Symptomology Associated with in Utero Exposures to Polysubstance in an Appalachian Population.

Neonatal abstinence syndrome (NAS) is seen as a very high rate at our institution in Huntington, West Virginia, and the majority of exposures are polysubstance in nature. Polysubstance can have different meaning for each region. At our institution, polysubstance is any combination of opioids, gabapentin, methamphetamine, cocaine, marijuana, benzodiazepines, nicotine or other neuroactive substances with 3-4 substances being the norm. Rapidly changing combinations of drug use and the lack of literature create a difficult situation for clinicians who are often reliant on treatment recommendations that lack references or conclusive data supporting the clinical approaches. Elucidating withdrawal symptoms consistent with in utero exposures to particular drug combinations is difficult. Many substances induce similar withdrawal symptoms in neonates and the vast majority of cases present as polysubstance exposure. Standard methodology often leads to a research approach which isolates populations and substance of exposure to determine the individual effects on the neonate. In some drug combinations, like opioid and gabapentin exposure, the substances in concert create symptoms and complications that are not observed with either drug alone. The history of responses to substance use epidemics has been to handle each drug as a separate disease process, this is no longer a viable option. The following is a review of the literature available discussing individual substance withdrawal characteristics in neonates combined with the clinical insight gained at our hospital from treating such high rates of complex polysubstance exposure

Bomb radiocarbon evidence for strong global carbon uptake and turnover in terrestrial vegetation

Vegetation and soils are taking up approximately 30% of anthropogenic CO2 emissions because of small imbalances in large gross carbon exchanges from productivity and turnover that are poorly constrained. We combine a new budget of radiocarbon (14C) produced by nuclear bomb testing in the 1960s with model simulations to evaluate carbon cycling in terrestrial vegetation. We find that most state-of-the-art vegetation models used in the Coupled Model Intercomparison Project underestimate the 14C accumulation in vegetation biomass. Our findings, combined with constraints on vegetation carbon stocks and productivity trends, imply that net primary productivity is likely at least 80 PgC/yr presently, compared to 43-76 PgC/yr predicted by current models. Storage of anthropogenic carbon in terrestrial vegetation is likely more short-lived and vulnerable than previously predicted

Evaluation of an Extended-duration Chemoprophylaxis Regimen for Venous Thromboembolism after Microsurgical Breast Reconstruction

Patients undergoing free flap breast reconstruction are at a high risk for venous thromboembolism based upon Caprini scores. Guidelines for venous thromboembolism prophylaxis recommend high-risk groups receive extended chemoprophylaxis for several weeks after gynecological, orthopedic, and surgical oncology cases. Extended prophylaxis has not been studied in free flap breast reconstruction. The purpose of this study was to compare outcomes of free flap breast reconstruction patients who received extended venous thromboembolism (VTE) prophylaxis with those who received standard inpatient-only prophylaxis. Methods: Patients undergoing microsurgical breast reconstruction were divided into two groups: standard VTE prophylaxis (Group I) and extended prophylaxis (Group II). Both groups received prophylactic subcutaneous heparin or enoxaparin preoperatively and enoxaparin 40 mg daily postoperatively while inpatient. Group II was discharged with a home regimen of enoxaparin 40 mg daily for an additional 14 days. Results: In total, 103 patients met inclusion criteria (36 patients in Group I, 67 patients in Group II). The incidence of VTE was 1.5% in Group II compared with 2.8% in Group I (P = 0.6). There was no difference in reoperative hematoma between Group I (n = 0) and Group II (n = 1) (P = 0.7). Total flap loss was 2.2%. Conclusions: Although this retrospective pilot study did not show statistical significance in VTE between those receiving extended home chemoprophylaxis (1.5% incidence) compared with inpatient-only chemoprophylaxis (2.8%), the risk of bleeding complications was similar. These results indicate that a larger, higher powered study is justified to assess if an extended home chemoprophylaxis protocol should be standard of care post free flap breast reconstruction

Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology.

Liver biopsy is required when clinically important information about the diagnosis, prognosis or management of a patient cannot be obtained by safer means, or for research purposes. There are several approaches to liver biopsy but predominantly percutaneous or transvenous approaches are used. A wide choice of needles is available and the approach and type of needle used will depend on the clinical state of the patient and local expertise but, for non-lesional biopsies, a 16-gauge needle is recommended. Many patients with liver disease will have abnormal laboratory coagulation tests or receive anticoagulation or antiplatelet medication. A greater understanding of the changes in haemostasis in liver disease allows for a more rational, evidence-based approach to peri-biopsy management. Overall, liver biopsy is safe but there is a small morbidity and a very small mortality so patients must be fully counselled. The specimen must be of sufficient size for histopathological interpretation. Communication with the histopathologist, with access to relevant clinical information and the results of other investigations, is essential for the generation of a clinically useful report

Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A.

INTRODUCTION: Valoctocogene roxaparvovec is an investigational AAV5-based factor VIII (FVIII) gene therapy that has demonstrated sustained clinical benefit in people with severe haemophilia A. AIM: To report safety, tolerability, efficacy, and quality of life (QOL) among participants who received valoctocogene roxaparvovec in a phase 1/2 clinical study (NCT02576795). METHODS: Men ≥18 years of age with severe haemophilia A (FVIII ≤1 IU/dl) without history of FVIII inhibitors or anti-AAV5 antibodies received a single infusion of valoctocogene roxaparvovec and were followed for 5 years (6 × 1013 vg/kg dose, n = 7) and 4 years (4 × 1013 vg/kg dose, n = 6). RESULTS: Over the past 2 years, few adverse events and no FVIII inhibitors were reported. Per chromogenic substrate (CSA) assay at years 5 and 4, four of seven and three of six participants in the 6 × 1013 and 4 × 1013 vg/kg cohorts, respectively, maintained median FVIII levels >5 IU/dl, corresponding to mild haemophilia. By regression analysis, rate of change in FVIII activity was -0.14 (95% confidence interval [CI]: -.32 to .03) IU/dl/wk in the 6 × 1013 vg/kg cohort in year 5 and -.06 (95% CI: -.14 to .01) IU/dl/wk in the 4 × 1013 vg/kg cohort in year 4. No participants resumed FVIII prophylaxis, and eight of 13 participants reported zero bleeds in the past 2 years. Improved QOL from baseline persisted in the 6 × 1013 vg/kg cohort; all six Haemo-QOL-A domain scores increased. For the 4 × 1013 vg/kg cohort, high baseline Haemo-QOL-A scores persisted. CONCLUSION: These results demonstrate transgene expression and haemostatic response for up to 5 years in individuals with haemophilia A

Rapid dopamine transmission within the nucleus accumbens: dramatic difference between morphine and oxycodone delivery

While most drugs of abuse increase dopamine neurotransmission, rapid neurochemical measurements show that different drugs evoke distinct dopamine release patterns within the nucleus accumbens. Rapid changes in dopamine concentration following psychostimulant administration have been well studied; however, such changes have never been examined following opioid delivery. Here, we provide novel measures of rapid dopamine release following intravenous infusion of two opioids, morphine and oxycodone, in drug‐naïve rats using fast‐scan cyclic voltammetry and rapid (1 min) microdialysis coupled with high‐performance liquid chromatography ‐ tandem mass spectrometry (HPLC‐MS). In addition to measuring rapid dopamine transmission, microdialysis HPLC‐MS measures changes in GABA, glutamate, monoamines, monoamine metabolites and several other neurotransmitters. Although both opioids increased dopamine release in the nucleus accumbens, their patterns of drug‐evoked dopamine transmission differed dramatically. Oxycodone evoked a robust and stable increase in dopamine concentration and a robust increase in the frequency and amplitude of phasic dopamine release events. Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that was coincident with a surge in GABA concentration and then both transmitters returned to baseline levels. Thus, by providing rapid measures of neurotransmission, this study reveals previously unknown differences in opioid‐induced neurotransmitter signaling. Investigating these differences may be essential for understanding how these two drugs of abuse could differentially usurp motivational circuitry and powerfully influence behavior

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations