Mapping deuterated methanol toward L1544: I. Deuterium fraction and comparison with modeling

The study of deuteration in pre-stellar cores is important to understand the physical and chemical initial conditions in the process of star formation. In particular, observations toward pre-stellar cores of methanol and deuterated methanol, solely formed on the surface of dust grains, may provide useful insights on surface processes at low temperatures. Here we analyze maps of CO, methanol, formaldehyde and their deuterated isotopologues toward a well-known pre-stellar core. This study allows us to test current gas-dust chemical models. Single-dish observations of CH$_3$OH, CH$_2$DOH, H$_2$CO, H_2\,^{13}CO, HDCO, D$_2$CO and C$^{17}$O toward the prototypical pre-stellar core L1544 were performed at the IRAM 30 m telescope. We analyze their column densities, distributions, and compare these observations with gas-grain chemical models. The maximum deuterium fraction derived for methanol is [CH$_2$DOH]/[CH$_3$OH] $\sim$ 0.08$\pm$0.02, while the measured deuterium fractions of formaldehyde at the dust peak are [HDCO]/[H$_2$CO] $\sim$ 0.03$\pm$0.02, [D$_2$CO]/[H$_2$CO] $\sim$ 0.04$\pm$0.03 and [D$_2$CO]/[HDCO] $\sim$ 1.2$\pm$0.3. Observations differ significantly from the predictions of models, finding discrepancies between a factor of 10 and a factor of 100 in most cases. It is clear though that to efficiently produce methanol on the surface of dust grains, quantum tunneling diffusion of H atoms must be switched on. It also appears that the currently adopted reactive desorption efficiency of methanol is overestimated and/or that abstraction reactions play an important role. More laboratory work is needed to shed light on the chemistry of methanol, an important precursor of complex organic molecules in space.Comment: Accepted for publication in A&

NH_3(1_0-0_0) in the pre-stellar core L1544

Pre-stellar cores represent the initial conditions in the process of star and planet formation, therefore it is important to study their physical and chemical structure. Because of their volatility, nitrogen-bearing molecules are key to study the dense and cold gas present in pre-stellar cores. The NH_3 rotational transition detected with Herschel-HIFI provides a unique combination of sensitivity and spectral resolution to further investigate physical and chemical processes in pre-stellar cores. Here we present the velocity-resolved Herschel-HIFI observations of the ortho-NH_3(1_0-0_0) line at 572 GHz and study the abundance profile of ammonia across the pre-stellar core L1544 to test current theories of its physical and chemical structure. Recently calculated collisional coefficients have been included in our non-LTE radiative transfer code to reproduce Herschel observations. A gas-grain chemical model, including spin-state chemistry and applied to the (static) physical structure of L1544 is also used to infer the abundance profile of ortho-NH_3 . The hyperfine structure of ortho-NH_3(1_0-0_0) is resolved for the first time in space. All the hyperfine components are strongly self-absorbed. The profile can be reproduced if the core is contracting in quasi-equilibrium, consistent with previous work, and if the NH_3 abundance is slightly rising toward the core centre, as deduced from previous interferometric observations of para-NH_3(1,1). The chemical model overestimates the NH_3 abundance at radii between ~ 4000 and 15000 AU by about two orders of magnitude and underestimates the abundance toward the core centre by more than one order of magnitude. Our observations show that chemical models applied to static clouds have problems in reproducing NH_3 observations.Comment: accepted for publication in A&A Letter

Modelling of 3D fields due to ferritic inserts and test blanket modules in toroidal geometry at ITER

Computations in toroidal geometry are systematically performed for the plasma response to 3D magnetic perturbations produced by ferritic inserts (FIs) and test blanket modules (TBMs) for four ITER plasma scenarios: the 15 MA baseline, the 12.5 MA hybrid, the 9 MA steady state, and the 7.5 MA half-field helium plasma. Due to the broad toroidal spectrum of the FI and TBM fields, the plasma response for all the n = 1-6 field components are computed and compared. The plasma response is found to be weak for the high-n (n > 4) components. The response is not globally sensitive to the toroidal plasma flow speed, as long as the latter is not reduced by an order of magnitude. This is essentially due to the strong screening effect occurring at a finite flow, as predicted for ITER plasmas. The ITER error field correction coils (EFCC) are used to compensate the n = 1 field errors produced by FIs and TBMs for the baseline scenario for the purpose of avoiding mode locking. It is found that the middle row of the EFCC, with a suitable toroidal phase for the coil current, can provide the best correction of these field errors, according to various optimisation criteria. On the other hand, even without correction, it is predicted that these n = 1 field errors will not cause substantial flow damping for the 15 MA baseline scenario

Efficacy of progressive aquatic resistance training for tibiofemoral cartilage in postmenopausal women with mild knee osteoarthritis : a randomised controlled trial

Objective: To study the efficacy of aquatic resistance training on biochemical composition of tibiofemoral cartilage in postmenopausal women with mild knee osteoarthritis (OA). Design: Eighty seven volunteer postmenopausal women, aged 60-68 years, with mild knee OA (Kellgren-Lawrence grades I/II and knee pain) were recruited and randomly assigned to an intervention (n = 43) and control (n = 44) group. The intervention group participated in 48 supervised aquatic resistance training sessions over 16 weeks while the control group maintained usual level of physical activity. The biochemical composition of the medial and lateral tibiofemoral cartilage was estimated using single-slice transverse relaxation time (T2) mapping and delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC index). Secondary outcomes were cardiorespiratory fitness, isometric knee extension and flexion force and knee injury and OA outcome (KOOS) questionnaire. Results: After 4-months aquatic training, there was a significant decrease in both T2 -1.2 ms (95% confidence interval (CI): -2.3 to -0.1, P = 0.021) and dGEMRIC index -23 ms (-43 to -3, P = 0.016) in the training group compared to controls in the full thickness posterior region of interest (ROI) of the medial femoral cartilage. Cardiorespiratory fitness significantly improved in the intervention group by 9.8% (P = 0.010). Conclusions: Our results suggest that, in postmenopausal women with mild knee OA, the integrity of the collagen-interstitial water environment (T2) of the tibiofemoral cartilage may be responsive to low shear and compressive forces during aquatic resistance training. More research is required to understand the exact nature of acute responses in dGEMRIC index to this type of loading. Further, aquatic resistance training improves cardiorespiratory fitness. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Role of the pedestal position on the pedestal performance in AUG, JET-ILW and TCV and implications for ITER

The role of the pedestal position on the pedestal performance has been investigated in AUG, JET-ILW and TCV. When the pedestal is peeling-ballooning (PB) limited, the three machines show a similar behaviour. The outward shift of the pedestal density relative to the pedestal temperature can lead to the outward shift of the pedestal pressure which, in turns, reduces the PB stability, degrades the pedestal confinement and reduces the pedestal width. Once the experimental density position is considered, the EPED model is able to correctly predict the pedestal height. An estimate of the impact of the density position on a ITER baseline scenario shows that the maximum reduction in the pedestal height is 10% while the reduction in the fusion power is between 10% and 40% depending on the assumptions for the core transport model usedIn other plasmas, where the pedestal density is shifted even more outwards relative to the pedestal temperature, the pedestal does not seem PB limited and a different behaviour is observed. The outward shift of the density is still empirically correlated with the pedestal degradation but no change in the pressure position is observed and the PB model is not able to correctly predict the pedestal height. On the other hand, the outward shift of the density leads to a significant increase of eta(e) and eta(i) (where eta(e,i) is the ratio of density to temperature scale lengths, eta(e,i) = L-eta e,L-i/L-Te,L-i) which leads to the increase of the growth rate of microinstabilities (mainly ETG and ITG) by 50%. This suggests that, in these plasmas, the increase in the turbulent transport due to the outward shift of the density might play an important role in the decrease of the pedestal performance.Peer reviewe

A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma

Glioblastoma (GBM) is a malignant brain tumor with few therapeutic options. The disease presents with a complex spectrum of genomic aberrations, but the pharmacological consequences of these aberrations are partly unknown. Here, we report an integrated pharmacogenomic analysis of 100 patient-derived GBM cell cultures from the human glioma cell culture (HGCC) cohort. Exploring 1,544 drugs, we find that GBM has two main pharmacological subgroups, marked by differential response to proteasome inhibitors and mutually exclusive aberrations in TP53 and CDKN2A/B. We confirm this trend in cell and in xenotransplantation models, and identify both Bcl-2 family inhibitors and p53 activators as potentiators of proteasome inhibitors in GBM cells, We can further predict the responses of individual cell cultures to several existing drug classes, presenting opportunities for drug repurposing and design of stratified trials. Our functionally profiled biobank provides a valuable resource for the discovery of new treatments for GBM.Patrik Johansson, Cecilia Krona and Soumi Kundu share first authorship</p

Change in antihypertensive drug prescribing after guideline implementation: a controlled before and after study

<p>Abstract</p> <p>Background</p> <p>Antihypertensive drug choices and treatment levels are not in accordance with the existing guidelines. We aimed to assess the impact of a guideline implementation intervention on antihypertensive drug prescribing.</p> <p>Methods</p> <p>In this controlled before and after study, the effects of a multifaceted (education, audit and feedback, local care pathway) quality programme was evaluated. The intervention was carried out in a health centre between 2002 and 2003. From each health care unit (n = 31), a doctor-nurse pair was trained to act as peer facilitators in the intervention.</p> <p>All antihypertensive drugs prescribed by 25 facilitator general practitioners (intervention GPs) and 53 control GPs were retrieved from the nationwide Prescription Register for three-month periods in 2001 and 2003. The proportions of patients receiving specific antihypertensive drugs and multiple antihypertensive drugs were measured before and after the intervention for three subgroups of hypertension patients: hypertension only, with coronary heart disease, and with diabetes.</p> <p>Results</p> <p>In all subgroups, the use of multiple concurrent medications increased. For intervention patients with hypertension only, the odds ratio (OR) was 1.12 (95% CI 0.99, 1.25; p = 0.06) and for controls 1.13 (1.05, 1.21; p = 0.002). We observed no statistically significant differences in the change in the prescribing of specific antihypertensive agents between the intervention and control groups. The use of agents acting on the renin-angiotensin-aldosterone system increased in all subgroups (hypertension only intervention patients OR 1.19 (1.06, 1.34; p = 0.004) and controls OR 1.24 (1.15, 1.34; p < 0.0001).</p> <p>Conclusions</p> <p>A multifaceted guideline implementation intervention does not necessarily lead to significant changes in prescribing performance. Rigorous planning of the interventions and quality projects and their evaluation are essential.</p

A machine learning approach based on generative topographic mapping for disruption prevention and avoidance at JET

The need for predictive capabilities greater than 95% with very limited false alarms are demanding requirements for reliable disruption prediction systems in tokamaks such as JET or, in the near future, ITER. The prediction of an upcoming disruption must be provided sufficiently in advance in order to apply effective disruption avoidance or mitigation actions to prevent the machine from being damaged. In this paper, following the typical machine learning workflow, a generative topographic mapping (GTM) of the operational space of JET has been built using a set of disrupted and regularly terminated discharges. In order to build the predictive model, a suitable set of dimensionless, machine-independent, physics-based features have been synthesized, which make use of 1D plasma profile information, rather than simple zero-D time series. The use of such predicting features, together with the power of the GTM in fitting the model to the data, obtains, in an unsupervised way, a 2D map of the multi-dimensional parameter space of JET, where it is possible to identify a boundary separating the region free from disruption from the disruption region. In addition to helping in operational boundaries studies, the GTM map can also be used for disruption prediction exploiting the potential of the developed GTM toolbox to monitor the discharge dynamics. Following the trajectory of a discharge on the map throughout the different regions, an alarm is triggered depending on the disruption risk of these regions. The proposed approach to predict disruptions has been evaluated on a training and an independent test set and achieves very good performance with only one tardive detection and a limited number of false detections. The warning times are suitable for avoidance purposes and, more important, the detections are consistent with physical causes and mechanisms that destabilize the plasma leading to disruptions.Peer reviewe