Several types of types in programming languages

Types are an important part of any modern programming language, but we often forget that the concept of type we understand nowadays is not the same it was perceived in the sixties. Moreover, we conflate the concept of "type" in programming languages with the concept of the same name in mathematical logic, an identification that is only the result of the convergence of two different paths, which started apart with different aims. The paper will present several remarks (some historical, some of more conceptual character) on the subject, as a basis for a further investigation. The thesis we will argue is that there are three different characters at play in programming languages, all of them now called types: the technical concept used in language design to guide implementation; the general abstraction mechanism used as a modelling tool; the classifying tool inherited from mathematical logic. We will suggest three possible dates ad quem for their presence in the programming language literature, suggesting that the emergence of the concept of type in computer science is relatively independent from the logical tradition, until the Curry-Howard isomorphism will make an explicit bridge between them.Comment: History and Philosophy of Computing, HAPOC 2015. To appear in LNC

Label-free, live optical imaging of reprogrammed bipolar disorder patient-derived cells reveals a functional correlate of lithium responsiveness

Development of novel treatments and diagnostic tools for psychiatric illness has been hindered by the absence of cellular models of disease. With the advent of cellular reprogramming, it may be possible to recapitulate the disease biology of psychiatric disorders using patient skin cells transdifferentiated to neurons. However, efficiently identifying and characterizing relevant neuronal phenotypes in the absence of well-defined pathophysiology remains a challenge. In this study, we collected fibroblast samples from patients with bipolar 1 disorder, characterized by their lithium response (n=12), and healthy control subjects (n=6). We identified a cellular phenotype in reprogrammed neurons using a label-free imaging assay based on a nanostructured photonic crystal biosensor and found that an optical measure of cell adhesion was associated with clinical response to lithium treatment. This cellular phenotype may represent a useful biomarker to evaluate drug response and screen for novel therapeutics

Information Retrieval on the World Wide Web and Active Logic: A Survey and Problem Definition

As more information becomes available on the World Wide Web (there are currently over 4 billion pages covering most areas of human endeavor), it becomes more difficult to provide effective search tools for information access. Today, people access web information through two main kinds of search interfaces: Browsers (clicking and following hyperlinks) and Query Engines (queries in the form of a set of keywords showing the topic of interest). The first process is tentative and time consuming and the second may not satisfy the user because of many inaccurate and irrelevant results. Better support is needed for expressing one's information need and returning high quality search results by web search tools. There appears to be a need for systems that do reasoning under uncertainty and are flexible enough to recover from the contradictions, inconsistencies, and irregularities that such reasoning involves. Active Logic is a formalism that has been developed with real-world applications and their challenges in mind. Motivating its design is the thought that one of the factors that supports the flexibility of human reasoning is that it takes place step-wise, in time. Active Logic is one of a family of inference engines (step-logics) that explicitly reason in time, and incorporate a history of their reasoning as they run. This characteristic makes Active Logic systems more flexible than traditional AI systems and therefore more suitable for commonsense, real-world reasoning. In this report we mainly will survey recent advances in machine learning and crawling problems related to the web. We will review the continuum of supervised to semi-supervised to unsupervised learning problems, highlight the specific challenges which distinguish information retrieval in the hypertext domain and will summarize the key areas of recent and ongoing research. We will concentrate on topic-specific search engines, focused crawling, and finally will propose an Information Integration Environment, based on the Active Logic framework. Keywords: Web Information Retrieval, Web Crawling, Focused Crawling, Machine Learning, Active Logic (Also UMIACS-TR-2001-69

Acute and Chronic Insomnia: What Has Time and/or Hyperarousal Got to Do with It?

Nearly one-third of the population reports new onset or acute insomnia in a given year. Similarly, it is estimated that approximately 10% of the population endorses sleep initiation and maintenance problems consistent with diagnostic criteria for chronic insomnia. For decades, acute and chronic insomnia have been considered variations of the same condition or disorder, only really differentiated in terms of chronicity of symptoms (days/weeks versus months). Whether or not acute and chronic insomnia are part of the same phenomena is an important question, one that has yet to be empirically evaluated. The goal of the present theoretical review was to summarize the definitions of acute and chronic insomnia and discuss the role that hyperarousal may have in explaining how the pathophysiology of acute and chronic insomnia is likely different (i.e., what biopsychological factors precipitate and/or perpetuate acute insomnia, chronic insomnia, or both?)

Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development

A Comparison of DSM-IV and DSM-5 Panel Members' Financial Associations with Industry: A Pernicious Problem Persists

Lisa Cosgrove and Sheldon Krimsky examine the new competing interest disclosure policy of the American Psychiatric Association (APA) and report that DSM panel members still have considerable financial conflicts of interest

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Symptoms predicting remission after divalproex augmentation with olanzapine in partially nonresponsive patients experiencing mixed bipolar I episode: a post-hoc analysis of a randomized controlled study

<p>Abstract</p> <p>Background</p> <p>Rating scale items in a 6-week clinical trial of olanzapine versus placebo augmentation in patients with mixed bipolar disorder partially nonresponsive to ≥14 days of divalproex monotherapy were analyzed to characterize symptom patterns that could predict remission. At baseline, the two treatment groups were similar.</p> <p>Findings</p> <p>Factor analysis with Varimax rotation was performed <it>post hoc </it>on baseline items of the 21-Item Hamilton Depression Rating Scale (HDRS-21) and Young Mania Rating Scale (YMRS). Backwards-elimination logistic regression ascertained factors predictive of protocol-defined endpoint remission (HDRS-21 score ≤ 8 and YMRS score ≤ 12) with subsequent determination of optimally predictive factor score cutoffs.</p> <p>Factors for Psychomotor activity (YMRS items for elevated mood, increased motor activity, and increased speech and HDRS-21 agitation item) and Guilt/Suicidality (HDRS-21 items for guilt and suicidality) significantly predicted endpoint remission in the divalproex+olanzapine group. No factor predicted remission in the divalproex+placebo group. Patients in the divalproex+olanzapine group with high pre-augmentation psychomotor activity (scores ≥10) were more likely to remit compared to those with lower psychomotor activity (odds ratio [OR] = 3.09, 95% confidence interval [CI] = 1.22-7.79), and patients with marginally high Guilt/Suicidality (scores ≥2) were less likely to remit than those with lower scores (OR = 0.37, 95% CI = 0.13-1.03). Remission rates for divalproex+placebo vs. divalproex+olanzapine patients with high psychomotor activity scores were 22% vs. 45% (p = 0.08) and 33% vs. 48% (p = 0.29) for patients with low Guilt/Suicidality scores.</p> <p>Conclusions</p> <p>Patients who were partially nonresponsive to divalproex treatment with remaining high vs. low psychomotor activity levels or minimal vs. greater guilt/suicidality symptoms were more likely to remit with olanzapine augmentation.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov; <url>http://clinicaltrials.gov/ct2/show/NCT00402324?term=NCT00402324&rank=1</url>, Identifier: NCT00402324</p