We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

We examined if cancer patients' health-related quality of life (HRQoL) scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 are affected by the specific time point, before or during treatment, at which the questionnaire is completed, and whether this could bias the overall treatment comparison analyses. A 'completion-time window' variable was created on three closed EORTC randomised control trials in lung (non-small cell lung cancer, NSCLC) and colorectal cancer (CRC) to indicate when the QLQ-30 was completed (...) relative to chemotherapy cycle dates, defined as 'before', 'on' and 'after'. HRQoL mean scores were calculated using a linear mixed model. Statistically significant differences (P < 0.05) were observed on 6 and 5 scales for 'on' and 'after' comparisons in the NSCLC and two-group CRC trial, respectively. As for the three-group CRC trial, several statistical differences were observed in the 'before' to 'on' and the 'on' to 'after' comparisons. For all three trials, including the 'completion-time window' variable in the model resulted in a better fit, but no substantial changes in the treatment effects were noted. We showed that considering the exact timing of completion within specified windows resulted in statistical and potentially clinically significant differences, but it did not alter the conclusions of treatment comparison in these studies. (shrink)

This paper argues that in modern biotechnology, naturalness as an argument contributed to a stalemate in public debate about innovative technologies. Naturalness in this is often placed opposite to human disruption. It also often serves as a label that shapes moral acceptance or rejection of agricultural innovative technologies. The cause of this lies in the use of nature as a closed, static reference to naturalness, while in fact ‘‘nature’’ is an open and dynamic concept with many different meanings. We propose (...) an approach for a dynamic framework that permits an integrative use of naturalness in debate, by connecting three sorts of meaning that return regularly in the arguments brought forward in debate; cultural, technological, and ecological. We present these as aspects of nature that are always present in the argument of naturalness. The approach proposes a dynamic relation between these aspects, formed by gradients of naturalness, which in turn are related to ethical concerns. In this way we come to an overview that makes it possible to give individual arguments a relative place and that does justice to the temporality of the concept of nature and the underlying ethical concerns stakeholders have in respect to innovation in agriculture. (shrink)

We formulate a discrete quantum-mechanical precursor to spacetime geometry. The objective is to provide the foundation for a quantum mechanics that is rooted exclusively in quantum-mechanical concepts, with all classical features, including the three-dimensional spatial continuum, emerging dynamically.

If a hereditary predisposition to colorectal cancer or breast cancer is diagnosed, most guidelines state that clinical geneticists should request index patients to inform their at-risk relatives about the existence of this condition in their family, thus enabling them to consider presymptomatic genetic testing. Those identified as mutation carriers can undertake strategies to reduce their risk of developing the disease or to facilitate early diagnosis. This procedure of informing relatives through the index patient has been criticised, as it results in (...) relatively few requests for genetic testing, conceivably because a certain number of relatives remain uninformed. This pilot study explored attitudes toward informing family members and relevant practices among clinical geneticists. In general, clinical geneticists consider it to be in the interests of family members to be informed and acknowledge that this goal is not accomplished by current procedures. The reasons given for maintaining present practices despite this include clinical ‘mores’, uncertainty about the legal right of doctors to inform family members themselves, and, importantly, a lack of resources. We discuss these reasons from an ethical point of view and conclude that they are partly uninformed and inconsistent. If informing relatives is considered to be in their best interests, clinical geneticists should consider informing relatives themselves. In the common situation in which index patients do not object to informing relatives, no legal obstacles prevent geneticists from doing so. An evaluation of these findings among professionals may lead to a more active approach in clinical practice. (shrink)

A construction is described of a cartesian closed category A with exactly two elements out of a C-monoid such that can be recovered from A without reference to the construction.

Meta-theories, base-theories and theories of practice in Pratical Theology The problem of meta-theories and base-theories, their interaction and the influence of each on the scientific process, have widely been debated in practical theology. In South Africa two meta-theories namely the system- theory together with the theory that social science is busy with the study of actions, are having the greater deal of attention. The purpose of this article is to point out the fact that an early and absolute choice of (...) particular meta-theories, restricts the work of practical theology because it will influence your base-theories, and can weaken the theological content of practical theology. An attempt is made to offer a model by which the interaction between, meta-theories, base-theories and theories of practice can he understood and which can also help the theologian, busy with practical theology, to steer clear of problems and understand the meta- influences in his own scientific work. (shrink)

Interactive technology assessment (iTA) provides an answer to the ethical problem of normative bias in evaluation research. This normative bias develops when relevant perspectives on the evaluand (the thing being evaluated) are neglected. In iTA this bias is overcome by incorporating different perspectives into the assessment. As a consequence, justification of decisions based on the assessment is provided by stakeholders having achieved agreement. In this article, agreement is identified with wide reflective equilibrium to show that it indeed has the potential (...) of justifying decisions. We work out several conditions for this agreement to be achievable and just. (shrink)

During his lifetime, F.C.S. Schiller was viewed as a major figure in the pragmatist movement, but his reputation has faded. This article will challenge the view that he was an unoriginal or less important figure. In particular, I will attempt a reconstruction of Schiller’s position on first philosophy, which will examine the differences between Schiller and the other major figures in the pragmatist movement. By using texts from Schiller’s writings, I attempt to create an undistorted reconstruction of what he wrote (...) in order to support this interpretation. I outline the implicit system contained in Schiller’s scattered writings and briefly examine the relation between Schiller’s humanism and other forms of pragmatism. The task seems both justified and worthwhile, since his work has been neglected, despite his prominence in the debates over pragmatism that took place when it emerged at the beginning of the twentieth century. (shrink)

The purpose of this study was to adapt the Austrian-German version of the Multidimensional Inventory for Religious/Spiritual Well-Being into the Italian language and culture, and to investigate possible associations between the RSWB dimensions, “Big Five” personality factors and mental illness within an Italian student sample. Hence, the first Italian translation of the MI-RSWB scale was applied on a sample of 412 undergraduate students in three different cities and regions of Italy: Padova, Rome, and Palermo. Like the original Austrian-German scale, we (...) were able to find convincing psychometric properties for the new Italian version of the scale. By mirroring previous research, the RSWB-dimensions turned out to be substantially associated with personality dimensions, as well as negatively related with a global measure of mental illness. Our initial results confirm that these RSWB-dimensions are important facets of personality and mental health. (shrink)

The DAMA project is an observatory for rare processes and it is operative deep underground at the Gran Sasso National Laboratory of the I.N.F.N. In particular, the DAMA/LIBRA (Large sodium Iodide Bulk for RAre processes) set-up consists of highly radiopure NaI(Tl) detectors for a total sensitive exposed mass of ≃250 kg. Recent results, obtained by this set-up by exploiting the model independent annual modulation signature of Dark Matter (DM) particles, have confirmed and improved those obtained by the former DAMA/NaI experiment. (...) A model independent evidence for the presence of Dark Matter particles in the galactic halo is cumulatively obtained at 8.2 σ C.L. No systematics or side reactions able to account for the measured modulation amplitude and to contemporaneously satisfy all the many specific requirements of the signature have been found or suggested by anyone over more than a decade. An example of one of the many possible model dependent corollary quests for the candidate particles and for the related astrophysical, nuclear and particle physics scenarios is presented considering the whole cumulative exposure. Future perspectives are shortly addressed. (shrink)

_ Source: _Volume 40, Issue 1, pp 104 - 115 It is intended in this study to present initial reliability and validity data for the Russian adaptation of the Multidimensional Inventory of Religious/Spiritual Well-being, as being related to personality factors and psychopathology. Therefore, the first version of the MI-RSWB-R was applied to a sample of 192 non-clinical subjects, together with the NEO Five Factor Inventory and the Symptom-Check-List. The original six-factor structure of the scale could be replicated for the MI-RSWB-R, (...) which also provides satisfying psychometric properties. In accordance with previous research the RSWB total score was linked to more favorable personality traits such as Extraversion, Openness to Experience, and Agreeableness, which was paralleled by substantial negative correlations with increased psychopathology. Our findings support the reliability and structural validity of the MI-RSWB-R as a standardized instrument for addressing the spiritual dimension in Russian populations. Further research in clinical surroundings is now recommended. (shrink)