Comparative Analysis of Existing Guidelines for Gender-Fair Language within the ITN LCG Network. ITN-LCG, Workpackage B: Report on Milestone 1

Guidelines for a gender-fair use of the languages represented in the ITN LCG network were analyzed comparatively for specific criteria. All institutional or governmental guidelines aim at attenuating male-biased representations that are brought about by certain grammatical structures of the respective language. These guidelines primarily focus on the use of masculine forms as generics because they reduce the visibility of women in language. The comparison shows that guidelines for English, a language without grammatical gender, emphasize neutralization as a means of referring to both sexes. This differs from grammatical gender languages, such as German and Italian, in which feminine-masculine word-pairs are recommended in order to avoid the masculine bias. The guidelines all aim to promote the formulation of comprehensive and readable texts that are free of discrimination.

IN.PACT Amphirion paclitaxel eluting balloon versus standard percutaneous transluminal angioplasty for infrapopliteal revascularization of critical limb ischemia: rationale and protocol for an ongoing randomized controlled trial

BACKGROUND The effectiveness and durability of endovascular revascularization therapies for chronic critical limb ischemia (CLI) are challenged by the extensive burden of infrapopliteal arterial disease and lesion-related characteristics (e.g., severe calcification, chronic total occlusions), which frequently result in poor clinical outcomes. While infrapopliteal vessel patency directly affects pain relief and wound healing, sustained patency and extravascular care both contribute to the ultimate "patient-centric" outcomes of functional limb preservation, mobility and quality of life (QoL). METHODS/DESIGN IN.PACT DEEP is a 2:1 randomized controlled trial designed to assess the efficacy and safety of infrapopliteal arterial revascularization between the IN.PACT Amphirion™ paclitaxel drug-eluting balloon (IA-DEB) and standard balloon angioplasty (PTA) in patients with Rutherford Class 4-5-6 CLI. DISCUSSION This multicenter trial has enrolled 358 patients at 13 European centers with independent angiographic core lab adjudication of the primary efficacy endpoint of target lesion late luminal loss (LLL) and clinically driven target lesion revascularization (TLR) in major amputation-free surviving patients through 12-months. An independent wound core lab will evaluate all ischemic wounds to assess the extent of healing and time to healing at 1, 6, and 12 months. A QoL questionnaire including a pain scale will assess changes from baseline scores through 12 months. A Clinical Events Committee and Data Safety Monitoring Board will adjudicate the composite primary safety endpoints of all-cause death, major amputation, and clinically driven TLR at 6 months and other trial endpoints and supervise patient safety throughout the study. All patients will be followed for 5 years. A literature review is presented of the current status of endovascular treatment of CLI with drug-eluting balloon and standard PTA. The rationale and design of the IN.PACT DEEP Trial are discussed. IN.PACT DEEP is a milestone, prospective, randomized, robust, independent core lab-adjudicated CLI trial that will evaluate the role of a new infrapopliteal revascularization technology, the IA-DEB, compared to PTA. It will assess the overall impact on infrapopliteal artery patency, limb salvage, wound healing, pain control, QoL, and patient mobility. The 1-year results of the adjudicated co-primary and secondary endpoints will be available in 2014. TRIAL REGISTRATION NCT00941733

EChO

A dedicated mission to investigate exoplanetary atmospheres represents a major milestone in our quest to understand our place in the universe by placing our Solar System in context and by addressing the suitability of planets for the presence of life. EChO—the Exoplanet Characterisation Observatory—is a mission concept specifically geared for this purpose. EChO will provide simultaneous, multi-wavelength spectroscopic observations on a stable platform that will allow very long exposures. The use of passive cooling, few moving parts and well established technology gives a low-risk and potentially long-lived mission. EChO will build on observations by Hubble, Spitzer and ground-based telescopes, which discovered the first molecules and atoms in exoplanetary atmospheres. However, EChO’s configuration and specifications are designed to study a number of systems in a consistent manner that will eliminate the ambiguities affecting prior observations. EChO will simultaneously observe a broad enough spectral region—from the visible to the mid-infrared—to constrain from one single spectrum the temperature structure of the atmosphere, the abundances of the major carbon and oxygen bearing species, the expected photochemically-produced species and magnetospheric signatures. The spectral range and resolution are tailored to separate bands belonging to up to 30 molecules and retrieve the composition and temperature structure of planetary atmospheres. The target list for EChO includes planets ranging from Jupiter-sized with equilibrium temperatures T eq up to 2,000 K, to those of a few Earth masses, with T eq \u223c 300 K. The list will include planets with no Solar System analog, such as the recently discovered planets GJ1214b, whose density lies between that of terrestrial and gaseous planets, or the rocky-iron planet 55 Cnc e, with day-side temperature close to 3,000 K. As the number of detected exoplanets is growing rapidly each year, and the mass and radius of those detected steadily decreases, the target list will be constantly adjusted to include the most interesting systems. We have baselined a dispersive spectrograph design covering continuously the 0.4–16 μm spectral range in 6 channels (1 in the visible, 5 in the InfraRed), which allows the spectral resolution to be adapted from several tens to several hundreds, depending on the target brightness. The instrument will be mounted behind a 1.5 m class telescope, passively cooled to 50 K, with the instrument structure and optics passively cooled to \u223c45 K. EChO will be placed in a grand halo orbit around L2. This orbit, in combination with an optimised thermal shield design, provides a highly stable thermal environment and a high degree of visibility of the sky to observe repeatedly several tens of targets over the year. Both the baseline and alternative designs have been evaluated and no critical items with Technology Readiness Level (TRL) less than 4–5 have been identified. We have also undertaken a first-order cost and development plan analysis and find that EChO is easily compatible with the ESA M-class mission framework.

Social stratigraphy in Late Iron Age Switzerland: Stable carbon, nitrogen and sulphur isotope analysis of human remains from Münsingen

The Iron Age cemetery of Münsingen in Switzerland with 220 abundantly equipped burials marked a milestone for Iron Age research. The horizontal spread throughout the time of its occupancy laid the foundation for the chronology system of the Late Iron Age. Today, skulls of 77 individuals and some postcranial bones are still preserved. The aim of the study was to obtain information about diet, mobility and social stratification of the individuals. Stable isotope ratios of carbon, nitrogen and sulphur were analysed for 63 individuals. For all of them C3 plants were found to be the staple food. There are significant differences between males and females in δ13C and δ15N values. This points to a gender restriction in the access to animal protein with males probably having more access to meat and dairy products. Differences in δ15N values were also observed for different age classes. δ34S values indicate a terrestrial-based diet with no significant intake of marine or freshwater fish. Seven adults with enriched δ34S values might have immigrated to Münsingen, four of which were found in the oldest part of the cemetery. Furthermore, possible changes of the vegetation are indicated by the more positive stable carbon ratios in the later phases. The results lead to the suggestion that especially males buried with weapons might have played a special role in the Iron Age society.

Expression, purification, and structural insights for the human uric acid transporter, GLUT9, using the Xenopus laevis oocytes system.

The urate transporter, GLUT9, is responsible for the basolateral transport of urate in the proximal tubule of human kidneys and in the placenta, playing a central role in uric acid homeostasis. GLUT9 shares the least homology with other members of the glucose transporter family, especially with the glucose transporting members GLUT1-4 and is the only member of the GLUT family to transport urate. The recently published high-resolution structure of XylE, a bacterial D-xylose transporting homologue, yields new insights into the structural foundation of this GLUT family of proteins. While this represents a huge milestone, it is unclear if human GLUT9 can benefit from this advancement through subsequent structural based targeting and mutagenesis. Little progress has been made toward understanding the mechanism of GLUT9 since its discovery in 2000. Before work can begin on resolving the mechanisms of urate transport we must determine methods to express, purify and analyze hGLUT9 using a model system adept in expressing human membrane proteins. Here, we describe the surface expression, purification and isolation of monomeric protein, and functional analysis of recombinant hGLUT9 using the Xenopus laevis oocyte system. In addition, we generated a new homology-based high-resolution model of hGLUT9 from the XylE crystal structure and utilized our purified protein to generate a low-resolution single particle reconstruction. Interestingly, we demonstrate that the functional protein extracted from the Xenopus system fits well with the homology-based model allowing us to generate the predicted urate-binding pocket and pave a path for subsequent mutagenesis and structure-function studies.

Diet and mobility of an Iron Age population in Switzerland; Stable carbon, nitrogen and sulphur isotope analysis of the human remains from Münsingen

The 220 abundantly equipped burials from the Late Iron Age cemetery of Münsingen (420 – 240 BC) marked a milestone for Iron Age research. The evident horizontal spread throughout the time of occupancy laid the foundation for the chronology system of the Late Iron Age. Today the skulls of 77 individuals and some postcranial bones are still preserved. The aim was to obtain information about nutrition, social stratification and migration of the individuals from Münsingen. Stable isotope ratios of carbon, nitrogen and sulphur were analysed. The results of 63 individuals show that all consumed C3 plants as staple food with significant differences between males and females in δ13C and δ15N values. The results indicate a gender restriction in access to animal protein. Stable isotope values of one male buried with weapons and meat as grave goods suggest a diet with more animal proteins than the other individuals. It is possible that he was privileged due to high status. Furthermore, the δ34S values indicate minor mobility. Assuming that the subadults represent the local signal of δ34S it is very likely that adults with enriched δ34S could have migrated to Münsingen at some point during their lives. This study presents stable isotope values of one of the most important Late Iron Age burial sites in Central Europe. The presented data provide new insight into diet, migration and social stratification of the population from Münsingen.

Social stratigraphy in Late Iron Age Switzerland: Analysis of human remains from Münsingen

The Iron Age cemetery of Münsingen in Switzerland with 220 abundantly equipped burials marked a milestone for Iron Age research. The horizontal spread throughout the time of its occupancy laid the foundation for the chronology system of the Late Iron Age. Today, skulls of 77 individuals and some postcranial bones are still preserved and were investigated anthropologically. Collagen was analysed via stable isotope mass spectrometry (carbon, nitrogen, and sulphur). Additionally, some bones showed pathologies or lesions which were examined via imaging and histological methods. The aim of the study was to obtain biological-anthropological information about the Iron Age population. There are significant differences between males and females in δ13C and δ15N values. This points to a gender restriction in the access to animal protein with males having more access to meat and dairy products. Differences in δ15N values were also observed for different age classes. δ34S values indicate a terrestrial-based diet with no significant intake of marine or freshwater fish. Seven adults with enriched δ34S values might have immigrated to Münsingen, four of which were found in the oldest part of the cemetery. Furthermore, possible changes of the vegetation are indicated by the more positive stable carbon ratios in the later phases. The results lead to the suggestion that especially males buried with weapons might have played a special role in the Iron Age society. Also, skull trepanations in two males suggest that surgical treatment of injuries caused by weapons may have been performed.

The hundred most cited articles in bariatric surgery

BACKGROUND Many studies quantitatively analyzing scientific papers have appeared in the last 2 years. Citation analysis is a commonly used bibliometric method. In spite of some limitations, it remains a good measure of the impact an article has on a specific field, specialty, or a journal. The aim of this study was to analyze the qualities and characteristics of the 100 most cited articles in the field of bariatric surgery. METHODS The Thomson Reuters Web of Knowledge was used to list all bariatric surgery-related articles (BSRA) published from 1945 to 2014. The top 100 most cited BSRA in 354 surgical and high impact general journals were selected for further analysis. RESULTS Most of the articles were published in the 2000s (60%). The top 100 most cited were published in 17 of the 354 journals. Leading countries were USA followed by Canada and Australia. Most of the articles published (76%) were clinical experience articles. The most common level of evidence was IV (42%). CONCLUSIONS Many of the milestone papers in bariatric surgery have been included in this bibliometric study. A huge increase in research activity during the last decade is clearly visible in the field. It is apparent that the number of citations of an article is not related to its level of evidence; a fact that is increasingly being emphasized in surgical research.

Developing drugs for use before, during and soon after percutaneous coronary intervention.

INTRODUCTION Percutaneous coronary intervention (PCI) is a milestone for treating coronary artery disease (CAD). Antithrombotic therapy is essential to prevent ischemic complications, including the microvascular no-reflow, while minimizing bleeding events. Areas covered: This overview discusses available and developing drugs for PCI including anticoagulants, antiplatelets and treatment of no-reflow. Expert opinion: For years unfractionated heparin (UFH) has been the unique anticoagulant to be used before and during PCI. Enoxaparin showed similar efficacy and safety, yet, based on recent trials, bivalirudin has been shown to have some benefits, particularly for patients with ST-segment elevation myocardial infarction (STEMI). The evidence concerning new anticoagulants is still preliminary, except for new oral anticoagulants, particularly rivaroxaban that showed intriguing findings and is currently under investigation. Dual antiplatelet therapy (DAPT) is the standard of care after PCI, but new developments have recently emerged. Indeed, ticagrelor and prasugrel are currently recommended over clopidogrel due to their significant reduction of ischemic events in acute coronary syndrome (ACS) whereas clopidogrel remains the choice in stable CAD. Among new agents, vorapaxar and cangrelor showed positive but limited evidence and might be considered at least in selected patients. Conversely, evidence on effective treatments for no-reflow remains limited and would require future dedicated research.