Graphically structured value-function compilation

AbstractClassical work on eliciting and representing preferences over multi-attribute alternatives has attempted to recognize conditions under which value functions take on particularly simple and compact form, making their elicitation much easier. In this paper we consider preferences over discrete domains, and show that for a certain class of simple and intuitive qualitative preference statements, one can always generate compact value functions consistent with these statements. These value functions maintain the independence structure implicit in the original statements. For discrete domains, these representation theorems are much more general than previous results. However, we also show that it is not always possible to maintain this compact structure if we add explicit ordering constraints among the available outcomes

Patterns of intron gain and conservation in eukaryotic genes

<p>Abstract</p> <p>Background:</p> <p>The presence of introns in protein-coding genes is a universal feature of eukaryotic genome organization, and the genes of multicellular eukaryotes, typically, contain multiple introns, a substantial fraction of which share position in distant taxa, such as plants and animals. Depending on the methods and data sets used, researchers have reached opposite conclusions on the causes of the high fraction of shared introns in orthologous genes from distant eukaryotes. Some studies conclude that shared intron positions reflect, almost entirely, a remarkable evolutionary conservation, whereas others attribute it to parallel gain of introns. To resolve these contradictions, it is crucial to analyze the evolution of introns by using a model that minimally relies on arbitrary assumptions.</p> <p>Results:</p> <p>We developed a probabilistic model of evolution that allows for variability of intron gain and loss rates over branches of the phylogenetic tree, individual genes, and individual sites. Applying this model to an extended set of conserved eukaryotic genes, we find that parallel gain, on average, accounts for only ~8% of the shared intron positions. However, the distribution of parallel gains over the phylogenetic tree of eukaryotes is highly non-uniform. There are, practically, no parallel gains in closely related lineages, whereas for distant lineages, such as animals and plants, parallel gains appear to contribute up to 20% of the shared intron positions. In accord with these findings, we estimated that ancestral introns have a high probability to be retained in extant genomes, and conversely, that a substantial fraction of extant introns have retained their positions since the early stages of eukaryotic evolution. In addition, the density of sites that are available for intron insertion is estimated to be, approximately, one in seven basepairs.</p> <p>Conclusion:</p> <p>We obtained robust estimates of the contribution of parallel gain to the observed sharing of intron positions between eukaryotic species separated by different evolutionary distances. The results indicate that, although the contribution of parallel gains varies across the phylogenetic tree, the high level of intron position sharing is due, primarily, to evolutionary conservation. Accordingly, numerous introns appear to persist in the same position over hundreds of millions of years of evolution. This is compatible with recent observations of a negative correlation between the rate of intron gain and coding sequence evolution rate of a gene, suggesting that at least some of the introns are functionally relevant.</p

Centre de Formentera: els inicis en qüestió de dependència

Fins ara l’atenció i els serveis sociosanitaris específics per a la tercera edat i els malalts crònics han estat gairebé inexistents a Formentera; el tipus d’assistència que s’ha donat ha estat majoritàriament d’ajuda o de suport mitjançant el curador informal. És un fet que els trets particulars que presenta Formentera plantegen unes necessitats especials; així, cal un esforç per aconseguir una equiparació en les prestacions i els serveis existents a la resta d’illes. La construcció d’un centre de dia suposa un pas important per superar aquesta mancança de recursos, i alhora és un projecte necessari i esperat a l’illa. Segons les dades demogràfiques, la de Formentera serà una població envellida; aquest centre garantirà a la població una millor qualitat d’atenció i de vida, donant resposta i cobertura a les necessitats de les persones dependents, amb serveis que, d’altra banda, són de primera necessitat. Aquest projecte suposa un repte tant institucional com professional. Les característiques de Formentera fan que el centre estigui plantejat per donar assistència als tres col·lectius més vulnerables i desprotegits: persones grans dependents, persones amb algun tipus de discapacitat i persones amb malaltia mental; d’aquesta manera ens trobam davant tres centres dins una mateixa instal·lació. Així, el Programa Bàsic del Centre s’inscriu dins una estratègia institucional dirigida a oferir un marc terapèutic que faciliti confiança i seguretat a l’usuari i que mitjançant el suport i l’ensenyament permeti treballar les capacitats conservades, millorant l’autonomia i alentint el procés de dependència. Cal destacar la novetat del recurs per als habitants de Formentera, juntament amb un factor cultural molt arrelat a l’illa, que estableix la cura de les persones grans a casa i sota la figura d’algun familiar. Malgrat això, les actuals previsions indiquen un debilitament d’aquesta xarxa de cures, circumstància que ve provocada per diversos factors: el canvi en el rol social de la dona, l’envelliment i augment de la fragilitat dels cuidadors, així com l’estrès del cuidador / la cuidadora, habitualment generat per una situació de cures llarga i intensa —i sovint difícil— en absència d’un suport adequat.Hasta ahora la atención y los servicios sociosanitarios específicos para la tercera edad y los enfermos crónicos han sido casi inexistentes en Formentera; el tipo de asistencia dirigida ha sido mayoritariamente de ayuda o apoyo mediante el cuidador informal. Es un hecho que las particulares condiciones que presenta la isla plantean unas necesidades especiales, así hace falta un esfuerzo para conseguir una equiparación en las prestaciones y servicios existentes en el resto de islas y donde la construcción de un centro de día en Formentera supone un paso importante para superar la carencia de recursos o estructuras sociosanitarias. Este Centro de día es un proyecto necesario y esperado en la isla, que prevé paliar el déficit sociosanitario existente hasta ahora. Según los datos demográficos, Formentera, en un futuro, será una población envejecida; este centro garantizará a la población una mejor calidad de atención y de vida, dando respuesta y cobertura a las necesidades de las persones dependientes con servicios que, por otro lado, son de primera necesidad. La puesta en marcha de este proyecto supone un reto tanto a nivel institucional como profesional. Las características de Formentera (tamaño, población, aislamiento, etc.), hacen que el proyecto de centro de día esté planteado para dar asistencia a los tres colectivos más vulnerables y desprotegidos: personas mayores dependientes, personas con algún tipo de discapacidad y personas con enfermedad mental, de este modo nos encontramos ante tres centros de día dentro de una misma instalación. Así, el Programa Básico del Centro se inscribe dentro de una estrategia institucional dirigida a ofrecer un marco terapéutico que facilite confianza y seguridad al usuario y que, a través del apoyo y la enseñanza, permita trabajar sobre las capacidades conservadas mejorando la autonomía y ralentizando el proceso de dependencia. También se tiene que destacar la novedad del recurso para los habitantes de la isla y un factor cultural muy arraigado en la población de Formentera que establece el cuidado de los mayores en casa y bajo la figura de algún familiar. Sin embargo, las actuales previsiones indican un debilitamiento de esta red de apoyo, circunstancia que viene provocada por varios factores: el cambio en el rol social de la mujer, el envejecimiento y aumento de la fragilidad de los cuidadores, así como el estrés del cuidador/a habitualmente generado por una situación de curas larga e intensa —y a menudo difícil— en ausencia de un apoyo adecuado

Volume Introduction

Medical devices have historically been less regulated than their drug and biologic counterparts. A benefit of this less demanding regulatory regime is facilitating innovation by making new devices available to consumers in a timely fashion. Nevertheless, there is increasing concern that this approach raises serious public health and safety concerns. The Institute of Medicine in 2011 published a critique of the American pathway allowing moderate-risk devices to be brought to the market through the less-rigorous 501(k) pathway,1 flagging a need for increased postmarket review and surveillance. High-profile recalls of medical devices, such as vaginal mesh products, along with reports globally of nearly two million injuries and more than 80,000 deaths linked to faulty medical devices,2 have raised public health critiques regarding the oversight of these products. Should we follow the recommendation of the Institute of Medicine to reduce the use of the 510(k) pathway, and, if so, what should replace it? What would an ideal regulatory pathway, reflecting the twin goals of innovation and patient protection, look like in the twenty-first century? These questions are complicated by new tools and mechanisms that can be used to achieve our goals. For example, in an era of big data, where we have the capabilities to better follow postmarket incidents, what should postmarket review look like

EREM: Parameter Estimation and Ancestral Reconstruction by Expectation-Maximization Algorithm for a Probabilistic Model of Genomic Binary Characters Evolution

Evolutionary binary characters are features of species or genes, indicating the absence (value zero) or presence (value one) of some property. Examples include eukaryotic gene architecture (the presence or absence of an intron in a particular locus), gene content, and morphological characters. In many studies, the acquisition of such binary characters is assumed to represent a rare evolutionary event, and consequently, their evolution is analyzed using various flavors of parsimony. However, when gain and loss of the character are not rare enough, a probabilistic analysis becomes essential. Here, we present a comprehensive probabilistic model to describe the evolution of binary characters on a bifurcating phylogenetic tree. A fast software tool, EREM, is provided, using maximum likelihood to estimate the parameters of the model and to reconstruct ancestral states (presence and absence in internal nodes) and events (gain and loss events along branches)

When Is a Change Significant? The Update Problem of Apps in Medical and Behavioral Research

Digital applications (apps) are commonly used across the research ecosystem. While apps are frequently updated in the course of clinical and behavioral research, there is limited guidance as to when an app update should trigger action related to human research participant protections and who should be responsible for monitoring and reviewing these updates. We term this the “update problem” and argue that, while it is the principal investigator\u27s duty to track all relevant updates, the level of involvement and re-review by the institutional review board (IRB) of an approved research protocol should vary depending on whether the update may be classified as minor, not minor, or significant. Minor updates require at most annual notification of the IRB, updates that are not minor require prompt notification of the IRB, and significant updates may require full board re-review or another response. We also suggest how these policies might be implemented