-IV-TR alcohol abuse/dependence, marijuana use/dependence, other substance abuse/dependence, generalized anxiety disorder, major depressive disorder, dysthymic disorder, and attention deficit/hyperactivity disorder occurred at waves 1 (mean age = 11.1 years), 4 (mean age = 14.3 years), 6 (mean age = 16.2 years), 8 (mean age = 18.3 years), and 9 (mean age = 26.3 years). Cumulative lifetime psychiatric disorders reached 77.3% and lifetime comorbidity 56.4% by wave 9. Past-year prevalence and comorbidity at wave 9 were 28.7% and 6.7%, respectively. Substance use disorders (SUDs) were most common with peak past-year prevalence observed when participants were on average 16.3 years old then declining thereafter. Trends in early life course psychiatric disorders in this study with Indigenous participants highlight cultural variations in psychiatric epidemiology including surprisingly low rates of internalizing disorders in the face of risk factors, disproportionately high rates of early-onset and lifetime SUD, and lower rates of past-year SUD in early adulthood compared with prior research.Peer reviewedSociolog

Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ transplantation. Both compounds are still widely used in the clinic as well as for basic research, even though they have dramatic side effects and modulate other pathways than calcineurin-NFATc, too. To answer the major open question - whether the adverse side effects are secondary to the actions of the drugs on the calcineurin-NFATc pathway - alternative inhibitors were developed. Ideal inhibitors should discriminate between the inhibition of (i) calcineurin and peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii) NFATc and other transcription factors. In this review we summarize the current knowledge about novel inhibitors, synthesized or identified in the last decades, and focus on their mode of action, specificity, and biological effects