IntroductionIdiopathic subglottic stenosis (iSGS) is an unexplained progressive obstruction of the upper airway that occurs almost exclusively in adult, Caucasian women. The disease is characterised ...by mucosal inflammation and localised fibrosis resulting in life-threatening blockage of the upper airway. Because of high recurrence rates, patients with iSGS will frequently require multiple procedures following their initial diagnosis. Both the disease and its therapies profoundly affect patients’ ability to breathe, communicate and swallow. A variety of treatments have been advanced to manage this condition. However, comparative data on effectiveness and side effects of the unique approaches have never been systematically evaluated. This study will create an international, multi-institutional prospective cohort of patients with iSGS. It will compare three surgical approaches to determine how well the most commonly used treatments in iSGS ‘work’ and what quality of life (QOL) trade-offs are associated with each approach.Methods and analysisA prospective pragmatic trial comparing the ‘Standard of Care’ for iSGS at multiple international institutions. Patients with a diagnosis of iSGS without clinical or laboratory evidence of vasculitis or a history of endotracheal intubation 2 years prior to symptom onset will be included in the study. Prospective evaluation of disease recurrence requiring operative intervention, validated patient-reported outcome (PRO) measures as well as patient-generated health data (mobile peak flow recordings and daily steps taken) will be longitudinally tracked for 36 months. The primary endpoint is treatment effectiveness defined as time to recurrent operative procedure. Secondary endpoints relate to treatment side effects and include PRO measures in voice, swallowing, breathing and global QOL as well as patient-generated health data.Ethics and disseminationThis protocol was approved by the local IRB Committee of the Vanderbilt University Medical Center in July 2015. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations and directly to patient with iSGS via social media-based support groups.Trial registration number NCT02481817.
Background
Consider a comparative, randomized clinical study with a specific event time as the primary end point. In the presence of censoring, standard methods of summarizing the treatment ...difference are based on Kaplan–Meier curves, the logrank test, and the point and interval estimates via Cox’s procedure. Moreover, for designing and monitoring the study, one usually utilizes an event-driven scheme to determine the sample sizes and interim analysis time points.
Purpose
When the proportional hazards (PHs) assumption is violated, the logrank test may not have sufficient power to detect the difference between two event time distributions. The resulting hazard ratio estimate is difficult, if not impossible, to interpret as a treatment contrast. When the event rates are low, the corresponding interval estimate for the ‘hazard ratio’ can be quite large due to the fact that the interval length depends on the observed numbers of events. This may indicate that there is not enough information for making inferences about the treatment comparison even when there is no difference between two groups. This situation is quite common for a postmarketing safety study. We need an alternative way to quantify the group difference.
Methods
Instead of quantifying the treatment group difference using the hazard ratio, we consider an easily interpretable and model-free parameter, the integrated survival rate difference over a prespecified time interval, as an alternative. We present the inference procedures for such a treatment contrast. This approach is purely nonparametric and does not need any model assumption such as the PHs. Moreover, when we deal with equivalence or noninferiority studies and the event rates are low, our procedure would provide more information about the treatment difference. We used a cardiovascular trial data set to illustrate our approach.
Results
The results using the integrated event rate differences have a heuristic interpretation for the treatment difference even when the PHs assumption is not valid. When the event rates are low, for example, for the cardiovascular study discussed in this article, the procedure for the integrated event rate difference provides tight interval estimates in contrast to those based on the event-driven inference method.
Limitations
The design of a trial with the integrated event rate difference may be more complicated than that using the event-driven procedure. One may use simulation to determine the sample size and the estimated duration of the study.
Conclusions
The procedure discussed in this article can be a useful alternative to the standard PHs method in the survival analysis.
The 2 + 2 photocycloaddition reaction between an imine and an alkene component, the aza Paternò-Büchi reaction, is one of the most efficient ways to synthesize functionalized azetidines. However, the ...application of the aza Paternò-Büchi reaction has been met with limited success due to the inherent challenges associated with this approach. This review covers the current scope and limitations of reported examples of aza Paternò-Büchi reactions in organic synthesis. An outlook is provided, which highlights recent improvements and the discovery of new reaction protocols that have overcome some long-standing challenges within this field of research.
This review discusses the current scope and limitations of the 2 + 2 photocycloaddition reaction between an imine and an alkene component, the aza Paternò-Büchi reaction, and highlights recent improvements within this area of research.
A mild method is presented for the formation of N-acylated oxazolidinones that employs acid fluorides and mild bases, such as i Pr2NEt and NEt3. Optimized reaction conditions for two types of ...substrates have been developed utilizing either the oxazolidinone itself or the corresponding in situ generated O-silyloxazolidinones resulting in the formation of the desired N-acylated products in high yields of up to 98%.
Early arthroplasty designs were associated with a high level of anterior knee pain as they failed to cater for the patello-femoral joint. Patellar resurfacing was heralded as the saviour safeguarding ...patient satisfaction and success but opinion on its necessity has since deeply divided the scientific community and has become synonymous to topics of religion or politics. Opponents of resurfacing contend that the native patella provides better patellar tracking, improved clinical function, and avoids implant-related complications, whilst proponents argue that patients have less pain, are overall more satisfied, and avert the need for secondary resurfacing. The question remains whether complications associated with patellar resurfacing including those arising from future component revision outweigh the somewhat increased incidence of anterior knee pain recorded in unresurfaced patients. The current scientific literature, which is often affected by methodological limitations and observer bias, remains confusing as it provides evidence in support of both sides of the argument, whilst blinded satisfaction studies comparing resurfaced and non-resurfaced knees generally reveal equivalent results. Even national arthroplasty register data show wide variations in the proportion of patellar resurfacing between countries that cannot be explained by cultural differences alone. Advocates who always resurface or never resurface indiscriminately expose the patella to a random choice. Selective resurfacing offers a compromise by providing a decision algorithm based on a propensity for improved clinical success, whilst avoiding potential complications associated with unnecessary resurfacing. Evidence regarding the validity of selection criteria, however, is missing, and the decision when to resurface is often based on intuitive reasoning. Our lack of understanding why, irrespective of pre-operative symptoms and patellar resurfacing, some patients may suffer pain following TKA and others may not have so far stifled our efforts to make the strategy of selective resurfacing succeed. We should hence devote our efforts in defining predictive criteria and indicators that will enable us to reliably identify those individuals who might benefit from a resurfacing procedure.
Level of evidence
V.
Modern cosmological observations allow us to study in great detail the evolution and history of the large scale structure hierarchy. The fundamental problem of accurate constraints on the ...cosmological parameters, within a given cosmological model, requires precise modelling of the observed structure. In this paper we briefly review the current most effective techniques of large scale structure simulations, emphasising both their advantages and shortcomings. Starting with basics of the direct
N
-body simulations appropriate to modelling cold dark matter evolution, we then discuss the direct-sum technique
GRAPE
, particle-mesh (
PM
) and hybrid methods, combining the
PM
and the tree algorithms. Simulations of baryonic matter in the Universe often use hydrodynamic codes based on both particle methods that discretise mass, and grid-based methods. We briefly describe Eulerian grid methods, and also some variants of Lagrangian smoothed particle hydrodynamics (
SPH
) methods.
Purpose
Raising awareness of respiratory diphtheria and for the importance of early antitoxin administration.
Methods
Report of a case of fulminant, imported respiratory diphtheria in an otherwise ...healthy 24-year-old Afghan refugee in Austria in May 2022.
Result
This was the first case of respiratory diphtheria in Austria since 1993. Diphtheria antitoxin was administered at an already progressed disease stage. This delay contributed to a fulminant disease course with multiorgan failure and death.
Conclusion
In high-income countries with low case numbers, awareness of respiratory diphtheria and for the importance of early antitoxin administration must be raised.
Swallowing Disorders in the Elderly Schindler, Joshua S.; Kelly, James H.
The Laryngoscope,
April 2002, Letnik:
112, Številka:
4
Journal Article
Recenzirano
Changes that occur as a natural part of senescence in the complex action of deglutition predispose us to dysphagia and aspiration. As the “baby‐boomers” begin to age, the onset of swallowing ...difficulties will begin to manifest in a greater number of our population. Recent advances in the evaluation of normal and abnormal swallowing make possible more precise anatomical and physiological diagnoses. Coupled with an understanding of swallowing physiology, such detailed evaluation allows greater opportunity to safely manage dysphagia with directed therapy and appropriate surgical intervention. The current study is a discussion of the changes that occur in deglutition with normal aging, contemporary evaluation of swallowing function, and some of the common causes of dysphagia in elderly patients.
Context. Aims. We derive rotation curves from optical emission lines of 182 disc galaxies (96 in the cluster and 86 in the field) in the region of Abell 901/902 located at z ~ 0.165. We continue the ...kinematic analysis presented in a previous paper. Here, we focus on the analysis of B-band and stellar-mass Tully-Fisher relations. We examine possible environmental dependencies and differences between normal spirals and dusty red galaxies, i.e. disc galaxies that have red colours because of relatively low star formation rates. Methods. Assuming a tilted ring model we simulate the spectroscopy of a given galaxy and reconstruct the maximum rotation velocity from the best-fitting simulated rotation curve. We fit regression lines adopting a maximum-likelihood method based on Bayes’ theorem to build B-band and stellar-mass Tully-Fisher relations. Results. We find no significant differences between the best-fit Tully-Fisher slope of cluster and field galaxies. At fixed slope, the field population with high-quality rotation curves (57 objects) is brighter by ΔMB = −0.m42 ± 0.m15 than the cluster population (55 objects). We show that this slight difference is at least in part an environmental effect. The scatter of the cluster Tully-Fisher relation increases for galaxies closer to the core region, also indicating an environmental effect. Interestingly, dusty red galaxies become fainter towards the core at a given rotation velocity (i.e. total mass). This indicates that the star formation in these galaxies is in the process of being quenched. The luminosities of normal spiral galaxies are slightly higher at fixed rotation velocity for smaller cluster-centric radii. These galaxies are probably gas-rich (compared to the dusty red population) and the onset of ram-pressure stripping increases their star-formation rates. Galaxies with smooth morphology show higher root mean square values in the fitting of their rotation curves. This is particularly the case for dusty red galaxies. A cluster-specific interaction process like ram-pressure stripping is the best explanation, since it only affects the gaseous disc but not the stellar morphology. Conclusions. The results from the Tully-Fisher analysis are consistent with and complement our previous findings. Dusty red galaxies might be an intermediate stage in the transformation of infalling field spiral galaxies into cluster lenticulars (also known as S0s), and this might explain the well-known increase of the S0 fraction in galaxy clusters with cosmic time.
The olefin metathesis reaction of two unsaturated substrates is one of the most powerful carbon-carbon-bond-forming reactions in organic chemistry. Specifically, the catalytic olefin metathesis ...reaction has led to profound developments in the synthesis of molecules relevant to the petroleum, materials, agricultural and pharmaceutical industries. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism. While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.
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