Clinical management and research priorities for high-risk prostate cancer in the UK:meeting report of a multidisciplinary panel in conjunction with the NCRI Prostate Cancer Clinical Studies Localised Subgroup

The management of high-risk prostate cancer has become increasingly sophisticated, with refinements in radical therapy and the inclusion of adjuvant local and systemic therapies. Despite this, high-risk prostate cancer continues to have significant treatment failure rates, with progression to metastasis, castrate resistance and ultimately disease-specific death. In an effort to discuss the challenges in this field, the UK National Clinical Research Institute’s Prostate Cancer Clinical Studies localised subgroup convened a multidisciplinary national meeting in the autumn of 2014. The remit of the meeting was to debate and reach a consensus on the key clinical and research challenges in high-risk prostate cancer and to identify themes that the UK would be best placed to pursue to help improve outcomes. This report presents the outcome of those discussions and the key recommendations for future research in this highly heterogeneous disease entity

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Diffusion tensor imaging correlates with lesion volume in cerebral hemisphere infarctions

Background Both a large lesion volume and abnormalities in diffusion tensor imaging are independently associated with a poor prognosis after cerebral infarctions. Therefore, we assume that they are associated. This study assessed the associations between lesion volumes and diffusion tensor imaging in patients with a right-sided cerebral infarction. Methods The lesion volumes of 33 patients (age 65.9 ± 8.7, 26 males and 7 females) were imaged using computed tomography (CT) in the acute phase (within 3-4 hours) and magnetic resonance imaging (MRI) in the chronic phase (follow-up at 12 months, with a range of 8-27 months). The chronic-phase fractional anisotropy (FA) and mean diffusivity (MD) values were measured at the site of the infarct and selected white matter tracts. Neurological tests in both the acute and chronic phases, and DTI lateralization were assessed with the Wilcoxon signed-rank test. The effects of thrombolytic therapy (n = 10) were assessed with the Mann-Whitney U test. The correlations between the measured parameters were analysed with Spearman's rho correlation. Bonferroni post-hoc correction was used to compensate for the familywise error rate in multiple comparisons. Results Several MD values in the right hemisphere correlated positively and FA values negatively with the lesion volumes. These correlations included both lesion area and healthy tissue. The results of the mini-mental state examination and the National Institutes of Health Stroke Scale also correlated with the lesion volume. Conclusions A larger infarct volume is associated with more pronounced tissue modifications in the chronic stage as observed with the MD and FA alterations.BioMed Central Open acces

Public health and economic impact of vaccination with 7-valent pneumococcal vaccine (PCV7) in the context of the annual influenza epidemic and a severe influenza pandemic

Background: Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1) outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. Methods: A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal disease incidence and mortality during a typical influenza season (13/100) and a severe influenza pandemic (30/100). Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd) protection of non-vaccinated persons. Results: The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save$7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd) protection in the unvaccinated. Conclusions: PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection

Electron-muon ranger: performance in the MICE muon beam

The Muon Ionization Cooling Experiment (MICE) will perform a detailed study of ionization cooling to evaluate the feasibility of the technique. To carry out this program, MICE requires an efficient particle-identification (PID) system to identify muons. The Electron-Muon Ranger (EMR) is a fully-active tracking-calorimeter that forms part of the PID system and tags muons that traverse the cooling channel without decaying. The detector is capable of identifying electrons with an efficiency of 98.6%, providing a purity for the MICE beam that exceeds 99.8%. The EMR also proved to be a powerful tool for the reconstruction of muon momenta in the range 100–280 MeV/c

Electron-muon ranger: performance in the MICE muon beam

The Muon Ionization Cooling Experiment (MICE) will perform a detailed study of ionization cooling to evaluate the feasibility of the technique. To carry out this program, MICE requires an efficient particle-identification (PID) system to identify muons. The Electron-Muon Ranger (EMR) is a fully-active tracking-calorimeter that forms part of the PID system and tags muons that traverse the cooling channel without decaying. The detector is capable of identifying electrons with an efficiency of 98.6%, providing a purity for the MICE beam that exceeds 99.8%. The EMR also proved to be a powerful tool for the reconstruction of muon momenta in the range 100–280 MeV/c

Congenital hypothyroidism

Congenital hypothyroidism (CH) occurs in approximately 1:2,000 to 1:4,000 newborns. The clinical manifestations are often subtle or not present at birth. This likely is due to trans-placental passage of some maternal thyroid hormone, while many infants have some thyroid production of their own. Common symptoms include decreased activity and increased sleep, feeding difficulty, constipation, and prolonged jaundice. On examination, common signs include myxedematous facies, large fontanels, macroglossia, a distended abdomen with umbilical hernia, and hypotonia. CH is classified into permanent and transient forms, which in turn can be divided into primary, secondary, or peripheral etiologies. Thyroid dysgenesis accounts for 85% of permanent, primary CH, while inborn errors of thyroid hormone biosynthesis (dyshormonogeneses) account for 10-15% of cases. Secondary or central CH may occur with isolated TSH deficiency, but more commonly it is associated with congenital hypopitiutarism. Transient CH most commonly occurs in preterm infants born in areas of endemic iodine deficiency. In countries with newborn screening programs in place, infants with CH are diagnosed after detection by screening tests. The diagnosis should be confirmed by finding an elevated serum TSH and low T4 or free T4 level. Other diagnostic tests, such as thyroid radionuclide uptake and scan, thyroid sonography, or serum thyroglobulin determination may help pinpoint the underlying etiology, although treatment may be started without these tests. Levothyroxine is the treatment of choice; the recommended starting dose is 10 to 15 mcg/kg/day. The immediate goals of treatment are to rapidly raise the serum T4 above 130 nmol/L (10 ug/dL) and normalize serum TSH levels. Frequent laboratory monitoring in infancy is essential to ensure optimal neurocognitive outcome. Serum TSH and free T4 should be measured every 1-2 months in the first 6 months of life and every 3-4 months thereafter. In general, the prognosis of infants detected by screening and started on treatment early is excellent, with IQs similar to sibling or classmate controls. Studies show that a lower neurocognitive outcome may occur in those infants started at a later age (> 30 days of age), on lower l-thyroxine doses than currently recommended, and in those infants with more severe hypothyroidism

First demonstration of ionization cooling by the muon ionization cooling experiment

High-brightness muon beams of energy comparable to those produced by state-of-the-art electron, proton and ion accelerators have yet to be realised. Such beams have the potential to carry the search for new phenomena in lepton-antilepton collisions to extremely high energy and also to provide uniquely well-characterised neutrino beams. A muon beam may be created through the decay of pions produced in the interaction of a proton beam with a target. To produce a high-brightness beam from such a source requires that the phase space volume occupied by the muons be reduced (cooled). Ionization cooling is the novel technique by which it is proposed to cool the beam. The Muon Ionization Cooling Experiment collaboration has constructed a section of an ionization cooling cell and used it to provide the first demonstration of ionization cooling. We present these ground-breaking measurements