Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia

Prior evidence has supported the existence of multiple susceptibility genes for schizophrenia. Multipoint linkage analysis of the 270 Irish high-density pedigrees that we have studied, as well as results from several other samples, suggest that at least one such gene is located in region 6p24-21. In the present study, family-based association analysis of 36 simple sequence-length-polymorphism markers and of 17 SNP markers implicated two regions, separated by approximately 7 Mb. The first region, and the focus of this report, is 6p22.3. In this region, single-nucleotide polymorphisms within the 140-kb gene DTNBP1 (dystrobrevin-binding protein 1, or dysbindin) are strongly associated with schizophrenia. Uncorrected, empirical P values produced by the program TRANSMIT were significant (P

Genome-wide scans of three independent sets of 90 Irish multiplex schizophrenia families and follow-up of selected regions in all families provides evidence for multiple susceptibility genes

From our linkage study of Irish families with a high density of schizophrenia, we have previously reported evidence for susceptibility genes in regions 5q21-31, 6p24-21, 8p22-21, and 10p15-p11. In this report, we describe the cumulative results from independent genome scans of three a priori random subsets of 90 families each, and from multipoint analysis of all 270 families in ten regions. Of these ten regions, three (13q32, 18p11-q11, and 18q22-23) did not generate scores above the empirical baseline pairwise scan results, and one (6q13-26) generated a weak signal. Six other regions produced more positive pairwise and multipoint results. They showed the following maximum multipoint H-LOD (heterogeneity LOD) and NPL scores: 2p14-13: 0.89 (P = 0.06) and 2.08 (P = 0.02), 4q24-32: 1.84 (P = 0.007) and 1.67 (P = 0.03), 5q21-31: 2.88 (P= 0.0007), and 2.65 (P = 0.002), 6p25-24: 2.13 (P = 0.005) and 3.59 (P = 0.0005), 6p23: 2.42 (P = 0.001) and 3.07 (P = 0.001), 8p22-21: 1.57 (P = 0.01) and 2.56 (P = 0.005), 10p15-11: 2.04 (P = 0.005) and 1.78 (P = 0.03). The degree of 'internal replication' across subsets differed, with 5q, 6p, and 8p being most consistent and 2p and 10p being least consistent. On 6p, the data suggested the presence of two susceptibility genes, in 6p25-24 and 6p23-22. Very few families were positive on more than one region, and little correlation between regions was evident, suggesting substantial locus heterogeneity. The levels of statistical significance were modest, as expected from loci contributing to complex traits. However, our internal replications, when considered along with the positive results obtained in multiple other samples, suggests that most of these six regions are likely to contain genes that influence liability to schizophrenia.

A systematic review evaluating the impact of online or blended learning vs. face-to-face learning of clinical skills in undergraduate nurse education.

Aim: To determine whether the use of an online or blended learning paradigm has the potential to enhance the teaching of clinical skills in undergraduate nursing.

Background: The need to adequately support and develop students in clinical skills is now arguably more important than previously considered due to reductions in practice opportunities. Online and blended teaching methods are being developed to try and meet this requirement, but knowledge about their effectiveness in teaching clinical skills is limited.

Design: Mixed methods systematic review, which follows the Joanna Briggs Institute User guide version 5.

Data Sources: Computerized searches of five databases were undertaken for the period 1995-August 2013.

Review Methods: Critical appraisal and data extraction were undertaken using Joanna Briggs Institute tools for experimental/observational studies and interpretative and critical research. A narrative synthesis was used to report results.

Results: Nineteen published papers were identified. Seventeen papers reported on online approaches and only two papers reported on a blended approach. The synthesis of findings focused on the following four areas: performance/clinical skill, knowledge, self-efficacy/clinical confidence and user experience/satisfaction. The e-learning interventions used varied throughout all the studies.

Conclusion: The available evidence suggests that online learning for teaching clinical skills is no less effective than traditional means. Highlighted by this review is the lack of available evidence on the implementation of a blended learning approach to teaching clinical skills in undergraduate nurse education. Further research is required to assess the effectiveness of this teaching methodology.

Tuneable magneto-optical metamaterials based on photonic resonances in nickel nanorod arrays

We investigate the magneto-optical properties of a nanostructured metamaterial comprised of arrays of nickel nanorods embedded in an anodized aluminum oxide template. The rods are grown using a self-assembly bottom-up technique that provides a uniform, quasi-hexagonal array over a large area, quickly and at low cost. The tuneability of the magneto-optic response of the material is investigated by varying the nanorod dimensions: diameter, length and inter-rod spacing as well as the overall thickness of the template. It is demonstrated that the system acts as a sub-wavelength light trap with enhanced magneto-optical properties occurring at reflectivity minima corresponding to photonic resonances of the metamaterial. Changes in dimensions of the nickel rods on the order of tens of nanometers cause a spectral blue-shift in the peak magneto-optical response of 270 nm in the visible range. A plasmonic enhancement is also observed at lower wavelengths, which becomes increasingly damped with larger diameters and increased volume fraction of nickel inclusions. This type of structure has potential applications in high density magneto-optical data storage (up to 1011–12 rods per square inch), ultrafast magneto-plasmonic switching and optical components for telecommunications.

Instrumentation for diagnostics and control of laser-accelerated proton (ion) beams

Suitable instrumentation for laser-accelerated proton (ion) beams is critical for development of integrated, laser-driven ion accelerator systems. Instrumentation aimed at beam diagnostics and control must be applied to the driving laser pulse, the laser-plasma that forms at the target and the emergent proton (ion) bunch in a correlated way to develop these novel accelerators. This report is a brief overview of established diagnostic techniques and new developments based on material presented at the first workshop on 'Instrumentation for Diagnostics and Control of Laser-accelerated Proton (Ion) Beams' in Abingdon, UK. It includes radiochromic film (RCF), image plates (IP), micro-channel plates (MCP), Thomson spectrometers, prompt inline scintillators, time and space-resolved interferometry (TASRI) and nuclear activation schemes. Repetition-rated instrumentation requirements for target metrology are also addressed. (C) 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

The Role of Victims in the International Criminal Tribunals of the Second World War

This article analyses the role of victims within the founding international criminal tribunals of the Second World War, drawing from historical research of the practice and judgements of the Nuremberg and Tokyo tribunals. While some commentators have decried the absence of victims at Nuremberg and Tokyo, numerous victim-witnesses testified before these tribunals. However, the outcome of these tribunals has been disappointing to victims who still seek justice over sixty-five years later. This article considers the implications of the Nuremberg and Tokyo tribunals not providing justice to victims and how this has impacted on their legacy. Although these tribunals are neglected in contemporary discussions of victim provisions, they can still provide some important lessons for modern international criminal justice mechanisms, such as the International Criminal Court, to learn from.

High shear granulation of binary mixtures: Effect of powder composition on granule properties: Effect of powder composition on granule properties

The granular product being designed in this work required the use of two different powders namely limestone and teawaste; these materials have different bulk and particle densities. The overall aim of the project was to obtain a granular product in the size range of 2 to 4. mm. The two powders were granulated in different proportions using carboxymethylcellulose (CMC) as the binder. The effect of amount of binder added, relative composition of the powder, and type of teawaste on the product yield was studied. The results show that the optimum product yield was a function of both relative powder composition and the amount of binder used; increasing the composition of teawaste in the powder increased the amount of binder required for successful granulation. An increase in the mass fraction of teawaste in the powder mix must be accompanied by an increase in the amount of binder to maintain the desired product yield.

When terror hits home: Identity Fused Americans who saw Boston bombing victims as “family” provided aid

When tragedy strikes a group, only some group members characteristically rush to the aid of the victims. What motivates the altruism of these exceptional individuals? Here, we provide one set of answers based on data collected before and shortly after the 15 April 2013, Boston Marathon bombings. The results of three studies indicated that Americans who were strongly “fused” with their country were especially inclined to provide various forms of support to the bombing victims. Moreover, the degree to which participants reported perceiving fellow Americans as psychological kin statistically mediated links between fusion and pro-group outcomes. Together, these findings shed new light on relationships between personal and group identity, cognitive representations of group members, and personally costly, pro-group actions.

Pitfalls in Protection: How Theory Can Enrich Our Understanding of Regulatory Compliance Problems in Planning Practice

This paper responds to demands for greater academic investigation into environmental protection, specifically the practical and structural problems which underpin regulatory compliance in the planning system. It critiques traditional theories of regulation and answers calls for the development of a thematic lens to facilitate the scrutiny of not only operational practice, but also the broader institutional regime. An empirical investigation builds upon the construct of really responsive regulation to study planning control and it becomes apparent that not only are there significant procedural planning difficulties facing regulatory compliance, but also that a much wider raft of issues must be considered if the complex equation is to be solved. The findings demonstrate how theory can be applied to enrich our rudimentary understanding of deep-seated problems and foster insights into areas of structural importance which are relevant to both planning and the wider regulatory arena.

Exploring the prevalence of and factors associated with pain: a cross-sectional study of community-dwelling people with dementia

Few pain studies have made community-dwelling people with dementia (PWD) their focus. The aim of this study was to determine the prevalence of pain among this patient population and to explore medication use. Moreover, we sought to investigate patient and caregiver variables associated with the presence of pain. Community-dwelling PWD and their caregivers were recruited between May 2009 and July 2012 from outpatient memory clinics in Northern Ireland to take part in a face-to-face structured interview with a researcher. Patients' cognitive status and presence of depression were established. A full medication history was taken. Both patients and caregivers were asked to rate patients' pain, at the time of the interview and on an average day, using a 7-point verbal descriptor scale. From the 206 patients who were eligible to take part, 75 patient-caregiver dyads participated in the study (participation rate = 36.4%). The majority of patients (92.0%) had dementia classed as mild or moderate. Pain was commonly reported among the sample, with 57.3% of patients and 70.7% of caregivers reporting patient pain on an average day. Significant differences were found between patients' and caregivers' reports of pain. Two-fifths of patients (40.0%) were prescribed analgesia. Antipsychotic, hypnotic and anxiolytic drug use was low, whereas antidepressant drugs were prescribed more commonly. Presence of pain was unaffected by dementia severity; however, the use of prescribed analgesic medication was a significant predictor of the presence of pain in these patients, whether reported by the patient or their caregiver 'right now' or 'on an average day' (P < 0.001). Patient and caregiver recruitment was challenging, and remains a barrier to research in this area in the future.

Molecular diagnostics of myeloproliferative neoplasms

Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. While many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations is considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future, play an increasing role in the molecular diagnosis of MPN. 

Combining multi-band and frequency-filtering techniques for speech recognition in noisy environments

While current speech recognisers give acceptable performance in carefully controlled environments, their performance degrades rapidly when they are applied in more realistic situations. Generally, the environmental noise may be classified into two classes: the wide-band noise and narrow band noise. While the multi-band model has been shown to be capable of dealing with speech corrupted by narrow-band noise, it is ineffective for wide-band noise. In this paper, we suggest a combination of the frequency-filtering technique with the probabilistic union model in the multi-band approach. The new system has been tested on the TIDIGITS database, corrupted by white noise, noise collected from a railway station, and narrow-band noise, respectively. The results have shown that this approach is capable of dealing with noise of narrow-band or wide-band characteristics, assuming no knowledge about the noisy environment.

Evidence supporting a role for N-epsilon-(3-formyl-3,4-dehydropiperidino)lysine accumulation in Muller glia dysfunction and death in diabetic retinopathy

Purpose: Recent evidence suggests that neuroglial dysfunction and degeneration contributes to the etiology and progression of diabetic retinopathy. Advanced lipoxidation end products (ALEs) have been implicated in the pathology of various diseases, including diabetes and several neurodegenerative disorders. The purpose of the present study was to investigate the possible link between the accumulation of ALEs and neuroretinal changes in diabetic retinopathy.

Methods: Retinal sections obtained from diabetic rats and age-matched controls were processed for immunohistochemistry using antibodies against several well defined ALEs. In vitro experiments were also performed using a human Muller (Moorfields/Institute of Ophthalmology-Muller 1 [ MIO-M1]) glia cell line. Western blot analysis was used to measure the accumulation of the acrolein-derived ALE adduct N epsilon-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) in Muller cells preincubated with FDP-lysine-modified human serum albumin (FDP-lysine-HSA). Responses of Muller cells to FDP-lysine accumulation were investigated by analyzing changes in the protein expression of heme oxygenase-1 (HO-1), glial fibrillary acidic protein (GFAP), and the inwardly rectifying potassium channel Kir4.1. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha) were determined by reverse transcriptase PCR (RT-PCR). Apoptotic cell death was evaluated by fluorescence-activated cell sorting (FACS) analysis after staining with fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide.

Results: No significant differences in the levels of malondialdehyde-, 4-hydroxy-2-nonenal-, and 4-hydroxyhexenal-derived ALEs were evident between control and diabetic retinas after 4 months of diabetes. By contrast, FDP-lysine immunoreactivity was markedly increased in the Muller glia of diabetic rats. Time-course studies revealed that FDP-lysine initially accumulated within Muller glial end feet after only a few months of diabetes and thereafter spread distally throughout their inner radial processes. Exposure of human Muller glia to FDP-lysine-HSA led to a concentration-dependent accumulation of FDP-lysine-modified proteins across a broad molecular mass range. FDP-lysine accumulation was associated with the induction of HO-1, no change in GFAP, a decrease in protein levels of the potassium channel subunit Kir4.1, and upregulation of transcripts for VEGF, IL-6, and TNF-alpha. Incubation of Muller glia with FDP-lysine-HSA also caused apoptosis at high concentrations.

Conclusions: Collectively, these data strongly suggest that FDP-lysine accumulation could be a major factor contributing to the Muller glial abnormalities occurring in the early stages of diabetic retinopathy.