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.

Melanin-specific life-history strategies.

Abstract The maintenance of genetic variation is a long-standing issue because the adaptive value of life-history strategies associated with each genetic variant is usually unknown. However, evidence for the coexistence of alternative evolutionary fixed strategies at the population level remains scarce. Because in the tawny owl (Strix aluco) heritable melanin-based coloration shows different physiological and behavioral norms of reaction, we investigated whether coloration is associated with investment in maintenance and reproduction. Light melanic owls had lower adult survival compared to dark melanic conspecifics, and color variation was related to the trade-off between offspring number and quality. When we experimentally enlarged brood size, light melanic males produced more fledglings but in poorer condition, and they were less often recruited in the local breeding population than those of darker melanic conspecifics. Our results also suggest that dark melanic males allocate a constant effort to raise their brood independently of environmental conditions, whereas lighter melanic males finely adjust reproductive effort in relation to changes in environmental conditions. Color traits can therefore be associated with life-history strategies, and stochastic environmental perturbation can temporarily favor one phenotype over others. The existence of fixed strategies implies that some phenotypes can sometimes display a "maladapted" strategy. Long-term population monitoring is therefore vital for a full understanding of how different genotypes deal with trade-offs.

Diagnosis of tuberculosis infection using interferon-γ-based assays

Interferon-γ-based assays, collectively known as IFN-γ release assays (IGRAs), have emerged as a reliable alternative to the old tuberculin skin test (TST) for the immunodiagnosis of tuberculosis (TB) infection. The 2 commercially available tests, the enzyme-linked immunosorbent assay (ELISA), QuantiFERON-TB Gold Intube (QFT-IT), and the enzyme-linked immunospot assay (ELISPOT), T-SPOT.TB, are more accurate than TST for the diagnosis of TB, since they are highly specific and correlate better with the existence of risk factors for the infection. According to the available data, T-SPOT.TB obtains a higher number of positive results than QFT-IT, while its specificity seems to be lower. Although the sensitivity of the IFN-γ -based assays may be impaired to some extent by cellular immunosuppression and extreme ages of life, they perform better than TST in these situations. Data from longitudinal studies suggest that IFN-γ-based tests are better predictors of subsequent development of active TB than TST; however this prognostic value has not been consistently demonstrated. This review focuses on the clinical use of the IFN-γ -based tests in different risk TB groups, and notes the main limitations and areas for future development.

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.

Prognostic value of cortically induced motor evoked activity by TMS in chronic stroke: caveats from a very revealing single clinical case

Background: We report the case of a chronic stroke patient (62 months after injury) showing total absence of motor activity evoked by transcranial magnetic stimulation (TMS) of spared regions of the left motor cortex, but near-to-complete recovery of motor abilities in the affected hand. Case presentation: Multimodal investigations included detailed TMS based motor mapping, motor evoked potentials (MEP), and Cortical Silent period (CSP) as well as functional magnetic resonance imaging (fMRI) of motor activity, MRI based lesion analysis and Diffusion Tensor Imaging (DTI) Tractography of corticospinal tract (CST). Anatomical analysis revealed a left hemisphere subinsular lesion interrupting the descending left CST at the level of the internal capsule. The absence of MEPs after intense TMS pulses to the ipsilesional M1, and the reversible suppression of ongoing electromyographic (EMG) activity (indexed by CSP) demonstrate a weak modulation of subcortical systems by the ipsilesional left frontal cortex, but an inability to induce efficient descending volleys from those cortical locations to right hand and forearm muscles. Functional MRI recordings under grasping and finger tapping patterns involving the affected hand showed slight signs of subcortical recruitment, as compared to the unaffected hand and hemisphere, as well as the expected cortical activations. Conclusions: The potential sources of motor voluntary activity for the affected hand in absence of MEPs are discussed. We conclude that multimodal analysis may contribute to a more accurate prognosis of stroke patients.

Determination of the critical activities of a public-private intermediary organization with the help of value chain analysis

Tämän diplomityön tavoitteena oli selvittää arvoketjuanalyysin avulla toiminnot, joilla voittoatavoittelemattoman, julkisen osakeyhtiön toimintaa voitaisiin kuvata. Tarkoituksena oli selvittää mainitut toiminnot yleisesti ja luoda malli kohdeyrityksen arvoketjusta ja sen toiminnoista. Tutkielma jakautuu teoreettiseen ja empiiriseen osaan. Ensimmäinen pohjautuu aikaisempaan tutkimukseen ja kirjallisuuteen sidosryhmistä, arvon muodostumisesta ja arvoketjuanalyysistä. Jälkimmäinen on laadullista tapaustutkimusta. Empiriassa mallinnettiin Lappeenranta Innovation Oy:nsisäisiä toimintoja ja sidosryhmien odotuksia. Empiirinen tutkimus perustui kohdeyrityksen omistajille ja henkilöstölle tehtyihin haastatteluihin sekä yrityksen toiminnan päivittäiseen seurantaan. Johtopäätöksenätodettiin, että julkisen, voittoa tavoittelemattoman yrityksen toiminnot on mahdollista kuvata arvoketjuanalyysin avulla. Alan ja yrityksen asettamat erityispiirteet toivat haasteita määrittelylle, mutta silti arvoketju antoi selkeän tavan kohdeyrityksen toimintojen mallintamiselle.

Variability of the nucleolar organizer activity in human lymphocytes via Ag-staining.

Chromosomes with Ag staining that varies from one metaphase to the other can be distinguished from those with an Ag-staining that is the same in all metaphases. The intercellular variation of an Ag-NOR can be attributed to many different factors. Whatever the importance of technical factors, they do not seem to account for the large variations in Ag-staining which were observed for each ac. This suggests the existence of a natural intercellular variability of the NOR's activity. The variation of the Ag-stainability of a given NOR, the diversity of Ag-stainings observed on the ten ac of one individual and the differences that exist between individuals raise the question of the existence of a compensation of activity between nucleolar organizers. The study, for each individual, of the mean sum of staining per metaphase reveals that this value is not absolutely constant from one individual to another; in the carriers of Robertsonian fusions it is smaller than in chromosomally normal individuals. The analysis of the transmission shows that inactive NORs remain inactive and that active NORs present a variation in the activity from one generation to the next.

Value Sales Approach in Digital Printing

Digitaalinen tulostus osana informaatiologistiikan toimialaa elää murroskautta kovankilpailun ja palveluiden kehittymisen myötä. Moderni teknologia mahdollistaa uudenlaisia älykkäitä palveluita, jotka antavat lisäarvoa niin yritysasiakkaille kuin kuluttajillekin. Siten myös myyntiprosesseja kehitetään tukemaan arvon luontia. Tutkimuksen teoreettisessa osuudessa sovellettiin arvon luomiseen ja myymiseen liittyviä keskeisiä teorioita, sekä organisaation ostokäyttäytymisen ja suhdemarkkinoinnin asioita. Empiirinen tutkimus toteutettiin asiakas- ja asiantuntijahaastatteluiden sekä kansainvälisten koulutuspäivien avulla. Työn tavoitteena oli luoda teoreettisen ja empiirisen tutkimuksen tulosten pohjalta ohjeistus digitaalisen tulostuksen palveluiden arvomyyntiin. Lisäksi työssä käsiteltiin myyntiprosessiin liittyviä kysymyksiä alan ominaispiirteet huomioon ottaen.