606 research outputs found
Genetic basis of cognitive disability
The importance of genetic influences on cognitive disability has been recognized for a long time, but molecular analysis has only recently begun to yield insights into the pathogenesis of this common and disabling condition. The availability of genome sequences has enabled the characterization of the chromosomal deletions and trisomies that result in cognitive disability, and mutations in rare single-gene conditions are being discovered. The molecular pathology of cognitive disability is turning out to be as heterogeneous as the condition itself, with unexpected complexities even in apparently simple gene-deletion syndromes. One remarkable finding from studies on X-linked mental retardation is that mutations in different small guanosine triphosphate (GTP)-binding proteins result in cognitive disability without other somatic features. Advances are also being made in cognitive disability with polygenic origins, such as dyslexia and autism. However, the genetic basis of mild intellectual disability has yet to be satisfactorily explained
Assumptions, Resources, and Inputs to Case Management: Implications for California’s Regional Center System
This project adds to knowledge of case management assumptions, resources, and inputs for California’s Regional Center system by surveying members of the Service Access and Equity working group, formed by the Department of Developmental Services (DDS). It recommends development of a logic model to evaluate case management activities because their intended societal impacts are difficult to directly measure. Additionally, it adds to the debate on health equity and racial disparities in Medicaid long-term services and supports (LTSS). In 1969, passage of the Lanterman Developmental Disabilities Services Act (The Lanterman Act) led to the first and still only entitlement to community-based services that is granted to people with developmental and intellectual disabilities (I/DD) by a state. Twenty-one private, nonprofit Regional Centers have exclusive rights to provide case management and to purchase community- based services for eligible consumers within their catchment area. By contracting with DDS, Regional Centers receive reimbursement for case management operations, pass-through rates to purchase community-based services, and administer various grants, projects, and funds.
This project contributes to understanding whether and how knowledge gaps in Regional Center case management affect expenditures of home- and community-based services (HCBS). In addition, Vogel et al. (2019) lay out systemic LTSS and demographic challenges in California: a higher percentage of people require services and have autism; a growing unpaid caregiver and adult consumer population aging-in-place at home; a struggle with rising labor costs to recruit and retain qualified personnel, high cost of housing for community living, and non-compliance with Medicaid HCBS regulation that may restrict federal funding. Surveying working group members’ knowledge of case management in home- and community-based services improves understanding of the disparities in service access for racial and non-English speaking consumers
Strategic restraint : modelling the role of moral weight in modern conflicts
Strategic Restraint: Modelling the Role of Moral Weight in Modern Conflicts is a PhD thesis that seeks to make the argument that restraint has a strategic purpose. It begins with a discussion of an understanding of ethics as the negotiation of hierarchies of ‘goods’ and develops an idea of Primary and Contingent goods, how those goods are decided and the role of morality, ethics and the law in human affairs. Following that is a consideration of strategy, and the nature of war. These discussions begin to form the basis of the following chapters. It develops a model for understanding the nature of war, and using this model makes suggestions about the controlled application of force and the effects of overapplication of force. The construction of the model is supported by examination of military history, concentrating on conflicts in the latter part of the of the 20th century to more recent conflicts.In considering the difficulties the model indicates in this overapplication, the work argues that there is need for the ‘artificial’ application of perceived mass, and suggests that it is here that the utility of ethical behaviour in warfare can be found for strategy. In using restraint, guided by higher ethical choices which necessarily reduce efficacy, it is argued that there is strategic advantage to be found. This is supported by analyses from modern Counter Insurgency campaigns, where such activity has been undertaken by commanders independently, while attempting to provide a theoretical explanation for the seeming success of these decisions. The work also considers outcomes from applying such strategic choices, from operational and policy concerns to the consequences in interstate relations before, during and after armed conflict
The Poetry In-Between: Presence and Absence in Whitman, Rimbaud, and Hopkins.
The Poetry In-Between: Presence and Absence in Whitman, Rimbaud, and Hopkins analyzes three major nineteenth-century poets and their development of a poetics which has as its chief focus of concern the issue of presencing an eternal and universal Other by which to assess self identity. After the Kantian critique and the seeming reduction of human knowledge to phenomenal perceptions, early nineteenth-century poets and theorists feared the entrapment and isolation of the self in subjective awareness. The romantics, such as Friedrich Schlegel, sought ways to overcome such alienating subjectivity and ultimately conceived of the poet as a privileged spokesman and arbiter for a harmonious and divine origin of life; it is through the poet\u27s imagination, argue Schlegel and his followers, that the noumenal or total, eternal Other is presenced. Through such presencing, which essentially involves the collapsing of boundaries between the phenomenal body and the transcendent soul, the individual self gains identity as part of an integrated, universal, and eternal cosmos. However, each poet faced crises of separation which challenged their presencing of this Other ; in general, the death of the body in war or sickness threatened to cut the poet off from his vision and participation in an eternal, harmonious Other. Ultimately, towards the end of their poetic careers, Whitman, Rimbaud, and Hopkins negotiated a poetic stance which views the self as in-between a full presence and a complete absence of cosmic totality; the desire of the self for the Other banishes its complete absence, but the self must also recognize the transiency of humanity and our inability to grasp individually the complete presence of an eternity
So You Want Your Child to Be a Genius?
Geneticist Jonathan Flint reviews David Plotz's book The Genius Factory: The Curious History of the Nobel Prize Sperm Bank
Association studies in outbred mice in a new era of full-genome sequencing
Thousands of loci that contribute to quantitative traits in outbred crosses of mice have been reported over the last two decades. In this review we discuss how outbred mouse populations can be used to map and identify the genes and sequence variants that give rise to quantitative variation. We discuss heterogeneous stocks, the diversity outbred, and commercially available outbred populations of mice. All of these populations are descended from a small number of progenitor strains. The availability of the complete sequence of laboratory strains means that in many cases it will be possible to reconstruct the genomes of the outbred animals so that in a genetic association study we can detect the effect of all variants, a situation that has so far eluded studies in completely outbred populations. These resources constitute a major advance and make it possible to progress from a quantitative trait locus to a gene at an unprecedented spee
The endophenotype concept in psychiatric genetics
The idea that some phenotypes bear a closer relationship to the biological
processes that give rise to psychiatric illness than diagnostic categories has
attracted considerable interest. Much effort has been devoted to finding such
endophenotypes, partly because it is believed that the genetic basis of
endophenotypes will be easier to analyse than that of psychiatric disease. This
belief depends in part on the assumption that the effect sizes of genetic loci
contributing to endophenotypes are larger than those contributing to disease
susceptibility, hence increasing the chance that genetic linkage and association
tests will detect them. We examine this assumption by applying meta-analytical
techniques to genetic association studies of endophenotypes. We find that the
genetic effect sizes of the loci examined to date are no larger than those
reported for other phenotypes. A review of the genetic architecture of traits in
model organisms also provides no support for the view that the effect sizes of
loci contributing to phenotypes closer to the biological basis of disease is any
larger than those contributing to disease itself. While endophenotype measures
may afford greater reliability, it should not be assumed that they will also
demonstrate simpler genetic architecture
Genomes and phenomes of a population of outbred rats and its progenitors
Finding genetic variants that contribute to phenotypic variation is one of the main challenges of modern genetics. We used an outbred population of rats (Heterogeneous Stock, HS) in a combined sequence-based and genetic mapping analysis to identify sequence variants and genes contributing to complex traits of biomedical relevance. Here we describe the sequences of the eight inbred progenitors of the HS and the variants that segregate between them. We report the genotyping of 1,407 HS rats, and the collection from 2,006 rats of 195 phenotypic measures that are relevant to models of anxiety, type 2 diabetes, hypertension and osteoporosis. We make available haplotype dosages for the 1,407 genotyped rats, since genetic mapping in the HS is best carried out by reconstructing each HS chromosome as a mosaic of the progenitor genomes. Finally, we have deposited an R object that makes it easy to incorporate our sequence data into any genetic study of HS rats. Our genetic data are available for both Rnor3.4 and Rnor5.0 rat assemblies
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Speechformer-CTC: Sequential Modeling of Depression Detection with Speech Temporal Classification.
Speech-based automatic depression detection systems have been extensively explored over the past few years. Typically, each speaker is assigned a single label (Depressive or Non-depressive), and most approaches formulate depression detection as a speech classification task without explicitly considering the non-uniformly distributed depression pattern within segments, leading to low generalizability and robustness across different scenarios. However, depression corpora do not provide fine-grained labels (at the phoneme or word level) which makes the dynamic depression pattern in speech segments harder to track using conventional frameworks. To address this, we propose a novel framework, Speechformer-CTC, to model non-uniformly distributed depression characteristics within segments using a Connectionist Temporal Classification (CTC) objective function without the necessity of input-output alignment. Two novel CTC-label generation policies, namely the Expectation-One-Hot and the HuBERT policies, are proposed and incorporated in objectives on various granularities. Additionally, experiments using Automatic Speech Recognition (ASR) features are conducted to demonstrate the compatibility of the proposed method with content-based features. Our results show that the performance of depression detection, in terms of Macro F1-score, is improved on both DAIC-WOZ (English) and CONVERGE (Mandarin) datasets. On the DAIC-WOZ dataset, the system with HuBERT ASR features and a CTC objective optimized using HuBERT policy for label generation achieves 83.15% F1-score, which is close to state-of-the-art without the need for phoneme-level transcription or data augmentation. On the CONVERGE dataset, using Whisper features with the HuBERT policy improves the F1-score by 9.82% on CONVERGE1 (in-domain test set) and 18.47% on CONVERGE2 (out-of-domain test set). These findings show that depression detection can benefit from modeling non-uniformly distributed depression patterns and the proposed framework can be potentially used to determine significant depressive regions in speech utterances
G = E:What GWAS Can Tell Us about the Environment
As our understanding of genetics has improved, genome-wide association studies (GWAS) have identified numerous variants associated with lifestyle behaviours and health outcomes. However, what is sometimes overlooked is the possibility that genetic variants identified in GWAS of disease might reflect the effect of modifiable risk factors as well as direct genetic effects. We discuss this possibility with illustrative examples from tobacco and alcohol research, in which genetic variants that predict behavioural phenotypes have been seen in GWAS of diseases known to be causally related to these behaviours. This consideration has implications for the interpretation of GWAS findings
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