Genetic diversity in caribou linked to past and future climate change

Climate-driven range fluctuations during the Pleistocene have continuously reshaped species distribution leading to populations of contrasting genetic diversity. Contemporary climate change is similarly influencing species distribution and population structure, with important consequences for patterns of genetic diversity and species' evolutionary potential1. Yet few studies assess the impacts of global climatic changes on intraspecific genetic variation2, 3, 4, 5. Here, combining analyses of molecular data with time series of predicted species distributions and a model of diffusion through time over the past 21 kyr, we unravel caribou response to past and future climate changes across its entire Holarctic distribution. We found that genetic diversity is geographically structured with two main caribou lineages, one originating from and confined to Northeastern America, the other originating from Euro-Beringia but also currently distributed in western North America. Regions that remained climatically stable over the past 21 kyr maintained a high genetic diversity and are also predicted to experience higher climatic stability under future climate change scenarios. Our interdisciplinary approach, combining genetic data and spatial analyses of climatic stability (applicable to virtually any taxon), represents a significant advance in inferring how climate shapes genetic diversity and impacts genetic structure.

De la Franche-Comté à Naples : la charbonnerie entre nation italienne et fédération européenne

Depuis les années quatre-vingt, la maçonnologie -soit l'étude des réseaux et des nouvelles formes de sociabilité constituées principalement par la Franc-Maçonnerie- s'est progressivement imposée comme une nouvelle discipline des sciences historiques, sociales et politiques. Sa démarche novatrice est interdisciplinaire et vise à comprendre l'origine sociale des adeptes, le rôle du secret comme facteur d'agrégation, ainsi que la philosophie et la morale prônées par l'ordre. Cette démarche ne s'adresse d'ailleurs pas exclusivement à la Franc-Maçonnerie ; elle peut sans problèmes être élargie à d'autres organisations secrètes telles : l'ordre des Illuminés de Bavière, la Charbonnerie, la Philadelphie etc... Les ouvrages pionniers de cette discipline -ceux de Maurice Agulhon et de Pierre-Yves Beaurepaire pour la France, de Carlo Francovich pour l'Italie et d'Helmut Reinalter pour l'Autriche et l'Allemagne- ont la particularité de s'être concentrés sur les sociétés secrètes du XVIIIe siècle : approfondissant leur dimension cosmopolite proche de la philosophie des Lumières. Cette thèse propose de se concentrer sur la Charbonnerie : une société aux origines compagnonniques encore active au début du XIXe siècle dans les provinces de Franche-Comté et de Bourgogne. Celle-ci a été transplantée dans le royaume de Naples, durant la période napoléonienne, et, dans cet environnement, elle s'est politisée épousant la cause de la lutte contre les régimes absolutistes et pour l'autodétermination des peuples. Depuis le royaume de Naples, la Charbonnerie s'est répandue, d'abord dans les autres États constituant la péninsule italienne d'alors, puis elle a été exportée, principalement par des exilés italiens, dans d'autres réalités telles: la France, l'Espagne, la Suisse, la Grande-Bretagne, la Grèce et la Russie. Son idéologie et son combat mêlent à la fois une dimension cosmopolite d'amitié entre les peuples et de secours pour les patriotes persécutés, ainsi que de lutte pour l'affirmation du principe de nationalité pour chaque peuple. - Since the 1980s, the study of Freemasonry - namely the study of the networks and forms of sociability associated with the Freemasons - has gradually established itself as a new field of historical, political and social research. This new interdisciplinary approach aims at exploring the social background of the affiliates, the role that secrecy played in their integration, and the philosophy and moral principles promoted by the Order. This approach is not confined to Freemasonry, but can be applied in the same way to other secret societies, such as the Illuminati, the Carbonari and the Philadelphians . The pioneering studies in this field - those developed by Maurice Agulhon and Pierre-Yves Beaurepaire on France, by Carlo Francovich on Italy and by Helmut Reinalter for Austria and Germany - focus on secret societies in the 18th century: consequently they emphasize their cosmopolitan dimension and their affinity to the philosophy of the Enlightenment. This doctoral thesis focuses more particularly on the Carbonari: a society that had its origins in the Compagnonnage, still present in the French provinces of the Franche-Comté and the Bourgogne in the early 19th century. During the Napoleonic period the Carboneria was imported into the Kingdom of Naples, where the society became more politicized, espousing the struggle against absolutism and for the peoples' right to self-determination. From the Kingdom of Naples, the society extended its influence first into the other countries of the Italian peninsula, then, thanks to exiled Italians, to France, Spain, Switzerland, Great Britain, Greece, and Russia. The ideals and objectives of the society combined the pursuit of cosmopolitan friendship between nations, the effort to save persecuted compatriots , and the assertion of the national identity of peoples.

Hidradenitis suppurativa of the groin treated by radical excision and defect closure by medial thigh lift: aesthetic surgery meets reconstructive surgery.

INTRODUCTION: Hidradenitis suppurativa of the groin is a chronic, relapsing inflammatory disease of the skin and subcutaneous tissues. Radical surgical excision is the treatment of choice. Often split-skin grafting or wound healing by secondary intention are used for defect closure, sometimes with disfiguring results. We describe our experience with radical excision of localised inguinal hidradenitis suppurativa and immediate defect closure with a medial thigh lift. PATIENTS AND METHODS: Our hospital database was searched for all patients presenting to our institution for surgical treatment of hidradenitis suppurativa between 2001 and 2006. Only patients with hidradenitis confined to the groin were included. Exclusion criteria were simple abscess incisions, recurrence after previous grafting or flap surgery and extension of the disease outside the groin and presence of clinical signs of infection at the time of surgery. We documented patient demographics, sizes of defects, complications, time of follow-up, recurrences and patient satisfaction. RESULTS: A total of 8 patients with localised inguinal hidradenitis suppurativa were identified and 15 thigh lifts were performed. Defect size assessed on pathologic examination of the excised specimens averaged 15.9 cm x 4.3 cm x 1.3 cm (length x width x depth). All wounds but one healed primarily. Functional and aesthetic results were satisfactory. No major complications and no irritations of the genital area were observed. No recurrences were observed either. CONCLUSION: We propose the medial thigh lift to be considered for immediate defect closure after radical excision of localised inguinal hidradenitis suppurativa provided that no perifocal signs of infection are present after debridement.

Modelling of crowded polymers elucidate effects of double-strand breaks in topological domains of bacterial chromosomes.

Using numerical simulations of pairs of long polymeric chains confined in microscopic cylinders, we investigate consequences of double-strand DNA breaks occurring in independent topological domains, such as these constituting bacterial chromosomes. Our simulations show a transition between segregated and mixed state upon linearization of one of the modelled topological domains. Our results explain how chromosomal organization into topological domains can fulfil two opposite conditions: (i) effectively repulse various loops from each other thus promoting chromosome separation and (ii) permit local DNA intermingling when one or more loops are broken and need to be repaired in a process that requires homology search between broken ends and their homologous sequences in closely positioned sister chromatid.

Consolidation whole abdomen irradiation following adjuvant carboplatin-paclitaxel based chemotherapy for advanced uterine epithelial cancer: feasibility, toxicity and outcomes.

BACKGROUND: To evaluate feasibility and preliminary outcomes associated with sequential whole abdomen irradiation (WAI) as consolidative treatment following comprehensive surgery and systemic chemotherapy for advanced endometrial cancer. METHODS: We conducted a retrospective analysis of patients treated at our institution from 2000 to 2011. Inclusion criteria were stage III-IV endometrial cancer patients with histological proof of one or more sites of extra-uterine abdomen-confined disease, treated with WAI as part of multimodal therapy. Endpoints were feasibility, acute toxicity, late effects, recurrence-free survival (RFS) and overall survival (OS). Twenty patients were identified. Chemotherapy consisted of 3 to 6 cycles of a platinum-paclitaxel regimen in 18 patients. WAI was delivered using conventional technique to a median total dose of 27.5 Gy. RESULTS: No grade 4 toxicities occurred during chemotherapy or radiotherapy. No radiation dose reduction was necessary. Three patients developed small bowel obstruction, all in the context of recurrent intraperitoneal disease. Kaplan-Meier estimates and 95% confidence intervals for RFS and OS at one year were 63% (38-80%) and 83% (56-94%) and at 3 years 57% (33-76%) and 62% (34-81%), respectively. On univariate Cox analysis, stage IVB and serous papillary (SP) histology were found to be statistically significantly (at the p = 0.05 level) associated with worse RFS and OS. The peritoneal cavity was the most frequent site of initial failure. CONCLUSIONS: Consolidative WAI following chemotherapy is feasible and can be performed without interruption with manageable acute and late toxicity. Patients with endometrioid adenocarcinoma, especially stage FIGO III, had favorable outcomes possibly meriting prospective evaluation of the addition of WAI following chemotherapy in selected patients. Patients with SP do poorly and do not routinely benefit from this approach.

Stochasticity and bistability in horizontal transfer control of a genomic island in Pseudomonas.

Genomic islands (GEI) comprise a recently recognized large family of potentially mobile DNA elements and play an important role in the rapid differentiation and adaptation of bacteria. Most importantly, GEIs have been implicated in the acquisition of virulence factors, antibiotic resistances or toxic compound metabolism. Despite detailed information on coding capacities of GEIs, little is known about the regulatory decisions in individual cells controlling GEI transfer. Here, we show how self-transfer of ICEclc, a GEI in Pseudomonas knackmussii B13 is controlled by a series of stochastic processes, the result of which is that only a few percent of cells in a population will excise ICEclc and launch transfer. Stochastic processes have been implicated before in producing bistable phenotypic transitions, such as sporulation and competence development, but never before in horizontal gene transfer (HGT). Bistability is instigated during stationary phase at the level of expression of an activator protein InrR that lays encoded on ICEclc, and then faithfully propagated to a bistable expression of the IntB13 integrase, the enzyme responsible for excision and integration of the ICEclc. Our results demonstrate how GEI of a very widespread family are likely to control their transfer rates. Furthermore, they help to explain why HGT is typically confined to few members within a population of cells. The finding that, despite apparent stochasticity, HGT rates can be modulated by external environmental conditions provides an explanation as to why selective conditions can promote DNA exchange.

Delivery of antisense oligonucleotide to the cornea by iontophoresis.

We wished to evaluate the potential of iontophoresis to promote the delivery of antisense oligonucleotides (ODN) directed at the vascular endothelial growth factor (VEGF)-R2 receptor (KDR/Flk) to the cornea of the rat eye. Fluorescence (CY5)-labeled ODNs in phosphate-buffered saline (PBS) (20 microM) were locally administered to rat eyes, and their fate within the anterior segment was studied. Thirty-four male, 5-week-old Wistar rats were used for all experiments. The rats were divided in four groups. In group I (12 rats, 12 eyes), the ODNs (20 microM) were delivered by iontophoresis (300 microA for 5 minutes) using a specially designed corneal applicator. In group II (12 rats, 12 eyes), the ODNs (20 microM) were delivered using the same applicator, but no electrical current was applied. In group III (6 rats, 6 eyes), a corneal neovascular reaction was induced prior to the application of ODNs (20 microM), and iontophoresis electrical current was delivered as for group I rats. Group IV (4 rats, 4 eyes) received ODN (60 microM) iontophoresis application (300 microA for 5 minutes) and were used for ODN integrity studies. The animals were killed 5 minutes, 90 minutes, and 24 hours after a single ODN application and studied. Topically applied ODNs using the same iontophoresis applicator but without current do not penetrate the cornea and remain confined to the superficial epithelial layer. ODNs delivered with transcorneoscleral iontophoresis penetrate into all corneal layers and are also detected in the iris. In corneas with neovascularization, ODNs were particularly localized within the vascular endothelial cells of the stroma. ODNs extracted from eye tissues 24 hours after iontophoresis remained unaltered. The iontophoresis current did not cause any detectable ocular damage under these conditions. Iontophoresis promotes the delivery of ODNs to the anterior segment of the eye, including all corneal layers. Iontophoresis of ODNs directed at VEGF-R2 may be used for the design of specific antiangiogenic strategy in diseases of the cornea.

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In 1959, Swerdlow reported a case of a 27-year-old woman with a pelvic tumour that seemed to arise from the peritoneum, in the presence of normal ovaries, fallopian tubes and uterus, and that was histologically similar to papillary serous carcinoma of the ovary [52]. Since then several authors have described this disease using different names, such as extraovarian primary peritoneal carcinoma (EOPPC), peritoneal papillary serous carcinoma, peritoneal adenocarcinoma of Müllerian type, serous surface papillary carcinoma, normal sized ovary carcinoma syndrome, peritoneal mesothelioma, and primary peritoneal carcinoma. This illustrates the confusion about definition, histogenesis and clinicopathologic features of this entity. In 1993, in an attempt to sort out these confounding variables, the Gynecologic Oncology Group (GOG) developed criteria to define EOPPC: - Both ovaries must be either physiologically normal in size or enlarged by a benign process. - The involvement in extraovarian sites must be greater than the involvement on the surface of either ovary. - Microscopically, the ovarian component must be one of the following: non existent; confined to ovarian surface epithelium with no evidence of cortical invasion; involving ovarian surface epithelium and underlying cortical stroma but with tumour size less than 5x5mm within ovarian substance with or without surface disease. The histological and cytological characteristics of the tumour must be predominantly of the serous type that is similar or identical to ovarian serous adenocarcinoma of any grade [8, 55].

Official Positions for FRAX® clinical regarding prior fractures from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

The 2010 Position Development Conference addressed four questions related to the impact of previous fractures on 10-year fracture risk as calculated by FRAX(®). To address these questions, PubMed was searched on the keywords "fracture, epidemiology, osteoporosis." Titles of retrieved articles were reviewed for an indication that risk for future fracture was discussed. Abstracts of these articles were reviewed for an indication that one or more of the questions listed above was discussed. For those that did, the articles were reviewed in greater detail to extract the findings and to find additional past work and citing works that also bore on the questions. The official positions and the supporting literature review are presented here. FRAX(®) underestimates fracture probability in persons with a history of multiple fractures (good, A, W). FRAX(®) may underestimate fracture probability in individuals with prevalent severe vertebral fractures (good, A, W). While there is evidence that hip, vertebral, and humeral fractures appear to confer greater risk of subsequent fracture than fractures at other sites, quantification of this incremental risk in FRAX(®) is not possible (fair, B, W). FRAX(®) may underestimate fracture probability in individuals with a parental history of non-hip fragility fracture (fair, B, W). Limitations of the methodology include performance by a single reviewer, preliminary review of the literature being confined to titles, and secondary review being limited to abstracts. Limitations of the evidence base include publication bias, overrepresentation of persons of European descent in the published studies, and technical differences in the methods used to identify prevalent and incident fractures. Emerging topics for future research include fracture epidemiology in non-European populations and men, the impact of fractures in family members other than parents, and the genetic contribution to fracture risk.

Systematic review of evidence and consensus on diverticulitis: an analysis of national and international guidelines.

AIM: The study aimed to analyse the currently available national and international guidelines for areas of consensus and contrasting recommendations in the treatment of diverticulitis and thereby to design questions for future research. METHOD: MEDLINE, EMBASE and PubMed were systematically searched for guidelines on diverticular disease and diverticulitis. Inclusion was confined to papers in English and those < 10 years old. The included topics were classified as consensus or controversy between guidelines, and the highest level of evidence was scored as sufficient (Oxford Centre of Evidence-Based Medicine Level of Evidence of 3a or higher) or insufficient. RESULTS: Six guidelines were included and all topics with recommendations were compared. Overall, in 13 topics consensus was reached and 10 topics were regarded as controversial. In five topics, consensus was reached without sufficient evidence and in three topics there was no evidence and no consensus. Clinical staging, the need for intraluminal imaging, dietary restriction, duration of antibiotic treatment, the protocol for abscess treatment, the need for elective surgery in subgroups of patients, the need for surgery after abscess treatment and the level of the proximal resection margin all lack consensus or evidence. CONCLUSION: Evidence on the diagnosis and treatment of diverticular disease and diverticulitis ranged from nonexistent to strong, regardless of consensus. The most relevant research questions were identified and proposed as topics for future research.

Application des méthodes géophysiques à l'étude de deux sites (Kappelen et Grenchen) de l'aquifère poreux complexe du Seeland

L'aquifère du Seeland représente une richesse en ressources hydriques qu'il est impératif de préserver contre tout risque de détérioration. Cet aquifère prolifique est constitué principalement de sédiments alluviaux post-glaciaires (graviers, sables et limons). Il est soumis aux contraintes environnementales des pratiques d'agriculture intensive, du réseau routier, des villes et de leurs activités industrielles. La connaissance optimale de ces ressources est donc primordiale pour leur protection. Dans cette optique, deux sites Kappelen et Grenchen représentatifs de l'aquifère du Seeland ont été étudiés. L'objectif de ce travail est de caractériser d'un point de vue hydrogéophysique l'aquifère au niveau de ces deux sites, c'est-à-dire, comprendre la dynamique des écoulements souterrains par l'application des méthodes électriques de surface associées aux diagraphies en intégrant des méthodes hydrogéologiques. Pour le site de Kappelen, les méthodes électriques de surface ont permis d'identifier les différents faciès géoélectriques en présence et de mettre en évidence leur disposition en une structure tabulaire et horizontale. Il s'agit d'un aquifère libre constitué d'une série de graviers allant jusqu'à 15 m de profondeur reposant sur de la moraine argileuse. Les diagraphies électriques, nucléaires et du fluide ont servis à la détermination des caractéristiques pétrophysiques et hydrauliques de l'aquifère qui contrôlent son comportement hydrodynamique. Les graviers aquifères de Kappelen présentent deux minéraux dominants: quartz et calcite. Les analyses minéralogiques indiquent que ces deux éléments constituent 65 à 75% de la matrice. La porosité totale obtenue par les diagraphies nucléaires varie de 20 à 30 %, et de 22 à 29 % par diagraphies électrique. Avec les faibles valeurs de Gamma Ray ces résultats indiquent que l'aquifère des graviers de Kappelen est dépourvu d'argile minéralogique. La perméabilité obtenue par diagraphies du fluide varie de 3.10-4 à 5.10-2 m/s, et par essais de pompage de 10-4 à 10-2 m/s. Les résultats des analyses granulométriques indiquent une hétérogénéité granulométrique au niveau des graviers aquifères. La fraction de sables, sables très fins, silts et limons constitue de 10 à 40 %. Ces éléments jouent un rôle important dans le comportement hydraulique de l'aquifère. La porosité efficace de 11 à 25% estimée à partir des résultats des analyses granulométriques suppose que les zones les plus perméables correspondent aux zones les plus graveleuses du site. Etablie sur le site de Kappelen, cette méthodologie a été utilisée sur le site de Grenchen. Les méthodes électriques de surface indiquent que l'aquifère captif de Grenchen est constitué des sables silteux comprenant des passages sableux, encadrés par des silts argileux imperméables. L'aquifère de Grenchen est disposé dans une structure relativement tabulaire et horizontale. Son épaisseur totale peut atteindre les 25 m vers le sud et le sud ouest ou les passages sableux sont les plus importants. La détermination des caractéristiques pétrophysiques et hydrauliques s'est faite à l'aide des diagraphies. Les intensités Gamma Ray varient de 30 à 100 cps, les plus fortes valeurs n'indiquent qu'une présence d'éléments argileux mais pas de bancs d'argile. Les porosités totales de 15 à 25% et les densités globales de 2.25 à 2.45 g/cm3 indiquent que la phase minérale (matrice) est composée essentiellement de quartz et de calcaire. Les densités de matrice varient entre 2.65 et 2.75 g/cm3. La perméabilité varie de 2 10-6 à 5 10-4 m/s. La surestimation des porosités totales à partir des diagraphies électriques de 25 à 42% est due à la présence d'argiles. -- The vast alluvial Seeland aquifer system in northwestern Switzerland is subjected to environmental challenges due to intensive agriculture, roads, cities and industrial activities. Optimal knowledge of the hydrological resources of this aquifer system is therefore important for their protection. Two representative sites, Kappelen and Grenchen, of the Seeland aquifer were investigated using surface-based geoelectric methods and geophysical borehole logging methods. By integrating of hydrogeological and hydrogeophysical methods, a reliable characterization of the aquifer system at these two sites can be performed in order to better understand the governing flow and transport process. At the Kappelen site, surface-based geoelectric methods allowed to identify various geoelectric facies and highlighted their tabular and horizontal structure. It is an unconfined aquifer made up of 15 m thick gravels with an important sandy fraction and bounded by a shaly glacial aquitard. Electrical and nuclear logging measurements allow for constraining the petrophysical and hydrological parameters of saturated gravels. Results indicate that in agreement with mineralogical analyses, matrix of the probed formations is dominated by quartz and calcite with densities of 2.65 and 2.71 g/cc, respectively. These two minerals constitute approximately 65 to 75 % of the mineral matrix. Matrix density values vary from 2.60 to 2.75 g/cc. Total porosity values obtained from nuclear logs range from 20 to 30 % and are consistent with those obtained from electrical logs ranging from 22 to 29 %. Together with the inherently low natural gamma radiation and the matrix density values obtained from other nuclear logging measurements, this indicates that at Kappelen site the aquifer is essentially devoid of clay. Hydraulic conductivity values obtained by the Dilution Technique vary between 3.10-4 and 5.10-2 m/s, while pumping tests give values ranging from 10-4 to 10-2 m/s. Grain size analysis of gravel samples collected from boreholes cores reveal significant granulometric heterogeneity of these deposits. Calculations based on these granulometric data have shown that the sand-, silt- and shale-sized fractions constitute between 10 and 40 % of the sample mass. The presence of these fine elements in general and their spatial distribution in particular are important as they largely control the distribution of the total and effective porosity as well as the hydraulic conductivity. Effective porosity values ranging from 11 to 25% estimated from grain size analyses indicate that the zones of higher hydraulic conductivity values correspond to the zones dominated by gravels. The methodology established at the Kappelen site was then applied to the Grenchen site. Results from surface-based geoelectric measurements indicate that it is a confined aquifer made up predominantly of shaly sands with intercalated sand lenses confined impermeable shally clay. The Grenchen confined aquifer has a relatively tabular and horizontal structure with a maximum thickness of 25 m in the south and the southwest with important sand passages. Petrophysical and hydrological characteristics were performed using electrical and nuclear logging. Natural gamma radiation values ranging from 30 to 100 cps indicate presence of a clay fraction but not of pure clay layers. Total porosity values obtained from electrical logs vary form 25 to 42%, whereas those obtained from nuclear logs values vary from 15 to 25%. This over-estimation confirms presences of clays. Density values obtained from nuclear logs varying from 2.25 to 2.45 g/cc in conjunction with the total porosity values indicate that the dominating matrix minerals are quartz and calcite. Matrix density values vary between 2.65 and 2.75 g/cc. Hydraulic conductivity values obtained by the Dilution Technique vary from 2 10-6 to 5 10-4 m/s.

Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling.

How a stimulus or a task alters the spontaneous dynamics of the brain remains a fundamental open question in neuroscience. One of the most robust hallmarks of task/stimulus-driven brain dynamics is the decrease of variability with respect to the spontaneous level, an effect seen across multiple experimental conditions and in brain signals observed at different spatiotemporal scales. Recently, it was observed that the trial-to-trial variability and temporal variance of functional magnetic resonance imaging (fMRI) signals decrease in the task-driven activity. Here we examined the dynamics of a large-scale model of the human cortex to provide a mechanistic understanding of these observations. The model allows computing the statistics of synaptic activity in the spontaneous condition and in putative tasks determined by external inputs to a given subset of brain regions. We demonstrated that external inputs decrease the variance, increase the covariances, and decrease the autocovariance of synaptic activity as a consequence of single node and large-scale network dynamics. Altogether, these changes in network statistics imply a reduction of entropy, meaning that the spontaneous synaptic activity outlines a larger multidimensional activity space than does the task-driven activity. We tested this model's prediction on fMRI signals from healthy humans acquired during rest and task conditions and found a significant decrease of entropy in the stimulus-driven activity. Altogether, our study proposes a mechanism for increasing the information capacity of brain networks by enlarging the volume of possible activity configurations at rest and reliably settling into a confined stimulus-driven state to allow better transmission of stimulus-related information.

Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes.

BACKGROUND: ALK-negative anaplastic large cell lymphoma associated with breast implant (i-ALCL) has been recently recognized as a distinct entity. Among 43 830 lymphomas registered in the French Lymphopath network since 2010, 300 breast lymphomas comprising 25 peripheral T-cell lymphomas (PTCL) were reviewed. Among PTCL, ALK-negative ALCL was the most frequent and all of them were associated with breast implants. PATIENTS AND METHODS: Since 2010, all i-ALCL cases were collected from different institutions through Lymphopath. Immuno-morphologic features, molecular data and clinical outcome of 19 i-ALCLs have been retrospectively analyzed. RESULTS: The median age of the patients was 61 years and the median length between breast implant and i-ALCL was 9 years. Most implants were silicone-filled and textured. Implant removal was performed in 17 out of 19 patients with additional treatment based on mostly CHOP or CHOP-like chemotherapy regimens (n = 10/19) or irradiation (n = 1/19). CHOP alone or ABVD following radiation without implant removal have been given in two patients. The two clinical presentations, i.e. effusion and less frequently tumor mass correlated with distinct histopathologic features: in situ i-ALCL (anaplastic cell proliferation confined to the fibrous capsule) and infiltrative i-ALCL (pleomorphic cells massively infiltrating adjacent tissue with eosinophils and sometimes Reed-Sternberg-like cells mimicking Hodgkin lymphoma). Malignant cells were CD30-positive, showed a variable staining for EMA and were ALK negative. Most cases had a cytotoxic T-cell immunophenotype with variable T-cell antigen loss and pSTAT3 nuclear expression. T-cell receptor genes were clonally rearranged in 13 out of 13 tested cases. After 18 months of median follow-up, the 2-year overall survival for in situ and infiltrative i-ALCL was 100% and 52.5%, respectively. CONCLUSIONS: In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal.

A rationalist perspective on the autonomy of international sport governing bodies : towards a pragmatic autonomy in the steering of sports

International sport governing bodies (ISGBs) are built on the foundations of freedom of association and traditionally enjoy a large degree of autonomy in their decision-making. Their autonomy is increasingly confined, however, and their hierarchical self-governance is giving way to a more networked governance, in which different stakeholders exert power in different ways and in different contexts in a complex web of interrelationships. Taking a rationalist perspective on the autonomy of ISGBs, this article demonstrates that ISGBs are deploying strategies to safeguard their waning governing monopoly over international sport. Opting for an inductive approach, the authors present four possible conceptualizations of autonomy as applied to ISGBs, namely political autonomy, legal autonomy, financial autonomy and pyramidal autonomy. For each dimension, they describe the different strategies ISGBs wield in order to safeguard different dimensions of their autonomy. This article uses governance theories to hypothesize that the autonomy of ISGBs can be understood as 'pragmatic autonomy' since ISGBs only cede certain aspects of their autonomy under particular circumstances and when being subject to specific threats. Acting in a rationalist manner, they are able to keep control over governance developments in sport by using indirect and more subtle forms of governance.