Susceptibility locus on chromosome 1q23-25 for a schizophrenia subtype resembling deficit schizophrenia identified by latent class analysis

Context: Identifying susceptibility genes for schizophrenia may be complicated by phenotypic heterogeneity, with some evidence suggesting that phenotypic heterogeneity reflects genetic heterogeneity. Objective: To evaluate the heritability and conduct genetic linkage analyses of empirically derived, clinically homogeneous schizophrenia subtypes. Design: Latent class and linkage analysis. Setting: Taiwanese field research centers. Participants: The latent class analysis included 1236 Han Chinese individuals with DSM-IV schizophrenia. These individuals were members of a large affected-sibling-pair sample of schizophrenia (606 ascertained families), original linkage analyses of which detected a maximum logarithm of odds (LOD) of 1.8 (z = 2.88) on chromosome 10q22.3. Main Outcome Measures: Multipoint exponential LOD scores by latent class assignment and parametric heterogeneity LOD scores. Results: Latent class analyses identified 4 classes, with 2 demonstrating familial aggregation. The first (LC2) described a group with severe negative symptoms, disorganization, and pronounced functional impairment, resembling “deficit schizophrenia.” The second (LC3) described a group with minimal functional impairment, mild or absent negative symptoms, and low disorganization. Using the negative/deficit subtype, we detected genome-wide significant linkage to 1q23-25 (LOD = 3.78, empiric genome-wide P = .01). This region was not detected using the DSM-IV schizophrenia diagnosis, but has been strongly implicated in schizophrenia pathogenesis by previous linkage and association studies.Variants in the 1q region may specifically increase risk for a negative/deficit schizophrenia subtype. Alternatively, these results may reflect increased familiality/heritability of the negative class, the presence of multiple 1q schizophrenia risk genes, or a pleiotropic 1q risk locus or loci, with stronger genotype-phenotype correlation with negative/deficit symptoms. Using the second familial latent class, we identified nominally significant linkage to the original 10q peak region. Conclusion: Genetic analyses of heritable, homogeneous phenotypes may improve the power of linkage and association studies of schizophrenia and thus have relevance to the design and analysis of genome-wide association studies.

Latent class and genetic analysis does not support migraine with aura and migraine without aura as separate entities

Latent class and genetic analyses were used to identify subgroups of migraine sufferers in a community sample of 6,265 Australian twins (55% female) aged 25-36 who had completed an interview based on International Headache Society (IHS) criteria. Consistent with prevalence rates from other population-based studies, 703 (20%) female and 250 (9%) male twins satisfied the IHS criteria for migraine without aura (MO), and of these, 432 (13%) female and 166 (6%) male twins satisfied the criteria for migraine with aura (MA) as indicated by visual symptoms. Latent class analysis (LCA) of IHS symptoms identified three major symptomatic classes, representing 1) a mild form of recurrent nonmigrainous headache, 2) a moderately severe form of migraine, typically without visual aura symptoms (although 40% of individuals in this class were positive for aura), and 3) a severe form of migraine typically with visual aura symptoms (although 24% of individuals were negative for aura). Using the LCA classification, many more individuals were considered affected to some degree than when using IHS criteria (35% vs. 13%). Furthermore, genetic model fitting indicated a greater genetic contribution to migraine using the LCA classification (heritability, h(2)=0.40; 95% CI, 0.29-0.46) compared with the IHS classification (h(2)=0.36; 95% CI, 0.22-0.42). Exploratory latent class modeling, fitting up to 10 classes, did not identify classes corresponding to either the IHS MO or MA classification. Our data indicate the existence of a continuum of severity, with MA more severe but not etiologically distinct from MO. In searching for predisposing genes, we should therefore expect to find some genes that may underlie all major recurrent headache subtypes, with modifying genetic or environmental factors that may lead to differential expression of the liability for migraine.

Zygosity diagnosis in the absence of genotypic data: An approach using latent class analysis

For zygosity diagnosis in the absence of genotypic data, or in the recruitment phase of a twin study where only single twins from same-sex pairs are being screened, or to provide a test for sample duplication leading to the false identification of a dizygotic pair as monozygotic, the appropriate analysis of respondents' answers to questions about zygosity is critical. Using data from a young adult Australian twin cohort (N = 2094 complete pairs and 519 singleton twins from same-sex pairs with complete responses to all zygosity items), we show that application of latent class analysis (LCA), fitting a 2-class model, yields results that show good concordance with traditional methods of zygosity diagnosis, but with certain important advantages. These include the ability, in many cases, to assign zygosity with specified probability on the basis of responses of a single informant (advantageous when one zygosity type is being oversampled); and the ability to quantify the probability of misassignment of zygosity, allowing prioritization of cases for genotyping as well as identification of cases of probable laboratory error. Out of 242 twins (from 121 like-sex pairs) where genotypic data were available for zygosity confirmation, only a single case was identified of incorrect zygosity assignment by the latent class algorithm. Zygosity assignment for that single case was identified by the LCA as uncertain (probability of being a monozygotic twin only 76%), and the co-twin's responses clearly identified the pair as dizygotic (probability of being dizygotic 100%). In the absence of genotypic data, or as a safeguard against sample duplication, application of LCA for zygosity assignment or confirmation is strongly recommended.

Emotional climate of a pre-service science teacher education class in Bhutan

This study explored pre-service secondary science teachers’ perceptions of classroom emotional climate in the context of the Bhutanese macro-social policy of Gross National Happiness. Drawing upon sociological perspectives of human emotions and using Interaction Ritual Theory this study investigated how pre-service science teachers may be supported in their professional development. It was a multi-method study involving video and audio recordings of teaching episodes supported by interviews and the researcher’s diary. Students also registered their perceptions of the emotional climate of their classroom at 3-minute intervals using audience response technology. In this way, emotional events were identified for video analysis. The findings of this study highlighted that the activities pre-service teachers engaged in matter to them. Positive emotional climate was identified in activities involving students’ presentations using video clips and models, coteaching, and interactive whole class discussions. Decreases in emotional climate were identified during formal lectures and when unprepared presenters led presentations. Emotions such as frustration and disappointment characterized classes with negative emotional climate. The enabling conditions to sustain a positive emotional climate are identified. Implications for sustaining macro-social policy about Gross National Happiness are considered in light of the climate that develops in science teacher education classes.

Classifying patients by their characteristics and clinical presentations; the use of latent class analysis

In this article, we introduce the general statistical analysis approach known as latent class analysis and discuss some of the issues associated with this type of analysis in practice. Two recent examples from the respiratory health literature are used to highlight the types of research questions that have been addressed using this approach.

A Bayesian latent class safety performance function for identifying motor vehicle crash blackspots

The current state of the practice in Blackspot Identification (BSI) utilizes safety performance functions based on total crash counts to identify transport system sites with potentially high crash risk. This paper postulates that total crash count variation over a transport network is a result of multiple distinct crash generating processes including geometric characteristics of the road, spatial features of the surrounding environment, and driver behaviour factors. However, these multiple sources are ignored in current modelling methodologies in both trying to explain or predict crash frequencies across sites. Instead, current practice employs models that imply that a single underlying crash generating process exists. The model mis-specification may lead to correlating crashes with the incorrect sources of contributing factors (e.g. concluding a crash is predominately caused by a geometric feature when it is a behavioural issue), which may ultimately lead to inefficient use of public funds and misidentification of true blackspots. This study aims to propose a latent class model consistent with a multiple crash process theory, and to investigate the influence this model has on correctly identifying crash blackspots. We first present the theoretical and corresponding methodological approach in which a Bayesian Latent Class (BLC) model is estimated assuming that crashes arise from two distinct risk generating processes including engineering and unobserved spatial factors. The Bayesian model is used to incorporate prior information about the contribution of each underlying process to the total crash count. The methodology is applied to the state-controlled roads in Queensland, Australia and the results are compared to an Empirical Bayesian Negative Binomial (EB-NB) model. A comparison of goodness of fit measures illustrates significantly improved performance of the proposed model compared to the NB model. The detection of blackspots was also improved when compared to the EB-NB model. In addition, modelling crashes as the result of two fundamentally separate underlying processes reveals more detailed information about unobserved crash causes.

Class-specific sparse codes for representing activities

In this paper we investigate the effectiveness of class specific sparse codes in the context of discriminative action classification. The bag-of-words representation is widely used in activity recognition to encode features, and although it yields state-of-the art performance with several feature descriptors it still suffers from large quantization errors and reduces the overall performance. Recently proposed sparse representation methods have been shown to effectively represent features as a linear combination of an over complete dictionary by minimizing the reconstruction error. In contrast to most of the sparse representation methods which focus on Sparse-Reconstruction based Classification (SRC), this paper focuses on a discriminative classification using a SVM by constructing class-specific sparse codes for motion and appearance separately. Experimental results demonstrates that separate motion and appearance specific sparse coefficients provide the most effective and discriminative representation for each class compared to a single class-specific sparse coefficients.

Critical Indigenous Studies: Engagements in First World Locations

With increasing speed, the emerging discipline of critical Indigenous studies is expanding and demarcating its territory from Indigenous studies through the work of a new generation of Indigenous scholars. Critical Indigenous Studies makes an important contribution to this expansion, disrupting the certainty of disciplinary knowledge produced in the twentieth century, when studying Indigenous peoples was primarily the domain of non-Indigenous scholars. Aileen Moreton-Robinson's introductory essay provides a context for the emerging discipline. The volume is organized into three sections: the first includes essays that interrogate the embedded nature of Indigenous studies within academic institutions; the second explores the epistemology of the discipline; and the third section is devoted to understanding the locales of critical inquiry and practice. Each essay places and contemplates critical Indigenous studies within the context of First World nations, which continue to occupy Indigenous lands in the twenty-first century. The contributors include Aboriginal, Metis, Maori, Kanaka Maoli, Filipino-Pohnpeian, and Native American scholars working and writing through a shared legacy born of British and later U.S. imperialism. In these countries, critical Indigenous studies is flourishing and transitioning into a discipline, a knowledge/power domain where distinct work is produced, taught, researched, and disseminated by Indigenous scholars.

3D QSAR studies of N-4-arylacryloylpiperazin-1-yl-phenyl-oxazolidinones: A novel class of antibacterial agents

Three-dimensional QSAR studies for N-4-arylacryloylpiperazin-1-yl-phenyl-oxazolidinones were conducted using TSAR 3.3. The in vitro activities (MICs) of the compounds against Staphylococcus aureus ATCC 25923 exhibited a strong correlation with the prediction made by the model developed in the present study.

A potent nonporphyrin class of photodynamic therapeutic agent: Cellular localisation, cytotoxic potential and influence of hypoxia

We have developed a totally new class of nonporphyrin photodynamic therapeutic agents with a specific focus on two lead candidates azadipyrromethene (ADPM)01 and ADPM06. Confocal laser scanning microscopy imaging showed that these compounds are exclusively localised to the cytosolic compartment, with specific accumulation in the endoplasmic reticulum and to a lesser extent in the mitochondria. Light-induced toxicity assays, carried out over a broad range of human tumour cell lines, displayed EC50 values in the micro-molar range for ADPM01 and nano-molar range for ADPM06, with no discernable activity bias for a specific cell type. Strikingly, the more active agent, ADPM06, even retained significant activity under hypoxic conditions. Both photosensitisers showed low to nondeterminable dark toxicity. Flow cytometric analysis revealed that ADPM01 and ADPM06 were highly effective at inducing apoptosis as a mode of cell death. The photophysical and biological characteristics of these PDT agents suggest that they have potential for the development of new anticancer therapeutics. © 2005 Cancer Research UK.

R1STM: One-class support tensor machine with randomised kernel

Identifying unusual or anomalous patterns in an underlying dataset is an important but challenging task in many applications. The focus of the unsupervised anomaly detection literature has mostly been on vectorised data. However, many applications are more naturally described using higher-order tensor representations. Approaches that vectorise tensorial data can destroy the structural information encoded in the high-dimensional space, and lead to the problem of the curse of dimensionality. In this paper we present the first unsupervised tensorial anomaly detection method, along with a randomised version of our method. Our anomaly detection method, the One-class Support Tensor Machine (1STM), is a generalisation of conventional one-class Support Vector Machines to higher-order spaces. 1STM preserves the multiway structure of tensor data, while achieving significant improvement in accuracy and efficiency over conventional vectorised methods. We then leverage the theory of nonlinear random projections to propose the Randomised 1STM (R1STM). Our empirical analysis on several real and synthetic datasets shows that our R1STM algorithm delivers comparable or better accuracy to a state-of-the-art deep learning method and traditional kernelised approaches for anomaly detection, while being approximately 100 times faster in training and testing.

The relationship between class participation and law students' learning, engagement and stress: Do demographics matter?

Student participation in the classroom has long been regarded as an important means of increasing student engagement and enhancing learning outcomes by promoting active learning. However, the approach to class participation common in U.S. law schools, commonly referred to as the Socratic method, has been criticised for its negative impacts on student wellbeing. A multiplicity of American studies have identified that participating in law class discussions can be alienating, intimidating and stressful for some law students, and may be especially so for women, and students from minority backgrounds. Using data from the Law School Student Assessment Survey (LSSAS), conducted at UNSW Law School in 2012, this Chapter provides preliminary insights into whether assessable class participation (ACP) at an Australian law school is similarly alienating and stressful for students, including the groups identified in the American literature. In addition, we compare the responses of undergraduate Bachelor of Laws (LLB) and graduate Juris Doctor (JD) students. The LSSAS findings indicate that most respondents recognise the potential learning and social benefits associated with class participation in legal education, but remain divided over their willingness to participate. Further, in alignment with general trends identified in American studies, LLB students, women, international students, and non-native English speakers perceive they contribute less frequently to class discussions than JD students, males, domestic students, and native English speakers, respectively. Importantly, the LSSAS indicates students are more likely to be anxious about contributing to class discussions if they are LLB students (compared to their JD counterparts), and if English is not their first language (compared to native English speakers). There were no significant differences in students’ self-reported anxiety levels based on gender, which diverges from the findings of American research.

'More like the kids than the other teachers': One working-class pre-service teacher's experiences in a middle-class profession

While teaching is largely a White, middle-class profession, some teachers, including White teachers, come from low socio-economic backgrounds. This paper examines how one working-class pe-service teacher in Australia experiences studying in a predominantly middle-class teacher education program. Drawing on Bourdieu, this paper seeks to explore what we can learn from the pre-service teaching reflections of one woman who is a member of this smaller group of teachers and who brings to her teaching the habitus and life history that aligns with many of her students and the low socio-economic communities in which she teaches.