Molecular evolution of the sheep prion protein gene

Transmissible spongiform encephalopathies (TSEs) are infectious, fatal neurodegenerative diseases characterized by aggregates of modified forms of the prion protein (PrP) in the central nervous system. Well known examples include variant Creutzfeldt-Jakob Disease (vCJD) in humans, BSE in cattle, chronic wasting disease in deer and scrapie in sheep and goats. In humans, sheep and deer, disease susceptibility is determined by host genotype at the prion protein gene (PRNP). Here I examine the molecular evolution of PRNP in ruminants and show that variation in sheep appears to have been maintained by balancing selection, a profoundly different process from that seen in other ruminants. Scrapie eradication programs such as those recently implemented in the UK, USA and elsewhere are based on the assumption that PRNP is under positive selection in response to scrapie. If, as these data suggest, that assumption is wrong, eradication programs will disrupt this balancing selection, and may have a negative impact on the fitness or scrapie resistance of national flocks

Microstructural characterisation of TiAlTiAu and TiAlPdAu ohmic contacts to AlGaN/GaN

Ti/Al/Ti/Au and Ti/Al/Pd/Au contacts to AlGaN/GaN have been investigated to ascertain the effect of annealing temperature on the structural evolution of the contacts. Ti/Al/Ti/Au contacts become ohmic after rapid thermal annealing at 750°C or higher, corresponding to the formation of an interfacial TiN phase, with inclusions penetrating through the AlGaN layer observed after annealing at 950°C. The Pd layer is shown to be more efficient at inhibiting diffusion of Au to the interface than Ti. Ohmic behaviour was not seen with the Ti/Al/Pd/Au scheme. Either the presence of Au at the interface may improve ohmic behaviour, or the Ti:Al ratio is insufficient in this scheme

Microstructural characterisation of TiAlTiAu and TiAlPdAu ohmic contacts to AlGaN/GaN

Ti/Al/Ti/Au and Ti/Al/Pd/Au contacts to AlGaN/GaN have been investigated to ascertain the effect of annealing temperature on the structural evolution of the contacts. Ti/Al/Ti/Au contacts become ohmic after rapid thermal annealing at 750°C or higher, corresponding to the formation of an interfacial TiN phase, with inclusions penetrating through the AlGaN layer observed after annealing at 950°C. The Pd layer is shown to be more efficient at inhibiting diffusion of Au to the interface than Ti. Ohmic behaviour was not seen with the Ti/Al/Pd/Au scheme. Either the presence of Au at the interface may improve ohmic behaviour, or the Ti:Al ratio is insufficient in this scheme

Bessel Process and Conformal Quantum Mechanics

Different aspects of the connection between the Bessel process and the conformal quantum mechanics (CQM) are discussed. The meaning of the possible generalizations of both models is investigated with respect to the other model, including self adjoint extension of the CQM. Some other generalizations such as the Bessel process in the wide sense and radial Ornstein- Uhlenbeck process are discussed with respect to the underlying conformal group structure.Comment: 28 Page

Delivery of antimicrobial stewardship competencies in UK pre-registration nurse education programmes: a national cross-sectional survey

Background: Registered nurses perform numerous functions critical to the success of antimicrobial stewardship but only 63% of pre-registration nursing programmes include any teaching about stewardship. Updated nursing standards highlight nurses require antimicrobial stewardship knowledge and skills. Aim: To explore the delivery of key antimicrobial stewardship competencies within updated pre-registration nursing programmes. Method: A cross-sectional survey design. Data was collected between March and June 2021. Findings: Lecturers from 35 universities responsible for teaching antimicrobial stewardship participated. The provision of antimicrobial stewardship teaching and learning was inconsistent across programmes with competencies in infection prevention and control, patient centred care, and interprofessional collaborative practice taking precedent over those pertaining to the use, management, and monitoring of antimicrobials. On-line learning and teaching surrounding hand hygiene, personal protective equipment, and immunisation theory was reported to have increased during the pandemic. Only a small number of respondents reported that students shared taught learning with other healthcare professional groups. Conclusion: There is a need to ensure consistency in antimicrobial stewardship across programmes, and greater knowledge pertaining to the use, management and monitoring of antimicrobials should be included. Programmes need to adopt teaching strategies and methods that allow nurses to develop interprofessional skill in order to practice collaboratively

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Aspirin as an adjuvant treatment for cancer:feasibility results from the Add-Aspirin randomised trial

BACKGROUND: Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer.METHODS: The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survival after radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment.FINDINGS: After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0·5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants).INTERPRETATION: Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes.FUNDING: Cancer Research UK, The National Institute for Health Research Health Technology Assessment Programme, The MRC Clinical Trials Unit at UCL.</p

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO