Assessment of intra- and inter-ventricular cardiac dyssynchrony in patients with repaired Tetralogy of Fallot: a cardiac magnetic resonance study

Using radiative magnetohydrodynamic simulations of the magnetized solar photosphere and detailed spectro-polarimetric diagnostics with the Fe I 6301.5 Å and 6302.5 Å photospheric lines in the local thermodynamic equilibrium approximation, we model active solar granulation as if it was observed at the solar limb. We analyze general properties of the radiation across the solar limb, such as the continuum and the line core limb darkening and the granulation contrast. We demonstrate the presence of profiles with both emission and absorption features at the simulated solar limb, and pure emission profiles above the limb. These profiles are associated with the regions of strong linear polarization of the emergent radiation, indicating the influence of the intergranular magnetic fields on the line formation. We analyze physical origins of the emission wings in the Stokes profiles at the limb, and demonstrate that these features are produced by localized heating and torsional motions in the intergranular magnetic flux concentrations

Assessment of intra- and inter-ventricular cardiac dyssynchrony in patients with repaired Tetralogy of Fallot: a cardiac magnetic resonance study

Background Patients with repaired tetralogy of Fallot (TOF) frequently have right bundle branch block. However, the contribution of cardiac dyssynchrony to dysfunction remains controversial. To better understand this phenomenon and ultimately study therapies, we developed a method to quantify left (LV), right (RV) and inter-ventricular cardiac dyssynchrony using standard cine CMR. Methods 30 patients with repaired TOF (age 28 ± 16, 46% female) and 17 healthy controls (age 29 ± 7, 12% female) underwent cine CMR. Patients were imaged twice to assess inter-test reproducibility. Circumferential strain vs time curves were generated with a custom feature tracking algorithm for 12 LV and 12 RV segments in 4-7 slices encompassing the ventricles. For each segment, the temporal offset (TO) of the strain curve relative to a global reference curve derived from the controls was calculated and expressed as a percent of the cardiac cycle. The intra-ventricular dyssynchrony index (DI) for each ventricle was computed as the standard deviation (SD) of the TOs (more dyssynchrony increases the SD). The inter-ventricular DI was calculated as the difference in median RV and median LV TOs. Regional dyssynchrony was quantified in 3 LV (septum, infero-lateral and antero-lateral wall) and 3 RV (septum, sinus, outflow tract) regions using median TOs. Results Compared to controls, patients with repaired TOF had a greater LV, RV and inter-ventricular DI. The greater inter-ventricular delay in the patients was primarily due to a global delay in RV contraction with the RV contracting 4.9 ± 3.5% later than the LV in patients vs 1.4 ± 3.2% earlier in controls. Median TOs were similar in the three LV regions between patients and controls, but all three RV regions were significantly delayed in patients compared to the controls. Contraction patterns in the RV were also distinct: in controls, the earliest contraction was seen in the outflow tract; in patients, contraction occurred first in the septum and last in the outflow tract. Inter-test reproducibility for the three DIs was good with all coefficients of variation Conclusions Patients with repaired TOF suffer from left, right and inter-ventricular cardiac dyssynchrony which can all be quantified from standard cine CMR with good inter-test reproducibility. Future studies need to determine whether these patients may benefit from resynchronization therapy

Process management in hospitals: an empirically grounded maturity model

In order to improve transparency and stabilise health care costs, several countries have decided to reform their healthcare system on the basis of diagnosis-related groups (DRG). DRGs are not only used for classifying medical treatments, but also for case-based reimbursement, hence induce active competition among hospitals, forcing them to become more efficient and effective. In consequence, hospitals are investing considerably in process orientation and management. However, to date there is neither a consensus on what capabilities hospitals need to acquire for becoming process-oriented, nor a general agreement on the sequence of development stages they have to traverse. To this end, this study proposes an empirically grounded conceptualisation of process management capabilities and presents a staged capability maturity model algorithmically derived on the basis of empirical data from 129 acute somatic hospitals in Switzerland. The five capability maturity levels start with 'encouragement of process orientation' (level 1), 'case-by-case handling' (level 2), and 'defined processes' (level 3). Ultimately, hospitals can reach the levels 'occasional corrective action' (level 4) and 'closed loop improvement' (level 5). The empirically derived model reveals why existing, generic capability maturity models for process management are not applicable in the hospitals context: their comparatively high complexity on the one hand and their strong focus on topics like an adequate IT integration and process automation on the other make them inadequate for solving the problems felt in the hospital sector, which are primarily of cultural and structural nature. We deem the proposed capability maturity model capable to overcome these shortcomings

A click-flipped enzyme substrate boosts the performance of the diagnostic screening for Hunter syndrome

Click-triggered flip of the conformation of a sulfated iduronyl azide afforded a superior enzyme substrate to screen for Hunter syndrome. We report on the unexpected finding that click modification of iduronyl azides results in a conformational flip of the pyranose ring, which led to the development of a new strategy for the design of superior enzyme substrates for the diagnostic assaying of iduronate-2-sulfatase (I2S), a lysosomal enzyme related to Hunter syndrome. Synthetic substrates are essential in testing newborns for metabolic disorders to enable early initiation of therapy. Our click-flipped iduronyl triazole showed a remarkably better performance with I2S than commonly used O -iduronates. We found that both O - and triazole-linked substrates are accepted by the enzyme, irrespective of their different conformations, but only the O -linked product inhibits the activity of I2S. Thus, in the long reaction times required for clinical assays, the triazole substrate substantially outperforms the O -iduronate. Applying our click-flipped substrate to assay I2S in dried blood spots sampled from affected patients and random newborns significantly increased the confidence in discriminating between these groups, clearly indicating the potential of the click-flip strategy to control the biomolecular function of carbohydrates

A click-flipped enzyme substrate boosts the performance of the diagnostic screening for Hunter syndrome

Click-triggered flip of the conformation of a sulfated iduronyl azide afforded a superior enzyme substrate to screen for Hunter syndrome. We report on the unexpected finding that click modification of iduronyl azides results in a conformational flip of the pyranose ring, which led to the development of a new strategy for the design of superior enzyme substrates for the diagnostic assaying of iduronate-2-sulfatase (I2S), a lysosomal enzyme related to Hunter syndrome. Synthetic substrates are essential in testing newborns for metabolic disorders to enable early initiation of therapy. Our click-flipped iduronyl triazole showed a remarkably better performance with I2S than commonly used O -iduronates. We found that both O - and triazole-linked substrates are accepted by the enzyme, irrespective of their different conformations, but only the O -linked product inhibits the activity of I2S. Thus, in the long reaction times required for clinical assays, the triazole substrate substantially outperforms the O -iduronate. Applying our click-flipped substrate to assay I2S in dried blood spots sampled from affected patients and random newborns significantly increased the confidence in discriminating between these groups, clearly indicating the potential of the click-flip strategy to control the biomolecular function of carbohydrates