Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke

Each year about 650,000 Europeans die from stroke and a similar number lives with the sequelae of multiple sclerosis (MS). Stroke and MS differ in their etiology. Although cause and likewise clinical presentation set the two diseases apart, they share common downstream mechanisms that lead to damage and recovery. Demyelination and axonal injury are characteristics of MS but are also observed in stroke. Conversely, hallmarks of stroke, such as vascular impairment and neurodegeneration, are found in MS. However, the most conspicuous common feature is the marked neuroinflammatory response, marked by glia cell activation and immune cell influx. In MS and stroke the blood-brain barrier is disrupted allowing bone marrow-derived macrophages to invade the brain in support of the resident microglia. In addition, there is a massive invasion of auto-reactive T-cells into the brain of patients with MS. Though less pronounced a similar phenomenon is also found in ischemic lesions. Not surprisingly, the two diseases also resemble each other at the level of gene expression and the biosynthesis of other proinflammatory mediators. While MS has traditionally been considered to be an autoimmune neuroinflammatory disorder, the role of inflammation for cerebral ischemia has only been recognized later. In the case of MS the long track record as neuroinflammatory disease has paid off with respect to treatment options. There are now about a dozen of approved drugs for the treatment of MS that specifically target neuroinflammation by modulating the immune system. Interestingly, experimental work demonstrated that drugs that are in routine use to mitigate neuroinflammation in MS may also work in stroke models. Examples include Fingolimod, glatiramer acetate, and antibodies blocking the leukocyte integrin VLA-4. Moreover, therapeutic strategies that were discovered in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, turned out to be also effective in experimental stroke models. This suggests that previous achievements in MS research may be relevant for stroke. Interestingly, the converse is equally true. Concepts on the neurovascular unit that were developed in a stroke context turned out to be applicable to neuroinflammatory research in MS. Examples include work on the important role of the vascular basement membrane and the BBB for the invasion of immune cells into the brain. Furthermore, tissue plasminogen activator (tPA), the only established drug treatment in acute stroke, modulates the pathogenesis of MS. Endogenous tPA is released from endothelium and astroglia and acts on the BBB, microglia and other neuroinflammatory cells. Thus, the vascular perspective of stroke research provides important input into the mechanisms on how endothelial cells and the BBB regulate inflammation in MS, particularly the invasion of immune cells into the CNS. In the current review we will first discuss pathogenesis of both diseases and current treatment regimens and will provide a detailed overview on pathways of immune cell migration across the barriers of the CNS and the role of activated astrocytes in this process. This article is part of a Special Issue entitled: Neuro inflammation: A common denominator for stroke, multiple sclerosis and Alzheimer's disease, guest edited by Helga de Vries and Markus Swaninger.

A novel colourimetric technique to assess chewing function using two-coloured specimens: Validation and application

OBJECTIVES Chewing efficiency may be evaluated using cohesive specimen, especially in elderly or dysphagic patients. The aim of this study was to evaluate three two-coloured chewing gums for a colour-mixing ability test and to validate a new purpose built software (ViewGum©). METHODS Dentate participants (dentate-group) and edentulous patients with mandibular two-implant overdentures (IOD-group) were recruited. First, the dentate-group chewed three different types of two-coloured gum (gum1-gum3) for 5, 10, 20, 30 and 50 chewing cycles. Subsequently the number of chewing cycles with the highest intra- and inter-rater agreement was determined visually by applying a scale (SA) and opto-electronically (ViewGum©, Bland-Altman analysis). The ViewGum© software determines semi-automatically the variance of hue (VOH); inadequate mixing presents with larger VOH than complete mixing. Secondly, the dentate-group and the IOD-group were compared. RESULTS The dentate-group comprised 20 participants (10 female, 30.3±6.7 years); the IOD-group 15 participants (10 female, 74.6±8.3 years). Intra-rater and inter-rater agreement (SA) was very high at 20 chewing cycles (95.00-98.75%). Gums 1-3 showed different colour-mixing characteristics as a function of chewing cycles, gum1 showed a logarithmic association; gum2 and gum3 demonstrated more linear behaviours. However, the number of chewing cycles could be predicted in all specimens from VOH (all p<0.0001, mixed linear regression models). Both analyses proved discriminative to the dental state. CONCLUSION ViewGum© proved to be a reliable and discriminative tool to opto-electronically assess chewing efficiency, given an elastic specimen is chewed for 20 cycles and could be recommended for the evaluation of chewing efficiency in a clinical and research setting. CLINICAL SIGNIFICANCE Chewing is a complex function of the oro-facial structures and the central nervous system. The application of the proposed assessments of the chewing function in geriatrics or special care dentistry could help visualising oro-functional or dental comorbidities in dysphagic patients or those suffering from protein-energy malnutrition.

Von Recht der Juden : Worinnen von denen Gesetzen, denen sie unterworffen, deren Heyrathen, Contracten, Wucher, Testamenten, Successionen oder Erbfolgen ... gründlich und deutlich gehandelt wird ; Aus denen Göttlichen und allgemeinen Reichs- und andern Special-Rechten und Gewohnheiten zusammen getragen, und mit Præjudiciis, Decisionibus und Responsis, überall bestärcket ; Denen Richtern, Amtleuten ... mit einem hierzu dienlichen Register versehen

hrsg. von Joh. Jodoco Beck

Entsetzlicher Sonnen-Stand, in dem Schwedischen Norder-Land : Welches von glaubwürdiger Hand, aus der Königlichen Residenz-Stadt Stockholm daselbst, an unterschiedliche Special-Freunde in Teutschland ist berichtet worden .̤

Original hat Fehlstelle rechts unten, Textverlust

The astrological works of Abraham Ibn Ezra : a literary and linguistic study with special reference to the Old French translation of Hagin

by Raphael Levy

NONLINEAR TIME SERIES/SYSTEM ANALYSIS (STATE-SPACE, DYNAMICS, INTERVENTION, RESILIENCE, KALMAN)

A discussion of nonlinear dynamics, demonstrated by the familiar automobile, is followed by the development of a systematic method of analysis of a possibly nonlinear time series using difference equations in the general state-space format. This format allows recursive state-dependent parameter estimation after each observation thereby revealing the dynamics inherent in the system in combination with random external perturbations.^ The one-step ahead prediction errors at each time period, transformed to have constant variance, and the estimated parametric sequences provide the information to (1) formally test whether time series observations y(,t) are some linear function of random errors (ELEM)(,s), for some t and s, or whether the series would more appropriately be described by a nonlinear model such as bilinear, exponential, threshold, etc., (2) formally test whether a statistically significant change has occurred in structure/level either historically or as it occurs, (3) forecast nonlinear system with a new and innovative (but very old numerical) technique utilizing rational functions to extrapolate individual parameters as smooth functions of time which are then combined to obtain the forecast of y and (4) suggest a measure of resilience, i.e. how much perturbation a structure/level can tolerate, whether internal or external to the system, and remain statistically unchanged. Although similar to one-step control, this provides a less rigid way to think about changes affecting social systems.^ Applications consisting of the analysis of some familiar and some simulated series demonstrate the procedure. Empirical results suggest that this state-space or modified augmented Kalman filter may provide interesting ways to identify particular kinds of nonlinearities as they occur in structural change via the state trajectory.^ A computational flow-chart detailing computations and software input and output is provided in the body of the text. IBM Advanced BASIC program listings to accomplish most of the analysis are provided in the appendix. ^

Using spatial linear models with SAR and CAR structure to examine Texas lung cancer incidence rates

Scholars have found that socioeconomic status was one of the key factors that influenced early-stage lung cancer incidence rates in a variety of regions. This thesis examined the association between median household income and lung cancer incidence rates in Texas counties. A total of 254 individual counties in Texas with corresponding lung cancer incidence rates from 2004 to 2008 and median household incomes in 2006 were collected from the National Cancer Institute Surveillance System. A simple linear model and spatial linear models with two structures, Simultaneous Autoregressive Structure (SAR) and Conditional Autoregressive Structure (CAR), were used to link median household income and lung cancer incidence rates in Texas. The residuals of the spatial linear models were analyzed with Moran's I and Geary's C statistics, and the statistical results were used to detect similar lung cancer incidence rate clusters and disease patterns in Texas.^

Targeting Special Populations for Family Preservation: The Influence of Worker Competence and Organizational Culture

Today there are approximately 581,000 children in the United States foster care system. Children of color, one special population group, are disproportionately represented in the foster care system. Family preservation, a program that aims to improve family functioning and thus decrease the need for foster care, has been examined closely. Some researchers believe that family preservation programs have failed partly due to practitioners' inability to target appropriate families (Feldman, 1990; Schuerman, Rzepnicki & Littell, 1994). Additionally, research confirms that children of color are not the target of family preservation services (Denby, Curtis, & Alford, 1998). Improvements in the effectiveness of family preservation will require many types of reform both internal and external to the program. Among the types of internal reform needed is accurate "targeting of services. " Given the overrepresentation of children of color in the foster care system, this group must be among those who are targeted for services. The results of a national survey of 254 family preservation workers reveal a "profile" of the worker who is likely to target special populations, including children of color, for family preservation services. A case is made for service improvements and training to facilitate the "profiled" workers' competencies.

Distribution of organic-walled dinoflagellate cysts in surface sediments of the Benguela upwelling system

To obtain insight in the relationship between the spatial distribution of organic-walled dinoflagellate cysts (dinocysts) and local environmental conditions, fifty-eight surface sediment samples from the coastal shelf off SW Africa were investigated on their dinocyst content with special focus on the two main river systems and the active upwelling that characterise this region. To avoid possible overprint by species-selective preservation, samples have been selected mainly from shelf sites where high sedimentation rates and/or low bottom water oxygen concentrations prevail. Multivariate ordination analyses have been carried out to investigate the relationship between the distribution patterns of individual species to environmental parameters of the upper water column and sediment transport processes. The main oceanographical variables at the surface (temperature, salinity, nutrients chlorophyll-a) in the region show onshore-offshore gradients. This pattern is reflected in the dinocyst associations with high relative abundances of heterotrophic dinocyst species in neritic regions characterised by high chlorophyll-aand low salinity conditions in surface waters. Phototrophic dinocyst species, notably Operculodinium centrocarpum, dominate in the more oceanic area. Differences in the distribution of phototrophic dinocyst species can be related to sea surface salinity and sea surface temperature gradients and to a lesser extent to chlorophyll-a concentrations. Apart from longitudinal gradients the dinocyst distribution clearly reflects regional environmental features. Six groups of species can be distinguished, characteristic for (1) coastal regions (cysts of Polykrikos kofoidii and Selenopemphix quanta), (2) the vicinity of active upwelling (Brigantedinium spp., Echinidinium aculeatum, Echinidinium spp. and Echinidinium transparantum), (3) river mouths (Lejeunecysta oliva, cysts of Protoperidinium americanum, Selenopemphix nephroides and Votadinium calvum), (4) slope and open ocean sediments (Dalella chathamense, Impagidinium patulum and Operculodinium centrocarpum, (5) the southern Benguela region (south of 24°S) (Spiniferites ramosus) and (6) the northern Benguela region (north of 24°S) (Nematosphaeropsis labyrinthus and Pyxidinopsis reticulata). No indication of overprint of the palaeo-ecological signal by lateral transport of allochthonous species could be observed.

Seawater carbonate chemistry, shell linear extension and calcification during calcein staining and 45Ca experiments with pteropod Limacina helicina, 2009

Thecosome pteropods (shelled pelagic molluscs) can play an important role in the food web of various ecosystems and play a key role in the cycling of carbon and carbonate. Since they harbor an aragonitic shell, they could be very sensitive to ocean acidification driven by the increase of anthropogenic CO2 emissions. The impact of changes in the carbonate chemistry was investigated on Limacina helicina, a key species of Arctic ecosystems. Pteropods were kept in culture under controlled pH conditions corresponding to pCO2 levels of 350 and 760 µatm. Calcification was estimated using a fluorochrome and the radioisotope 45Ca. It exhibits a 28 % decrease at the pH value expected for 2100 compared to the present pH value. This result supports the concern for the future of pteropods in a high-CO2 world, as well as of those species dependent upon them as a food resource. A decline of their populations would likely cause dramatic changes to the structure, function and services of polar ecosystems.

Normative Influences of "Special and Differential Treatment" on North-South RTAs

Recently, there has been a surge in bilateral and regional trade arrangements between developed and developing countries, which are known as North-South RTAs. Under the current legal system of the WTO, North-South RTAs are governed by Article XXIV of the GATT or Article V of the GATS, which means such RTAs must be reciprocal and must cover substantially all the trade. On the other hand, there is another category of rules on RTAs based on the so-called Enabling Clause, which, in exceptional circumstances, provides special and differential treatment (SDT) for RTAs among developing countries. This paper considers the applicability of the SDT concept to North-South RTAs by examining why rules on RTAs and the concept of SDT were incorporated into the GATT/WTO legal framework so as to permit the derogation of most-favored-nation (MFN) obligations.

Regional differences regarding land tenancy in rural Rwanda, with special reference to sharecropping in a coffee production area

This paper examines land tenancy systems and tenant contracts in Rwanda, with respect to socioeconomic contexts. Our research in southern and eastern Rwanda produced data suggesting that land borrowing with fixed rents has been generally practiced, and that rent levels have been low in comparison to expected revenues from field production. In the western areas of coffee production, however, the practice of sharecropping has recently appeared. This system is advantageous to landowners, as they are able to acquire half of the harvests; in addition, the fixed rent levels in this region are much higher than those of other regions. In the southern and eastern regions, because land borrowing with fixed rents has been the only tenancy pattern and rent levels have remained low, the economic situation should be interpreted in the context of a continuing traditional Rwandan land tenure system. In contrast, in the western coffee production area, the soaring of fixed rents and the emergence of sharecropping have been brought about by high pressures for land use, which were caused not only by a population increase but also by the development of cash crop production and the existence of a labor exchange system. The increase in rent levels has therefore been offset by a corresponding increase in agricultural productivity.