MARK-AGE biomarkers of ageing

Many candidate biomarkers of human ageing have been proposed in the scientific literature but in all cases their variability in cross-sectional studies is considerable, and therefore no single measurement has proven to serve a useful marker to determine, on its own, biological age. A plausible reason for this is the intrinsic multi-causal and multi-system nature of the ageing process. The recently completed MARK-AGE study was a large-scale integrated project supported by the European Commission. The major aim of this project was to conduct a population study comprising about 3200 subjects in order to identify a set of biomarkers of ageing which, as a combination of parameters with appropriate weighting, would measure biological age better than any marker in isolation.

The Beginning of a Partnership in the Process of Studying Mathematics

In this paper we present the beginning of a partnership between the students in the upper classes and those in the beginner classes in 21st Secondary School “Hristo Botev”, Sofia. We examine deeply two of the used types of cooperative activity. The work shows the main steps in the organization of the project. We have included the motives for work both of the teachers and the students. The present work shows the concrete advantages for the different age groups and the reflection on the parents, as well.

Branching Stochastic Processes: History, Theory, Applications

Косто В. Митов - Разклоняващите се стохастични процеси са модели на популационната динамика на обекти, които имат случайно време на живот и произвеждат потомци в съответствие с дадени вероятностни закони. Типични примери са ядрените реакции, клетъчната пролиферация, биологичното размножаване, някои химични реакции, икономически и финансови явления. В този обзор сме се опитали да представим съвсем накратко някои от най-важните моменти и факти от историята, теорията и приложенията на разклоняващите се процеси.

Maximal Number of Successors in a Nginar(1) Process

2000 Mathematics Subject Classification: 60J80, 60J20, 60J10, 60G10, 60G70, 60F99.

Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ

Differences in lipid metabolism associate with age-related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids (FAs) initiate pro-inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age-associated changes in individual FAs in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FAs by gas chromatography in 26 healthy younger individuals (age < 30 years) and 21 healthy FA individuals (age > 50 years). Linear mixed models were used to explore the association between circulating FAs, age and cytokines. We showed that plasma saturated, poly- and mono-unsaturated FAs increase with age. Circulating TNF-α and IL-6 concentrations increased with age, whereas IL-10 and TGF-β1 concentrations decreased. Oxidation of MitoSOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FAs, indicative of their metabolic relationships. Higher levels of the saturated FAs C18:0 and C24:0 were associated with lower TGF-β1 concentrations, and higher C16:0 were associated with higher TNF-α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro-inflammatory cytokines in response to phorbol myristate acetate-induced differentiation through ceramide-dependent inhibition of PPARγ activity. Conversely, C18:1 primed a pro-resolving macrophage which was PPARγ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti-inflammatory macrophages through metabolic reprogramming.

Limit Theorems for Maxima of Heavy-Tailed Terms with Random Dependent Weights

2000 Mathematics Subject Classification: Primary 60F17, 60G52, 60G70 secondary 60E07, 62E20.

Nonparametric Estimation in the Class of Bisexual Processes with Population-Size Dependent Mating

2000 Mathematics Subject Classification: 60J80, 62M05

A Computational Approach for the Statistical Estimation of Discrete Time Branching Processes with Immigration

2010 Mathematics Subject Classification: 60J80.

Lp Microlocal Supercritical Markov Branching Processes with Non-Homogeneous Poisson Immigration

2010 Mathematics Subject Classification: 60J80.

Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ

Differences in lipid metabolism associate with age-related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids (FAs) initiate pro-inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age-associated changes in individual FAs in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FAs by gas chromatography in 26 healthy younger individuals (age < 30 years) and 21 healthy FA individuals (age > 50 years). Linear mixed models were used to explore the association between circulating FAs, age and cytokines. We showed that plasma saturated, poly- and mono-unsaturated FAs increase with age. Circulating TNF-α and IL-6 concentrations increased with age, whereas IL-10 and TGF-β1 concentrations decreased. Oxidation of MitoSOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FAs, indicative of their metabolic relationships. Higher levels of the saturated FAs C18:0 and C24:0 were associated with lower TGF-β1 concentrations, and higher C16:0 were associated with higher TNF-α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro-inflammatory cytokines in response to phorbol myristate acetate-induced differentiation through ceramide-dependent inhibition of PPARγ activity. Conversely, C18:1 primed a pro-resolving macrophage which was PPARγ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti-inflammatory macrophages through metabolic reprogramming.

Multispectral retinal image analysis (MRIA) for the assessment of subretinal fibrosis in neovascular age-related macular degeneration (nAMD)

Purpose: To investigate the use of MRIA for quantitative characterisation of subretinal fibrosis secondary to nAMD. Methods: MRIA images of the posterior pole were acquired over 4 months from 20 eyes including those with inactive subretinal fibrosis and those being treated with ranibizumab for nAMD. Changes in morphology of the macula affected by nAMD were modelled and reflectance spectra at the MRIA acquisition wavelengths (507, 525, 552, 585, 596, 611 and 650nm) were computed using Monte Carlo simulation. Quantitative indicators of fibrosis were derived by matching image spectra to the model spectra of known morphological properties. Results: The model spectra were comparable to the image spectra, both normal and pathological. The key morphological changes that the model associated with nAMD were gliosis of the IS-OS junction, decrease in retinal blood and decrease in RPE melanin. However, these changes were not specific to fibrosis and none of the quantitative indicators showed a unique association with the degree of fibrosis. Moderate correlations were found with the clinical assessment, but not with the treatment program. Conclusion: MRIA can distinguish subretinal fibrosis from healthy tissue. The methods used show high sensitivity but low specificity, being unable to distinguish scarring from other abnormalities like atrophy. Quantification of scarring was not achieved with the wavelengths used due to the complex structural changes to retinal tissues in the process of nAMD. Further studies, incorporating other wavelengths, will establish whether MRIA has a role in the assessment of subretinal fibrosis in the context of retinal and choroidal pathology

Toward a scalable and consistent manufacturing process for the production of human MSCs

The development of novel, affordable and efficacious therapeutics will be necessary to ensure the continued progression in the standard of global healthcare. With the potential to address previously unmet patient needs as well as tackling the social and economic effects of chronic and age-related conditions, cell therapies will lead the new generation of healthcare products set to improve health and wealth across the globe. However, if many of the small to medium enterprises (SMEs) engaged in much of the commercialization efforts are to successfully traverse the ‘Valley of Death’ as they progress through clinical trials, there are a number of challenges that must be overcome. No longer do the challenges remain biological but rather a series of engineering and manufacturing issues must also be considered and addressed.

The political construction of old age as reflected in online discussions

The present paper examines the political construction of ageing and conflicts between generations. The process of construction is driven not merely by institutional actors and opinion leaders in the media, but also by citizens who talk to each other about politics. In my paper I have focused on the latter by observing online discussions that appear on the political forum Index.hu. Disagreement between old people’ and ‘young people’ evolved mainly about the pension system, thus the examination of ageing constructions is embedded in this context. In spite of its numerous limits, the method used seems to be suitable for providing hypotheses for further research. In the first part of the study I present the applied theoretical approach in which the concept of stereotype is connected with the concept of social construction. After that I focus on investigating the activity, origin and contents of the stereotypes that influence the construction of ageing. In the third part of the study the components of the constructions are demonstrated.

Assessing the effectiveness of the internationalization process in Higher Education Institutions: A case study of Florida International University

The purpose of this study was to examine a Higher Education Institution’s (HEI) process of internationalization. The theoretical model developed by Van Dijk and Miejer (1997) was used to review Florida International University (FIU)’s policy, support, and implementation dimensions and determine its position on the Internationalization Cube, and assess how FIU’s international activities fit into its different organizational processes. In addition, the study sought to shed light on student and faculty attitudes toward internationalization. Qualitative and quantitative data were collected from examining organizational documents, interviews, descriptive data on FIU’s international activities using the International Dimension Index, and the Student and Faculty Survey on Internationalization. FIU’s international activities results were analyzed in relation to a panel of experts’ item relevancy index. The Likert-type survey scales’ frequencies and percentages were calculated as well as Spearman Rho correlations between the survey’s three scales and demographic and experiences variables. The study found that FIU is located on position six of a possible eight positions on the Van Dijk and Meijer Internationalization Cube with the following characteristics: Priority Policy, One-Sided Support, and Structured Implementation toward internationalization. The analysis of FIU’s results on international activities showed that FIU exhibits all the activities considered to be strong indicators of internationalization but for position seven placement special attention is needed in the areas of foreign language study, international students, study abroad, faculty movement and involvement in international projects. The survey indicated students and faculty rated the Benefits of Internationalization highly but didn’t perceive strong institutional Support for Internationalization. Faculty age and offshore programs participation; student gender, race/ethnicity and class status; and for both, study abroad and knowledge of students travel grant had significant positive correlations with student and faculty attitudes. The study concluded that an association exists between FIU’s position on the Internationalization Cube and its international activities. Recommendations for policy, implementation, and future studies were made. It was concluded that advancing FIU’s position on the Cube will require adjustments in FIU’s policy, support and implementation dimensions. Differences in student and faculty views toward internationalization should be taken into account when planning internationalization efforts.

Left behind: A farmer's fate in the age of sustainable development

Globalization is eroding the livelihoods of small farmers, a significant and vulnerable class, particularly in the developing world. The cost-price squeeze stemming from trade liberalization places farmers in a race to the bottom that leads to displacement, poverty, and environmental degradation. Scholars and activists have proposed that alternative trade initiatives offer a unique opportunity to reverse this trend by harnessing the power of the markets to reward producers of goods with embedded superior cultural, environmental, and social values. Alternative trade via certification schemes have become a de facto prescription for any location where there is a need to conciliate economic interest with conservation imperatives. Partnerships among commodity production farmers, elite manufacturers and wealthy northern consumers/activists do not necessarily have win-win outcomes. Paradoxically, the partnerships of farmers with external agencies have unexpected results. These partnerships develop into dependent relationships that become unsustainable in the absence of further transfers of capital. The institutions born of these partnerships are fragile. When these fledging institutions fail, farmers are left in the same situation that they were before the partnership, with only minor improvements to show after spending considerable amounts of social and financial capital. I hypothesize that these failures are born out of a belief in a universal understanding of sustainability. A discursive emphasis on consensus, equity and mutual benefit hides the fact that what for consumers it is a matter of choice, for producers is a matter of survival. The growth in consumers’ demand for certified products creates a race for farmers to meet these standards. My findings suggest that this race generates economically perverse effects. First, producers enter into a certification treadmill. Second, the local need for economic sustainability is ignored. Third, commodity based alternative trade schemes increase the exposure of communities to global shocks. I conclude by calling for a careful reassessment of sustainable development projects that promote certification schemes. The designers and implementers of these programs must include farmers’ agenda in the planning of these programs.