'Le Siège de Calais' by Pierre-Laurent de Belloy

Le Siège de Calais, hailed by its author in 1765 as France’s ‘première tragédie nationale’, rolled into Paris like a storm. Pierre-Laurent de Belloy’s play about French bravery during the Hundred Years’ War (1337-1453) appeared on the heels of France’s defeat in the Seven Years’ War (1756-1763). Le Siège de Calais was performed throughout Europe and published numerous times during the second half of the eighteenth century. De Belloy emerged as a national hero, receiving prizes from Louis XV, accolades from the city of Calais, and membership to the prestigious Académie française. Since the French Revolution, however, the popularity of Le Siège de Calais has eclipsed, owing to its overt glorification of France’s royal machine. Several hundred years later, the play warrants a fresh look from a holistic perspective. De Belloy’s tragedy and the varied responses it provoked – many of which are included in this edition – offer complex representations of French political history and patriotic sentiment. Le Siège de Calais reveals conflicting images of gender roles, political debate and family values during the twilight of the Ancien régime; it also constituted one of the last moments when serious drama asserted its role as a popular force.

The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies

Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September, 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles.18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies.A detailed explanation and elaboration document is published separately and is freely available on the websites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE statement will contribute to improving the quality of reporting of observational studies

Testing the GlaaS algorithm for dose measurements on low- and high-energy photon beams using an amorphous silicon portal imager

The GLAaS algorithm for pretreatment intensity modulation radiation therapy absolute dose verification based on the use of amorphous silicon detectors, as described in Nicolini et al. [G. Nicolini, A. Fogliata, E. Vanetti, A. Clivio, and L. Cozzi, Med. Phys. 33, 2839-2851 (2006)], was tested under a variety of experimental conditions to investigate its robustness, the possibility of using it in different clinics and its performance. GLAaS was therefore tested on a low-energy Varian Clinac (6 MV) equipped with an amorphous silicon Portal Vision PV-aS500 with electronic readout IAS2 and on a high-energy Clinac (6 and 15 MV) equipped with a PV-aS1000 and IAS3 electronics. Tests were performed for three calibration conditions: A: adding buildup on the top of the cassette such that SDD-SSD = d(max) and comparing measurements with corresponding doses computed at d(max), B: without adding any buildup on the top of the cassette and considering only the intrinsic water-equivalent thickness of the electronic portal imaging devices device (0.8 cm), and C: without adding any buildup on the top of the cassette but comparing measurements against doses computed at d(max). This procedure is similar to that usually applied when in vivo dosimetry is performed with solid state diodes without sufficient buildup material. Quantitatively, the gamma index (gamma), as described by Low et al. [D. A. Low, W. B. Harms, S. Mutic, and J. A. Purdy, Med. Phys. 25, 656-660 (1998)], was assessed. The gamma index was computed for a distance to agreement (DTA) of 3 mm. The dose difference deltaD was considered as 2%, 3%, and 4%. As a measure of the quality of results, the fraction of field area with gamma larger than 1 (%FA) was scored. Results over a set of 50 test samples (including fields from head and neck, breast, prostate, anal canal, and brain cases) and from the long-term routine usage, demonstrated the robustness and stability of GLAaS. In general, the mean values of %FA remain below 3% for deltaD equal or larger than 3%, while they are slightly larger for deltaD = 2% with %FA in the range from 3% to 8%. Since its introduction in routine practice, 1453 fields have been verified with GLAaS at the authors' institute (6 MV beam). Using a DTA of 3 mm and a deltaD of 4% the authors obtained %FA = 0.9 +/- 1.1 for the entire data set while, stratifying according to the dose calculation algorithm, they observed: %FA = 0.7 +/- 0.9 for fields computed with the analytical anisotropic algorithm and %FA = 2.4 +/- 1.3 for pencil-beam based fields with a statistically significant difference between the two groups. If data are stratified according to field splitting, they observed %FA = 0.8 +/- 1.0 for split fields and 1.0 +/- 1.2 for nonsplit fields without any significant difference.

Hemostasis management in pediatric mechanical circulatory support

In a 9-year-old boy, bridging to transplantation was successful with an external biventricular device, the Berlin Heart Excor (Berlin Heart, Berlin, Germany), during a 7-month period. Main long-term complications consisted of infection and hypercoagulability with clotting inside the chambers necessitating six pump exchanges, but without thromboembolic events. This report reviews hemostasis monitoring and management of long-term mechanical circulatory support.

The moderating role of personal mastery on the relationship between caregiving status and multiple dimensions of fatigue

OBJECTIVE: A substantial proportion of chronically-stressed spousal dementia caregivers report fatigue. The objective of this study was to examine whether personal mastery moderates the relationship between caregiving status (caregiver/non-caregiver) and multiple dimensions of fatigue. METHODS: Seventy-three elderly Alzheimer's caregivers and 41 elderly non-caregivers completed the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) and questionnaires assessing mastery. RESULTS: Regression analyses indicated that global fatigue was significantly higher for caregivers (M = 38.0 +/- 21.0) compared to non-caregivers (M = 18.2 +/- 10.4). However, personal mastery moderated the relation between caregiving status and global fatigue (t = -2.03, df = 107, p = 0.045), such that for those with low mastery, caregivers' fatigue scores were 18.1 points higher than non-caregivers, and for those with high mastery, this difference was only 7.5 points. For specific dimensions of fatigue, mastery moderated the relations between caregiving status and both emotional (t = -2.01, df = 107, p = 0.047) and physical (t = -2.51, df = 107, p = 0.014) fatigue. Specifically, association between caregiving status and emotional fatigue was greater when mastery was low than when mastery was high. Caregiving status was significantly associated with physical fatigue when mastery was low, but not when mastery was high. Significant main effects were found between mastery and general fatigue and vigor. CONCLUSION: Given the proportion of fatigued caregivers and the impact fatigue has on health; these findings provide important information regarding mastery's relationship with fatigue and may inform interventions aiming to alleviate fatigue in caregivers. Copyright (c) 2009 John Wiley ; Sons, Ltd.

The potential association between gingival crevicular fluid inflammatory mediators and adverse pregnancy outcomes: a systematic review

OBJECTIVES The association between periodontal disease and adverse pregnancy outcomes (APO), primarily preterm birth (PTB), is still controversially discussed in the literature. Therefore, the aim of the present systematic review was to analyze the existing literature on the potential association between inflammatory mediators detected in gingival crevicular fluid (GCF) and APO. MATERIALS AND METHODS MEDLINE (PubMed) and EMBASE databases were searched for entries up to April 2012 and studies were selected by two independent reviewers. RESULTS The majority of the eight studies included confirmed a positive association between GCF mediators, such as interleukin-1β, prostaglandin E2, and tumor necrosis factor-alpha, and APO. Due to the heterogeneity and variability of the available studies, no meta-analysis could be performed. CONCLUSIONS A positive association between GCF inflammatory mediator levels and APO/PTB might be present but the results need to be considered with great caution because of the heterogeneity and variability among the studies. Further studies with an adequate number of patients allowing for an appropriate analysis are warranted to definitely confirm this association. CLINICAL RELEVANCE The present findings suggest that an association between GCF inflammatory mediator levels and APO might exist.

Effekte spezifischer Interventionen im Sportunterricht auf die exekutiven Funktionen von Primarschulkindern

Einleitung Die Annahme, dass Sport nicht nur positive Effekte auf die körperliche Gesundheit, sondern auch auf die kognitive Leistung haben kann, konnte anhand experimenteller Studien mit Erwachsenen weitgehend bestätigt werden. Ob dieselben Effekte auch bei Kindern und Jugendlichen vorzufinden sind, kann mit Blick auf die mangelnde empirische Evidenz in dieser Altersgruppe kaum zufriedenstellend beantwortet werden (Chang et al., 2012). Will man zudem der Frage nach den Wirkmechanismen nachgehen, sind Unter-suchungsdesigns angezeigt, die theoriegeleitet verschiedene Sportinterventionen mit unterschiedlichen Beanspruchungsmodalitäten kombinieren. So ist unter der Annahme der cardiovascular fitness hypothesis (Etnier et al., 2006) zur gezielten Förderung der kognitiven Leistungsfähigkeit ein systematisches Ausdauertraining sinnvoll, während theoretische Ansätze, die neurophysiologische Korrelate zur Erklärung des Zusammenhangs zwischen Sport und Kognition heranziehen (Diamond, 2000) eher kognitiv sowie koordinativ anspruchsvolle Sportangebote nahelegen würden. Daher geht der vorliegende Beitrag der Frage nach, ob spezifisch konzipierte langfristige Interventionen im Sportunterricht einen spezifischen Effekt auf die kognitive Leistungsfähigkeit von Primarschulkindern haben können. Methode Im Rahmen der quasiexperimentellen Längsschnittstudie „Sport und Kognition“ (SpuK_5.0) wurden insgesamt 250 Schülerinnen und Schüler von 16 fünften Klassen untersucht. Während knapp zwei Monaten absolvierten je vier Klassen während zwei Lektionen des obligatorischen Sportunterrichts entweder ein spielsportbezogenes EF-Training oder ein Ausdauertraining resp. ein kognitives oder kein spezifisches Training (Kontrollgruppe mit regulärem Sportunterricht). Durch die Konzeption dieser vier Experi-mentalbedingungen wurde sichergestellt, dass alle vier möglichen Kombinationen aus hoher resp. niedriger kognitiver und körperlicher Beanspruchung im Design repräsentiert waren. Ergebnisse und Diskussion Im Beitrag werden erste Ergebnisse der noch laufendenden SpuK_5.0-Studie vorgestellt und vor dem Hintergrund aktueller theoretischer Annahmen zu den zugrundeliegenden Wirkmechanismen diskutiert. Literatur Chang, Y. K., Labban, J. D., Gapin, J. I., & Etnier, J. L. (2012). The effects of acute exercise on cognitive performance: A meta-analysis. Brain Research, 1453, 87-101. Diamond, A. (2000). Close interrelation of motor development and cognitive development and of the cere-bellum and prefrontal cortex. Child Development, 71, 44-56. Etnier, J. L., Nowell, P. M., Landers, D. M., & Sibley, B. A. (2006). A meta-regression to examine the rela-tionship between aerobic fitness and cognitive performance. BRAIN RESEARCH, 52, 119-130.

Genetic diversity, phenotypic variation and local adaptation in the alpine landscape: case studies with alpine plant species

Plant survival in alpine landscapes is constantly challenged by the harsh and often unpredictable environmental conditions. Steep environmental gradients and patchy distribution of habitats lead to small size and spatial isolation of populations and restrict gene flow. Agricultural land use has further increased the diversity of habitats below and above the treeline. We studied the consequences of the highly structured alpine landscape for evolutionary processes in four study plants: Epilobium fleischeri, Geum reptans, Campanula thyrsoides and Poa alpina. The main questions were: (1) How is genetic diversity distributed within and among populations and is it affected by altitude, population size or land use? (2) Do reproductive traits such as allocation to sexual or vegetative reproduction vary with altitude or land use? Furthermore, we studied if seed weight increases with altitude. Within-population genetic diversity of the four species was high and mostly not related to altitude and population size. Nevertheless, genetic differentiation among populations was pronounced and strongly increasing with distance. In Poa alpina genetic diversity was affected by land use. Results suggest considerable genetic drift among populations of alpine plants. Reproductive allocation was affected by altitude and land use in Poa alpina and by succession in Geum reptans. Seed weight was usually higher in alpine species than in related lowland species. We conclude that the evolutionary potential to respond to global change is mostly intact in alpine plants, even at high altitude. Phenotypic variability is shaped by adaptive as well as by random evolutionary processes; moreover plastic responses to growth conditions seem to be crucial for survival of plants in the alpine landscape.

Support of hepatic regeneration by trophic factors from liver-derived mesenchymal stromal/stem cells

Mesenchymal stromal/stem cells (MSCs) have multilineage differentiation potential and as such are known to promote regeneration in response to tissue injury. However, accumulating evidence indicates that the regenerative capacity of MSCs is not via transdifferentiation but mediated by their production of trophic and other factors that promote endogenous regeneration pathways of the tissue cells. In this chapter, we provide a detailed description on how to obtain trophic factors secreted by cultured MSCs and how they can be used in small animal models. More specific, in vivo models to study the paracrine effects of MSCs on regeneration of the liver after surgical resection and/or ischemia and reperfusion injury are described.

Colon-specific deletion of epithelial sodium channel causes sodium loss and aldosterone resistance

Aldosterone promotes electrogenic sodium reabsorption through the amiloride-sensitive epithelial sodium channel (ENaC). Here, we investigated the importance of ENaC and its positive regulator channel-activating protease 1 (CAP1/Prss8) in colon. Mice lacking the αENaC subunit in colonic superficial cells (Scnn1a(KO)) were viable, without fetal or perinatal lethality. Control mice fed a regular or low-salt diet had a significantly higher amiloride-sensitive rectal potential difference (∆PDamil) than control mice fed a high-salt diet. In Scnn1a(KO) mice, however, this salt restriction-induced increase in ∆PDamil did not occur, and the circadian rhythm of ∆PDamil was blunted. Plasma and urinary sodium and potassium did not change with regular or high-salt diets or potassium loading in control or Scnn1a(KO) mice. However, Scnn1a(KO) mice fed a low-salt diet lost significant amounts of sodium in their feces and exhibited high plasma aldosterone and increased urinary sodium retention. Mice lacking the CAP1/Prss8 in colonic superficial cells (Prss8(KO)) were viable, without fetal or perinatal lethality. Compared with controls, Prss8(KO) mice fed regular or low-salt diets exhibited significantly reduced ∆PDamil in the afternoon, but the circadian rhythm was maintained. Prss8(KO) mice fed a low-salt diet also exhibited sodium loss through feces and higher plasma aldosterone levels. Thus, we identified CAP1/Prss8 as an in vivo regulator of ENaC in colon. We conclude that, under salt restriction, activation of the renin-angiotensin-aldosterone system in the kidney compensated for the absence of ENaC in colonic surface epithelium, leading to colon-specific pseudohypoaldosteronism type 1 with mineralocorticoid resistance without evidence of impaired potassium balance.

Novel mitochondrial tRNA(Ile) m.4282A>G gene mutation leads to chronic progressive external ophthalmoplegia plus phenotype

BACKGROUND/AIM To investigate the underlying pathomechanism in a 33-year-old female Caucasian patient presenting with chronic progressive external ophthalmoplegia (CPEO) plus symptoms. METHODS Histochemical analysis of skeletal muscle and biochemical measurements of individual oxidative phosphorylation (OXPHOS) complexes. Genetic analysis of mitochondrial DNA in various tissues with subsequent investigation of single muscle fibres for correlation of mutational load. RESULTS The patient's skeletal muscle showed 20% of cytochrome c oxidase-negative fibres and 8% ragged-red fibres. Genetic analysis of the mitochondrial DNA revealed a novel point mutation in the mitochondrial tRNA(Ile) (MTTI) gene at position m.4282G>A. The heteroplasmy was determined in blood, buccal cells and muscle by restriction fragment length polymorphism (RFLP) combined with a last fluorescent cycle. The total mutational load was 38% in skeletal muscle, but was not detectable in blood or buccal cells of the patient. The phenotype segregated with the mutational load as determined by analysis of single cytochrome c oxidase-negative/positive fibres by laser capture microdissection and subsequent LFC-RFLP. CONCLUSIONS We describe a novel MTTI transition mutation at nucleotide position m.4282G>A associated with a CPEO plus phenotype. The novel variant at position m.4282G>A disrupts the middle bond of the D-stem of the tRNA(Ile) and is highly conserved. The conservation and phenotype-genotype segregation strongly suggest pathogenicity and is in good agreement with the MTTI gene being frequently associated with CPEO. This novel variant broadens the spectrum of MTTI mutations causing CPEO.