Extended Maternal and Paternal Hereditary Risk for Alzheimer’s Disease Examined by Sex in a Sample of Community Dwelling Older Adults in Cache County, Utah

More than 6 million Americans are living with Alzheimer’s Disease (AD) and this number is expected to rise and surpass 12.7million individuals by the year 2050. Currently there is no cure for the disease and prior research has focused on prevention by identifying risk factors. Known risk factors associated with AD include older age, female sex, genetics, family history of AD, genotype of the apolipoprotein E (APOE) gene, and vascular risk factors (e.g., cholesterol, hypertension) and conditions or events (e.g., CHF, stroke). The effects of many of the above risk factors have differed in men and women, but few studies have examined how family history of AD, direct maternal or paternal lineage of AD, parental longevity, and cardiovascular risk factors and conditions might influence risk for AD differently for men and women. This project analyzed existing data from a population-based longitudinal study, the Cache County Study on Memory in Aging (CCSMA), that included permanent residents of Cache County, Utah who were aged 65 years or older in 1995. The study’s data were enriched through additional data obtained for extended family history and Medicare claims and death certificates that were made available through data linkage with the Utah Population Database. The original study ran from 1995-2007, but with the additional Medicare claims and death certificates, identification of AD related outcomes and risk factors were extended to 2019. The aim of this current study was to examine whether the risk for AD differed between men and women with regards to family history of AD, maternal and paternal lineage of AD, longer-lived parents, and whether vascular health conditions affected these risks. Results from this dissertation showed that having a first-degree relative (parents, siblings, or offspring) with AD increased the risk for AD in men by 58%, Odds Ratio (OR)= 1.58, p= .003, and women by 66%, OR= 1.66, p=\u3c .001. Among women, direct maternal but not paternal lineage of AD was associated with a 56% increased risk for AD, OR= 1.56, p=.005, whereas in men, history of maternal or paternal lineage of AD(above age 87) did not affect their risk of developing AD. Having a longer-lived mother or longer-lived father was not associated with AD risk in women. However, men with a history of a longer-lived mother and who had an APOE Ɛ4 positive genotype had three times the risk of AD, OR= 3.15, p= .020. Men who had both a longer-lived mother and a longer-lived father compared to men without had an 11% reduction in risk for AD, OR= 0.89, p=.041. In relation to cardiovascular conditions and risk in women, those with a history of congestive heart failure (CHF) and a direct paternal lineage of AD had double the risk of AD compared to those without, though those women with no paternal lineage of AD were at an 11 times greater risk, OR= 11.15, p=\u3c 0.001. For men there were no associations between family history of AD and cardiovascular conditions. Among both men and women, several cardiovascular risk factors increased risk for AD. For instance, men and women with a history of stroke or CHF had an increased risk for AD. Men with a history of hypertension and high cholesterol/triglycerides/atherosclerosis were also at increased risk of developing AD. Notably, women with a history of myocardial infarction had a reduction in risk. Although this study is observational in nature and thus does not prove a direct causal relationship between familial history and AD, it does support previous research that found having a first-degree relative with AD regardless of sex increased the risk for AD. The study also highlighted the importance of studying risk factors like family history, separately for men and women. Thus, women with a maternal history of AD were at greater risk than those with a paternal history of AD, but no such association was found in men. Men were at slightly reduced risk for AD when having both longer-lived parents and there were slight differences by sex in cardiovascular risk factors that predicted risk for AD. The different results obtained for men and women have clinical implications in monitoring for AD risk in older adults and suggest aggressive treatment for vascular risk factors and conditions amongst women in particular, with CHF and family history. Further research is needed to understand the underlying mechanisms with how these risks vary in males and females

Epilepsy and Deafness: The Issue of Violence

The leading etiologies of deafness and of epilepsy are similar resulting in significantly more epilepsy in the deaf population. This study of 50 deaf epileptics reveals more males than females, a high rate of multiple disabilities, and a lower mean I.Q. The major finding was that 36 percent of the sample had serious problems with violent behavior

How lateral inhibition and fast retinogeniculo-cortical oscillations create vision: A new hypothesis

The role of the physiological processes involved in human vision escapes clarification in current literature. Many unanswered questions about vision include: 1) whether there is more to lateral inhibition than previously proposed, 2) the role of the discs in rods and cones, 3) how inverted images on the retina are converted to erect images for visual perception, 4) what portion of the image formed on the retina is actually processed in the brain, 5) the reason we have an after-image with antagonistic colors, and 6) how we remember space. This theoretical article attempts to clarify some of the physiological processes involved with human vision. The global integration of visual information is conceptual; therefore, we include illustrations to present our theory. Universally, the eyeball is 2.4 cm and works together with membrane potential, correspondingly representing the retinal layers,photoreceptors, and cortex. Images formed within the photoreceptors must first be converted into chemical signals on the photoreceptors’ individual discs and the signals at each disc are transduced from light photons into electrical signals. We contend that the discs code the electrical signals into accurate distances and are shown in our figures. The pre-existing oscillations among the various cortices including the striate and parietal cortex,and the retina work in unison to create an infrastructure of visual space that functionally ‘‘places” the objects within this ‘‘neural” space. The horizontal layers integrate all discs accurately to create a retina that is pre-coded for distance. Our theory suggests image inversion never takes place on the retina,but rather images fall onto the retina as compressed and coiled, then amplified through lateral inhibition through intensification and amplification on the OFF-center cones. The intensified and amplified images are decompressed and expanded in the brain, which become the images we perceive as external vision

Big Data Privacy Scenarios

This paper is the first in a series on privacy in Big Data. As an outgrowth of a series of workshops on the topic, the Big Data Privacy Working Group undertook a study of a series of use scenarios to highlight the challenges to privacy that arise in the Big Data arena. This is a report on those scenarios. The deeper question explored by this exercise is what is distinctive about privacy in the context of Big Data. In addition, we discuss an initial list of issues for privacy that derive specifically from the nature of Big Data. These derive from observations across the real world scenarios and use cases explored in this project as well as wider reading and discussions:* Scale: The sheer size of the datasets leads to challenges in creating, managing and applying privacy policies.* Diversity: The increased likelihood of more and more diverse participants in Big Data collection, management, and use, leads to differing agendas and objectives. By nature, this is likely to lead to contradictory agendas and objectives.* Integration: With increased data management technologies (e.g. cloud services, data lakes, and so forth), integration across datasets, with new and often surprising opportunities for cross-product inferences, will also come new information about individuals and their behaviors.* Impact on secondary participants: Because many pieces of information are reflective of not only the targeted subject, but secondary, often unattended, participants, the inferences and resulting information will increasingly be reflective of other people, not originally considered as the subject of privacy concerns and approaches.* Need for emergent policies for emergent information: As inferences over merged data sets occur, emergent information or understanding will occur. Although each unique data set may have existing privacy policies and enforcement mechanisms, it is not clear that it is possible to develop the requisite and appropriate emerged privacy policies and appropriate enforcement of them automatically

Investing in 4-H Volunteers Through State Leadership Forums

State volunteer forums can be an invaluable resource for providing opportunities for volunteer training on positive youth development. Some western states have experienced decreasing attendance and have questioned the practicality of hosting such forums. In this article, we showcase successes that one western state has experienced as a result of implementing innovative approaches. An online survey of participants showed increased capacity of volunteers to lead 4-H programs. Additionally, we outline implications for Extension professionals to inform their efforts to achieve successful volunteer forums

Integration of gene expression, clinical, and epidemiologic data to characterize Chronic Fatigue Syndrome

BACKGROUND: Chronic fatigue syndrome (CFS) has no diagnostic clinical signs or diagnostic laboratory abnormalities and it is unclear if it represents a single illness. The CFS research case definition recommends stratifying subjects by co-morbid conditions, fatigue level and duration, or functional impairment. But to date, this analysis approach has not yielded any further insight into CFS pathogenesis. This study used the integration of peripheral blood gene expression results with epidemiologic and clinical data to determine whether CFS is a single or heterogeneous illness. RESULTS: CFS subjects were grouped by several clinical and epidemiological variables thought to be important in defining the illness. Statistical tests and cluster analysis were used to distinguish CFS subjects and identify differentially expressed genes. These genes were identified only when CFS subjects were grouped according to illness onset and the majority of genes were involved in pathways of purine and pyrimidine metabolism, glycolysis, oxidative phosphorylation, and glucose metabolism. CONCLUSION: These results provide a physiologic basis that suggests CFS is a heterogeneous illness. The differentially expressed genes imply fundamental metabolic perturbations that will be further investigated and illustrates the power of microarray technology for furthering our understanding CFS

Bioelectronic DNA detection of human papillomaviruses using eSensor™: a model system for detection of multiple pathogens

BACKGROUND: We used human papillomaviruses (HPV) as a model system to evaluate the utility of a nucleic acid, hybridization-based bioelectronic DNA detection platform (eSensor™) in identifying multiple pathogens. METHODS: Two chips were spotted with capture probes consisting of DNA oligonucleotide sequences specific for HPV types. Electrically conductive signal probes were synthesized to be complementary to a distinct region of the amplified HPV target DNA. A portion of the HPV L1 region that was amplified by using consensus primers served as target DNA. The amplified target was mixed with a cocktail of signal probes and added to a cartridge containing a DNA chip to allow for hybridization with complementary capture probes. RESULTS: Two bioelectric chips were designed and successfully detected 86% of the HPV types contained in clinical samples. CONCLUSIONS: This model system demonstrates the potential of the eSensor platform for rapid and integrated detection of multiple pathogens

Exercise responsive genes measured in peripheral blood of women with Chronic Fatigue Syndrome and matched control subjects

BACKGROUND: Chronic fatigue syndrome (CFS) is defined by debilitating fatigue that is exacerbated by physical or mental exertion. To search for markers of CFS-associated post-exertional fatigue, we measured peripheral blood gene expression profiles of women with CFS and matched controls before and after exercise challenge. RESULTS: Women with CFS and healthy, age-matched, sedentary controls were exercised on a stationary bicycle at 70% of their predicted maximum workload. Blood was obtained before and after the challenge, total RNA was extracted from mononuclear cells, and signal intensity of the labeled cDNA hybridized to a 3800-gene oligonucleotide microarray was measured. We identified differences in gene expression among and between subject groups before and after exercise challenge and evaluated differences in terms of Gene Ontology categories. Exercise-responsive genes differed between CFS patients and controls. These were in genes classified in chromatin and nucleosome assembly, cytoplasmic vesicles, membrane transport, and G protein-coupled receptor ontologies. Differences in ion transport and ion channel activity were evident at baseline and were exaggerated after exercise, as evidenced by greater numbers of differentially expressed genes in these molecular functions. CONCLUSION: These results highlight the potential use of an exercise challenge combined with microarray gene expression analysis in identifying gene ontologies associated with CFS