Marked global reduction in mGluR5 receptor binding in smokers and ex-smokers determined by [11C]ABP688 positron emission tomography

Nicotine addiction is a major public health problem, resulting in primary glutamatergic dysfunction. We measured the glutamate receptor binding in the human brain and provided direct evidence for the abnormal glutamate system in smokers. Because antagonism of the metabotropic glutamate receptor 5 (mGluR5) reduced nicotine self-administration in rats and mice, mGluR5 is suggested to be involved in nicotine addiction. mGluR5 receptor binding specifically to an allosteric site was observed by using positron emission tomography with [(11)C]ABP688. We found a marked global reduction (20.6%; P < 0.0001) in the mGluR5 distribution volume ratio (DVR) in the gray matter of 14 smokers. The most prominent reductions were found in the bilateral medial orbitofrontal cortex. Compared with 14 nonsmokers, 14 ex-smokers had global reductions in the average gray matter mGluR5 DVR (11.5%; P < 0.005), and there was a significant difference in average gray matter mGluR5 DVR between smokers and ex-smokers (9.2%; P < 0.01). Clinical variables reflecting current nicotine consumption, dependence and abstinence were not correlated with mGluR5 DVR. This decrease in mGluR5 receptor binding may be an adaptation to chronic increases in glutamate induced by chronic nicotine administration, and the decreased down-regulation seen in the ex-smokers could be due to incomplete recovery of the receptors, especially because the ex-smokers were abstinent for only 25 wk on average. These results encourage the development and testing of drugs against addiction that directly target the glutamatergic system.

Methods and representativeness of a European survey in children and adolescents: the KIDSCREEN study

BACKGROUND: The objective of the present study was to compare three different sampling and questionnaire administration methods used in the international KIDSCREEN study in terms of participation, response rates, and external validity. METHODS: Children and adolescents aged 8-18 years were surveyed in 13 European countries using either telephone sampling and mail administration, random sampling of school listings followed by classroom or mail administration, or multistage random sampling of communities and households with self-administration of the survey materials at home. Cooperation, completion, and response rates were compared across countries and survey methods. Data on non-respondents was collected in 8 countries. The population fraction (PF, respondents in each sex-age, or educational level category, divided by the population in the same category from Eurostat census data) and population fraction ratio (PFR, ratio of PF) and their corresponding 95% confidence intervals were used to analyze differences by country between the KIDSCREEN samples and a reference Eurostat population. RESULTS: Response rates by country ranged from 18.9% to 91.2%. Response rates were highest in the school-based surveys (69.0%-91.2%). Sample proportions by age and gender were similar to the reference Eurostat population in most countries, although boys and adolescents were slightly underrepresented (PFR <1). Parents in lower educational categories were less likely to participate (PFR <1 in 5 countries). Parents in higher educational categories were overrepresented when the school and household sampling strategies were used (PFR = 1.78-2.97). CONCLUSION: School-based sampling achieved the highest overall response rates but also produced slightly more biased samples than the other methods. The results suggest that the samples were sufficiently representative to provide reference population values for the KIDSCREEN instrument.

Two-step postmortem angiography with a modified heart-lung machine: preliminary results

OBJECTIVE: The purpose of this study was to adapt and improve a minimally invasive two-step postmortem angiographic technique for use on human cadavers. Detailed mapping of the entire vascular system is almost impossible with conventional autopsy tools. The technique described should be valuable in the diagnosis of vascular abnormalities. MATERIALS AND METHODS: Postmortem perfusion with an oily liquid is established with a circulation machine. An oily contrast agent is introduced as a bolus injection, and radiographic imaging is performed. In this pilot study, the upper or lower extremities of four human cadavers were perfused. In two cases, the vascular system of a lower extremity was visualized with anterograde perfusion of the arteries. In the other two cases, in which the suspected cause of death was drug intoxication, the veins of an upper extremity were visualized with retrograde perfusion of the venous system. RESULTS: In each case, the vascular system was visualized up to the level of the small supplying and draining vessels. In three of the four cases, vascular abnormalities were found. In one instance, a venous injection mark engendered by the self-administration of drugs was rendered visible by exudation of the contrast agent. In the other two cases, occlusion of the arteries and veins was apparent. CONCLUSION: The method described is readily applicable to human cadavers. After establishment of postmortem perfusion with paraffin oil and injection of the oily contrast agent, the vascular system can be investigated in detail and vascular abnormalities rendered visible.

Schul-, Praxis- und habituelles Herrschaftswissen. Bildung ländlicher Eliten mit Blick auf die korporative Selbstverwaltung in der frühmodernen Schweiz (18. und 19. Jahrhundert)

Knowledge taught at schools, everyday skills and practical know-how. The relevancy of formation for local elites and the corporative self-government of Early Modern Switzerland Daniel Schläppi, Bern There were different kinds of rural elites in Early Modern Switzerland. The diverse parts of the country developed in very dissimilar ways politically and economically. Some regions were dominated by traditional types of agriculture. Some territories were ruled by major cities. In some of the rural Cantons like Uri, Schwyz, Unterwalden, Glarus and Zug a political elite took control over generations and practiced a cultural lifestyle comparable to the famous aristocracies in cities like Bern, Basel, Freiburg, Luzern, Solothurn and Zurich. Intense proto-industrialization formed a completely different sort of elite with strong affinities to industry and trade in other regions. Meanwhile the habitants of the valley close-by stayed farmers like their ancestors (like in Appenzell). In the most conservative parts of the country mercenary business played an important role till the very end of the Ancien Regime and even furthermore. In summery the variety of historical circumstances caused heterogeneous elites all over. Such socio-political diversity provoked a variety of educational backgrounds. I an academic understanding of the term we know only little about literacy in local rural elites. But there is strong evidence that a lively culture of reading and story-telling existed. This means that even simple countrymen seem to have been in possession of some books. The organisation and capacity of the school system is subject of controversial discussions among up to date researchers. The state of research makes us suppose that the people designed to political careers learned their essential skills not only in school but also in everyday life or on the job. Based on the fact that every community and countless public corporations managed their affairs by their own it’s evident that the local elite’s key-players had a large repertoire of techniques and skills like writing, calculating, strategic thinking or knowledge of oral tradition, old usage or important rituals. Unfortunately the historical actors left not that many sources that would tell us precisely how knowledge and know-how were transferred in former times. Hardly any private account books or common correspondence have been conserved. But a huge bunch of sources that originate from corporative self-administration shows us that most local elites were well-educated and had the necessary skills anyway. Above all other sources like for instance the «Topographische Beschreibungen» (topographic descriptions) that were initiated by the «Ökonomische Gesellschaft» of Berne since the sixties of the 18th century provide an insight into pre-modern classrooms. More important information on the historical formation-reality can be gained by the autobiography of the famous poor peasant Ulrich Bräker (1735‒1798) or some of the novels by Albert Bitzius (1797‒1854, better known as Jeremias Gotthelf). The pedagogic writings by Johann Heinrich Pestalozzi (1746‒1827) and the influences by his mentors Johann Rudolf Tschiffeli (1716‒1780) or Philipp Emanuel von Fellenberg (1771‒1884) are quite illustrative as well.

Use of modern and traditional products to self-treat symptoms of sexually transmitted infections in South African women

The objective of the study is to investigate products used by women self-treating symptoms of reproductive tract infections (RTIs), including sexually transmitted infections (STIs), and their methods of administration. A household survey using a multi-stage cluster sample design was undertaken in KwaZulu-Natal, South Africa. Women aged 18-60 years were interviewed (n = 867) and information was collected on demographics, reproductive health and sexual behaviours. A fifth of women reported having RTI/STI symptoms (20.5%), of whom 41.9% were treating these symptoms (mostly discharge [79.1%], ulcers [6.8%] and itching [7.7%]). Only three women were using medication prescribed by a health provider, while the remainder were self-treating using traditional medicines and modern products, including antiseptics, soaps, petroleum jelly, menthol creams and alum. Products were administered in various ways. Although RTI/STI treatment is widely available and free in public health facilities, many women are still self-treating. Potential harm of products for self-treatment requires further investigation and efforts should be made to improve STI service uptake.

ADAM: Administration and Deployment of Adhoc Mesh Networks

Costly on-site node repairs in wireless mesh networks (WMNs) can be required due to misconfiguration, corrupt software updates, or unavailability during updates. We propose ADAM as a novel management framework that guarantees accessibility of individual nodes in these situations. ADAM uses a decentralised distribution mechanism and self-healing mechanisms for safe configuration and software updates. In order to implement the ADAM management and self-healing mechanisms, an easy-to-learn and extendable build system for a small footprint embedded Linux distribution for WMNs has been developed. The paper presents the ADAM concept, the build system for the Linux distribution and the management architecture.