A multi-exon deletion within WWOX is associated with a 46,XY disorder of sex development

Disorders of sex development (DSD) are congenital conditions where chromosomal, gonad or genital development is atypical. In a significant proportion of 46,XY DSD cases it is not possible to identify a causative mutation, making genetic counseling difficult and potentially hindering optimal treatment. Here, we describe the analysis of a 46,XY DSD patient that presented at birth with ambiguous genitalia. Histological analysis of the surgically removed gonads showed bilateral undifferentiated gonadal tissue and immature testis, both containing malignant germ cells. We screened genomic DNA from this patient for deletions and duplications using an Illumina whole-genome SNP microarray. This analysis revealed a heterozygous deletion within the WWOX gene on chromosome 16, removing exons 6-8. Analysis of parental DNA showed that the deletion was inherited from the mother. cDNA analysis confirmed that the deletion maintained the reading frame, with exon 5 being spliced directly onto exon 9. This deletion is the first description of a germline rearrangement affecting the coding sequence of WWOX in humans. Previously described Wwox knockout mouse models showed gonadal abnormalities, supporting a role for WWOX in human gonad development

Augmenting the 6-3-5 method with design information

This paper describes a comparative study between the 6-3-5 Method and the ICR Grid. The ICR Grid is an evolved variant of 6-3-5 intended to better integrate information into the concept generation process. Unlike a conventional 6-3-5 process where participants continually sketch concepts, using the ICR Grid (the name derived from its Inform, Create, Reflect activities and structured, grid-like output) participants are additionally required to undertake information search tasks, use specific information items for concept development, and reflect on the merit of concepts as the session progresses. The results indicate that although the quantity of concepts was lower, the use of information had a positive effect in a number of areas, principally the quality and variety of output. Although grounded in the area of product development, this research is applicable to any organisation undertaking idea generation and problem solving. As well as providing insights on the transference of information to concepts, it holds additional interest for studies on the composition and use of digital libraries

Intelligent Cooperative Control Architecture: A Framework for Performance Improvement Using Safe Learning

Planning for multi-agent systems such as task assignment for teams of limited-fuel unmanned aerial vehicles (UAVs) is challenging due to uncertainties in the assumed models and the very large size of the planning space. Researchers have developed fast cooperative planners based on simple models (e.g., linear and deterministic dynamics), yet inaccuracies in assumed models will impact the resulting performance. Learning techniques are capable of adapting the model and providing better policies asymptotically compared to cooperative planners, yet they often violate the safety conditions of the system due to their exploratory nature. Moreover they frequently require an impractically large number of interactions to perform well. This paper introduces the intelligent Cooperative Control Architecture (iCCA) as a framework for combining cooperative planners and reinforcement learning techniques. iCCA improves the policy of the cooperative planner, while reduces the risk and sample complexity of the learner. Empirical results in gridworld and task assignment for fuel-limited UAV domains with problem sizes up to 9 billion state-action pairs verify the advantage of iCCA over pure learning and planning strategies

In Vivo MR Imaging of Magnetically Labeled Mesenchymal Stem Cells in a Rat Model of Renal Ischemia

Objective: This study was designed to evaluate in vivo MR imaging for the depiction of intraarterially injected superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in an experimental rat model of renal ischemia. Materials and Methods: Left renal ischemia was induced in 12 male Sprague-Dawley rats by use of the catheter lodging method. In vivo MR signal intensity variations depicted on T2*-weighted sequences were evaluated in both the left and right kidneys prior to injection (n = 2), two hours (n = 4), 15 hours (n = 2), 30 hours (n = 2) and 72 hours (n = 2) after injection of SPIO-labeled MSCs in both kidneys. Signal intensity variations were correlated with the number of Prussian blue stain-positive cells as visualized in histological specimens. Results: In an in vivo study, it was determined that there was a significant difference in signal intensity variation for both the left and right cortex (40.8 +/- 4.12 and 26.4 +/- 7.92, respectively) and for both the left and right medulla (23.2 +/- 3.32 and 15.2 +/- 3.31, respectively) until two hours after injection (p < 0.05). In addition, signal intensity variation in the left renal cortex was well correlated with the number of Prussian blue stain-positive cells per high power field (r = 0.98, p < 0.05). Conclusion: Intraarterial injected SPIO-labeled MSCs in an experimental rat model of renal ischemia can be detected with the use of in vivo MR imaging immediately after injection.This study was partly supported by a grant from the Seoul Research and Business Development Program 10548 and by a grant (A062260) from the Innovative Research Institute for Cell Therapy, Republic of Korea.Ittrich H, 2007, J MAGN RESON IMAGING, V25, P1179, DOI 10.1002/jmri.20925Hauger O, 2006, RADIOLOGY, V238, P200, DOI 10.1148/radiol.2381041668Togel F, 2005, AM J PHYSIOL-RENAL, V289, pF31, DOI 10.1152/ajprenal.00007.2005Bos C, 2004, RADIOLOGY, V233, P781, DOI 10.1148/radiol.2333031714Bulte JWM, 2004, NMR BIOMED, V17, P484, DOI 10.1002/nbm.924Grove JE, 2004, STEM CELLS, V22, P487Herzog EL, 2003, BLOOD, V102, P3483, DOI 10.1182/blood-2003-05-1664Kalish H, 2003, MAGNET RESON MED, V50, P275, DOI 10.1002/mrm.10556Frank JA, 2003, RADIOLOGY, V228, P480, DOI 10.1148/radiol.2281020638Jo SK, 2003, KIDNEY INT, V64, P43Kale S, 2003, J CLIN INVEST, V112, P42, DOI 10.1172/JCI200317856Bulte JWM, 2003, MAGNET RESON MED, V50, P201, DOI 10.1002/mrm.10511Kraitchman DL, 2003, CIRCULATION, V107, P2290, DOI 10.1161/01.CIR.0000070931.62772.4EGupta S, 2002, KIDNEY INT, V62, P1285Krause DS, 2002, GENE THER, V9, P754Bulte JWM, 2001, NAT BIOTECHNOL, V19, P1141Lewin M, 2000, NAT BIOTECHNOL, V18, P410Kelly KJ, 2000, SEMIN NEPHROL, V20, P4Firbank MJ, 1999, PHYS MED BIOL, V44, pN261, DOI 10.1088/0031-9155/44/12/403Josephson L, 1999, BIOCONJUGATE CHEM, V10, P186Sutton TA, 1998, SEMIN NEPHROL, V18, P490Thadhani R, 1996, NEW ENGL J MED, V334, P1448SHANLEY PF, 1986, AM J PATHOL, V122, P462

Silver hake tracks changes in Northwest Atlantic circulation

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Communications 2 (2011): 412, doi:10.1038/ncomms1420.Recent studies documenting shifts in spatial distribution of many organisms in response to a warming climate highlight the need to understand the mechanisms underlying species distribution at large spatial scales. Here we present one noteworthy example of remote oceanographic processes governing the spatial distribution of adult silver hake, Merluccius bilinearis, a commercially important fish in the Northeast US shelf region. Changes in spatial distribution of silver hake over the last 40 years are highly correlated with the position of the Gulf Stream (GS). These changes in distribution are in direct response to local changes in bottom temperature on the continental shelf that are responding to the same large scale circulation change affecting the GS path, namely changes in the Atlantic Meridional Overturning Circulation (AMOC). If AMOC weakens as is suggested by global climate models, silver hake distribution will remain in a poleward position, the extent to which could be forecast at both decadal and multidecadal scales.J.A.N. was supported by the NOAA Fisheries and the Environment program (FATE). T.M.J. and Y.O.K. were supported by the WHOI Ocean Climate Change Institute and Ocean Life Institute

Diagnostic Benefit of Thyroglobulin Measurement in Fine-Needle Aspiration for Diagnosing Metastatic Cervical Lymph Nodes from Papillary Thyroid Cancer: Correlations with US Features

Objective: Our goals were to determine the added value of fine-needle aspiration biopsy (FNAB)-thyroglobulin (Tg) measurements over FNAB-cytology alone for diagnosing metastatic nodes, and to determine whether the ultrasound features of lymph nodes can be used to identify lymph nodes that may benefit from FNAB-Tg measurement in patients with papillary thyroid cancer. Materials and Methods: We retrospectively evaluated 76 surgically proven cervical lymph nodes. Twenty-nine patients were awaiting surgery and 18 patients had undergone thyroid surgery for papillary thyroid cancer. Ultrasound-guided FNAB and Tg measurements were performed and the ultrasound features were evaluated. Results: The accuracies, sensitivities, and specificities of FNAB-cytology, FNAB-Tg, and combined FNAB-Tg/cytology were 90%, 80%, and 100%; 92%, 95%, and 90%; and 93%, 96%, and 90%, respectively. The diagnostic sensitivity of FNAB-Tg for metastatic nodes was significantly higher than that of FNAB-cytology (p = 0.011). Furthermore, combined FNAB-Tg/cytology significantly increased sensitivity (p = 0.002) and accuracy (p = 0.03) as compared with FNAB-cytology. Conclusion: Combined FNAB-Tg/cytology is significantly more sensitive and accurate at detecting metastatic nodes than FNAB-cytology alone. FNAB-Tg was better at diagnosing metastases in small lymph nodes

Planck intermediate results. XLI. A map of lensing-induced B-modes

The secondary cosmic microwave background (CMB) $B$-modes stem from the post-decoupling distortion of the polarization $E$-modes due to the gravitational lensing effect of large-scale structures. These lensing-induced $B$-modes constitute both a valuable probe of the dark matter distribution and an important contaminant for the extraction of the primary CMB $B$-modes from inflation. Planck provides accurate nearly all-sky measurements of both the polarization $E$-modes and the integrated mass distribution via the reconstruction of the CMB lensing potential. By combining these two data products, we have produced an all-sky template map of the lensing-induced $B$-modes using a real-space algorithm that minimizes the impact of sky masks. The cross-correlation of this template with an observed (primordial and secondary) $B$-mode map can be used to measure the lensing $B$-mode power spectrum at multipoles up to $2000$. In particular, when cross-correlating with the $B$-mode contribution directly derived from the Planck polarization maps, we obtain lensing-induced $B$-mode power spectrum measurement at a significance level of $12\,\sigma$, which agrees with the theoretical expectation derived from the Planck best-fit $\Lambda$CDM model. This unique nearly all-sky secondary $B$-mode template, which includes the lensing-induced information from intermediate to small ($10\lesssim \ell\lesssim 1000$) angular scales, is delivered as part of the Planck 2015 public data release. It will be particularly useful for experiments searching for primordial $B$-modes, such as BICEP2/Keck Array or LiteBIRD, since it will enable an estimate to be made of the lensing-induced contribution to the measured total CMB $B$-modes.Comment: 20 pages, 12 figures; Accepted for publication in A&A; The B-mode map is part of the PR2-2015 Cosmology Products; available as Lensing Products in the Planck Legacy Archive http://pla.esac.esa.int/pla/#cosmology; and described in the 'Explanatory Supplement' https://wiki.cosmos.esa.int/planckpla2015/index.php/Specially_processed_maps#2015_Lensing-induced_B-mode_ma

Bioassay studies support the potential for latrogenic transmission of variant Creutzfeldt Jakob disease through dental procedures

Background: Evidence is required to quantify the potential risks of transmission of variant Creutzfeldt Jakob (vCJD) through dental procedures. Studies, using animal models relevant to vCJD, were performed to address two questions. Firstly, whether oral tissues could become infectious following dietary exposure to BSE? Secondly, would a vCJD-contaminated dental instrument be able to transmit disease to another patient? Methods: BSE-301V was used as a clinically relevant model for vCJD. VM-mice were challenged by injection of infected brain homogenate into the small intestine (Q1) or by five minute contact between a deliberately-contaminated dental file and the gingival margin (Q2). Ten tissues were collected from groups of challenged mice at three or four weekly intervals, respectively. Each tissue was pooled, homogenised and bioassayed in indicator mice. Findings: Challenge via the small intestine gave a transmission rate of 100% (mean incubation 157±17 days). Infectivity was found in both dental pulp and the gingival margin within 3 weeks of challenge and was observed in all tissues tested within the oral cavity before the appearance of clinical symptoms. Following exposure to deliberately contaminated dental files, 97% of mice developed clinical disease (mean incubation 234±33 days). Interpretation: Infectivity was higher than expected, in a wider range of oral tissues, than was allowed for in previous risk assessments. Disease was transmitted following transient exposure of the gingiva to a contaminated dental file. These observations provide evidence that dental procedures could be a route of cross-infection for vCJD and support the enforcement of single-use for certain dental instruments

Mission impossible? The paradoxes of stretch goal setting

© 2016, © The Author(s) 2016. Stretch goal setting is a process involving multiple and nested paradoxes. The paradoxical side of stretch is attractive because it holds great promise yet dangerous because it triggers processes that are hard to control. Paradoxes are not readily managed by assuming a linear relation between the here and now and the intended future perfect. Before adopting stretch goal setting, managers should thus be prepared for the tensions and contradictions created by nested or interwoven paradoxes. Achieving stretch goals can be as difficult for the managers seeking to direct the process as for designated delegates. While the increasing popularity of stretch goal setting is understandable, its unexpected consequences must be taken into account. The inadequate use of stretch goals can jeopardize the social sustainability of organizations as well as their societal support systems

Search for a narrow charmed baryonic state decaying to D^*+/- p^-/+ in ep collisions at HERA

A resonance search has been made in the D^*+/- p^-/+ invariant-mass spectrum with the ZEUS detector at HERA using an integrated luminosity of 126 pb^-1. The decay channels D^*+ -> D^0 pi^+_s -> (K^- pi^+) pi^+_s and D^*+ -> D^0 pi^+_s -> (K^- pi^+ pi^+ pi^-) pi^+_s (and the corresponding antiparticle decays) were used to identify D^*+/- mesons. No resonance structure was observed in the D^*+/- p^-/+ mass spectrum from more than 60000 reconstructed D^*+/- mesons. The results are not compatible with a report of the H1 Collaboration of a charmed pentaquark, Theta^0_c.Comment: 22 pages, 7 figures, 1 table; minor text revisions; 2 references adde