The case for the development and use of "ecologically valid" measures of executive function in experimental and clinical neuropsychology

This article considers the scientific process whereby new and better clinical tests of executive function might be developed, and what form they might take. We argue that many of the traditional tests of executive function most commonly in use (e.g., the Wisconsin Card Sorting Test; Stroop) are adaptations of procedures that emerged almost coincidentally from conceptual and experimental frameworks far removed from those currently in favour, and that the prolongation of their use has been encouraged by a sustained period of concentration on “construct-driven” experimentation in neuropsychology. This resulted from the special theoretical demands made by the field of executive function, but was not a necessary consequence, and may not even have been a useful one. Whilst useful, these tests may not therefore be optimal for their purpose. We consider as an alternative approach a function-led development programme which in principle could yield tasks better suited to the concerns of the clinician because of the transparency afforded by increased “representativeness” and “generalisability.” We further argue that the requirement of such a programme to represent the interaction between the individual and situational context might also provide useful constraints for purely experimental investigations. We provide an example of such a programme with reference to the Multiple Errands and Six Element tests

Motion-Compensation Techniques in Neonatal and Fetal MR Imaging

Fetal and neonatal MR imaging is increasingly used as a complementary diagnostic tool to sonography. MR imaging is an ideal technique for imaging fetuses and neonates because of the absence of ionizing radiation, the superior contrast of soft tissues compared with sonography, the availability of different contrast options, and the increased FOV. Motion in the normally mobile fetus and the unsettled, sleeping, or sedated neonate during a long acquisition will decrease image quality in the form of motion artifacts, hamper image interpretation, and often necessitate a repeat MR imaging to establish a diagnosis. This article reviews current techniques of motion compensation in fetal and neonatal MR imaging, including the following: 1) motion-prevention strategies (such as adequate patient preparation, patient coaching, and sedation, when required), 2) motion-artifacts minimization methods (such as fast imaging protocols, data undersampling, and motion-resistant sequences), and 3) motion-detection/correction schemes (such as navigators and self-navigated sequences, external motion-tracking devices, and postprocessing approaches) and their application in fetal and neonatal brain MR imaging. Additionally some background on the repertoire of motion of the fetal and neonatal patient and the resulting artifacts will be presented, as well as insights into future developments and emerging techniques of motion compensation

Reconstructing the 3-D Trajectories of CMEs in the Inner Heliosphere

A method for the full three-dimensional (3-D) reconstruction of the trajectories of coronal mass ejections (CMEs) using Solar TErrestrial RElations Observatory (STEREO) data is presented. Four CMEs that were simultaneously observed by the inner and outer coronagraphs (COR1 and 2) of the Ahead and Behind STEREO satellites were analysed. These observations were used to derive CME trajectories in 3-D out to ~15Rsun. The reconstructions using COR1/2 data support a radial propagation model. Assuming pseudo-radial propagation at large distances from the Sun (15-240Rsun), the CME positions were extrapolated into the Heliospheric Imager (HI) field-of-view. We estimated the CME velocities in the different fields-of-view. It was found that CMEs slower than the solar wind were accelerated, while CMEs faster than the solar wind were decelerated, with both tending to the solar wind velocity.Comment: 17 pages, 10 figures, 1 appendi

4pi Models of CMEs and ICMEs

Coronal mass ejections (CMEs), which dynamically connect the solar surface to the far reaches of interplanetary space, represent a major anifestation of solar activity. They are not only of principal interest but also play a pivotal role in the context of space weather predictions. The steady improvement of both numerical methods and computational resources during recent years has allowed for the creation of increasingly realistic models of interplanetary CMEs (ICMEs), which can now be compared to high-quality observational data from various space-bound missions. This review discusses existing models of CMEs, characterizing them by scientific aim and scope, CME initiation method, and physical effects included, thereby stressing the importance of fully 3-D ('4pi') spatial coverage.Comment: 14 pages plus references. Comments welcome. Accepted for publication in Solar Physics (SUN-360 topical issue

Increasing prevalence of a fluoroquinolone resistance mutation amongst Campylobacter jejuni isolates from four human infectious intestinal disease studies in the United Kingdom

Background: Campylobacter jejuni is the most common bacterial cause of human infectious intestinal disease. Methods: We genome sequenced 601 human C. jejuni isolates, obtained from two large prospective studies of infectious intestinal disease (IID1 [isolates from 1993–1996; n = 293] and IID2 [isolates from 2008–2009; n = 93]), the INTEGRATE project [isolates from 2016–2017; n = 52] and the ENIGMA project [isolates from 2017; n = 163]. Results: There was a significant increase in the prevalence of the T86I mutation conferring resistance to fluoroquinolone between each of the three later studies (IID2, INTEGRATE and ENIGMA) and IID1. Although the distribution of major multilocus sequence types (STs) was similar between the studies, there were changes in both the abundance of minority STs associated with the T86I mutation, and the abundance of clones within single STs associated with the T86I mutation. Discussion: Four population-based studies of community diarrhoea over a 25 year period revealed an increase over time in the prevalence of the T86I amongst isolates of C. jejuni associated with human gastrointestinal disease in the UK. Although associated with many STs, much of the increase is due to the expansion of clones associated with the resistance mutation

Fibroblast Growth Factor 7 Releasing Particles Enhance Islet Engraftment and Improve Metabolic Control Following Islet Transplantation in Mice with Diabetes

open access articleTransplantation of islets in Type 1 diabetes is limited by poor islet engraftment into the liver, with 2-3 donor pancreases required per recipient. We aimed to condition the liver to enhance islet engraftment to improve long-term graft function. Diabetic mice received a non-curative islet transplant (n=400 islets) via the hepatic portal vein (HPV) with Fibroblast Growth Factor 7 loaded galactoslyated poly(DL-lactide-co-glycolic acid) (FGF7-GAL-PLGA) particles; 26μm diameter particles specifically targeted the liver, promoting hepatocyte proliferation in short-term experiments: in mice receiving 0.1mg FGF7-GAL-PLGA particles (60ng FGF7) versus vehicle, cell proliferation was induced specifically in the liver with greater efficacy and specificity than subcutaneous FGF7 (1.25mg/kg ×2 doses; ~75μg FGF7). Numbers of engrafted islets and vascularisation were greater in liver sections of mice receiving islets and FGF7-GAL-PLGA particles versus mice receiving islets alone, 72 hours post-transplant. More mice (6 out of 8) that received islets and FGF7-GAL-PLGA particles normalised blood glucose concentrations by 30- days post-transplantation, versus 0 of 8 mice receiving islets alone with no evidence of increased proliferation of cells within the liver at this stage and normal liver function tests. This work shows liver targeted FGF7-GAL-PLGA particles achieve selective FGF7 delivery to the liver promoting islet engraftment to help normalise blood glucose levels with a good safety profile

Operation of an optoelectronic crossbar switch containing a terabit-per-second free-space optical interconnect

The experimental operation of a terabit-per-second scale optoelectronic connection to a silicon very-large-scale-integrated circuit is described. A demonstrator system, in the form of an optoelectronic crossbar switch, has been constructed as a technology test bed. The assembly and testing of the components making up the system, including a flip-chipped InGaAs-GaAs optical interface chip, are reported. Using optical inputs to the electronic switching chip, single-channel routing of data through the system at the design rate of 250 Mb/s (without internal fan-out) was achieved. With 4000 optical inputs, this corresponds to a potential aggregate data input of a terabit per second into the single 14.6 /spl times/ 15.6 mm CMOS chip. In addition 50-Mb/s data rates were switched utilizing the full internal optical fan-out included in the system to complete the required connectivity. This simultaneous input of data across the chip corresponds to an aggregate data input of 0.2 Tb/s. The experimental system also utilized optical distribution of clock signals across the CMOS chip

Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy.

Osteosarcoma, the most common primary bone sarcoma, is a genetically complex disease with no widely accepted biomarker to allow stratification of patients for treatment. After a recent report of one osteosarcoma cell line and one tumor exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the aim of this work was to assess the frequency of FGFR1 amplification in a larger cohort of osteosarcoma and to determine if this biomarker could be used for stratification of patients for treatment. About 352 osteosarcoma samples from 288 patients were analyzed for FGFR1 amplification by interphase fluorescence in situ hybridization. FGFR1 amplification was detected in 18.5% of patients whose tumors revealed a poor response to chemotherapy, and no patients whose tumors responded well to therapy harbored this genetic alteration. FGFR1 amplification is present disproportionately in the rarer histological variants of osteosarcoma. This study provides a rationale for inclusion of patients with osteosarcoma in clinical trials using FGFR kinase inhibitors

SJS/TEN 2019: From Science to Translation

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs