Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis

Increased rates of brain atrophy measured from serial magnetic resonance imaging precede symptom onset in Alzheimer's disease and may be useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. Fifty-two healthy individuals (72.3 ± 6.9 years) from Australian Imaging, Biomarkers and Lifestyle Study of Aging had serial (0, 18 m, 36 m) magnetic resonance imaging, (0, 18 m) Pittsburgh compound B positron emission tomography, and clinical assessments. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over 3 years, rates of whole brain atrophy (p < 0.001), left and right hippocampal atrophy (p = 0.001, p = 0.023), and ventricular expansion (p < 0.001) were associated with baseline β-amyloid load. Whole brain atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p = 0.003). Acceleration of left hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p < 0.02). We provide evidence that rates of atrophy are associated with both baseline β-amyloid load and accumulation, and that there is presymptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the presymptomatic phase

Stigma Of Mental Illness And Substance Use Disorders: Does Religious Fundamentalism Play A Role?

Stigmatization of severe mental illness and substance use disorders is widespread and associated with poorer health outcomes. At the same time, religious fundamentalism - defined as strict adherence to religious dogma - is an increasingly relevant ideology in the United States. This ideology is associated with a tendency to stigmatize individuals who do not adhere to established values and may therefore have negative implications for perceptions of mental illness. For the present study, participants from Amazon’s Mechanical Turk (N = 380) identified as evangelical or not and were randomly assigned to view one of three illness vignettes: schizophrenia, alcohol use disorder, and asthma (control). Then, each participant responded to the Stigmatizing Attitudes Toward Mental Illness scale for the character presented in the vignette. Evangelical participants reported significantly higher stigmatization of schizophrenia compared to non-evangelicals, but did not differ on stigma in relation to alcohol use disorder. These findings might be explained by religious factors in the presentation and treatment of the disorders, base rates, and general population stigmatization trends. Although limited by the use of vignettes and a self-report measure of stigma, these findings underscore the need to address religious belief adherence in stigma research and psychological treatment

“no key to the tangle”: History And Poetic Consciousness In Louis Zukofsky’s “A”

This thesis explores the question of poetry’s relationship with history. My inquiry is centered on the epic poem “A” (1974) by American author Louis Zukofsky, considering the ways in which Zukofsky reconceptualizes the role that the past plays in the construction of a modern poetic consciousness. The project is divided into two sequences: historical representation of movements “A”-22 and “A”-23 and historical engagement in movements “A”-21 and “A”-24. The first sequence is a survey of the ways in which Zukofsky recreates the last 6,000 years of history in a manner that resists linearity and narrative. I read his poetry alongside Walter Benjamin’s “On the Concept of History” (1940) and Gilles Deleuze’s Essays Clinical and Critical (1997) in order to consider the extent to which Zukofsky problematizes historical and literary language in the poetic-now. The second sequence focuses on the historical materials with which Zukofsky engages, primarily the Roman playwright Plautus, as well as Zukofsky’s own previous writing. I contend that Zukofsky method of participating with history in his work is a kind of creative engagement with the past, one that acknowledges history as a living thing and seeks to absorb it into the formation of a new poetics

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

THE EFFECTS OF CLASSROOM SIMULATION USING STATIC PICTURE PROMPTS TO TEACH STUDENTS WITH DISABILITIES TO MAKE PURCHASES WITH A DEBIT CARD AND TRACK THEIR EXPENSES

This study used a multiple probe design across participants to examine the effects of classroom simulation using static picture prompts to teach students to make a purchase using a debit card and track expenses by subtracting purchase amounts and adding deposits into a check register. Results demonstrated a functional relation between simulated instruction and students’ ability to complete a 20-step task analysis of debit card use and expense and deposit tracking in a check register. Students were also able to generalize the skills of purchasing with a debit card and tracking expenses and deposits in community settings up to five weeks post-intervention. Implications for practice and recommendations for future research are described

Developing a tool to measure health worker motivation in district hospitals in Kenya

BACKGROUND: We wanted to try to account for worker motivation as a key factor that might affect the success of an intervention to improve implementation of health worker practices in eight district hospitals in Kenya. In the absence of available tools, we therefore aimed to develop a tool that could enable a rapid measurement of motivation at baseline and at subsequent points during the 18-month intervention study. METHODS: After a literature review, a self-administered questionnaire was developed to assess the outcomes and determinants of motivation of Kenyan government hospital staff. The initial questionnaire included 23 questions (from seven underlying constructs) related to motivational outcomes that were then used to construct a simpler tool to measure motivation. Parallel qualitative work was undertaken to assess the relevance of the questions chosen and the face validity of the tool. RESULTS: Six hundred eighty-four health workers completed the questionnaires at baseline. Reliability analysis and factor analysis were used to produce the simplified motivational index, which consisted of 10 equally-weighted items from three underlying factors. Scores on the 10-item index were closely correlated with scores for the 23-item index, indicating that in future rapid assessments might be based on the 10 questions alone. The 10-item motivation index was also able to identify statistically significant differences in mean health worker motivation scores between the study hospitals (p<0.001). The parallel qualitative work in general supported these conclusions and contributed to our understanding of the three identified components of motivation. CONCLUSION: The 10-item score developed may be useful to monitor changes in motivation over time within our study or be used for more extensive rapid assessments of health worker motivation in Kenya

Blocking M1 Repolarization Of M2 THP-1 Macrophages Through Inhibition Of The Type I Interferon Response By Vesicular Stomatitis Virus

Matrix protein mutant strains of VSV, such as rM51R-M virus, are currently being investigated as oncolytic agents due to their ability to target and kill cancer cells while also stimulating innate immunity. We seek to examine the ability of rM51R-M virus to modulate tumor promoting M2 macrophages as a means to inhibit the progression of cancer. In the tumor microenvironment, M2 macrophage activity has a suppressive effect on the immune system, which can lead to tolerance of tumor cells. M1 macrophages, in contrast, stimulate an immune response and reduce tumor cell viability. Our lab has previously shown that rM51R-M virus re-educates M2 macrophages to an M1-like phenotype, but the mechanism by which it does so remains unknown. In THP-1 polarized M2 macrophages, we have observed increased levels of IFNa, total STAT1, and p-STAT1 upon infection with rM5IR-M virus. We hypothesize that the ability of rM51R-M virus to stimulate the type I IFN antiviral pathway in M2 macrophages may coerce them to an M1-like phenotype. To test this hypothesis, we seek to examine the effects of the p-STAT1 inhibitor fludarabine on macrophage polarization by rM51R-M virus. M2 macrophages were pretreated with different concentrations of fludarabine (50, 100, or 150 µM), infected with rM51R-M virus (MOI 1 or 10 pfu/cell) for 24 hours, and subjected to immunoblot analysis for total and phosphorylated STAT1. Results indicated that when cells were infected with rM51R-M virus at an MOI of 1, STAT1 phosphorylation was reduced to between 23% (50 µM fludarabine) and 16 % (100 and 150 µM fludarabine) of control levels. Similar results were obtained when cells were infected at an MOI of 10. These results confirm that fludarabine is capable of inhibiting the accumulation of p-STAT1. Therefore, this reagent can be used to reduce type I IFN signaling in order to determine the extent to which this pathway modulates macrophage identity during rM51R-M infection. Such mechanistic insights will be important in understanding the multipotent effects of VSV as an oncolytic agent

Determinations And Comparisons Of The Water Quality Above And Below The Watauga County Sanitary Landfill

The effects of the Watauga County Sanitary Landfill leachate on surface water quality at the lower end of the landfill were studied over a 10-month period. Results of the study indicate that the landfill is contributing excessively to the ammonia nitrogen and iron concentrations of the surface water below the landfill. The grand mean for ammonia nitrogen was 82 times greater below the landfill than the grand mean above the landfill. The grand mean for iron below the landfill was 126 times greater than the grand mean above the landfill

Mood and cognition in healthy older European adults: the Zenith study

YesBackground: The study aim was to determine if state and trait intra-individual measures of everyday affect predict cognitive functioning in healthy older community dwelling European adults (n = 387), aged 55-87 years. Methods: Participants were recruited from centres in France, Italy and Northern Ireland. Trait level and variability in positive and negative affect (PA and NA) were assessed using self-administered PANAS scales, four times a day for four days. State mood was assessed by one PANAS scale prior to assessment of recognition memory, spatial working memory, reaction time and sustained attention using the CANTAB computerized test battery. Results: A series of hierarchical regression analyses were carried out, one for each measure of cognitive function as the dependent variable, and socio-demographic variables (age, sex and social class), state and trait mood measures as the predictors. State PA and NA were both predictive of spatial working memory prior to looking at the contribution of trait mood. Trait PA and its variability were predictive of sustained attention. In the final step of the regression analyses, trait PA variability predicted greater sustained attention, whereas state NA predicted fewer spatial working memory errors, accounting for a very small percentage of the variance (1-2%) in the respective tests. Conclusion: Moods, by and large, have a small transient effect on cognition in this older sample

Constructing gender with a bag of sand, two swords, and some rocks : trans mutable embodiment in The Sandman, The Witcher, and Broken Earth

Due to the limits of Euro-American conceptions of gender, bodies are seen as static representations of a person’s interiority. Attempts to change one’s physical form, as in the case of gender-affirming medical care, have been met with increasing resistance in the political structures of the United States and the United Kingdom. Even the most common pro-trans narrative, of someone “born in the wrong body” perpetuates notions of interiority and exteriority that must sometimes be made to match but are otherwise fixed. Speculative creative works such as the Broken Earth trilogy, The Sandman, and The Witcher, however, present realities in which interiority and exteriority are fluid and dynamic, and mutable bodies are naturalized (whether or not those mutations occur through ‘natural’ means). Using a trans analytic, this project interrogates the racialized and (dis)abled dynamics of trans mutable embodiment to explore the limitations of medicalized and social transition and the possibilities of other kinds of being-in- the-world that rely on intersubjectivity rather than individuation