Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions.

OBJECTIVES: Gouty arthritis patients for whom non-steroidal anti-inflammatory drugs and colchicine are inappropriate have limited treatment options. Canakinumab, an anti-interleukin-1β monoclonal antibody, may be an option for such patients. The authors assessed the efficacy/safety of one dose of canakinumab 150 mg (n=230) or triamcinolone acetonide (TA) 40 mg (n=226) at baseline and upon a new flare in frequently flaring patients contraindicated for, intolerant of, or unresponsive to non-steroidal anti-inflammatory drugs and/or colchicine. Core study co-primary endpoints were pain intensity 72 h postdose (0-100 mm visual analogue scale and time to first new flare. METHODS: Two 12-week randomised, multicentre, active-controlled, double-blind, parallel-group core studies with double-blind 12-week extensions (response in acute flare and in prevention of episodes of re-flare in gout (β-RELIEVED and β-RELIEVED-II)). RESULTS: 82.6% patients had comorbidities. Mean 72-h visual analogue scale pain score was lower with canakinumab (25.0 mm vs 35.7 mm; difference, -10.7 mm; 95% CI -15.4 to -6.0; p<0.0001), with significantly less physician-assessed tenderness and swelling (ORs=2.16 and 2.74; both p≤0.01) versus TA. Canakinumab significantly delayed time to first new flare, reduced the risk of new flares by 62% versus TA (HR: 0.38; 95% CI 0.26 to 0.57) in the core studies and by 56% (HR: 0.44; 95% CI 0.32 to 0.60; both p≤0.0001) over the entire 24-week period, and decreased median C-reactive protein levels (p≤0.0001 at 72 h and 7 days). Over the 24-week period, adverse events were reported in 66.2% (canakinumab) and 52.8% (TA) and serious adverse events were reported in 8.0% (canakinumab) and 3.5% (TA) of patients. Adverse events reported more frequently with canakinumab included infections, low neutrophil count and low platelet count. CONCLUSION: Canakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis.

Monocular-based 3-D seafloor reconstruction and ortho-mosaicing by piecewise planar representation

Photo-mosaicing techniques have become popular for seafloor mapping in various marine science applications. However, the common methods cannot accurately map regions with high relief and topographical variations. Ortho-mosaicing borrowed from photogrammetry is an alternative technique that enables taking into account the 3-D shape of the terrain. A serious bottleneck is the volume of elevation information that needs to be estimated from the video data, fused, and processed for the generation of a composite ortho-photo that covers a relatively large seafloor area. We present a framework that combines the advantages of dense depth-map and 3-D feature estimation techniques based on visual motion cues. The main goal is to identify and reconstruct certain key terrain feature points that adequately represent the surface with minimal complexity in the form of piecewise planar patches. The proposed implementation utilizes local depth maps for feature selection, while tracking over several views enables 3-D reconstruction by bundle adjustment. Experimental results with synthetic and real data validate the effectiveness of the proposed approach

Non-pharmacological interventions for chronic pain in people with spinal cord injury.

BACKGROUND: Chronic pain is frequent in persons living with spinal cord injury (SCI). Conventionally, the pain is treated pharmacologically, yet long-term pain medication is often refractory and associated with side effects. Non-pharmacological interventions are frequently advocated, although the benefit and harm profiles of these treatments are not well established, in part because of methodological weaknesses of available studies. OBJECTIVES: To critically appraise and synthesise available research evidence on the effects of non-pharmacological interventions for the treatment of chronic neuropathic and nociceptive pain in people living with SCI. SEARCH METHODS: The search was run on the 1st March 2011. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), four other databases and clinical trials registers. In addition, we manually searched the proceedings of three major scientific conferences on SCI. We updated this search in November 2014 but these results have not yet been incorporated. SELECTION CRITERIA: Randomised controlled trials of any intervention not involving intake of medication or other active substances to treat chronic pain in people with SCI. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias in the included studies. The primary outcome was any measure of pain intensity or pain relief. Secondary outcomes included adverse events, anxiety, depression and quality of life. When possible, meta-analyses were performed to calculate standardised mean differences for each type of intervention. MAIN RESULTS: We identified 16 trials involving a total of 616 participants. Eight different types of interventions were studied. Eight trials investigated the effects of electrical brain stimulation (transcranial direct current stimulation (tDCS) and cranial electrotherapy stimulation (CES); five trials) or repetitive transcranial magnetic stimulation (rTMS; three trials). Interventions in the remaining studies included exercise programmes (three trials); acupuncture (two trials); self-hypnosis (one trial); transcutaneous electrical nerve stimulation (TENS) (one trial); and a cognitive behavioural programme (one trial). None of the included trials were considered to have low overall risk of bias. Twelve studies had high overall risk of bias, and in four studies risk of bias was unclear. The overall quality of the included studies was weak. Their validity was impaired by methodological weaknesses such as inappropriate choice of control groups. An additional search in November 2014 identified more recent studies that will be included in an update of this review.For tDCS the pooled mean difference between intervention and control groups in pain scores on an 11-point visual analogue scale (VAS) (0-10) was a reduction of -1.90 units (95% confidence interval (CI) -3.48 to -0.33; P value 0.02) in the short term and of -1.87 (95% CI -3.30 to -0.45; P value 0.01) in the mid term. Exercise programmes led to mean reductions in chronic shoulder pain of -1.9 score points for the Short Form (SF)-36 item for pain experience (95% CI -3.4 to -0.4; P value 0.01) and -2.8 pain VAS units (95% CI -3.77 to -1.83; P value < 0.00001); this represented the largest observed treatment effects in the included studies. Trials using rTMS, CES, acupuncture, self-hypnosis, TENS or a cognitive behavioural programme provided no evidence that these interventions reduce chronic pain. Ten trials examined study endpoints other than pain, including anxiety, depression and quality of life, but available data were too scarce for firm conclusions to be drawn. In four trials no side effects were reported with study interventions. Five trials reported transient mild side effects. Overall, a paucity of evidence was found on any serious or long-lasting side effects of the interventions. AUTHORS' CONCLUSIONS: Evidence is insufficient to suggest that non-pharmacological treatments are effective in reducing chronic pain in people living with SCI. The benefits and harms of commonly used non-pharmacological pain treatments should be investigated in randomised controlled trials with adequate sample size and study methodology.

Transaortic Fallot repair in a grown-up patient: advantages in a situs inversus setting.

We present the case studies of two adult patients with tetralogy of Fallot who were scheduled for surgery. After addressing the right ventricular outflow tract obstruction, the aorta was opened and the ventricular septal defect was approached in a straightforward manner as it was located just under the overriding aortic valve. The second patient presented with was a situs inversus, dextroapex Fallot. In this setting, the aortic approach simplified the repair expeditiously. After 2 years, both patients are in New York Heart Association class I, with no residual ventricular septal defect, no aortic regurgitation, and complete relief of right ventricular outflow tract obstruction.

Undertreatment of acute pain (oligoanalgesia) and medical practice variation in prehospital analgesia of adult trauma patients: a 10 yr retrospective study.

BACKGROUND: Prehospital oligoanalgesia is prevalent among trauma victims, even when the emergency medical services team includes a physician. We investigated if not only patients' characteristics but physicians' practice variations contributed to prehospital oligoanalgesia. METHODS: Patient records of conscious adult trauma victims transported by our air rescue helicopter service over 10 yr were reviewed retrospectively. Oligoanalgesia was defined as a numeric rating scale (NRS) >3 at hospital admission. Multilevel logistic regression analysis was used to predict oligoanalgesia, accounting first for patient case-mix, and then physician-level clustering. The intraclass correlation was expressed as the median odds ratio (MOR). RESULTS: A total of 1202 patients and 77 physicians were included in the study. NRS at the scene was 6.9 (1.9). The prevalence of oligoanalgesia was 43%. Physicians had a median of 5.7 yr (inter-quartile range: 4.2-7.5) of post-graduate training and 27% were female. In our multilevel analysis, significant predictors of oligoanalgesia were: no analgesia [odds ratio (OR) 8.8], National Advisory Committee for Aeronautics V on site (OR 4.4), NRS on site (OR 1.5 per additional NRS unit >4), female physician (OR 2.0), and years of post-graduate experience [>4.0 to ≤5.0 (OR 1.3), >3.0 to ≤4.0 (OR 1.6), >2.0 to ≤3.0 (OR 2.6), and ≤2.0 yr (OR 16.7)]. The MOR was 2.6, and was statistically significant. CONCLUSIONS: Physicians' practice variations contributed to oligoanalgesia, a factor often overlooked in analyses of prehospital pain management. Further exploration of the sources of these variations may provide innovative targets for quality improvement programmes to achieve consistent pain relief for trauma victims.

Postoperative epidural hematoma contributes to delayed upper cord tethering after decompression of Chiari malformation type I.

Symptomatic arachnoiditis after posterior fossa surgical procedures such as decompression of Chiari malformation is a possible complication. Clinical presentation is generally insidious and delayed by months or years. It causes disturbances in the normal flow of cerebrospinal fluid and enlargement of a syrinx cavity in the upper spinal cord. Surgical de-tethering has favorable results with progressive collapse of the syrinx and relief of the associated symptoms. Case Description: A 30-year-old male with Chiari malformation type I was treated by performing posterior fossa bone decompression, dura opening and closure with a suturable bovine pericardium dural graft. Postoperative period was uneventful until the fifth day in which the patient suffered intense headache and progressive loose of consciousness caused by an acute posterior fossa epidural hematoma. It was quickly removed with complete clinical recovering. One year later, the patient experienced progressive worsened of his symptoms. Upper spinal cord tethering was diagnosed and a new surgery for debridement was required. Conclusions: The epidural hematoma compressing the dural graft against the neural structures contributes to the upper spinal cord tethering and represents a nondescribed cause of postoperative fibrosis, adhesion formation, and subsequent recurrent hindbrain compression.

Endometriosis: alternative methods of medical treatment.

Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included "endometriosis" matched with "medical treatment", "new treatment", "GnRH antagonists", "Aromatase inhibitors", "selective progesterone receptor modulators", "anti-TNF α", and "anti-angiogenic factors". Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs.

Block of the superior cervical ganglion, description of a novel ultrasound-guided technique in human cadavers.

OBJECTIVE.: Injection of opioids to the superior cervical ganglion (SCG) has been reported to provide pain relief in patients suffering from different kinds of neuropathic facial pain conditions, such as trigeminal neuralgia, postherpetic neuralgia, and atypical facial pain. The classic approach to the SCG is a transoral technique using a so-called "stopper" to prevent accidental carotid artery puncture. The main disadvantage of this technique is that the needle tip is positioned distant from the actual target, possibly impeding successful block of the SCG. A further limitation is that injection of local anesthetics due to potential carotid artery puncture is contraindicated. We hypothesized that the SCG can be identified and blocked using ultrasound imaging, potentially increasing precision of this technique. INTERVENTIONS.: In this pilot study, 20 US-guided simulated blocks of the SCG were performed in 10 human cadavers in order to determine the accuracy of this novel block technique. After injection of 0.1 mL of dye, the cadavers were dissected to evaluate the needle position and coloring of the SCG. RESULTS.: Nineteen of the 20 needle tips were located in or next to the SCG. This corresponded to a simulated block success rate of 95% (95% confidence interval 85-100%). In 17 cases, the SCG was completely colored, and in two cases, the caudal half of the SCG was colored with dye. CONCLUSIONS.: The anatomical dissections confirmed that our ultrasound-guided approach to the SCG is accurate. Ultrasound could become an attractive alternative to the "blind" transoral technique of SCG blocks.

Application of low temperature thermochronology to understanding cooling and exhumation in the Central Swiss Alps

THESIS ABSTRACT : Low-temperature thermochronology relies on application of radioisotopic systems whose closure temperatures are below temperatures at which the dated phases are formed. In that sense, the results are interpreted as "cooling ages" in contrast to "formation ages". Owing to the low closure-temperatures, it is possible to reconstruct exhumation and cooling paths of rocks during their residence at shallow levels of the crust, i.e. within first ~10 km of depth. Processes occurring at these shallow depths such as final exhumation, faulting and relief formation are fundamental for evolution of the mountain belts. This thesis aims at reconstructing the tectono-thermal history of the Aar massif in the Central Swiss Alps by means of zircon (U-Th)/He, apatite (U-Th)/He and apatite fission track thermochronology. The strategy involved acquisition of a large number of samples from a wide range of elevations in the deeply incised Lötschen valley and a nearby NEAT tunnel. This unique location allowed to precisely constrain timing, amount and mechanisms of exhumation of the main orographic feature of the Central Alps, evaluate the role of topography on the thermochronological record and test the impact of hydrothermal activity. Samples were collected from altitudes ranging between 650 and 3930 m and were grouped into five vertical profiles on the surface and one horizontal in the tunnel. Where possible, all three radiometric systems were applied to each sample. Zircon (U-Th)/He ages range from 5.1 to 9.4 Ma and are generally positively correlated with altitude. Age-elevation plots reveal a distinct break in slope, which translates into exhumation rate increasing from ~0.4 to ~3 km/Ma at 6 Ma. This acceleration is independently confirmed by increased cooling rates on the order of 100°C/Ma constrained on the basis of age differences between the zircon (U-Th)/He and the remaining systems. Apatite fission track data also plot on a steep age-elevation curve indicating rapid exhumation until the end of the Miocene. The 6 Ma event is interpreted as reflecting tectonically driven uplift of the Aar massif. The late Miocene timing implies that the increase of precipitation in the Pliocene did not trigger rapid exhumation in the Aar massif. The Messinian salinity crisis in the Mediterranean could not directly intensify erosion of the Aar but associated erosional output from the entire Alps may have tapered the orogenic wedge and caused reactivation of thrusting in the Aar massif. The high exhumation rates in the Messinian were followed by a decrease to ~1.3 km/Ma as evidenced by ~8 km of exhumation during last 6 Ma. The slowing of exhumation is also apparent from apatite (U-Th)1He age-elevation data in the northern part of the Lötschen valley where they plot on a ~0.5km/Ma line and range from 2.4 to 6.4 Ma However, from the apatite (U-Th)/He and fission track data from the NEAT tunnel, there is an indication of a perturbation of the record. The apatite ages are youngest under the axis of the valley, in contrast to an expected pattern where they would be youngest in the deepest sections of the tunnel due to heat advection into ridges. The valley however, developed in relatively soft schists while the ridges are built of solid granitoids. In line with hydrological observations from the tunnel, we suggest that the relatively permeable rocks under the valley floor, served as conduits of geothermal fluids that caused reheating leading to partial Helium loss and fission track annealing in apatites. In consequence, apatite ages from the lowermost samples are too young and the calculated exhumation rates may underestimate true values. This study demonstrated that high-density sampling is indispensable to provide meaningful thermochronological data in the Alpine setting. The multi-system approach allows verifying plausibility of the data and highlighting sources of perturbation. RÉSUMÉ DE THÈSE : La thermochronologie de basse température dépend de l'utilisation de systèmes radiométriques dont la température de fermeture est nettement inférieure à la température de cristallisation du minéral. Les résultats obtenus sont par conséquent interprétés comme des âges de refroidissement qui diffèrent des âges de formation obtenus par le biais d'autres systèmes de datation. Grâce aux températures de refroidissement basses, il est aisé de reconstruire les chemins de refroidissement et d'exhumation des roches lors de leur résidence dans la croute superficielle (jusqu'à 10 km). Les processus qui entrent en jeu à ces faibles profondeurs tels que l'exhumation finale, la fracturation et le faillage ainsi que la formation du relief sont fondamentaux dans l'évolution des chaînes de montagne. Ces dernières années, il est devenu clair que l'enregistrement thermochronologique dans les orogènes peut être influencé par le relief et réinitialisé par l'advection de la chaleur liée à la circulation de fluides géothermaux après le refroidissement initial. L'objectif de cette thèse est de reconstruire l'histoire tectono-thermique du massif de l'Aar dans les Alpes suisses Centrales à l'aide de trois thermochronomètres; (U-Th)/He sur zircon, (U-Th)/He sur apatite et les traces de fission sur apatite. Afin d'atteindre cet objectif, nous avons récolté un grand nombre d'échantillons provenant de différentes altitudes dans la vallée fortement incisée de Lötschental ainsi que du tunnel de NEAT. Cette stratégie d'échantillonnage nous a permis de contraindre de manière précise la chronologie, les quantités et les mécanismes d'exhumation de cette zone des Alpes Centrales, d'évaluer le rôle de la topographie sur l'enregistrement thermochronologique et de tester l'impact de l'hydrothermalisme sur les géochronomètres. Les échantillons ont été prélevés à des altitudes comprises entre 650 et 3930m selon 5 profils verticaux en surface et un dans le tunnel. Quand cela à été possible, les trois systèmes radiométriques ont été appliqués aux échantillons. Les âges (U-Th)\He obtenus sur zircons sont compris entre 5.l et 9.4 Ma et sont corrélés de manière positive avec l'altitude. Les graphiques représentant l'âge et l'élévation montrent une nette rupture de la pente qui traduisent un accroissement de la vitesse d'exhumation de 0.4 à 3 km\Ma il y a 6 Ma. Cette accélération de l'exhumation est confirmée par les vitesses de refroidissement de l'ordre de 100°C\Ma obtenus à partir des différents âges sur zircons et à partir des autres systèmes géochronologiques. Les données obtenues par traces de fission sur apatite nous indiquent également une exhumation rapide jusqu'à la fin du Miocène. Nous interprétons cet évènement à 6 Ma comme étant lié à l'uplift tectonique du massif de l'Aar. Le fait que cet évènement soit tardi-miocène implique qu'une augmentation des précipitations au Pliocène n'a pas engendré cette exhumation rapide du massif de l'Aar. La crise Messinienne de la mer méditerranée n'a pas pu avoir une incidence directe sur l'érosion du massif de l'Aar mais l'érosion associée à ce phénomène à pu réduire le coin orogénique alpin et causer la réactivation des chevauchements du massif de l'Aar. L'exhumation rapide Miocène a été suivie pas une diminution des taux d'exhumation lors des derniers 6 Ma (jusqu'à 1.3 km\Ma). Cependant, les âges (U-Th)\He sur apatite ainsi que les traces de fission sur apatite des échantillons du tunnel enregistrent une perturbation de l'enregistrement décrit ci-dessus. Les âges obtenus sur les apatites sont sensiblement plus jeunes sous l'axe de la vallée en comparaison du profil d'âges attendus. En effet, on attendrait des âges plus jeunes sous les parties les plus profondes du tunnel à cause de l'advection de la chaleur dans les flancs de la vallée. La vallée est creusée dans des schistes alors que les flancs de celle-ci sont constitués de granitoïdes plus durs. En accord avec les observations hydrologiques du tunnel, nous suggérons que la perméabilité élevée des roches sous l'axe de la vallée à permi l'infiltration de fluides géothermaux qui a généré un réchauffement des roches. Ce réchauffement aurait donc induit une perte d'Hélium et un recuit des traces de fission dans les apatites. Ceci résulterait en un rajeunissement des âges apatite et en une sous-estimation des vitesses d'exhumation sous l'axe de la vallée. Cette étude à servi à démontrer la nécessité d'un échantillonnage fin et précis afin d'apporter des données thermochronologiques de qualité dans le contexte alpin. Cette approche multi-système nous a permi de contrôler la pertinence des données acquises ainsi que d'identifier les sources possibles d'erreurs lors d'études thermochronologiques. RÉSUMÉ LARGE PUBLIC Lors d'une orogenèse, les roches subissent un cycle comprenant une subduction, de la déformation, du métamorphisme et, finalement, un retour à la surface (ou exhumation). L'exhumation résulte de la déformation au sein de la zone de collision, menant à un raccourcissement et un apaissessement de l'édifice rocheux, qui se traduit par une remontée des roches, création d'une topographie et érosion. Puisque l'érosion agit comme un racloir sur la partie supérieure de l'édifice, des tentatives de corrélation entre les épisodes d'exhumation rapide et les périodes d'érosion intensive, dues aux changements climatiques, ont été effectuées. La connaissance de la chronologie et du lieu précis est d'une importance capitale pour une quelconque reconstruction de l'évolution d'une chaîne de montagne. Ces critères sont donnés par un retraçage des changements de la température de la roche en fonction du temps, nous donnant le taux de refroidissement. L'instant auquel les roches ont refroidit, passant une certaine température, est contraint par l'application de techniques de datation par radiométrie. Ces méthodes reposent sur la désintégration des isotopes radiogéniques, tels que l'uranium et le potassium, tous deux abondants dans les roches de la croûte terrestre. Les produits de cette désintégration ne sont pas retenus dans les minéraux hôtes jusqu'au moment du refroidissement de la roche sous une température appelée 'de fermeture' , spécifique à chaque système de datation. Par exemple, la désintégration radioactive des atomes d'uranium et de thorium produit des atomes d'hélium qui s'échappent d'un cristal de zircon à des températures supérieures à 200°C. En mesurant la teneur en uranium-parent, l'hélium accumulé et en connaissant le taux de désintégration, il est possible de calculer à quel moment la roche échantillonnée est passée sous la température de 200°C. Si le gradient géothermal est connu, les températures de fermeture peuvent être converties en profondeurs actuelles (p. ex. 200°C ≈ 7km), et le taux de refroidissement en taux d'exhumation. De plus, en datant par système radiométrique des échantillons espacés verticalement, il est possible de contraindre directement le taux d'exhumation de la section échantillonnée en observant les différences d'âges entre des échantillons voisins. Dans les Alpes suisses, le massif de l'Aar forme une structure orographique majeure. Avec des altitudes supérieures à 4000m et un relief spectaculaire de plus de 2000m, le massif domine la partie centrale de la chaîne de montagne. Les roches aujourd'hui exposées à la surface ont été enfouies à plus de 10 km de profond il y a 20 Ma, mais la topographie actuelle du massif de l'Aar semble surtout s'être développée par un soulèvement actif depuis quelques millions d'années, c'est-à-dire depuis le Néogène supérieur. Cette période comprend un changement climatique soudain ayant touché l'Europe il y a environ 5 Ma et qui a occasionné de fortes précipitations, entraînant certainement une augmentation de l'érosion et accélérant l'exhumation des Alpes. Dans cette étude, nous avons employé le système de datation (U-TH)/He sur zircon, dont la température de fermeture de 200°C est suffisamment basse pour caractériser l'exhumation du Néogène sup. /Pliocène. Les échantillons proviennent du Lötschental et du tunnel ferroviaire le plus profond du monde (NEAT) situé dans la partie ouest du massif de l'Aar. Considérés dans l'ensemble, ces échantillons se répartissent sur un dénivelé de 3000m et des âges de 5.1 à 9.4 Ma. Les échantillons d'altitude supérieure (et donc plus vieux) documentent un taux d'exhumation de 0.4 km/Ma jusqu'à il y a 6 Ma, alors que les échantillons situés les plus bas ont des âges similaires allant de 6 à 5.4 Ma, donnant un taux jusqu'à 3km /Ma. Ces données montrent une accélération dramatique de l'exhumation du massif de l'Aar il y a 6 Ma. L'exhumation miocène sup. du massif prédate donc le changement climatique Pliocène. Cependant, lors de la crise de salinité d'il y a 6-5.3 Ma (Messinien), le niveau de la mer Méditerranée est descendu de 3km. Un tel abaissement de la surface d'érosion peut avoir accéléré l'exhumation des Alpes, mais le bassin sud alpin était trop loin du massif de l'Aar pour influencer son érosion. Nous arrivons à la conclusion que la datation (U-Th)/He permet de contraindre précisément la chronologie et l'exhumation du massif de l'Aar. Concernant la dualité tectonique-érosion, nous suggérons que, dans le cas du massif de l'Aar, la tectonique prédomine.

La geografía en los relatos de viajes castellanos del ocaso de la Edad Media : análisis del discurso y léxico

Résumé Le travail poursuit un triple objectif: A) présenter la place qu'occupe la géographie physique et la géographie urbaine dans un corpus de cinq récits de voyages castillans de la fin du Moyen-Age, en se centrant particulièrement sur le relief, les eaux continentales, les mers, les côtes, le climat, la végétation, la faune et les villes; B) analyser les ressources discursives dont se servent les rédacteurs pour transmettre ces contenus; C) et réunir le lexique géographique des textes, en l'organisant autour des thématiques mentionnées, en définissant les mots et en faisant ressortir leur valeur dans le contexte discursif. L'étude est introduite par une analyse de la situation communicative dans laquelle se forgent les récits du corpus: contexte historique, social, culturel et textuel, d'une part; identité des voyageurs- rédacteurs, identité des destinataires, et objectifs divers aussi bien des voyages que de leur mise en écriture, d'autre part. De cette analyse ressortent quelques intentions et préoccupations communes aux voyageurs-rédacteurs qui pourraient se résumer en: A) une conscience de la difficulté du voyage; B) une conscience de réaliser un mouvement vers un monde éloigné et étrange; C) une volonté de transmettre des connaissances sur le monde; D) un désir de présenter ce qu'ils racontent comme le fruit d'une expérience vécue et de le faire avec véracité. L'analyse introductoire montre également que cette approche du voyage et la conception du récit qui en découle déterminent le choix de certains contenus géographiques et une façon précise d'exposer l'expérience du voyage: les textes transmettent des connaissances sur le monde et construisent un discours informatif sur l'espace, tout en décrivant un univers étrange et en insistant sur leur caractère testimonial. Le corps du travail est articulé en trois parties. Le premier volet permet de faire émerger la place réservée à la géographie, surtout physique, dans les récits. Il dévoile l'intérêt naissant manifesté par les voyageurs-rédacteurs pour la géographie physique et témoigne de la typologie diversifiée des descriptions urbaines. Il éclaire également le rapport intime liant les thématiques privilégiées dans les textes, les intérêts des rédacteurs et de leur public, et les objectifs de chaque récit. La géographie transmise est non-livresque, issue de l'expérience et, par conséquent, partielle. Le deuxième volet montre le fonctionnement d'une description qui est porteuse d'informations sur l'espace et qui véhicule des savoirs sur le monde, en particulier sur le monde inconnu. Les opérations de nommer, mesurer et adjectiver l'espace parcouru, en le comparant ensuite à l'espace connu sont analysées en détail. Cette partie du travail met en exergue les connaissances, les croyances et les valeurs partagées entre rédacteurs et récepteurs sur lesquelles se construit un discours destiné à transmettre de nouveaux savoirs sur le monde. Les textes se présentent, en outre, comme un témoignage basé sur l'expérience des voyageurs: l'importance de l'information acquise par l'ouïe porte les rédacteurs à incorporer dans leurs récits de nombreuses voix qui racontent le monde et fait du discours géographique un discours clairement polyphonique. Enfin, le troisième volet réunit pour la première fois le lexique géographique castillan en usage à la fin du Moyen-Âge. Procédant de textes rédigés par des non spécialistes, il nous permet d'évaluer les connaissances géographiques d'un homme de l'époque et inclut définitions, exemples d'usage des mots en contexte, données étymologiques, diachroniques, morphosyntaxiques, sémantiques et encyclopédiques. Dans son ensemble, la thèse témoigne de l'intérêt d'une approche des récits de voyage par le triple axe thématique, discursif et lexical.

Faire connaître la poésie suisse romande outre-Atlantique: Lausanne - New York aller-retour. Récit d'une verticalité entre identité et altérité

Cet article présente la synthèse du travail de traduction à quatre mains par My. Moraz et Tim Keane un collègue new-yorkais des poètes romands Pierre-Alain Tâche et Pierre Chappuis. Nous avons essayé de revenir sur notre manière de travailler et de mettre en relief les choix opérés dans le passage du français à l'anglais dans ce que ces deux langues ont de spécifique.

FIB-SEM tomography in biology.

Three-dimensional information is much easier to understand than a set of two-dimensional images. Therefore a layman is thrilled by the pseudo-3D image taken in a scanning electron microscope (SEM) while, when seeing a transmission electron micrograph, his imagination is challenged. First approaches to gain insight in the third dimension were to make serial microtome sections of a region of interest (ROI) and then building a model of the object. Serial microtome sectioning is a tedious and skill-demanding work and therefore seldom done. In the last two decades with the increase of computer power, sophisticated display options, and the development of new instruments, an SEM with a built-in microtome as well as a focused ion beam scanning electron microscope (FIB-SEM), serial sectioning, and 3D analysis has become far easier and faster.Due to the relief like topology of the microtome trimmed block face of resin-embedded tissue, the ROI can be searched in the secondary electron mode, and at the selected spot, the ROI is prepared with the ion beam for 3D analysis. For FIB-SEM tomography, a thin slice is removed with the ion beam and the newly exposed face is imaged with the electron beam, usually by recording the backscattered electrons. The process, also called "slice and view," is repeated until the desired volume is imaged.As FIB-SEM allows 3D imaging of biological fine structure at high resolution of only small volumes, it is crucial to perform slice and view at carefully selected spots. Finding the region of interest is therefore a prerequisite for meaningful imaging. Thin layer plastification of biofilms offers direct access to the original sample surface and allows the selection of an ROI for site-specific FIB-SEM tomography just by its pronounced topographic features.

Influence of preoperative leg pain and radiculopathy on outcomes in mono-segmental lumbar total disc replacement: results from a nationwide registry.

PURPOSE: Currently, many pre-conditions are regarded as relative or absolute contraindications for lumbar total disc replacement (TDR). Radiculopathy is one among them. In Switzerland it is left to the surgeon's discretion when to operate if he adheres to a list of pre-defined indications. Contraindications, however, are less clearly specified. We hypothesized that, the extent of pre-operative radiculopathy results in different benefits for patients treated with mono-segmental lumbar TDR. We used patient perceived leg pain and its correlation with physician recorded radiculopathy for creating the patient groups to be compared. METHODS: The present study is based on the dataset of SWISSspine, a government mandated health technology assessment registry. Between March 2005 and April 2009, 577 patients underwent either mono- or bi-segmental lumbar TDR, which was documented in a prospective observational multicenter mode. A total of 416 cases with a mono-segmental procedure were included in the study. The data collection consisted of pre-operative and follow-up data (physician based) and clinical outcomes (NASS form, EQ-5D). A receiver operating characteristic (ROC) analysis was conducted with patients' self-indicated leg pain and the surgeon-based diagnosis "radiculopathy", as marked on the case report forms. As a result, patients were divided into two groups according to the severity of leg pain. The two groups were compared with regard to the pre-operative patient characteristics and pre- and post-operative pain on Visual Analogue Scale (VAS) and quality of life using general linear modeling. RESULTS: The optimal ROC model revealed a leg pain threshold of 40 ≤ VAS > 40 for the absence or the presence of "radiculopathy". Demographics in the resulting two groups were well comparable. Applying this threshold, the mean pre-operative leg pain level was 16.5 points in group 1 and 68.1 points in group 2 (p < 0.001). Back pain levels differed less with 63.6 points in group 1 and 72.6 in group 2 (p < 0.001). Pre-operative quality of life showed considerable differences with an 0.44 EQ-5D score in group 1 and 0.29 in group 2 (p < 0.001, possible score range -0.6 to 1). At a mean follow-up time of 8 months, group 1 showed a mean leg pain improvement of 3.6 points and group 2 of 41.1 points (p < 0.001). Back pain relief was 35.6 and 39.1 points, respectively (p = 0.27). EQ-5D score improvement was 0.27 in group 1 and 0.41 in group 2 (p = 0.11). CONCLUSIONS: Patients labeled as having radiculopathy (group 2) do mostly have pre-operative leg pain levels ≥ 40. Applying this threshold, the patients with pre-operative leg pain do also have more severe back pain and a considerably lower quality of life. Their net benefit from the lumbar TDR is higher and they do have similar post-operative back and leg pain levels as well as the quality of life as patients without pre-operative leg pain. Although randomized controlled trials are required to confirm these findings, they put leg pain and radiculopathy into perspective as absolute contraindications for TDR.

Le grand nymphée de Leptis Magna : étude historiographique, urbanistique et architecturale

RESUME en français Centrée sur le grand nymphée de Leptis Magna la recherche met en évidence l'évolution et la signification de ce monument des eaux dans l'une des plus importantes cités africaines de l'époque romaine en mettant en lumière trois thèmes principaux. L'étude historiographique permet tout d'abord d'appréhender, à l'aide des témoignages littéraires des siècles derniers et d'une abondante documentation d'archive, l'histoire de l'édifice de son ensablement à sa remise au jour, puis de suivre les différentes étapes de son dégagement et de sa restauration, mettant ainsi en relief la perception des divers observateurs à l'encontre du monument. L'étude urbanistique permet ensuite de dégager la signification de l'édifice dans la cité par rapport aux autres monuments du secteur aux différentes périodes de son histoire, ainsi que de reconstituer l'approvisionnement en eau de Leptis Magna. Enfin, l'étude architecturale s'intéresse à l'analyse détaillée des structures, permettant la mise en évidence de la conception initiale, du fonctionnement et des transformations du nymphée. Cette dernière approche, qui s'accompagne d'un catalogue circonstancié des éléments du décor, fait intervenir des considérations sur les techniques de constructions, le traitement des blocs d'ornementation et, d'une manière plus générale, sur ('économie du chantier. Cette recherche permet non seulement de reconstituer l'aspect, le rôle et l'histoire du monument et de le replacer dans la série des nymphées romains, mais aussi de percevoir son impact sur les habitants du lieu aux différents moments de son histoire, cherchant ainsi à rejoindre par l'archéologie des considérations sociologiques. THE GREAT SEVERAN NYMPHAEUM OF LEPTIS MAGNA: HISTORIOGRAPHICAL, URBANISTIC AND ARCHITECTURAL STUDY RESUME en anglais Based on the great nymphaeum of Leptis Magna, the research considers the development and significance of this water monument in one of the most important African cities of the Roman period, through three principal aspects. The historiographical study aboards the subject through literary testimony from the last centuries and an abundance of documentary archives, the history of the edifice from its burial to its reconstruction, studying the different stages of its unearthing and its restoration, thus pinpointing perspectives from various observers of the monument. The urban study divulges the significance of the edifice in the city, in comparison with other monuments in the region over different periods of its history, as well as reconstituting Leptis Magna's water supply. Finally, the architectural study undertakes a detailed analysis of the structures, which highlights the conception and the transformations of the nymphaeum, as well as its hydraulic functions. This architectural approach, which is accompanied by a detailed catalogue of the decorative elements, juxtaposes the technical considerations of construction with the ornamental treatment of the marble blocks, accounting for the economical aspects of the site of the nymphaeum. This research proposes not only a consideration of the appearance, the role and the history of the monument and situates it within the series of Roman nymphaea, but also the perception of its impact on the local inhabitants at different moments in its history, looking for accomplish by archaeology some sociological considerations.