Stereology meets electron tomography: towards quantitative 3D electron microscopy

Stereological tools are the gold standard for accurate (i.e., unbiased) and precise quantification of any microscopic sample. The past decades have provided a broad spectrum of tools to estimate a variety of parameters such as volumes, surfaces, lengths, and numbers. Some of them require pairs of parallel sections that can be produced by either physical or optical sectioning, with optical sectioning being much more efficient when applicable. Unfortunately, transmission electron microscopy could not fully profit from these riches, mainly because of the large depth of field. Hence, optical sectioning was a long-time desire for electron microscopists. This desire was fulfilled with the development of electron tomography that yield stacks of slices from electron microscopic sections. Now, parallel optical slices of a previously unimagined small thickness (2-5 nm axial resolution) can be produced. These optical slices minimize problems related to overprojection effects, and allow for direct stereological analysis, e.g., volume estimation with the Cavalieri principle and number estimation with the optical disector method. Here, we demonstrate that the symbiosis of stereology and electron tomography is an easy and efficient way for quantitative analysis at the electron microscopic level. We call this approach quantitative 3D electron microscopy.

Reprint of "Stereology meets electron tomography: towards quantitative 3D electron microscopy" [J. Struct. Biol. 159 (2007) 443-450]

Stereological tools are the gold standard for accurate (i.e., unbiased) and precise quantification of any microscopic sample. The past decades have provided a broad spectrum of tools to estimate a variety of parameters such as volumes, surfaces, lengths, and numbers. Some of them require pairs of parallel sections that can be produced by either physical or optical sectioning, with optical sectioning being much more efficient when applicable. Unfortunately, transmission electron microscopy could not fully profit from these riches, mainly because of the large depth of field. Hence, optical sectioning was a long-time desire for electron microscopists. This desire was fulfilled with the development of electron tomography that yield stacks of slices from electron microscopic sections. Now, parallel optical slices of a previously unimagined small thickness (2-5nm axial resolution) can be produced. These optical slices minimize problems related to overprojection effects, and allow for direct stereological analysis, e.g., volume estimation with the Cavalieri principle and number estimation with the optical disector method. Here, we demonstrate that the symbiosis of stereology and electron tomography is an easy and efficient way for quantitative analysis at the electron microscopic level. We call this approach quantitative 3D electron microscopy.

Updated method guidelines for cochrane musculoskeletal group systematic reviews and metaanalyses.

The Cochrane Musculoskeletal Group (CMSG), one of 53 groups of the not-for-profit, international Cochrane Collaboration, prepares, maintains, and disseminates systematic reviews of treatments for musculoskeletal diseases. It is important that authors conducting CMSG reviews and the readers of our reviews be aware of and use updated, state-of-the-art systematic review methodology. One hundred sixty reviews have been published. Previous method guidelines for systematic reviews of interventions in the musculoskeletal field published in 2006 have been substantially updated to incorporate methodological advances that are mandatory or highly desirable in Cochrane reviews and knowledge translation advances. The methodological advances include new guidance on searching, new risk-of-bias assessment, grading the quality of the evidence, the new Summary of Findings table, and comparative effectiveness using network metaanalysis. Method guidelines specific to musculoskeletal disorders are provided by CMSG editors for various aspects of undertaking a systematic review. These method guidelines will help improve the quality of reporting and ensure high standards of conduct as well as consistency across CMSG reviews.

Decision-Making Processes in Voluntary Football Clubs in Relation to External Counselling

Introduction Recruiting and retaining volunteers who are prepared to make a long-term commitment is a major problem for Swiss sports clubs. With the inclusion of external counselling for the change and systematisation of volunteer management, sports clubs have a possibility to develop and defuse problems in spite of existing barriers and gaps in knowledge. To what extent is external counselling for personnel problems effective? It is often observed that standardised counselling inputs lead to varying consequences for sports clubs. It can be assumed that external impulses are interpreted and transformed differently into the workings of the club. However, this cannot be solely attributed to the situational or structural conditions of the clubs. It is also important to consider the underlying decision-making processes of a club. According to Luhmann’s organisational sociological considerations (2000), organisations (sports clubs) have to be viewed as social systems consisting of (communicated) decisions. This means that organisations are continually reproduced by decision-making processes. All other (observable) factors such as an organisation’s goals, recruiting strategies, support schemes for volunteers etc., have to be seen as an outcome of the operation of prior organisational decisions. Therefore: How do decision-making processes in sports clubs work in the context of the implementation of external counselling? Theoretical Framework An examination of the actual situation in sports clubs shows that decisions frequently appear to be shaped by inconsistency, unexpected outcomes, and randomness (Amis & Slack, 2003). Therefore, it must be emphasised that these decisions cannot be analysed according to any rational decision-making model. Their specific structural characteristics only permit a limited degree of rationality – bounded rationality. Non-profit organisations in particular are shaped by a specific mode of decisionmaking that Cohen, March, and Olsen (1972) have called the “garbage can model”. As sport clubs can also be conceived as “organised anarchies”, this model seems to offer an appropriate approach to understanding their practices and analysing their decision-making processes. The key concept in the garbage can model is the assumption that decision-making processes in organisations consist of four “streams”: (a) problems, (b) actors, (c) decision-making opportunities, and (d) solutions. Method Before presenting the method of the analysis of the decision-making processes in sports clubs, the external counselling will be described. The basis of the counselling is generated by a sports clubs’ capability to change. Due to the specific structural characteristics and organisational principles, change processes in sports clubs often merge with barriers and restrictions. These need to be considered when developing counselling guidelines for a successful planning and realisation of change processes. Furthermore, important aspects of personnel management in sports clubs and especially volunteer management must be implied in order to elaborate key elements for the counselling to recruit new volunteers (e.g., approach, expectations). A counselling of four system-counselling workshops was conceptualised by considering these specific characteristics. The decision-making processes in the sports clubs were analysed during the counselling and the implementation process. A case study is designed with the appropriate methodological approach for such explorative research. The approach adopted for these single case analyses was oriented toward the research program of behavioural decision-making theory (garbage can model). This posits that in-depth insights into organisational decision-making processes can only be gained through relevant case studies of existing organisational situations (Skille, 2013). Before, during and after the intervention, questionnaires and guided interviews were conducted with the project teams of the twelve par-ticipating football clubs to assess the different components of the “streams” in the context of external counselling. These interviews have been analysed using content analysis following guidelines as for-mulated by Mayring (2010). Results The findings show that decision-making processes in football clubs occur differently in the context of external counselling. Different initial positions and problems are the triggers for these decision-making processes. Furthermore, the implementation of the solutions and the external counselling is highly dependent on the commitment of certain people as central players within the decision-mak-ing process. The importance of these relationships is confirmed by previous findings in regard to decision-making and change processes in sports clubs. The decision-making processes in sports clubs can be theoretically analysed using behavioural decision-making theory and the “garbage can model”. Bounded rationality characterises all “streams” of the decision-making processes. Moreo-ver, the decision-making process of the football clubs can be well illustrated in the framework, and the interplay of the different dimensions illustrates the different decision-making practices within the football clubs. References Amis, J., & Slack, T. (2003). Analysing sports organisations: Theory and practice. In B. Houlihan (Eds.), Sport & Society (pp. 201–217). London, England: Sage. Cohen, M.D., March, J.G., & Olsen, J.P. (1972). A garbage can model of organisational choice. Ad-ministrative Science Quarterly, 17, 1-25. Luhmann, N. (2000). Organisation und Entscheidung. Opladen: Westdeutscher Verlag. Mayring, P. (2010). Qualitative Inhaltsanalyse. Grundlagen und Techniken. Weinheim: Beltz. Skille, E. Å. (2013). Case study research in sport management: A reflection upon the theory of science and an empirical example. In S. Söderman & H. Dolles (Eds.), Handbook of research on sport and business (pp. 161–175). Cheltenham, England: Edward Elgar.

Diazepam versus fentanyl for premedication during percutaneous coronary intervention: results from the Myocardial Protection by Fentanyl during Coronary Intervention (PROFIT) Trial

BACKGROUND: Sedation is a cornerstone in the premedication for percutaneous coronary intervention (PCI). Benzodiazepines and opioids are frequently used. Previous results suggest that opioids mimic the adaptation to ischemia during repeated balloon inflations and may provide direct myocardial protection in addition to their sedative effect. However, no comparative data exist. METHODS: We conducted a prospective, randomized, controlled, single-blind trial comparing diazepam and fentanyl in 276 patients undergoing elective PCI. Patients were randomized to either diazepam 5 mg sublingually or fentanyl 0.05 mg or 0.1 mg intravenously at least 5 minutes prior to the first balloon inflation. The primary end-point was the postprocedural elevation of myocardial markers of necrosis defined as an elevation of cardiac troponin T > or = 0.01 ng/ml. RESULTS: The three groups had similar baseline clinical, angiographic, and procedural characteristics, with no significant differences in lesion morphology, procedural complexity, or adjunctive medical treatment. No significant variation in the hemodynamic response to the study drugs was observed in the three groups. The rate of postprocedural troponin T elevation was 28% in the diazepam group, 20% in the fentanyl 0.05 mg group, and 30% in the fentanyl 0.1 mg group (P = 0.26). Rates of postprocedural myocardial infarction were 3%, 2%, and 2%, respectively (P = 0.84), with one case of in-hospital death in the diazepam group and no urgent TVR in the whole study population. CONCLUSION: Although providing a well-tolerated alternative to diazepam for sedation during PCI, fentanyl did not provide additional cardioprotection assessed through the postinterventional elevation of cardiac troponin T during elective coronary intervention.

One size does not fit all: Entrepreneurial families’ reliance on family offices

Family offices are organisations dedicated to the management of entrepreneurial families’ private wealth. Based on agency theory, we analyse types of family offices with regard to the families’ goals and the control mechanisms used to ensure goal achievement. Family-dominant management and private client structures involve stronger emphasis on non-financial goals in single and multi-family offices than in non-family-dominant management and open client structures. Variations in family involvement, ranging from family dominance to the complete absence of family ownership and/or management, and diverse client structures justify the differential reliance on formal and informal control mechanisms.

Architektura a ideologie. Výchovné instituce Adolfa Hitlera v protektorátu Čechy a Morava a v Říšské župě Sudety

This article examines the architecture of the Nazi regime in two occupied cities of Czechoslovakia, Praha/Prag and Jihlava/Iglau (the latter being one of the traditionally German-speaking island in the bohemia country), and focuses specifically on the process by which Hitler youth organisations (Hitlerjugend) in case of ‘education’ and indoctrination of youth were or were not successfully established in these cities. As comparison, he takes the political-administrative centres of the Sudeten Reichsgau, Ústí/Aussig, Opava/Troppau, Karlovy Vary/Karlsbad and Liberec/Reichenberg. Drawing on Czech and German archive materials, the extensive body of modern analytical literature, and propagandist literature from the period studied, the author examines the extent to which architecture served as a projection screen for Fascist propaganda in the Occupied Eastern territories. He describes the role played by the Reichsstelle für Raumordnung and shows how the Reich’s propagandist objectives came to be reflected in a high specific typology and stylistic lexicon/configuration for the architecture of Hitler youth hostels and homes He examines the process by which these organisations were powerful implanted into the space of occupied Czechoslovakia (and Sudeten) too, a topic that has not yet been addressed in (art) history too. The building projects developed for the Protectorate (published here for the first time) and managed by the Reich’s Hitler Youth Leadership in Berlin (Kulturamt, Reichsjugendführung, RJF, Abteilung HJ) reveal the ties that existed between the construction authorities in the Reich and the Protectorate, including the Planning Committee for the City of Prague. The author asks how many German and Czech architects participated for their own profit in the Nazi system, and for future research raises the hitherto taboo question of guilt and collaboration with the Nazis and the perception of this phenomenon in art history, i.e. the measure of active cooperation of not just German but also Czech architects who contributed to the planning and implementation of projects and thereby unequivocally had a hand in consolidating the totalitarian regime and de facto in the forced „Germanification” of their own people under occupation.

CAP Reform vs WTO: Crop Diversification or Crop Rotation? : Legal opinion prepared by Dr. Christian Häberli at the request of APRODEV, the Association of World Council of Churches related Development Organisations in Europe

The European Commission’s proposals for the Legislative Framework of the Common Agricultural Policy (CAP) in the period 2014-2020 include, inter alia, the introduction of a “strong greening component”. For the first time, all EU farmers in receipt of support are to “go beyond the requirements of cross compliance and deliver environmental and climate benefits as part of their everyday activities crop diversification as a contribution to all EU farmers in receipt of support go beyond the requirements of cross compliance and deliver environmental and climate benefits as part of their everyday activities.” In a legal opinion prepared at the request of APRODEV, the Association of World Council of Churches related Development Organisations in Europe (www.aprodev.eu), Christian Häberli examines the WTO implications of this proposal, as compared with an alternative proposal to rather link direct payments to crop rotation. The conclusions are twofold: 1. Crop rotation is at least as likely to be found Green Box-compatible as crop diversification. Moreover, it will be more difficult to argue that crop diversification is “not more than minimally production-distorting” because it entails for most farmers less cost and work. 2. Even if (either of the two cropping schemes) were to be found “amber”, the EU would not have to relinquish this conditionality. This is because the direct payments involved would in all likelihood not, together with the other price support instruments, exceed the amount available under the presently scheduled maximum.

Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV

The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874