502 research outputs found
Victims and Survivors: Displaced Persons and Other War Victims in Vietnam, 1954-1975
https://digitalcommons.cedarville.edu/cr_launch_party_2016/1002/thumbnail.jp
Cellular model system to dissect the isoform-selectivity of Akt inhibitors
The protein kinase Akt plays a pivotal role in cellular processes. However, its isoforms’ distinct functions have not been resolved to date, mainly due to the lack of suitable biochemical and cellular tools. Against this background, we present the development of an isoform-dependent Ba/F3 model system to translate biochemical results on isoform specificity to the cellular level. Our cellular model system complemented by protein X-ray crystallography and structure-based ligand design results in covalent-allosteric Akt inhibitors with unique selectivity profiles. In a first proof-of-concept, the developed molecules allow studies on isoform-selective effects of Akt inhibition in cancer cells. Thus, this study will pave the way to resolve isoform-selective roles in health and disease and foster the development of next-generation therapeutics with superior on-target properties
The acute-to-chronic workload ratio:An inaccurate scaling index for an unnecessary normalisation process?
BACKGROUND: Problematic use of alcohol and other drugs (AOD) is highly prevalent among people living with the human immunodeficiency virus (PLWH), and untreated AOD use disorders have particularly detrimental effects on human immunodeficiency virus (HIV) outcomes. The Healthcare Effectiveness Data and Information Set (HEDIS) measures of treatment initiation and engagement are important benchmarks for access to AOD use disorder treatment. To inform improved patient care, we compared HEDIS measures of AOD use disorder treatment initiation and engagement and health care utilization among PLWH and patients without an HIV diagnosis.
METHODS: Patients with a new AOD use disorder diagnosis documented between October 1, 2014, and August 15, 2015, were identified using electronic health records (EHR) and insurance claims data from 7 health care systems in the United States. Demographic characteristics, clinical diagnoses, and health care utilization data were also obtained. AOD use disorder treatment initiation and engagement rates were calculated using HEDIS measure criteria. Factors associated with treatment initiation and engagement were examined using multivariable logistic regression models.
RESULTS: There were 469 PLWH (93% male) and 86,096 patients without an HIV diagnosis (60% male) in the study cohort. AOD use disorder treatment initiation was similar in PLWH and patients without an HIV diagnosis (10% vs. 11%, respectively). Among those who initiated treatment, few engaged in treatment in both groups (9% PLWH vs. 12% patients without an HIV diagnosis). In multivariable analysis, HIV status was not significantly associated with either AOD use disorder treatment initiation or engagement.
CONCLUSIONS: AOD use disorder treatment initiation and engagement rates were low in both PLWH and patients without an HIV diagnosis. Future studies need to focus on developing strategies to efficiently integrate AOD use disorder treatment with medical care for HIV
Perceptual and Neural Response to Affective Tactile Texture Stimulation in Adults with Autism Spectrum Disorders
Autism spectrum disorders (ASD) are associated with differences in sensory sensitivity and affective response to sensory stimuli, the neural basis of which is still largely unknown. We used psychophysics and functional magnetic resonance imaging (fMRI) to investigate responses to somatosensory stimulation with three textured surfaces that spanned a range of roughness and pleasantness in a sample of adults with ASD and a control group. While psychophysical ratings of roughness and pleasantness were largely similar across the two groups, the ASD group gave pleasant and unpleasant textures more extreme average ratings than did controls. In addition, their ratings for a neutral texture were more variable than controls, indicating they are less consistent in evaluating a stimulus that is affectively ambiguous. Changes in brain blood oxygenation level-dependent (BOLD) signal in response to stimulation with these textures differed substantially between the groups, with the ASD group exhibiting diminished responses compared to the control group, particularly for pleasant and neutral textures. For the most unpleasant texture, the ASD group exhibited greater BOLD response than controls in affective somatosensory processing areas such as the posterior cingulate cortex and the insula. The amplitude of response in the insula in response to the unpleasant texture was positively correlated with social impairment as measured by the Autism Diagnostic Interview-Revised (ADI-R). These results suggest that people with ASD tend to show diminished response to pleasant and neutral stimuli, and exaggerated limbic responses to unpleasant stimuli, which may contribute to diminished social reward associated with touch, perpetuating social withdrawal, and aberrant social development
A Cognitive Model of an Epistemic Community: Mapping the Dynamics of Shallow Lake Ecosystems
We used fuzzy cognitive mapping (FCM) to develop a generic shallow lake
ecosystem model by augmenting the individual cognitive maps drawn by 8
scientists working in the area of shallow lake ecology. We calculated graph
theoretical indices of the individual cognitive maps and the collective
cognitive map produced by augmentation. The graph theoretical indices revealed
internal cycles showing non-linear dynamics in the shallow lake ecosystem. The
ecological processes were organized democratically without a top-down
hierarchical structure. The steady state condition of the generic model was a
characteristic turbid shallow lake ecosystem since there were no dynamic
environmental changes that could cause shifts between a turbid and a clearwater
state, and the generic model indicated that only a dynamic disturbance regime
could maintain the clearwater state. The model developed herein captured the
empirical behavior of shallow lakes, and contained the basic model of the
Alternative Stable States Theory. In addition, our model expanded the basic
model by quantifying the relative effects of connections and by extending it.
In our expanded model we ran 4 simulations: harvesting submerged plants,
nutrient reduction, fish removal without nutrient reduction, and
biomanipulation. Only biomanipulation, which included fish removal and nutrient
reduction, had the potential to shift the turbid state into clearwater state.
The structure and relationships in the generic model as well as the outcomes of
the management simulations were supported by actual field studies in shallow
lake ecosystems. Thus, fuzzy cognitive mapping methodology enabled us to
understand the complex structure of shallow lake ecosystems as a whole and
obtain a valid generic model based on tacit knowledge of experts in the field.Comment: 24 pages, 5 Figure
Political activism across the life course
The study of political activism has neglected people’s personal and social relationships to time. Age, life course and generation have become increasing important experiences for understanding political participation and political outcomes (e.g. Brexit), and current policies of austerity across the world are affecting people of all ages. At a time when social science is struggling to understand the rapid and unexpected changes to the current political landscape, the essay argues that the study of political activism can be enriched by engaging with the temporal dimensions of people’s everyday social experiences because it enables the discovery of political activism in mundane activities as well as in banal spaces. The authors suggest that a values-based approach that focuses on people’s relationships of concern would be a suitable way to surface contemporary political sites and experiences of activism across the life course and for different generations
Supporting Children with Disabilities in Low- and Middle- Income Countries: Promoting Inclusive Practice within Community-Based Childcare Centres in Malawi through a Bioecological Systems Perspective
RLOsGiven the narrow scope and conceptualisation of inclusion for young children with disabilities in research within low- and middle income countries (LMICs) contexts, we draw on a bioecological systems perspective to propose the parameters for a broader unit of analysis. This perspective situates human development within a specific cultural context in which family, peers and schooling are regarded as key in responding to young children with disabilities in a given setting. We outline a new bioecological model to illustrate the proximal and distal factors that can influence inclusive early development for children with disabilities within LMICs. To illustrate the relevance of this model to early child development research, we consider its application, as a conceptual framework, with reference to a research study in Malawi. The study was designed to promote greater inclusive practice for young children with disabilities in Community-Based Childcare Centres (CBCCs) with a particular focus on the role of the CBCC volunteer ‘caregiver’ in rural Malawi. It has significance for educators, service providers and researchers concerned with facilitating inclusive early development across national boundaries and contexts.ESRC-DFI
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