The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism.

Causes and contributing factors for autism are poorly understood. Evidence suggests that prevalence is rising, but the extent to which diagnostic changes and improvements in ascertainment contribute to this increase is unclear. Both genetic and environmental factors are likely to contribute etiologically. Evidence from twin, family, and genetic studies supports a role for an inherited predisposition to the development of autism. Nonetheless, clinical, neuroanatomic, neurophysiologic, and epidemiologic studies suggest that gene penetrance and expression may be influenced, in some cases strongly, by the prenatal and early postnatal environmental milieu. Sporadic studies link autism to xenobiotic chemicals and/or viruses, but few methodologically rigorous investigations have been undertaken. In light of major gaps in understanding of autism, a large case-control investigation of underlying environmental and genetic causes for autism and triggers of regression has been launched. The CHARGE (Childhood Autism Risks from Genetics and Environment) study will address a wide spectrum of chemical and biologic exposures, susceptibility factors, and their interactions. Phenotypic variation among children with autism will be explored, as will similarities and differences with developmental delay. The CHARGE study infrastructure includes detailed developmental assessments, medical information, questionnaire data, and biologic specimens. The CHARGE study is linked to University of California-Davis Center for Children's Environmental Health laboratories in immunology, xenobiotic measurement, cell signaling, genomics, and proteomics. The goals, study design, and data collection protocols are described, as well as preliminary demographic data on study participants and on diagnoses of those recruited through the California Department of Developmental Services Regional Center System

On the derivative of the associated Legendre function of the first kind of integer order with respect to its degree

In our recent works [R. Szmytkowski, J. Phys. A 39 (2006) 15147; corrigendum: 40 (2007) 7819; addendum: 40 (2007) 14887], we have investigated the derivative of the Legendre function of the first kind, $P_{\nu}(z)$, with respect to its degree $\nu$. In the present work, we extend these studies and construct several representations of the derivative of the associated Legendre function of the first kind, $P_{\nu}^{\pm m}(z)$, with respect to the degree $\nu$, for $m\in\mathbb{N}$. At first, we establish several contour-integral representations of $\partial P_{\nu}^{\pm m}(z)/\partial\nu$. They are then used to derive Rodrigues-type formulas for $[\partial P_{\nu}^{\pm m}(z)/\partial\nu]_{\nu=n}$ with $n\in\mathbb{N}$. Next, some closed-form expressions for $[\partial P_{\nu}^{\pm m}(z)/\partial\nu]_{\nu=n}$ are obtained. These results are applied to find several representations, both explicit and of the Rodrigues type, for the associated Legendre function of the second kind of integer degree and order, $Q_{n}^{\pm m}(z)$; the explicit representations are suitable for use for numerical purposes in various regions of the complex $z$-plane. Finally, the derivatives $[\partial^{2}P_{\nu}^{m}(z)/\partial\nu^{2}]_{\nu=n}$, $[\partial Q_{\nu}^{m}(z)/\partial\nu]_{\nu=n}$ and $[\partial Q_{\nu}^{m}(z)/\partial\nu]_{\nu=-n-1}$, all with $m>n$, are evaluated in terms of $[\partial P_{\nu}^{-m}(\pm z)/\partial\nu]_{\nu=n}$.Comment: LateX, 40 pages, 1 figure, extensive referencin

Magnetic field dependence of the internal quality factor and noise performance of lumped-element kinetic inductance detectors

We present a technique for increasing the internal quality factor of kinetic inductance detectors (KIDs) by nulling ambient magnetic fields with a properly applied magnetic field. The KIDs used in this study are made from thin-film aluminum, they are mounted inside a light-tight package made from bulk aluminum, and they are operated near $150 \, \mathrm{mK}$. Since the thin-film aluminum has a slightly elevated critical temperature ($T_\mathrm{c} = 1.4 \, \mathrm{K}$), it therefore transitions before the package ($T_\mathrm{c} = 1.2 \, \mathrm{K}$), which also serves as a magnetic shield. On cooldown, ambient magnetic fields as small as approximately $30 \, \mathrm{\mu T}$ can produce vortices in the thin-film aluminum as it transitions because the bulk aluminum package has not yet transitioned and therefore is not yet shielding. These vortices become trapped inside the aluminum package below $1.2 \, \mathrm{K}$ and ultimately produce low internal quality factors in the thin-film superconducting resonators. We show that by controlling the strength of the magnetic field present when the thin film transitions, we can control the internal quality factor of the resonators. We also compare the noise performance with and without vortices present, and find no evidence for excess noise beyond the increase in amplifier noise, which is expected with increasing loss.Comment: 5 pages, 4 figure

Squamous cell carcinoma of the nipple following radiation therapy for ductal carcinoma in situ: a case report

<p>Abstract</p> <p>Introduction</p> <p>Radiation-induced nonmelanoma skin cancer was first reported seven years after the discovery of X-rays, but has received relatively little consideration in the literature. Specifically, nonmelanoma skin cancer after conservative surgery and radiation for early stage breast cancer has not been well studied. We report the case of a woman who developed squamous cell carcinoma of the nipple nine years after conservative surgery and radiation for ductal carcinoma <it>in situ </it>of the ipsilateral breast. We also review the relevant literature available to date.</p> <p>Case presentation</p> <p>A 66-year-old African-American woman presented to the hospital with a non-healing ulcer of the right nipple. Her past medical history was significant for right breast ductal carcinoma <it>in situ </it>for which she had undergone lumpectomy and whole breast radiation therapy nine years previously. Mammography and magnetic resonance imaging studies were negative for recurrent breast cancer. However, the latter demonstrated abnormal enhancement in the nipple-areolar region. An incisional biopsy of the lesion demonstrated invasive squamous cell carcinoma. Subsequently, the patient underwent wide excision of the nipple-areolar complex. Sentinel lymph-node biopsy was offered but our patient declined. She was considered to have local disease and hence no further treatment was recommended.</p> <p>Conclusion</p> <p>This case represents the first reported occurrence of squamous cell carcinoma of the nipple to follow conservative surgery and radiation for ductal carcinoma <it>in situ </it>of the ipsilateral breast. It is likely that radiation overexposure resulted in a radiation burn and subsequent radiodermatitis, placing it at risk for squamous cell carcinoma. A diagnosis of squamous cell carcinoma should be considered in a patient with a nipple lesion following radiation therapy for breast cancer.</p

Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations

Ewing's sarcoma family of tumours comprises a group of very aggressive diseases that are potentially curable with multimodality treatment. Despite the undoubted success of current treatment, approximately 30% of patients will relapse and ultimately die of disease. The insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the genesis, growth, proliferation, and the development of metastatic disease in Ewing's sarcoma. In addition, IGF1-R has been validated, both in vitro and in vivo, as a potential therapeutic target in Ewing's sarcoma. Phase I studies of IGF-1R monoclonal antibodies reported several radiological and clinical responses in Ewing's sarcoma patients, and initial reports of several Phase II studies suggest that about a fourth of the patients would benefit from IGF-1R monoclonal antibodies as single therapy, with approximately 10% of patients achieving objective responses. Furthermore, these therapies are well tolerated, and thus far severe toxicity has been rare. Other studies assessing IGF-1R monoclonal antibodies in combination with traditional cytotoxics or other targeted therapies are expected. Despite, the initial promising results, not all patients benefit from IGF-1R inhibition, and consequently, there is an urgent need for the identification of predictive markers of response

Proper motion of very low mass stars and brown dwarfs in the Pleiades cluster

We report proper motion measurements for 25 very-low mass (VLM) star and brown dwarf (BD) candidates of the Pleiades cluster previously identified by Bouvier et al. (1998). Proper motions are measured with an accuracy of 9 mas/yr, compared to an expected tangential motion of about 50 mas/yr for Pleiades members. Of the 25 candidates, 15 have a membership probability of 95% or more and 7 are rejected as being field dwarfs. The 3 remaining candidates exhibit independent evidence for membership (lithium absorption or long-term proper motion). From the firm identification of Pleiades VLM and BD members, the cluster's substellar mass function is revised to dN/dM \propto M^{-0.5} in the mass range from 0.04 to 0.3 M_solar.Comment: 7 pages, 2 tables, 2 figures, accepted by A&

A Borescope Design Tool for Laser Measurements in Fluids

This paper presents the method, implementation and validation of a borescope probe design tool devised for the challenges of optical fluid measurement techniques. The design tool is capable of predicting the path and power distribution of the laser beam through the probe and into the region interest, ensuring a cost and time-efficient design process that removes the need for experimental trials. The associated code is available as supplementary material. Optical measurement techniques have become established methods within fluid dynamics research. In contrast, their application to turbomachinery rigs is usually limited due to the restricted optical access. A small number of studies have circumvented this problem by employing borescopes to introduce the laser beam into the measurement region but wider application is inhibited because these probes are difficult to design, expensive and usually require several iterations until a suitable design is achieved. The first part of the paper presents the structure of the software program and the mathematical modelling of the optics for predicting the beam path into the measurement region. The second part presents different design options and the manufacture of a typical probe with validation in a wind tunnel facility using volumetric velocimetry. The borescope results agree very well with measurements acquired using direct illumination through a window demonstrating the efficacy of the method

Development and Validation of a Predictive Model of Acute Glucose Response to Exercise in Individuals With Type 2 Diabetes

Background: Our purpose was to develop and test a predictive model of the acute glucose response to exercise in individuals with type 2 diabetes. Design and methods: Data from three previous exercise studies (56 subjects, 488 exercise sessions) were combined and used as a development dataset. A mixed-effects Least Absolute Shrinkage Selection Operator (LASSO) was used to select predictors among 12 potential predictors. Tests of the relative importance of each predictor were conducted using the Lindemann Merenda and Gold (LMG) algorithm. Model structure was tested using likelihood ratio tests. Model accuracy in the development dataset was assessed by leave-one-out cross-validation. Prospectively captured data (47 individuals, 436 sessions) was used as a test dataset. Model accuracy was calculated as the percentage of predictions within measurement error. Overall model utility was assessed as the number of subjects with ≤ 1 model error after the third exercise session. Model accuracy across individuals was assessed graphically. In a post-hoc analysis, a mixed-effects logistic regression tested the association of individuals\u27 attributes with model error. Results: Minutes since eating, a non-linear transformation of minutes since eating, post-prandial state, hemoglobin A1c, sulfonylurea status, age, and exercise session number were identified as novel predictors. Minutes since eating, its transformations, and hemoglobin A1c combined to account for 19.6% of the variance in glucose response. Sulfonylurea status, age, and exercise session each accounted for \u3c1.0% of the variance. In the development dataset, a model with random slopes for pre-exercise glucose improved fit over a model with random intercepts only (likelihood ratio 34.5, p \u3c 0.001). Cross-validated model accuracy was 83.3%. In the test dataset, overall accuracy was 80.2%. The model was more accurate in pre-prandial than postprandial exercise (83.6% vs. 74.5% accuracy respectively). 31/47 subjects had ≤1 model error after the third exercise session. Model error varied across individuals and was weakly associated with within-subject variability in pre-exercise glucose (Odds ratio 1.49, 95% Confidence interval 1.23-1.75). Conclusions: The preliminary development and test of a predictive model of acute glucose response to exercise is presented. Further work to improve this model is discussed

Early responses to H7N9 in southern mainland China

This article is made available through the Brunel Open Access Publishing Fund. © 2014 Goodwin and Sun; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: H7N9 posed potentially serious health challenges for Chinese society. The previous SARS outbreak in this country was accompanied by contradictory information, while worries about wide-spread influenza led to discrimination worldwide. Early understanding of public threat perceptions is therefore important for effective public health communication and intervention. Methods: We interviewed 1011 respondents by phone two weeks after the first case. Questions examined risk awareness and media use, beliefs about the emergence of the threat and those most at risk, anxiety about infection and preventive and avoidant behaviours. Results: Results demonstrate moderate levels of anxiety but relatively high levels of trust towards government officials. Threat emergence was associated with hygiene levels, temperature change, floating pigs in the Huangpu River and migration to the city. Anxiety predicted both recommended and non-recommended behavioural changes. Conclusions: Comparatively high levels of trust in Chinese government advice about H7N9 contrast positively with previous pandemic communications in China. Anxiety helped drive both recommended and non-recommended behaviours, with potentially important economic and social implications. This included evidence of 'othering’ of those associated with the threat (e.g. migrants). Findings emphasise the need to manage public communications early during new influenza outbreaks.Fudan Tydall Centre and Fudan Media and Public Opinion Center