Affective Bias Through the Lens of Signal Detection Theory

Affective bias – a propensity to focus on negative information at the expense of positive information – is a core feature of many mental health problems. However, it can be caused by wide range of possible underlying cognitive mechanisms. Here we illustrate this by focusing on one particular behavioural signature of affective bias – increased tendency of anxious/depressed individuals to predict lower rewards – in the context of the Signal Detection Theory (SDT) modelling framework. Specifically, we show how to apply this framework to measure affective bias and compare it to the behaviour of an optimal observer. We also show how to extend the framework to make predictions about bias when the individual holds incorrect assumptions about the decision context. Building on this theoretical foundation, we propose five experiments to test five hypothetical sources of this affective bias: beliefs about prior probabilities, beliefs about performance, subjective value of reward, learning differences, and need for accuracy differences. We argue that greater precision about the mechanisms driving affective bias may eventually enable us to better understand the mechanisms underlying mood and anxiety disorders

Community psychiatry care: an urgent need in Nigeria

Nigeria’s mental health policy was formulated in 1991, but it did not make adequate provision for community-based psychiatric care. Since there are only seven government-owned psychiatry facilities in Nigeria and these are always overwhelmed, there is the need to overhaul the existing policy and emphasise the urgency of a shift from inpatient psychiatric mental healthcare towards a community-based multidisciplinary psychiatric healthcare system

Processed meat consumption and Lung function: modification by antioxidants and smoking

This article has supplementary material available from www.erj.ersjournals.com: This study was supported by the Medical Research Council, UK. H. Okubo was supported in part by fellowship of the Astellas Foundation for Research on Metabolic Disorders, Japan and the Naito Memorial Grant for Research Abroad from the Naito Foundation, Japan

Continuity for s-convex fuzzy processes

In a previous paper we introduced the concept of s-convex fuzzy mapping and established some properties. In this work we study the continuity for s-convex fuzzy processes

Stereotactic Body Radiation Therapy Reirradiation for Locally Recurrent Rectal Cancer: Outcomes and Toxicity

PURPOSE: Stereotactic body radiation therapy (SBRT) has emerged as a potential therapeutic option for locally recurrent rectal cancer (LRRC) but contemporaneous clinical data are limited. We aimed to evaluate the local control, toxicity, and survival outcomes in a cohort of patients previously treated with neoadjuvant pelvic radiation therapy for nonmetastatic locally recurrent rectal cancer, now treated with SBRT. METHODS AND MATERIALS: Inoperable rectal cancer patients with ≤3 sites of pelvic recurrence and >6 months since prior pelvic radiation therapy were identified from a prospective registry over 4 years. SBRT dose was 30 Gy in 5 fractions, daily or alternate days, using cumulative organ at risk dose constraints. Primary outcome was local control (LC). Secondary outcomes were progression free survival, overall survival, toxicity, and patient reported quality of life scores using the EQ visual analog scale (EQ-VAS) tool. RESULTS: Thirty patients (35 targets) were included. Median gross tumor volume size was 14.3 cm3. In addition, 27 of 30 (90%) previously received 45 to 50.4 Gy in 25 of 28 fractions, with 10% receiving an alternative prescription. All patients received the planned reirradiation SBRT dose. The median follow-up was 24.5 months (interquartile range, 17.8-28.8). The 1-year LC was 84.9% (95% confidence interval [CI], 70.6-99) and a 2-year LC was 69% (95% CI, 51.8-91.9). The median progression free survival was 12.1 months (95% CI, 8.6-17.66), and median overall survival was 28.3 months (95% CI, 17.88-39.5 months). No patient experienced >G2 acute toxicity and only 1 patient experienced late G3 toxicity. Patient-reported QoL outcomes were improved at 3 months after SBRT (Δ EQ-VAS, +10 points, Wilcoxon signed-rank, P = .009). CONCLUSIONS: Thirty patients (35 targets) were included. Median gross tumor volume size was 14.3 cm3. In addition, 27 of 30 (90%) previously received 45 to 50.4 Gy in 25 of 28 fractions, with 10% receiving an alternative prescription. All patients received the planned reirradiation SBRT dose. The median follow-up was 24.5 months (interquartile range, 17.8-28.8). The 1-year LC was 84.9% (95% confidence interval [CI], 70.6-99) and a 2-year LC was 69% (95% CI, 51.8-91.9). The median progression free survival was 12.1 months (95% CI, 8.6-17.66), and median overall survival was 28.3 months (95% CI, 17.88-39.5 months). No patient experienced >G2 acute toxicity and only 1 patient experienced late G3 toxicity. Patient-reported QoL outcomes were improved at 3 months after SBRT (Δ EQ-VAS, +10 points, Wilcoxon signed-rank, P = .009)

3D-electrical resistivity tomography monitoring of salt transport in homogeneous and layered soil samples

Monitoring transport of dissolved substances in soil deposits is particularly relevant where safety is concerned, as in the case of geo-environmental barriers. Geophysical methods are very appealing, since they cover a wide domain, localising possible preferential flow paths and providing reliable links between geophysical quantities and hydrological variables. This paper describes a 3D laboratory application of Electrical Resistivity Tomography (ERT) used to monitor solute transport processes. Dissolution and transport tests on both homogeneous and heterogeneous samples were conducted in an instrumented oedometer cell. ERT was used to create maps of electrical conductivity of the monitored domain at different time intervals and to estimate concentration variations within the interstitial fluid. Comparisons with finite element simulations of the transport processes were performed to check the consistency of the results. Tests confirmed that the technique can monitor salt transport, infer the hydro-chemical behaviour of heterogeneous geomaterials and evaluate the performances of clay barrier

Proteomics and phylogenetic analysis of the cathepsin L protease family of the helminth pathogen Fasciola hepatica: Expansion of a repertoire of virulence-associated factors

Cathepsin L proteases secreted by the helminth pathogen Fasciola hepatica have functions in parasite virulence including tissue invasion and suppression of host immune responses. Using proteomics methods alongside phylogenetic studies we characterized the profile of cathepsin L proteases secreted by adult F. hepatica and hence identified those involved in host-pathogen interaction. Phylogenetic analyses showed that the Fasciola cathepsin L gene family expanded by a series of gene duplications followed by divergence that gave rise to three clades associated with mature adult worms (Clades 1, 2, and 5) and two clades specific to infective juvenile stages (Clades 3 and 4). Consistent with these observations our proteomics studies identified representatives from Clades 1, 2, and 5 but not from Clades 3 and 4 in adult F. hepatica secretory products. Clades 1 and 2 account for 67.39 and 27.63% of total secreted cathepsin Ls, respectively, suggesting that their expansion was positively driven and that these proteases are most critical for parasite survival and adaptation. Sequence comparison studies revealed that the expansion of cathepsin Ls by gene duplication was followed by residue changes in the S2 pocket of the active site. Our biochemical studies showed that these changes result in alterations in substrate binding and suggested that the divergence of the cathepsin L family produced a repertoire of enzymes with overlapping and complementary substrate specificities that could cleave host macromolecules more efficiently. Although the cathepsin Ls are produced as zymogens containing a prosegment and mature domain, all secreted enzymes identified by MS were processed to mature active enzymes. The prosegment region was highly conserved between the clades except at the boundary of prosegment and mature enzyme. Despite the lack of conservation at this section, sites for exogenous cleavage by asparaginyl endopeptidases and a Leu-Ser ↓ His motif for autocatalytic cleavage by cathepsin Ls were preserved. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc

Clustering and Alignment of Polymorphic Sequences for HLA-DRB1 Genotyping

Located on Chromosome 6p21, classical human leukocyte antigen genes are highly polymorphic. HLA alleles associate with a variety of phenotypes, such as narcolepsy, autoimmunity, as well as immunologic response to infectious disease. Moreover, high resolution genotyping of these loci is critical to achieving long-term survival of allogeneic transplants. Development of methods to obtain high resolution analysis of HLA genotypes will lead to improved understanding of how select alleles contribute to human health and disease risk. Genomic DNAs were obtained from a cohort of n = 383 subjects recruited as part of an Ulcerative Colitis study and analyzed for HLA-DRB1. HLA genotypes were determined using sequence specific oligonucleotide probes and by next-generation sequencing using the Roche/454 GSFLX instrument. The Clustering and Alignment of Polymorphic Sequences (CAPSeq) software application was developed to analyze next-generation sequencing data. The application generates HLA sequence specific 6-digit genotype information from next-generation sequencing data using MUMmer to align sequences and the R package diffusionMap to classify sequences into their respective allelic groups. The incorporation of Bootstrap Aggregating, Bagging to aid in sorting of sequences into allele classes resulted in improved genotyping accuracy. Using Bagging iterations equal to 60, the genotyping results obtained using CAPSeq when compared with sequence specific oligonucleotide probe characterized 4-digit genotypes exhibited high rates of concordance, matching at 759 out of 766 (99.1%) alleles. © 2013 Ringquist et al

Novel constructs and 1-step chromatography protocols for the production of Porcine Circovirus 2d (PCV2d) and Circovirus 3 (PCV3) subunit vaccine candidates

Porcine circovirus type 2 (PCV2) has been a major problem for the pig production industry worldwide for decades. While the majority of commercially available vaccines are based on the original PCV2a genotype, the current dominant genotype is PCV2d. The notable differences between genotypes could lead to incomplete cross-protection. Moreover, most current subunit PCV2 vaccines are generated from expensive insect cell culture technology. In this work, we present a new workflow for production of an updated and relatively inexpensive PCV2d vaccine candidate. After expression in fed-batch Escherichia coli fermentation systems with a simple one-step ion-exchange chromatography purification protocol, the yield of purified PCV2d-based antigen reached over 1 g per litre bacterial culture. Using similar procedures, we also demonstrated even higher PCV2d-based antigen yields from a chimeric PCV2d-PCV3 capsid construct, which is cleaved during fermentation to release PCV2d- and PCV3-related polypeptides. Although the PCV2d-based recombinant protein from this protocol did not form viral-like particles as analysed by size-exclusion chromatography, it could effectively induce capsid-specific and PCV2d-neutralising antibodies in immunised animals, indicating significant potential as a new vaccine candidate that can be easily manufactured at commercial scale