Alterations in Task-Related Brain Activation in Children, Adolescents and Young Adults at Familial High-Risk for Schizophrenia or Bipolar Disorder - A Systematic Review.

Children, adolescents, and young adults with at least one first-degree relative [familial high-risk (FHR)] with either schizophrenia (SZ) or bipolar disorder (BD) have a one-in-two risk of developing a psychiatric disorder. Here, we review functional magnetic resonance imaging (fMRI) studies which examined task-related brain activity in young individuals with FHR-SZ and FHR-BD. A systematic search identified all published task-related fMRI studies in children, adolescents, and young adults below an age of 27 years with a first-degree relative with SZ or BD, but without manifest psychotic or affective spectrum disorder themselves. The search identified 19 cross-sectional fMRI studies covering four main cognitive domains: 1) working memory (n = 3), 2) cognitive control (n = 4), 3) reward processing (n = 3), and 4) emotion processing (n = 9). Thirteen studies included FHR-BD, five studies included FHR-SZ, and one study included a pooled FHR group. In general, task performance did not differ between the respective FHR groups and healthy controls, but 18 out of the 19 fMRI studies revealed regional alterations in task-related activation. Brain regions showing group differences in peak activation were regions associated with the respective task domain and showed little overlap between FHR-SZ and FHR-BD. The low number of studies, together with the low number of subjects, and the substantial heterogeneity of employed methodological approaches within the domain of working memory, cognitive control, and reward processing impedes finite conclusions. Emotion processing was the most investigated task domain in FHR-BD. Four studies reported differences in activation of the amygdala, and two studies reported differences in activation of inferior frontal/middle gyrus. Together, these studies provide evidence for altered brain processing of emotions in children, adolescents, and young adults at FHR-BD. More studies of higher homogeneity, larger sample sizes and with a longitudinal study design are warranted to prove a shared or specific FHR-related endophenotypic brain activation in young first-degree relatives of individuals with SZ or BD, as well as to pinpoint specific alterations in brain activation during cognitive-, emotional-, and reward-related tasks

Association between plasma activities of semicarbazide-sensitive amine oxidase and angiotensin-converting enzyme in patients with type 1 diabetes mellitus

Aims/hypothesis: Plasma semicarbazide-sensitive amine oxidase (SSAO) is elevated in patients with type 1 and type 2 diabetes and has been implicated in the pathophysiology of diabetic late complications. The regulation of SSAO production remains unknown. We studied correlations between plasma SSAO activity and parameters associated with diabetic late complications. Methods: Plasma SSAO was measured in a well-characterised group of 287 patients with type 1 diabetes. Standard statistical methods were used to investigate correlations with clinical parameters and components of the renin-angiotensin system. Results: Overall, plasma SSAO was elevated, at 693±196 mU/l (mean±SD; normal controls 352±102 mU/l). Plasma SSAO was higher in the group with late complications or hypertension, and in patients treated with ACE-inhibitors. In univariate analysis a significant positive correlation (p<0.001, r=0.27) was found between plasma SSAO and serum ACE activity in patients untreated with ACE inhibitors or angiotensin II receptor antagonists (n=221), but plasma SSAO did not differ by ACE I/D genotype. Plasma SSAO correlated positively with duration of diabetes, HbA1c and plasma renin, and negatively with plasma angiotensinogen and body mass index. A multiple regression analysis including these variables resulted in serum ACE activity (p<0.001), ACE genotype (negatively, p<0.001) and HbA 1c (p=0.023) as explaining variables. Conclusions/interpretation: Results suggest that a common factor is involved in the regulation of both plasma SSAO and serum ACE, which is different from the genetic determination of ACE activity

Donor Centers and Absorption Spectra in Quantum Dots

We have studied the electronic properties and optical absorption spectra of three different cases of donor centers, D^{0}, D^{-} and D^{2-}, which are subjected to a perpendicular magnetic field, using the exact diagonalization method. The energies of the lowest lying states are obtained as function of the applied magnetic field strength B and the distance zeta between the positive ion and the confinement xy-plane. Our calculations indicate that the positive ion induces transitions in the ground-state, which can be observed clearly in the absorption spectra, but as zeta goes to 0 the strength of the applied magnetic field needed for a transition to occur tends to infinity.Comment: 5 pages, 4 figures, REVTeX 4, gzipped tar fil

Diffusion of digital innovation in construction: a case study of a UK engineering firm

The UK government is mandating the use of building information modelling (BIM) in large public projects by 2016. As a result, engineering firms are faced with challenges related to embedding new technologies and associated working practices for the digital delivery of major infrastructure projects. Diffusion of innovations theory is used to investigate how digital innovations diffuse across complex firms. A contextualist approach is employed through an in-depth case study of a large, international engineering project-based firm. The analysis of the empirical data, which was collected over a four-year period of close interaction with the firm, reveals parallel paths of diffusion occurring across the firm, where both the innovation and the firm context were continually changing. The diffusion process is traced over three phases: centralization of technology management, standardization of digital working practices, and globalization of digital resources. The findings describe the diffusion of a digital innovation as multiple and partial within a complex social system during times of change and organizational uncertainty, thereby contributing to diffusion of innovations studies in construction by showing a range of activities and dynamics of a non-linear diffusion process

Mathematical practice, crowdsourcing, and social machines

The highest level of mathematics has traditionally been seen as a solitary endeavour, to produce a proof for review and acceptance by research peers. Mathematics is now at a remarkable inflexion point, with new technology radically extending the power and limits of individuals. Crowdsourcing pulls together diverse experts to solve problems; symbolic computation tackles huge routine calculations; and computers check proofs too long and complicated for humans to comprehend. Mathematical practice is an emerging interdisciplinary field which draws on philosophy and social science to understand how mathematics is produced. Online mathematical activity provides a novel and rich source of data for empirical investigation of mathematical practice - for example the community question answering system {\it mathoverflow} contains around 40,000 mathematical conversations, and {\it polymath} collaborations provide transcripts of the process of discovering proofs. Our preliminary investigations have demonstrated the importance of "soft" aspects such as analogy and creativity, alongside deduction and proof, in the production of mathematics, and have given us new ways to think about the roles of people and machines in creating new mathematical knowledge. We discuss further investigation of these resources and what it might reveal. Crowdsourced mathematical activity is an example of a "social machine", a new paradigm, identified by Berners-Lee, for viewing a combination of people and computers as a single problem-solving entity, and the subject of major international research endeavours. We outline a future research agenda for mathematics social machines, a combination of people, computers, and mathematical archives to create and apply mathematics, with the potential to change the way people do mathematics, and to transform the reach, pace, and impact of mathematics research.Comment: To appear, Springer LNCS, Proceedings of Conferences on Intelligent Computer Mathematics, CICM 2013, July 2013 Bath, U

Exercise and pregnancy in recreational and elite athletes: 2016 evidence summary from the IOC expert group meeting, Lausanne. Part 2 - The effect of exercise on the fetus, labour and birth

This is Part 2 of 5 in the series of evidence statements from the IOC expert committee on exercise and pregnancy in recreational and elite athletes. Part 1 focused on the effects of training during pregnancy and on the management of common pregnancy-related symptoms experienced by athletes. In Part 2, we focus on maternal and fetal perinatal outcomes

Ten years of the Hunter Outcome Survey (HOS) : insights, achievements, and lessons learned from a global patient registry

Mucopolysaccharidosis type II (MPS II; Hunter syndrome; OMIM 309900) is a rare lysosomal storage disease with progressive multisystem manifestations caused by deficient activity of the enzyme iduronate-2-sulfatase. Diseasespecific treatment is available in the form of enzyme replacement therapy with intravenous idursulfase (Elaprase®, Shire). Since 2005, the Hunter Outcome Survey (HOS) has collected real-world, long-term data on the safety and effectiveness of this therapy, as well as the natural history of MPS II. Individuals with a confirmed diagnosis of MPS II who are untreated or who are receiving/have received treatment with idursulfase or bone marrow transplant can be enrolled in HOS. A broad range of disease- and treatment-related information is captured in the registry and, over the past decade, data from more than 1000 patients from 124 clinics in 29 countries have been collected. Evidence generated from HOS has helped to improve our understanding of disease progression in both treated and untreated patients and has extended findings from the formal clinical trials of idursulfase. As a long-term, global, observational registry, various challenges relating to data collection, entry, and analysis have been encountered. These have resulted in changes to the HOS database platform, and novel approaches to maximize the value of the information collected will also be needed in the future. The continued evolution of the registry should help to ensure that HOS provides further insights into the burden of the disease and patient care and management in the coming years

D-brane anti-D-brane effective action and brane interaction in open string channel

We construct the effective action of a $D_p$-brane-anti-$D_p$-brane system by making use of the non-abelian extension of tachyonic DBI action. We succeed the construction by restricting the Chan-Paton factors of two non-BPS $D_p$-branes in the action to the Chan-Paton factors of a $D_p\bar{D}_p$ system. For the special case that both branes are coincident, the action reduces to the one proposed by A. Sen. \\The effective $D_p\bar{D}_p$ potential indicates that when branes separation is larger than the string length scale, there are two minima in the tachyon direction. As branes move toward each other under the gravitational force, the tachyon tunneling from false to true vacuum may make a bubble formation followed by a classical evolution of the bubble. On the other hand, when branes separation is smaller than the string length scale, the potential shows one maximum and one minimum. In this case, a homogeneous tachyon rolling in real time makes an attractive potential for the branes distance. This classical force is speculated to be the effective force between the two branes.Comment: Latex, 14 pages, 1 figure, the version appears in JHE