ABCtoolbox: a versatile toolkit for approximate Bayesian computations

Background The estimation of demographic parameters from genetic data often requires the computation of likelihoods. However, the likelihood function is computationally intractable for many realistic evolutionary models, and the use of Bayesian inference has therefore been limited to very simple models. The situation changed recently with the advent of Approximate Bayesian Computation (ABC) algorithms allowing one to obtain parameter posterior distributions based on simulations not requiring likelihood computations. Results Here we present ABCtoolbox, a series of open source programs to perform Approximate Bayesian Computations (ABC). It implements various ABC algorithms including rejection sampling, MCMC without likelihood, a Particle-based sampler and ABC-GLM. ABCtoolbox is bundled with, but not limited to, a program that allows parameter inference in a population genetics context and the simultaneous use of different types of markers with different ploidy levels. In addition, ABCtoolbox can also interact with most simulation and summary statistics computation programs. The usability of the ABCtoolbox is demonstrated by inferring the evolutionary history of two evolutionary lineages of Microtus arvalis. Using nuclear microsatellites and mitochondrial sequence data in the same estimation procedure enabled us to infer sex-specific population sizes and migration rates and to find that males show smaller population sizes but much higher levels of migration than females. Conclusion ABCtoolbox allows a user to perform all the necessary steps of a full ABC analysis, from parameter sampling from prior distributions, data simulations, computation of summary statistics, estimation of posterior distributions, model choice, validation of the estimation procedure, and visualization of the results.

Promoting palliative care in the community: production of the primary palliative care toolkit by the European Association of Palliative Care Taskforce in primary palliative care

BACKGROUND A multidisciplinary European Association of Palliative Care Taskforce was established to scope the extent of and learn what facilitates and hinders the development of palliative care in the community across Europe. AIM To document the barriers and facilitators for palliative care in the community and to produce a resource toolkit that palliative care specialists, primary care health professionals or policymakers, service developers, educationalists and national groups more generally could use to facilitate the development of palliative care in their own country. DESIGN (1) A survey instrument was sent to general practitioners with knowledge of palliative care services in the community in a diverse sample of European countries. We also conducted an international systematic review of tools used to identify people for palliative care in the community. (2) A draft toolkit was then constructed suggesting how individual countries might best address these issues, and an online survey was then set up for general practitioners and specialists to make comments. Iterations of the toolkit were then presented at international palliative care and primary care conferences. RESULTS Being unable to identify appropriate patients for palliative care in the community was a major barrier internationally. The systematic review identified tools that might be used to help address this. Various facilitators such as national strategies were identified. A primary palliative care toolkit has been produced and refined, together with associated guidance. CONCLUSION Many barriers and facilitators were identified. The primary palliative care toolkit can help community-based palliative care services to be established nationally.

A versatile toolkit to produce sensitive FRET biosensors to visualize signaling in time and space

Genetically encoded, ratiometric biosensors based on fluorescence resonance energy transfer (FRET) are powerful tools to study the spatiotemporal dynamics of cell signaling. However, many biosensors lack sensitivity. We present a biosensor library that contains circularly permutated mutants for both the donor and acceptor fluorophores, which alter the orientation of the dipoles and thus better accommodate structural constraints imposed by different signaling molecules while maintaining FRET efficiency. Our strategy improved the brightness and dynamic range of preexisting RhoA and extracellular signal-regulated protein kinase (ERK) biosensors. Using the improved RhoA biosensor, we found micrometer-sized zones of RhoA activity at the tip of F-actin bundles in growth cone filopodia during neurite extension, whereas RhoA was globally activated throughout collapsing growth cones. RhoA was also activated in filopodia and protruding membranes at the leading edge of motile fibroblasts. Using the improved ERK biosensor, we simultaneously measured ERK activation dynamics in multiple cells using low-magnification microscopy and performed in vivo FRET imaging in zebrafish. Thus, we provide a construction toolkit consisting of a vector set, which enables facile generation of sensitive biosensors.

Retrospective analysis of stored dried blood spots from children with cystic fibrosis and matched controls to assess the performance of a proposed newborn screening protocol in Switzerland

Newborn screening (NBS) for Cystic Fibrosis (CF) has been introduced in many countries, but there is no ideal protocol suitable for all countries. This retrospective study was conducted to evaluate whether the planned two step CF NBS with immunoreactive trypsinogen (IRT) and 7 CFTR mutations would have detected all clinically diagnosed children with CF in Switzerland.

Stress and pain response of neonates after spontaneous birth and vacuum-assisted and cesarean delivery

The objective of the study was to compare the stress response and pain expression of newborns (NBs) in the early postpartum period.

Newborn screening for cystic fibrosis in Switzerland - Consequences after analysis of a 4 months pilot study

BACKGROUND: Switzerland introduced newborn screening (NBS) for CF in 2011, using an IRT/DNA/IRT protocol. This paper describes the results of the first year and compares two versions of the protocol with different IRT cut-offs, particularly effects on recall rate, sensitivity and specificity. METHODS: IRT cut-offs were >45ng/ml (99.0th percentile) in period 1 (months 1-4) and >50ng/ml (99.2nd percentile) in period 2 (months 5-12). In period 2 we abstained from recalls when none of the 7 most common CF mutations were detected and IRT was <60ng/ml. RESULTS: In periods 1 and 2, 26,535 and 56,663 tests were performed. Recall rates were 0.94% and 0.48%, respectively (p<0.001), PPV increased from 23% to 47% (p=0.024) and sensitivity was 90% and 100%. CONCLUSIONS: Raising initial IRT cut-off from the 99.0th to the 99.2nd percentile and abstaining from recalls for children with an IRT<60ng/ml and carrying no major CFTR mutation significantly reduced the recall rate without affecting sensitivity.

Distribution Map

Understanding large software systems is a challenging task, and to support it many approaches have been developed. Often, the result of these approaches categorize existing entities into new groups or associates them with mutually exclusive properties. In this paper we present the Distribution Map as a generic technique to visualize and analyze this type of result. Our technique is based on the notion of focus, which shows whether a property is well-encapsulated or cross-cutting, and the notion of spread, which shows whether the property is present in several parts of the system. We present a basic visualization and complement it with measurements that quantify focus and spread. To validate our technique we show evidence of applying it on the result sets of different analysis approaches. As a conclusion we propose that the Distribution Map technique should belong to any reverse engineering toolkit.

EC Electronic Communications and Competition Law

Telecommunications have developed at an incredible speed over the last couple of decades. The decreasing size of our phones and the increasing number of ways in which we can communicate are barely the only result of this (r)evolutionary development. The latter has indeed multiple implications. The change of paradigm for telecommunications regulation, epitomised by the processes of liberalisation and reregulation, was not sufficient to answer all regulatory questions pertinent to communications. Today, after the transition from monopoly to competition, we are faced perhaps with an even harder regulatory puzzle, since we must figure out how to regulate a sector that is as dynamic and as unpredictable as electronic communications have proven to be, and as vital and fundamental to the economy and to society at large. The present book addresses the regulatory puzzle of contemporary electronic communications and suggests the outlines of a coherent model for their regulation. The search for such a model involves essentially deliberations on the question "Can competition law do it all?", since generic competition rules are largely seen as the appropriate regulatory tool for the communications domain. The latter perception has been the gist of the 2002 reform of the European Community (EC) telecommunications regime, which envisages a withdrawal of sectoral regulation, as communications markets become effectively competitive and ultimately bestows the regulation of the sector upon competition law only. The book argues that the question of whether competition law is the appropriate tool needs to be examined not in the conventional contexts of sector specific rules versus competition rules or deregulation versus regulation but in a broader governance context. Consequently, the reader is provided with an insight into the workings and specific characteristics of the communications sector as network-bound, converging, dynamic and endowed with a special societal role and function. A thorough evaluation of the regulatory objectives in the communications environment contributes further to the comprehensive picture of the communications industry. Upon this carefully prepared basis, the book analyses the communications regulatory toolkit. It explores the interplay between sectoral communications regulation, competition rules (in particular Article 82 of the EC Treaty) and the rules of the World Trade Organization (WTO) relevant to telecommunications services. The in-depth analysis of multilevel construct of EC communications law is up-to-date and takes into account important recent developments in the EC competition law in practice, in particular in the field of refusal to supply and tying, of the reform of the EC electronic communications framework and new decisions of the WTO dispute settlement body, such as notably the Mexico-Telecommunications Services Panel Report. Upon these building elements, an assessment of the regulatory potential of the EC competition rules is made. The conclusions drawn are beyond the scope of the current situation of EC electronic communications and the applicable law and explore the possible contours of an optimal regulatory framework for modern communications. The book is of particular interest to communications and antitrust law experts, as well as policy makers, government agencies, consultancies and think-tanks active in the field. Experts on other network industries (such as electricity or postal communications) can also profit from the substantial experience gathered in the communications sector as the most advanced one in terms of liberalisation and reregulation.

A Skull-Stripping Filter for ITK

Skull-stripping (or brain extraction) is an important pre-processing step in neuroimage analysis. This document describes a skull-stripping filter implemented using the Insight Toolkit ITK, which we named itk::StripTsImageFilter. It is a composite filter based on existing ITK classes. The filter has been implemented with usability, robustness, speed and versatility in mind, rather than accuracy. This makes it useful for many pre-processing tasks in neuroimage analysis. This paper is accompanied by the source code, input data and a testing environment.

One-year evaluation of a neonatal screening program for cystic fibrosis in Switzerland

BACKGROUND From January 2011 onward, the Swiss newborn screening (NBS) program has included a test for cystic fibrosis (CF). In this study, we evaluate the first year of implementation of the CF-NBS program. METHODS The CF-NBS program consists of testing in two steps: a heel prick sample is drawn (= Guthrie test) for measurement of immunoreactive trypsinogen (IRT) and for DNA screening. All children with a positive screening test are referred to a CF center for further diagnostic testing (sweat test and genetic analysis). After assessment in the CF center, the parents are given a questionnaire. All the results of the screening process and the parent questionnaires were centrally collected and evaluated. RESULTS In 2011, 83 198 neonates were screened, 84 of whom (0.1%) had a positive screening result and were referred to a CF center. 30 of these 84 infants were finally diagnosed with CF (positive predictive value: 35.7%). There was an additional infant with CF and meconium ileus whose IRT value was normal. The 31 diagnosed children with CF correspond to an incidence of 1 : 2683. The average time from birth to genetically confirmed diagnosis was 34 days (range: 13-135). 91% of the parents were satisfied that their child had undergone screening. All infants receiving a diagnosis of CF went on to receive further professional care in a CF center. CONCLUSION The suggested procedure for CF-NBS has been found effective in practice; there were no major problems with its implementation. It reached high acceptance among physicians and parents.

Using virtual reality to teach special populations how to cope in crisis: the case of a virtual earthquake

The unique characteristics of special populations such as pre-school children and Down syndrome kids in crisis and their distorted self-image were never studied before, because of the difficulty of crisis reproduction. This study proposes a VR setting that tries to model some special population's behaviour in the time of crises and offers them a training scenario. The sample population consisted of 30 pre-school children and 20 children with Down syndrome. The VR setting involved a high-speed PC, a VPL EyePhone 1, a MR toolkit, a vibrations plate, a motion capture system and other sensors. The system measured and modelled the typical behaviour of these special populations in a Virtual Earthquake scenario with sight and sound and calculated a VR anthropomorphic model that reproduced their behaviour and emotional state. Afterwards one group received an emotionally enhanced VR self-image as feedback for their training, one group received a plain VR self-image and another group received verbal instructions. The findings strongly suggest that the training was a lot more biased by the emotionally enhanced VR self-image than the other approaches. These findings could highlight the special role of the self-image to therapy and training and the interesting role of imagination to emotions, motives and learning. Further studies could be done with various scenarios in order to measure the best-biased behaviour and establish the most natural and affective VR model. This presentation is going to highlight the main findings and some theories behind them.

EC Electronic Communications and Competition Law

Telecommunications have developed at an incredible speed over the last couple of decades. The decreasing size of our phones and the increasing number of ways in which we can communicate are barely the only result of this (r)evolutionary development. The latter has indeed multiple implications. The change of paradigm for telecommunications regulation, epitomised by the processes of liberalisation and reregulation, was not sufficient to answer all regulatory questions pertinent to communications. Today, after the transition from monopoly to competition, we are faced perhaps with an even harder regulatory puzzle, since we must figure out how to regulate a sector that is as dynamic and as unpredictable as electronic communications have proven to be, and as vital and fundamental to the economy and to society at large. The present book addresses the regulatory puzzle of contemporary electronic communications and suggests the outlines of a coherent model for their regulation. The search for such a model involves essentially deliberations on the question "Can competition law do it all?", since generic competition rules are largely seen as the appropriate regulatory tool for the communications domain. The latter perception has been the gist of the 2002 reform of the European Community (EC) telecommunications regime, which envisages a withdrawal of sectoral regulation, as communications markets become effectively competitive and ultimately bestows the regulation of the sector upon competition law only. The book argues that the question of whether competition law is the appropriate tool needs to be examined not in the conventional contexts of sector specific rules versus competition rules or deregulation versus regulation but in a broader governance context. Consequently, the reader is provided with an insight into the workings and specific characteristics of the communications sector as network-bound, converging, dynamic and endowed with a special societal role and function. A thorough evaluation of the regulatory objectives in the communications environment contributes further to the comprehensive picture of the communications industry. Upon this carefully prepared basis, the book analyses the communications regulatory toolkit. It explores the interplay between sectoral communications regulation, competition rules (in particular Article 82 of the EC Treaty) and the rules of the World Trade Organization (WTO) relevant to telecommunications services. The in-depth analysis of multilevel construct of EC communications law is up-to-date and takes into account important recent developments in the EC competition law in practice, in particular in the field of refusal to supply and tying, of the reform of the EC electronic communications framework and new decisions of the WTO dispute settlement body, such as notably the Mexico-Telecommunications Services Panel Report. Upon these building elements, an assessment of the regulatory potential of the EC competition rules is made. The conclusions drawn are beyond the scope of the current situation of EC electronic communications and the applicable law and explore the possible contours of an optimal regulatory framework for modern communications. The book is of particular interest to communications and antitrust law experts, as well as policy makers, government agencies, consultancies and think-tanks active in the field. Experts on other network industries (such as electricity or postal communications) can also profit from the substantial experience gathered in the communications sector as the most advanced one in terms of liberalisation and reregulation.

Typology of the Tools of EC Communications Regulation

The present article is an abridged version of a chapter to the book EC Electronic Communications and Competition Law (London: Cameron May 2007). It explores in a neutral manner the pros and cons of the currently applied toolkit of European Community communications law, i.e. the generic competition law rules and the sector specific regulatory framework. A number of criteria are introduced and these tools are then tested as to their efficiency and efficacy.

Promoting Local Innovations: A tool for adaptation to climate change and sustainable development in Mountains

Throughout their history mountain communities have had to adapt to changing environmental and socio-economic conditions. They have developed strategies and specialized knowledge to sustain their livelihoods in a context of adverse climatic events and constant change. As negotiations and discussions on climate change emphasize the critical need for locally relevant and community owned adaptation strategies, there is a need for new tools to capitalize on this local knowledge and endogenous potential for innovation. The toolkit Promoting Local Innovation (PLI) was designed by the Centre for Development and Environment (CDE) of the University of Bern, Switzerland, to facilitate a participatory social learning process which identifies locally available innovations that can be implemented for community development. It is based on interactive pedagogy and joint learning among different stakeholders in the local context. The tried-and-tested tool was developed in the Andean region in 2004, and then used in International Union for Conservation of Nature (IUCN) climate change adaptation projects in Thailand, Burkina Faso, Senegal, and Chile. These experiences showed that PLI can be used to involve all relevant stakeholders in establishing strategies and actions needed for rural communities to adapt to climate change impacts, while building on local innovation potential and promoting local ownership