Alien Registration- Skoog, Fritz J. (Vinalhaven, Knox County)

https://digitalmaine.com/alien_docs/12958/thumbnail.jp

Development and Evaluation of Extracorporeal Gas Exchangers for Multi-Function Use in Respiratory Failure.

In the U.S., there are 400,000 respiratory failure deaths. Conventional treatment for acute respiratory failure employs lung damaging mechanical ventilation. The only long term treatment for chronic respiratory failure is lung transplantation. However, only 1800 transplants are performed each year due to donor shortages, resulting in the need for a destination therapy. Extracorporeal gas exchangers have been used as an alternative to mechanical ventilation in acute respiratory failure and as a bridge to transplantation in chronic respiratory failure. Blood is diverted to an extracorporeal gas exchanger, where oxygen is added and carbon dioxide is removed before returning the blood to the patient. Current gas exchangers are limited by their high resistance and low biocompatibility that lead to patient complications and device clot formation. This dissertation discusses three gas exchangers; the compliant thoracic artificial lung (cTAL), the compact cardiopulmonary support device (CCSD), and the pulmonary assist device (PAD). Fourteen day in vivo studies evaluated the cTAL’s long term performance and biocompatibility. The uncoated cTAL was capable of 14 days of support without a resistance increase or clot formation. In the future, the cTAL will be coated with anti-coagulant coatings and tested in vivo for 2 months. Individual components of the CCSD were designed and when tested, met design goals. However, enclosure pressures of negative 197 mmHg at flowrates of 4 L/min were encountered in CCSD system testing, causing gas embolus formation. The risk of gas embolus resulted in the discontinuation of CCSD development. The PAD was designed for long term use as a bridge to transplantation and destination therapy. Computational simulations were used to design the PAD with a theoretical resistance of 1.50 mmHg/(L/min) and a 98.3 percent blood outlet oxyhemoglobin saturation at blood flowrates of 1.25 L/min. In vitro testing of the PAD yielded lower gas exchange performance (88.4 percent saturation) and higher resistance (3.47 mmHg/(L/min)). However, the gas exchange performance was skewed negatively by two devices with fabrication defects. PADs without defects were closer to the gas exchange goal. Future computational models will be improved, and the PAD will be redesigned for lower resistance and higher gas exchange.PhDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/120702/1/djskoog_1.pd

Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer's Disease: Results from the Gothenburg H70 Birth Cohort Studies

BACKGROUND: We have previously shown that older adults with preclinical Alzheimer's disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology. OBJECTIVE: We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology. METHODS: The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n = 316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories. RESULTS: Among participants with CDR 0 (n = 259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p = 0.003), object Delayed (p = 0.042) and Immediate recall (p = 0.033)). Among participants with CDR 0.5 (n = 57), those with amyloid pathology (A+) scored worse in category fluency (p = 0.003). CONCLUSION: Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline

Effects of amyloid pathology and the APOE ε4 allele on the association between cerebrospinal fluid Aβ38 and Aβ40 and brain morphology in cognitively normal 70-years-olds

The association between cerebrospinal fluid (CSF) amyloid beta (Aβ) Aβ38 or Aβ40 and brain grey- and white matter integrity is poorly understood. We studied this in 213 cognitively normal 70-year-olds, and in subgroups defined by presence/absence of the APOE ε4 allele and Aβ pathology: Aβ−/APOE−, Aβ+/APOE−, Aβ−/APOE+ and Aβ+/APOE+. CSF Aβ was quantified using ELISA and genotyping for APOE was performed. Low CSF Aβ42 defined Aβ plaque pathology. Brain volumes were assessed using Freesurfer-5.3, and white matter integrity using tract-based statistics in FSL. Aβ38 and Aβ40 were positively correlated with cortical thickness, some subcortical volumes and white matter integrity in the total sample, and in 3 of the subgroups: Aβ−/APOE−, Aβ+/APOE− and Aβ−/APOE+. In Aβ+/APOE+ subjects, higher Aβ38 and Aβ40 were linked to reduced cortical thickness and subcortical volumes. We hypothesize that production of all Aβ species decrease in brain regions with atrophy. In Aβ+/APOE+, Aβ-dysregulation may be linked to cortical atrophy in which high Aβ levels is causing pathological changes in the gray matter of the brain

Coordinated analysis of age, sex, and education effects on change in MMSE scores

Objectives. We describe and compare the expected performance trajectories of older adults on the Mini-Mental Status Examination (MMSE) across six independent studies from four countries in the context of a collaborative network of longitudinal studies of aging. A coordinated analysis approach is used to compare patterns of change conditional on sample composition differences related to age, sex, and education. Such coordination accelerates evaluation of particular hypotheses. In particular, we focus on the effect of educational attainment on cognitive decline.Method. Regular and Tobit mixed models were fit to MMSE scores from each study separately. The effects of age, sex, and education were examined based on more than one centering point.Results. Findings were relatively consistent across studies. On average, MMSE scores were lower for older individuals and declined over time. Education predicted MMSE score, but, with two exceptions, was not associated with decline in MMSE over time.Conclusion. A straightforward association between educational attainment and rate of cognitive decline was not supported. Thoughtful consideration is needed when synthesizing evidence across studies, as methodologies adopted and sample characteristics, such as educational attainment, invariably differ. © 2012 The Author

Gait speed as predictor of transition into cognitive impairment: Findings from three longitudinal studies on aging

Objectives: Very few studies looking at slow gait speed as early marker of cognitive decline investigated the competing risk of death. The current study examines associations between slow gait speed and transitions between cognitive states and death in later life. / Methods: We performed a coordinated analysis of three longitudinal studies with 9 to 25 years of follow-up. Data were used from older adults participating in H70 (Sweden; n = 441; aged ≥70 years), InCHIANTI (Italy; n = 955; aged ≥65 years), and LASA (the Netherlands; n = 2824; aged ≥55 years). Cognitive states were distinguished using the Mini-Mental State Examination. Slow gait speed was defined as the lowest sex-specific quintile at baseline. Multistate models were performed, adjusted for age, sex and education. / Results: Most effect estimates pointed in the same direction, with slow gait speed predicting forward transitions. In two cohort studies, slow gait speed predicted transitioning from mild to severe cognitive impairment (InCHIANTI: HR = 2.08, 95%CI = 1.40–3.07; LASA: HR = 1.33, 95%CI = 1.01–1.75) and transitioning from a cognitively healthy state to death (H70: HR = 3.30, 95%CI = 1.74–6.28; LASA: HR = 1.70, 95%CI = 1.30–2.21). / Conclusions: Screening for slow gait speed may be useful for identifying older adults at risk of adverse outcomes such as cognitive decline and death. However, once in the stage of more advanced cognitive impairment, slow gait speed does not seem to predict transitioning to death anymore

Subtle Differences in Cognition in 70-Year-Olds with Elevated Cerebrospinal Fluid Neurofilament Light and Neurogranin: A H70 Cross-Sectional Study

BACKGROUND: Most research on cerebrospinal fluid (CSF) neurofilament light protein (NfL) as a marker for neurodegeneration and neurogranin (Ng) for synaptic dysfunction has largely focused on clinical cohorts rather than population-based samples. OBJECTIVE: We hypothesized that increased CSF levels of NfL and Ng are associated with subtle cognitive deficits in cognitively unimpaired (CU) older adults. METHODS: The sample was derived from the Gothenburg H70 Birth Cohort Studies and comprised 258 CU 70-year-olds, with a Clinical Dementia Rating score of zero. All participants underwent extensive cognitive testing. CSF levels of NfL and Ng, as well as amyloid β1 - 42, total tau, and phosphorylated tau, were measured. RESULTS: Participants with high CSF NfL performed worse in one memory-based test (Immediate recall, p = 0.013) and a language test (FAS, p = 0.016). Individuals with high CSF Ng performed worse on the memory-based test Supra Span (p = 0.035). When stratified according to CSF tau and Aβ42 concentrations, participants with high NfL and increased tau performed worse on a memory test than participants normal tau concentrations (Delayed recall, p = 0.003). In participants with high NfL, those with pathologic Aβ42 concentrations performed worse on the Delayed recall memory (p = 0.044). In the high Ng group, participants with pathological Aβ42 concentrations had lower MMSE scores (p = 0.027). However, in regression analysis we found no linear correlations between CSF NfL or CSF Ng in relation to cognitive tests when controlled for important co-variates. CONCLUSION: Markers of neurodegeneration and synaptic pathology might be associated with subtle signs of cognitive decline in a population-based sample of 70-year-olds

Draft genome sequence of Desulfurobacterium sp. Strain AV08, a Thermophilic Chemolithoautotroph isolated from a deep-sea hydrothermal vent

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Skoog, E. J., Huber, J. A., Serres, M. H., Levesque, A., & Zeigler Allen, L. Draft genome sequence of Desulfurobacterium sp. Strain AV08, a Thermophilic Chemolithoautotroph isolated from a deep-sea hydrothermal vent. Microbiology Resource Announcements, 10(34), (2021): e0061521, https://doi.org/10.1128/MRA.00615-21.A thermophilic chemolithoautotrophic bacterium was isolated from vent fluids at Axial Seamount, an active deep-sea volcano in the northeast Pacific Ocean. We present the draft genome sequence of Desulfurobacterium sp. strain AV08.This research was supported by the National Aeronautics and Space Administration Exobiology Program (grant 80NSSC18K1076 to L.Z.A. and J.A.H.). This study was also partially supported by the NSF Center for Dark Energy Biosphere Investigations (C-DEBI) (grant OCE-0939564 to J.A.H.)