Demonstrating Loss of Control Over Technology: A Narrative Criticism

This study focuses on how individuals through their talk about computer mediated technology demonstrate a loss of control over that technology. Three separate computer mediated communication classes were involved in this study through the use of autoethnographies. The students in all three classes were asked at the beginning of the semester to keep field notes on their experiences with the technology. At the end of the semester the students were to summarize and report their experiences. Because of the qualitative nature of the data, a narrative criticism of the stories students told about their experiences seemed to provide the most valuable insight. Narratives or stories provide clues to an individual\u27s subjective interpretation of the world around them. Through stories people create and sustain their world giving the rhetorical critic a means through which they can look into an individuals perceived reality. The results of this study reveal that people often surrender control to technology unaware of the larger social implications. They demonstrate this through the way they talk about technology and the future

Developing Effective Alzheimer's Disease Therapies: Clinical Experience and Future Directions

Alzheimer's disease (AD) clinical trials, focused on disease modifying drugs and conducted in patients with mild to moderate AD, as well as prodromal (early) AD, have failed to reach efficacy endpoints in improving cognitive function in most cases to date or have been terminated due to adverse events. Drugs that have reached clinical stage were reviewed using web resources (such as clinicaltrials.gov, alzforum.org, company press releases, and peer reviewed literature) to identify late stage (Phase II and Phase III) efficacy clinical trials and summarize reasons for their failure. For each drug, only the latest clinical trials and ongoing trials that aimed at improving cognitive function were included in the analysis. Here we highlight the potential reasons that have hindered clinical success, including clinical trial design and choice of outcome measures, heterogeneity of patient populations, difficulties in diagnosing and staging the disease, drug design, mechanism of action, and toxicity related to the long-term use. We review and suggest approaches for AD clinical trial design aimed at improving our ability to identify novel therapies for this devastating disease

Ultrasonographic assessment of costochondral cartilage for microtia reconstruction

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149363/1/lary27390_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149363/2/lary27390.pd

Seroepidemiology and molecular diversity of Leishmania donovani complex in Georgia

Background Leishmaniasis includes multiple clinical syndromes, most notably visceral, cutaneous, and mucosal forms. Visceral leishmaniasis (VL), also known as kala-azar, is a potentially fatal disease endemic to large parts of Africa and Asia, and in South-Eastern Europe (Greece, Turkey, Georgia). Visceral leishmaniasis is a parasitic zoonosis caused by species of the L. donovani complex. In the classical epidemiological model the main reservoir for VL are canines. Methods The study included a cohort of 513 individuals of both genders (190 males and 323 females) from the ages of 1 to 70 years that were screened in ten villages across two districts in Kakheti using the Kalazar Detect™ rK39 rapid diagnostic test. The phylogenetic diversity patterns of local strains, based on the rDNA internal transcribed spacer (ITS) sequences, were assessed for samples obtained from patients with suspected L. donovani infection, from canine reservoirs and from Phlebotomus sand flies obtained from different geographical areas of Georgia and from Azerbaijan. Results Out of a total of 600 domestic dog blood samples 95 (15.8 %) were positive by rK39 rapid diagnostic tests. For symptomatic domestic dogs, the testing of conjunctival swabs or bone marrow aspirates revealed a higher VL incidence in Kvareli District (Kvareli; 19.4 %, n = 329) compared with that observed for Sagarejo District (Sagarejo; 11.4 %, n = 271). A total of 231 sand flies of both genders were collected during the 2-month period; of the 114 females, 1.75 % were PCR positive for the presence of Leishmania spp. Conclusions VL infection rates remain high in both canines and humans in Georgia, with disease in several known natural foci. The genetic relationships derived from rDNA internal transcribed spacer (ITS) sequence comparisons identified genetic subgroups, revealing preliminary insights into the genetic structure of L. donovani complex members currently circulating in the South Caucasus and demonstrates the utility of ITS-based genotyping in the resource-limited country of Georgia

Genome-wide association of familial late-onset alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE

Late-onset Alzheimer's disease (LOAD) is the most common form of dementia in the elderly. The National Institute of Aging-Late Onset Alzheimer's Disease Family Study and the National Cell Repository for Alzheimer's Disease conducted a joint genome-wide association study (GWAS) of multiplex LOAD families (3,839 affected and unaffected individuals from 992 families plus additional unrelated neurologically evaluated normal subjects) using the 610 IlluminaQuad panel. This cohort represents the largest family-based GWAS of LOAD to date, with analyses limited here to the European-American subjects. SNPs near APOE gave highly significant results (e.g., rs2075650, p = 3.2×10-81), but no other genome-wide significant evidence for association was obtained in the full sample. Analyses that stratified on APOE genotypes identified SNPs on chromosome 10p14 in CUGBP2 with genome-wide significant evidence for association within APOE ε4 homozygotes (e.g., rs201119, p = 1.5×10-8). Association in this gene was replicated in an independent sample consisting of three cohorts. There was evidence of association for recently-reported LOAD risk loci, including BIN1 (rs7561528, p = 0.009 with, and p = 0.03 without, APOE adjustment) and CLU (rs11136000, p = 0.023 with, and p = 0.008 without, APOE adjustment), with weaker support for CR1. However, our results provide strong evidence that association with PICALM (rs3851179, p = 0.69 with, and p = 0.039 without, APOE adjustment) and EXOC3L2 is affected by correlation with APOE, and thus may represent spurious association. Our results indicate that genetic structure coupled with ascertainment bias resulting from the strong APOE association affect genome-wide results and interpretation of some recently reported associations. We show that a locus such as APOE, with large effects and strong association with disease, can lead to samples that require appropriate adjustment for this locus to avoid both false positive and false negative evidence of association. We suggest that similar adjustments may also be needed for many other large multi-site studies. © 2011 Wijsman et al

Olfactory identification in subjective cognitive decline and mild cognitive impairment: Association with tau but not amyloid positron emission tomography

Introduction We investigated the association between olfactory identification and Alzheimer's disease biomarkers, including amyloid, tau, and neurodegeneration. Methods Thirty-four older adults, including 19 cognitively normal (CN), 10 subjective cognitive decline (SCD), and 5 mild cognitive impairment, underwent amyloid positron emission tomography, magnetic resonance imaging, and the University of Pennsylvania Smell Identification Test (UPSIT). Twenty-six also underwent tau positron emission tomography. Associations between the UPSIT and regionally sampled amyloid, tau, and temporal atrophy were evaluated. Voxel-wise regression models were also utilized. Analyses were conducted with the full sample and only CN/SCD. Results Lower UPSIT scores were associated with increased temporal and parietal tau burden in regional and voxel-wise analyses in the full sample and in CN and SCD only. Temporal lobe atrophy was associated with lower UPSIT score. Amyloid was not associated with the UPSIT. Discussion Impairment on the UPSIT may be a good marker for tau and neurodegeneration in preclinical or prodromal Alzheimer's disease

Cerebral hypometabolism and grey matter density in MAPT intron 10 +3 mutation carriers

Multiple systems tauopathy with presenile dementia (MSTD), a form of frontotemporal dementia with parkinsonism-17 with tau inclusions (FTDP-17T), is a neurodegenerative disorder caused by an (a) to (g) transition at position +3 of intron 10 of the microtubule associated protein tau (MAPT) gene. The mutation causes overexpression of 4 repeat (4R) tau isoforms with increased 4R/3R ratio leading to neurodegeneration. Clinically, these patients primarily present with behavioral variant FTD (bvFTD) and show disinhibition, disordered social comportment, and impaired executive function, memory, and speech. While altered glucose metabolism has been reported in subjects with sporadic bvFTD, it has yet to be investigated in an FTDP-17 sample of this size. In this study, eleven mutation carriers (5 males; mean age = 48.0 ± 6.9 years) and eight non-carriers (2 males; mean age = 43.7 ± 12.0 years) from a MSTD family were imaged using [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Eight of the MAPT intron 10 +3 mutation carriers met diagnostic criteria for bvFTD at the time of the PET scan, while three MAPT intron 10 +3 carriers were not cognitively impaired at the time of scan. Non-carriers had no clinically-relevant cognitive impairment at the time of the PET scan. Additionally, ten mutation carriers (5 males; mean age = 48.04 ± 2.1 years) and seven non-carriers (2 males; mean age 46.1 ± 4.1 years) underwent magnetic resonance imaging (MRI) which is an expanded sample size from a previous study. Seven MAPT mutation carriers met diagnostic criteria for bvFTD at the time of the MRI scan. Images were assessed on a voxel-wise basis for the effect of mutation carrier status. SPM8 was used for preprocessing and statistical analyses. Compared to non-carriers, MAPT mutation carriers showed lower [(18)F]FDG uptake bilaterally in the medial temporal lobe, and the parietal and frontal cortices. Anatomical changes were predominantly seen bilaterally in the medial temporal lobe areas which substantially overlapped with the hypometabolism findings. These anatomical and metabolic changes overlap previously described patterns of neurodegeneration in MSTD patients and are consistent with the characteristics of their cognitive dysfunction. These results suggest that neuroimaging can describe the neuropathology associated with this MAPT mutation

Francisella tularensis in the United States

Subpopulations A.I and A.II. of Francisella tularensis subsp. tularensis are associated with unique biotic and abiotic factors that maintain disease foci

Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies.

IntroductionQuantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B-based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design.MethodsPittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally.ResultsGlobal amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers.DiscussionAlthough the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers