Simultaneous analysis of elastic scattering and transfer/breakup channels for the 6He+208Pb reaction at energies near the Coulomb barrier

The elastic and alpha-production channels for the 6He+208Pb reaction are investigated at energies around the Coulomb barrier (E_{lab}=14, 16, 18, 22, and 27 MeV). The effect of the two-neutron transfer channels on the elastic scattering has been studied within the Coupled-Reaction-Channels (CRC) method. We find that the explicit inclusion of these channels allows a simultaneous description of the elastic data and the inclusive alpha cross sections at backward angles. Three-body Continuum-Discretized Coupled-Channels (CDCC) calculations are found to reproduce the elastic data, but not the transfer/breakup data. The trivially-equivalent local polarization potential (TELP) derived from the CRC and CDCC calculations are found to explain the features found in previous phenomenological optical model calculations for this system.Comment: 7 pages, 6 figures (replaced with updated version

The short term debt vs. long term debt puzzle: a model for the optimal mix

This paper argues that the existing finance literature is inadequate with respect to its coverage of capital structure of small and medium sized enterprises (SMEs). In particular it is argued that the cost of equity (being both conceptually ill defined and empirically non quantifiable) is not applicable to the capital structure decisions for a large proportion of SMEs and the optimal capital structure depends only on the mix of short and long term debt. The paper then presents a model, developed by practitioners for optimising the debt mix and demonstrates its practical application using an Italian firm's debt structure as a case study

A tool to improve pre-selection for deep brain stimulation in patients with Parkinson’s disease

Determining the eligibility of patients with Parkinson’s disease (PD) for deep brain stimulation (DBS) can be challenging for general (non-specialised) neurologists. We evaluated the use of an online screening tool (Stimulus) that aims to support appropriate referral to a specialised centre for the further evaluation of DBS. Implementation of the tool took place via an ongoing European multicentre educational programme, currently completed in 15 DBS centres with 208 referring neurologists. Use of the tool in daily practice was monitored via an online data capture programme. Selection decisions of patients referred with the assistance of the Stimulus tool were compared to those of patients outside the screening programme. Three years after the start of the programme, 3,128 patient profiles had been entered. The intention for referral was made for 802 patients and referral intentions were largely in accordance with the tool recommendations. Follow-up at 6 months showed that actual referral took place in only 28%, predominantly due to patients’ reluctance to undergo brain surgery. In patients screened with the tool and referred to a DBS centre, the acceptance rate was 77%, significantly higher than that of the unscreened population (48%). The tool showed a sensitivity of 99% and a specificity of 12% with a positive and negative predictive value of 79 and 75%, respectively. The Stimulus tool is useful in assisting general neurologists to identify appropriate candidates for DBS consideration. The principal reason for not referring potentially eligible patients is their reluctance to undergo brain surgery

Stability of Terrestrial Planets in the Habitable Zone of Gl 777 A, HD 72659, Gl 614, 47 Uma and HD 4208

We have undertaken a thorough dynamical investigation of five extrasolar planetary systems using extensive numerical experiments. The systems Gl 777 A, HD 72659, Gl 614, 47 Uma and HD 4208 were examined concerning the question of whether they could host terrestrial like planets in their habitable zones (=HZ). First we investigated the mean motion resonances between fictitious terrestrial planets and the existing gas giants in these five extrasolar systems. Then a fine grid of initial conditions for a potential terrestrial planet within the HZ was chosen for each system, from which the stability of orbits was then assessed by direct integrations over a time interval of 1 million years. The computations were carried out using a Lie-series integration method with an adaptive step size control. This integration method achieves machine precision accuracy in a highly efficient and robust way, requiring no special adjustments when the orbits have large eccentricities. The stability of orbits was examined with a determination of the Renyi entropy, estimated from recurrence plots, and with a more straight forward method based on the maximum eccentricity achieved by the planet over the 1 million year integration. Additionally, the eccentricity is an indication of the habitability of a terrestrial planet in the HZ; any value of e>0.2 produces a significant temperature difference on a planet's surface between apoapse and periapse. The results for possible stable orbits for terrestrial planets in habitable zones for the five systems are summarized as follows: for Gl 777 A nearly the entire HZ is stable, for 47 Uma, HD 72659 and HD 4208 terrestrial planets can survive for a sufficiently long time, while for Gl 614 our results exclude terrestrial planets moving in stable orbits within the HZ.Comment: 14 pages, 18 figures submitted to A&

A DEBRIS disk around the planet hosting M-star GJ 581 spatially resolved with Herschel

Debris disks have been found primarily around intermediate and solar mass stars (spectral types A-K) but rarely around low mass M-type stars. We have spatially resolved a debris disk around the remarkable M3-type star GJ 581 hosting multiple planets using deep PACS images at 70, 100 and 160 μm as part of the DEBRIS Program on the Herschel Space Observatory. This is the second spatially resolved debris disk found around an M-type star, after the one surrounding the young star AU Mic (12 Myr). However, GJ 581 is much older (2-8 Gyr), and is X-ray quiet in the ROSAT data. We fit an axisymmetric model of the disk to the three PACS images and found that the best fit model is for a disk extending radially from 25 ± 12 AU to more than 60 AU. Such a cold disk is reminiscent of the Kuiper belt but it surrounds a low mass star (0.3 Mθ) and its fractional dust luminosity Ldust/L * of ∼ 10-4 is much higher. The inclination limits of the disk found in our analysis make the masses of the planets small enough to ensure the long-term stability of the system according to some dynamical simulations. The disk is collisionally dominated down to submicron-sized grains and the dust cannot be expelled from the system by radiation or wind pressures because of the low luminosity and low X-ray luminosity of GJ 581. We suggest that the correlation between low-mass planets and debris disks recently found for G-type stars also applies to M-type stars. Finally, the known planets, of low masses and orbiting within 0.3 AU from the star, cannot dynamically perturb the disk over the age of the star, suggesting that an additional planet exists at larger distance that is stirring the disk to replenish the dust

Maturation of the Language Network: From Inter- to Intrahemispheric Connectivities

Language development must go hand-in-hand with brain maturation. Little is known about how the brain develops to serve language processing, in particular, the processing of complex syntax, a capacity unique to humans. Behavioral reports indicate that the ability to process complex syntax is not yet adult-like by the age of seven years. Here, we apply a novel method to demonstrate that the basic neural basis of language, as revealed by low frequency fluctuation stemming from functional MRI data, differs between six-year-old children and adults in crucial aspects. Although the classical language regions are actively in place by the age of six, the functional connectivity between these regions clearly is not. In contrast to adults who show strong connectivities between frontal and temporal language regions within the left hemisphere, children's default language network is characterized by a strong functional interhemispheric connectivity, mainly between the superior temporal regions. These data indicate a functional reorganization of the neural network underlying language development towards a system that allows a close interplay between frontal and temporal regions within the left hemisphere

Effectiveness of an mHealth intervention combining a smartphone app and smart band on body composition in an overweight and obese population: Randomized controlled trial (EVIDENT 3 study)

Background: Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear. Objective: This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese. Methods: A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire. Results: The mHealth intervention produced a greater loss of body weight (–1.97 kg, 95% CI –2.39 to –1.54) relative to standard counselling at 3 months (–1.13 kg, 95% CI –1.56 to –0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; –1.84 kg, 95% CI –2.48 to –1.20), percentage of body fat (PBF; –1.22%, 95% CI –1.82% to 0.62%), and BMI (–0.77 kg/m2, 95% CI –0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of –1.18 kg (95% CI –2.30 to –0.06) and BMI of –0.47 kg/m2 (95% CI –0.80 to –0.13), whereas the obese group only experienced a change in BMI of –0.53 kg/m2 (95% CI –0.86 to –0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of –1.03 kg (95% CI –1.74 to –0.33), PBF of –0.76% (95% CI –1.32% to –0.20%), and BMI of –0.5 kg/m2 (95% CI –0.83 to –0.19). Conclusions: The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m2 and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect

Safety and efficacy of GABAA α5 antagonist S44819 in patients with ischaemic stroke: a multicentre, double-blind, randomised, placebo-controlled trial

Background: S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke. Methods: RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18–85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7–20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0–1 versus 2–6 and 0–2 versus 3–6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov, NCT02877615. Findings: Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64–1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81–1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0–2 vs 3–6 or mRS 0–1 vs 2–6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2–8] in 150 mg S44819 group, 4 [2–7] in 300 mg S44819 group, and 4 [2–6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0–26·0] in 150 mg S44819 group, 23·0 [19·0–26·5] in 300 mg S44819 group, and 22·0 [17·0–26·0] in placebo group), time needed to complete parts A (50 s [IQR 42–68] in 150 mg S44819 group, 49 s [36–63] in 300 mg S44819 group, and 50 s [38–68] in placebo group) and B (107 s [81–144] in 150 mg S44819 group, 121 s [76–159] in 300 mg S44819 group, and 130 s [86–175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60–100] in 150 mg S44819 group, 90 [70–100] in 300 mg S44819 group, and 90 [70–100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths. Interpretation: There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans. Funding: Servier

Computing Highly Correlated Positions Using Mutual Information and Graph Theory for G Protein-Coupled Receptors

G protein-coupled receptors (GPCRs) are a superfamily of seven transmembrane-spanning proteins involved in a wide array of physiological functions and are the most common targets of pharmaceuticals. This study aims to identify a cohort or clique of positions that share high mutual information. Using a multiple sequence alignment of the transmembrane (TM) domains, we calculated the mutual information between all inter-TM pairs of aligned positions and ranked the pairs by mutual information. A mutual information graph was constructed with vertices that corresponded to TM positions and edges between vertices were drawn if the mutual information exceeded a threshold of statistical significance. Positions with high degree (i.e. had significant mutual information with a large number of other positions) were found to line a well defined inter-TM ligand binding cavity for class A as well as class C GPCRs. Although the natural ligands of class C receptors bind to their extracellular N-terminal domains, the possibility of modulating their activity through ligands that bind to their helical bundle has been reported. Such positions were not found for class B GPCRs, in agreement with the observation that there are not known ligands that bind within their TM helical bundle. All identified key positions formed a clique within the MI graph of interest. For a subset of class A receptors we also considered the alignment of a portion of the second extracellular loop, and found that the two positions adjacent to the conserved Cys that bridges the loop with the TM3 qualified as key positions. Our algorithm may be useful for localizing topologically conserved regions in other protein families

Overview of the TCV tokamak experimental programme

The tokamak a configuration variable (TCV) continues to leverage its unique shaping capabilities, flexible heating systems and modern control system to address critical issues in preparation for ITER and a fusion power plant. For the 2019-20 campaign its configurational flexibility has been enhanced with the installation of removable divertor gas baffles, its diagnostic capabilities with an extensive set of upgrades and its heating systems with new dual frequency gyrotrons. The gas baffles reduce coupling between the divertor and the main chamber and allow for detailed investigations on the role of fuelling in general and, together with upgraded boundary diagnostics, test divertor and edge models in particular. The increased heating capabilities broaden the operational regime to include T (e)/T (i) similar to 1 and have stimulated refocussing studies from L-mode to H-mode across a range of research topics. ITER baseline parameters were reached in type-I ELMy H-modes and alternative regimes with \u27small\u27 (or no) ELMs explored. Most prominently, negative triangularity was investigated in detail and confirmed as an attractive scenario with H-mode level core confinement but an L-mode edge. Emphasis was also placed on control, where an increased number of observers, actuators and control solutions became available and are now integrated into a generic control framework as will be needed in future devices. The quantity and quality of results of the 2019-20 TCV campaign are a testament to its successful integration within the European research effort alongside a vibrant domestic programme and international collaborations