Developing core sets for persons following amputation based on the International Classification of Functioning, Disability and Health as a way to specify functioning

Amputation is a common late stage sequel of peripheral vascular disease and diabetes or a sequel of accidental trauma, civil unrest and landmines. The functional impairments affect many facets of life including but not limited to: Mobility; activities of daily living; body image and sexuality. Classification, measurement and comparison of the consequences of amputations has been impeded by the limited availability of internationally, multiculturally standardized instruments in the amputee setting. The introduction of the International Classification of Functioning, Disability and Health (ICF) by the World Health Assembly in May 2001 provides a globally accepted framework and classification system to describe, assess and compare function and disability. In order to facilitate the use of the ICF in everyday clinical practice and research, ICF core sets have been developed that focus on specific aspects of function typically associated with a particular disability. The objective of this paper is to outline the development process for the ICF core sets for persons following amputation. The ICF core sets are designed to translate the benefits of the ICF into clinical routine. The ICF core sets will be defined at a Consensus conference which will integrate evidence from preparatory studies, namely: (a) a systematic literature review regarding the outcome measures of clinical trails and observational studies, (b) semi-structured patient interviews, (c) international experts participating in an internet-based survey, and (d) cross-sectional, multi-center studies for clinical applicability. To validate the ICF core sets field-testing will follow. Invitation for participation: The development of ICF Core Sets is an inclusive and open process. Anyone who wishes to actively participate in this process is invited to do so

Conceptual Design of the LHC Interaction Region Upgrade: Phase-I

The LHC is starting operation with beam. The primary goal of CERN and the LHC community is to ensure that the collider is operated efficiently and that it achieves nominal performance in the shortest term. Since several years the community has been discussing the directions for maximizing the physics reach of the LHC by upgrading the experiments, in particular ATLAS and CMS, the LHC machine and the CERN proton injector complex, in a phased approach. The first phase of the LHC interaction region upgrade was approved by Council in December 2007. This phase relies on the mature Nb-Ti superconducting magnet technology with the target of increasing the LHC luminosity to 2 to 3 10^34 cm^-2s^-1, while maximising the use of the existing infrastructure. In this report, we present the goals and the proposed conceptual solutions for the LHC IR Upgrade Phase-I which include the recommendations of the conceptual design review

Magnet Acceptance and Allocation at the LHC Magnet Evaluation Board

The normal and superconducting magnets for the LHC ring have been carefully examined to insure that each of about 1900 assemblies is suitable for the operation in the accelerator. Hardware experts and accelerator physicists have contributed to this work that consisted in magnet acceptance, and sorting according to geometry, field quality and quench level. This paper gives a description of the magnet approval mechanism that has been running since four years, reporting in a concise summary the main results achieved

Circuit dissection of the role of somatostatin in itch and pain

Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide

High intensity neutrino oscillation facilities in Europe

The EUROnu project has studied three possible options for future, high intensity neutrino oscillation facilities in Europe. The first is a Super Beam, in which the neutrinos come from the decay of pions created by bombarding targets with a 4 MW proton beam from the CERN High Power Superconducting Proton Linac. The far detector for this facility is the 500 kt MEMPHYS water Cherenkov, located in the Fréjus tunnel. The second facility is the Neutrino Factory, in which the neutrinos come from the decay of μ+ and μ− beams in a storage ring. The far detector in this case is a 100 kt magnetized iron neutrino detector at a baseline of 2000 km. The third option is a Beta Beam, in which the neutrinos come from the decay of beta emitting isotopes, in particular He6 and Ne18, also stored in a ring. The far detector is also the MEMPHYS detector in the Fréjus tunnel. EUROnu has undertaken conceptual designs of these facilities and studied the performance of the detectors. Based on this, it has determined the physics reach of each facility, in particular for the measurement of CP violation in the lepton sector, and estimated the cost of construction. These have demonstrated that the best facility to build is the Neutrino Factory. However, if a powerful proton driver is constructed for another purpose or if the MEMPHYS detector is built for astroparticle physics, the Super Beam also becomes very attractive

Oncogenic LMO3 Collaborates with HEN2 to Enhance Neuroblastoma Cell Growth through Transactivation of Mash1

Expression of Mash1 is dysregulated in human neuroblastoma. We have also reported that LMO3 (LIM-only protein 3) has an oncogenic potential in collaboration with neuronal transcription factor HEN2 in neuroblastoma. However, the precise molecular mechanisms of its transcriptional regulation remain elusive. Here we found that LMO3 forms a complex with HEN2 and acts as an upstream mediator for transcription of Mash1 in neuroblastoma. The high levels of LMO3 or Mash1 mRNA expression were significantly associated with poor prognosis in 100 primary neuroblastomas. The up-regulation of Mash1 remarkably accelerated the proliferation of SH-SY5Y neuroblastoma cells, while siRNA-mediated knockdown of LMO3 induced inhibition of growth of SH-SY5Y cells in association with a significant down-regulation of Mash1. Additionally, overexpression of both LMO3 and HEN2 induced expression of Mash1, suggesting that they might function as a transcriptional activator for Mash1. Luciferase reporter assay demonstrated that the co-expression of LMO3 and HEN2 attenuates HES1 (a negative regulator for Mash1)-dependent reduction of luciferase activity driven by the Mash1 promoter. Chromatin immunoprecipitation assay revealed that LMO3 and HEN2 reduce the amount of HES1 recruited onto putative HES1-binding sites and E-box within the Mash1 promoter. Furthermore, both LMO3 and HEN2 are physically associated with HES1 by immunoprecipitation assay. Thus, our present results suggest that a transcriptional complex of LMO3 and HEN2 may contribute to the genesis and malignant phenotype of neuroblastoma by inhibiting HES1 which suppresses the transactivation of Mash1

Neutrinos from Stored Muons nuSTORM: Expression of Interest

The nuSTORM facility has been designed to deliver beams of electron and muon neutrinos from the decay of a stored muon beam with a central momentum of 3.8 GeV/c and a momentum spread of 10%. The facility is unique in that it will: serve the future long- and short-baseline neutrino-oscillation programmes by providing definitive measurements of electron-neutrino- and muon-neutrino-nucleus cross sections with percent-level precision; allow searches for sterile neutrinos of exquisite sensitivity to be carried out; and constitute the essential first step in the incremental development of muon accelerators as a powerful new technique for particle physics. Of the world's proton-accelerator laboratories, only CERN and FNAL have the infrastructure required to mount nuSTORM. Since no siting decision has yet been taken, the purpose of this Expression of Interest (EoI) is to request the resources required to: investigate in detail how nuSTORM could be implemented at CERN; and develop options for decisive European contributions to the nuSTORM facility and experimental programme wherever the facility is sited. The EoI defines a two-year programme culminating in the delivery of a Technical Design Report

Light sterile neutrino sensitivity at the nuSTORM facility

A facility that can deliver beams of electron and muon neutrinos from the decay of a stored muon beam has the potential to unambiguously resolve the issue of the evidence for light sterile neutrinos that arises in short-baseline neutrino oscillation experiments and from estimates of the effective number of neutrino flavors from fits to cosmological data. In this paper, we show that the nuSTORM facility, with stored muons of 3.8 GeV/c ± 10%, will be able to carry out a conclusive muon neutrino appearance search for sterile neutrinos and test the LSND and MiniBooNE experimental signals with 10σ sensitivity, even assuming conservative estimates for the systematic uncertainties. This experiment would add greatly to our knowledge of the contribution of light sterile neutrinos to the number of effective neutrino flavors from the abundance of primordial helium production and from constraints on neutrino energy density from the cosmic microwave background. The appearance search is complemented by a simultaneous muon neutrino disappearance analysis that will facilitate tests of various sterile neutrino models

Trends in incidence and outcomes of revision total hip arthroplasty in Spain: A population based study

<p>Abstract</p> <p>Background</p> <p>To analyze changes in incidence and outcomes of patients undergoing revision total hip arthroplasty (RTHA) over an 8-year study period in Spain.</p> <p>Methods</p> <p>We selected all surgical admissions in individuals aged ≥ 40 years who underwent RTHA (ICD-9-CM procedure code 81.53) between 2001 and 2008 from the Spanish National Hospital Discharge Database. Age- and sex-specific incidence rates, Charlson co-morbidity index, length of stay (LOS), costs and in-hospital mortality (IHM) were estimated for each year. Multivariate analyses were conducted to asses time trends.</p> <p>Results</p> <p>32, 280 discharges of patients (13, 391 men/18, 889 women) having undergone RTHA were identified. Overall crude incidence showed a small but significant increase from 20.2 to 21.8 RTHA per 100, 000 inhabitants from 2001 to 2008 (p < 0.01).</p> <p>The incidence increased for men (17.7 to 19.8 in 2008) but did not vary for women (22.3 in 2001 and 22.2 in 2008). Greater increments were observed in patients older than 84 years and in the age group 75-84. In 2001, 19% of RTHA patients had a Charlson Index ≥ 1 and this proportion rose to 24.6% in 2008 (p < 0.001). The ratio RTHA/THA remained stable and around 20% in Spain along the entire period</p> <p>The crude overall in-hospital mortality (IHM) increased from 1.16% in 2001 to 1.77% (p = 0.025) in 2008. For both sexes the risk of death was higher with age, with the highest mortality rates found among those aged 85 or over. After multivariate analysis no change was observed in IHM over time. The mean inflation adjusted cost per patient increased by 78.3%, from 9, 375 to 16, 715 Euros from 2001 to 2008.</p> <p>After controlling for possible confounders using Poisson regression models, we observed that the incidence of RTHA hospitalizations significantly increased for men and women over the period 2001 to 2008 (IRR 1.10, 95% CI 1.03-1.18 and 1.08, 95% CI 1.02-1.14 respectively).</p> <p>Conclusions</p> <p>The crude incidence of RTHA in Spain showed a small but significant increase from 2001 to 2008 with concomitant reductions in LOS, significant increase in co-morbidities and cost per patient.</p

ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus

Accumulated knowledge in the molecular processes of tumour development combined with the availability of genetically modified viruses resemble the basis for new promising cancer therapeutics. The main advantages of employing replication-competent viruses are achievement of tumour selective killing and amplification of their oncolytic potential within the tumour mass. In this review, we describe the development of ONYX-015, one of the first and most advanced replication-competent viruses for cancer therapy. We discuss the molecular biology of this therapeutic approach and the interesting results obtained with this virus in clinical trials