Individual cognitive-behavioural anger treatment for people with mild-borderline intellectual disabilities and histories of aggression: a controlled trial

Objectives - Anger is a significant predictor and activator of violent behaviour in patients living in institutional settings. There is some evidence for the value of cognitive-behavioural treatments for anger problems with people with intellectual disabilities. In this study, a newly designed treatment targeted at anger disposition, reactivity, and control was provided to intellectually disabled offenders with aggression histories living in secure settings. Design - About forty detained patients with mild-borderline intellectual disabilities and histories of serious aggression were allocated to specially modified cognitive-behavioural anger treatment (AT group) or to routine care waiting-list control (RC group) conditions. Methods - AT group participants received 18 sessions of individual treatment. The AT and RC groups were assessed simultaneously at 4 time points: screen, pre- and post-treatment, and at 4-month follow-up using a range of self- and staff-rated anger measures. The effectiveness of the treatment was evaluated using ANCOVA linear trend analyses of group differences on the main outcome measures. Results - The AT group's self-reported anger scores on a number of measures were significantly lower following treatment, compared with the RC wait-list condition, and these improvements were maintained at follow-up. Limited evidence for the effectiveness of treatment was provided by staffs' ratings of patient behaviour post-treatment. Conclusions - Detained men with mild-moderate intellectual disabilities and histories of severe aggression can successfully engage in, and benefit from, an intensive individual cognitive-behavioural anger treatment that also appears to have beneficial systemic effects

Advances towards norovirus antivirals

Human noroviruses are a leading cause of gastroenteritis worldwide, yet there are no licensed antivirals. There is an urgent need for norovirus therapeutics, particularly for chronic infections in immunocompromised individuals, but also a potential need for prophylactic use in epidemics. Continued research has led to the identification of compounds that inhibit norovirus replication in vitro and, at least in some cases, are also effective in vivo against murine norovirus. Progress has included classical approaches targeting viral proteins and harnessing the antiviral action of interferon, strategies targeting essential host cell factors, and novel strategies exploiting the high mutation rate of noroviruses.The authors declare no conflict in interest. This work was supported by the Wellcome Trust (Ref: WT097997MA)This is the final version of the article. It was first available from Oxford University Press via http://dx.doi.org/10.1093/infdis/jiv28

miR-155 induction is a marker of murine norovirus infection but does not contribute to control of replication in vivo.

Background: Due to their role in fine-tuning cellular protein expression, microRNAs both promote viral replication and contribute to antiviral responses, for a range of viruses. The interactions between norovirus and the microRNA machinery have not yet been studied. Here, we investigated the changes that occur in microRNA expression during murine norovirus (MNV) infection. Methods: Using RT-qPCR-based arrays, we analysed changes in miRNA expression during infection with the acute strain MNV-1 in two permissive cell lines, a murine macrophage cell line, RAW264.7, and a murine microglial cell line, BV-2. By RT-qPCR, we further confirmed and analysed the changes in miR-155 expression in the infected cell lines, bone-marrow derived macrophage, and tissues harvested from mice infected with the persistent strain MNV-3. Using miR-155 knockout (KO) mice, we investigated whether loss of miR-155 affected viral replication and pathogenesis during persistent MNV-3 infection in vivo and monitored development of a serum IgG response by ELISA. Results: We identified cell-specific panels of miRNAs whose expression were increased or decreased during infection. Only two miRNAs, miR-687 and miR-155, were induced in both cell lines. miR-155, implicated in innate immunity, was also upregulated in bone-marrow derived macrophage and infected tissues. MNV-3 established a persistent infection in miR-155 knockout (KO) mice, with comparable levels of secreted virus and tissue replication observed as for wildtype mice. However, serum anti-MNV IgG levels were significantly reduced in miR-155 KO mice compared to wildtype mice. Conclusions: We have identified a panel of miRNAs whose expression changes with MNV infection. miR-155 induction is a marker of MNV infection in vitro and in vivo, however it does not contribute to the control of persistent infections in vivo. This finding suggests that the immune defects associated with miR-155 deletion, such as lower serum IgG levels, are also not important for control of persistent MNV-3 infection

Norovirus Polymerase Fidelity Contributes to Viral Transmission In Vivo.

Intrahost genetic diversity and replication error rates are intricately linked to RNA virus pathogenesis, with alterations in viral polymerase fidelity typically leading to attenuation during infections in vivo. We have previously shown that norovirus intrahost genetic diversity also influences viral pathogenesis using the murine norovirus model, as increasing viral mutation frequency using a mutagenic nucleoside resulted in clearance of a persistent infection in mice. Given the role of replication fidelity and genetic diversity in pathogenesis, we have now investigated whether polymerase fidelity can also impact virus transmission between susceptible hosts. We have identified a high-fidelity norovirus RNA-dependent RNA polymerase mutant (I391L) which displays delayed replication kinetics in vivo but not in cell culture. The I391L polymerase mutant also exhibited lower transmission rates between susceptible hosts than the wild-type virus and, most notably, another replication defective mutant that has wild-type levels of polymerase fidelity. These results provide the first experimental evidence that norovirus polymerase fidelity contributes to virus transmission between hosts and that maintaining diversity is important for the establishment of infection. This work supports the hypothesis that the reduced polymerase fidelity of the pandemic GII.4 human norovirus isolates may contribute to their global dominance. IMPORTANCE Virus replication fidelity and hence the intrahost genetic diversity of viral populations are known to be intricately linked to viral pathogenesis and tropism as well as to immune and antiviral escape during infection. In this study, we investigated whether changes in replication fidelity can impact the ability of a virus to transmit between susceptible hosts by the use of a mouse model for norovirus. We show that a variant encoding a high-fidelity polymerase is transmitted less efficiently between mice than the wild-type strain. This constitutes the first experimental demonstration that the polymerase fidelity of viruses can impact transmission of infection in their natural hosts. These results provide further insight into potential reasons for the global emergence of pandemic human noroviruses that display alterations in the replication fidelity of their polymerases compared to nonpandemic strains

Template banks to search for compact binaries with spinning components in gravitational wave data

Gravitational waves from coalescing compact binaries are one of the most promising sources for detectors such as LIGO, Virgo and GEO600. If the components of the binary posess significant angular momentum (spin), as is likely to be the case if one component is a black hole, spin-induced precession of a binary's orbital plane causes modulation of the gravitational-wave amplitude and phase. If the templates used in a matched-filter search do not accurately model these effects then the sensitivity, and hence the detection rate, will be reduced. We investigate the ability of several search pipelines to detect gravitational waves from compact binaries with spin. We use the post-Newtonian approximation to model the inspiral phase of the signal and construct two new template banks using the phenomenological waveforms of Buonanno, Chen and Vallisneri. We compare the performance of these template banks to that of banks constructed using the stationary phase approximation to the non-spinning post-Newtonian inspiral waveform currently used by LIGO and Virgo in the search for compact binary coalescence. We find that, at the same false alarm rate, a search pipeline using phenomenological templates is no more effective than a pipeline which uses non-spinning templates. We recommend the continued use of the non-spinning stationary phase template bank until the false alarm rate associated with templates which include spin effects can be substantially reduced.Comment: 11 pages, 3 figure

Erroneous arctic temperature trends in the ERA-40 reanalysis: A closer look

© Copyright 2011 American Meteorological Society (AMS). Permission to use figures, tables, and brief excerpts from this work in scientific and educational works is hereby granted provided that the source is acknowledged. Any use of material in this work that is determined to be “fair use” under Section 107 of the U.S. Copyright Act September 2010 Page 2 or that satisfies the conditions specified in Section 108 of the U.S. Copyright Act (17 USC §108, as revised by P.L. 94-553) does not require the AMS’s permission. Republication, systematic reproduction, posting in electronic form, such as on a web site or in a searchable database, or other uses of this material, except as exempted by the above statement, requires written permission or a license from the AMS. Additional details are provided in the AMS Copyright Policy, available on the AMS Web site located at (http://www.ametsoc.org/) or from the AMS at 617-227-2425 or [email protected] reanalyses can be useful tools for examining climate variability and change; however, they must be used cautiously because of time-varying biases that can induce artificial trends. This study explicitly documents a discontinuity in the 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40) that leads to significantly exaggerated warming in the Arctic mid- to lower troposphere, and demonstrates that the continuing use of ERA-40 to study Arctic temperature trends is problematic. The discontinuity occurs in 1997 in response to refined processing of satellite radiances prior to their assimilation into the reanalysis model. It is clearly apparent in comparisons of ERA-40 output against satellite-derived air temperatures, in situ observations, and alternative reanalyses. Decadal or multidecadal Arctic temperature trends calculated over periods that include 1997 are highly inaccurate, particularly below 600 hPa. It is shown that ERA-40 is poorly suited to studying Arctic temperature trends and their vertical profile, and conclusions based upon them must be viewed with extreme caution. Consequently, its future use for this purpose is discouraged. In the context of the wider scientific debate on the suitability of reanalyses for trend analyses, the results show that a series of alternative reanalyses are in broad-scale agreement with observations. Thus, the authors encourage their discerning use instead of ERA-40 for examining Arctic climate change while also reaffirming the importance of verifying reanalyses with observations whenever possibl

In Situ U–Pb Monazite and Xenotime Geochronology of the Abra Polymetallic Deposit and Associated Sedimentary and Volcanic Rocks, Bangemall Supergroup, Western Australia

Abra is a major lead–silver–copper–gold deposit within the Bangemall Supergroup that has a total indicated and inferred resource estimate of 93 million tonnes at 4.0% lead and 10 g/t silver and 14 million tonnes at 0.6% copper and 0.5 g/t gold. The mineralization lies within the upper part of the locally defi ned Gap Well Formation, and in the lower part of the overlying West Creek Formation. These units correlate respectively with the Irregully and lower Kiangi Creek Formations of the Edmund Group.The Abra deposit is characterized by a funnel-shaped brecciated zone, interpreted as a breccia feeder-pipe, overlain by stratabound mineralization made up of the Red Zone, an underlying Black Zone, and a stringer (feeder) zone. The Red Zone is characterized by banded jaspilite, hematite, galena, pyrite, quartz, abundant barite, and siderite. The Black Zone consists of veins and rhythmically banded Pb, Zn, and minor Cu sulfi des, laminated and/or brecciated hematite, magnetite, Fe-rich carbonate, barite, and scheelite.In situ Sensitive high-resolution ion microprobe (SHRIMP) U–Pb geochronology of detrital zircon, monazite, and xenotime in sandstones from the Abra deposit yields a range of dates from c. 2450 Ma to c. 1675 Ma, consistent with results from previous detrital zircon studies. SHRIMP dating of hydrothermal monazite from the Abra deposit suggests that a mineralization event occurred at c. 1385 Ma. The presence of c. 1465 Ma metamorphic/hydrothermal monazite in sandstones from Abra indicates that the host rocks are older and therefore belong to the Edmund Group. SHRIMP geochronology of xenotime extracted from the Tangadee Rhyolite, which outcrops within the lower Kiangi Creek Formation close to the Abra deposit, yields two main age components corresponding to oscillatory-zoned cores and unzoned rims. The cores are interpreted as magmatic in origin and indicate a possible eruption age of c. 1235 Ma, whereas the rims are interpreted to record a later hydrothermal event at c. 1030 Ma. If this interpretation is correct, then the sedimentary succession containing the rhyolite is younger than the Edmund Group (1465 Ma), and may belong to the basal Collier Group (1070 Ma) although the geological setting does not support this

Involving service users in trials: developing a standard operating procedure

<p>BACKGROUND: Many funding bodies require researchers to actively involve service users in research to improve relevance, accountability and quality. Current guidance to researchers mainly discusses general principles. Formal guidance about how to involve service users operationally in the conduct of trials is lacking. We aimed to develop a standard operating procedure (SOP) to support researchers to involve service users in trials and rigorous studies.</p> <p>METHODS: Researchers with experience of involving service users and service users who were contributing to trials collaborated with the West Wales Organisation for Rigorous Trials in Health, a registered clinical trials unit, to develop the SOP. Drafts were prepared in a Task and Finish Group, reviewed by all co-authors and amendments made.</p> <p>RESULTS: We articulated core principles, which defined equality of service users with all other research team members and collaborative processes underpinning the SOP, plus guidance on how to achieve these. We developed a framework for involving service users in research that defined minimum levels of collaboration plus additional consultation and decision-making opportunities. We recommended service users be involved throughout the life of a trial, including planning and development, data collection, analysis and dissemination, and listed tasks for collaboration. We listed people responsible for involving service users in studies and promoting an inclusive culture. We advocate actively involving service users as early as possible in the research process, with a minimum of two on all formal trial groups and committees. We propose that researchers protect at least 1% of their total research budget as a minimum resource to involve service users and allow enough time to facilitate active involvement.</p> <p>CONCLUSIONS: This SOP provides guidance to researchers to involve service users successfully in developing and conducting clinical trials and creating a culture of actively involving service users in research at all stages. The UK Clinical Research Collaboration should encourage clinical trials units actively to involve service users and research funders should provide sufficient funds and time for this in research grants.</p&gt

Acoustic scattering characteristics and inversions for suspended concentration and particle size above mixed sand and mud beds

The majority of reported field studies, using acoustic backscattering, for the measurement of nearbed suspended sediment processes, have been focussed on field sites with sand size fractions and unimodal size distributions. However, in many sedimentary environments, and particularly for estuaries and rivers, sands and muds coexist in the bed sediment substrate, forming a size regime that is often bimodal in nature. To examine the interaction of sound in these more complex sedimentary environments a numerical study is presented based on observations of sediment size distributions measured in the Dee estuary, UK. The work explores the interpretation of the backscatter signal from a mixed sediment composition in suspension, with mud-sand fractions varying with height above the bed. Consideration is given to the acoustical scattering properties and the inversion of the backscatter signal to extract information on the suspension. In common with most field deployments, the scenarios presented here use local bed sediments for the acoustic inversion of the backscattered signal. The results indicate that in general it is expected that particle size and concentration will diverge from what is actually in suspension, with the former being overestimated and the latter underestimated