A multi-national comparison of antipsychotic drug use in children and adolescents, 2005-2012

Over the last decades, an increase in antipsychotic (AP) prescribing and a shift from first-generation antipsychotics (FGA) to second-generation antipsychotics (SGA) among youth have been reported. However, most AP prescriptions for youth are off-label, and there are worrying long-term safety data in youth. The objective of this study was to assess multinational trends in AP use among children and adolescents. A repeated cross-sectional design was applied to cohorts from varied sources from Denmark, Germany, the Netherlands, the United Kingdom (UK) and the United States (US) for calendar years 2005/2006–2012. The annual prevalence of AP use was assessed, stratified by age group, sex and subclass (FGA/SGA). The prevalence of AP use increased from 0.78 to 1.03% in the Netherlands’ data, from 0.26 to 0.48% in the Danish cohort, from 0.23 to 0.32% in the German cohort, and from 0.1 to 0.14% in the UK cohort. In the US cohort, AP use decreased from 0.94 to 0.79%. In the US cohort, nearly all ATP dispensings were for SGA, while among the European cohorts the proportion of SGA dispensings grew to nearly 75% of all AP dispensings. With the exception of the Netherlands, AP use prevalence was highest in 15–19 year-olds. So, from 2005/6 to 2012, AP use prevalence increased in all youth cohorts from European countries and decreased in the US cohort. SGA were favoured in all countries’ cohorts

Neural processing of criticism and positive comments from relatives in individuals with schizotypal personality traits

Objectives. High negative expressed emotion by family members towards schizophrenia patients increases the risk of subsequent relapse. The study aimed to determine whether individuals with high schizotypy (HS) and low schizotypy (LS) would differ in activation of brain areas involved in cognitive control when listening to relative criticism

The link between volcanism and plutonism in epizonal magma systems; high-precision U–Pb zircon geochronology from the Organ Mountains caldera and batholith, New Mexico

The Organ Mountains caldera and batholith expose the volcanic and epizonal plutonic record of an Eocene caldera complex. The caldera and batholith are well exposed, and extensive previous mapping and geochemical analyses have suggested a clear link between the volcanic and plutonic sections, making this an ideal location to study magmatic processes associated with caldera volcanism. Here we present high-precision thermal ionization mass spectrometry U–Pb zircon dates from throughout the caldera and batholith, and use these dates to test and improve existing petrogenetic models. The new dates indicate that Eocene volcanic and plutonic rocks in the Organ Mountains formed from ~44 to 34 Ma. The three largest caldera-related tuff units yielded weighted mean [superscript 206]Pb/[superscript 238]U dates of 36.441 ± 0.020 Ma (Cueva Tuff), 36.259 ± 0.016 Ma (Achenback Park tuff), and 36.215 ± 0.016 Ma (Squaw Mountain tuff). An alkali feldspar granite, which is chemically similar to the erupted tuffs, yielded a synchronous weighted mean [superscript 206]Pb/[superscript 238]U date of 36.259 ± 0.021 Ma. Weighted mean [superscript 206]Pb/[superscript 238]U dates from the larger volume syenitic phase of the underlying Organ Needle pluton range from 36.130 ± 0.031 to 36.071 ± 0.012 Ma, and the youngest sample is 144 ± 20 to 188 ± 20 ka younger than the Squaw Mountain and Achenback Park tuffs, respectively. Younger plutonism in the batholith continued through at least 34.051 ± 0.029 Ma. We propose that the Achenback Park tuff, Squaw Mountain tuff, alkali feldspar granite and Organ Needle pluton formed from a single, long-lived magma chamber/mush zone. Early silicic magmas generated by partial melting of the lower crust rose to form an epizonal magma chamber. Underplating of the resulting mush zone led to partial melting and generation of a high-silica alkali feldspar granite cap, which erupted to form the tuffs. The deeper parts of the chamber underwent continued recharge and crystallization for 144 ± 20 ka after the final eruption. Calculated magmatic fluxes for the Organ Needle pluton range from 0.0006 to 0.0030 km3/year, in agreement with estimates from other well-studied plutons. The petrogenetic evolution proposed here may be common to many small-volume silicic volcanic systems

How managers can build trust in strategic alliances: a meta-analysis on the central trust-building mechanisms

Trust is an important driver of superior alliance performance. Alliance managers are influential in this regard because trust requires active involvement, commitment and the dedicated support of the key actors involved in the strategic alliance. Despite the importance of trust for explaining alliance performance, little effort has been made to systematically investigate the mechanisms that managers can use to purposefully create trust in strategic alliances. We use Parkhe’s (1998b) theoretical framework to derive nine hypotheses that distinguish between process-based, characteristic-based and institutional-based trust-building mechanisms. Our meta-analysis of 64 empirical studies shows that trust is strongly related to alliance performance. Process-based mechanisms are more important for building trust than characteristic- and institutional-based mechanisms. The effects of prior ties and asset specificity are not as strong as expected and the impact of safeguards on trust is not well understood. Overall, theoretical trust research has outpaced empirical research by far and promising opportunities for future empirical research exist

Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Displaced distal forearm fractures in children with an indication for reduction under general anesthesia should be percutaneously fixated

Surger

Exogenous spatial precuing reliably modulates object processing but not object substitution masking

Object substitution masking (OSM) is used in behavioral and imaging studies to investigate processes associated with the formation of a conscious percept. Reportedly, OSM occurs only when visual attention is diffusely spread over a search display or focused away from the target location. Indeed, the presumed role of spatial attention is central to theoretical accounts of OSM and of visual processing more generally (Di Lollo, Enns, & Rensink, Journal of Experimental Psychology: General 129:481–507, 2000). We report a series of five experiments in which valid spatial precuing is shown to enhance the ability of participants to accurately report a target but, in most cases, without affecting OSM. In only one experiment (Experiment 5) was a significant effect of precuing observed on masking. This is in contrast to the reliable effect shown across all five experiments in which precuing improved overall performance. The results are convergent with recent findings from Argyropoulos, Gellatly, and Pilling (Journal of Experimental Psychology: Human Perception and Performance 39:646–661, 2013), which show that OSM is independent of the number of distractor items in a display. Our results demonstrate that OSM can operate independently of focal attention. Previous claims of the strong interrelationship between OSM and spatial attention are likely to have arisen from ceiling or floor artifacts that restricted measurable performance

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role