American Academy of Pediatrics (AAP) and American College of Medical Genetics (ACMG) recently provided two recommendations about predictive genetic testing of children. The Clinical Sequencing Exploratory Research Consortium's Pediatrics Working Group compared these recommendations, focusing on operational and ethical issues specific to decision making for children. Content analysis of the statements addresses two issues: (1) how these recommendations characterize and analyze locus of decision making, as well as the risks and benefits of testing, and (2) whether the guidelines conflict or (...) come to different but compatible conclusions because they consider different testing scenarios. These statements differ in ethically significant ways. AAP/ACMG analyzes risks and benefits using best interests of the child and recommends that, absent ameliorative interventions available during childhood, clinicians should generally decline to order testing. Parents authorize focused tests. ACMG analyzes risks and benefits using the interests of the child and other family members and recommends that sequencing results be examined for additional variants that can lead to ameliorative interventions, regardless of age, which laboratories should report to clinicians who should contextualize the results. Parents must accept additional analysis. The ethical arguments in these statements appear to be in tension with each other. (shrink)

Let T 1 , T 2 be countable first-order theories, M i ⊨ T i , and ������ any regular ultrafilter on λ ≥ $\aleph_{0}$ . A longstanding open problem of Keisler asks when T 2 is more complex than T 1 , as measured by the fact that for any such λ, ������, if the ultrapower (M 2 ) λ /������ realizes all types over sets of size ≤ λ, then so must the ultrapower (M 1 ) λ /������. (...) In this paper, building on the author's prior work [12] [13] [14], we show that the relative complexity of first-order theories in Keisler's sense is reflected in the relative graph-theoretic complexity of sequences of hypergraphs associated to formulas of the theory. After reviewing prior work on Keisler's order, we present the new construction in the context of ultrapowers, give various applications to the open question of the unstable classification, and investigate the interaction between theories and regularizing sets. We show that there is a minimum unstable theory, a minimum TP 2 theory, and that maximality is implied by the density of certain graph edges (between components arising from Szemerédi-regular decompositions) remaining bounded away from 0, 1. We also introduce and discuss flexible ultrafilters, a relevant class of regular ultrafilters which reflect the sensitivity of certain unstable (non low) theories to the sizes of regularizing sets, and prove that any ultrafilter which saturates the minimal TP 2 theory is flexible. (shrink)

For a first-order formula φ(x; y) we introduce and study the characteristic sequence ⟨P n : n < ω⟩ of hypergraphs defined by P n (y₁…., y n ):= $(\exists x)\bigwedge _{i\leq n}\varphi (x;y_{i})$ . We show that combinatorial and classification theoretic properties of the characteristic sequence reflect classification theoretic properties of φ and vice versa. The main results are a characterization of NIP and of simplicity in terms of persistence of configurations in the characteristic sequence. Specifically, we show that (...) some tree properties are detected by the presence of certain combinatorial configurations in the characteristic sequence while other properties such as instability and the independence property manifest themselves in the persistence of complicated configurations under localization. (shrink)

In this paper a semantics for dynamic predicate logic is developed that uses sequence valued assignments. This semantics is compared with the usual relational semantics for dynamic predicate logic: it is shown that the most important intuitions of the usual semantics are preserved. Then it is shown that the refined semantics reflects out intuitions about information growth. Some other issues in dynamic semantics are formulated and discussed in terms of the new sequence semantics.

In the article the basic procedures for finding of connective elements and resolving conflicts of references is analyzed. On the basis of this, a generalized algorithm is proposed that combines advantages of existing procedures for search for connective elements between phrases. The advantages of the selected procedures and their sequence are described, the formal description of input data and the results of the algorithm are presented. To optimize the procedure for scanning the text, the algorithm is performed as an iterative (...) reduction of the candidates for communication elements. This is achieved through the confirmation of non-conflict links and the gradual resolution of conflicts. (shrink)

Theories of truth and vagueness are closely connected; in this article, I draw another connection between these areas of research. Gupta and Belnap’s Revision Theory of Truth is converted into an approach to vagueness. I show how revision sequences from a general theory of definitions can be used to understand the nature of vague predicates. The revision sequences show how the meaning of vague predicates are interconnected with each other. The approach is contrasted with the similar supervaluationist approach.

It is suggested that bifurcation of parallel fibres in the cerebellar cortex assists the spatiotemporal convergence of temporally dispersed and asomatotopic inputs to granule cells. This increases the number of combinations of inputs which can be compared for the purpose of sequence recognition.

The reanalysis of genomic sequencing results has the potential to provide results that are of considerable medical and personal importance to recipients. Employing interviews with forty-seven predominantly medically underserved families and ethnographic observations we argue that there is pressing need to standardize the approach taken to reanalysis. Our findings highlight that study participants were unclear as to the likelihood of reanalysis happening, the process of initiating reanalysis, and whether they would receive revised results. Their reflections mirror the lack a specific (...) focus upon reanalysis within consent and results sessions as observed in clinical settings. Mechanisms need to be put into place that standardize the approach to reanalysis in research and in clinical contexts. This would enable clinicians and genetic counsellors to communicate clearly with research participants with respect to potential for reanalysis of results and the process of reanalysis. We argue that that the role of reanalysis is too important to be referred to in an ad-hoc manner. Furthermore, the ad-hoc nature of the current process may increase health inequities given the likelihood that only those families who have the means to press for reanalysis are likely to receive it. (shrink)

Developing ethical standards for clinical use of large-scale genome and exome sequencing has proven challenging, in part due to the inevitability of incidental or secondary findings. Policy of the American College of Medical Genetics and Genomics has evolved but remains problematic. In 2013, ACMG issued policy recommending mandatory analysis of 56 extra genes whenever sequencing was ordered for any indication, in order to ascertain positive findings in pathogenic and actionable genes. Widespread objection yielded a 2014 amendment allowing patients to opt-out (...) from analysis of the extra genes. In 2015, ACMG published the amended policy, providing that patients could opt out of the full set of extra genes, but not a subset. In 2016, ACMG enlarged the set and indicated planned expansion of the roster of extra genes to include pharmacogenetic findings. ACMG policy does not protect the respect for patient choice that prevails in other domains of clinical medicine, where informed consent allows patients to opt in to desired testing. By creating an expanding domain of genomic testing that will be routinely conducted unless patients reject the entire set of extra tests, ACMG creates an exceptional domain clinical practice that is not supported by ethics or science. (shrink)

Salmon genomics is an emerging field that represents a convergence between socially important scientific innovation and a politically volatile topic of significant interest to the public. These factors provide a strong rationale for public input. This report describes such input from a public engagement event based on the principles of deliberative democracy. The event involved a random, demographically stratified sample of 25 British Columbians (Canada). While some participants opposed sequencing the salmon genome on principle, on the whole participants responded favourably, (...) citing the value of increased knowledge of human impacts on salmon, potentially slowing or reversing this impact, and assisting sustainable management of salmon resources. Participants discussed many of the potential implications of the sequencing project and formulated recommendations pertaining to regulations, international treaties, public education and engagement. Overall, the project illustrates that the specific design and implementation of this event is capable of producing sound policy advice from the general public on genomic-related issues. (shrink)

Massively parallel sequencing, also known as next‐generation sequencing, has the potential to significantly improve newborn screening programs in the United States and around the world. Compared to genetic tests whose use is well established, sequencing allows for the analysis of large amounts of DNA, providing more comprehensive and rapid results at a lower cost. It is already being used in limited ways by some public health newborn screening laboratories in the United States and other countries—and it is under study for (...) broader and more widespread use, including as a core part of newborn screening programs. Sequencing technology has the potential to significantly improve these essential public health programs. For many of the conditions that newborns are already screened for, sequencing can return more specific and more sensitive results. The technology could also enable newborn screening programs to expand the list of rare pediatric conditions that they look for, thereby identifying more infants who can benefit from immediate care. (shrink)

Consider an axiomatic set theory in which there is a distinction between “sets” and “classes,” only sets being allowable as elements. How can one define a finite sequence of classes? This problem was proposed to me by A. Tarski, and a solution is given in this note. We shall assume the axiom system Σ used by Godei in his study of the continuum hypothesis, and shall use the same notation.1.

Recent analysis of the contribution of replication slippage to genome evolution shows that it has played a significant role in all species from eubacteria to humans. The overall level of repetition in genomes is related to genome size and to the degree of repetition that can be measured within individual ribosomai RNA genes, suggesting that the entire genome accepts simple sequences in a concerted manner when its size increases. Although coding sequences accept simple sequences much less readily than non‐coding sequences, (...) they accept some repeats, particularly (CAG)n, preferentially. This may have consequences for the evolution of the genes involved in trinucleotide expansion diseases and the transcriptional networks of which they may form a part. (shrink)

The informed consent process for genetic testing does not commonly address preferences regarding disclosure of results in the event of the patient's death. Adults being tested for familial colorectal cancer were asked whether they want their exome sequencing results disclosed to another person in the event of their death prior to receiving the results. Of 78 participants, 92% designated an individual and 8% declined to. Further research will help refine practices for informed consent.

Routine action sequences critically rely on neural mechanisms maintaining contextual and temporal information to disambiguate similar tasks (e.g. making coffee or tea). In this study we show the involvement of areas in temporal and lateral prefrontal cortices in maintaining temporal and contextual information for the execution of hierarchically‐organized action sequences.

This article proposes using structural description for graphical objects to solve an urgent task of trajectory analysis. A range of modern trajectory analysis approaches were analyzed and the best that is based on Graph Convolutional Neural Networks and Suffix Tree Clustering algorithm was chosen. Descripted ways to reduce computational sources for this neural network approach. This neural network was adapted to analyze structural description and advantages of this approach are shown.

Now widely adopted, SCID newborn screening has proven effective for early identification and treatment of SCID. In addition, screening has improved our understanding of SCID and related disorders, which are more diverse than originally believed. Newborn screening for SCID illustrates how adding new disorders to newborn screening panels can be enormously beneficial if evidence‐based guidelines are adhered to and if mechanisms are in place to track outcomes and learn along the way. These lessons should guide all additions to newborn screening, (...) including those involving sequencing. (shrink)

Whole-genome analysis and whole-exome analysis generate many more clinically actionable findings than traditional targeted genetic analysis. These findings may be relevant to research participants themselves as well as for members of their families. Though researchers performing genomic analyses are likely to find medically significant genetic variations for nearly every research participant, what they will find for any given participant is unpredictable. The ubiquity and diversity of these findings complicate questions about disclosing individual genetic test results. We outline an approach for (...) disclosing a select range of genetic results to the relatives of research participants who have died, developed in response to relatives? requests during a pilot study of large-scale medical genetic sequencing. We also argue that studies that disclose individual research results to participants should, at a minimum, passively disclose individual results to deceased participants? relatives. (shrink)

We study the influence of the individual behaviour of animals on predator-prey models. Populations of preys and predators are divided into sub-populations corresponding to different activity classes. The animals are assumed to do many activities all day long such as searching for food of different types. The preys are more vulnerable when doing some activities during which they are very exposed to predators attacks rather than for others during which they are hidden. We study activity sequences of the animals and (...) also the effect of a change in the average individual behaviour of the animals on Lotka-Volterra prey-predator interactions. Numerical simulations are realized for the whole sets of equations (governing the subpopulations) and are compared to the simulations of the reduced sets of equation (governing the populations). We look for the validity of the method with respect to a scaling factor which measures the differences between the two time scales associated to the fast-varying variables and to the slow-time varying global variables. It is shown that when the two time scales differ of about two orders of magnitude, the approximation is satisfying. (shrink)

The characteristic sequence of hypergraphs Pn:n<ω associated to a formula φ, introduced in Malliaris [5], is defined by Pn=i≤nφ. We continue the study of characteristic sequences, showing that graph-theoretic techniques, notably Szemerédi’s celebrated regularity lemma, can be naturally applied to the study of model-theoretic complexity via the characteristic sequence. Specifically, we relate classification-theoretic properties of φ and of the Pn to density between components in Szemerédi-regular decompositions of graphs in the characteristic sequence. In addition, we use Szemerédi regularity to calibrate (...) model-theoretic notions of independence by describing the depth of independence of a constellation of sets and showing that certain failures of depth imply Shelah’s strong order property SOP3; this sheds light on the interplay of independence and order in unstable theories. (shrink)

Hypotrichous ciliates extensively process genomic DNA during their life cycle. Processing occurs after cell mating, beginning with multiple rounds of DNA replication to form polytene chromosomes. Thousands of transposonlike elements are then excised from the chromosomes and destroyed, and thousands of short, internal eliminated sequences (IESs) are excised from coding and noncoding parts of genes and destroyed. IES removal from a gene is accompanied by splicing of the remaining chromosomal DNA segments to form a transcriptionally competent gene. For some genes (...) these DNA segments are in a scrambled order and are ligated into a genetically correct order at the time of IES removal. Next the polytene chromosomes are cut up band‐by‐band and all genes are excised from the chromosomes as short, linear molecules averaging 2.2 kbp (in Oxytricha nova). Gene excision is accompanied by destruction of all nongenic DNA, which, together with the transposonlike elements and IESs, accounts for ∼95% of the total sequence complexity of the genome in O. nova. Telomeric sequences are added to the excised gene‐sized DNA molecules. Finally, the gene‐sized molecules are replicated several times to form the macronucleus of the organism. (shrink)

Given their commitment to practices, science studies have bestowed considerable attention upon objects. We have the boundary object, the standardized package, the network object, the immutable mobile, the fluid object, even a fire object has entered the scene. However, these objects do not provide us with a way of understanding their historicity. They are timeless, motionless pictures rather than things that change over time, and while enacting ‘historical moments’ they do not make visible the histories they contain within them. What (...) kind of object could embody history and make that history visible? Inspired by Michel Serres, I suggest the folded object is a way to attend to the temporality and spatiality of objects. In this article I explore this new object by unravelling the history of a DNA reference sequence. I show how, ever since it was produced in the early 1980s, attempts have been made to filter race out of the sequence. That effort has failed due to what one could call ‘political noise’. Making and remaking the sequence have left traces that cannot be erased. (shrink)

This study is concerned with processes for discovering new theories in science. It considers a computational approach to scientific discovery, as applied to the discovery of theories in cognitive science. The approach combines two ideas. First, a process-based scientific theory can be represented as a computer program. Second, an evolutionary computational method, genetic programming, allows computer programs to be improved through a process of computational trialand-error. Putting these two ideas together leads to a system that can automatically generate and improve (...) scientific theories. The application of this method to the discovery of theories in cognitive science is examined. Theories are built up from primitive operators. These are contained in a theory language that defines the space of possible theories. An example of a theory generated by this method is described. These results support the idea that scientific discovery can be achieved through a heuristic search process, even for theories involving a sequence of steps. However, this computational approach to scientific discovery does not eliminate the need for human input. Human judgment is needed to make reasonable prior assumptions about the characteristics of operators used in the theory generation process, and to interpret and provide context for the computationally generated theories. (shrink)

This book examines all verses of the Quran involving knowledge related concepts. It begins with the argument that an analysis of the Quranic concept of ignorance points to epistemic virtues that can pave our way towards gaining knowledge and/or understanding. It deals with the Quranic concepts of perceptual, rational, and revelatory knowledge as well as understanding and wisdom in the light of recent discussions in Western analytic epistemology. It also argues that the relevant Quranic verses seem to involve concept of (...) an epistemic conscience whose proper exercise can yield knowledge or understanding. While not overlooking the Quranic emphasis on revelation as a source of knowledge, the book draws our attention to a remarkable overlap between some strains of contemporary virtue epistemology and Quranic approach to knowledge. It shows that the Quranic verses suggest a progressive sequence from propositional knowledge to understanding to wisdom. (shrink)