Predictive value of the MGMT promoter methylation status in metastatic melanoma patients receiving first-line temozolomide plus bevacizumab in the trial SAKK 50/07.

The O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical trials with temozolomide plus bevacizumab therapy in metastatic melanoma patients are ongoing, although the predictive value of the MGMT promoter methylation status in this setting remains unclear. We assessed MGMT promoter methylation in formalin-fixed, primary tumor tissue of metastatic melanoma patients treated with first-line temozolomide and bevacizumab from the trial SAKK 50/07 by methylation-specific polymerase chain reaction. In addition, the MGMT expression levels were also analyzed by MGMT immunohistochemistry. Eleven of 42 primary melanomas (26%) revealed a methylated MGMT promoter. Promoter methylation was significantly associated with response rates CR + PR versus SD + PD according to RECIST (response evaluation criteria in solid tumors) (p<0.05) with a trend to prolonged median progression-free survival (8.1 versus 3.4 months, p>0.05). Immunohistochemically different protein expression patterns with heterogeneous and homogeneous nuclear MGMT expression were identified. Negative MGMT expression levels were associated with overall disease stabilization CR + PR + SD versus PD (p=0.05). There was only a poor correlation between MGMT methylation and lack of MGMT expression. A significant proportion of melanomas have a methylated MGMT promoter. The MGMT promoter methylation status may be a promising predictive marker for temozolomide therapy in metastatic melanoma patients. Larger sample sizes may help to validate significant differences in survival type endpoints.

Bayesian Networks and the Value of the Evidence for the Forensic Two-Trace Transfer Problem

Forensic scientists face increasingly complex inference problems for evaluating likelihood ratios (LRs) for an appropriate pair of propositions. Up to now, scientists and statisticians have derived LR formulae using an algebraic approach. However, this approach reaches its limits when addressing cases with an increasing number of variables and dependence relationships between these variables. In this study, we suggest using a graphical approach, based on the construction of Bayesian networks (BNs). We first construct a BN that captures the problem, and then deduce the expression for calculating the LR from this model to compare it with existing LR formulae. We illustrate this idea by applying it to the evaluation of an activity level LR in the context of the two-trace transfer problem. Our approach allows us to relax assumptions made in previous LR developments, produce a new LR formula for the two-trace transfer problem and generalize this scenario to n traces.

Clypeal patterning in the paper wasp Polistes dominulus: no evidence of adaptive value in the wild

Status signals function in a number of species to communicate competitive ability to conspecific rivals during competition for resources. In the paper wasp Polistes dominulus, variable black clypeal patterns are thought to be important in mediating competition among females. Results of previous behavioral experiments in the lab indicate that P dominulus clypeal patterns provide information about an individual's competitive ability to rivals during agonistic interactions. To date, however, there has been no detailed examination of the adaptive value of clypeal patterns in the wild. To address this, we looked for correlations between clypeal patterning and various fitness measures, including reproductive success, hierarchical rank, and survival, in a large, free-living population of P. dominulus in southern Spain. Reproductive success over the nesting season was not correlated with clypeal patterning. Furthermore, there was no relationship between a female's clypeal patterning and the rank she achieved within the hierarchy or her survival during nest founding. Overall, we found no evidence that P dominulus clypeal patterns are related to competitive ability or other aspects of quality in our population. This result is consistent with geographical variation in the adaptive value of clypeal patterns between P. dominulus populations; however, data on the relationship between patterning and fitness from other populations are required to test this hypothesis.

Maltraitance: une formation évaluée à dix ans: Une démarche originale [Abuse: training evaluated at 10 years: an original approach]

[Introduction (extrait)] Il existe de nombreuses formations destinées à prévenir la maltraitance envers les personnes âgées. A ce jour, leur efficacité n'est cependant pas prouvée, faute d'évaluation de leur impact sur les pratiques professionnelles. La formation PREMALPA, qui existe depuis 2003, a fait l'objet d'une évaluation en 2013.

Arthro-IRM directe en traction axiale: technique et intérêt [Technique and value of direct MR arthrography applying articular distraction]

Direct MR arthrography has a better diagnostic accuracy than MR imaging alone. However, contrast material is not always homogeneously distributed in the articular space. Lesions of cartilage surfaces or intra-articular soft tissues can thus be misdiagnosed. Concomitant application of axial traction during MR arthrography leads to articular distraction. This enables better distribution of contrast material in the joint and better delineation of intra-articular structures. Therefore, this technique improves detection of cartilage lesions. Moreover, the axial stress applied on articular structures may reveal lesions invisible on MR images without traction. Based on our clinical experience, we believe that this relatively unknown technique is promising and should be further developed.

Diagnostic and prognostic value of cerebral 31P magnetic resonance spectroscopy in neonates with perinatal asphyxia.

The impact of depressed neonatal cerebral oxidative phosphorylation for diagnosing the severity of perinatal asphyxia was estimated by correlating the concentrations of phosphocreatine (PCr) and ATP as determined by magnetic resonance spectroscopy with the degree of hypoxic-ischemic encephalopathy (HIE) in 23 asphyxiated term neonates. Ten healthy age-matched neonates served as controls. In patients, the mean concentrations +/- SD of PCr and ATP were 0.99 +/- 0.46 mmol/L (1.6 +/- 0.2 mmol/L) and 0.99 +/- 0.35 mmol/L (1.7 +/- 0.2 mmol/L), respectively (normal values in parentheses). [PCr] and [ATP] correlated significantly with the severity of HIE (r = 0.85 and 0.9, respectively, p < 0.001), indicating that the neonatal encephalopathy is the clinical manifestation of a marred brain energy metabolism. Neurodevelopmental outcome was evaluated in 21 children at 3, 9, and 18 mo. Seven infants had multiple impairments, five were moderately handicapped, five had only mild symptoms, and four were normal. There was a significant correlation between the cerebral concentrations of PCr or ATP at birth and outcome (r = 0.8, p < 0.001) and between the degree of neonatal neurologic depression and outcome (r = 0.7). More important, the outcome of neonates with moderate HIE could better be predicted with information from quantitative 31P magnetic resonance spectroscopy than from neurologic examinations. In general, the accuracy of outcome predictability could significantly be increased by adding results from 31P magnetic resonance spectroscopy to the neonatal neurologic score, but not vice versa. No correlation with outcome was found for other perinatal risk factors, including Apgar score.

Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution

Résumé Etude de la valeur pronostique de la biopsie du ganglion sentinelle dans une étude prospective monocentrique de 327 patients atteints de mélanome malin But II s'agit de confirmer la validité de la biopsie du ganglion sentinelle, d'en définir la morbidité, d'investiguer les facteurs prédictifs pour le statut du ganglion sentinelle ainsi que de déterminer les facteurs pronostiques pour la survie sans récidive et la survie spécifique liée à la maladie. Matériel et méthode D'octobre 1997 à décembre 2004, 327 patients consécutifs présentant un mélanome cutané primaire des membres, du tronc et de la tête, sans adénopathie clinique ni métastase à distance ont été inclus. La biopsie du ganglion sentinelle a été réalisée selon la triple technique (lymphoscintigraphie, colorant bleu vital et sonde de détection gamma). Les paramètres et la survie ont été évalués par différentes analyses de régression logistique multiple selon Cox et la survie évaluée selon Kaplan Meier. Résultats Vingt-trois pour cent des patients présentaient au moins un ganglion sentinelle métastatique, ce qui était associé de façon significative à l'épaisseur selon Breslow (p<0.001). Le taux de succès de la biopsie du ganglion sentinelle était de 99.1% et sa morbidité de 7.6%. Avec une durée médiane de suivi de 33 mois, la survie sans récidive à 5 ans était de 43% pour les patients avec un ganglion sentinelle positif et de 83.5% pour ceux avec un ganglion sentinelle négatif. La survie spécifique liée à la maladie à 5 ans était de 49% pour les patients avec un ganglion sentinelle positif et de 87.4% pour ceux avec un ganglion sentinelle négatif. Le taux de faux négatif de la biopsie du ganglion sentinelle était de 8.6%. L'analyse multivariée a démontré que la survie sans récidive était significativement péjorée par :l'épaisseur selon Breslow (RR=5.6, p<0.001), un ganglion sentinelle positif (RR=5.0, p<0.001), et le sexe masculin (RR=2.9, p=0.001). La survie spécifique liée à la maladie était significativement diminuée par : un ganglion sentinelle métastatique (RR=8.4, p<O.OOI), le sexe masculin (RR=6.1, p<0.001), l'épaisseur selon Breslow (RR=3.2, p=0.013), et la présence d'une ulcération (RR=2.6, p=0.015). Conclusion La biopsie du ganglion sentinelle est une procédure fiable avec une haute sensibilité (91.4%) et une faible morbidité (7.6%). L'épaisseur selon Breslow était le seul facteur prédictif significatif pour le statut du ganglion sentinelle. La survie sans récidive était péjorée selon un ordre décroissant par :l'épaisseur selon Breslow, un ganglion sentinelle métastatique, et le sexe masculin. De façon similaire la survie spécifique liée à la maladie était péjorée par : un ganglion sentinelle métastatique, le sexe masculin, l'épaisseur selon Breslow, et une ulcération. Ces données renforcent le statut du ganglion sentinelle en tant que puissant moyen pour évaluer le stade tumoral ainsi que le pronostic.

Value / personality - attitude - behavior hierarchy and its impact on individual performance in the context of market orientation

The purpose of this dissertation is to better understand how individual employees? values and personality traits influence their attitudes toward market orientation; how such attitudes impact their market-oriented behaviors; and how in turn, these behaviors lead to their superior individual performance. To investigate these relationships, an empirical study was conducted in the French speaking part of Switzerland and data were collected from a sample of service firms? employees from diverse departments and hierarchical levels. To a large extent, the results support the hypothesis of a hierarchical chain moving from value / personality to attitude to behavior to individual performance in relation to market orientation. Le sujet de cette thèse de doctorat est de mieux comprendre comment les valeurs et les traits de personnalité des employés influencent leurs attitudes envers l'orientation vers le marché ; comment ces attitudes ont un effet sur les comportements orientés vers le marché de ces employés et enfin, comment ces comportements conduisent à une meilleure performance individuelle. Afin d'étudier ces relations, une enquête a été conduite en Suisse romande et des données ont été collectées auprès d'un échantillon d'employés d'entreprises de service de différents départements et niveaux hiérarchiques. Les résultats sont concordants avec l'hypothèse d'une chaîne causale allant des valeurs / traits de personnalité aux attitudes, aux comportements et finalement à la performance individuelle dans le contexte de l'orientation vers le marché.

Signalling value of maternal and paternal melanism in the barn owl : implication for the resolution of the lek paradox

Secondary sexual characters often signal qualities such as physiological processes associated with resistance to various sources of stress. When the expression of an ornament is not sex-limited, we can identify the costs and benefits of displaying a trait that is typical of its own sex or of the other sex. Indeed, the magnitude and sign of the covariation between physiology and the extent to which an ornament is expressed could differ between males and females if, for instance, the regulation of physiological processes is sensitive to sex hormones. Using data collected over 14 years in the nocturnal barn owl Tyto alba, we investigated how nestling body mass covaries with a heritable melanin-based sex-trait, females displaying on average larger black feather spots than males. Independently of nestling sex, year and time of the day large-spotted nestlings were heavier than small-spotted nestlings. In contrast, the magnitude and sign of the covariation between nestling body mass and the size of parental spots varied along the day in a way that depended on the year and parental gender. In poor years, offspring of smaller-spotted mothers were heavier throughout the resting period; in the morning, offspring sired by larger-spotted fathers were heavier than offspring of smaller-spotted fathers, while in the evening the opposite pattern was found. Thus, maternal and paternal coloration is differentially associated with behaviour or physiology, processes that are sensitive to time of the day and environmental factors. Interestingly, the covariation between offspring body mass and paternal coloration is more sensitive to these environmental factors than the covariation with maternal coloration. This indicates that the benefit of pairing with differently spotted males may depend on environmental conditions, which could help maintain genetic variation in the face of intense directional (sexual) selection.

Was bringt die Masern-Passivimpfung nach Exposition? [What is the value of measles passive vaccination after exposure?].

In der Schweiz, wie in vielen anderen Ländern, ist die Durchimpfungsrate zu tief, um die Verbreitung von Masern zu stoppen. Es kommt immer wieder zu Masern-Ausbrüchen. Die Gabe von Immunglobulinen (Passivimpfung) ist für nicht-immune Personen gedacht, die Kontakt zu Masernvirus-Ausscheidern hatten. Sie wird in der Schweiz für Hochrisiko-Personen wie z.B. schwangere Frauen, immunsupprimierte Personen und Säuglinge <6 Monate ohne nachgewiesene Immunität empfohlen. Schätzungen über die Wirksamkeit der Passivimpfung variieren; es wurde keine minimalwirksame Dosierung festgelegt. Ziel dieses Reviews war, die Wirksamkeit und Sicherheit einer intramuskulären oder intravenösen Gabe von Immunglobulinen zur Masern-Prophylaxe nach Exposition jedoch vor Symptombeginn bei für Masern empfänglichen Personen zu untersuchen.