EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay.

We studied three patients with severe skeletal dysplasia, T cell immunodeficiency, and developmental delay. Whole-exome sequencing revealed homozygous missense mutations affecting exostosin-like 3 (EXTL3), a glycosyltransferase involved in heparan sulfate (HS) biosynthesis. Patient-derived fibroblasts showed abnormal HS composition and altered fibroblast growth factor 2 signaling, which was rescued by overexpression of wild-type EXTL3 cDNA. Interleukin-2-mediated STAT5 phosphorylation in patients' lymphocytes was markedly reduced. Interbreeding of the extl3-mutant zebrafish (box) with Tg(rag2:green fluorescent protein) transgenic zebrafish revealed defective thymopoiesis, which was rescued by injection of wild-type human EXTL3 RNA. Targeted differentiation of patient-derived induced pluripotent stem cells showed a reduced expansion of lymphohematopoietic progenitor cells and defects of thymic epithelial progenitor cell differentiation. These data identify EXTL3 mutations as a novel cause of severe immune deficiency with skeletal dysplasia and developmental delay and underline a crucial role of HS in thymopoiesis and skeletal and brain development

The IASLC/ITMIG thymic epithelial tumors staging project: Proposals for the T component for the forthcoming (8th) edition of the TNM classification of malignant tumors

Despite longstanding recognition of thymic epithelial neoplasms, there is no official American Joint Committee on Cancer/ Union for International Cancer Control stage classification. This article summarizes proposals for classification of the T component of stage classification for use in the 8th edition of the tumor, node, metastasis classification for malignant tumors. This represents the output of the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group Staging and Prognostics Factor Committee, which assembled and analyzed a worldwide database of 10,808 patients with thymic malignancies from 105 sites. The committee proposes division of the T component into four categories, representing levels of invasion. T1 includes tumors localized to the thymus and anterior mediastinal fat, regardless of capsular invasion, up to and including infiltration through the mediastinal pleura. Invasion of the pericardium is designated as T2. T3 includes tumors with direct involvement of a group of mediastinal structures either singly or in combination: lung, brachiocephalic vein, superior vena cava, chest wall, and phrenic nerve. Invasion of more central structures constitutes T4: aorta and arch vessels, intrapericardial pulmonary artery, myocardium, trachea, and esophagus. Size did not emerge as a useful descriptor for stage classification. This classification of T categories, combined with a classification of N and M categories, provides a basis for a robust tumor, node, metastasis classification system for the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control stage classification

Double spin asymmetry in exclusive rho^0 muoproduction at COMPASS

The longitudinal double spin asymmetry A_1^rho for exclusive leptoproduction of rho^0 mesons, mu + N -> mu + N + rho, is studied using the COMPASS 2002 and 2003 data. The measured reaction is incoherent exclusive rho^0 production on polarised deuterons. The Q^2 and x dependence of A_1^rho is presented in a wide kinematical range: 3x10^-3 < Q^2 < 7 (GeV/c)^2 and 5x10^-5 < x < 0.05. The presented results are the first measurements of A_1^rho at small Q2 (Q2 < 0.1 (GeV/c)^2) and small x (x < 3x10^-3). The asymmetry is in general compatible with zero in the whole kinematical range.Comment: 6 Figures, 15 pages, version 2 with updated author list, technical latex problem fixe

Human factors issues in the collocation of URET, TMA, and CPDLC

The Federal Aviation Administration (FAA) Free Flight Program individually deployed the user request evaluation tool (URET), traffic management advisor (TMA), and controller-pilot data link communications (CPDLC) to a limited number of air route traffic control centers (ARTCCs). Before deployment expands nationwide, it was important to identify any potential human factors issues that may arise due to the collocation of these tools at the controller's workstation. In this paper, we present the results of a high fidelity human-in-the-loop simulation we conducted to evaluate the impact of URET, TMA, and CPDLC collocation on air traffic controllers. We examined collocation issues with a "stovepipe" independent configuration where none of the tools were integrated or directly communicated with each other. Twelve certified professional controllers participated in the simulation working in two-person teams consisting of a radar (R-side) and data (D-side) controller. The most important collocation issue identified was that controllers had difficulty accessing important information on the D-side display when URET and CPDLC were both operational (i.e., display clutter). Although neither tool alone caused display clutter, both tools in combination made it difficult for D-side controllers to find the information they needed quickly. This was especially true for accessing CPDLC windows, which became covered when controllers used URET. Good human factors design principles prescribe that users must have immediate access to important information and that critical information should never be covered. A "stovepipe" independent deployment of these tools will result in impaired access to timely information. The results of this study indicated that better efforts should be made to integrate the information from URET, TMA, and CPDLC on the D-side monitor prior to deployment of all three tools at the controller's workstation

Shouldice technique versus other open techniques for inguinal hernia repair

Inguinal hernia repair is the most frequent operation in general surgery. There are several techniques: the Shouldice technique is sometimes considered the best method but different techniques are used as the "gold standard" for open hernia repair. Outcome measures, such as recurrence rates, complications and length of post operative stay, vary considerably among the various techniques