Prehospital critical care is associated with increased survival in adult trauma patients in Scotland

Background Scotland has three prehospital critical care teams (PHCCTs) providing enhanced care support to a usually paramedic-delivered ambulance service. The effect of the PHCCTs on patient survival following trauma in Scotland is not currently known nationally. Methods National registry-based retrospective cohort study using 2011-2016 data from the Scottish Trauma Audit Group. 30-day mortality was compared between groups after multivariate analysis to account for confounding variables. Results Our data set comprised 17 157 patients, with a mean age of 54.7 years and 8206 (57.5%) of male gender. 2877 patients in the registry were excluded due to incomplete data on their level of prehospital care, leaving an eligible group of 14 280. 13 504 injured adults who received care from ambulance clinicians (paramedics or technicians) were compared with 776 whose care included input from a PHCCT. The median Injury Severity Score (ISS) across all eligible patients was 9; 3076 patients (21.5%) met the ISS>15 criterion for major trauma. Patients in the PHCCT cohort were statistically significantly (all p < 0.01) more likely to be male; be transported to a prospective Major Trauma Centre; have suffered major trauma; have suffered a severe head injury; be transported by air and be intubated prior to arrival in hospital. Following multivariate analysis, the OR for 30-day mortality for patients seen by a PHCCT was 0.56 (95% CI 0.36 to 0.86, p=0.01). Conclusion Prehospital care provided by a physician-led critical care team was associated with an increased chance of survival at 30 days when compared with care provided by ambulance clinicians

The Knee Arthroplasty Trial (KAT) : design features, baseline characteristics and two-year functional outcomes after alternative approaches to knee replacement

Background: The aim of continued development of total knee replacement systems has been the further improvement of the quality of life and increasing the duration of prosthetic survival. Our goal was to evaluate the effects of several design features, including metal backing of the tibial component, patellar resurfacing, and a mobile bearing between the tibial and femoral components, on the function and survival of the implant. Methods: A pragmatic, multicenter, randomized, controlled trial involving 116 surgeons in thirty-four centers in the United Kingdom was performed; 2352 participants were randomly allocated to be treated with or without a metal backing of the tibial component (409), with or without patellar resurfacing (1715), and/or with or without a mobile bearing (539). Randomization to more than one comparison was allowed. The primary outcome measures were the Oxford Knee Score (OKS), Short Form-12, EuroQol-5D, and the need for additional surgery. The results up to two years postoperatively are reported. Results: Functional status and quality-of-life scores were low at baseline but improved markedly across all trial groups following knee replacement (mean overall OKS, 17.98 points at baseline and 34.82 points at two years). Most of the change was observed at three months after the surgery. Six percent of the patients had additional knee surgery within two years. There was no evidence of differences in clinical, functional, or quality-of-life measures between the randomized groups at two years. Conclusions: Patients have substantial improvement following total knee replacement. This is the first adequately powered randomized controlled trial, of which we are aware, in which the effects of metal backing, patellar resurfacing, and a mobile bearing were investigated. We found no evidence of an effect of these variants on the rate of early complications or on functional recovery up to two years after total knee replacement. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.NIHR Health Technology Assessment Programme (Project Number 95/10/01); Howmedica Osteonics; Zimmer; DePuy, a Johnson and Johnson company; Corin Medical; Smith and Nephew Healthcare. Biomet Merck; and Wright CremascoliPeer reviewe

Contributions of the RhoGEF activity of p210 BCR/ABL to disease progression

We have previously identified a tyrosine kinase-independent, guanine nucleotide exchange factor (GEF) activity that is contained within the region of p210 BCR/ABL that distinguishes it from p190 BCR/ABL. In the current study we have compared the transforming activity of p190 BCR/ABL, p210 BCR/ABL, and a mutant that lacks GEF activity (p210 BCR/ABL(S509A)). In cell-based, ex vivo, and murine bone marrow transplantation assays (BMT) the transforming activity of p210 BCR/ABL(S509A) mimics p190 BCR/ABL, and is distinct from p210 BCR/ABL. Thus, in the BMT assay, the p190 BCR/ABL and p210 BCR/ABL(S509A) transplanted mice exhibit a more rapid onset of disease than mice transplanted with p210 BCR/ABL. The reduced disease latency is associated with erythroid hyperplasia in the absence of anemia, and expansion of the MEP, CMP and GMP populations, producing a phenotype that is similar to acute myeloid leukemia (AML-M6). The disease phenotype is readily transplantable into secondary recipients. This is consistent with ex vivo clonogenicity assays where p210 BCR/ABL preferentially supports the growth of CFU-GM, while p190 BCR/ABL and the mutant preferentially support the growth of BFU-E. These results suggest that the GEF activity that distinguishes p210 BCR/ABL from p190 BCR/ABL actively regulates disease progression

Response to comment on "Human-specific gain of function in a developmental enhancer"

Duret and Galtier argue that human-specific sequence divergence and gain of function in the HACNS1 enhancer result from deleterious biased gene conversion (BGC) with no contribution from positive selection. We reinforce our previous conclusion by analyzing hypothesized BGC events genomewide and assessing the effect of recombination rates on human-accelerated conserved noncoding sequence ascertainment. We also provide evidence that AT → GC substitution bias can coexist with positive selection

Effective Conformal Theory and the Flat-Space Limit of AdS

We develop the idea of an effective conformal theory describing the low-lying spectrum of the dilatation operator in a CFT. Such an effective theory is useful when the spectrum contains a hierarchy in the dimension of operators, and a small parameter whose role is similar to that of 1/N in a large N gauge theory. These criteria insure that there is a regime where the dilatation operator is modified perturbatively. Global AdS is the natural framework for perturbations of the dilatation operator respecting conformal invariance, much as Minkowski space naturally describes Lorentz invariant perturbations of the Hamiltonian. Assuming that the lowest-dimension single-trace operator is a scalar, O, we consider the anomalous dimensions, gamma(n,l), of the double-trace operators of the form O (del^2)^n (del)^l O. Purely from the CFT we find that perturbative unitarity places a bound on these dimensions of |gamma(n,l)|<4. Non-renormalizable AdS interactions lead to violations of the bound at large values of n. We also consider the case that these interactions are generated by integrating out a heavy scalar field in AdS. We show that the presence of the heavy field "unitarizes" the growth in the anomalous dimensions, and leads to a resonance-like behavior in gamma(n,l) when n is close to the dimension of the CFT operator dual to the heavy field. Finally, we demonstrate that bulk flat-space S-matrix elements can be extracted from the large n behavior of the anomalous dimensions. This leads to a direct connection between the spectrum of anomalous dimensions in d-dimensional CFTs and flat-space S-matrix elements in d+1 dimensions. We comment on the emergence of flat-space locality from the CFT perspective.Comment: 46 pages, 2 figures. v2: JHEP published versio

Anomalous Dimensions of Non-Chiral Operators from AdS/CFT

Non-chiral operators with positive anomalous dimensions can have interesting applications to supersymmetric model building. Motivated by this, we develop a new method for obtaining the anomalous dimensions of non-chiral double-trace operators in N=1 superconformal field theories (SCFTs) with weakly-coupled AdS duals. Via the Hamiltonian formulation of AdS/CFT, we show how to directly compute the anomalous dimension as a bound state energy in the gravity dual. This simplifies previous approaches based on the four-point function and the OPE. We apply our method to a class of effective AdS5 supergravity models, and we find that the binding energy can have either sign. If such models can be UV completed, they will provide the first calculable examples of SCFTs with positive anomalous dimensions.Comment: 38 pages, 2 figures, refs adde

Measuring the Polarization of Boosted Hadronic Tops

We propose a new technique for measuring the polarization of hadronically decaying boosted top quarks. In particular, we apply a subjet-based technique to events where the decay products of the top are clustered within a single jet. The technique requires neither b-tagging nor W-reconstruction, and does not rely on assumptions about either the top production mechanism or the sources of missing energy in the event. We include results for various new physics scenarios made with different Monte Carlo generators to demonstrate the robustness of the technique.Comment: v2: version accepted for publication in JHE

The Fermi GBM Gamma-Ray Burst Spectral Catalog: Four Years Of Data

In this catalog we present the updated set of spectral analyses of GRBs detected by the Fermi Gamma-Ray Burst Monitor (GBM) during its first four years of operation. It contains two types of spectra, time-integrated spectral fits and spectral fits at the brightest time bin, from 943 triggered GRBs. Four different spectral models were fitted to the data, resulting in a compendium of more than 7500 spectra. The analysis was performed similarly, but not identically to Goldstein et al. 2012. All 487 GRBs from the first two years have been re-fitted using the same methodology as that of the 456 GRBs in years three and four. We describe, in detail, our procedure and criteria for the analysis, and present the results in the form of parameter distributions both for the observer-frame and rest-frame quantities. The data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center (HEASARC).Comment: Accepted for publication in ApJ

Familial recurrence of SOX2 anophthalmia syndrome:phenotypically normal mother with two affected daughters

The SOX2 anophthalmia syndrome is emerging as a clinically recognizable disorder that has been identified in 10–15% of individuals with bilateral anophthalmia. Extra-ocular anomalies are common. The majority of SOX2 mutations identified appear to arise de novo in probands ascertained through the presence of anophthalmia or microphthalmia. In this report, we describe two sisters with bilateral anophthalmia/microphthalmia, brain anomalies and a novel heterozygous SOX2 gene single-base pair nucleotide deletion, c.551delC, which predicts p.Pro184ArgfsX19. The hypothetical protein product is predicted to lead to haploinsufficient SOX2 function. Mosaicism for this mutation in the SOX2 gene was also identified in their clinically unaffected mother in peripheral blood DNA. Thus it cannot be assumed that all SOX2 mutations in individuals with anophthalmia /microphthalmia are de novo. Testing of parents is indicated when a SOX2 mutation is identified in a proband