Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population

Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of that risk are unclear in people not ascertained for neuropsychiatric symptoms. Using several large ASD consortia and population based resources, we find genetic links between ASDs and typical variation in social behavior and adaptive functioning. This finding is evidenced through both inherited and de novo variation, indicating that multiple types of genetic risk for ASDs influence a continuum of behavioral and developmental traits, the severe tail of which can result in an ASD or other neuropsychiatric disorder diagnosis. A continuum model should inform the design and interpretation of studies of neuropsychiatric disease biology

Similarity solutions for unsteady shear-stress-driven flow of Newtonian and power-law fluids : slender rivulets and dry patches

Unsteady flow of a thin film of a Newtonian fluid or a non-Newtonian power-law fluid with power-law index N driven by a constant shear stress applied at the free surface, on a plane inclined at an angle α to the horizontal, is considered. Unsteady similarity solutions representing flow of slender rivulets and flow around slender dry patches are obtained. Specifically, solutions are obtained for converging sessile rivulets (0 < α < π/2) and converging dry patches in a pendent film (π/2 < α < π), as well as for diverging pendent rivulets and diverging dry patches in a sessile film. These solutions predict that at any time t, the rivulet and dry patch widen or narrow according to |x|3/2, and the film thickens or thins according to |x|, where x denotes distance down the plane, and that at any station x, the rivulet and dry patch widen or narrow like |t|−1, and the film thickens or thins like |t|−1, independent of N

Oral cancer treatment: developments in chemotherapy and beyond

Oncology is one of the few areas of medicine where most patients are treated intravenously rather than receiving oral drugs. Recently, several oral anti-cancer drugs have been approved and there are many more in development. Oral chemotherapy is attractive because of its convenience and ease of administration, particularly in the palliative setting. With an increasing number of oral agents emerging, we can expect to see a rapid rise in the use of oral chemotherapy in years to come. This article reviews recent developments in oral chemotherapy, both of traditional cytotoxics and novel, targeted agents, from the viewpoint of patients, physicians, drug developers and health-care providers

The Rossiter-McLaughlin effect in Exoplanet Research

The Rossiter-McLaughlin effect occurs during a planet's transit. It provides the main means of measuring the sky-projected spin-orbit angle between a planet's orbital plane, and its host star's equatorial plane. Observing the Rossiter-McLaughlin effect is now a near routine procedure. It is an important element in the orbital characterisation of transiting exoplanets. Measurements of the spin-orbit angle have revealed a surprising diversity, far from the placid, Kantian and Laplacian ideals, whereby planets form, and remain, on orbital planes coincident with their star's equator. This chapter will review a short history of the Rossiter-McLaughlin effect, how it is modelled, and will summarise the current state of the field before describing other uses for a spectroscopic transit, and alternative methods of measuring the spin-orbit angle.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H. Deeg & J.A. Belmont

Repeatability and validity of a standardised maximal step-up test for leg function-a diagnostic accuracy study

<p>Abstract</p> <p>Background</p> <p>Objectively assessed physical performance is a strong predictor for morbidity and premature death and there is an increasing interest in the role of sarcopenia in many chronic diseases. There is a need for robust and valid functional tests in clinical practice. Therefore, the repeatability and validity of a newly developed maximal step up test (MST) was assessed.</p> <p>Methods</p> <p>The MST, assessing maximal step-up height (MSH) in 3-cm increments, was evaluated in 60 healthy middle-aged subjects, 30 women and 30 men. The repeatability of MSH and the correlation between MSH and isokinetic knee extension peak torque (IKEPT), self-reported physical function (SF-36, PF), patient demographics and self-reported physical activity were investigated.</p> <p>Results</p> <p>The repeatability between occasions and between testers was 6 cm. MSH (range 12-45 cm) was significantly correlated to IKEPT, (<it>r </it>= 0.68, <it>P </it>< 0.001), SF-36 PF score, (<it>r </it>= 0.29, <it>P </it>= 0.03), sex, age, weight and BMI. The results also show that MSH above 32 cm discriminates subjects in our study with no limitation in self-reported physical function.</p> <p>Conclusions</p> <p>The standardised MST is considered a reliable leg function test for clinical practice. The MSH was related to knee extension strength and self-reported physical function. The precision of the MST for identification of limitations in physical function needs further investigation.</p

Hypoxia-driven cell motility reflects the interplay between JMY and HIF-1α.

Junction-mediating and regulatory protein (JMY) is a novel p53 cofactor that regulates p53 activity during stress. JMY interacts with p300/CBP, which are ubiquitous transcriptional co-activators that interact with a variety of sequence-specific transcription factors, including hypoxia-inducible factor-1α (HIF-1α). In addition, JMY is an actin-nucleating protein, which, through its WH2 domains, stimulates cell motility. In this study, we show that JMY is upregulated during hypoxia in a HIF-1α-dependent manner. The JMY gene contains HIF-responsive elements in its promoter region and HIF-1α is recruited to its promoter during hypoxia. HIF-1α drives transcription of JMY, which accounts for its induction under hypoxia. Moreover, the enhanced cell motility and invasion that occurs during hypoxia requires JMY, as depleting JMY under hypoxic conditions causes decreased cell motility. Our results establish the interplay between JMY and HIF-1α as a new mechanism that controls cell motility under hypoxic stress

A longitudinal twin study of the association between childhood autistic traits and psychotic experiences in adolescence

- Background: This twin study investigated whether autistic traits during childhood were associated with adolescent psychotic experiences. - Methods: Data were collected from a community sample of approximately 5000 twin pairs, which included 32 individuals with diagnosed autism spectrum conditions (ASC). Parents rated autistic traits in the twins at four points between ages 8–16 years. Positive, negative, and cognitive psychotic experiences were assessed at age 16 years using self- and parent-report scales. Longitudinal twin analyses tested the associations between these measures. - Results: Autistic traits correlated weakly or nonsignificantly with positive psychotic experiences (paranoia, hallucinations, and grandiosity), and modestly with cognitive psychotic experiences (cognitive disorganisation). Higher correlations were observed for parent-rated negative symptoms and self-reported anhedonia, although the proportion of variance in both accounted for by autistic traits was low (10 and 31 %, respectively). The majority of the genetic influences on negative symptoms and anhedonia were independent of autistic traits. Additionally, individuals with ASC displayed significantly more negative symptoms, anhedonia, and cognitive disorganisation than controls. - Conclusions: Autistic traits do not appear to be strongly associated with psychotic experiences in adolescence; associations were also largely restricted to negative symptoms. Of note, the degree to which the genetic and environmental causes of autistic traits influenced psychotic experiences was limited. These findings thus support a phenotypic and etiological distinction between autistic traits and psychotic experiences

Growth in Children with Cerebral Palsy during five years after Selective Dorsal Rhizotomy: a practice-based study

Background: Overweight is reported as a side effect of SDR. The aims were to study the development of weight, height and body mass index (BMI) during five years after SDR. Methods: This prospective, longitudinal and practice-based study included all 56 children with CP spastic diplegia undergoing SDR from the start in March 1993 to April 2003 in our hospital. The preoperative Gross Motor Function Classification System (GMFCS) levels were I-II in 17, III in 15, IV-V in 24 children. Median age at SDR was 4.3 years (range 2.4-7.4 years). Weight and height/recumbent length were measured. Swedish growth charts for typically developing children generated weight, height and BMI z-scores for age and gender. Results: The preoperative median z-scores were for height-1.92 and for body mass index (BMI)-0.22. Five years later, the median BMI z-score was increased by + 0.57 (p + 2 SD) increased (p < 0.05). Baseline BMI and age at the start of follow-up influenced the BMI change during the five years (p < 0.001 and p < 0.05 respectively). The individual growth was highly variable, but a tendency towards increasing stunting with age was seen in severe gross motor dysfunction (GMFCS levels IV-V) and the opposite, a slight catch-up of height in children with walking ability (GMFCS levels I-III). Conclusions: These are the first available subtype-and GMFCS-specific longitudinal growth data for children with CP spastic diplegia. Their growth potential according to these data should be regarded as a minimum, as some children were undernourished. It is unknown whether the spasticity reduction through SDR increased the weight gain velocity, or if the relative weight increase was part of the general "obesity epidemic". For some children the weight increase was highly desirable. In others, it resulted in overweight and obesity with risk of negative health effects. Weight and height should be monitored to enable early prevention of weight aberrations also causing problems with mobility, activity and participation

Water relations of evergreen and drought-deciduous trees along a seasonally dry tropical forest chronosequence

Seasonally dry tropical forests (SDTF) are characterized by pronounced seasonality in rainfall, and as a result trees in these forests must endure seasonal variation in soil water availability. Furthermore, SDTF on the northern Yucatan Peninsula, Mexico, have a legacy of disturbances, thereby creating a patchy mosaic of different seral stages undergoing secondary succession. We examined the water status of six canopy tree species, representing contrasting leaf phenology (evergreen vs. drought-deciduous) at three seral stages along a fire chronosequence in order to better understand strategies that trees use to overcome seasonal water limitations. The early-seral forest was characterized by high soil water evaporation and low soil moisture, and consequently early-seral trees exhibited lower midday bulk leaf water potentials (ΨL) relative to late-seral trees (−1.01 ± 0.14 and −0.54 ± 0.07 MPa, respectively). Although ΨL did not differ between evergreen and drought-deciduous trees, results from stable isotope analyses indicated different strategies to overcome seasonal water limitations. Differences were especially pronounced in the early-seral stage where evergreen trees had significantly lower xylem water δ18O values relative to drought-deciduous trees (−2.6 ± 0.5 and 0.3 ± 0.6‰, respectively), indicating evergreen species used deeper sources of water. In contrast, drought-deciduous trees showed greater enrichment of foliar 18O (∆18Ol) and 13C, suggesting lower stomatal conductance and greater water-use efficiency. Thus, the rapid development of deep roots appears to be an important strategy enabling evergreen species to overcome seasonal water limitation, whereas, in addition to losing a portion of their leaves, drought-deciduous trees minimize water loss from remaining leaves during the dry season