I provide a critical commentary regarding the attitude of the logician and the philosopher towards the physicist and physics. The commentary is intended to showcase how a general change in attitude towards making scientific inquiries can be beneficial for science as a whole. However, such a change can come at the cost of looking beyond the categories of the disciplines of logic, philosophy and physics. It is through self-inquiry that such a change is possible, along with the realization of the (...) essence of the middle that is otherwise excluded by choice. The logician, who generally holds a reverential attitude towards the physicist, can then actively contribute to the betterment of physics by improving the language through which the physicist expresses his experience. The philosopher, who otherwise chooses to follow the advancement of physics and gets stuck in the trap of sophistication of language, can then be of guidance to the physicist on intellectual grounds by having the physicist’s experience himself. In course of this commentary, I provide a glimpse of how a truthful conversion of verbal statements to physico-mathematical expressions unravels the hitherto unrealized connection between Heisenberg uncertainty relation and Cauchy’s definition of derivative that is used in physics. The commentary can be an essential reading if the reader is willing to look beyond the categories of logic, philosophy and physics by being ‘nobody’. (shrink)

Physical dimensions like “mass”, “length”, “charge”, represented by the symbols [M], [L], [Q], are not numbers, but used as numbers to perform dimensional analysis in particular, and to write the equations of physics in general, by the physicist. The law of excluded middle falls short of explaining the contradictory meanings of the same symbols. The statements like “m tends to 0”, “r tends to 0”, “q tends to 0”, used by the physicist, are inconsistent on dimensional grounds because “m”, “r”, (...) “q” represent quantities with physical dimensions of [M], [L], [Q] respectively and “0” represents just a number—devoid of physical dimension. Consequently, due to the involvement of the statement “q tends to 0'', where q is the test charge” in the definition of electric field leads to either circular reasoning or a contradiction regarding the experimental verification of the smallest charge in the Millikan–Fletcher oil drop experiment. Considering such issues as problematic, by choice, I make an inquiry regarding the basic language in terms of which physics is written, with an aim of exploring how truthfully the verbal statements can be converted to the corresponding physico-mathematical expressions, where “physico-mathematical” signifies the involvement of physical dimensions. Such investigation necessitates an explanation by demonstration of “self inquiry”, “middle way”, “dependent origination”, “emptiness/relational existence”, which are certain terms that signify the basic tenets of Buddhism. In light of such demonstration I explain my view of “definition”; the relations among quantity, physical dimension and number; meaninglessness of “zero quantity” and the associated logico-linguistic fallacy; difference between unit and unity. Considering the importance of the notion of electric field in physics, I present a critical analysis of the definitions of electric field due to Maxwell and Jackson, along with the physico-mathematical conversions of the verbal statements. The analysis of Jackson’s definition points towards an expression of the electric field as an infinite series due to the associated “limiting process” of the test charge. However, it brings out the necessity of a postulate regarding the existence of charges, which nevertheless follows from the definition of quantity. Consequently, I explain the notion of undecidable charges that act as the middle way to resolve the contradiction regarding the Millikan–Fletcher oil drop experiment. In passing, I provide a logico-linguistic analysis, in physico-mathematical terms, of two verbal statements of Maxwell in relation to his definition of electric field, which suggests Maxwell’s conception of dependent origination of distance and charge ) and that of emptiness in the context of relative vacuum. This work is an appeal for the dissociation of the categorical disciplines of logic and physics and on the large, a fruitful merger of Eastern philosophy and Western science. Nevertheless, it remains open to how the reader relates to this work, which is the essence of emptiness. (shrink)

The capacity to generate recursive sequences is a marker of rich, algorithmic cognition, and perhaps unique to humans. Yet, the precise processes driving recursive sequence generation remain mysterious. We investigated three potential cognitive mechanisms underlying recursive pattern processing: hierarchical reasoning, ordinal reasoning, and associative chaining. We developed a Bayesian mixture model to quantify the extent to which these three cognitive mechanisms contribute to adult humans’ performance in a sequence generation task. We further tested whether recursive rule discovery depends upon relational (...) information, either perceptual or semantic. We found that the presence of relational information facilitates hierarchical reasoning and drives the generation of recursive sequences across novel depths of center embedding. In the absence of relational information, the use of ordinal reasoning predominates. Our results suggest that hierarchical reasoning is an important cognitive mechanism underlying recursive pattern processing and can be deployed across embedding depths and relational domains. (shrink)

Epistemologies and research methods are not free of metaphysics. This is to say that they are both, supported by (or presumed by), and support (or presume) fundamental ontologies. A discussion of the epistemological foundations of "multimethod" research in the social sciences—in as much as such research claims to unearth "causal" relations—therefore cannot avoid the ontological presuppositions or implications of such a discussion. But though there isn’t necessarily a perfect correspondence between ontology, epistemology, and methodology, they do constrain each other. As (...) such it is possible to make methodological choices that are at odds with one’s (implicit) ontology or argue from an ontology that is inconsistent one’s choice of methods.Yet lack of recognition of this fact has hampered methodological discussions in political science, especially with respect to the discussion on the merits of multimethod research. The ontology implicitly accepted in such discussions is "reductionist" and "regularist," that is, one that respectively defines causes in terms of noncausal relations and states of affair and affirms that such noncausal relations are regularities in nature. This article will argue that any attempt to fit "multimethod" research (where "multimethod" signifies some combination of inferential statistics and case studies) within this narrow ontology is destined to fail since such a metaphysics logically cannot accord case studies a necessary or sufficient role in the in the establishment of causal relations. However, there are metaphysical positions within the ambit of an empiricist philosophy of science that can accommodate multiple methods without contradiction. The article discusses two such ontologies and suggests ways in which they might allow the establishment of a coherent epistemological foundation for multimethod research, however, within a decidedly empiricist philosophy of science. (shrink)

Hierarchical cognitive mechanisms underlie sophisticated behaviors, including language, music, mathematics, tool-use, and theory of mind. The origins of hierarchical logical reasoning have long been, and continue to be, an important puzzle for cognitive science. Prior approaches to hierarchical logical reasoning have often failed to distinguish between observable hierarchical behavior and unobservable hierarchical cognitive mechanisms. Furthermore, past research has been largely methodologically restricted to passive recognition tasks as compared to active generation tasks that are stronger tests of hierarchical rules. We argue (...) that it is necessary to implement learning studies in humans, non-human species, and machines that are analyzed with formal models comparing the contribution of different cognitive mechanisms implicated in the generation of hierarchical behavior. These studies are critical to advance theories in the domains of recursion, rule-learning, symbolic reasoning, and the potentially uniquely human cognitive origins of hierarchical logical reasoning. (shrink)

Dennett (_Synthese,_ _53_(2), 159–180, 1982, 1991, _Journal of Consciousness Studies,_ _10_(9–10), 19–30, 2003, _Phenomenology and the Cognitive Sciences,_ _6_, 247–270, 2007 ) proposes and defends a method called _heterophenomenology_. Heterophenomenology is a method to study consciousness _from a third-person objective point of view_ as opposed to a first-person subjective point of view or (auto)-phenomenology. The method of heterophenomenology serves a necessary role in Dennett’s schema of bridging the gap between the manifest and the scientific image of the world. In this (...) paper, I attempt to present a limited critique of the method of heterophenomenology. The objection raised in this paper is limited to one of the steps involved in the method, i.e., the interpretation of the heterophenomenological text as analogous to novelist fiction. I attempt to show that the assumptions made by Dennett about the interpretation of fiction are contradictory in nature and therefore the same cannot be applied to the interpretation of a heterophenomenological text. The assumptions fail in justifying the interpretation of fiction itself and hence exporting them by analogy to interpret a heterophenomenological text is a mistake. (shrink)

Recent advances in genomic and imaging techniques have revealed the complex manner of organizing billions of base pairs of DNA necessary for maintaining their functionality and ensuring the proper expression of genetic information. The SMC proteins and cohesin complex primarily contribute to forming higher‐order chromatin structures, such as chromosomal territories, compartments, topologically associating domains (TADs) and chromatin loops anchored by CCCTC‐binding factor (CTCF) protein or other genome organizers. Cohesin plays a fundamental role in chromatin organization, gene expression and regulation. This (...) review aims to describe the current understanding of the dynamic nature of the cohesin‐DNA complex and its dependence on cohesin for genome maintenance. We discuss the current 3C technique and numerous bioinformatics pipelines used to comprehend structural genomics and epigenetics focusing on the analysis of Cohesin‐centred interactions. We also incorporate our present comprehension of Loop Extrusion (LE) and insights from stochastic modelling. (shrink)

Observational discrepancies in galactic rotation curves and cluster dispersion data have been interpreted to imply the existence of dark matter. Numerous efforts at its detection, however, have failed to turn up any positive result. As a dynamical theory is always operative on the assumed mass distribution to predict kinematic observations, some scientists see the discrepancy as telling against General Relativity. Among the many theories that seek to modify gravity, those that are built on Modified Newtonian Dynamics (MOND), or yield MOND (...) behaviour at appropriate scales, achieve remarkable empirical success without assuming dark matter. The continued non-detection of dark matter and the empirical success of MOND supports the claim that the current evidential and theoretical context underdetermines General Relativity. In this article, I clarify the kind of underdetermination that can be said to threaten General Relativity. Specifically, I argue that the present evidential and theoretical context increase the possibility of an unconceived alternative to GR which would be just as well supported by the available evidence. (shrink)

There has been in recent decades very substantial work done on the concept of a nation, nationality and nationalism. In spite of the world coming together on many fronts—particularly, economy and a multicultural habitat formations especially in Europe and North America—these ideas remain politically volatile. In modern times, the idea of a nation has become powerfully associated with the idea of the state and the two notions are frequently used almost interchangeably. If among the emotional ties that form the basis (...) of the idea of a nation, we add a strong sense of belonging to a specific culture with its own history, traditions and the sharing of ethical and aesthetic values—it may quite naturally lead to the idea of one-nation, one-state and one culture. Such indeed has been a trend in the European concept of the idea of a nation of the 18th, 19th and partly of the twentieth century. However, same cannot be said about Indian nation. If we closely look at the growth of Indian nationalism in the backdrop of anti-colonial movement and formation of Indian state after gaining independence, we find lack of unanimity among thinkers. This paper explores the growth of Indian Nationalism and formation of Indian Nation through the eyes of one of the most seminal contemporary Indian thinkers Sri Aurobindo. (shrink)

The relationship between ethical ideology and job stress appears to be complex. This study is based on a model presented by Forsyth (Journal of Personality and Social Psychology 39:175, 1980), showing two dimensions (idealism and relativism) that play an important role in ethical evaluation and behavior. Based on a survey of 561 employees of hotel industry in India, ethical ideologies were found to be negatively associated with job stress. The data were analyzed using Pearson correlations and multiple regressions. The result (...) showed that relativism is negatively correlated with job stress. Further, it has been established that idealism and relativism interacted in such a way that there is a negative relationship between idealism and job stress when relativism is low and positive relationship when relativism is high. The findings imply that ethical ideology adversely influences the job stress in the organization. (shrink)

Durán et al argue in ‘Who is afraid of black box algorithms? On the epistemological and ethical basis of trust in medical AI’1 that traditionally proposed solutions to make black box machine learning models in medicine less opaque and more transparent are, though necessary, ultimately not sufficient to establish their overall trustworthiness. This is because transparency procedures currently employed, such as the use of an interpretable predictor,2 cannot fully overcome the opacity of such models. Computational reliabilism, an alternate approach to (...) adjudicating trustworthiness that goes beyond transparency solutions, is argued to be a more promising approach. CR can bring the benefits of traditional process reliabilism in epistemology to bear on this problem of model trustworthiness. Durán et al ’s explicitly reliabilist epistemology to assess the trustworthiness of black box models is a timely addition to current transparency-focused approaches in the literature. Their delineation of the epistemic from the ethical also serves the debate by clarifying the nature of the different problems. However, their overall account underestimates the epistemic value of certain transparency-enabling approaches by conflating different types of opacity and also oversimplifies transparency-advocating arguments in the literature. First, it is unclear why Durán et al consider transparency approaches as insufficient to overcome epistemic opacity, if heiraccount of opacity is the traditional one from the machine learning literature: opacity stemming from the mismatch between mathematical optimisation in high dimensionality that is characteristic of machine learning and the demands of human-scale reasoning and styles of semantic interpretation.3 …. (shrink)

Einsteinian gravity, of which Newtonian gravity is a part, is fraught with the problem of singularity that has been established as a theorem by Hawking and Penrose. The _hypothesis_ that founds the basis of both Einsteinian and Newtonian theories of gravity is that bodies with unequal magnitudes of masses fall with the same acceleration under the gravity of a source object. Since, the Einstein’s equations is one of the assumptions that underlies the proof of the singularity theorem, therefore, the above (...) hypothesis is implicitly one of the founding pillars of the same. In this work, I demonstrate how one can possibly write a non-singular theory of gravity which manifests that the above mentioned hypothesis is only valid in an approximate sense in the “large distance” scenario. To mention a specific instance, under the gravity of the earth, a 5 kg and a 500 kg fall with accelerations which differ by approximately \(113.148\times 10^{-32}\) meter/sec \(^2\) and the more massive object falls with less acceleration. Further, I demonstrate why the concept of gravitational field is not definable in the “small distance” regime which automatically justifies why the Einstein’s and Newton’s theories fail to provide any “small distance” analysis. In course of writing down this theory, I demonstrate why the continuum hypothesis as spelled out by Goedel, is undecidable. The theory has several aspects which provide the following realizations: (i) Descartes’ self-skepticism concerning exact representation of numbers by drawing lines (ii) Born’s wish of taking into account “natural uncertainty in all observations” while describing “a physical situation” by means of “real numbers” (iii) Klein’s vision of having “a fusion of arithmetic and geometry” where “a point is replaced by a small spot” (iv) Goedel’s assertion about “non-standard analysis, in some version” being “the analysis of the future”. (shrink)

SummaryExamining waiting time to birth among newlywed couples is likely to provide insights into the desire for spacing births among newlywed husbands and wives. Data from the Indian National Family Health Survey of 2005–06 are used to examine the desired waiting time to birth among newlywed couples. The dependent variable is spousal concordance on desired waiting times. Overall 65% of couples have concordant desired waiting times. Among discordant couples, wives were more likely to want to wait longer than their husbands. (...) Couples from richer wealth quintiles were more likely than couples from the poorest quintile to have concordant desired waiting times. Muslims were less likely than Hindus to have concordant desires. There is a need for spacing contraceptive methods among newlyweds in India. This may have implications for the Indian Family Planning Programme, which to date has largely focused on sterilization. Programmes need to include newlywed husbands to promote use of spacing methods. (shrink)

In response to Morningstar’s release of carbon risk (CR) scores in May 2018, (environmentally) sustainable mutual funds in the U.S. showed a greater reduction in their portfolio CR relative to conventional funds. The observed causal impact of this third-party disclosure is consistent with the funds’ primary investment objectives. Differences in fund names, potentially driven by marketing considerations, appear irrelevant to the behavior of sustainable funds. Conventional funds that are signatories to the UN’s Principles for Responsible Investment (PRI) or those with (...) secondary sustainability mandates behave more like other conventional funds rather than sustainable funds. These funds appear relatively insensitive to disclosures as their sustainability considerations are superseded by other primary investment criteria. Fiduciary and legal bonding influences fund managers’ response to sustainability disclosures. Sustainable funds lower their CR score by reducing exposure to fossil fuels, not by increasing exposure to renewables. (shrink)

This note establishes a new identification result for additive random utility discrete choice models. A decision-maker associates a random utility Uj+mj\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$U_{j}+m_{j}$$\end{document} to each alternative in a finite set j∈1,…,J\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$j\in \left\{ 1,\ldots,J\right\} $$\end{document}, where U=U1,…,UJ\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf {U}=\left\{ U_{1},\ldots,U_{J}\right\} $$\end{document} is unobserved by the researcher and random with an unknown joint distribution, while the perturbation m=m1,…,mJ\documentclass[12pt]{minimal} \usepackage{amsmath} (...) \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf {m}=\left $$\end{document} is observed. The decision-maker chooses the alternative that yields the maximum random utility, which leads to a choice probability system m→Pr1|m,…,PrJ|m\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf { m\rightarrow }\left,\ldots,\Pr \left \right) $$\end{document}. Previous research has shown that the choice probability system is identified from the observation of the relationship m→Pr1|m\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \mathbf {m}\rightarrow \Pr \left $$\end{document}. We show that the complete choice probability system is identified from observation of a relationship m→∑j=1sPrj|m\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathbf {m}\rightarrow \sum _{j=1}^{s}\Pr \left $$\end{document}, for any sshrink)

Minichromosome maintenance (Mcm) proteins are well‐known for their functions in DNA replication. However, their roles in chromosome segregation are yet to be reviewed in detail. Following the discovery in 1984, a group of Mcm proteins, known as the ARS‐nonspecific group consisting of Mcm13, Mcm16‐19, and Mcm21‐22, were characterized as bonafide kinetochore proteins and were shown to play significant roles in the kinetochore assembly and high‐fidelity chromosome segregation. This review focuses on the structure, function, and evolution of this group of Mcm (...) proteins. Our in silico analysis of the physical interactors of these proteins reveals that they share non‐overlapping functions despite being copurified in biochemically stable complexes. We have discussed the contrasting results reported in the literature and experimental strategies to address them. Taken together, this review focuses on the structure‐function of the ARS‐nonspecific Mcm proteins and their evolutionary flexibility to maintain genome stability in various organisms. (shrink)

Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a “transcriptional switch,” repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to (...) the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway. Wnt targets are regulated by a “switch” where TLE co-repressors are displaced from TCFs by β-catenin, leading to activation of transcription. Recent reports challenge this view and suggest that additional processes, including exchange of specific TCF proteins and Wnt-dependent ubiquitination of TLEs, play important roles in the Wnt transcriptional switch. (shrink)

The purpose of this study is to examine the impact of two comparative leadership styles on organizational performance outcomes. The leadership styles undertaken is transformational and servant leadership. A sample of 155 participants is taken from profit-oriented service sector of Pakistan. Data through survey gathered on a five point likert scale from organizations. AMOS and SPSS are used for statistical analysis. The result shows that, transformational leadership has more impact on organizational learning than servant leadership. Furthermore organizational learning enhances organizational (...) performance. Managers and leaders of corporate sector can get benefited from this study. Their main objective is to maximize the profitability of organization thus, they can choose leadership style which polishes their abilities and helps them to achieve profit maximization. (shrink)

Advances in AI research have brought increasingly sophisticated capabilities to AI systems and heightened the societal consequences of their use. Researchers and industry professionals have responded by contemplating responsible principles and practices for AI system design. At the same time, defense institutions are contemplating ethical guidelines and requirements for the development and use of AI for warfare. However, varying ethical and procedural approaches to technological development, research emphasis on offensive uses of AI, and lack of appropriate venues for multistakeholder dialogue (...) have led to differing operationalization of responsible AI principles and practices among civilian and defense entities. We argue that the disconnect between civilian and defense responsible development and use practices leads to underutilization of responsible AI research and hinders the implementation of responsible AI principles in both communities. We propose a research roadmap and recommendations for dialogue to increase exchange of responsible AI development and use practices for AI systems between civilian and defense communities. We argue that generating more opportunities for exchange will stimulate global progress in the implementation of responsible AI principles. (shrink)

Honor killings are graceless and ferocious murders by chauvinists with an antediluvian mind. These are categorized separately because these killings are committed for the prime reason of satisfying the ego of the people whom the victim trusts and always looks up to for support and protection. It is for this sole reason that honor killings demand strict and stern punishment, not only for the person who committed the murder but also for any person who contributed or was party to the (...) act. A positive change can occur with stricter legislation and changes in the ethos of the society we live in today. (shrink)

Most of the theories of rights propounded by philosophers, right from the beginning till the twentieth century, conceive rights either as a claim against the state or an obligation upon the state. Certainly such a conception has had something to do with the prevailing social, political and economic systems of the time concerned. Social, political and economic systems also had a particular relationship amongst them. Change in individual and social perspectives, values, priorities and beliefs has affected the philosophy of right. (...) From the ages of Locke and Hobbes when natural right was taken in obvious terms to the times of communitarians like Michael Sandel and thinkers like Ronald Dworkin the term “Right” has earned many dimensions. Progress and changing arrangements of systems complicates the status of a philosophical theory of rights propounded at a particular time, in the sense that its losses its teeth in any new found milieu. This paper evaluates the notion of abstract universalism of individual rights in the light of Gandhian notion of duty. (shrink)

Underdetermination of theory choice claims that empirical evidence fails to provide sufficient grounds for choosing a theory over its rivals. We explore the epistemological and methodological significance of this thesis by utilising a classificatory scheme to situate three arguments that purport to establish its plausibility. Proponents of these three arguments, W.V.O Quine, John Earman, and Kyle Stanford, use different premises to arrive at the conclusion that theory choice is empirically underdetermined and their classification along the proposed schema brings out the (...) variety in underdetermination arguments and the historical trajectory of the thesis. Although the epistemological significance of underdetermination—it is seen as undermining the doctrine of scientific realism—is widely discussed in the literature, Quine understood the acceptance of the thesis as interrogating the attitude one is justified in adopting towards rival theories. We argue that sticking with one’s own theory in the face of underdetermination leads to a distinct type of disagreement, which we present as the methodological significance of underdetermination. The examination of the methodological significance of underdetermination allows us to propose weak underdetermination as a philosophically interesting variant of underdetermination. (shrink)

Many are calling for concrete mechanisms of oversight for health research involving artificial intelligence (AI). In response, institutional review boards (IRBs) are being turned to as a familiar model of governance. Here, we examine the IRB model as a form of ethics oversight for health research that uses AI. We consider the model's origins, analyze the challenges IRBs are facing in the contexts of both industry and academia, and offer concrete recommendations for how these committees might be adapted in order (...) to provide an effective mechanism of oversight for health‐related AI research. (shrink)

© 2014 Shapiro, Tassone, Choudhary and Simon.Chromosome 22q11.2 Deletion Syndrome is caused by the most common human microdeletion, and it is associated with cognitive impairments across many domains. While impairments in cognitive control have been described in children with 22q11.2DS, the nature and development of these impairments are not clear. Children with 22q11.2DS and typically developing children were tested on four well-validated tasks aimed at measuring specific foundational components of cognitive control: response inhibition, cognitive flexibility, and working memory. Molecular (...) assays were also conducted in order to examine genotype of catechol-O-methyltransferase, a gene located within the deleted region in 22q11.2DS and hypothesized to play a role in cognitive control. Mixed model regression analyses were used to examine group differences, as well as age-related effects on cognitive control component processes in a cross-sectional analysis. Regression models with COMT genotype were also conducted in order to examine potential effects of the different variants of the gene. Response inhibition, cognitive flexibility, and working memory were impaired in children with 22q11.2DS relative to TD children, even after accounting for global intellectual functioning. When compared with TD individuals, children with 22q11.2DS demonstrated atypical age-related patterns of response inhibition and cognitive flexibility. Both groups demonstrated typical age-related associations with working memory. The results of this cross-sectional analysis suggest a specific aberration in the development of systems mediating response inhibition in a sub-set of children with 22q11.2DS. It will be important to follow up with longitudinal analyses to directly examine these developmental trajectories, and correlate neurocognitive variables with clinical and adaptive outcome measures. (shrink)

Rare copy number variants have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large CNVs at several loci, including microdeletions at 1q21.1, 3q29, 15q13.3 and 22q11.2 and microduplication at 16p11.2. However, these CNVs collectively account for a small fraction of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy (...) number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 patients versus 2 of 7,431 controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs. © 2011 Macmillan Publishers Limited. All rights reserved. (shrink)