Azathioprine and 6-Mercaptopurine use in the Swiss IBD cohort : adverse effects, causes of discontinuation and risk of "flares" according to 6-TG levels

Background: To characterize and analyze in the Swiss IBD Cohort: a) reported Azathioprine (AZA) and 6-Mercaptopurine (6-MP) adverse effects (AE), b) causes of discontinuation and c) response to therapy according to gastroenterologists' clinical judgment, d) whether level of 6-TGN < 235pmol/8 x108 red blood cells (RBC) is associated with a higher risk of "flare" occurrence. Methods: Retrospective statistical description, Cox model and Kaplan-Meier survival estimation. Results: 1499 patients with Crohn's Disease (CD) and 1066 with Ulcerative colitis (UC)

Beyond stroke: Impact of the lesion side on the recovery of between-hands coordination

ObjectiveOne-fit-all post-stroke rehabilitation has limited plausibility. Better understanding the effects of the lesion location on the recovery process may help to develop new tailored therapeutic strategies to individuals. The purpose of this study was to assess the natural evolution of bimanual coordination over standard rehabilitation according to the lesion side, aiming to identify a potential responder-profile for bimanual-oriented therapy.Material/patientsTwelve hemiparetic, moderately impaired patients were included within 30 days after a first unilateral stroke. The kinematic and clinical assessments were performed once a week for 6 weeks and at 3 months after inclusion. The patients performed a reach-to-grasp task in unimanual condition followed by a synchronous bimanual condition. The clinical evaluation included the Fugl-Meyer Assessment, Box and Block Test, 9-Hole Peg Test and Barthel Index.ResultsThe clinical scores indicated no difference in motor function between left- (LHD) and right-hemispheric damaged (RHD) patients over time. Interestingly, the LHD patients produced smoother bimanual reaching movements than the RHD patients while we found no effect of the lesion side on reaching kinematics of the paretic UL in unimanual condition. These inter-group differences disappeared after 5 weeks of standard therapy, likely indicating a time lag in motor recovery.DiscussionBecause the RHD patients were less prematurely coordinated again during bimanual movements than the LHD patients, they may benefit differently from a bimanual rehabilitation, and especially from the simultaneous involvement of the ipsilesional UL. It becomes necessary to investigate to what extent this difference due to lesion side may be integrated into the design of rehabilitation protocols

Charge redistribution at Pd surfaces: ab initio grounds for tight-binding interatomic potentials

A simplified tight-binding description of the electronic structure is often necessary for complex studies of surfaces of transition metal compounds. This requires a self-consistent parametrization of the charge redistribution, which is not obvious for late transition series elements (such as Pd, Cu, Au), for which not only d but also s-p electrons have to be taken into account. We show here, with the help of an ab initio FP-LMTO approach, that for these elements the electronic charge is unchanged from bulk to the surface, not only per site but also per orbital. This implies different level shifts for each orbital in order to achieve this orbital neutrality rule. Our results invalidate any neutrality rule which would allow charge redistribution between orbitals to ensure a common rigid shift for all of them. Moreover, in the case of Pd, the power law which governs the variation of band energy with respect to coordination number, is found to differ significantly from the usual tight-binding square root.Comment: 6 pages, 2 figures, Latex; Phys.Rev. B 56 (1997

Isokinetic muscle strengthening after acquired cerebral damage: A literature review

AbstractObjectiveIsokinetic strengthening is a rehabilitation technique rarely used in stroke patients. However, the potential benefits of force and endurance training in this population are strongly suspected.MethodThis literature review synthesizes the results of clinical trials on this topic. The research was conducted on PubMed, using “Stroke”, “rehabilitation”, “isokinetic”, “upper limb” and “training” as keywords.ResultsSeventeen studies focusing on the use of isokinetics in assessment or rehabilitation (six studies) following stroke were reviewed. For the lower limb, muscle strength and walking ability improved after isokinetic rehabilitation programs. For the upper limb, the only two studies found in the literature suggest improvement in the strength of the trained muscles, of grip force, of the Fugl-Meyer motor score and of global functional capacities. This review does not reveal any consensus on the protocols to be implemented: type of muscle contraction, velocities….ConclusionWhile isokinetic strengthening has not proven its efficiency in rehabilitation of the upper limb following stroke, its interest with regard to rehabilitation of the lower limbs has been recognized. Randomized controlled trials in this field are necessary to confirm its efficiency, especially concerning upper arm rehabilitation

A domain decomposition non-intrusive reduced order model for turbulent flows

In this paper, a new Domain Decomposition Non-Intrusive Reduced Order Model (DDNIROM) is developed for turbulent flows. The method works by partitioning the computational domain into a number of subdomains in such a way that the summation of weights associated with the finite element nodes within each subdomain is approximately equal, and the communication between subdomains is minimised. With suitably chosen weights, it is expected that there will be approximately equal accuracy associated with each subdomain. This accuracy is maximised by allowing the partitioning to occur through areas of the domain that have relatively little flow activity, which, in this case, is characterised by the pointwise maximum Reynolds stresses.A Gaussian Process Regression (GPR) machine learning method is used to construct a set of local approximation functions (hypersurfaces) for each subdomain. Each local hypersurface represents not only the fluid dynamics over the subdomain it belongs to, but also the interactions of the flow dynamics with the surrounding subdomains. Thus, in this way, the surrounding subdomains may be viewed as providing boundary conditions for the current subdomain.We consider a specific example of turbulent air flow within an urban neighbourhood at a test site in London and demonstrate the effectiveness of the proposed DDNIROM

Mechanisms of Improved Exercise Performance under Hyperoxia

BACKGROUND The impact of hyperoxia on exercise limitation is still incompletely understood. OBJECTIVES We investigated to which extent breathing hyperoxia enhances the exercise performance of healthy subjects and which physiologic mechanisms are involved. METHODS A total of 32 healthy volunteers (43 ± 15 years, 12 women) performed 4 bicycle exercise tests to exhaustion with ramp and constant-load protocols (at 75% of the maximal workload [Wmax] on FiO2 0.21) on separate occasions while breathing ambient (FiO2 0.21) or oxygen-enriched air (FiO2 0.50) in a random, blinded order. Workload, endurance, gas exchange, pulse oximetry (SpO2), and cerebral (CTO) and quadriceps muscle tissue oxygenation (QMTO) were measured. RESULTS During the final 15 s of ramp exercising with FiO2 0.50, Wmax (mean ± SD 270 ± 80 W), SpO2 (99 ± 1%), and CTO (67 ± 9%) were higher and the Borg CR10 Scale dyspnea score was lower (4.8 ± 2.2) than the corresponding values with FiO2 0.21 (Wmax 257 ± 76 W, SpO2 96 ± 3%, CTO 61 ± 9%, and Borg CR10 Scale dyspnea score 5.7 ± 2.6, p < 0.05, all comparisons). In constant-load exercising with FiO2 0.50, endurance was longer than with FiO2 0.21 (16 min 22 s ± 7 min 39 s vs. 10 min 47 s ± 5 min 58 s). With FiO2 0.50, SpO2 (99 ± 0%) and QMTO (69 ± 8%) were higher than the corresponding isotime values to end-exercise with FiO2 0.21 (SpO2 96 ± 4%, QMTO 66 ± 9%), while minute ventilation was lower in hyperoxia (82 ± 18 vs. 93 ± 23 L/min, p < 0.05, all comparisons). CONCLUSION In healthy subjects, hyperoxia increased maximal power output and endurance. It improved arterial, cerebral, and muscle tissue oxygenation, while minute ventilation and dyspnea perception were reduced. The findings suggest that hyperoxia enhanced cycling performance through a more efficient pulmonary gas exchange and a greater availability of oxygen to muscles and the brain (cerebral motor and sensory neurons)

Long-term follow-up of pulmonary function in Fabry disease: A bi-center observational study.

Fabry disease (FD) is a lysosomal storage disorder leading to decreased α-galactosidase A enzyme activity and subsequent abnormal accumulation of glycosphingolipids in various organs. Although histological evidence of lung involvement has been demonstrated, the functional impact of these changes is less clear. Adult patients with FD who had yearly pulmonary function tests (PFT) at two centers from 1999 thru 2015 were eligible for this observational study. Primary outcome measures were the change in forced expiratory volume in the first second (FEV1) and FEV1/FVC over time. As secondary outcome we investigated sex, smoking, enzyme replacement therapy (ERT), residual enzyme activity, and Mainz Severity Score Index as possible predictors. 95 patients (41% male, 38.2 ± 14.5 years) were included. The overall prevalence of bronchial obstruction (BO, (FEV1/FVC &lt; 70%)) was 46%, with male sex, age and smoking as significant predictors. FEV1 decreased 29 ml per year (95% CI -36, -22 ml, p&lt;0.0001). FEV1 decline was significantly higher in males (p = 0.009) and in patients on ERT (p = 0.004). Conclusion: Pulmonary involvement seems to be a relevant manifestation of Fabry disease, and routine PFTs should therefore be included in the multidisciplinary follow-up of these patients

A Geometric Formulation of Quantum Stress Fields

We present a derivation of the stress field for an interacting quantum system within the framework of local density functional theory. The formulation is geometric in nature and exploits the relationship between the strain tensor field and Riemannian metric tensor field. Within this formulation, we demonstrate that the stress field is unique up to a single ambiguous parameter. The ambiguity is due to the non-unique dependence of the kinetic energy on the metric tensor. To illustrate this formalism, we compute the pressure field for two phases of solid molecular hydrogen. Furthermore, we demonstrate that qualitative results obtained by interpreting the hydrogen pressure field are not influenced by the presence of the kinetic ambiguity.Comment: 22 pages, 2 figures. Submitted to Physical Review B. This paper supersedes cond-mat/000627