Alternate, Easy and practical synthesis of allyl amines from acetyl derivatives of Baylis-Hillman adducts using Methanolic Ammonia

A methanolic ammonia-mediated alternate, easy and practical stereoselective synthesis of allyl amines from the acetyl derivatives of Baylis-Hillman adducts is described.

Practical, Pluggable Types for a Dynamic Language

Most languages fall into one of two camps: either they adopt a unique, static type system, or they abandon static type-checks for run-time checks. Pluggable types blur this division by (i) making static type systems optional, and (ii) supporting a choice of type systems for reasoning about different kinds of static properties. Dynamic languages can then benefit from static-checking without sacrificing dynamic features or committing to a unique, static type system. But the overhead of adopting pluggable types can be very high, especially if all existing code must be decorated with type annotations before any type-checking can be performed. We propose a practical and pragmatic approach to introduce pluggable type systems to dynamic languages. First of all, only annotated code is type-checked. Second, limited type inference is performed on unannotated code to reduce the number of reported errors. Finally, external annotations can be used to type third-party code. We present Typeplug, a Smalltalk implementation of our framework, and report on experience applying the framework to three different pluggable type systems.

Practical Object-Oriented Back-in-Time Debugging

Back-in-time debuggers are extremely useful tools for identifying the causes of bugs, as they allow us to inspect the past states of objects no longer present in the current execution stack. Unfortunately the "omniscient" approaches that try to remember all previous states are impractical because they either consume too much space or they are far too slow. Several approaches rely on heuristics to limit these penalties, but they ultimately end up throwing out too much relevant information. In this paper we propose a practical approach to back-in-time debugging that attempts to keep track of only the relevant past data. In contrast to other approaches, we keep object history information together with the regular objects in the application memory. Although seemingly counter-intuitive, this approach has the effect that past data that is not reachable from current application objects (and hence, no longer relevant) is automatically garbage collected. In this paper we describe the technical details of our approach, and we present benchmarks that demonstrate that memory consumption stays within practical bounds. Furthermore since our approach works at the virtual machine level, the performance penalty is significantly better than with other approaches.

What is the Relation between Human Practical Action and an Accompanying Discourse? Discussing the Status of Practical Theory

The article discusses the function of an accompanying discourse in relation to the genesis of human practical action. On the one side, theory cannot be taken as the ground for practical action; practical action is not a realisation of intentions. On the other hand, human practical action is accompanied by series of explanations, justifications, declarations of intent, pre‑ and post-rationalisations, motivations etc. These accompanying discourses seem in one way or the other to be necessary for the actual realisation of human practical action. Following Pierre Bourdieu, it is suggested that an accompanying discourse cannot in a meaningful manner be separated from the human practical action, that practical theory should be regarded not as theory but as part of practice, and that practical theory first of all provides a common language for talking about practice and hence for reproducing a fundamentally arbitrary idea of the genesis of human practical action. Parallels are drawn to the education/formal training of semi-professionals.

A practical posture for hand grip dynamometry in the clinical setting

The optimal testing position for hand grip strength, which is a useful functional measure of nutritional status, is open to debate. We therefore examined the systematic difference between different postures in order to establish a methodology that is clinically relevant, easy to perform and reproducible.

Methodological considerations and practical recommendations for the application of peripheral arterial tonometry in children and adolescents

Endothelial dysfunction is recognized as the primum movens in the development of atherosclerosis. Its crucial role in both cardiovascular morbidity and mortality has been confirmed. In the past, research was hampered by the invasive character of endothelial function assessment. The development of non-invasive and feasible techniques to measure endothelial function has facilitated and promoted research in various adult and paediatric subpopulations. To avoid user dependence of flow-mediated dilation (FMD), which evaluates nitric oxide dependent vasodilation in large vessels, a semi-automated, method to assess peripheral microvascular function, called peripheral arterial tonometry (Endo-PAT®), was recently introduced. The number of studies using this technique in children and adolescents is rapidly increasing, yet there is no consensus with regard to either measuring protocol or data analysis of peripheral arterial tonometry in children and adolescents. Most paediatric studies simply applied measuring and analysing methodology established in adults, a simplification that may not be appropriate. This paper provides a detailed description of endothelial function assessment using the Endo-PAT for researchers and clinicians. We discuss clinical and methodological considerations and point out the differences between children, adolescents and adults. Finally, the main aim of this paper is to provide recommendations for a standardised application of Endo-PAT in children and adolescents, as well as for population-specific data analysis methodology.

Bullous pemphigoid: therapeutic algrorithm and practical management

Introduction: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucosae. BP typically affects the elderly and manifests with severe itch, localised or generalised eczematous, urticated and/or bullous lesions. Its morbidity and impact on the quality of life are important. The disease is significantly associated with neurological disorders, such as stroke, Parkinson disease, major cognitive impairment and multiple sclerosis. Diagnosis of BP critically relies on immunopathologic examinations, particularly direct immunofluorescence microscopy studies. Areas covered: This paper looks at the evidence of therapies commonly used in bullous pemphigoid. Expert opinion: Treatment of BP has been a challenge, given the relative rarity of the disease, lack of good quality randomised controlled trials, the presence of co-morbidities in the affected elderly population and the high mortality rate. Recent controlled studies have indicated that potent topical corticosteroids constitute a more effective therapy for BP when compared to oral corticosteroids in terms of control of the disease, side effect profile and overall survival. Other therapies have been employed with varying success, but are not validated yet. Improved knowledge of the pathophysiology of BP will hopefully allow the development of new immunomodulatory treatments for this debilitating disease.

Practical use of dabigatran etexilate for stroke prevention in atrial fibrillation

Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists (VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio (INR). Multiple new oral anticoagulants have been developed as potential replacements for VKAs for stroke prevention in AF. Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have predictable pharmacokinetics that allow fixed dosing without routine laboratory monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to be approved by the United States Food and Drug Administration and the European Medicines Agency for stroke prevention in patients with non-valvular AF, represents an effective and safe alternative to VKAs. Under the auspices of the Regional Anticoagulation Working Group, a multidisciplinary group of experts in thrombosis and haemostasis from Central and Eastern Europe, an expert panel with expertise in AF convened to discuss practical, clinically important issues related to the long-term use of dabigatran for stroke prevention in non-valvular AF. The practical information reviewed in this article will help clinicians make appropriate use of this new therapeutic option in daily clinical practice.

My patient is thrombocytopenic! Is (s)he? Why? And what shall I do? A practical approach to thrombocytopenia

Solving the riddle of a thrombocytopenic patient is a difficult and fascinating task. The spectrum of possible aetiologies is wide, ranging from an in vitro artefact to severe treatment-resistant thrombocytopenic bleeding conditions, or even life-threatening prothrombotic states. Moreover, thrombocytopenia by itself does not protect from thrombosis and sometimes a patient with a low platelet count requires concomitant antithrombotic treatment as well. In order to identify and treat the cause and the effects of the thrombocytopenia, you have to put together several pieces of information, solving a unique jig-jaw puzzle. The present work is not a textbook article about thrombocytopenia, rather a collection of differential diagnostic thoughts, treatment concepts, and some basic knowledge, that you can retrieve when facing your next thrombocytopenic patient. Enjoy reading it, but most importantly enjoy taking care of patients with a low platelet count. I bet the present work will assist you in this challenging and rewarding clinical task.

Expertise in Clinical Psychology. The Effects of University Training and Practical Experience on Expertise in Clinical Psychology

How do university training and subsequent practical experience affect expertise in clinical psychology? To answer this question we developed methods to assess psychological knowledge and the competence to diagnose, construct case conceptualizations, and plan psychotherapeutic treatment: a knowledge test and short case studies in a first study, and a complex, dynamically evolving case study in the second study. In our cross-sectional studies, psychology students, trainees in a certified postgraduate psychotherapist curriculum, and behavior therapists with more than 10 years of experience were tested (100 in total: 20 each of novice, intermediate, and advanced university students, postgraduate trainees, and therapists). Clinical knowledge and competence increased up to the level of trainees but unexpectedly decreased at the level of experienced therapists. We discuss the results against the background of expertise research and the training of clinical psychologists (in Germany). Important factors for the continuing professional development of psychotherapists are proposed.