The association between retinal vascular geometry changes and diabetic retinopathy and their role in prediction of progression: an exploratory study

Background: The study describes the relationship of retinal vascular geometry (RVG) to severity of diabetic retinopathy (DR), and its predictive role for subsequent development of proliferative diabetic retinopathy (PDR). Methods. The research project comprises of two stages. Firstly, a comparative study of diabetic patients with different grades of DR. (No DR: Minimal non-proliferative DR: Severe non-proliferative DR: PDR) (10:10: 12: 19). Analysed RVG features including vascular widths and branching angles were compared between patient cohorts. A preliminary statistical model for determination of the retinopathy grade of patients, using these features, is presented. Secondly, in a longitudinal predictive study, RVG features were analysed for diabetic patients with progressive DR over 7 years. RVG at baseline was examined to determine risk for subsequent PDR development. Results: In the comparative study, increased DR severity was associated with gradual vascular dilatation (p = 0.000), and widening of the bifurcating angle (p = 0.000) with increase in smaller-child-vessel branching angle (p = 0.027). Type 2 diabetes and increased diabetes duration were associated with increased vascular width (p = <0.05 In the predictive study, at baseline, reduced small-child vascular width (OR = 0.73 (95 CI 0.58-0.92)), was predictive of future progression to PDR. Conclusions: The study findings suggest that RVG alterations can act as novel markers indicative of progression of DR severity and establishment of PDR. RVG may also have a potential predictive role in determining the risk of future retinopathy progression. © 2014 Habib et al.; licensee BioMed Central Ltd

A multicenter, randomized controlled trial of immediate total-body CT scanning in trauma patients (REACT-2)

Contains fulltext : 110874.pdf (publisher's version ) (Open Access)BACKGROUND: Computed tomography (CT) scanning has become essential in the early diagnostic phase of trauma care because of its high diagnostic accuracy. The introduction of multi-slice CT scanners and infrastructural improvements made total-body CT scanning technically feasible and its usage is currently becoming common practice in several trauma centers. However, literature provides limited evidence whether immediate total-body CT leads to better clinical outcome then conventional radiographic imaging supplemented with selective CT scanning in trauma patients. The aim of the REACT-2 trial is to determine the value of immediate total-body CT scanning in trauma patients. METHODS/DESIGN: The REACT-2 trial is an international, multicenter randomized clinical trial. All participating trauma centers have a multi-slice CT scanner located in the trauma room or at the Emergency Department (ED). All adult, non-pregnant, severely injured trauma patients according to predefined criteria will be included. Patients in whom direct scanning will hamper necessary cardiopulmonary resuscitation or who require an immediate operation because of imminent death (both as judged by the trauma team leader) are excluded. Randomization will be computer assisted. The intervention group will receive a contrast-enhanced total-body CT scan (head to pelvis) during the primary survey. The control group will be evaluated according to local conventional trauma imaging protocols (based on ATLS guidelines) supplemented with selective CT scanning. Primary outcome will be in-hospital mortality. Secondary outcomes are differences in mortality and morbidity during the first year post trauma, several trauma work-up time intervals, radiation exposure, general health and quality of life at 6 and 12 months post trauma and cost-effectiveness. DISCUSSION: The REACT-2 trial is a multicenter randomized clinical trial that will provide evidence on the value of immediate total-body CT scanning during the primary survey of severely injured trauma patients. If immediate total-body CT scanning is found to be the best imaging strategy in severely injured trauma patients it could replace conventional imaging supplemented with CT in this specific group. TRIAL REGISTRATION: ClinicalTrials.gov: (NCT01523626)

Non-native hydrophobic interactions detected in unfolded apoflavodoxin by paramagnetic relaxation enhancement

Transient structures in unfolded proteins are important in elucidating the molecular details of initiation of protein folding. Recently, native and non-native secondary structure have been discovered in unfolded A. vinelandii flavodoxin. These structured elements transiently interact and subsequently form the ordered core of an off-pathway folding intermediate, which is extensively formed during folding of this α–β parallel protein. Here, site-directed spin-labelling and paramagnetic relaxation enhancement are used to investigate long-range interactions in unfolded apoflavodoxin. For this purpose, glutamine-48, which resides in a non-native α-helix of unfolded apoflavodoxin, is replaced by cysteine. This replacement enables covalent attachment of nitroxide spin-labels MTSL and CMTSL. Substitution of Gln-48 by Cys-48 destabilises native apoflavodoxin and reduces flexibility of the ordered regions in unfolded apoflavodoxin in 3.4 M GuHCl, because of increased hydrophobic interactions in the unfolded protein. Here, we report that in the study of the conformational and dynamic properties of unfolded proteins interpretation of spin-label data can be complicated. The covalently attached spin-label to Cys-48 (or Cys-69 of wild-type apoflavodoxin) perturbs the unfolded protein, because hydrophobic interactions occur between the label and hydrophobic patches of unfolded apoflavodoxin. Concomitant hydrophobic free energy changes of the unfolded protein (and possibly of the off-pathway intermediate) reduce the stability of native spin-labelled protein against unfolding. In addition, attachment of MTSL or CMTSL to Cys-48 induces the presence of distinct states in unfolded apoflavodoxin. Despite these difficulties, the spin-label data obtained here show that non-native contacts exist between transiently ordered structured elements in unfolded apoflavodoxin

Design of analog front-ends for the RD53 demonstrator chip

The RD53 collaboration is developing a large scale pixel front-end chip, which will be a tool to evaluate the performance of 65 nm CMOS technology in view of its application to the readout of the innermost detector layers of ATLAS and CMS at the HL-LHC. Experimental results of the characterization of small prototypes will be discussed in the frame of the design work that is currently leading to the development of the large scale demonstrator chip RD53A to be submitted in early 2017. The paper is focused on the analog processors developed in the framework of the RD53 collaboration, including three time over threshold front-ends, designed by INFN Torino and Pavia, University of Bergamo and LBNL and a zero dead time front-end based on flash ADC designed by a joint collaboration between the Fermilab and INFN. The paper will also discuss the radiation tolerance features of the front-end channels, which were exposed to up to 800 Mrad of total ionizing dose to reproduce the system operation in the actual experiment

Trauma management incorporating focused assessment with computed tomography in trauma (FACTT) - potential effect on survival

Background Immediate recognition of life-threatening conditions and injuries is the key to trauma management. To date, the impact of focused assessment with computed tomography in trauma (FACTT) has not been formally assessed. We aimed to find out whether the concept of using FACTT during primary trauma survey has a negative or positive effect on survival. Methods In a retrospective, multicentre study, we compared our time management and probability of survival (Ps) in major trauma patients who received FACTT during trauma resuscitation with the trauma registry of the German Trauma Society (DGU). FACTT is defined as whole-body computed tomography (WBCT) during primary trauma survey. We determined the probability of survival according to the Trauma and Injury Severity Score (TRISS), the Revised Injury Severity Classification score (RISC) and the standardized mortality ratio (SMR). Results We analysed 4.817 patients from the DGU database from 2002 until 2004, 160 (3.3%) were from our trauma centre at the Ludwig-Maximilians-University (LMU) and 4.657 (96.7%) from the DGU group. 73.2% were male with a mean age of 42.5 years, a mean ISS of 29.8. 96.2% had suffered from blunt trauma. Time from admission to FAST (focused assessment with sonography for trauma)(4.3 vs. 8.7 min), chest x-ray (8.1 vs. 16.0 min) and whole-body CT (20.7 vs. 36.6 min) was shorter at the LMU compared to the other trauma centres (p < 0.001). SMR calculated by TRISS was 0.74 (CI95% 0.40-1.08) for the LMU (p = 0.24) and 0.92 (CI95% 0.84-1.01) for the DGU group (p = 0.10). RISC methodology revealed a SMR of 0.69 (95%CI 0.47-0.92) for the LMU (p = 0.043) and 1.00 (95%CI 0.94-1.06) for the DGU group (p = 0.88). Conclusion Trauma management incorporating FACTT enhances a rapid response to life-threatening problems and enables a comprehensive assessment of the severity of each relevant injury. Due to its speed and accuracy, FACTT during primary trauma survey supports rapid decision-making and may increase survival

Insights into SusCD-mediated glycan import by a prominent gut symbiont

In Bacteroidetes, one of the dominant phyla of the mammalian gut, active uptake of large nutrients across the outer membrane is mediated by SusCD protein complexes via a “pedal bin” transport mechanism. However, many features of SusCD function in glycan uptake remain unclear, including ligand binding, the role of the SusD lid and the size limit for substrate transport. Here we characterise the β2,6 fructo-oligosaccharide (FOS) importing SusCD from Bacteroides thetaiotaomicron (Bt1762-Bt1763) to shed light on SusCD function. Co-crystal structures reveal residues involved in glycan recognition and suggest that the large binding cavity can accommodate several substrate molecules, each up to ~2.5 kDa in size, a finding supported by native mass spectrometry and isothermal titration calorimetry. Mutational studies in vivo provide functional insights into the key structural features of the SusCD apparatus and cryo-EM of the intact dimeric SusCD complex reveals several distinct states of the transporter, directly visualising the dynamics of the pedal bin transport mechanism

ATHENIS_3D: Automotive tested high-voltage and embedded non-volatile integrated SoC platform with 3D technology

The ATHENIS_3D FP7 EU project aims at providing new enabling technologies (analog, digital and power components) for high-voltage and high-temperature applications, tested for power systems of new hybrid/electrical vehicles. Innovation is exploited at process/device level (3D chip stacking, wafer level packaging, trench capacitors and TSV-inductors integrated in the interposer, high-reliable non-volatile Magnetic RAM), circuit-level (inductorless high-voltage DC-DC converter, high-temperature 28nm System-on-Chip platform) and system-level (compact 3D embedded power mechatronic system). Enabling high integration levels of complex systems, operating in harsh environments, in a single packaged 3D device, ATHENIS_3D allows for one order of magnitude area reduction vs. today PCB-based power and control systems. Integration costs will be consequently reduced in key industrial sectors for Europe where high-voltage/temperature operations are mandatory (vehicles, avionics, space/defense, industrial automation, energy)