Validation and reclassification of MGAP and GAP in hospital settings using data from the Trauma Audit and Research Network.

BACKGROUND Recently, two simple clinical scores were published to predict survival in trauma patients. Both scores may successfully guide major trauma triage, but neither has been independently validated in a hospital setting. METHODS This is a cohort study with 30-day mortality as the primary outcome to validate two new trauma scores-Mechanism, Glasgow Coma Scale (GCS), Age, and Pressure (MGAP) score and GCS, Age and Pressure (GAP) score-using data from the UK Trauma Audit and Research Network. First, an assessment of discrimination, using the area under the receiver operating characteristic (ROC) curve, and calibration, comparing mortality rates with those originally published, were performed. Second, we calculated sensitivity, specificity, predictive values, and likelihood ratios for prognostic score performance. Third, we propose new cutoffs for the risk categories. RESULTS A total of 79,807 adult (≥16 years) major trauma patients (2000-2010) were included; 5,474 (6.9%) died. Mean (SD) age was 51.5 (22.4) years, median GCS score was 15 (interquartile range, 15-15), and median Injury Severity Score (ISS) was 9 (interquartile range, 9-16). More than 50% of the patients had a low-risk GAP or MGAP score (1% mortality). With regard to discrimination, areas under the ROC curve were 87.2% for GAP score (95% confidence interval, 86.7-87.7) and 86.8% for MGAP score (95% confidence interval, 86.2-87.3). With regard to calibration, 2,390 (3.3%), 1,900 (28.5%), and 1,184 (72.2%) patients died in the low, medium, and high GAP risk categories, respectively. In the low- and medium-risk groups, these were almost double the previously published rates. For MGAP, 1,861 (2.8%), 1,455 (15.2%), and 2,158 (58.6%) patients died in the low-, medium-, and high-risk categories, consonant with results originally published. Reclassifying score point cutoffs improved likelihood ratios, sensitivity and specificity, as well as areas under the ROC curve. CONCLUSION We found both scores to be valid triage tools to stratify emergency department patients, according to their risk of death. MGAP calibrated better, but GAP slightly improved discrimination. The newly proposed cutoffs better differentiate risk classification and may therefore facilitate hospital resource allocation. LEVEL OF EVIDENCE Prognostic study, level II.

Using 18O/2H, 3H/3He, 85Kr and CFCs to determine mean residence times and water origin in the Grazer and Leibnitzer Feld groundwater bodies (Austria)

Two groundwater bodies, Grazer Feld and Leibnitzer Feld, with surface areas of 166 and 103 km2 respectively are characterised for the first time by measuring the combination of d18O/d2H, 3H/3He, 85Kr, CFC-11, CFC-12 and hydrochemistry in 34 monitoring wells in 2009/2010. The timescales of groundwater recharge have been characterised by 131 d18O measurements of well and surface water sampled on a seasonal basis. Most monitoring wells show a seasonal variation or indicate variable contributions of the main river Mur (0–30%, max. 70%) and/or other rivers having their recharge areas in higher altitudes. Combined d18O/d2H-measurements indicate that 65–75% of groundwater recharge in the unusual wet year of 2009 was from precipitation in the summer based on values from the Graz meteorological station. Monitoring wells downstream of gravel pit lakes show a clear evaporation trend. A boron–nitrate differentiation plot shows more frequent boron-rich water in the more urbanised Grazer Feld and more frequent nitrate-rich water in the more agricultural used Leibnitzer Feld indicating that a some of the nitrate load in the Grazer Feld comes from urban sewer water. Several lumped parameter models based on tritium input data from Graz and monthly data from the river Mur (Spielfeld) since 1977 yield a Mean Residence Time (MRT) for the Mur-water itself between 3 and 4 years in this area. Data from d18O, 3H/3He measurements at the Wagna lysimeter station supports the conclusion that 90% of the groundwaters in the Grazer Feld and 73% in the Leibnitzer Feld have MRTs of <5 years. Only in a few groundwaters were MRTs of 6–10 or 11–25 years as a result of either a long-distance water inflow in the basins or due to longer flow path in somewhat deeper wells (>20 m) with relative thicker unsaturated zones. The young MRT of groundwater from two monitoring wells in the Leibnitzer Feld was confirmed by 85Kr-measurements. Most CFC-11 and CFC-12 concentrations in the groundwater exceed the equilibration concentrations of modern concentrations in water and are therefore unsuitable for dating purposes. An enrichment factor up to 100 compared to atmospheric equilibrium concentrations and the obvious correlation of CFC-12 with SO4, Na, Cl and B in the ground waters of the Grazer Feld suggest that waste water in contact with CFC-containing material above and below ground is the source for the contamination. The dominance of very young groundwater (<5 years) indicates a recent origin of the contamination by nitrate and many other components observed in parts of the groundwater bodies. Rapid measures to reduce those sources are needed to mitigate against further deterioration of these waters.

Bone dimensions in the posterior mandible: a retrospective radiographic study using cone beam computed tomography. Part 2- analysis of edentulous sites.

A precise radiographic evaluation of the local bone dimensions and morphology is important for preoperative planning of implant placement. The purpose of this retrospective study was to analyze dimensions and morphology of edentulous sites in the posterior mandible using cone beam computed tomography (CBCT) images. This retrospective radiographic study measured the bone width (BW) of the mandible at three locations on CBCT scans for premolars (PM1, PM2) and molars (M1, M2): at 1 mm and 4 mm below the most cranial point of the alveolar crest (BW1, BW2) and at the superior border of the mandibular canal (BW3). Furthermore, the height (H) of the alveolar process (distance between the measuring points BW1 and BW3), as well as the presence of lingual undercuts, were analyzed. A total of 56 CBCTs met the inclusion criteria, resulting in a sample size of 127 cross sections. There was a statistically significant increase from PM1 to M2 for the BW2 (P < .001), which was not present for BW1 and BW3 values. For the height of the alveolar process, the values exhibited a decrease from PM1 to M2 sites. Sex was a statistically significant parameter for H (P = .001) and for BW1 (P = .03). Age was not a statistically significant parameter for bone width (BW1: P = .37; BW2: P = .31; BW3: P = .51) or for the height of the alveolar process (P = .41) in the posterior mandible. Overall, 73 (57.5%) edentulous sites were evaluated to be without visible lingual undercuts; 13 (10.2%) sites exhibited lingual undercuts classified as influential for implant placement. Precise evaluation of the alveolar crest by cross-sectional imaging is of great value to analyze vertical and buccolingual bone dimensions in different locations in the posterior mandible. In addition, CBCTs are valuable to diagnosing the presence of and potential problems caused by lingual undercuts prior to implant placement.

Evaluation of the diagnostic value of the ELISA tests developed by using EgHF, Em2 and EmII/3-10 antigens in the serological diagnosis of alveolar echinococcosis

Alveolar echinococcosis (AE), caused by larva stage of Echinococcus multilocularis, is one of the lethal parasitic diseases of man and a major public health problem in many countries in the northern hemisphere. When the living conditions and habits in Turkey were considered in terms of relation with the life cycle of the parasite, it was suggested that AE has been much more common than reported mainly from the Eastern Anatolia region of Turkey. Since in vitro serologic diagnosis tests with high specificity for AE have not been used in our country, most of the cases with liver lesions were misdiagnosed by radiological investigations as malignancies. The aim of this study was to evaluate the diagnostic value of the in-house ELISA methods developed by using three different antigens (EgHF, Em2, EmII/3-10) in the serological diagnosis of AE. The study samples included a total of 100 sera provided by Bern University Parasitology Institute where samples were obtained from patients with helminthiasis and all were confirmed by clinical, parasitological and/or histopathological means. Ten samples from each of the cases infected by E.multilocularis, E.granulosus, Taenia solium, Wuchereria bancrofti, Strongyloides stercolaris, Ascaris lumbricoides, Toxocara canis, Trichinella spiralis, Fasciola hepatica and Schistosoma haematobium were studied. In the study, EgHF (E.granulosus hydatid fluid) antigens were prepared in our laboratory from the liver cyst fluids of sheeps with cystic echinococcosis, however Em2 (E.multilocularis metacestode-purified laminated layer) and EmII/3-10 (E.multilocularis recombinant protoscolex tegument) antigens were provided by Bern University Parasitology Institute. Flat bottom ELISA plates were covered with EgHF, Em2 and EmII/3-10 antigens in the concentrations of 2.5 µg, 1 µg and 0.18 µg per well, respectively, and all sera were tested by EgHF-ELISA, Em2-ELISA and EmII/3-10-ELISA methods. For each tests, the samples which were reactive above the cut-off value (mean OD of negative controls+2 SD) were accepted as positive. The sensitivity of the ELISA tests performed with EgHF, Em2 and Em2II/3-10 antigens were estimated as 100%, 90% and 90%, respectively, whereas the specificity were 63%, 91% and 91%, respectively. When Em2-ELISA and EmII/3-10-ELISA tests were evaluated together, the specificity increased to 96%. Our data indicated that the highest sensitivity (100% with EgHF-ELISA) and specificity (96% with Em2-ELISA + EmII/3-10-ELISA) for the serodiagnosis of AE can be achieved by the combined use of the ELISA tests with three different antigens. It was concluded that the early and accurate diagnosis of AE in our country which is endemic for that disease, could be supported by the use of highly specific serological tests such as Em2-ELISA ve EmII/3-10-ELISA contributing radiological data.

Using Informatics and the Electronic Medical Record to Describe Antimicrobial Use in the Clinical Management of Diarrhea Cases at 12 Companion Animal Practices

Antimicrobial drugs may be used to treat diarrheal illness in companion animals. It is important to monitor antimicrobial use to better understand trends and patterns in antimicrobial resistance. There is no monitoring of antimicrobial use in companion animals in Canada. To explore how the use of electronic medical records could contribute to the ongoing, systematic collection of antimicrobial use data in companion animals, anonymized electronic medical records were extracted from 12 participating companion animal practices and warehoused at the University of Calgary. We used the pre-diagnostic, clinical features of diarrhea as the case definition in this study. Using text-mining technologies, cases of diarrhea were described by each of the following variables: diagnostic laboratory tests performed, the etiological diagnosis and antimicrobial therapies. The ability of the text miner to accurately describe the cases for each of the variables was evaluated. It could not reliably classify cases in terms of diagnostic tests or etiological diagnosis; a manual review of a random sample of 500 diarrhea cases determined that 88/500 (17.6%) of the target cases underwent diagnostic testing of which 36/88 (40.9%) had an etiological diagnosis. Text mining, compared to a human reviewer, could accurately identify cases that had been treated with antimicrobials with high sensitivity (92%, 95% confidence interval, 88.1%-95.4%) and specificity (85%, 95% confidence interval, 80.2%-89.1%). Overall, 7400/15,928 (46.5%) of pets presenting with diarrhea were treated with antimicrobials. Some temporal trends and patterns of the antimicrobial use are described. The results from this study suggest that informatics and the electronic medical records could be useful for monitoring trends in antimicrobial use.

Search for nonpointing and delayed photons in the diphoton and missing transverse momentum final state in 8 TeV pp collisions at the LHC using the ATLAS detector

A search has been performed, using the full 20.3  fb −1 data sample of 8 TeV proton-proton collisions collected in 2012 with the ATLAS detector at the LHC, for photons originating from a displaced vertex due to the decay of a neutral long-lived particle into a photon and an invisible particle. The analysis investigates the diphoton plus missing transverse momentum final state, and is therefore most sensitive to pair production of long-lived particles. The analysis technique exploits the capabilities of the ATLAS electromagnetic calorimeter to make precise measurements of the flight direction, as well as the time of flight, of photons. No excess is observed over the Standard Model predictions for background. Exclusion limits are set within the context of gauge mediated supersymmetry breaking models, with the lightest neutralino being the next-to-lightest supersymmetric particle and decaying into a photon and gravitino with a lifetime in the range from 250 ps to about 100 ns.

Search for contact interactions and large extra dimensions in the dilepton channel using proton-proton collisions at s√ = 8 TeV with the ATLAS detector

A search is conducted for non-resonant new phenomena in dielectron and dimuon final states, originating from either contact interactions or large extra spatial dimensions. The LHC 2012 proton–proton collision dataset recorded by the ATLAS detector is used, corresponding to 20 fb−1 at √ s = 8 TeV. The dilepton invariant mass spectrum is a discriminating variable in both searches, with the contact interaction search additionally utilizing the dilepton forward-backward asymmetry. No significant deviations from the Standard Model expectation are observed. Lower limits are set on the ℓℓqq contact interaction scale ʌ between 15.4 TeVand 26.3 TeV, at the 95%credibility level. For large extra spatial dimensions, lower limits are set on the string scale MS between 3.2 TeV to 5.0 TeV.

Search for WZ resonances in the fully leptonic channel using pp collisions at √s = 8 TeV with the ATLAS detector

A search for resonant WZ production in the ℓνℓ′ℓ′ℓνℓ′ℓ′ (ℓ,ℓ′=e,μℓ,ℓ′=e,μ) decay channel using 20.3 fb−1 of View the MathML sources=8 TeVpp collision data collected by the ATLAS experiment at LHC is presented. No significant deviation from the Standard Model prediction is observed and upper limits on the production cross sections of WZ resonances from an extended gauge model W′W′ and from a simplified model of heavy vector triplets are derived. A corresponding observed (expected) lower mass limit of 1.52 (1.49) TeV is derived for the W′W′ at the 95% confidence level.

Positive and negative mutant selection in the human histone hairpin-binding protein using the yeast three-hybrid system.

We have used the yeast three-hybrid system in a positive selection for mutants of the human histone hairpin-binding protein (HBP) capable of interacting with non-canonical hairpins and in a negative selection for loss-of-binding mutants. Interestingly, all mutations from the positive selection are located in the N- and C-terminal regions flanking a minimal RNA-binding domain (RBD) previously defined between amino acids 126 and 198. Further, in vitro binding studies demonstrate that the RBD, which shows no obvious similarity to other RNA-binding motifs, has a relaxed sequence specificity compared to full-length HBP, allowing it to bind to mutant hairpin RNAs not normally found in histone genes. These findings indicate that the sequences flanking the RBD are important for restricting binding to the highly conserved histone hairpin structure. Among the loss-of-binding mutations, about half are nonsense mutations distributed throughout the N-terminal part and the RBD whereas the other half are missense mutations restricted to the RBD. Whereas the nonsense mutations permit a more precise definition of the C-terminal border of the RBD, the missense mutations identify critical residues for RNA binding within the RBD.

Comparison of proximal femur and vertebral body strength improvements in the FREEDOM trial using an alternative finite element methodology

Denosumab reduced the incidence of new fractures in postmenopausal women with osteoporosis by 68% at the spine and 40% at the hip over 36 months compared with placebo in the FREEDOM study. This efficacy was supported by improvements from baseline in vertebral (18.2%) strength in axial compression and femoral (8.6%) strength in sideways fall configuration at 36 months, estimated in Newtons by an established voxel-based finite element (FE) methodology. Since FE analyses rely on the choice of meshes, material properties, and boundary conditions, the aim of this study was to independently confirm and compare the effects of denosumab on vertebral and femoral strength during the FREEDOM trial using an alternative smooth FE methodology. Unlike the previous FE study, effects on femoral strength in physiological stance configuration were also examined. QCT data for the proximal femur and two lumbar vertebrae were analyzed by smooth FE methodology at baseline, 12, 24, and 36 months for 51 treated (denosumab) and 47 control (placebo) subjects. QCT images were segmented and converted into smooth FE models to compute bone strength. L1 and L2 vertebral bodies were virtually loaded in axial compression and the proximal femora in both fall and stance configurations. Denosumab increased vertebral body strength by 10.8%, 14.0%, and 17.4% from baseline at 12, 24, and 36 months, respectively (p < 0.0001). Denosumab also increased femoral strength in the fall configuration by 4.3%, 5.1%, and 7.2% from baseline at 12, 24, and 36 months, respectively (p < 0.0001). Similar improvements were observed in the stance configuration with increases of 4.2%, 5.2%, and 5.2% from baseline (p ≤ 0.0007). Differences between the increasing strengths with denosumab and the decreasing strengths with placebo were significant starting at 12 months (vertebral and femoral fall) or 24 months (femoral stance). Using an alternative smooth FE methodology, we confirmed the significant improvements in vertebral body and proximal femur strength previously observed with denosumab. Estimated increases in strength with denosumab and decreases with placebo were highly consistent between both FE techniques.

Provenance analysis using Raman spectroscopy of carbonaceous material: A case study in the Southern Alps of New Zealand

Detrital provenance analyses in orogenic settings, in which sediments are collected at the outlet of a catchment, have become an important tool to estimate how erosion varies in space and time. Here we present how Raman Spectroscopy on Carbonaceous Material (RSCM) can be used for provenance analysis. RSCM provides an estimate of the peak temperature (RSCM-T) experienced during metamorphism. We show that we can infer modern erosion patterns in a catchment by combining new measurements on detrital sands with previously acquired bedrock data. We focus on the Whataroa catchment in the Southern Alps of New Zealand and exploit the metamorphic gradient that runs parallel to the main drainage direction. To account for potential sampling biases, we also quantify abrasion properties using flume experiments and measure the total organic carbon content in the bedrock that produced the collected sands. Finally, we integrate these parameters into a mass-conservative model. Our results first demonstrate that RSCM-T can be used for detrital studies. Second, we find that spatial variations in tracer concentration and erosion have a first-order control on the RSCM-T distributions, even though our flume experiments reveal that weak lithologies produce substantially more fine particles than do more durable lithologies. This result implies that sand specimens are good proxies for mapping spatial variations in erosion when the bedrock concentration of the target mineral is quantified. The modeling suggests that highest present-day erosion rates (in Whataroa catchment) are not situated at the range front but around 10 km into the mountain belt.

Privacy-preserving genomic testing in the clinic: a model using HIV treatment

PURPOSE The implementation of genomic-based medicine is hindered by unresolved questions regarding data privacy and delivery of interpreted results to health-care practitioners. We used DNA-based prediction of HIV-related outcomes as a model to explore critical issues in clinical genomics. METHODS We genotyped 4,149 markers in HIV-positive individuals. Variants allowed for prediction of 17 traits relevant to HIV medical care, inference of patient ancestry, and imputation of human leukocyte antigen (HLA) types. Genetic data were processed under a privacy-preserving framework using homomorphic encryption, and clinical reports describing potentially actionable results were delivered to health-care providers. RESULTS A total of 230 patients were included in the study. We demonstrated the feasibility of encrypting a large number of genetic markers, inferring patient ancestry, computing monogenic and polygenic trait risks, and reporting results under privacy-preserving conditions. The average execution time of a multimarker test on encrypted data was 865 ms on a standard computer. The proportion of tests returning potentially actionable genetic results ranged from 0 to 54%. CONCLUSIONS The model of implementation presented herein informs on strategies to deliver genomic test results for clinical care. Data encryption to ensure privacy helps to build patient trust, a key requirement on the road to genomic-based medicine.Genet Med advance online publication 14 January 2016Genetics in Medicine (2016); doi:10.1038/gim.2015.167.