Alpine and pre-Alpine magmatism in the root-zone of the western Central Alps

The highest grade of metamorphism and associated structural elements in orogenic belts may be inherited from earlier orogenic events. We illustrate this point using magmatic and metamorphic rocks from the southern steep belt of the Lepontine Gneiss Dome (Central Alps). The U-Pb zircon ages from an anatectic granite at Verampio and migmatites at Corcapolo and Lavertezzo yield 280-290 Ma, i.e., Hercynian ages. These ages indicate that the highest grade of metamorphism in several crystalline nappes of the Lepontine Gneiss Dome is pre-Alpine. Alpine metamorphism reached sufficiently high grade to reset the Rb-Sr and K-Ar systematics of mica and amphibole, but generally did not result in crustal melting, except in the steep belt to the north of the Insubric Line, where numerous 29 to 26 Ma old pegmatites and aplites had intruded syn- and post-kinematically into gneisses of the ductile Simplon Shear Zone. The emplacement age of these pegmatites gives a minimum estimate for the age of the Alpine metamorphic peak in the Monte Rosa nappe. The U-Pb titanite ages of 33 to 31 Ma from felsic porphyritic veins represent a minimum-age estimate for Alpine metamorphism in the Sesia Zone. A porphyric vein emplaced at 448 +/- 5 Ma (U-Pb monazite) demonstrates that there existed a consolidated Caledonian basement in the Sesia Zone.

EACTS Day in the new EACTS House.

There is no doubt that the European Association for Cardio-Thoracic Surgery is a success story. In 2011, we celebrated the 25th anniversary of this professional organization. In 2012, we will celebrate the 25th anniversary of the European Journal of Cardio-Thoracic Surgery. In addition, two other journals have been initiated, Interactive CardioVascular and Thoracic Surgery and the Multimedia Manual of Cardio-Thoracic Surgery, and all of them can be accessed through CTSnet (www.ctsnet.org). The most recent development was the birth of EACTS House, and it was to celebrate the official opening of EACTS House on 10 February 2011, that we held the second Strategic meeting, 'EACTS in the Future'. On this occasion, the EACTS council and delegates of the EACTS Domains (Domain of Thoracic Disease, Domain of Vascular Disease, Domain of Congenital Cardiac Disease and Domain of Adult Cardiac Disease) came together with representative thoracic and cardio-vascular surgeons from North America, Asia and BRICS countries as well as senior managers from industry in order to decide where to go from there. As a basis for starting the discussions, a sector analysis of the activities of the Department of Cardio-Vascular Surgery at CHUV in Lausanne, Switzerland was performed in order to identify the trends in the activities of our group of surgeons by pulling the consolidated data for the period running from 1 January 1995 to 31 December 2010. Interestingly enough, the most frequent procedures like coronary artery bypass graft and valve repair/replacement did not increase despite a growing programme. In our setting, the compensation came mainly from vascular surgery and mechanical circulatory support. These data have to be put in perspective by the reports provided by the EACTS domain chairs in order to identify the challenges and opportunities for the future development of our specialties.

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci.

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.

Rapid Improvement In Health-Related Quality Of Life In Gouty Arthritis Patients Treated With Canakinumab (Acz885) Compared To Triamcinolone Acetonide

Background : Canakinumab, a fully human anti-IL-1b antibody has been shown to control inflammation in gouty arthritis. This study evaluated changes in health-related quality of life (HRQoL) in patients treated with canakinumab or triamcinolone acetonide (TA).Methods : An 8-wk, dose-ranging, active controlled, single-blind study in patients (_18 to _80 years) with acute gouty arthritis flare, refractory to or contraindicated to NSAlDs and/or colchicine, were randomized to canakinumab 10, 25, 50, 90, 150mg sc or TA 40mg im. HRQoL was assessed using patient reported outcomes evaluating PCS and MCS, and subscale scores of SF-36_ [acute version 2]) and functional disability (HAQ-DI_).Results : In canakinumab 150mg group, the most severe impairment at baseline was reported for physical functioning and bodily pain; levels of 41.5 and 36.0, respectively, which improved in 7 days to 80.0 and 72.2 (mean increases of 39.0 and 35.6) and at 8 wks improved to 86.1 and 86.6 (mean increases of 44.6 and 50.6); these were higher than levels seen in the general US population. TA group, showed less improvement in 7 days (mean increases of 23.3 and 21.3 for physical function and bodily pain). Functional disability scores, measured by the HAQ-DI_ decreased in both treatment groups (Table 1).Conclusions : Gouty arthritis patients treated with canakinumab showed a rapid improvement in physical and mental well-being based on SF-36_ scores. In contrast to the TA group, patients treated with canakinumab showed improvement in 7 days in physical function and bodily pain approaching levels of the general population.Disclosure statement : U.A., A.F., V.M., D.R., P.S. and K.S. are employees and shareholders of Novartis Pharma AG. A.P. has received research support from Novartis Pharma AG. N.S. has received research support and consultancy fees from Novartis Pharmaceuticals Corporation, has served on advisory boards for Novartis, Takeda, Savient, URL Pharma and EnzymeRx, and is/has been a member of a speakers' bureau for Takeda. A.S. has received consultation fees from Novartis Pharma AG, Abbott, Bristol-Myers Squibb, Essex, Pfizer, MSD, Roche, UCB and Wyeth. All other authors have declared no conflicts of interest.

Monitoring Disease Activity and Progression in Crohn's Disease. A Swiss Perspective on the IBD Ahead 'Optimised Monitoring' Recommendations.

BACKGROUND AND AIMS: The structured IBD Ahead 'Optimised Monitoring' programme was designed to obtain the opinion, insight and advice of gastroenterologists on optimising the monitoring of Crohn's disease activity in four settings: (1) assessment at diagnosis, (2) monitoring in symptomatic patients, (3) monitoring in asymptomatic patients, and (4) the postoperative follow-up. For each of these settings, four monitoring methods were discussed: (a) symptom assessment, (b) endoscopy, (c) laboratory markers, and (d) imaging. Based on literature search and expert opinion compiled during an international consensus meeting, recommendations were given to answer the question 'which diagnostic method, when, and how often'. The International IBD Ahead Expert Panel advised to tailor this guidance to the healthcare system and the special prerequisites of each country. The IBD Ahead Swiss National Steering Committee proposes best-practice recommendations adapted for Switzerland. METHODS: The IBD Ahead Steering Committee identified key questions and provided the Swiss Expert Panel with a structured literature research. The expert panel agreed on a set of statements. During an international expert meeting the consolidated outcome of the national meetings was merged into final statements agreed by the participating International and National Steering Committee members - the IBD Ahead 'Optimized Monitoring' Consensus. RESULTS: A systematic assessment of symptoms, endoscopy findings, and laboratory markers with special emphasis on faecal calprotectin is deemed necessary even in symptom-free patients. The choice of recommended imaging methods is adapted to the specific situation in Switzerland and highlights the importance of ultrasonography and magnetic resonance imaging besides endoscopy. CONCLUSION: The recommendations stress the importance of monitoring disease activity on a regular basis and by objective parameters, such as faecal calprotectin and endoscopy with detailed documentation of findings. Physicians should not rely on symptoms only and adapt the monitoring schedule and choice of options to individual situations. © 2014 S. Karger AG, Basel.

Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures.

INTRODUCTION: Breast cancer subtyping and prognosis have been studied extensively by gene expression profiling, resulting in disparate signatures with little overlap in their constituent genes. Although a previous study demonstrated a prognostic concordance among gene expression signatures, it was limited to only one dataset and did not fully elucidate how the different genes were related to one another nor did it examine the contribution of well-known biological processes of breast cancer tumorigenesis to their prognostic performance. METHOD: To address the above issues and to further validate these initial findings, we performed the largest meta-analysis of publicly available breast cancer gene expression and clinical data, which are comprised of 2,833 breast tumors. Gene coexpression modules of three key biological processes in breast cancer (namely, proliferation, estrogen receptor [ER], and HER2 signaling) were used to dissect the role of constituent genes of nine prognostic signatures. RESULTS: Using a meta-analytical approach, we consolidated the signatures associated with ER signaling, ERBB2 amplification, and proliferation. Previously published expression-based nomenclature of breast cancer 'intrinsic' subtypes can be mapped to the three modules, namely, the ER-/HER2- (basal-like), the HER2+ (HER2-like), and the low- and high-proliferation ER+/HER2- subtypes (luminal A and B). We showed that all nine prognostic signatures exhibited a similar prognostic performance in the entire dataset. Their prognostic abilities are due mostly to the detection of proliferation activity. Although ER- status (basal-like) and ERBB2+ expression status correspond to bad outcome, they seem to act through elevated expression of proliferation genes and thus contain only indirect information about prognosis. Clinical variables measuring the extent of tumor progression, such as tumor size and nodal status, still add independent prognostic information to proliferation genes. CONCLUSION: This meta-analysis unifies various results of previous gene expression studies in breast cancer. It reveals connections between traditional prognostic factors, expression-based subtyping, and prognostic signatures, highlighting the important role of proliferation in breast cancer prognosis.

Canakinumab (Acz885) Relieves Pain And Controls Inflammation Rapidly In Patients With Difficult-To-Treat Gouty Arthritis : Comparison With Triamcinolone Acetonide

Background : Monosodium urate (MSU) crystals stimulate the productionof interleukin-1b (IL-1b), a potent inflammatory cytokine. Targeted IL-1b blockade with canakinumab, a fully human monoclonal anti-IL-1b antibody, is a novel treatment for gouty arthritis. Its effects on pain and inflammation in acute gouty arthritis flares were compared with triamcinolone acetonide (TA). TA has been shown to be effective in the treatment of acute gouty arthritis flares.Methods : This was an 8-week, dose-ranging, multicenter, blinded, active-controlled trial. Patients _18 to _80 years with an acute gouty arthritis flare, refractory to or contraindicated to NSAIDs and/or colchicine were randomized to one subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg; n¼143) or one intramuscular dose of TA (40 mg; n¼57). Primary outcome was pain intensity at 72 hours post dose on VAS scale (0-100 mm). Secondary outcomes included Creactive protein (CRP), serum amyloid A (SAA), and physician's assessment of tenderness, swelling and erythema of target joint at 72 hours, 7 days, 4 and 8-weeks post dose.Results : 191/200 patients completed the study. Canakinumab showed a statistically significant dose response at 72 hours. The 150mg dose group reached superior pain relief compared to TA group starting from 24 hours as previously reported. At 72 hours post dose, 78% of canakinumab 150mg treated patients achieved _75% and 96% achieved _50% reduction in pain from baseline. In contrast, 45% and 61% of patients treated with TA achieved _75% and _50% pain reduction, respectively. Median CRP/SAA levels were normalized by Day 7 for all canakinumab doses above 10mg and remained below the upper limit of normal [(ULN): CRP 3.0 mg/L; SAA 6.7 mg/L)] for rest of the study. In TA group, median CRP levels remained above the ULN throughout the study while median SAA levels decreased below ULN only 28 days after first dose. At 72 hours post dose, canakinumab 150mg group was 3.2 (95% CI, 1.27-7.89) times more likely to have less joint tenderness and 2.7 (95% CI, 1.09-6.5) times more likely to have less joint swelling than TA group (p<0.05). At 72 hours post dose, erythema disappeared in 74.1% of patients receiving canakinumab150mg and 69.6% of patients receiving TA. At 7 days post dose, erythema was absent in 96.3% of canakinumab 150mg treated patients vs. 83.9% of patients receiving TA. The overall incidence of AEs was similar for canakinumab (41%) and triamcinolone acetonide (42%). Serious AEs (canakinumab treatment groups n¼4, TA n¼1) were not considered treatment-related by investigators. No discontinuationsdue to AEs occurred.Conclusions : Canakinumab 150mg provided superior pain relief compared to TA for acute flares in difficult-to-treat gouty arthritis patients. Canakinumab provided rapid normalization of markers of inflammation accompanied by reduction of clinical signs and symptoms of inflammation.Disclosure statement : U.A., V.M., D.R. and P.S. are shareholders and employees of Novartis Pharma AG. A.P. has received research support from Novartis Pharma AG. N.S. has received research support from and acts as a consultant for Novartis Pharmaceuticals Corporation, has served on advisory boards for Novartis, Takeda, Savient, URL Pharma and Enzyme Rx, and is/has been a member of a speakers' bureau for Takeda. A.S. has received consultancy fees from Novartis Pharma AG, Abbott, Wyeth, UCB, Roche, MSD, Pfizer, Essex and Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

The role of stereotactic ablative radiotherapy in oncological and non-oncological clinical settings: highlights from the 7th Meeting of AIRO - Young Members Working Group (AIRO Giovani).

Stereotactic ablative radiotherapy is a modern cancer treatment strategy able to deliver highly focused radiation in one or a few fractions with a radical intent in several clinical settings. Young radiation oncologists need a constant and tailored update in this context to improve patient care in daily clinical practice. A recent meeting of AIRO Giovani (AIRO - Young Members Working Group) was specifically addressed to this topic, presenting state-of-the-art knowledge, based on the latest evidence in this field. Highlights of the congress are summarized and presented in this report, including thorough contributions of the speakers dealing with the role of stereotactic ablative radiotherapy in both oncological and non-oncological diseases, divided according to anatomical and clinical scenarios: intra-cranial settings (brain malignant primary tumors, metastases, benign tumors and functional disorders) and extra-cranial indications (lung primary tumors and metastases, thoracic re-irradiation, liver, lymph node and bone metastases, prostate cancer). With literature data discussed during the congress as a background, stereotactic ablative radiotherapy has proved to be a consolidated treatment approach in specific oncological and non-oncological scenarios, as well as a promising option in other clinical settings, requiring a further prospective validation in the near future. We herein present an updated overview of stereotactic ablative radiotherapy use in the clinic.

Les cadres intermédiaires entre contraintes managériales et défense des identités professionnelles : l'exemple des hôpitaux de Suisse romande

Cet article porte sur les cadres intermédiaires des hôpitaux de Suisse romande. Nous proposons une double lecture : l'évolution de l'identité professionnelle et de la santé au travail des cadres intermédiaires confrontés à de multiples transformations managériales et organisationnelles de leur environnement de travail. Nous soulignons que les réformes hospitalières contemporaines ont des effets sur la manière dont les cadres perçoivent leur rôle et leur mission. Par ailleurs, leur situation au sein de la hiérarchie les place dans une position paradoxale : mettre en oeuvre les décisions prises par les directions hospitalières tout en devant préserver les membres de leur corporation professionnelle des conséquences néfastes de ces décisions. De tels dilemmes provoquent un mal-être au travail. Au final, les cadres intermédiaires se plaignent du rôle impossible qui leur est attribué : encadrer sans autonomie ni ressources.

Laparoscopic Pancreatic Enucleation With End-to-End Pancreatic Duct Reconstruction.

BACKGROUND: Laparoscopic enucleation for neuroendocrine pancreatic tumors has become a feasible technique, with a reported incidence of pancreatic fistula ranging from 13 to 29 %.1 (-) 3 This report describes the first successful case of laparoscopic pancreatic enucleation with resection of the main pancreatic duct followed by end-to-end anastomosis. METHODS: A 41-year-old woman was admitted to the authors' hospital for repeated syncope. Hypoglycemia also was noted. A contrast-enhanced computed tomography examination showed a highly enhanced tumor measuring 22 mm in diameter on the ventral side of the pancreatic body adjacent to the main pancreatic duct. The patient's blood insulin level was elevated, and her diagnosis was determined to be pancreatic insulinoma. Laparoscopic pancreatic enucleation was performed. Approximately 2 cm of the main pancreatic duct was segmentally resected, and a short stent (Silicone tube: Silastic, Dow Corning Corporation, Midland, MI) was inserted. The direct anastomosis of the main pancreatic duct was performed using four separate sutures with an absorbable monofilament (6-0 PDS). RESULTS: The operation time was 166 min, and the estimated blood loss was 100 mL. The postoperative course was uneventful, and the patient was discharged from hospital on postoperative day 7. The pathologic findings showed a well-differentiated insulinoma and a negative surgical margin. A computed tomography examination performed 1 month after the operation showed a successful anastomosis with a patent main pancreatic duct. CONCLUSIONS: Laparoscopic segmental resection of the main pancreatic duct and end-to-end anastomosis can be performed safely with the insertion of a short stent. This technique also can be used for a central pancreatectomy.

Corporate responsibility in the postnational constellation : a multiple-case study

In my thesis I present the findings of a multiple-case study on the CSR approach of three multinational companies, applying Basu and Palazzo's (2008) CSR-character as a process model of sensemaking, Suchman's (1995) framework on legitimation strategies, and Habermas (1996) concept of deliberative democracy. The theoretical framework is based on the assumption of a postnational constellation (Habermas, 2001) which sends multinational companies onto a process of sensemaking (Weick, 1995) with regards to their responsibilities in a globalizing world. The major reason is that mainstream CSR-concepts are based on the assumption of a liberal market economy embedded in a nation state that do not fit the changing conditions for legitimation of corporate behavior in a globalizing world. For the purpose of this study, I primarily looked at two research questions: (i) How can the CSR approach of a multinational corporation be systematized empirically? (ii) What is the impact of the changing conditions in the postnational constellation on the CSR approach of the studied multinational corporations? For the analysis, I adopted a holistic approach (Patton, 1980), combining elements of a deductive and inductive theory building methodology (Eisenhardt, 1989b; Eisenhardt & Graebner, 2007; Glaser & Strauss, 1967; Van de Ven, 1992) and rigorous qualitative data analysis. Primary data was collected through 90 semi-structured interviews in two rounds with executives and managers in three multinational companies and their respective stakeholders. Raw data originating from interview tapes, field notes, and contact sheets was processed, stored, and managed using the software program QSR NVIVO 7. In the analysis, I applied qualitative methods to strengthen the interpretative part as well as quantitative methods to identify dominating dimensions and patterns. I found three different coping behaviors that provide insights into the corporate mindset. The results suggest that multinational corporations increasingly turn towards relational approaches of CSR to achieve moral legitimacy in formalized dialogical exchanges with their stakeholders since legitimacy can no longer be derived only from a national framework. I also looked at the degree to which they have reacted to the postnational constellation by the assumption of former state duties and the underlying reasoning. The findings indicate that CSR approaches become increasingly comprehensive through integrating political strategies that reflect the growing (self-) perception of multinational companies as political actors. Based on the results, I developed a model which relates the different dimensions of corporate responsibility to the discussion on deliberative democracy, global governance and social innovation to provide guidance for multinational companies in a postnational world. With my thesis, I contribute to management research by (i) delivering a comprehensive critique of the mainstream CSR-literature and (ii) filling the gap of thorough qualitative research on CSR in a globalizing world using the CSR-character as an empirical device, and (iii) to organizational studies by further advancing a deliberative view of the firm proposed by Scherer and Palazzo (2008).

Brief alcohol intervention as pragmatic intervention: Who is voluntarily taking an offered intervention?

Brief alcohol interventions (BAI) have shown the potential to decrease problematic alcohol use among adolescents and young adults. Most of the BAI studies have been efficacy trials designed to achieve high internal validity but have raised questions regarding the feasibility of large-scale implementation. Providing interventions for those voluntarily wanting them might offer an alternative, and studies using this design would be more similar to effectiveness studies. The present research compares randomly selected 20-year-old men who took part in a scientific trial (efficacy) with those who voluntarily sought an intervention (effectiveness). Sampling took place during army recruitment procedures that are mandatory for all males in Switzerland. At-risk drinking (20+ drinks per week, or more than one risky drinking occasion of 6+ drinks per month) was determined a posteriori; there was no screening. There were a higher percentage of at-risk drinkers in the volunteer arm at baseline, but at-risk drinkers did not differ from those in the trial arm on any of the assessed alcohol measures. This suggests that offering BAI on a large-scale, voluntary basis may reach at-risk drinkers as effectively as do more scientifically oriented trials, without needing to adhere to screening and stringent research procedures. Nevertheless, BAI was more effective for at-risk drinkers who were invited for trial participation versus those who volunteered. This could be due to behavior that is already consolidated and is difficult to change. Lacking further modifications, real-world implementations of BAI for young men may be less effective than randomized controlled trials designed to test the efficacy of BAI.

Novel FGF8 mutations associated with recessive holoprosencephaly, craniofacial defects, and hypothalamo-pituitary dysfunction.

Context: Fibroblast growth factor (FGF) 8 is important for GnRH neuronal development with human mutations resulting in Kallmann syndrome. Murine data suggest a role for Fgf8 in hypothalamo-pituitary development; however, its role in the etiology of wider hypothalamo-pituitary dysfunction in humans is unknown.Objective: The objective of this study was to screen for FGF8 mutations in patients with septo-optic dysplasia (n = 374) or holoprosencephaly (HPE)/midline clefts (n = 47).Methods: FGF8 was analyzed by PCR and direct sequencing. Ethnically matched controls were then screened for mutated alleles (n = 480-686). Localization of Fgf8/FGF8 expression was analyzed by in situ hybridization in developing murine and human embryos. Finally, Fgf8 hypomorphic mice (Fgf8(loxPNeo/-)) were analyzed for the presence of forebrain and hypothalamo-pituitary defects.Results: A homozygous p.R189H mutation was identified in a female patient of consanguineous parentage with semilobar HPE, diabetes insipidus, and TSH and ACTH insufficiency. Second, a heterozygous p.Q216E mutation was identified in a female patient with an absent corpus callosum, hypoplastic optic nerves, and Moebius syndrome. FGF8 was expressed in the ventral diencephalon and anterior commissural plate but not in Rathke's pouch, strongly suggesting early onset hypothalamic and corpus callosal defects in these patients. This was consolidated by significantly reduced vasopressin and oxytocin staining neurons in the hypothalamus of Fgf8 hypomorphic mice compared with controls along with variable hypothalamo-pituitary defects and HPE.Conclusion: We implicate FGF8 in the etiology of recessive HPE and potentially septo-optic dysplasia/Moebius syndrome for the first time to our knowledge. Furthermore, FGF8 is important for the development of the ventral diencephalon, hypothalamus, and pituitary. (J Clin Endocrinol Metab 96: E1709-E1718, 2011)