A Prospective Open-Label Observational Study of a Buffered Soluble 70 mg Alendronate Effervescent Tableton Upper Gastrointestinal Safety and Medication Errors: The GastroPASS Study

Upper gastrointestinal (GI) side effects are a main reason for discontinuing bisphosphonate treatment, an important therapeuticoption for osteoporosis patients. Consequently, the development of novel formulations with improved tolerability is warranted. Inthis multicenter prospective, observational, postauthorization safety study conducted in Italy and Spain, postmenopausal women(PMW) with osteoporosis (naïve to bisphosphonates) were treated weekly with a buffered soluble alendronate 70 mg effervescent(ALN-EFF) tablet (Binosto®) and followed for 12 3 months. Information was collected on adverse events (AEs), medication errors,persistence, and compliance using the Morisky-Green questionnaire. Patients (N = 1028) aged 67 9 years (mean SD) receivedALN-EFF weekly. The cumulative incidence of upper GI AEs (oesophageal toxicity, gastritis, gastric ulcers, and duodenitis) relatedto ALN-EFF (primary endpoint) was 9.6% (95% condence interval [CI] 7.9–11.6%), the vast majority being of mild intensity. The mostfrequently occurring upper GI AEs related to ALN-EFF were dyspepsia (2.7%), gastroesophageal reux disease (2.4%), and nausea(2.2%). None of the relevant upper GI AEs listed in the primary endpoint and no serious AEs were reported. At least one medicationerror occurred in 29.9% (95% CI 27.1–32.8%) of patients. However, the majority of medication errors were associated with adminis-tration instructions applicable to any oral bisphosphonate and only seven medication errors were associated with the ALN-EFF for-mulation. ALN-EFF was discontinued in 209 of 1028 (20.3%) patients. The most frequent reasons for discontinuation were AEsrelated to ALN-EFF (46.9%) and patients’ decision (42.6%). Compliance with ALN-EFF was high, reected by a mean Morisky-Greenscore of 92.8 18.6. PMW with osteoporosis treated with ALN-EFF in a real-world setting experienced few upper GI AEs. In addition,they had a low discontinuation and high compliance compared with other formulations, suggesting that ALN-EFF may increasepatient satisfaction and therefore long-term adherence and efcac

Probing RS scenarios of flavour at LHC via leptonic channels

We study a purely leptonic signature of the Randall-Sundrum scenario with Standard Model fields in the bulk at LHC: the contribution from the exchange of Kaluza-Klein (KK) excitations of gauge bosons to the clear Drell-Yan reaction. We show that this contribution is detectable (even with the low luminosities of the LHC initial regime) for KK masses around the TeV scale and for sufficiently large lepton couplings to KK gauge bosons. Such large couplings can be compatible with ElectroWeak precision data on the Zff coupling in the framework of the custodial O(3) symmetry recently proposed, for specific configurations of lepton localizations (along the extra dimension). These configurations can simultaneously reproduce the correct lepton masses, while generating acceptably small Flavour Changing Neutral Current (FCNC) effects. This LHC phenomenological analysis is realistic in the sense that it is based on fermion localizations which reproduce all the quark/lepton masses plus mixing angles and respect FCNC constraints in both the hadron and lepton sectors.Comment: 15 pages, 6 Figures, Latex fil

GRB Polarimetry with POET

POET (Polarimeters for Energetic Transients) represents a concept for a Small Explorer (SMEX) satellite mission, whose principal scientific goal is to understand the structure of GRB sources through sensitive X‐ray and γ‐ray polarization measurements. The payload consists of two wide field‐of‐view (FoV) instruments: a Low Energy Polarimeter (LEP) capable of polarization measurements in the energy range from 2–15 keV and a high energy polarimeter (Gamma‐Ray Polarimeter Experiment or GRAPE) that would measure polarization in the 60–500 keV energy range. The POET spacecraft provides a zenith‐pointed platform for maximizing the exposure to deep space. Spacecraft rotation provides a means of effectively dealing with any residual systematic effects in the polarization response. POET provides sufficient sensitivity and sky coverage to measure statistically significant polarization (for polarization levels in excess of 20%) for ∼80 GRBs in a two‐year mission. High energy polarization data would also be obtained for SGRs, solar flares, pulsars and other sources of astronomical interest

Influence of sun zenith angle on canopy clumping and the resulting impacts on photosynthesis

Addressing the impact of vegetation architecture on shortwave radiation transfer in land surface models is important for accurate weather forecasting, carbon budget estimates, and climate predictions. This paper investigates to what extent it is possible to retrieve structural parameters of two different parameterization schemes from direct transmittance derived from digital hemispherical photography and 3D radiative transfer modeling for two study sites with different vegetation canopy architectures. Neglecting the representation of 3D canopy structure in radiative transfer schemes leads to significant errors in shortwave radiation partitioning (up to 3.5 times more direct transmittance in the 3D model). Structural parameters, referred to as whole canopy ‘clumping indices’, were obtained in order to evaluate the impact of angular variation in clumping on shortwave radiation transfer. Impacts on photosynthesis were evaluated at site level with the UKESM land surface model, JULES. A comparison between flux tower derived and modeled photosynthesis indicates that considering zenith angular variations of structural parameters in the radiative transfer scheme of the UKESM land surface model significantly improves photosynthesis prediction in light limited ecosystems (from RMSE = 2.91 mol CO2.m-2.s-1 to RMSE = 1.51 mol CO2.m-2.s-1, 48% smaller), typically with enhanced photosynthesis from bottom layers

OxyCAP UK: Oxyfuel Combustion - academic Programme for the UK

The OxyCAP-UK (Oxyfuel Combustion - Academic Programme for the UK) programme was a £2 M collaboration involving researchers from seven UK universities, supported by E.On and the Engineering and Physical Sciences Research Council. The programme, which ran from November 2009 to July 2014, has successfully completed a broad range of activities related to development of oxyfuel power plants. This paper provides an overview of key findings arising from the programme. It covers development of UK research pilot test facilities for oxyfuel applications; 2-D and 3-D flame imaging systems for monitoring, analysis and diagnostics; fuel characterisation of biomass and coal for oxyfuel combustion applications; ash transformation/deposition in oxyfuel combustion systems; materials and corrosion in oxyfuel combustion systems; and development of advanced simulation based on CFD modelling

Continuous Interaction with a Virtual Human

Attentive Speaking and Active Listening require that a Virtual Human be capable of simultaneous perception/interpretation and production of communicative behavior. A Virtual Human should be able to signal its attitude and attention while it is listening to its interaction partner, and be able to attend to its interaction partner while it is speaking – and modify its communicative behavior on-the-fly based on what it perceives from its partner. This report presents the results of a four week summer project that was part of eNTERFACE’10. The project resulted in progress on several aspects of continuous interaction such as scheduling and interrupting multimodal behavior, automatic classification of listener responses, generation of response eliciting behavior, and models for appropriate reactions to listener responses. A pilot user study was conducted with ten participants. In addition, the project yielded a number of deliverables that are released for public access

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. METHODS: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. FINDINGS: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. INTERPRETATION: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. FUNDING: National Institute for Health Research, Health Technology Assessment programme

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson