Nanoradian angular stabilization of x-ray optical components

An x-ray free electron laser oscillator (XFELO) has been recently proposed [K. Kim, Y. Shvyd'ko, and S. Reiche, Phys. Rev. Lett. 100, 244802 (2008)]. Angular orientation and position in space of Bragg mirrors of the XFELO optical cavity must be continuously adjusted to compensate instabilities and maximize the output intensity. An angular stability of about 10 nrad (rms) is required [K. Kim and Y. Shvyd'ko Phys. Rev. STAB 12, 030703 (2009)]. To approach this goal, a feedback loop based on a null-detection principle was designed and used for stabilization of a high energy resolution x-ray monochromator ($\Delta E/E \simeq 4 \times 10^{-8}$, $E$ = 23.7 keV) and a high heat load monochromator. Angular stability of about 13 nrad (rms) has been demonstrated for x-ray optical elements of the monochromators.Comment: 8 figure

Should valproate be taken during pregnancy?

The Australian Registry of Antiepileptic Drug Use in Pregnancy includes 172 instances in which women took sodium valproate, with or without other antiepileptic drugs, during pregnancy. These pregnancies resulted in a substantially higher (p < 0.05) rate of malformed offspring (15.1%) compared with 348 pregnant women who took antiepileptic drugs other than valproate (2.3%) and 40 pregnancies in epileptic women who took no antiepileptic drugs (2.5%). At valproate doses of 1400 mg and below per day, the mean rate of pregnancies with fetal malformations was 6.42% and did not seem to be dose-dependent. At higher valproate doses, the mean rate of pregnancy with fetal malformation was 33.9% and appeared to increase with increasing drug dosage. This finding suggests the need for reappraisal of the use of valproate in women who may become pregnant or are pregnant whilst the drug is taken. The therapeutic policy adopted may depend on whether valproate doses below 1400 mg per day are regarded as safe for the fetus. This study indicates that the risk of malformation associated with such doses was just statistically significantly (p < 0.05) higher than that associated with other antiepileptic drugs. Various possible clinical scenarios are discussed

Comparison of the Efficacy of Caudal, Interlaminar, and Transforaminal Epidural Injections in Managing Lumbar Disc Herniation: Is One Method Superior to the Other?

Background: Epidural injections are performed utilizing 3 approaches in the lumbar spine: caudal, interlaminar, and transforaminal. The literature on the efficacy of epidural injections has been sporadic. There are few high-quality randomized trials performed under fluoroscopy in managing disc herniation that have a long-term follow-up and appropriate outcome parameters. There is also a lack of literature comparing the efficacy of these 3 approaches. Methods: This manuscript analyzes data from 3 randomized controlled trials that assessed a total of 360 patients with lumbar disc herniation. There were 120 patients per trial either receiving local anesthetic alone (60 patients) or local anesthetic with steroids (60 patients). Results: Analysis showed similar efficacy for caudal, interlaminar, and transforaminal approaches in managing chronic pain and disability from disc herniation. The analysis of caudal epidural injections showed the potential superiority of steroids compared with local anesthetic alone a 2-year follow-up, based on the average relief per procedure. In the interlaminar group, results were somewhat superior for pain relief in the steroid group at 6 months and functional status at 12 months. Interlaminar epidurals provided improvement in a significantly higher proportion of patients. The proportion of patients nonresponsive to initial injections was also lower in the group for local anesthetic with steroid in the interlaminar trial. Conclusions: The results of this assessment show significant improvement in patients suffering from chronic lumbar disc herniation with 3 lumbar epidural approaches with local anesthetic alone, or using steroids with long-term follow-up of up to 2 years, in a contemporary interventional pain management setting

Regional variations in ex-vivo diffusion tensor anisotropy are associated with cardiomyocyte remodeling in rats after left ventricular pressure overload

Background Pressure overload left ventricular (LV) hypertrophy is characterized by increased cardiomyocyte width and ventricle wall thickness, however the regional variation of this remodeling is unclear. Cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) may provide a non-invasive, comprehensive, and geometrically accurate method to detect regional differences in structural remodeling in hypertrophy. We hypothesized that DTI parameters, such as fractional and planar anisotropy, would reflect myocyte remodeling due to pressure overload in a regionally-dependent manner. Methods We investigated the regional distributions of myocyte remodeling in rats with or without transverse aortic constriction (TAC) via direct measurement of myocyte dimensions with confocal imaging of thick tissue sections, and correlated myocyte cross-sectional area and other geometric features with parameters of diffusivity from ex-vivo DTI in the same regions of the same hearts. Results We observed regional differences in several parameters from DTI between TAC hearts and SHAM controls. Consistent with previous studies, helix angles from DTI correlated strongly with those measured directly from histological sections (p < 0.001, R2 = 0.71). There was a transmural gradient in myocyte cross-sectional area in SHAM hearts that was diminished in the TAC group. We also found several regions of significantly altered DTI parameters in TAC LV compared to SHAM, especially in myocyte sheet angle dispersion and planar anisotropy. Among others, these parameters correlated significantly with directly measured myocyte aspect ratios. Conclusions These results show that structural remodeling in pressure overload LV hypertrophy is regionally heterogeneous, especially transmurally, with a greater degree of remodeling in the sub-endocardium compared to the sub-epicardium. Additionally, several parameters derived from DTI correlated significantly with measurements of myocyte geometry from direct measurement in histological sections. We suggest that DTI may provide a non-invasive, comprehensive method to detect regional structural myocyte LV remodeling during disease

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure

Establishing the values for patient engagement (PE) in health-related quality of life (HRQoL) research: an international, multiple-stakeholder perspective

PurposeActive patient engagement is increasingly viewed as essential to ensuring that patient-driven perspectives are considered throughout the research process. However, guidance for patient engagement (PE) in HRQoL research does not exist, the evidence-base for practice is limited, and we know relatively little about underpinning values that can impact on PE practice. This is the first study to explore the values that should underpin PE in contemporary HRQoL research to help inform future good practice guidance. MethodsA modified ‘World Café’ was hosted as a collaborative activity between patient partners, clinicians and researchers: self-nominated conference delegates participated in group discussions to explore values associated with the conduct and consequences of PE. Values were captured via post-it notes and by nominated note-takers. Data were thematically analysed: emergent themes were coded and agreement checked. Association between emergent themes, values and the Public Involvement Impact Assessment Framework were explored. ResultsEighty participants, including 12 patient partners, participated in the 90-min event. Three core values were defined: (1) building relationships; (2) improving research quality and impact; and (3) developing best practice. Participants valued the importance of building genuine, collaborative and deliberative relationships—underpinned by honesty, respect, co-learning and equity—and the impact of effective PE on research quality and relevance. Conclusions An explicit statement of values seeks to align all stakeholders on the purpose, practice and credibility of PE activities. An innovative, flexible and transparent research environment was valued as essential to developing a trustworthy evidence-base with which to underpin future guidance for good PE practice.Peer reviewe

Role of interleukin-10 in endochondral bone formation in mice: Anabolic effect via the bone morphogenetic protein/Smad pathway

Objective: Interleukin-10 (IL-10) is a pleiotropic immunoregulatory cytokine with a chondroprotective effect that is elevated in cartilage and synovium in patients with osteoarthritis. However, the role of IL-10 during endochondral bone formation and its mechanism of action have not been elucidated. Methods: IL-10-/- mice and IL-10-treated tibial organ cultures were used to study loss and gain of IL-10 functions, respectively, during endochondral bone formation. Primary chondrocytes from the long bones of mouse embryos were cultured with and without IL-10. To assess the role of IL-10 in chondrogenic differentiation, we conducted mesenchymal cell micromass cultures. Results: The lengths of whole skeletons from IL-10-/- mice were similar to those of their wild-type littermates, although their skull diameters were smaller. The tibial growth plates of IL-10-/- mice showed shortening of the proliferating zone. Treatment with IL-10 significantly increased tibial lengths in organ culture. IL-10 also induced chondrocyte proliferation and hypertrophic differentiation in primary chondrocytes in vitro. Mechanistically, IL-10 activated STAT-3 and the Smad1/5/8 and ERK-1/2 MAP kinase pathways and induced the expression of bone morphogenetic protein 2 (BMP-2) and BMP-6 in primary chondrocytes. Furthermore, the blocking of BMP signaling attenuated the IL-10-mediated induction of cyclin D1 and RUNX-2 in primary chondrocytes and suppressed Alcian blue and alkaline phosphatase staining in mesenchymal cell micromass cultures. Conclusion: These results indicate that IL-10 acts as a stimulator of chondrocyte proliferation and chondrogenic or hypertrophic differentiation via activation of the BMP signaling pathway. © 2013, American College of Rheumatology

Selection of tuning parameters in bridge regression models via Bayesian information criterion

We consider the bridge linear regression modeling, which can produce a sparse or non-sparse model. A crucial point in the model building process is the selection of adjusted parameters including a regularization parameter and a tuning parameter in bridge regression models. The choice of the adjusted parameters can be viewed as a model selection and evaluation problem. We propose a model selection criterion for evaluating bridge regression models in terms of Bayesian approach. This selection criterion enables us to select the adjusted parameters objectively. We investigate the effectiveness of our proposed modeling strategy through some numerical examples.Comment: 20 pages, 5 figure

Predictors of Successful Decannulation Using a Tracheostomy Retainer in Patients with Prolonged Weaning and Persisting Respiratory Failure

Background: For percutaneously tracheostomized patients with prolonged weaning and persisting respiratory failure, the adequate time point for safe decannulation and switch to noninvasive ventilation is an important clinical issue. Objectives: We aimed to evaluate the usefulness of a tracheostomy retainer (TR) and the predictors of successful decannulation. Methods: We studied 166 of 384 patients with prolonged weaning in whom a TR was inserted into a tracheostoma. Patients were analyzed with regard to successful decannulation and characterized by blood gas values, the duration of previous spontaneous breathing, Simplified Acute Physiology Score (SAPS) and laboratory parameters. Results: In 47 patients (28.3%) recannulation was necessary, mostly due to respiratory decompensation and aspiration. Overall, 80.6% of the patients could be liberated from a tracheostomy with the help of a TR. The need for recannulation was associated with a shorter duration of spontaneous breathing within the last 24/48 h (p < 0.01 each), lower arterial oxygen tension (p = 0.025), greater age (p = 0.025), and a higher creatinine level (p = 0.003) and SAPS (p < 0.001). The risk for recannulation was 9.5% when patients breathed spontaneously for 19-24 h within the 24 h prior to decannulation, but 75.0% when patients breathed for only 0-6 h without ventilatory support (p < 0.001). According to ROC analysis, the SAPS best predicted successful decannulation {[}AUC 0.725 (95% CI: 0.634-0.815), p < 0.001]. Recannulated patients had longer durations of intubation (p = 0.046), tracheostomy (p = 0.003) and hospital stay (p < 0.001). Conclusion: In percutaneously tracheostomized patients with prolonged weaning, the use of a TR seems to facilitate and improve the weaning process considerably. The duration of spontaneous breathing prior to decannulation, age and oxygenation describe the risk for recannulation in these patients. Copyright (c) 2012 S. Karger AG, Base