Thioredoxin as a putative biomarker and candidate target in age-related immune decline

The oxidoreductase Trx-1 (thioredoxin 1) is highly conserved and found intra- and extra-cellularly in mammalian systems. There is increasing interest in its capacity to regulate immune function based on observations of altered distribution and expression during ageing and disease. We have investigated previously whether extracellular T-cell or peripheral blood mononuclear cell Trx-1 levels serve as a robust marker of ageing. In a preliminary study of healthy older adults compared with younger adults, we showed that therewas a significant, butweak, relationshipwith age. Interestingly, patientswith rheumatoid arthritis and cancer have been described by others to secrete or express greater surface Trx-1 than predicted. It is interesting to speculate whether a decline in Trx-1 during ageing protects against such conditions, but correspondingly increases risk of disease associated with Trx-1 depletion such as cardiovascular disease. These hypotheses are being explored in the MARK-AGE study, and preliminary findings confirm an inverse correlation of surface Trx-1 with age. We review recent concepts around the role of Trx-1 and its partners in T-cell function on the cell surface and as an extracellular regulator of redox state in a secreted form. Further studies on the redox state and binding partners of surface and secreted Trx-1 in larger patient datasets are needed to improve our understanding of why Trx-1 is important for lifespan and immune function. © The Authors Journal compilation © 2014 Biochemical Society.

Manoeuvring towards research decline:the RAE and the decline of Britain's international research standing

Purpose: This research paper aims to examine the global trends in publishing in the leading marketing journals between 1964 and 2008, focusing on how public policy intervention in the assessment and funding of academic research has influenced Britain's relative productivity in the world's leading marketing journals. Design/methodology/approach: The method was an audit of contributions to the leading journals based on the authors' affiliation, country of origin and country in which they obtained their doctoral training. Findings: The results show that the proportion of leading marketing publications by authors affiliated to British universities have held steady at about 2 per cent, while the productivity of several other countries has accelerated past Britain. However, to retain that share, Britain has increasingly depended upon importing people whose PhD is not British. This contrasts with some other European countries that are now more productive than Britain, but mainly recruit locals with local PhDs. The pattern of decline in the UK is related to the impact of Britain's research assessment exercise and the continuation of relatively weak social science research training. Research limitations/implications: The analysis is limited by only looking at one academic discipline and only the top few academic journals in the field. Practical implications: The findings have implications at several levels. At a national policy level it questions the value of the research assessment exercises that appear to have presided over a decline in research productivity. For institutions, it questions the value in investing in developing local talent when success has come to those who buy talent internationally. Perhaps, the major implication arises from Britain's academic productivity declining while neighbouring countries have grown in international excellence. Originality/value: At a time when the continuation of expensive university research assessments is being questioned the research findings add value to the current debate in showing how that very process has accompanied academic decline. © Emerald Group Publishing Limited.

Conservation implications of the reproductive biology of the endangered vine Ipomoea microdactyla Griseb. (Convolvulaceae)

A plant's reproductive biology exerts a significant influence on both population persistence within changing environments and successful establishment of new populations. However, the interaction between extrinsic (i.e. ecological) and intrinsic (i.e. genetic) factors also is an important driver of demographic performance for plant populations. It is light of this that I performed a multidisciplinary investigation of the breeding system, seed and seedling establishment dynamics, and population genetic structure of the endangered Caribbean vine Ipomoea microdactyla Griseb. (Convolvulaceae). The results from the breeding system study show individuals from Florida, USA and Andros Island, Bahamas to be self-incompatible. Plants from the two regions are cross-compatible but there is evidence for outbreeding depression in their progeny. Significant regional differences were found in floral traits and progeny traits that suggests incipient speciation for the Florida populations. The results from the seed and seedling establishment dynamics experiment demonstrate that the restoration of small populations in Florida via seed and seedling augmentation is a successful strategy. The demographic performance of the outplanted individuals was driven significantly by ecological factors (e.g. herbivory) rather than by genetic factors which emphasizes that the ecological context is very important for successful restoration attempts. The results from the population genetic study using an analysis of molecular variation (AMOVA) reveal significant differences in genetic variation among individuals from Florida, Andros, and Cuba. A Bayesian analysis of population genetic structuring coincided with the previous AMOVA results among the three regions. The Mantel test indicated significant 'isolation by distance' for these regional populations implying restricted gene flow over relatively short distances. Overall, the Florida populations had the lowest measures of genetic diversity which is most likely due to the effects of both colonization founder events and habitat fragmentation. The results of my study highlight the value of performing multidisciplinary studies in relation to species conservation as knowledge of both extrinsic and intrinsic factors can best guide decisions for species preservation.

An Analysis on the Decline in the Authoritative Powers of the Papacy and its Application to Challenges to Authoritative Powers Faced By the Permanent Membership of the UN Security Council

The organizational authority of the Papacy in the Roman Catholic Church and the permanent membership of the UN Security Council are unique from institutions that are commonly compared with the UN, like the Concert of Europe and the League of Nations, in that these institutional organs possessed strong authoritative and veto powers. Both organs also owe their strong authority during their founding to a need for stability: The Papacy after the crippling of Western Roman Empire and the P-5 to deal with the insecurities of the post-WWII world. While the P-5 still possesses similar authoritative powers within the Council as it did after WWII, the historical authoritative powers of the Papacy within the Church was debilitated to such a degree that by the time of the Reformation in Europe, condemnations of practices within the Church itself were not effective. This paper will analyze major challenges to the authoritative powers of the Papacy, from the crowning of Charlemagne to the beginning of the Reformation, and compare the analysis to challenges affecting the authoritative powers of the P-5 since its creation. From research conducted thus far, I hypothesize that common themes affecting the authoritative powers of the P-5 and the Papacy would include: major changes in the institutions organization (i.e. the Avignon Papacy and Japan’s bid to become a permanent member); the decline in power of actors supporting the institutional organ (i.e. the Holy Roman Empire and the P-5 members); and ideological clashes affecting the institution’s normative power (i.e. the Great Western Schism and Cold War politics).

An Analysis on the Decline in the Authoritative Powers of the Papacy and its Application to Challenges to Authoritative Powers Faced By the Permanent Membership of the UN Security Council

The organizational authority of the Papacy in the Roman Catholic Church and the permanent membership of the UN Security Council are unique from institutions that are commonly compared with the UN, like the Concert of Europe and the League of Nations, in that these institutional organs possessed strong authoritative and veto powers. Both organs also owe their strong authority during their founding to a need for stability: The Papacy after the crippling of Western Roman Empire and the P-5 to deal with the insecurities of the post-WWII world. While the P-5 still possesses similar authoritative powers within the Council as it did after WWII, the historical authoritative powers of the Papacy within the Church was debilitated to such a degree that by the time of the Reformation in Europe, condemnations of practices within the Church itself were not effective. This paper will analyze major challenges to the authoritative powers of the Papacy, from the crowning of Charlemagne to the beginning of the Reformation, and compare the analysis to challenges affecting the authoritative powers of the P-5 since its creation. From research conducted thus far, I hypothesize that common themes affecting the authoritative powers of the P-5 and the Papacy would include: major changes in the institutions organization (i.e. the Avignon Papacy and Japan’s bid to become a permanent member); the decline in power of actors supporting the institutional organ (i.e. the Holy Roman Empire and the P-5 members); and ideological clashes affecting the institution’s normative power (i.e. the Great Western Schism and Cold War politics).

Age, Period and Cohort effects in the Decline of Party Identification in Germany

Party identification traditionally is seen as an important linkage mechanism, connecting voters to the party system. Previous analyses have suggested that the level of party identity is in decline in Germany, and in this article, we first expand previous observations with more recent data. These suggest that the erosion of party identity continues up to the present time. An age-period-cohort analysis of the panel data of the SOEP panel suggests that period effects are significantly negative. Furthermore, it can be observed that throughout the 1992-2009 observation period, education level and political interest have become more important determinants of party identity. Contrary to some of the literature, therefore, it can be shown that the loss of party identity is concentrated among groups with lower levels of political sophistication, indicating that the socio-economic profile of the group with a sense of party identification has become more distinct compared to the population as a whole. In the discussion, we investigate the theoretical and democratic consequences of this trend.

The effects of centrally acting ACE inhibitors on the rate of cognitive and functional decline in dementia: a KDD approach

Alzheimer’s Disease and other dementias are one of the most challenging illnesses confronting countries with ageing populations. Treatment options for dementia are limited, and the costs are significant. There is a growing need to develop new treatments for dementia, especially for the elderly. There is also growing evidence that centrally acting angiotensin converting enzyme (ACE) inhibitors, which cross the blood-brain barrier, are associated with a reduced rate of cognitive and functional decline in dementia, especially in Alzheimer’s disease (AD). The aim of this research is to investigate the effects of centrally acting ACE inhibitors (CACE-Is) on the rate of cognitive and functional decline in dementia, using a three phased KDD process. KDD, as a scientific way to process and analysis clinical data, is used to find useful insights from a variety of clinical databases. The data used are from three clinic databases: Geriatric Assessment Tool (GAT), the Doxycycline and Rifampin for Alzheimer’s Disease (DARAD), and the Qmci validation databases, which were derived from several different geriatric clinics in Canada. This research involves patients diagnosed with AD, vascular or mixed dementia only. Patients were included if baseline and end-point (at least six months apart) Standardised Mini-Mental State Examination (SMMSE), Quick Mild Cognitive Impairment (Qmci) or Activities Daily Living (ADL) scores were available. Basically, the rates of change are compared between patients taking CACE-Is, and those not currently treated with CACE-Is. The results suggest that there is a statistically significant difference in the rate of decline in cognitive and functional scores between CACE-I and NoCACE-I patients. This research also validates that the Qmci, a new short assessment test, has potential to replace the current popular screening tests for cognition in the clinic and clinical trials.

A geographical perspective on the decline and extermination of the Irish wolf Canis lupus - an initial assessment

Wolves were a component of the Irish landscape until 1786 when the last one was killed. It had taken a concerted effort by Cromwell and his Government in Ireland to bring this about particularly through deforestation and landscape change, legislation, bounties and the efforts of a few professional wolf hunters. This paper estimates the wolf population in Ireland at three lime periods in the 1600s and examines how each of the forces already mentioned led to their eventual extermination. The 87 dated and documented wolf incidents which include wolf attacks on both animals and humans, wolf observations and the hunting and killing of wolves over the period 1560-1789 show both spatial and temporal variations.

Cape Breton Provides Pointers for the Adjustment Programs Required by the Decline of the Old Economy (Working Paper 14)

The Cape Breton Development Corporation need not, should not, be dying in the way it is. “Devco” has been widely represented as a failure dragged out too long. In fact it had for a time considerable success in a role too difficult to be often attempted. The main failure was in the political will to stick to its purpose. This commentary is in three parts. The first, major section discusses the purpose of Devco and the policies that served the purpose quite well but were maintained for little more than a decade. It suggests that the benefits would have been greater if Devco had been started earlier in the period of postwar prosperity. The second section comments on the enfeeblement of Devco in the 1980s. The removal of its development function also weakened, and has eventually led to the abandonment of, Devco’s social purpose in the operation of coal mining. Third, a short epilogue pointing out that, while the Cape Breton case is extreme, there will be increasing need to moderate the socially disruptive consequences of accelerating economic change. There are lessons from the Devco experience: the longer remedial action is delayed, the more difficult and expensive it becomes, and the more necessary for its effectiveness is a steady political will.

Deep Decline

Thesis (Ph.D.)--University of Washington, 2016-08

Accelerated age-related olfactory decline among type 1 Usher patients

Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin' Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome.

Accelerated age-related olfactory decline among type 1 Usher patients

Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin' Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome.