The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures.

In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests

Staff attitudes and the associations with treatment organisation, clinical practices and outcomes in opioid maintenance treatment

<p>Abstract</p> <p>Background</p> <p>In opioid maintenance treatment (OMT) there are documented treatment differences both between countries and between OMT programmes. Some of these differences have been associated with staff attitudes. The aim of this study was to 1) assess if there were differences in staff attitudes within a national OMT programme, and 2) investigate the associations of staff attitudes with treatment organisation, clinical practices and outcomes.</p> <p>Methods</p> <p>This study was a cross-sectional multicentre study. Norwegian OMT staff (<it>n </it>= 140) were invited to participate in this study in 2007 using an instrument measuring attitudes towards OMT. The OMT programme comprised 14 regional centres. Data describing treatment organisation, clinical practices and patient outcomes in these centres were extracted from the annual OMT programme assessment 2007. Centres were divided into three groups based upon mean attitudinal scores and labelled; "rehabilitation-oriented", "harm reduction-oriented" and "intermediate" centres.</p> <p>Results</p> <p>All invited staff (<it>n </it>= 140) participated. Staff attitudes differed between the centres. "Rehabilitation-oriented" centres had smaller caseloads, more frequent urine drug screening and increased case management (interdisciplinary meetings). In addition these centres had less drug use and more social rehabilitation among their patients in terms of long-term living arrangements, unemployment, and social security benefits as main income. "Intermediate" centres had the lowest treatment termination rate.</p> <p>Conclusions</p> <p>This study identified marked variations in staff attitudes between the regional centres within a national OMT programme. These variations were associated with measurable differences in caseload, intensity of case management and patient outcomes.</p

Accurate Whole-Genome Sequencing and Haplotyping from 10 to 20 Human Cells

Recent advances in whole genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, Long Fragment Read (LFR) technology, similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ~100 pg of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants (SNVs) were assembled into long haplotype contigs. Removal of false positive SNVs not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 Mb. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications

Exclusive Photoproduction of the Cascade (Xi) Hyperons

We report on the first measurement of exclusive Xi-(1321) hyperon photoproduction in gamma p --> K+ K+ Xi- for 3.2 < E(gamma) < 3.9 GeV. The final state is identified by the missing mass in p(gamma,K+ K+)X measured with the CLAS detector at Jefferson Laboratory. We have detected a significant number of the ground-state Xi-(1321)1/2+, and have estimated the total cross section for its production. We have also observed the first excited state Xi-(1530)3/2+. Photoproduction provides a copious source of Xi's. We discuss the possibilities of a search for the recently proposed Xi5-- and Xi5+ pentaquarks.Comment: submitted to Phys. Rev.

Combining RNAscope and immunohistochemistry to visualize inflammatory gene products in neurons and microglia

A challenge for central nervous system (CNS) tissue analysis in neuroscience research has been the difficulty to codetect and colocalize gene and protein expression in the same tissue. Given the importance of identifying gene expression relative to proteins of interest, for example, cell-type specific markers, we aimed to develop a protocol to optimize their codetection. RNAscope fluorescent in situ hybridization (FISH) combined with immunohistochemistry (IHC) in fixed (CNS) tissue sections allows for reliable quantification of gene transcripts of interest within IHC-labeled cells. This paper describes a new method for simultaneous visualization of FISH and IHC in thicker (14-μm), fixed tissue samples, using spinal cord sections. This method’s effectiveness is shown by the cell-type-specific quantification of two genes, namely the proinflammatory cytokine interleukin-1beta (IL-1b) and the inflammasome NLR family pyrin domain containing 3 (NLRP3). These genes are challenging to measure accurately using immunohistochemistry (IHC) due to the nonspecificity of available antibodies and the hard-to-distinguish, dot-like visualizations of the labeled proteins within the tissue. These measurements were carried out in spinal cord sections after unilateral chronic constriction injury of the sciatic nerve to induce neuroinflammation in the spinal cord. RNAscope is used to label transcripts of genes of interest and IHC is used to label cell-type specific antigens (IBA1 for microglia, NeuN for neurons). This combination allowed for labeled RNA transcripts to be quantified within cell-type specific boundaries using confocal microscopy and standard image analysis methods. This method makes it easy to answer empirical questions that are intractable with standard IHC or in situ hybridization alone. The method, which has been optimized for spinal cord tissue and to minimize tissue preparation time and costs, is described in detail from tissue collection to image analysis. Further, the relative expression changes in inflammatory genes NLRP3 and IL-1b in spinal cord microglia vs. neurons of somatotopically relevant laminae are described for the first time

Empirical Evidence on Inflation and Unemployment in the Long Run

We examine the relationship between inflation and unemployment in the long run, using quarterly US data from 1952 to 2010. Using a band-pass filter approach, we find strong evidence that a positive relationship exists, where inflation leads unemployment by some 3 to 3 1/2 years, in cycles that last from 8 to 25 or 50 years. Our statistical approach is atheoretical in nature, but provides evidence in accordance with the predictions of Friedman (1977) and the recent New Monetarist model of Berentsen, Menzio, and Wright (2011): the relationship between inflation and unemployment is positive in the long run

The Influence of Perceptual Training on Working Memory in Older Adults

Normal aging is associated with a degradation of perceptual abilities and a decline in higher-level cognitive functions, notably working memory. To remediate age-related deficits, cognitive training programs are increasingly being developed. However, it is not yet definitively established if, and by what mechanisms, training ameliorates effects of cognitive aging. Furthermore, a major factor impeding the success of training programs is a frequent failure of training to transfer benefits to untrained abilities. Here, we offer the first evidence of direct transfer-of-benefits from perceptual discrimination training to working memory performance in older adults. Moreover, using electroencephalography to evaluate participants before and after training, we reveal neural evidence of functional plasticity in older adult brains, such that training-induced modifications in early visual processing during stimulus encoding predict working memory accuracy improvements. These findings demonstrate the strength of the perceptual discrimination training approach by offering clear psychophysical evidence of transfer-of-benefit and a neural mechanism underlying cognitive improvement

Five-Factor Model personality profiles of drug users

<p>Abstract</p> <p>Background</p> <p>Personality traits are considered risk factors for drug use, and, in turn, the psychoactive substances impact individuals' traits. Furthermore, there is increasing interest in developing treatment approaches that match an individual's personality profile. To advance our knowledge of the role of individual differences in drug use, the present study compares the personality profile of tobacco, marijuana, cocaine, and heroin users and non-users using the wide spectrum Five-Factor Model (FFM) of personality in a diverse community sample.</p> <p>Method</p> <p>Participants (<it>N </it>= 1,102; mean age = 57) were part of the Epidemiologic Catchment Area (ECA) program in Baltimore, MD, USA. The sample was drawn from a community with a wide range of socio-economic conditions. Personality traits were assessed with the Revised NEO Personality Inventory (NEO-PI-R), and psychoactive substance use was assessed with systematic interview.</p> <p>Results</p> <p>Compared to never smokers, current cigarette smokers score lower on Conscientiousness and higher on Neuroticism. Similar, but more extreme, is the profile of cocaine/heroin users, which score very high on Neuroticism, especially Vulnerability, and very low on Conscientiousness, particularly Competence, Achievement-Striving, and Deliberation. By contrast, marijuana users score high on Openness to Experience, average on Neuroticism, but low on Agreeableness and Conscientiousness.</p> <p>Conclusion</p> <p>In addition to confirming high levels of negative affect and impulsive traits, this study highlights the links between drug use and low Conscientiousness. These links provide insight into the etiology of drug use and have implications for public health interventions.</p

Probing the Interstellar Medium in Early type galaxies with ISO observations

Four IRAS-detected early type galaxies were observed with ISO. With the exception of the 15 micron image of NGC1052, the mid-IR emission from NGC1052, NGC1155, NGC5866 and NGC6958 at 4.5, 7 and 15 microns show extended emission. Mid-IR emission from NGC1052, NGC1155, and NGC6958 follows a de Vaucouleurs profile. The ratio of 15/7 micron flux decreases with radius in these galaxies, approaching the values empirically observed for purely stellar systems. In NGC5866, the 7 and 15 micron emission is concentrated in the edge-on dust lane. All the galaxies are detected in the [CII] line, and the S0s NGC1155 and NGC5866 are detected in the [OI] line as well. The ISO-LWS observations of the [CII] line are more sensitive measures of cool, neutral ISM than HI and CO by about a factor of 10-100. Three of four early type galaxies, namely NGC1052, NGC6958 and NGC5866, have low ratio FIR/Blue and show a lower [CII]/FIR, which is due to a softer radiation field from old stellar populations. The low [CII]/CO ratio in NGC5866 ([CII]/CO(1-0) < 570) confirms this scenario. We estimate the UV radiation expected from the old stellar populations in these galaxies and compare it to that needed to heat the gas to account for the cooling observed [CII] and [OI] lines. In three out of four galaxies, NGC1052, NGC5866 and NGC6958, the predicted UV radiation falls short by a factor of 2-3. In view of the observed intrinsic scatter in the "UV-upturn" in elliptical galaxies and its great sensitivity to age and metallicity effects, this is not significant. However, the much larger difference (about a factor of 20) between the UV radiation from old stars and that needed to produce the FIR lines for NGC 1155 is strong evidence for the presence of young stars, in NGC1155.Comment: To appear in the Astrophysical Journal. Figure 1 appears as a separate jpg figur

DNA Methylation of the First Exon Is Tightly Linked to Transcriptional Silencing

Tissue specific patterns of methylated cytosine residues vary with age, can be altered by environmental factors, and are often abnormal in human disease yet the cellular consequences of DNA methylation are incompletely understood. Although the bodies of highly expressed genes are often extensively methylated in plants, the relationship between intragenic methylation and expression is less clear in mammalian cells. We performed genome-wide analyses of DNA methylation and gene expression to determine how the pattern of intragenic methylation correlates with transcription and to assess the relationship between methylation of exonic and intronic portions of the gene body. We found that dense exonic methylation is far more common than previously recognized or expected statistically, yet first exons are relatively spared compared to more downstream exons and introns. Dense methylation surrounding the transcription start site (TSS) is uncoupled from methylation within more downstream regions suggesting that there are at least two classes of intragenic methylation. Whereas methylation surrounding the TSS is tightly linked to transcriptional silencing, methylation of more downstream regions is unassociated with the magnitude of gene expression. Notably, we found that DNA methylation downstream of the TSS, in the region of the first exon, is much more tightly linked to transcriptional silencing than is methylation in the upstream promoter region. These data provide direct evidence that DNA methylation is interpreted dissimilarly in different regions of the gene body and suggest that first exon methylation blocks transcript initiation, or vice versa. Our data also show that once initiated, downstream methylation is not a significant impediment to polymerase extension. Thus, the consequences of most intragenic DNA methylation must extend beyond the modulation of transcription magnitude