Information in a message can either be fully expressed (explicitly) or indirectly stated (implied) and understood by inference or association. Previous research suggested an age-related decline in performance of implicit compared to explicit information and that this relationship is moderated by prior knowledge. Whereas previous studies mainly obtained quantitative data of inferencing performance, the current study employed both quantitative and qualitative techniques to understand age-related differences in inferencing. Twenty younger and older participants evaluated whether a series of one-sentence statements were true or false based on specific two-sentence text passages. Text passages either resembled real warnings (taken from actual products) or were novel (the opposite of a warning found on an actual product). Statements either explicitly stated information from the text passage or required participants to go beyond information given in the text. Quantitative analysis showed that older adults accuracy compared to that of younger adults when evaluating real text passages, with explicit items being evaluated more accurately than implicit items. For novel text passages (generally lower accuracy scores), younger adults showed the same pattern as for real text passages, whereas older adults accuracy was low for both explicit and implicit statements. Qualitative analyses supported that participants correct answers generally reflected that the intended inference was drawn and that for incorrect answers the inference was not mentioned. The data also suggested that accuracy scores may underestimate the actual ability to infer. Both age groups mentioned most often that text-related factors (e.g., clarity) influenced their decision and brought outside information (e.g., education, experience, expectations) to the task regardless of text passage or statement type. Older adults more often referred to outside information than younger adults, particularly when evaluating novel text passages and their answer was wrong. This study substantiated that age-related differences in a task requiring inferencing may be explained by a combination of the factors of working memory (time and availability of information) and prior knowledge as well as a possible decline in inferencing ability. Prior knowledge is important for both age groups and especially so for older adults. Important implications for designers are to make information available and explicit.

Although bevacizumab is one of the most commonly used treatments for DME and AMD, there are concerns regarding safety and effectiveness due to its off-label use. The study objectives were to determine if: 1) the risk of cardiovascular/ hemorrhagic events (safety) and visual impairment (effectiveness) differed by bevacizumab use (i.e., use vs. non-use and number of treatments) among DME and AMD patients; and 2) direct medical costs differed between DME and DME control patients. A retrospective cohort analysis was conducted with Texas Medicaid medical and prescription data (9/1/07-12/31/12) for patients: 18- 63 years, continuously enrolled 1-year pre- and post-index, and diagnosed with DME or AMD. The index date was the first date of diagnosis. The dependent variables were: 1) cardiovascular/hemorrhagic risk; 2) visual impairment; 3) direct medical costs. The independent variables were bevacizumab use and number of bevacizumab treatments. Covariates were disease state, Charlson Comorbidity Index (CCI) score, total medication use, number of laser treatments, and demographics. Propensity scoring technique was used to match: 1) bevacizumab users and non-users; and 2) DME and DME control cohorts. Descriptive analyses, logistic regression, Cox-regression, and generalized linear models were employed. A final cohort of 3,647 DME, 297 AMD, and 57,897 DME control patients were included. The majority (DME and AMD) was between 45-63 years of age (86.6%), Hispanic (54.0%), and female (65.1%). The mean total number of unique medications and mean CCI were 2.7 ± 3.4 and 6.0 ± 3.3, respectively. Total direct medical costs/person (Mean (±SD)) incurred by DME, DME control, and AMD subjects in the post-index period were $6,704(±9,338), $5,495(±10,153), and $4,935(±12,702), respectively. No differences in cardiovascular/ hemorrhagic risk were found between bevacizumab users and non-users. The claims data lacks the detail to determine the effectiveness of bevacizumab. DME control patients had lower overall direct medical costs than DME patients (p<0.0001). In conclusion, although bevacizumab is a less expensive off-label alternative of ranibizumab, the choice between bevacizumab and ranibizumab should be made through careful consideration. However, as the use of anti-VEGF agent increases, further research should be conducted to determine if any changes in cardiovascular adverse events occur. / text

It is often difficult for people to understand speech when there are other ongoing conversations in the background. This dissertation investigates how different background maskers interfere with our ability to comprehend speech and the reasons why older listeners have more difficulties than younger listeners in these tasks. An ecologically valid approach was applied: instead of words or short sentences, participants were presented with two fairly lengthy lectures simultaneously, and their task was to listen to the target lecture, and ignore the competing one. Afterwards, they answered questions regarding the target lecture. Experiment 1 found that both normal-hearing and hearing-impaired older adults performed poorer than younger adults when everyone was tested in identical listening situations. However, when the listening situation was individually adjusted to compensate for age-related differences in the ability to recognize individual words in noise, age-related difference in comprehension disappeared. Experiment 2 compared the masking effects of a single-talker competing lecture to a babble of 12 voices, and the signal-to-noise ratio (SNR) was manipulated so that the masker was either of similar volume as the target, or much louder. The results showed that the competing speech was much more distracting than babble. Moreover, increasing the masker level negatively affected speech comprehension only when the masker was babble; when it was a single-talker lecture, the performance plateaued as the SNR decreased from -2 to -12 dB. Experiment 3 compared the effects of semantic content and acoustic similarity on speech comprehension by comparing a normal speech masker with a time-reversed one (to examine the effect of semantic content) and a normal speech masker with an 8-band vocoded speech (to examine the effect of acoustic similarity). The results showed that both semantic content and acoustic similarity contributed to informational masking, but the latter seemed to play a bigger role than the former. Together, the results indicated that older adults&rsquo; speech comprehension difficulties with maskers were mainly due to declines in their hearing capacities rather than their cognitive functions. The acoustic similarity between the target and competing speech may be the main reason for informational masking, with semantic interference playing a secondary role.

It is often difficult for people to understand speech when there are other ongoing conversations in the background. This dissertation investigates how different background maskers interfere with our ability to comprehend speech and the reasons why older listeners have more difficulties than younger listeners in these tasks. An ecologically valid approach was applied: instead of words or short sentences, participants were presented with two fairly lengthy lectures simultaneously, and their task was to listen to the target lecture, and ignore the competing one. Afterwards, they answered questions regarding the target lecture. Experiment 1 found that both normal-hearing and hearing-impaired older adults performed poorer than younger adults when everyone was tested in identical listening situations. However, when the listening situation was individually adjusted to compensate for age-related differences in the ability to recognize individual words in noise, age-related difference in comprehension disappeared. Experiment 2 compared the masking effects of a single-talker competing lecture to a babble of 12 voices, and the signal-to-noise ratio (SNR) was manipulated so that the masker was either of similar volume as the target, or much louder. The results showed that the competing speech was much more distracting than babble. Moreover, increasing the masker level negatively affected speech comprehension only when the masker was babble; when it was a single-talker lecture, the performance plateaued as the SNR decreased from -2 to -12 dB. Experiment 3 compared the effects of semantic content and acoustic similarity on speech comprehension by comparing a normal speech masker with a time-reversed one (to examine the effect of semantic content) and a normal speech masker with an 8-band vocoded speech (to examine the effect of acoustic similarity). The results showed that both semantic content and acoustic similarity contributed to informational masking, but the latter seemed to play a bigger role than the former. Together, the results indicated that older adults&rsquo; speech comprehension difficulties with maskers were mainly due to declines in their hearing capacities rather than their cognitive functions. The acoustic similarity between the target and competing speech may be the main reason for informational masking, with semantic interference playing a secondary role.

This study is an investigation into the relationship between numeric cognition and aging. Specifically, older and younger adults engaged in an experimental protocol that allowed observation of number comparison accuracy and response time latencies associated with the SNARC effect, the distance effect, and number format. The experimental protocol featured a computerized magnitude comparison task wherein the participants were prompted to identify the larger of two numbers. Half of the trials featured whole numbers and half featured fractions. The number stimuli were consistently mapped such that half of all trials were at near distance (i.e., difference of 2) or far distance (i.e., difference of 4) and half of all trials had the larger numerosity on the left side of space and the other half with the larger numerosity on the right side of space. Older adults were significantly slower and less accurate than young adults. Both age groups were significantly slower and less accurate when comparing fractions as opposed to comparing whole numbers. The SNARC effect impaired accuracy in both age groups but did not significantly impact response times. The distance effect impacted both age cohorts in accuracy but differentially impacted older adult response times more than young adult response times. The results of this study support the model of numeric cognition as an automatic process when comparing whole numbers at a far distance and this process is not disrupted by the SNARC effect but is when comparing whole numbers at near distance. The results also indicate that fraction comparison is a controlled process even when the fraction stimuli are consistently mapped. Further investigation is necessary to understand the amount of cognitive resources necessitated by fraction processing and if training can improve fraction comparison.

Age-related macular degeneration (AMD) is the leading cause of blindness inAmerica. The fact that AMD wreaks most of the damage in the center of the retina raises the question of whether light, integrated over long periods, is more concentrated in the macula. A method, based on eye-tracking, was developed to measure the distribution of light in the retina under natural viewing conditions. The hypothesis was that integrated over time, retinal illumination peaked in the macula. Additionally a possible relationship between age and retinal illumination was investigated. The eye tracker superimposed the subject’s gaze position on a video recorded by a scene camera. Five informed subjects were employed in feasibility tests, and 58 naïve subjects participated in 5 phases. In phase 1 the subjects viewed a gray-scale image. In phase 2, they observed a sequence of photographic images. In phase 3 they viewed a video. In phase 4, they worked on a computer; in phase 5, the subjects walked around freely. The informed subjects were instructed to gaze at bright objects in the field of view and then at dark objects. Naïve subjects were allowed to gaze freely for all phases. Using the subject’s gaze coordinates, and the video provided by the scene camera, the cumulative light distribution on the retina was calculated for ~15° around the fovea. As expected for control subjects, cumulative retinal light distributions peaked and dipped in the fovea when they gazed at bright or dark objects respectively. The light distribution maps obtained from the naïve subjects presented a tendency to peak in the macula for phases 1, 2, and 3, a consistent tendency in phase 4 and a variable tendency in phase 5. The feasibility of using an eye-tracker system to measure the distribution of light in the retina was demonstrated, thus helping to understand the role played by light exposure in the etiology of AMD. Results showed that a tendency for light to peak in the macula is a characteristic of some individuals and of certain tasks. In these situations, risk of AMD could be increased. No significant difference was observed based on age.

Indiana University-Purdue University Indianapolis (IUPUI) / Age-related hearing loss is an acute health problem affecting people worldwide, often arising due to defects in the proper functioning of sensory hair cells in the inner ear. The apical surface of sensory hair cells contains actin-based protrusions known as stereocilia, which detect sound and head movements. Since hair cells are not regenerated in mammals, it is important to maintain the functioning of stereocilia for the life of an organism to maintain hearing ability. The actin filaments within a stereocilium are extensively crosslinked by various actin crosslinking proteins, which are important for stereocilia development and maintenance. Multiple studies have shown that the stereocilia actin core is exceptionally stable whereas actin is dynamic only at the tips of stereocilia. However, whether the actin crosslinking proteins, which are nearly as abundant as actin itself, are similarly stable or can freely move in and out of the core remains unknown. Loss or mutation of crosslinkers like plastin-1, fascin-2, and XIRP2 causes progressive hearing loss along with stereocilia degeneration while loss of espin prevents stereocilia from even developing properly. Do these phenotypes stem from an unstable stereocilia core? Does crosslinking confer stability to the core? To address these questions, we generated novel transgenic reporter lines to monitor the dynamics of actin in mice carrying fascin-2R109H mutation and espin null mice and also to study the dynamics of actin crosslinkers, in vivo and ex-vivo. We established that actin crosslinkers readily exchange within the highly stable F-actin structure of the stereocilia core. In addition, we determined that stereocilia degeneration in mice carrying fascin-2R109H mutation and espin null mice could possibly occur due to a less stable actin core. These studies suggest that dynamic crosslinks stabilize the core to maintain proper stereocilia functioning. Future work warrants understanding the reason behind the importance of dynamic crosslinks within a stable stereocilia core. Actin stability not only depends on actin crosslinkers, but also on actin filament composition as evident from distinct stereocilia degeneration and progressive hearing loss patterns in hair-cell specific knockout of actin isoforms. Although beta- and gamma- actin polypeptide sequences differ by only 14 four amino acids, whether the latter determine the unique function of each cytoplasmic actin isoform was previously unknown. Here we determined that these four critical amino acids determine the unique functional importance of beta-actin isoform in sensory hair cells. Taken together, our study demonstrates that actin cytoskeletal proteins are important for the morphogenesis and maintenance of stereocilia.

Yes / PURPOSE. To compare microperimetric sensitivity around the monocular preferred retinal locus (mPRL) in age-related macular degeneration (AMD) to normative data, and to describe the characteristics of visual field defects around the mPRL in AMD. METHODS. Participants with AMD (total n ¼ 185) were either prospectively recruited (n ¼ 135) or retrospectively reviewed from an existing database (n ¼ 50). Participants underwent microperimetry using a test pattern (37 point, 58 radius) centered on their mPRL. Sensitivities were compared to normative data by spatial interpolation, and conventional perimetric indices were calculated. The location of the mPRL relative to the fovea and to visual field defects was also investigated. RESULTS. Location of mPRL varied approximately 158 horizontally and vertically. Visual field loss within 58 of the mPRL was considerable in the majority of participants (median mean deviation 14.7 dB, interquartile range [IQR] 19.6 to 9.6 dB, median pattern standard deviation 7.1 dB [IQR 4.8–9.0 dB]). Over 95% of participants had mean total deviation worse than 2 dB across all tested locations and similarly within 18 of their mPRL. A common pattern of placing the mPRL just foveal to a region of normal pattern deviation was found in 78% of participants. Total deviation was outside normal limits in this region in 68%. CONCLUSIONS. Despite altering fixation to improve vision, people with AMD exhibit considerable visual field loss at and around their mPRL. The location of the mPRL was typically just foveal to, but not within, a region of relatively normal sensitivity for the individual, suggesting that a combination of factors drives mPRL selection. / This report presents independent research funded by the NIHR

As Arabidopsis thaliana ages it becomes more resistant to virulent Pseudomonas syringae pv. tomato (Pst) bacteria. This is known as age-related resistance (ARR). ARR is associated with flowering and intercellular accumulation of salicylic acid (SA). A microarray experiment identified a number of jasmonic acid/ethylene (JA/ET)-associated genes whose expression was up-regulated during ARR. This thesis explores the role of JA/ET signaling during ARR by characterizing the role of two JA/ET-associated No Apical Meristem Cup-shaped Cotyledons (NAC) transcription factors: ANAC055 and ANAC092. Analysis of nae single and double mutants suggests that the NACs play nonredundant roles during ARR. The partial ARR defect of anac092 is followed one week later by an enhanced ARR response, and this is associated with a delay in flowering. Furthermore, mature 35S:ANAC092 exhibits increased susceptibility to Pst. Collectively, this data suggests that ANAC092 is a negative regulator of ARR and it contributes to positive regulation of flowering and the onset of ARR. The late flowering mutant luminidependens1 also exhibits a partial ARR defect, suggesting that the autonomous flowering pathway contributes to ARR. Gene expression data suggests that ANAC055 and ANAC092 regulate expression of some JA/ET-associated genes during ARR. The JA/ET signaling mutant ethylene insensitive2 (ein2) exhibits a partial ARR defect and reduced expression of ANAC055 and ANAC092, suggesting that EIN2 is a positive regulator of expression of ANAC055 and ANAC092 during ARR. Phytohormone analyses reveal that JA accumulates to similar levels in young and mature wild-type plants after inoculation with Pst, suggesting that increased expression of some JA/ET-associated genes in mature compared to young plants after inoculation with Pst is not associated with elevated levels of JA. This thesis contributes to our understanding of ARR by identifying some components of the NAC pathway, exploring the relationship between flowering and ARR, and conducting some phytohormone analysis. / Thesis / Doctor of Philosophy (PhD)

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