Once-daily treatment of ADHD with guanfacine: patient implications

The standard of care for treating ADHD is to use a psychostimulant as the first line agent. Recent medical literature reports that approximately 70%–90% of patients with ADHD received some benefit from a stimulant medication. Even though psychostimulants have a high rate of efficacy, an estimated 30%–50% of children and adults may discontinue psychostimulants secondary to adverse effects or inadequate response. Guanfacine has been used for a number of years as an off label alternative to psychostimulants. This article reviews the current literature on the effectiveness of guanfacine in treating ADHD. It also introduces the preliminary data for guanfacine extended release and its effectiveness in decreasing the symptoms of ADHD

An inherited duplication at the gene p21 protein-activated Kinase 7 (PAK7) is a risk factor for psychosis

FUNDING Funding for this study was provided by the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z), the Wellcome Trust (072894/Z/03/Z, 090532/Z/09/Z and 075491/Z/04/B), NIMH grants (MH 41953 and MH083094) and Science Foundation Ireland (08/IN.1/B1916). We acknowledge use of the Trinity Biobank sample from the Irish Blood Transfusion Service; the Trinity Centre for High Performance Computing; British 1958 Birth Cohort DNA collection funded by the Medical Research Council (G0000934) and the Wellcome Trust (068545/Z/02) and of the UK National Blood Service controls funded by the Wellcome Trust. Chris Spencer is supported by a Wellcome Trust Career Development Fellowship (097364/Z/11/Z). Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust. ACKNOWLEDGEMENTS The authors sincerely thank all patients who contributed to this study and all staff who facilitated their involvement. We thank W. Bodmer and B. Winney for use of the People of the British Isles DNA collection, which was funded by the Wellcome Trust. We thank Akira Sawa and Koko Ishzuki for advice on the PAK7–DISC1 interaction experiment and Jan Korbel for discussions on mechanism of structural variation.Peer reviewedPublisher PD

So what do we really mean when we say that systems biology is holistic?

Background: An old debate has undergone a resurgence in systems biology: that of reductionism versus holism. At least 35 articles in the systems biology literature since 2003 have touched on this issue. The histories of holism and reductionism in the philosophy of biology are reviewed, and the current debate in systems biology is placed in context. Results: Inter-theoretic reductionism in the strict sense envisaged by its creators from the 1930s to the 1960s is largely impractical in biology, and was effectively abandoned by the early 1970s in favour of a more piecemeal approach using individual reductive explanations. Classical holism was a stillborn theory of the 1920s, but the term survived in several fields as a loose umbrella designation for various kinds of anti-reductionism which often differ markedly. Several of these different anti-reductionisms are on display in the holistic rhetoric of the recent systems biology literature. This debate also coincides with a time when interesting arguments are being proposed within the philosophy of biology for a new kind of reductionism. Conclusions: Engaging more deeply with these issues should sharpen our ideas concerning the philosophy of systems biology and its future best methodology. As with previous decisive moments in the history of biology, only those theories that immediately suggest relatively easy experiments will be winners

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Sampling density and date along with species selection influence spatial representation of tree-ring reconstructions

Our understanding of the natural variability of hydroclimate before the instrumental period (ca. 1900 CE in the United States) is largely dependent on tree-ring-based reconstructions. Large-scale soil moisture reconstructions from a network of tree-ring chronologies have greatly improved our understanding of the spatial and temporal variability in hydroclimate conditions, particularly extremes of both drought and pluvial (wet) events. However, certain regions within these large-scale network reconstructions in the US are modeled by few tree-ring chronologies. Further, many of the chronologies currently publicly available on the International Tree-Ring Data Bank (ITRDB) were collected in the 1980s and 1990s, and thus our understanding of the sensitivity of radial growth to soil moisture in the US is based on a period that experienced multiple extremely severe droughts and neglects the impacts of recent, rapid global change. In this study, we expanded the tree-ring network of the Ohio River valley in the US, a region with sparse coverage. We used a total of 72 chronologies across 15 species to examine how increasing the density of the tree-ring network influences the representation of reconstructing the Palmer Meteorological Drought Index (PMDI). Further, we tested how the sampling date and therefore the calibration period influenced the reconstruction models by creating reconstructions that ended in the year 1980 and compared them to reconstructions ending in 2010 from the same chronologies. We found that in- creasing the density of the tree-ring network resulted in reconstructed values that better matched the spatial variability of instrumentally recorded droughts and, to a lesser extent, pluvials. By extending the calibration period to 2010 compared to 1980, the sensitivity of tree rings to PMDI decreased in the southern portion of our region where severe drought conditions have been absent over recent decades. We emphasize the need of building a high-density tree-ring network to better represent the spatial variability of past droughts and pluvials. Further, chronologies on the ITRDB need updating regularly to better understand how the sensitivity of tree rings to climate may vary through time.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Sampling Density and Date Along With Species Selection Influence Spatial Representation of Tree-Ring Reconstructions

© 2020 Royal Society of Chemistry. All rights reserved. Our understanding of the natural variability of hydroclimate before the instrumental period (ca. 1900 CE in the United States) is largely dependent on tree-ring-based reconstructions. Large-scale soil moisture reconstructions from a network of tree-ring chronologies have greatly improved our understanding of the spatial and temporal variability in hydroclimate conditions, particularly extremes of both drought and pluvial (wet) events. However, certain regions within these large-scale network reconstructions in the US are modeled by few tree-ring chronologies. Further, many of the chronologies currently publicly available on the International Tree-Ring Data Bank (ITRDB) were collected in the 1980s and 1990s, and thus our understanding of the sensitivity of radial growth to soil moisture in the US is based on a period that experienced multiple extremely severe droughts and neglects the impacts of recent, rapid global change. In this study, we expanded the tree-ring network of the Ohio River valley in the US, a region with sparse coverage. We used a total of 72 chronologies across 15 species to examine how increasing the density of the tree-ring network influences the representation of reconstructing the Palmer Meteorological Drought Index (PMDI). Further, we tested how the sampling date and therefore the calibration period influenced the reconstruction models by creating reconstructions that ended in the year 1980 and compared them to reconstructions ending in 2010 from the same chronologies. We found that increasing the density of the tree-ring network resulted in reconstructed values that better matched the spatial variability of instrumentally recorded droughts and, to a lesser extent, pluvials. By extending the calibration period to 2010 compared to 1980, the sensitivity of tree rings to PMDI decreased in the southern portion of our region where severe drought conditions have been absent over recent decades.We emphasize the need of building a high-density tree-ring network to better represent the spatial variability of past droughts and pluvials. Further, chronologies on the ITRDB need updating regularly to better understand how the sensitivity of tree rings to climate may vary through time

Downhill from devaluation: The battle for sterling, 1967–1972

The devaluation of 1967 and the float of 1972 have become two of the key cornerstones in the analysis of sterling under the Bretton Woods system. Sterling’s fortunes between 1968 and 1972 have not been so well documented. This article uncovers new evidence about the pound for this period, including the British government’s contingency plans for blocking the sterling balances as a means to negate the weakness of sterling following the 1967 devaluation, the discussions with the United States on the reform of the international monetary system, and the preparations made for floating the pound

Genome-wide Association Study Implicates HLA-C*01:02 as a Risk Factor at the Major Histocompatibility Complex Locus in Schizophrenia

BACKGROUND: We performed a genome-wide association study (GWAS) to identify common risk variants for schizophrenia. METHODS: The discovery scan included 1606 patients and 1794 controls from Ireland, using 6,212,339 directly genotyped or imputed single nucleotide polymorphisms (SNPs). A subset of this sample (270 cases and 860 controls) was subsequently included in the Psychiatric GWAS Consortium-schizophrenia GWAS meta-analysis. RESULTS: One hundred eight SNPs were taken forward for replication in an independent sample of 13,195 cases and 31,021 control subjects. The most significant associations in discovery, corrected for genomic inflation, were (rs204999, p combined = 1.34 × 10(-9) and in combined samples (rs2523722 p combined = 2.88 × 10(-16)) mapped to the major histocompatibility complex (MHC) region. We imputed classical human leukocyte antigen (HLA) alleles at the locus; the most significant finding was with HLA-C*01:02. This association was distinct from the top SNP signal. The HLA alleles DRB1*03:01 and B*08:01 were protective, replicating a previous study. CONCLUSIONS: This study provides further support for involvement of MHC class I molecules in schizophrenia. We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci

Do industry 4.0 technologies matter when companies backshore manufacturing activities? An explorative study comparing Europe and the US

The objective of this chapter is to analyze the impact (if any) of Industry 4.0 enabling technology on firms’ decision to relocate to the home country their offshored production activities. In particular, the chapter analyzes whether Industry 4.0 technologies may represent a driver/motivation or an enabling factor for companies which are evaluating such a strategic alternative. In order to reach such an objective, a two-step explorative methodology has been applied. After implementing a structured literature review, empirical evidence of backshoring decisions implemented by both European and US companies has been analyzed. Collected findings show that the majority of sampled articles conceptualize Industry 4.0 technologies as a driver. At the same time, empirical findings show some interesting differences between European and US companies adopting backshoring decisions based on/enabled by Industry 4.0 technologies. Finally, competences (related to both the manufacturing activities as a whole and the Industry 4.0 technologies) emerge as one of the most critical issue for investigated companies