Association between a single-pass whole-body computed tomography policy and survival after blunt major trauma: a retrospective cohort study

<p>Abstract</p> <p>Introduction</p> <p>Single-pass, whole-body computed tomography (pan-scan) remains a controversial intervention in the early assessment of patients with major trauma. We hypothesized that a liberal pan-scan policy is mainly an indicator of enhanced process quality of emergency care that may lead to improved survival regardless of the actual use of the method.</p> <p>Methods</p> <p>This retrospective cohort study included consecutive patients with blunt trauma referred to a trauma center prior to (2000 to 2002) and after (2002 to 2007) the introduction of a liberal single-pass pan-scan policy. The overall mortality between the two periods was compared and stratified according to the availability and actual use of the pan-scan. Logistic regression analysis was employed to adjust mortality estimates for demographic and injury-related independent variables.</p> <p>Results</p> <p>The study comprised 313 patients during the pre-pan-scan period, 223 patients after the introduction of the pan-scan policy but not undergoing a pan-scan and 608 patients undergoing a pan-scan. The overall mortality was 23.3, 14.8 and 7.9% (<it>P </it>< 0.001), respectively. By univariable logistic regression analysis, both the availability (odds ratio (OR) 0.57, 95% confidence interval (CI): 0.36 to 0.90) and the actual use of the pan-scan (OR 0.28, 95% CI: 0.19 to 0.42) were associated with a lower mortality. The final model contained the Injury Severity Score, the Glasgow Coma Scale, age, emergency department time and the use of the pan-scan. 2.7% of the explained variance in mortality was attributable to the use of the pan-scan. This contribution increased to 7.1% in the highest injury severity quartile.</p> <p>Conclusions</p> <p>In this study, a liberal pan-scan policy was associated with lower trauma mortality. The causal role of the pan-scan itself must be interpreted in the context of improved structural and process quality, is apparently moderate and needs further investigation with regard to the diagnostic yield and changes in management decisions. (The Pan-Scan for Trauma Resuscitation [PATRES] Study Group, <a href="http://www.controlled-trials.com/ISRCTN35424832">ISRCTN35424832</a> and <a href="http://www.controlled-trials.com/ISRCTN41462125">ISRCTN41462125</a>)</p

Deletion of LBR N-terminal domains recapitulates Pelger-Huet anomaly phenotypes in mouse without disrupting X chromosome inactivation

Mutations in the gene encoding Lamin B receptor (LBR), a nuclear-membrane protein with sterol reductase activity, have been linked to rare human disorders. Phenotypes range from a benign blood disorder, such as Pelger-Huet anomaly (PHA), affecting the morphology and chromatin organization&nbsp;of white blood cells, to embryonic lethality as for Greenberg dysplasia (GRBGD). Existing PHA mouse models do not fully recapitulate the human phenotypes, hindering efforts to understand the molecular etiology of this disorder. Here we show, using CRISPR/Cas-9 gene editing technology, that a 236bp N-terminal deletion in the mouse Lbr gene, generating a protein missing&nbsp;the N-terminal domains of LBR, presents a superior model of human PHA. Further, we address recent reports of a link between Lbr and defects in X chromosome inactivation (XCI) and show that our mouse mutant displays minor X chromosome inactivation defects that do not lead to any overt phenotypes in vivo. We suggest that our N-terminal deletion model provides a valuable pre-clinical tool to the research community and will aid in further understanding the etiology of PHA and the diverse functions of LBR

Trochanteric fracture pattern is associated with increased risk for nonunion independent of open or closed reduction technique

PURPOSE Soft tissue injury and soft tissue injury as risk factors for nonunion following trochanteric femur fractures (TFF) are marginally investigated. The aim of this study was to identify risk factors for impaired fracture healing in geriatric trauma patients with TFF following surgical treatment with a femoral nail. METHODS This retrospective cohort study included geriatric trauma patients (aged > 70 years) with TFF who were treated with femoral nailing. Fractures were classified according to AO/OTA. Nonunion was defined as lack of callus-formation after 6 months, material breakage, and requirement of revision surgery. Risk factors for nonunion included variables of clinical interest (injury pattern, demographics, comorbidities), as well as type of approach (open versus closed) and were assessed with uni- and multivariate regression analyses. RESULTS This study included 225 geriatric trauma patients. Nonunion was significantly more frequently following AO/OTA 31A3 fractures (N = 10, 23.3%) compared with AO/OTA type 31A2 (N = 6, 6.9%) or AO/OTA 31A1 (N = 3, 3.2%, p < 0.001). Type 31A3 fractures had an increased risk for nonunion compared with type 31A1 (OR 10.3 95%CI 2.2 to 48.9, p = 0.003). Open reduction was not associated with increased risk for nonunion (OR 0.9, 95%CI 0.1 to 6.1. p = 0.942) as was not the use of cerclage (OR 1.0, 95%CI 0.2 to 6.5, p = 0.995). Factors such as osteoporosis, polytrauma or diabetes were not associated with delayed union or nonunion. CONCLUSION The fracture morphology of TFF is an independent risk factor for nonunion in geriatric patients. The reduction technique is not associated with increased risk for nonunion, despite increased soft tissue damage following open reduction

Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques

We evaluated the ability of simple and complex surrogate-indices to identify individuals from an overweight/obese cohort with hepatic insulin-resistance (HEP-IR). Five indices, one previously defined and four newly generated through step-wise linear regression, were created against a single-cohort sample of 77 extensively characterised participants with the metabolic syndrome (age 55.6±1.0 years, BMI 31.5±0.4 kg/m2; 30 males). HEP-IR was defined by measuring endogenous-glucose-production (EGP) with [6–62H2] glucose during fasting and euglycemic-hyperinsulinemic clamps and expressed as EGP*fasting plasma insulin. Complex measures were incorporated into the model, including various non-standard biomarkers and the measurement of body-fat distribution and liver-fat, to further improve the predictive capability of the index. Validation was performed against a data set of the same subjects after an isoenergetic dietary intervention (4 arms, diets varying in protein and fiber content versus control). All five indices produced comparable prediction of HEP-IR, explaining 39–56% of the variance, depending on regression variable combination. The validation of the regression equations showed little variation between the different proposed indices (r2 = 27–32%) on a matched dataset. New complex indices encompassing advanced measurement techniques offered an improved correlation (r = 0.75, P<0.001). However, when validated against the alternative dataset all indices performed comparably with the standard homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.54, P<0.001). Thus, simple estimates of HEP-IR performed comparable to more complex indices and could be an efficient and cost effective approach in large epidemiological investigations

The mass-hierarchy and CP-violation discovery reach of the LBNO long-baseline neutrino experiment

The next generation neutrino observatory proposed by the LBNO collaboration will address fundamental questions in particle and astroparticle physics. The experiment consists of a far detector, in its first stage a 20 kt LAr double phase TPC and a magnetised iron calorimeter, situated at 2300 km from CERN and a near detector based on a highpressure argon gas TPC. The long baseline provides a unique opportunity to study neutrino flavour oscillations over their 1st and 2nd oscillation maxima exploring the L/E behaviour, and distinguishing effects arising from δCP and matter. In this paper we have reevaluated the physics potential of this setup for determining the mass hierarchy (MH) and discovering CP-violation (CPV), using a conventional neutrino beam from the CERN SPS with a power of 750 kW. We use conservative assumptions on the knowledge of oscillation parameter priors and systematic uncertainties. The impact of each systematic error and the precision of oscillation prior is shown. We demonstrate that the first stage of LBNO can determine unambiguously the MH to > 5δ C.L. over the whole phase space. We show that the statistical treatment of the experiment is of very high importance, resulting in the conclusion that LBNO has ~ 100% probability to determine the MH in at most 4-5 years of running. Since the knowledge of MH is indispensable to extract δCP from the data, the first LBNO phase can convincingly give evidence for CPV on the 3δ C.L. using today’s knowledge on oscillation parameters and realistic assumptions on the systematic uncertainties

Shaping Synthetic Multicellular and Complex Multimaterial Tissues via Embedded Extrusion-Volumetric Printing of Microgels

In living tissues, cells express their functions following complex signals from their surrounding microenvironment. Capturing both hierarchical architectures at the micro- and macroscale, and anisotropic cell patterning remains a major challenge in bioprinting, and a bottleneck toward creating physiologically-relevant models. Addressing this limitation, a novel technique is introduced, termed Embedded Extrusion-Volumetric Printing (EmVP), converging extrusion-bioprinting and layer-less, ultra-fast volumetric bioprinting, allowing spatially pattern multiple inks/cell types. Light-responsive microgels are developed for the first time as bioresins (µResins) for light-based volumetric bioprinting, providing a microporous environment permissive for cell homing and self-organization. Tuning the mechanical and optical properties of gelatin-based microparticles enables their use as support bath for suspended extrusion printing, in which features containing high cell densities can be easily introduced. µResins can be sculpted within seconds with tomographic light projections into centimeter-scale, granular hydrogel-based, convoluted constructs. Interstitial microvoids enhanced differentiation of multiple stem/progenitor cells (vascular, mesenchymal, neural), otherwise not possible with conventional bulk hydrogels. As proof-of-concept, EmVP is applied to create complex synthetic biology-inspired intercellular communication models, where adipocyte differentiation is regulated by optogenetic-engineered pancreatic cells. Overall, EmVP offers new avenues for producing regenerative grafts with biological functionality, and for developing engineered living systems and (metabolic) disease models

Shaping Synthetic Multicellular and Complex Multimaterial Tissues via Embedded Extrusion-Volumetric Printing of Microgels

In living tissues, cells express their functions following complex signals from their surrounding microenvironment. Capturing both hierarchical architectures at the micro- and macroscale, and anisotropic cell patterning remains a major challenge in bioprinting, and a bottleneck toward creating physiologically-relevant models. Addressing this limitation, a novel technique is introduced, termed Embedded Extrusion-Volumetric Printing (EmVP), converging extrusion-bioprinting and layer-less, ultra-fast volumetric bioprinting, allowing spatially pattern multiple inks/cell types. Light-responsive microgels are developed for the first time as bioresins (µResins) for light-based volumetric bioprinting, providing a microporous environment permissive for cell homing and self-organization. Tuning the mechanical and optical properties of gelatin-based microparticles enables their use as support bath for suspended extrusion printing, in which features containing high cell densities can be easily introduced. µResins can be sculpted within seconds with tomographic light projections into centimeter-scale, granular hydrogel-based, convoluted constructs. Interstitial microvoids enhanced differentiation of multiple stem/progenitor cells (vascular, mesenchymal, neural), otherwise not possible with conventional bulk hydrogels. As proof-of-concept, EmVP is applied to create complex synthetic biology-inspired intercellular communication models, where adipocyte differentiation is regulated by optogenetic-engineered pancreatic cells. Overall, EmVP offers new avenues for producing regenerative grafts with biological functionality, and for developing engineered living systems and (metabolic) disease models

Evaluation of Type-Specific Real-Time PCR Assays Using the LightCycler and J.B.A.I.D.S. for Detection of Adenoviruses in Species HAdV-C

Sporadically, HAdVs from species HAdV-C are detected in acute respiratory disease outbreaks. To rapidly type these viruses, we designed real-time PCR assays that detect and discriminate between adenovirus types HAdV-C1, -C2, -C5, and -C6. Sixteen clinical isolates from the California Department of Public Health were used to validate the new assays. Type-specific TaqMan real-time PCR assays were designed and used independently to successfully identify 16 representative specimens. The lower limit of detection for our LightCycler singleplex real-time PCR assays were calculated to be 100, 100, 100, and 50 genomic copies per reaction for HAdV-C1, HAdV-C2, HAdV-C5 and HAdV-C6, respectively. The results for the singleplex J.B.A.I.D.S. assays were similar. Our assays did not cross-react with other adenoviruses outside of species HAdV-C, respiratory syncytial virus, influenza, or respiratory disease causing bacteria. These assays have the potential to be useful as diagnostic tools for species HAdV-C infection

A Long Baseline Neutrino Oscillation Experiment Using J-PARC Neutrino Beam and Hyper-Kamiokande

Document submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresHyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hep-ex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW $\times$ 10$^7$ sec integrated proton beam power (corresponding to $1.56\times10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5$-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the $CP$ phase $\delta_{CP}$ can be determined to better than 19 degrees for all possible values of $\delta_{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\,\sigma$ ($5\,\sigma$) for $76$ ($58$) of the $\delta_{CP}$ parameter space