Pre-existing astrocytes form functional perisynaptic processes on neurons generated in the adult hippocampus.

The adult dentate gyrus produces new neurons that morphologically and functionally integrate into the hippocampal network. In the adult brain, most excitatory synapses are ensheathed by astrocytic perisynaptic processes that regulate synaptic structure and function. However, these processes are formed during embryonic or early postnatal development and it is unknown whether astrocytes can also ensheathe synapses of neurons born during adulthood and, if so, whether they play a role in their synaptic transmission. Here, we used a combination of serial-section immuno-electron microscopy, confocal microscopy, and electrophysiology to examine the formation of perisynaptic processes on adult-born neurons. We found that the afferent and efferent synapses of newborn neurons are ensheathed by astrocytic processes, irrespective of the age of the neurons or the size of their synapses. The quantification of gliogenesis and the distribution of astrocytic processes on synapses formed by adult-born neurons suggest that the majority of these processes are recruited from pre-existing astrocytes. Furthermore, the inhibition of astrocytic glutamate re-uptake significantly reduced postsynaptic currents and increased paired-pulse facilitation in adult-born neurons, suggesting that perisynaptic processes modulate synaptic transmission on these cells. Finally, some processes were found intercalated between newly formed dendritic spines and potential presynaptic partners, suggesting that they may also play a structural role in the connectivity of new spines. Together, these results indicate that pre-existing astrocytes remodel their processes to ensheathe synapses of adult-born neurons and participate to the functional and structural integration of these cells into the hippocampal network.

Amiodarone biokinetics, the formation of its major oxidative metabolite and neurotoxicity after acute and repeated exposure of brain cell cultures.

The difficulty in mimicking nervous system complexity and cell-cell interactions as well as the lack of kinetics information has limited the use of in vitro neurotoxicity data. Here, we assessed the biokinetic profile as well as the neurotoxicity of Amiodarone after acute and repeated exposure in two advanced rodent brain cell culture models, consisting of both neurons and glial cells organized in 2 or 3 dimensions to mimic the brain histiotypic structure and function. A strategy was applied to evidence the abiotic processes possibly affecting Amiodarone in vitro bioavailability, showing its ability to adsorb to the plastic devices. At clinically relevant Amiodarone concentrations, known to induce neurotoxicity in some patients during therapeutic treatment, a complete uptake was observed in both models in 24h, after single exposure. After repeated treatments, bioaccumulation was observed, especially in the 3D cell model, together with a greater alteration of neurotoxicity markers. After 14days, Amiodarone major oxidative metabolite (mono-N-desethylamiodarone) was detected at limited levels, indicating the presence of active drug metabolism enzymes (i.e. cytochrome P450) in both models. The assessment of biokinetics provides useful information on the relevance of in vitro toxicity data and should be considered in the design of an Integrated Testing Strategy aimed to identify specific neurotoxic alerts, and to improve the neurotoxicity assay predictivity for human acute and repeated exposure.

Sonographic diagnosis of carpal tunnel syndrome: a study in 200 hospital workers

AbstractObjective:To describe the prevalence of carpal tunnel syndrome in a sample of 200 healthy hospital workers, establishing the respective epidemiological associations.Materials and Methods:Two hundred individuals were submitted to wrist ultrasonography to measure the median nerve area. They were questioned and examined for epidemiological data, body mass index, carpal tunnel syndrome signs and symptoms, and submitted to the Boston carpal tunnel questionnaire (BCTQ) to evaluate the carpal tunnel syndrome severity. A median nerve area ≥ 9 mm2 was considered to be diagnostic of carpal tunnel syndrome.Results:Carpal tunnel syndrome was diagnosed by ultrasonography in 34% of the sample. It was observed the association of carpal tunnel syndrome with age (p < 0.0001), paresthesia (p < 0.0001), Tinel's test (p < 0.0001), Phalen's test (p< 0.0001), BCTQ score (p < 0.0001), and years of formal education (p < 0.0001). Years of formal education was the only variable identified as an independent risk factor for carpal tunnel syndrome (95% CI = 1.03 to 1.24).Conclusion:The prevalence of carpal tunnel syndrome in a population of hospital workers was of 34%. The number of years of formal education was the only independent risk factor for carpal tunnel syndrome.

An Explanatory Approach to the Political Uses of ICT Initiatives for Participation : Institutions, Context, and Characteristics of the Actors

Political actors use ICTs in a different manner and in different degrees when it comes to achieving a closer relationship between the public and politicians. Usually, political parties develop ICT strategies only for electoral campaigning and therefore restrain ICT usages to providing information and establishing a few channels of communication. By contrast, local governments make much more use of ICT tools for participatory and deliberative purposes. These differences in usages have not been well explained in the literature because of a lack of a comprehensive explanatory model. This chapter seeks to build the basis for this model, that is, to establish which factors affect and condition different political uses of ICTs and which principles underlie that behaviour. We consider that political actors are intentional and their behaviour is mediated by the political institutions and the socioeconomic context of the country. Also, though, the actor¿s own characteristics, such as the type and size of the organization or the model of e-democracy that the actor upholds, can have an influence in launching ICT initiatives for approaching the public.

Inhibition of nociceptive responses after systemic administration of amidated kyotorphin

BACKGROUND AND PURPOSE Kyotorphin (KTP; L-Tyr-L-Arg), an endogenous neuropeptide, is potently analgesic when delivered directly to the central nervous system. Its weak analgesic effects after systemic administration have been explained by inability to cross the blood-brain barrier (BBB) and detract from the possible clinical use of KTP as an analgesic. In this study, we aimed to increase the lipophilicity of KTP by amidation and to evaluate the analgesic efficacy of a new KTP derivative (KTP-amide - KTP-NH 2). EXPERIMENTAL APPROACH We synthesized KTP-NH 2. This peptide was given systemically to assess its ability to cross the BBB. A wide range of pain models, including acute, sustained and chronic inflammatory and neuropathic pain, were used to characterize analgesic efficacies of KTP-NH 2. Binding to opioid receptors and toxicity were also measured. KEY RESULTS KTP-NH 2, unlike its precursor KTP, was lipophilic and highly analgesic following systemic administration in several acute and chronic pain models, without inducing toxic effects or affecting motor responses and blood pressure. Binding to opioid receptors was minimal. KTP-NH 2 inhibited nociceptive responses of spinal neurons. Its analgesic effects were prevented by intrathecal or i.p. administration of naloxone. CONCLUSIONS AND IMPLICATIONS Amidation allowed KTP to show good analgesic ability after systemic delivery in acute and chronic pain models. The indirect opioid-mediated actions of KTP-NH 2 may explain why this compound retained its analgesic effects although the usual side effects of opioids were absent, which is a desired feature in next-generation pain medications

The Determinants of Entrepreneurship in Developing Countries

We address the question of what determines entrepreneurship in developing countries. In particular, because of the influence that this may have on the design of entrepreneurship policies, our main concern is whether the determinants of entrepreneurship are the same and/or have the same impact in developed and developing countries. To this end, we discuss the arguments put forward in the literature in support of the existence of differences in the determinants of entrepreneurship between developed and developing countries. We also analyse the results found in empirical studies on the determinants of formal firm entry (following the World Bank, our proxy of entrepreneurship) in developing countries and compare these results with those typically found in developed countries. Our main conclusion is that policy makers in developing economies should be careful when using evidence from developed countries to design entrepreneurship-promoting policies. Key words: entrepreneurship, developing countries. JEL: O1; O12; L26; M13

Implications, large and small, from chemical education research for the teaching of chemistry

Research studies in chemical education pose a communication problem for chemists. Unlike the findings from other specializations in chemistry the findings in chemical education tend to be reported in education journals that are not readily accessible to most chemists or chemistry teachers. This lecture is an attempt to remedy this gap in communication. Research studies fall into three broad categories. (i) issues related to the content of chemistry itself, that is, What content to teach? And What meaning of each topic is to be conveyed? (ii) issues related to how chemical content is taught, such as, the role of lectures, practical work, particular pedagogies, etc. and (iii) issues related to its learning, that is, learning of concepts, conceptual change, motivation, etc. Findings in each of these categories of research over the last twenty years have drawn attention to opportunities for improving the quality of chemical education in each of the levels of formal education where chemistry is taught. Sometimes the research findings seem small since they, in fact, merely diagnose the actual problem in teaching and learning. At other times, the research findings are large because they provide a solution to these problems. What remains to be done is to disseminate the findings so that appropriate teaching occurs more widely, with its consequent gains in the quality of learning. Research findings, of these small and large types will be used to illustrate the potential of research to make the practice of chemical education more effective.

Estudi sobre el perfil de persones grans amb dependència del servei d'ajuda a domicili del Consell Comarcal d'Osona i el tipus de suport formal i informal

The aim of this study is to determine the profile of dependent elderly people users of the home care services (SAD) of the regional council in Osona (Consell Comarcal d´Osona) , and the characteristics of formal and informal types of support they use. Methodology. An observational study of a transversal format has been carried out, with retrospective and descriptive purposes. The target population is 63 people (26 men and 37 women) included in the program of the regional SAD They have a recognized dependence grade approved by the law 39 /2006, December 14th , promoting the individual autonomy and care of elderly people in a dependent situation. The data were collected by social workers of basic social services, first with a home visit and followed by handed out questionnaires, specifically designed for this study, in order to obtain information on socio-demographic characteristics, and the type of support formal and informal. The obtained results on the SAD users are women in a 58.7% and a 41.3 % are men. The 84% of the total sampling are 80 years old and more, being the average age of 85.2 years old. 45% of them are married, 41% are widows and widowers and 14% are single. 54% are rated with severe dependence (grade II), 42.8% with high dependence (grade III). 86% live accompanied. 100% have an informal caregiver and a 95% of the times, the caregiver is a relative who in 73% of the cases the dedication time is permanent. The coverage of the SAD has an average of 4.27 hours per week and per user. The formal services most used are the technical (62%), also the assessment of an occupational therapist at home (57%) and the telecare service in a (56%). Conclusions. The SAD is used primarily for women in an advanced age and severe dependence. The informal assistance structures have an informal caregiver, being a member of the family mostly, living with the dependent, and mainly in a permanent dedication basis. The SAD has a varied intensity in each case. The formal support services complementary to the SAD, are largely used in all cases.

Formal and informal mechanisms for knowledge protection and sharing

The most important knowledge in firms is mostly tacit and embedded in individuals within the organization. This background knowledge that firms possess is used for creation of new knowledge and innovations. As firms today greatly concentrate on their core competencies, they need external knowledge from various collaboration partners. Thus, collaborative relationship governance, as well as control (use of appropriability mechanisms) over background (the input from each firm in innovative activities) and foreground knowledge (the output of collaboration activities) is needed in order to successfully create and capture value from innovative activities without losing core knowledge and competitiveness. Even though research has concentrated on knowledge protection and knowledge sharing, studies that combine both of these views and examine the effects of sharing and protection on value creation and capture have been rather limited. Studies have mainly focused on the protection of the output of innovation while forgetting the protection of the input of innovation. On the other hand, as the research concentrating on the output of innovation tends to favor formal mechanisms, informal mechanisms have remained more unknown to researchers as well as managers. This research aims to combine the perspectives of knowledge sharing and knowledge protection and their relationship with value creation and value capture. The sharing and protection are viewed from two points of view: the use of appropriability mechanisms, as well as governance of the collaborative relationship. The study consists of two parts. The first part introduces the research topic and discusses the overall results. The second part comprises six complementary research publications. Both qualitative and quantitative research methods are used in the study. In terms of results, the findings enhance understanding of the combined use of formal and informal mechanisms for knowledge protection and sharing. Informal mechanisms appear to be emphasized in the protection of background knowledge, and thus are prerequisites for innovation, whereas formal mechanisms are relied on more for protecting the results of innovative activities. However, the simultaneous use of the formal and informal mechanisms that are relevant to the particular industry and innovation context is recommendedthroughout the collaborative innovation process. Further, the study adds to the current knowledge on HRM as an appropriability mechanism: on the firm level its uses include assessing and hedging against employee-related risks such as knowledge leaking and knowledge leaving. A further contribution is to the research on HRM protection and its interrelations with other appropriability mechanisms, its constituents, and its potential use in the area of knowledge protection.

Developing markets of energy biomass – local and global perspectives

The thesis explores global and national-level issues related to the development of markets for biomass for energy. The thesis consists of five separate papers and provides insights on selected issues. The aim of Paper I was to identify methodological and statistical challenges in assessing international solid and liquid biofuels trade and provide an overview of the Finnish situation with respect to the status of international solid and liquid biofuels trade. We found that, for the Finnish case, it is possible to qualify direct and indirect trade volumes of biofuels. The study showed that indirect trade of biofuels has a highly significant role in Finland and may be a significant sector also in global biofuels trade. The purpose of Paper II was to provide a quantified insight into Finnish prospects for meeting the national 2020 renewable energy targets and concurrently becoming a largescale producer of forest-biomass-based second-generation biofuels for feeding increasing demand in European markets. We found that Finland has good opportunities to realise a scenario to meet 2020 renewable energy targets and for large-scale production of wood-based biofuels. The potential net export of transport biofuels from Finland in 2020 would correspond to 2–3% of European demand. Paper III summarises the global status of international solid and liquid biofuels trade as illuminated by several separate sources. International trade of biofuels was estimated at nearly 1 EJ for 2006. Indirect trade of biofuels through trading of industrial roundwood and material by-products comprises the largest proportion of the trading, with a share of about two thirds. The purpose of Paper IV was to outline a comprehensive picture of the coverage of various certification schemes and sustainability principles relating to the entire value-added chain of biomass and bioenergy. Regardless of the intensive work that has been done in the field of sustainability schemes and principles concerning use of biomass for energy, weaknesses still exist. The objective of Paper V was to clarify the alternative scenarios for the international biomass market until 2020 and identify the underlying steps needed toward a wellfunctioning and sustainable market for biomass for energy purposes. An overall conclusion drawn from this analysis concerns the enormous opportunities related to the utilisation of biomass for energy in the coming decades.

On the impact of rigorous approaches on the quality of development

Software systems are expanding and becoming increasingly present in everyday activities. The constantly evolving society demands that they deliver more functionality, are easy to use and work as expected. All these challenges increase the size and complexity of a system. People may not be aware of a presence of a software system, until it malfunctions or even fails to perform. The concept of being able to depend on the software is particularly significant when it comes to the critical systems. At this point quality of a system is regarded as an essential issue, since any deficiencies may lead to considerable money loss or life endangerment. Traditional development methods may not ensure a sufficiently high level of quality. Formal methods, on the other hand, allow us to achieve a high level of rigour and can be applied to develop a complete system or only a critical part of it. Such techniques, applied during system development starting at early design stages, increase the likelihood of obtaining a system that works as required. However, formal methods are sometimes considered difficult to utilise in traditional developments. Therefore, it is important to make them more accessible and reduce the gap between the formal and traditional development methods. This thesis explores the usability of rigorous approaches by giving an insight into formal designs with the use of graphical notation. The understandability of formal modelling is increased due to a compact representation of the development and related design decisions. The central objective of the thesis is to investigate the impact that rigorous approaches have on quality of developments. This means that it is necessary to establish certain techniques for evaluation of rigorous developments. Since we are studying various development settings and methods, specific measurement plans and a set of metrics need to be created for each setting. Our goal is to provide methods for collecting data and record evidence of the applicability of rigorous approaches. This would support the organisations in making decisions about integration of formal methods into their development processes. It is important to control the software development, especially in its initial stages. Therefore, we focus on the specification and modelling phases, as well as related artefacts, e.g. models. These have significant influence on the quality of a final system. Since application of formal methods may increase the complexity of a system, it may impact its maintainability, and thus quality. Our goal is to leverage quality of a system via metrics and measurements, as well as generic refinement patterns, which are applied to a model and a specification. We argue that they can facilitate the process of creating software systems, by e.g. controlling complexity and providing the modelling guidelines. Moreover, we find them as additional mechanisms for quality control and improvement, also for rigorous approaches. The main contribution of this thesis is to provide the metrics and measurements that help in assessing the impact of rigorous approaches on developments. We establish the techniques for the evaluation of certain aspects of quality, which are based on structural, syntactical and process related characteristics of an early-stage development artefacts, i.e. specifications and models. The presented approaches are applied to various case studies. The results of the investigation are juxtaposed with the perception of domain experts. It is our aspiration to promote measurements as an indispensable part of quality control process and a strategy towards the quality improvement.

Winning time in land warfare : a reading of the classical strategists prior to the age of mechanization

We live in an age where rationalization and demands of efficiency taint every aspect of our lives both as individuals and as a society. Even warfare cannot escape the increased speed of human interaction. Time is a resource to be managed. It has to be optimized, saved and won in military affairs as well. The purpose of this research paper is to analyze the dogmatic texts of military thought to search for answers what the classics of strategy saw in the interrelations of temporality and warfare and if their thoughts remain meaningful in the contemporary conjunction. Since the way a society functions is reflected in the way it conducts its wars, there naturally are differences between an agrarian, industrial and information society. Theorists of different eras emphasize things specific to their times, but warfare, like any human interaction, is always bounded by temporality. Not only is the pace of warfare dependent on the progress of the society, but time permeates warfare in all its aspects. This research paper focuses on two specific topics that arose from the texts themselves; how should time be managed and manipulated in warfare and how to economize and “win” it from the enemy. A method where lengthy quotations are used to illustrate the main point of the strategists has been chosen for this research paper. While Clausewitz is the most prominent source of quotations, thoughts from ancient India and China are represented as well to prove that the combination of right force in the right place at the right time is still the way of the victorious. Tactics change in the course of time but the principles of strategy remain unaltered and are only adapted to suit new situations. While ancient and pre-modern societies had their focus on finding auspicious moments for battle in the flow of kronos-time based on divinities, portents and auguries, we can trace elements of manipulation of time in warfare from the earliest surviving texts. While time as a fourth dimension of the battlespace emerged only in the modern era, all through the history of military thought it has had a profound meaning. In the past time could be squandered, today it always has to be won. This paper asks the question “why”.

Scheduling of guarded command based models

Formal methods provide a means of reasoning about computer programs in order to prove correctness criteria. One subtype of formal methods is based on the weakest precondition predicate transformer semantics and uses guarded commands as the basic modelling construct. Examples of such formalisms are Action Systems and Event-B. Guarded commands can intuitively be understood as actions that may be triggered when an associated guard condition holds. Guarded commands whose guards hold are nondeterministically chosen for execution, but no further control flow is present by default. Such a modelling approach is convenient for proving correctness, and the Refinement Calculus allows for a stepwise development method. It also has a parallel interpretation facilitating development of concurrent software, and it is suitable for describing event-driven scenarios. However, for many application areas, the execution paradigm traditionally used comprises more explicit control flow, which constitutes an obstacle for using the above mentioned formal methods. In this thesis, we study how guarded command based modelling approaches can be conveniently and efficiently scheduled in different scenarios. We first focus on the modelling of trust for transactions in a social networking setting. Due to the event-based nature of the scenario, the use of guarded commands turns out to be relatively straightforward. We continue by studying modelling of concurrent software, with particular focus on compute-intensive scenarios. We go from theoretical considerations to the feasibility of implementation by evaluating the performance and scalability of executing a case study model in parallel using automatic scheduling performed by a dedicated scheduler. Finally, we propose a more explicit and non-centralised approach in which the flow of each task is controlled by a schedule of its own. The schedules are expressed in a dedicated scheduling language, and patterns assist the developer in proving correctness of the scheduled model with respect to the original one.

Theorizing Formal and Informal Feedback Practices in Management Accounting Through Three Dimensions

The purpose of this doctoral thesis is to widen and develop our theoretical frameworks for discussion and analyses of feedback practices in management accounting, particularly shedding light on its formal and informal aspects. The concept of feedback in management accounting has conventionally been analyzed within cybernetic control theory, in which feedback flows as a diagnostic or comparative loop between measurable outputs and pre-set goals (see e.g. Flamholtz et al. 1985; Flamholtz 1996, 1983), i.e. as a formal feedback loop. However, the everyday feedback practices in organizations are combinations of formal and informal elements. In addition to technique-driven feedback approaches (like budgets, measurement, and reward systems) we could also categorize social feedback practices that managers see relevant and effective in the pursuit of organizational control. While cybernetics or control theories successfully capture rational and measured aspects of organizational performance and offer a broad organizational context for the analysis, many individual and informal aspects remain vague and isolated. In order to discuss and make sense of the heterogeneous field of interpretations of formal and informal feedback, both in theory and practice, dichotomous approaches seem to be insufficient. Therefore, I suggest an analytical framework of formal and informal feedback with three dimensions (3D’s): source, time, and rule. Based on an abductive analysis of the theoretical and empirical findings from an interpretive case study around a business unit called Division Steelco, the 3Dframework and formal and informal feedback practices are further elaborated vis-á-vis the four thematic layers in the organizational control model by Flamholtz et al. (1985; Flamholtz 1996, 1983): core control system, organizational structure, organizational culture, and external environment. Various personal and cultural meanings given to the formal and informal feedback practices (“feedback as something”) create multidimensional interpretative contexts. Multidimensional frameworks aim to capture and better understand both the variety of interpretations and their implications to the functionality of feedback practices, important in interpretive research.

Effects of infection with Toxoplasma gondii oocysts on the intestinal wall and the myenteric plexus of chicken (Gallus gallus)

This paper aims to analyze the effects of the Toxoplasma gondii infection in the intestinal wall and myenteric plexus of chicken (Gallus gallus). Ten 36-day-old chickens were separated into two groups: control and experimental, orally inoculated with oocysts of the T. gondii strain M7741 genotype III. After 60 days the birds were submitted to euthanasia and had their duodenum removed. Part of the intestinal segments was submitted to histological routine, HE staining, PAS histochemical technique, and Alcian Blue. Qualitative analysis of the intestinal wall and comparative measurements among the groups with respect to total wall thickness, muscle tunic, mucosa, and tunica mucosa were carried out. Caliciform cells were quantified. The other part of the intestinal segments was fixed in formol acetic acid and dissected having the tunica mucosa and the tela submucosa removed. Neurons were stained with Giemsa, counted, and measured. Chickens from the experimental group presented diarrhea and inflammatory infiltrates in the tunica mucosa, thickness reduction of all the parameters assessed in the intestinal wall, and an increase of the number of caliciform cells. There was a ~70% reduction regarding the intensity of myenteric neurons; and the remaining cells presented a reduction of ~2.4% of the perikarion and ~40.5% of the nucleus (p<0.05). Chronic infection induced by T. gondii oocysts resulted in intestinal wall atrophy, mucin secretion increase, death and atrophy of chicken myenteric plexus neurons. Death and atrophy of myenteric plexus neurons may be related with the causes of diarrhea observed in chickens with toxoplasmosis.