No description available.

ABSTRACT IMPORTANCE: Age-related macular degeneration (AMD) is a leading cause of low vision in elderly population. The association of vascular and renal conditions has been reported inconsistently. Unfolding the association may provide the insight to eye care providers to take account general health management into eye care. OBJECTIVES: To investigate the prevalence of the vascular and renal comorbidities with AMD, examine the association of a single or combination of these comorbidities with AMD. DSIGN AND PARTICIPANTS: Population-base cross-sectional study involved the adults aged 40 years or older (N=4596) who participated in the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES), a national representative population-based survey of non-institutionalized US residents. MAIN OUTCOMES AND MEASURES: AMD was defined by the presence of drusen and presence of pigmental abnormality. Angina pectoris (AP), coronary heart disease (CHD), congestive heart failure (CHF) and myocardial infarction (MI), and stroke, assessed by self-report by the questionnaire of medical conditions, Chronic kidney disease (CKD), assessed by self-report and estimation of glomerular filtration rate (GFR) and the level of urine albumin. Heart disease (HD) was defined as having AP or CHF or CHD or MI. RESULTS: Among individuals with AMD, 6% had AP, 10% had CHD, 7% had CHF, 10% had MI, 13% had stroke, and 29% had CKD. The weighted prevalence of these conditions were significantly higher than those without AMD (All P-values CONCLUSION AND RELEVANCE: These findings from the nationally-representative sample of the US population highlight the prevalence of vascular and renal comorbidities associated with AMD, the modest evidence of relationship of each single comorbidity, and strong association of combination of stroke and CKD to AMD independent of age, gender, and other factors. Because of the cross-sectional design, the results of this study can not address a causal relationship between AMD and the examined comorbidities. It is unclear whether AMD and comorbidities arise from individual predisposition to vascular and renal diseases or whether complications from these morbidities increase the risk of AMD. However, the important caveat is that preventive and care management for the examined comorbidities may lessen the severity of symptoms or prevent AMD.

The present research sought to describe and explain age related changes to associative learning processes. Eleven experiments were conducted using a human conditional learning paradigm. Background data on health, lifestyle, and cognitive ability were collected and used as predictor variables in multiple regression analyses. Experiments 1 to 8 were formative, and found that older participants showed an overall age related decline in learning ability exacerbated by the number of stimuli and outcomes used, and the concurrent presentation of different problem types. Configural models of learning (e.g. Pearce, 1994, 2002) best predicted young participants’ learning whereas older people’s learning was more consistent with elemental models (e.g. Rescorla-Wagner, 1972), suggesting an age related change in generalisation processes. Those who learned problems better were also more likely to be able to articulate a rule that had helped them learn the problem. Age itself was the most predominant predictor of accuracy in these experiments. Experiments 9, 10, and 11 were multiple stage experiments that looked at the extent of pro- and retro-active interference in learning. Experiments 9 and 10 used easy and hard HCL problems to examine the role of rule induction in learning. Older participants who had learned initial discriminations better were more prone to pro-active interference in both experiments, the extent of which was predicted most reliably by fluid intelligence. Rule learning had a profound effect on participants’ predictions during the unreinforced test stage. In Experiment 9 (Easy-Hard) younger participants suffered from more retroactive interference than older people. This pattern was far less pronounced in Experiment 10, (Hard-Easy) suggesting that problem order affected the way participants generalised from rule-based knowledge. This observation is inexplicable by associative learning theories, and explanation may require a problem solving approach. Experiment 11 examined feature-based generalisation. Again older participants suffered more proactive and retroactive interference and elemental theories predicted their responses best, whereas younger participants responses were consistent with configural models of learning. In this instance, resistance to pro- and retro-active interference was predicted by fluid intelligence. Overall the research concluded that there is a demonstrable, complexity dependent change in associative learning processes in later life. It appears that humans have an increasing tendency to rely on elemental, rather than configural processes of generalisation in later life, and this leads to overgeneralisation between stimuli and an inability to resist pro- and retroactive interference in learning. This may be as a result of an inhibitory or source monitoring failure as a consequence of atrophy in the frontal lobes of the brain, although some of the learning deficits are explicable through mnemonic decline.

Age-related declines in hearing abilities are common and can be attributed to changes in the peripheral and central levels of the auditory system. Although central auditory processing is enhanced in younger musicians, the influence of lifelong musicianship on age-related decline in central auditory processing has not yet been investigated. Therefore, the purpose of this dissertation was to investigate whether lifelong musicianship can mitigate age-related decline in central auditory processing. In the first experiment, age-related declines on four hearing assessments were compared between musicians and non-musicians. Speech-in-noise and gap-detection thresholds were found to decline at a slower rate in musicians, providing an increasing advantage with age. Furthermore, musicians had a lifelong advantage in detecting a mistuned harmonic, although the rate of age-related decline was similar for both musicians and non-musicians. Importantly, there was no significant effect of musicianship on pure-tone thresholds, suggesting that lifelong musicianship can mitigate age-related decline in central but not peripheral auditory processing. To test this hypothesis, a second experiment compared auditory evoked responses (AERs) between groups of older and younger musicians and non-musicians. Results indicated that exogenous neural activity was enhanced in musicians, but that age-related changes were similar between musicians and nonmusicians. Furthermore, endogenous, attention-dependent neural activity was enhanced in older adults, suggesting a compensatory cognitive strategy. Importantly, endogenous activity was preferentially enhanced in older musicians, suggesting that lifelong musicianship enhanced cognitive processes related to auditory perception. In the final experiment, the ability to segregate simultaneous sounds was tested in older and younger musicians and non-musicians by using a mistuned harmonic paradigm, where AERs to harmonic complexes were compared to AERs when one of the harmonics was mistuned. Results indicated that musical training in older adults has little effect on early automatic registration of the mistuned harmonic. In contrast, late attention-dependent activity, associated with the perception of the mistuned harmonic as a separate sound, was influenced by musical training in older adults, suggesting that lifelong musicianship preserves or enhances cognitive components of concurrent sound segregation. In summary, musical training was found to reduce age-related decline in hearing abilities due to enhanced central processing of auditory information.

No description available.

Eine der häufigsten Behinderungen des alternden Menschen stellt die Beeinträchtigung der Hörfunktion durch degenerative Veränderungen der Cochlea, beispielsweise am Ganglion spirale, am CORTI-Organs oder an der Stria vascularis dar. Basierend auf histologischen und funktionellen Untersuchungen, wird die Altersschwerhörigkeit (Presbycusis) beim Menschen durch SCHUKNECHT und GACEK (1993) in sechs verschiedenene Typen eingeteilt: sensorisch, strial/metabolisch, neural, cochlear-konduktiv, gemischt, unbestimmt. Die in diesem Rahmen auftretenden pathophysiologischen und pathomorphologischen Veränderungen der Cochlea sind bedingt durch hörschädigende Faktoren (u.a. Lärm, ototoxische Substanzen, Infektionen sowie genetische Ursachen), die im Laufe des Lebens im Bereich des peripheren Hörorgans und der zentral auditiven Verarbeitung gewirkt haben. Die meisten in der Literatur beschriebenen Untersuchungen, die sich mit cochleären Alterationen mit zunehmendem Alter befassen, wurden an Labortieren unternommen und beschreiben oft nur Alterationen einzelner Strukturen, nicht aber der gesamten Cochlea. Bei Hunden sind in der Literatur überwiegend ausführliche Untersuchungen bezüglich der kongenitalen vererbten Taubheit, z.B. bei Dalmatinern, beschrieben. Es existieren jedoch kaum Studien über altersbedingte morphologische und funktionelle Veränderungen der Cochlea bei Hunden. Das Ziel dieser Arbeit besteht daher in der (immun-) histologischen Untersuchung der Cochlea von 50 Hunden im Alter von 7 Tagen bis 16 Jahren, um altersbedingte morphologische und funktionelle Veränderungen in der Cochlea von Hunden, die nicht unter Laborbedingungen gehalten wurden, zu charakterisieren und sie mit den Befunden an Innenohren von anderen Tierarten und des Menschen zu vergleichen. Anhand der erhobenen Befunde sollen anschließend eventuelle Rückschlüsse auf intra vitam vorhandene Hörstörungen gezogen werden.

Glaucoma is a common eye disease that affects the optic nerve. It is the second leading cause of visual loss globally and while it can occur in all age groups, it is most common in the elderly. The main symptom of glaucoma is the progressive deterioration of the visual field. Management of glaucoma involves careful monitoring of the progress of disease with regular visual field tests. Accurate identification and early intervention can potentially prevent advanced vision loss. A number of mathematical, statistical, and data mining methods have been proposed to identify glaucomatous progression. However, all criteria used to assess change are hampered by noise that arises from individual visual field measurement. In addition, different clinical trials use different definitions of “progressing”. Currently there is no standard method for classifying changes in visual field measurements. The purpose of this thesis is to improve existing methods and to develop new methods for classification of glaucoma. / The thesis first describes a glaucoma modeling software according to a patient’s clinical behaviour. The software can handle age-related visual decline, different types and rates of deterioration, and noise. Simulated data is a good resource for testing the efficiency of different methods in detecting progression, and for developing new methods with minimal cost. / The thesis then investigates four classification techniques, including Event Analysis( EA), sequence matching, point-wise linear regression (PLR) and machine learning. For EA methods, the thesis proposed an algorithm “baseline-follow-up” for building a 95% (or 99%) confidence interval using a database of repeated Standard Automated Perimetry (SAP) tests of stable visual fields. Experimental results show that the proposed algorithm can improve the sensitivity compared with other EA methods. A major novel contribution is our introduction of sequence matching techniques to the application of glaucomatous visual field data. Sequence matching techniques typically rely on similarity measure. However, visual field measurements are very noisy, particularly in people with glaucoma, and there is lack of a standard definition of progression. It is therefore difficult to establish a reference dataset including both stable and progressive visual fields. We describe two different matching methods,Weighted Sequence Matching (SM) and Baseline Matching Stable Sequences (BMS). SM uses either the Euclidean or Manhattan distance function to select matches in a stable database R for a given query sequence. BMS uses a baseline computed from a query sequence to match means of stable sequences in R. Matches are used to determine whether a query sequence is progressive or not. For PLR methods, the thesis explores the influence of updating a PLR method by adding or deleting an observation, and discusses the application of Kappa statistic for agreement between methods. We finally investigate the application of machine learning methods for the classification of visual field data. Various input features are defined. The feature datasets are extracted from visual field data, in which each patient has been classified by experts. For this study we used the WEKA package, which provides implementations for Decision Tree, Decision Stump, Naive Bayes, and Bayes Network classifiers, as well as Bagging and Boosting methods for applying the classifiers. The accuracy of classification is presented to illustrate the ability of machine learning for classifying visual field change.

Age-related macular degeneration (AMD) is a prevalent cause of vision loss and irreversible blindness that affects more than 11 million Americans. AMD is a multifactorial disease with a number of genetic, demographic, and environmental risk factors. Currently the etiology of AMD is still unclear and there are no effective cure for this devastating disease, but recent studies have demonstrated that RORA is a candidate gene involved in AMD pathophysiology. RORA is a critical regulator of multiple biological processes and has been implicated in various physiological processes including circadian rhythm, lipid metabolism, photoreceptor development, autism, and inflammation. Our current study will explore in depth the role of RORA in AMD. We will look at the effects of RORA in the retina of mice. Localization studies of retinal tissues obtained from mice with a conditional knockout of RORA in epithelial cells showed little effect of RORA on structural cells of the retina. However, there was a decrease in VEGF and TGF-B proteins in RORA knockout. This is an interesting finding because VEGF and TGF-B has an important function in angiogenesis and neovascularization which are pathophysiological effects of AMD. In addition, we will try to identify gene targets of RORA that have also been linked with AMD. By identifying the targets of RORA and discovering how RORA regulates these targets, we hope to better understand the role of RORA in AMD pathophysiology. ChIP-seq and software analysis of the data was performed to identify all genomic targets of RORA linked with AMD. A number of promising genes were found in both RORA and AMD networks. The next step of this study is to perform quantitative analysis of these genes and how their expression is affected by RORA. Also, we will perform additional conditional RORA knockout models in cone cells and developing retinal cells to further understand the role of RORA in the retina and AMD pathogenesis.

As the 21st century proceeds, individuals are increasingly working into later years to support themselves and maintain their quality of life. This changing pattern of employment has implications for workers, employers and society alike. Although older workers have much to contribute, individuals may experience health issues or physical, sensory or psychological changes related to ageing. Health and safety statistics indicate that older workers are a vulnerable group. Employers then, have a responsibility to examine the working environment and protect those with reduced capabilities. For society to function, older workers need to be able to remain in work, otherwise this will impact on both the economy and older individuals quality of life. This thesis aimed to understand the opportunities and challenges employers encounter when trying to protect and promote the health and safety of older workers. The research used qualitative approaches, combining interviews and focus groups to provide rich data on the circumstances of older workers. Triangulation was used, collecting data over different time periods, from different sources, to help balance out any weaknesses across the studies. Data were analysed using thematic analysis. A review of the literature found that there is no consistent definition of ageing or older worker. Many researchers have used chronological age and, therefore, this thesis used 50 as a threshold. The literature highlights that older workers have a wealth of knowledge and skills to bring to the workplace. Negative perceptions, however, regarding natural ageing and adaptability exist. Other authors have argued that organisations need to provide a safe environment for older workers and implement measures to mitigate changes in abilities, whilst recognising that there is no one size fits all strategy. First, an initial scoping study was undertaken with employers, which sought to understand their perceptions concerning the ageing workforce. The study also collected information on the health and safety age management strategies that have been implemented within the organisations. Interviews with employers (senior managers who influence health and safety management strategies) (n=41) revealed that, in line with literature, there is recognition that older workers bring benefits to the workplace. However, some comments demonstrated inaccurate stereotyping. The interviews found that these employers were uncertain how to proceed with implementing actions to protect the health and safety of their older workers. Two subsequent studies, consisting of focus groups (n=10) and interviews (n=50) were then conducted, which explored older workers experiences of working into later life and their views on the issues identified by the employer interview study. The older worker interviews also examined their perceptions regarding their health and capabilities, appropriate health and safety measures in response to this and interviewees anticipated future in the workforce. Older workers explained that they do not feel supported or engaged. They are fearful of reporting capability changes that may affect their ability to perform work tasks, as they believe this may have negative consequences for their future employment. During discussions, they suggested various measures that may help them remain in the workforce for longer. The information gathered during the literature review and the findings from the first three studies, were then used to develop examples of good practice health and safety measures that organisations could implement to help protect and promote the health and safety of older workers. A final interview study with key employer representatives (n=16) was conducted, to understand whether the health and safety good practice measures might be considered beneficial and achievable. This study found that although organisations recognised the benefits of health and safety measures tailored for older workers, the feasibility of some of the suggestions was in doubt. Budgetary constraints, insufficient time and lack of necessary knowledge were seen as particular obstacles to implementation. This thesis has identified that although research evidence exists in relation to measures to support the health and safety of older workers, e.g. the benefits of health promotion, improved work scheduling, workplace assessments etc, this is rarely translated into practice. Within organisations, there is uncertainty about age management for older workers and limited understanding of the divergent needs as workers capabilities change. The default position then becomes to cater for a typical worker. A coordinated multi-disciplinary approach between health and safety, occupational health, human resources and operational management is required. This thesis argues for an integrated age management strategy, with an emphasis on proactive prevention, in the interests of protecting and promoting the health and safety of older workers.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown aetiology, characterised by the progressive and irreversible scarring of parenchymal lung tissue that leads to respiratory failure and death. The disease is understood to be driven by an impaired and aberrant wound healing response, with an inappropriate reactivation of developmental signalling. The greatest risk factor for the disease is age, which is a process intimately associated with an increase in the burden of senescent cells. Such cells acquire a unique secretory phenotype and are known to have a significant impact on their local micro-environment. It was hypothesised that an alteration in epithelial-mesenchymal secretory communication, due to senescent-like changes in the fibroblast phenotype, may detrimentally contribute to lung homeostasis. An in vitro model of the lung airway was established in which primary human lung fibroblasts (HLFs) were co-cultured with human bronchial epithelial cells (HBECs). HBECs were cultured on a semi-permeable, transwell insert and co-cultured with either normal (NHLF), fibrotic (FHLF) or senescent fibroblasts. Over 72 hrs of co-culture, wound healing was assessed, via an epithelial scratch assay, and epithelial regeneration was measured, via trans-epithelial electrical resistance. Co-culture with NHLFs improves epithelial regeneration, however, FHLFs and senescent cells in co-culture show a diminished ability to promote epithelial regeneration and wound repair. The secretory repertoire of these cells contains elevated levels of IL-6, CXCL8, CXCL1 and GCSF (when assessed at both an RNA and protein level), factors strongly associated with the senescent phenotype. Targeting this secretome via treatment with the JAK 1/2 inhibitor Ruxolitinib attenuates these impairments and may point towards a new therapeutic strategy for the treatment of IPF.