Are internists in an non-prescriptive setting favourable to guidelines? A survey in a Department of Internal Medicine in Switzerland.

A cross-sectional anonymous postal survey was carried out in a Department of Internal Medicine in order to assess physicians' knowledge about and attitudes towards clinical practice guidelines and to evaluate the role of age in determining their use and opinions. The study took place in a Swiss University Hospital where exposure to guidelines had been limited. The questionnaire was sent to the 174 physicians of the Department. The response rate was 67% (116/174). The spontaneous definitions of guidelines were heterogeneous and referred to information of uncertain validity. Most participants, especially the younger groups of junior and senior residents, reported using guidelines and were favourable to their development. Less favourable attitudes were observed among senior staff physicians and consultants. For instance, the latter more often held the opinion that guidelines are too rigid to apply to individual patients, were likely to decrease physician reimbursement and to hamper research (respectively, 32% vs 24%, 50% vs 31% and 18% vs 7% when compared with the opinions of residents). In conclusion, in a non-prescriptive hospital setting, where the development, dissemination and implementation of guidelines are emerging, the concept of 'guideline' was heterogeneous. Despite generally positive attitudes towards guidelines, the opinion of senior staff physicians constitute a barrier to their dissemination and implementation

Digital Deblurring of CMB Maps II: Asymmetric Point Spread Function

In this second paper in a series dedicated to developing efficient numerical techniques for the deblurring Cosmic Microwave Background (CMB) maps, we consider the case of asymmetric point spread functions (PSF). Although conceptually this problem is not different from the symmetric case, there are important differences from the computational point of view because it is no longer possible to use some of the efficient numerical techniques that work with symmetric PSFs. We present procedures that permit the use of efficient techniques even when this condition is not met. In particular, two methods are considered: a procedure based on a Kronecker approximation technique that can be implemented with the numerical methods used with symmetric PSFs but that has the limitation of requiring only mildly asymmetric PSFs. The second is a variant of the classic Tikhonov technique that works even with very asymmetric PSFs but that requires discarding the edges of the maps. We provide details for efficient implementations of the algorithms. Their performance is tested on simulated CMB maps.Comment: 9 pages, 13 Figure

Impact of numerical integration on gas curtain simulations

In recent years, we have presented a less than glowing experimental comparison of hydrodynamic codes with the gas curtain experiment (e.g., Kamm et al. 1999a). Here, we discuss the manner in which the details of the hydrodynamic integration techniques may conspire to produce poor results. This also includes some progress in improving the results and agreement with experimental results. Because our comparison was conducted on the details of the experimental images (i.e., their detailed structural information), our results do not conflict with previously published results of good agreement with Richtmyer-Meshkov instabilities based on the integral scale of mixing. New experimental and analysis techniques are also discussed

Morphological Transformation and Force Generation of Active Cytoskeletal Networks

Cells assemble numerous types of actomyosin bundles that generate contractile forces for biological processes, such as cytokinesis and cell migration. One example of contractile bundles is a transverse arc that forms via actomyosin-driven condensation of actin filaments in the lamellipodia of migrating cells and exerts significant forces on the surrounding environments. Structural reorganization of a network into a bundle facilitated by actomyosin contractility is a physiologically relevant and biophysically interesting process. Nevertheless, it remains elusive how actin filaments are reoriented, buckled, and bundled as well as undergo tension buildup during the structural reorganization. In this study, using an agent-based computational model, we demonstrated how the interplay between the density of myosin motors and cross-linking proteins and the rigidity, initial orientation, and turnover of actin filaments regulates the morphological transformation of a cross-linked actomyosin network into a bundle and the buildup of tension occurring during the transformation

The cascade structure of linear instability in collapsible channel flows

This paper studies the unsteady behaviour and linear stability of the flow in a collapsible channel using a fluid–beam model. The solid mechanics is analysed in a plane strain configuration, in which the principal stretch is defined with a zero initial strain. Two approaches are employed: unsteady numerical simulations solving the nonlinear fully coupled fluid–structure interaction problem; and the corresponding linearized eigenvalue approach solving the Orr–Sommerfeld equations modified by the beam. The two approaches give good agreement with each other in predicting the frequencies and growth rates of the perturbation modes, close to the neutral curves. For a given Reynolds number in the range of 200–600, a cascade of instabilities is discovered as the wall stiffness (or effective tension) is reduced. Under small perturbation to steady solutions for the same Reynolds number, the system loses stability by passing through a succession of unstable zones, with mode number increasing as the wall stiffness is decreased. It is found that this cascade structure can, in principle, be extended to many modes, depending on the parameters. A puzzling ‘tongue’ shaped stable zone in the wall stiffness–Re space turns out to be the zone sandwiched by the mode-2 and mode-3 instabilities. Self-excited oscillations dominated by modes 2–4 are found near their corresponding neutral curves. These modes can also interact and form period-doubling oscillations. Extensive comparisons of the results with existing analytical models are made, and a physical explanation for the cascade structure is proposed

Randomised trial of once- or twice-daily MMX mesalazine for maintenance of remission in ulcerative colitis

AIM: Maintenance treatment in ulcerative colitis should be as convenient as possible, to increase the chance of compliance. MMX mesalazine is a once-daily, high-strength (1.2 g/tablet) formulation of 5-aminosalicylic acid. This study evaluated the safety and efficacy of MMX mesalazine dosed once or twice daily as maintenance therapy in patients with ulcerative colitis. METHODS: This multicentre, randomised, open-label trial enrolled patients with strictly defined clinical and endoscopic remission, immediately following an episode of mild to moderate ulcerative colitis. Patients were randomised to MMX mesalazine 2.4 g/day as a single (2x1.2 g tablet) or divided dose (1x1.2 g tablet twice daily) for 12 months. RESULTS: 174 patients (37.9%; safety population n = 459) experienced 384 adverse events, the majority of which were mild or moderate in intensity. Eighteen patients (3.9%), nine in each group, experienced a total of 22 serious adverse events (10 in the once-daily and 12 in the twice-daily group). Most serious adverse events were gastrointestinal, experienced by 5 patients in the once-daily and 4 in the twice-daily group. At month 12, 64.4% (efficacy population, n = 451) of patients in the once-daily and 68.5% of patients in the twice-daily group were in clinical and endoscopic remission (p = 0.351). At month 12, 88.9% and 93.2% in each group, respectively, had maintained clinical remission (were relapse free). CONCLUSIONS: MMX mesalazine 2.4 g/day administered as a single or divided dose demonstrated a good safety profile, was well tolerated and was effective as maintenance treatment. High clinical and endoscopic remission rates can be achieved with once-daily dosing. TRIAL REGISTRATION NUMBER: NCT00151944

Sequence-independent activation of photocycloadditions using two colours of light

We exploit two reactive chromophores to establish sequence-independent photochemical activation, employing ortho-methyl benzaldehyde (oMBA) and N,N-(dimethylamino)pyrene aryl tetrazole (APAT) with N-(2-hydroxy)ethyl maleimide (NHEM), without any additives. Critically, the order of the irradiation sequence is irrelevant, as the shorter wavelength does not activate the higher wavelength activated species. Therefore, full sequence-independent λ-orthogonality is achieved through differences in both the reaction quantum yields (Φr,oMBA and Φr,APAT) and wavelength-dependent reactivity profiles of the employed chromophore

Knowledge of Objective 'Oughts': Monotonicity and the New Miners Puzzle

In the classic Miners case, an agent subjectively ought to do what they know is objectively wrong. This case shows that the subjective and objective ‘oughts’ are somewhat independent. But there remains a powerful intuition that the guidance of objective ‘oughts’ is more authoritative—so long as we know what they tell us. We argue that this intuition must be given up in light of a monotonicity principle, which undercuts the rationale for saying that objective ‘oughts’ are an authoritative guide for agents and advisors