Photoproduction of the f_{2}(1270) Meson Using the CLAS Detector.

The quark structure of the f_{2}(1270) meson has, for many years, been assumed to be a pure quark-antiquark (qq[over ¯]) resonance with quantum numbers J^{PC}=2^{++}. Recently, it was proposed that the f_{2}(1270) is a molecular state made from the attractive interaction of two ρ mesons. Such a state would be expected to decay strongly to final states with charged pions due to the dominant decay ρ→π^{+}π^{-}, whereas decay to two neutral pions would likely be suppressed. Here, we measure for the first time the reaction γp→π^{0}π^{0}p, using the CEBAF Large Acceptance Spectrometer detector at Jefferson Lab for incident beam energies between 3.6 and 5.4 GeV. Differential cross sections, dσ/dt, for f_{2}(1270) photoproduction are extracted with good precision due to low backgrounds and are compared to theoretical calculations.

Observation of Coulomb-Assisted Nuclear Bound State of Ξ

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

Improved Λp Elastic Scattering Cross Sections between 0.9 and 2.0 GeV/c as a Main Ingredient of the Neutron Star Equation of State.

Strange matter is believed to exist in the cores of neutron stars based on simple kinematics. If this is true, then hyperon-nucleon interactions will play a significant part in the neutron star equation of state. Yet, compared to other elastic scattering processes, there is very little data on Λ-N scattering. This experiment utilized the CEBAF Large Acceptance Spectrometer (CLAS) detector to study the Λp→Λp elastic scattering cross section in the incident Λ momentum range 0.9-2.0 GeV/c. These are the first data on this reaction since the 1970s. The new cross sections have significantly better accuracy and precision than the existing world data, and the techniques developed here can also be used in future experiments.

Search for η

We measured missing mass spectrum of the ^{12}C(γ,p) reaction for the first time in coincidence with potential decay products from η^{'} bound nuclei. We tagged an (η+p) pair associated with the η^{'}N→ηN process in a nucleus. After applying kinematical selections to reduce backgrounds, no signal events were observed in the bound-state region. An upper limit of the signal cross section in the opening angle cosθ_{lab}^{ηp}<-0.9 was obtained to be 2.2 nb/sr at the 90% confidence level. It is compared with theoretical cross sections, whose normalization ambiguity is suppressed by measuring a quasifree η^{'} production rate. Our results indicate a small branching fraction of the η^{'}N→ηN process and/or a shallow η^{'}-nucleus potential.

Cost-effectiveness of an Adjuvanted Recombinant Zoster Vaccine in older adults in the United States.

In the United States, herpes zoster (HZ) and related complications are estimated to result in approximately $1.3 billion in medical care costs and $1.7 billion in indirect costs annually. In this study, we compared the cost-effectiveness of a new Adjuvanted Recombinant Zoster Vaccine (RZV), containing recombinant varicella-zoster virus glycoprotein E and the AS01B Adjuvant System, versus No Vaccine, as well as versus the live attenuated HZ vaccine (Zoster Vaccine Live (ZVL)) in subjects aged 60+ years of age (YOA) and other age cohorts aged 50+ YOA. A multi-cohort Markov model was developed which follows 1 million individuals over their remaining lifetimes from the year of vaccination with annual cycle lengths. Second dose compliance for RZV was assumed to be 69%. Efficacy and waning parameters were derived from clinical trials for both vaccines. Epidemiological parameters, costs and utility model inputs were derived from US-specific population-based data. Costs and outcomes were discounted at 3% per year. Deterministic and probabilistic sensitivity analysis, along with scenario and threshold analysis were carried out to explore the overall uncertainty in the model. The model estimated that, compared to No Vaccine against HZ, RZV would prevent 103,603 HZ cases, 11,197 postherpetic neuralgia (PHN) cases, and 14,455 other complications, at an incremental cost of $11,863 per quality-adjusted life-year saved from a societal perspective. Compared to ZVL, the model estimated that, RZV would prevent 71,638 additional HZ cases, 6403 PHN cases, and over 10,582 other complications, resulting in net total societal cost savings of over $96 million. The results were robust to a wide range of sensitivity analyses. Vaccination against HZ with RZV is cost-effective compared to No Vaccine and cost-saving compared to ZVL, in the US population aged 60+ YOA. Clinicaltrial.gov. registered#: NA.

Differential Cross Section and Photon-Beam Asymmetry for the γ[over →]p → π

Differential cross sections and photon-beam asymmetries for the γ[over →]p→π^{-}Δ^{++}(1232) reaction have been measured for 0.7

Masses and ß-Decay Spectroscopy of Neutron-Rich Odd-Odd

The structure of deformed neutron-rich nuclei in the rare-earth region is of significant interest for both the astrophysics and nuclear structure fields. At present, a complete explanation for the observed peak in the elemental abundances at A∼160 eludes astrophysicists, and models depend on accurate quantities, such as masses, lifetimes, and branching ratios of deformed neutron-rich nuclei in this region. Unusual nuclear structure effects are also observed, such as the unexpectedly low energies of the first 2^{+} levels in some even-even nuclei at N=98. In order to address these issues, mass and ß-decay spectroscopy measurements of the ^{160}Eu_{97} and ^{162}Eu_{99} nuclei were performed at the Californium Rare Isotope Breeder Upgrade radioactive beam facility at Argonne National Laboratory. Evidence for a gap in the single-particle neutron energies at N=98 and for large deformation (ß_{2}∼0.3) is discussed in relation to the unusual phenomena observed at this neutron number.

FRAX calculated without BMD does not correctly identify Caucasian men with densitometric evidence of osteoporosis.

The FRAX algorithm assesses the patient's probability of sustaining an osteoporotic fracture and can be calculated with or without densitometric data. This study seeks to determine whether in men, FRAX scores calculated without BMD, correctly identify patients with BMD-defined osteoporosis. INTRODUCTION: The diagnosis of osteoporosis is based on densitometric data, the presence of a fragility fracture or increased fracture risk. The FRAX algorithm estimates the patient's 10-year probability of sustaining an osteoporotic fracture and can be calculated with or without BMD data. The purpose of this study is to determine whether in men, FRAX calculated without BMD, can correctly identify patients with BMD-defined osteoporosis. METHODS: Retrospectively retrieved data from 726 consecutive Caucasian males, 50 to 70 years old referred to our Osteoporosis Center. RESULTS: In the population studied, 11.8 and 25.3% had BMD-defined osteoporosis when female and male reference populations were used respectively. When the National Osteoporosis Foundation thresholds to initiate treatment are used, only 27% of patients with BMD-defined osteoporosis, but 4% with normal BMD reached/exceeded these thresholds. Lowering the threshold increased sensitivity, but decreased specificity. CONCLUSIONS: Our results suggest that FRAX without BMD is not sensitive/specific enough to be used to identify Caucasian men 50 to 70 years old with BMD-defined osteoporosis.

Oral contraceptive pill use and the susceptibility to markers of exercise-induced muscle damage.

PURPOSE: Firstly, to establish whether oral contraceptive pill (OCP) users are more susceptible to muscle damage compared to non-users, and secondly, to establish whether differences can be attributed to differences in patella tendon properties. METHODS: Nine female OCP users and 9 female non-users participated in the investigation. Combining dynamometry, electromyography and ultrasonography, patella tendon properties and vastus lateralis architectural properties were measured pre and during the first of 6 sets of 12 maximal voluntary eccentric knee extensions. Serum oestrogen levels were measured on the 7th day of the pill cycle and the 14th day of menstrual cycle in OCP users and non-users, respectively. Maximal voluntary isometric knee extension torque loss, creatine kinase and muscle soreness were measured 48 h pre-damage, post-damage, and 48, 96 and 168 h post-damage. RESULTS: Oestrogen levels were significantly lower in OCP users compared to non-users (209 ± 115 and 433 ± 147 pg/ml, respectively, p = 0.004). Proposed determinants of muscle damage, patella tendon stiffness and maximal eccentric torque did not differ between OCP users and non-users. The change in creatine kinase from pre to peak was significantly higher in OCP users compared to non-users (962 ± 968 and 386 ± 474 Ul, respectively, p = 0.016). There were no other differences in markers of muscle damage. CONCLUSION: Although our findings suggest that, when compared to non-users, the OCP may augment the creatine kinase response following eccentric exercise, it does not increase the susceptibility to any other markers of muscle damage.

Interference Effect between ϕ and Λ(1520) Production Channels in the γp→K

The ϕ-Λ(1520) interference effect in the γp→K^{+}K^{-}p reaction has been measured for the first time in the energy range from 1.673 to 2.173 GeV. The relative phases between ϕ and Λ(1520) production amplitudes were obtained in the kinematic region where the two resonances overlap. The measurement results support strong constructive interference when K^{+}K^{-} pairs are observed at forward angles but destructive interference for proton emission at forward angles. Furthermore, the observed interference effect does not account for the sqrt[s]=2.1 GeV bump structure in forward differential cross sections for ϕ photoproduction. This fact suggests possible exotic structures such as a hidden-strangeness pentaquark state, a new Pomeron exchange, or rescattering processes via other hyperon states.

Safety, tolerability, efficacy and pharmacodynamics of the selective JAK1 inhibitor GSK2586184 in patients with systemic lupus erythematosus.

We aimed to evaluate the pharmacodynamics, efficacy, safety and tolerability of the JAK1 inhibitor GSK2586184 in adults with systemic lupus erythematosus (SLE). In this adaptive, randomized, double-blind, placebo-controlled study, patients received oral GSK2586184 50-400 mg, or placebo twice daily for 12 weeks. Primary endpoints included interferon-mediated messenger RNA transcription over time, changes in Safety of Estrogen in Lupus National Assessment-SLE Disease Activity Index score, and number/severity of adverse events. A pre-specified interim analysis was performed when ≥ 5 patients per group completed 2 weeks of treatment. In total, 84-92% of patients were high baseline expressors of the interferon transcriptional biomarkers evaluated. At interim analysis, GSK2586184 showed no significant effect on mean interferon transcriptional biomarker expression (all panels). The study was declared futile and recruitment was halted at 50 patients. Shortly thereafter, significant safety data were identified, including elevated liver enzymes in six patients (one confirmed and one suspected case of Drug Reaction with Eosinophilia and Systemic Symptoms), leading to immediate dosing cessation. Safety of Estrogen in Lupus National Assessment-SLE Disease Activity Index scores were not analysed due to the small number of patients completing the study. The study futility and safety data described for GSK2586184 do not support further evaluation in patients with SLE. Study identifiers: GSK Study JAK115919; ClinicalTrials.gov identifier: NCT01777256.

Subcutaneous Administration of Otelixizumab is Limited by Injection Site Reactions: Results of an Exploratory Study in Type 1 Diabetes Mellitus Patients.

Targeting CD3 antigens on human T lymphocytes with monoclonal antibodies has been shown to reduce the rate of decline of C-peptides in recent-onset type 1 diabetes mellitus patients. However, effective doses are associated with infusion reactions typical of "cytokine release syndrome" and appear to be dose-limiting when administered as short-duration infusions. A possible alternative approach, which may reduce the rate of T cell activation and consequent systemic cytokine release, is to inject subcutaneously. We investigated single- and repeat-dose subcutaneous administration of the anti-CD3 monoclonal antibody otelixizumab in small cohorts of patients with type 1 diabetes. Transient reductions in free or unbound CD3 antigen on CD4+ and CD8+ cells and absolute lymphocyte count were observed in the blood of these patients during treatment, consistent with the known mechanism of action of otelixizumab and other anti-CD3 monoclonal antibodies. This was despite the very low systemic exposure of antibodies measured during the same time period. With the exception of sporadic headaches, other symptoms associated with cytokine release syndrome, such as fever, nausea, vomiting, myalgia, and arthralgia, were absent in treated patients. However, treatment-related injection site reactions were consistently observed. The reactions were erythematous and their sizes were dose-dependent; in some cases, reactions persisted for up to 2 weeks following the start of treatment. While patients responded well to topical corticosteroid treatment and prophylaxis reduced the intensity of injection site reactions, the reactions were considered dose-limiting and higher doses were not investigated.

Muscle Damage following Maximal Eccentric Knee Extensions in Males and Females.

AIM: To investigate whether there is a sex difference in exercise induced muscle damage. MATERIALS AND METHOD: Vastus Lateralis and patella tendon properties were measured in males and females using ultrasonography. During maximal voluntary eccentric knee extensions (12 reps x 6 sets), Vastus Lateralis fascicle lengthening and maximal voluntary eccentric knee extensions torque were recorded every 10° of knee joint angle (20-90°). Isometric torque, Creatine Kinase and muscle soreness were measured pre, post, 48, 96 and 168 hours post damage as markers of exercise induced muscle damage. RESULTS: Patella tendon stiffness and Vastus Lateralis fascicle lengthening were significantly higher in males compared to females (p<0.05). There was no sex difference in isometric torque loss and muscle soreness post exercise induced muscle damage (p>0.05). Creatine Kinase levels post exercise induced muscle damage were higher in males compared to females (p<0.05), and remained higher when maximal voluntary eccentric knee extension torque, relative to estimated quadriceps anatomical cross sectional area, was taken as a covariate (p<0.05). CONCLUSION: Based on isometric torque loss, there is no sex difference in exercise induced muscle damage. The higher Creatine Kinase in males could not be explained by differences in maximal voluntary eccentric knee extension torque, Vastus Lateralis fascicle lengthening and patella tendon stiffness. Further research is required to understand the significant sex differences in Creatine Kinase levels following exercise induced muscle damage.

Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled phase IIa study.

BACKGROUND: GSK2586184 is a selective oral Janus kinase (JAK)1 inhibitor being evaluated as a treatment for moderate-to-severe plaque-type psoriasis. OBJECTIVES: To assess the relationship between dose of GSK2586184 and clinical response, primarily by the Psoriasis Area Severity Index (PASI). METHODS: Sixty patients with moderate-to-severe plaque psoriasis were randomized to cohort A: 100 mg, 200 mg or 400 mg GSK2586184 twice daily or placebo; and eight were randomized to open-label cohort B, a small exploratory cohort treated with 400 mg GSK2586184 twice daily, to explore differential gene expression. RESULTS: At week 12, a 75% reduction in PASI (PASI 75) response rates in the intent-to-treat population were 0% in the placebo group compared with 13%, 25% and 57% in the 100 mg, 200 mg and 400 mg GSK2586184 twice-daily groups, respectively. Increases in the proportion of PASI 75 responses were seen across all dose levels by week 4. Improvement in itch and quality of life were observed at all doses relative to placebo with the greatest improvement seen in the 400-mg dose group. Overall, the incidence of adverse events (AEs) was similar across treatment groups, and no relationship between frequency of AE and GSK2586184 dose was identified. Differential gene expression was observed in involved and uninvolved skin at baseline and in involved skin after 2 weeks of treatment with GSK2586184. CONCLUSIONS: Our study demonstrates that 12 weeks of treatment with GSK2586184 resulted in clinical improvement and was generally well tolerated in patients with moderate-to-severe plaque-type psoriasis.

Gender differences in fascicular lengthening during eccentric contractions: the role of the patella tendon stiffness.

AIM: Elastic tendons have been suggested to attenuate fascicle lengthening during eccentric contractions; however, there is no in vivo evidence to support this hypothesis. Therefore, the aim of this study was to determine whether patella tendon stiffness modulates vastus lateralis (VL) fascicle lengthening during eccentric contractions in males and females. METHOD: Vastus lateralis and patella tendon properties were measured in males and females owing to previously reported intrinsic gender differences in tendon properties. During maximal voluntary eccentric knee extensions, VL fascicle lengthening and torque were recorded at every 10° (range of motion 20-90°). RESULTS: A significant correlation between maximal patella tendon stiffness and change in fascicle length (r=0.476, P=0.023) was observed. Similarly, there was a significant correlation between maximal Young's modulus and change in fascicle length (r=0.470, P=0.049). As expected, patella tendon stiffness and Young's modulus were significantly higher in males compared with females (P<0.05). Interestingly, change in VL fascicle length during the eccentric contractions was significantly greater in males compared with females (P<0.05). Based on patella tendon moment arm measurements, VL muscle-tendon unit elongation was estimated to be significantly greater in males compared with females (5.24 and 4.84 cm respectively). CONCLUSION: The significant difference in fascicle lengthening during eccentric contractions may be partly explained by the significantly higher patella tendon moment arm, patella tendon stiffness and Young's modulus found in males compared with females. The current study provides in vivo evidence to support the hypothesis that the tendon acts as a 'mechanical buffer' during eccentric contractions.

Qualification of cardiac troponins for nonclinical use: a regulatory perspective.

The US Food and Drug Administration (FDA) Biomarker Qualification Review Team presents its perspective on the recent qualification of cardiac troponins for use in nonclinical safety assessment studies. The goal of this manuscript is to provide greater transparency into the qualification process and factors that were considered in reaching a regulatory decision. This manuscript includes an overview of the data that were submitted and a discussion of the strengths and shortcomings of these data supporting the qualification decision. The cardiac troponin submission is the first literature-based biomarker application to be reviewed by the FDA and insights gained from this experience may aid future submissions and help streamline the characterization and qualification of future biomarkers.

Spin-density matrix elements for γp→K*0Σ+ at Eγ=1.85-3.0 GeV with evidence for the κ(800) meson exchange.

The exclusive reaction γp→K(+)π(-)Σ(+) was measured for the first time using linearly polarized photons at beam energies from 1.85 to 2.96 GeV. Angular distributions in the rest frame of the K(+)π(-) system were fitted to extract spin-density matrix elements of the K(*0) decay. The measured parity spin asymmetry shows that natural-parity exchange is dominant in this reaction. This result clearly indicates the need for t-channel exchange of the κ(800) scalar meson.

EVerT: cryotherapy versus salicylic acid for the treatment of verrucae--a randomised controlled trial.

OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of cryotherapy using liquid nitrogen versus patient daily self-treatment with 50% salicylic acid for the treatment of verrucae (plantar warts). DESIGN: A multicentre, pragmatic, open, two-armed randomised controlled trial with an economic evaluation. Randomisation was simple, with the allocation sequence generated by a computer in a 1 : 1 ratio. SETTING: Podiatry clinics, university podiatry schools and primary care in England, Scotland and Ireland. PARTICIPANTS: Patients were eligible if they presented with a verruca which, in the opinion of the health-care professional, was suitable for treatment with both salicylic acid and cryotherapy, and were aged 12 years and over. INTERVENTIONS: Cryotherapy using liquid nitrogen delivered by a health-care professional compared with daily patient self-treatment with 50% salicylic acid (Verrugon, William Ransom & Son Plc, Hitchin, UK) for a maximum of 8 weeks. MAIN OUTCOME MEASURES: The primary outcome was complete clearance of all verrucae at 12 weeks. Secondary outcomes were complete clearance of all verrucae at 12 weeks, controlling for age, whether or not the verrucae had been previously treated and type of verrucae, with a second model to explore the effect of patient preferences, time to clearance of verrucae, clearance of verrucae at 6 months, number of verrucae at 12 weeks and patient satisfaction with the treatment. RESULTS: In total, 240 eligible patients were recruited, with 117 patients allocated to the cryotherapy group and 123 to the salicylic acid group. There was no evidence of a difference in clearance rates between the treatment groups in the primary outcome [17/119 (14.3%) in the salicylic acid group vs 15/110 (13.6%) in the cryotherapy group; p = 0.89]. The results of the study did not change when controlled for age, whether or not the verrucae had been previously treated and type of verrucae, or when patient preferences were explored. There was no evidence of a difference in time to clearance of verrucae between the two groups [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.51 to 1.25; p = 0.33] or in the clearance of verrucae at 6 months (33.7% cryotherapy vs 30.5% salicylic acid). There was no evidence of a difference in the number of verrucae at 12 weeks between the two groups (incidence rate ratio 1.08, 95% CI 0.81 to 1.43; p = 0.62). Nineteen participants reported 28 adverse events, 14 in each group, with two treatment-related non-serious adverse events in the cryotherapy group. Cryotherapy was also associated with higher mean costs per additional healed patient (£101.17, 95% bias-corrected and accelerated CI £85.09 to £117.26). The probability of cryotherapy being cost-effective is 40% for a range of willingness-to-pay thresholds of £15,000-30,000 per patient healed. CONCLUSIONS: There is no evidence for a difference in terms of clearance of verrucae between cryotherapy and salicylic acid (at both 12 weeks and 6 months), number of verrucae at 12 weeks and time to clearance of verrucae. Cryotherapy was associated with higher mean costs per additional healed patient compared with salicylic acid. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18994246. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 32. See the HTA programme website for further project information.

Identification of community-residing individuals with dementia and their unmet needs for care.

BACKGROUND: Innovative approaches to the widespread delivery of evidence-based dementia care are needed. The aims of this study were to determine whether a telephone screening method could efficiently identify individuals in the community in need of care for dementia and to develop a multidimensional needs assessment tool for identifying the type and frequency of unmet needs related to memory disorders in the home setting. METHODS: This was a cross-sectional evaluation of 292 community-residing individuals aged 70 and older in Maryland. Participants were given a brief cognitive telephone screen. A subsample (n=43) received a comprehensive in-home assessment for dementia and dementia-related needs. Cognitive, functional, behavioral, and clinical factors were assessed. The Johns Hopkins Dementia Care Needs Assessment (JHDCNA) was used to identify unmet needs related to dementia. RESULTS: Telephone screening for the sample took 350 h, and 27% screened positive for dementia. Virtually all participants with dementia who received an in-home assessment had at least one unmet need, with the most frequent unmet needs being for a dementia workup, general medical care, environmental safety, assistance with ADL impairments, and access to meaningful activities. Caregivers, when present, also had a number of unmet needs, with the most common being caregiver education about dementia, knowledge of community resources, and caregiver mental health care. CONCLUSIONS: Effective and efficient means for identifying community-residing individuals with dementia are needed so that dementia care interventions can be provided to address unmet care needs of patients and their caregivers.