π+\pi^+ photoproduction on the proton for photon energies from 0.725 to 2.875 GeV

Differential cross sections for the reaction $\gamma p \to n \pi^+$ have been measured with the CEBAF Large Acceptance Spectrometer (CLAS) and a tagged photon beam with energies from 0.725 to 2.875 GeV. Where available, the results obtained here compare well with previously published results for the reaction. Agreement with the SAID and MAID analyses is found below 1 GeV. The present set of cross sections has been incorporated into the SAID database, and exploratory fits have been made up to 2.7 GeV. Resonance couplings have been extracted and compared to previous determinations. With the addition of these cross sections to the world data set, significant changes have occurred in the high-energy behavior of the SAID cross-section predictions and amplitudes.Comment: 18 pages, 10 figure

New semiquantitative ultrasonographic score for peripheral arterial disease assessment and its association with cardiovascular risk factors

The data concerning the distribution, extent and progression of peripheral arterial disease (PAD), as well as its association with traditional cardiovascular (CV) risk factors, have generally been obtained from studies of patients in advanced stages of the disease undergoing surgical or endovascular treatment. In this study, we have introduced a new semiquantitative ultrasonographic score (ultrasonographic lower limb atherosclerosis (ULLA) score) that is able to categorize lower limb atherosclerotic lesions at all stages of PAD. We then associated these ultrasonographic categories with a CV risk profile. We enrolled 320 consecutive subjects with symptoms suggestive of PAD or with known CV risk factors referring to our angiology unit between 1 July 2014 and 30 June 2015 for ultrasonographic evaluation of the lower limb arteries. Femoropopliteal and run-off segments were categorized together and separately based on their ultrasonographic characteristics. In univariate and multivariate analyses, the ULLA scores were significantly associated with the main CV risk factors, that is, age, male gender, cigarette smoking, arterial hypertension, diabetes, dyslipidemia, sedentary lifestyle, previous CV events and family history of CV disease, and also confirming the specific association of single risk factors with different segments of lower limb arteries. The proposed ULLA score enables a complete evaluation of the entire lower limb atherosclerotic burden, extending the results concerning the association of PAD with CV risk factors to all stages of the disease, including the early stages. It can be feasible that this new score will facilitate better evaluation of the progression of PAD and its prospective role in CV risk stratification

Photodisintegration of 4^4He into p+t

The two-body photodisintegration of $^4$He into a proton and a triton has been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system in the energy range from 0.35 to 1.55 GeV were incident on a liquid $^4$He target. This is the first measurement of the photodisintegration of $^4$He above 0.4 GeV. The differential cross sections for the $\gamma$$^4$He$\to pt$ reaction have been measured as a function of photon-beam energy and proton-scattering angle, and are compared with the latest model calculations by J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the calculations that include three-body mechanisms, thus confirming their importance. These results reinforce the conclusion of our previous study of the three-body breakup of $^3$He that demonstrated the great importance of three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22 postscrip figure

Exclusive Photoproduction of the Cascade (Xi) Hyperons

We report on the first measurement of exclusive Xi-(1321) hyperon photoproduction in gamma p --> K+ K+ Xi- for 3.2 < E(gamma) < 3.9 GeV. The final state is identified by the missing mass in p(gamma,K+ K+)X measured with the CLAS detector at Jefferson Laboratory. We have detected a significant number of the ground-state Xi-(1321)1/2+, and have estimated the total cross section for its production. We have also observed the first excited state Xi-(1530)3/2+. Photoproduction provides a copious source of Xi's. We discuss the possibilities of a search for the recently proposed Xi5-- and Xi5+ pentaquarks.Comment: submitted to Phys. Rev.

Dysbindin Promotes the Post-Endocytic Sorting of G Protein-Coupled Receptors to Lysosomes

BackgroundDysbindin, a cytoplasmic protein long known to function in the biogenesis of specialized lysosome-related organelles (LROs), has been reported to reduce surface expression of D2 dopamine receptors in neurons. Dysbindin is broadly expressed, and dopamine receptors are members of the large family of G protein-coupled receptors (GPCRs) that function in diverse cell types. Thus we asked if dysbindin regulates receptor number in non-neural cells, and further investigated the cellular basis of this regulation.Methodology/principal findingsWe used RNA interference to deplete endogenous dysbindin in HEK293 and HeLa cells, then used immunochemical and biochemical methods to assess expression and endocytic trafficking of epitope-tagged GPCRs. Dysbindin knockdown up-regulated surface expression of D2 receptors compared to D1 receptors, as reported previously in neurons. This regulation was not mediated by a change in D2 receptor endocytosis. Instead, dysbindin knockdown specifically reduced the subsequent trafficking of internalized D2 receptors to lysosomes. This distinct post-endocytic sorting function explained the minimal effect of dysbindin depletion on D1 receptors, which recycle efficiently and traverse the lysosomal pathway to only a small degree. Moreover, dysbindin regulated the delta opioid receptor, a more distantly related GPCR that is also sorted to lysosomes after endocytosis. Dysbindin was not required for lysosomal trafficking of all signaling receptors, however, as its depletion did not detectably affect down-regulation of the EGF receptor tyrosine kinase. Dysbindin co-immunoprecipitated with GASP-1 (or GPRASP-1), a cytoplasmic protein shown previously to modulate lysosomal trafficking of D2 dopamine and delta opioid receptors by direct interaction, and with HRS that is a core component of the conserved ESCRT machinery mediating lysosome biogenesis and sorting.Conclusions/significanceThese results identify a distinct, and potentially widespread function of dysbindin in promoting the sorting of specific GPCRs to lysosomes after endocytosis

Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial

BACKGROUND: The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III trial comparing carboplatin plus paclitaxel to carboplatin plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with ovarian cancer. Due to the paucity of published phase I data on the 3-weekly experimental schedule used, an early safety analysis was planned. METHODS: Patients with ovarian cancer (stage Ic-IV), aged < 75 years, ECOG performance status ≤ 2, were randomized to carboplatin AUC 5 plus paclitaxel 175 mg/m(2), every 3 weeks or to carboplatin AUC 5 plus pegylated liposomal doxorubicin 30 mg/m(2), every 3 weeks. Treatment was planned for 6 cycles. Toxicity was coded according to the NCI-CTC version 2.0. RESULTS: The pre-planned safety analysis was performed in July 2004. Data from the first 50 patients treated with carboplatin plus pegylated liposomal doxorubicin were evaluated. Median age was 60 years (range 34–75). Forty-three patients (86%) completed 6 cycles. Two thirds of the patients had at least one cycle delayed due to toxicity, but 63% of the cycles were administered on time. In most cases the reason for chemotherapy delay was neutropenia or other hematological toxicity. No delay due to palmar-plantar erythrodysesthesia (PPE) was recorded. No toxic death was recorded. Reported hematological toxicities were: grade (G) 3 anemia 16%, G3/G4 neutropenia 36% and 10% respectively, G3/4 thrombocytopenia 22% and 4% respectively. Non-haematological toxicity was infrequent: pulmonary G1 6%, heart rhythm G1 4%, liver toxicity G1 6%, G2 4% and G3 2%. Complete hair loss was reported in 6% of patients, and G1 neuropathy in 2%. PPE was recorded in 14% of the cases (G1 10%, G2 2%, G3 2%). CONCLUSION: This safety analysis shows that the adopted schedule of carboplatin plus pegylated liposomal doxorubicin given every 3 weeks is feasible as first line treatment in ovarian cancer patients, although 37% of the cycles were delayed due to haematological toxicity. Toxicities that are common with standard combination of carboplatin plus paclitaxel (neurotoxicity and hair loss) are infrequent with this experimental schedule, and skin toxicity appears manageable

2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation

HEMA (2-hydroxyethyl methacrylate), a methacrylate commonly used in dentistry, was reported to induce genotoxic effects, but their mechanism is not fully understood. HEMA may be degraded by the oral cavity esterases or through mechanical stress following the chewing process. Methacrylic acid (MAA) is the primary product of HEMA degradation. In the present work we compared cytotoxic and genotoxic effects induced by HEMA and MAA in human gingival fibroblasts (HGFs). A 6-h exposure to HEMA or MAA induced a weak decrease in the viability of HGFs. Neither HEMA nor MAA induced strand breaks in the isolated plasmid DNA, but both compounds evoked DNA damage in HGFs, as evaluated by the alkaline comet assay. Oxidative modifications to the DNA bases were monitored by the DNA repair enzymes Endo III and Fpg. DNA damage induced by HEMA and MAA was not persistent and was removed during a 120 min repair incubation. Results from the neutral comet assay indicated that both compounds induced DNA double strand breaks (DSBs) and they were confirmed by the γ-H2AX assay. Both compounds induced apoptosis and perturbed the cell cycle. Therefore, methacrylic acid, a product of HEMA degradation, may be involved in its cytotoxic and genotoxic action

Genetic variation in Wnt/β-catenin and ER signalling pathways in female and male elite dancers and its associations with low bone mineral density: a cross-section and longitudinal study.

The association of genetic polymorphisms with low bone mineral density in elite athletes have not been considered previously. The present study found that bone mass phenotypes in elite and pre-elite dancers are related to genetic variants at the Wnt/β-catenin and ER pathways. Some athletes (e.g. gymnasts, dancers, swimmers) are at increased risk for low bone mineral density (BMD) which, if untreated, can lead to osteoporosis. To investigate the association of genetic polymorphisms in the oestrogen receptor (ER) and the Wnt/β-catenin signalling pathways with low BMD in elite and pre-elite dancers (impact sport athletes). The study included three phases: (1) 151 elite and pre-elite dancers were screened for the presence of low BMD and traditional osteoporosis risk factors (low body weight, menstrual disturbances, low energy availability); (2) a genetic association study was conducted in 151 elite and pre-elite dancers and age- and sex- controls; (3) serum sclerostin was measured in 101 pre-elite dancers and age- and sex-matched controls within a 3-year period. Eighty dancers revealed low BMD: 56.3% had at least one traditional osteoporosis risk factor, whereas 28.6% did not display any risk factor (37.2% revealed traditional osteoporosis risk factors, but had normal BMD). Body weight, menstrual disturbances and energy availability did not fully predict bone mass acquisition. Instead, genetic polymorphisms in the ER and Wnt/β-catenin pathways were found to be risk factors for low BMD in elite dancers. Sclerostin was significantly increased in dancers compared to controls during the 3-year follow-up (p < 0.05)

Communicating simply, but not too simply: Reporting of participants and speech and language interventions for aphasia after stroke

Purpose: Speech and language pathology (SLP) for aphasia is a complex intervention delivered to a heterogeneous population within diverse settings. Simplistic descriptions of participants and interventions in research hinder replication, interpretation of results, guideline and research developments through secondary data analyses. This study aimed to describe the availability of participant and intervention descriptors in existing aphasia research datasets. Method: We systematically identified aphasia research datasets containing ≥10 participants with information on time since stroke and language ability. We extracted participant and SLP intervention descriptions and considered the availability of data compared to historical and current reporting standards. We developed an extension to the Template for Intervention Description and Replication checklist to support meaningful classification and synthesis of the SLP interventions to support secondary data analysis. Result: Of 11, 314 identified records we screened 1131 full texts and received 75 dataset contributions. We extracted data from 99 additional public domain datasets. Participant age (97.1%) and sex (90.8%) were commonly available. Prior stroke (25.8%), living context (12.1%) and socio-economic status (2.3%) were rarely available. Therapy impairment target, frequency and duration were most commonly available but predominately described at group level. Home practice (46.3%) and tailoring (functional relevance 46.3%) were inconsistently available. Conclusion : Gaps in the availability of participant and intervention details were significant, hampering clinical implementation of evidence into practice and development of our field of research. Improvements in the quality and consistency of participant and intervention data reported in aphasia research are required to maximise clinical implementation, replication in research and the generation of insights from secondary data analysis

Utilising a systematic review-based approach to create a database of individual participant data for meta- and network meta-analyses: the RELEASE database of aphasia after stroke

Background: Collation of aphasia research data across settings, countries and study designs using big data principles will support analyses across different language modalities, levels of impairment, and therapy interventions in this heterogeneous population. Big data approaches in aphasia research may support vital analyses, which are unachievable within individual trial datasets. However, we lack insight into the requirements for a systematically created database, the feasibility and challenges and potential utility of the type of data collated. Aim: To report the development, preparation and establishment of an internationally agreed aphasia after stroke research database of individual participant data (IPD) to facilitate planned aphasia research analyses. Methods: Data were collated by systematically identifying existing, eligible studies in any language (≥10 IPD, data on time since stroke, and language performance) and included sourcing from relevant aphasia research networks. We invited electronic contributions and also extracted IPD from the public domain. Data were assessed for completeness, validity of value-ranges within variables, and described according to pre-defined categories of demographic data, therapy descriptions, and language domain measurements. We cleaned, clarified, imputed and standardised relevant data in collaboration with the original study investigators. We presented participant, language, stroke, and therapy data characteristics of the final database using summary statistics. Results: From 5256 screened records, 698 datasets were potentially eligible for inclusion; 174 datasets (5928 IPD) from 28 countries were included, 47/174 RCT datasets (1778 IPD) and 91/174 (2834 IPD) included a speech and language therapy (SLT) intervention. Participants’ median age was 63 years (interquartile range [53, 72]), 3407 (61.4%) were male and median recruitment time was 321 days (IQR 30, 1156) after stroke. IPD were available for aphasia severity or ability overall (n = 2699; 80 datasets), naming (n = 2886; 75 datasets), auditory comprehension (n = 2750; 71 datasets), functional communication (n = 1591; 29 datasets), reading (n = 770; 12 datasets) and writing (n = 724; 13 datasets). Information on SLT interventions were described by theoretical approach, therapy target, mode of delivery, setting and provider. Therapy regimen was described according to intensity (1882 IPD; 60 datasets), frequency (2057 IPD; 66 datasets), duration (1960 IPD; 64 datasets) and dosage (1978 IPD; 62 datasets). Discussion: Our international IPD archive demonstrates the application of big data principles in the context of aphasia research; our rigorous methodology for data acquisition and cleaning can serve as a template for the establishment of similar databases in other research areas