O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

Background: The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. Methods A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Results Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Conclusions Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably.

Making Sense of Women Managers’ Identities through the Constructions of Managerial Career and Gender

This doctoral thesis is about gendered managerial identity construction of women managers. Finnish women managers have been researched from the viewpoints of equality and discrimination issues, careers, and women’s overall positions in work life. However, managerial identity has remained as an unexplored territory. The phenomenon is approached discourse analytically; an interview material that is gathered from 13 women managers in the South-Karelian region is in focus. By studying discourses it is possible to open up understandings how meanings are given to experiences. Women managers’ identity construction is examined from the perspectives of managerial career, managerial practices, and gender. Gender is a meta-concept in this research, as it so profoundly affects our sense of being and acting, although the meaning of it often remains undervalued, invisible, or even denied. This research shows that gender becomes highly visible in managerial contexts, when it is used for some specific purpose, that is, treated as a strategy. By studying women managers it is possible to demystify often so abstract managerial ideals, and open up their taken-for-granted masculine subtexts. It is argued that from the point of view of conducting managerial work, the meaning of self-knowledge appears as critical.

Studies on formation of chromium niobates

The precise nature of the reaction between chromium chloride and potassium niobate at specific pH levels 12.0, 10.8 and 7.6 has been studied by means of electrometric techniques involving pH and conductometric titrations. The well defined breaks and inflections in the titration curves provide cogent evidence for the formation and precipitation of chromium ortho-Cr2O3.3Nb2 O5, hexa-4Cr2O3.9Nb2 O5 and meta-Cr2O3.3Nb2 O5 niobates in the vicinity of pH 7.5, 6.8 and 5.6, respectively. Analytical investigations of the precipitates have also been carried out which substantiate the results of the electrometric study.

No androcentric perspective in studies of one parent families. Relections and methodological implications

This paper presents a discussion on the process that led us to a progressively developing of a specific methodological approach for research on one parent families. This process has been systematized and built from the contributions of feminist epistemologies to the methodological design and participatory forms of work. From it derives a scientific and technical contribution, internationally unpublisheduntil now: Single Parenthood and family diversity Survey (EMODIF), which we propose as a not androcentric measuring tool of single parenthood, their profiles,experiences, expectations and realities. With this article we want to offer a systematization of the implications that has had our implementation of the feminist perspective in studies of one parent families.

Bile duct stones, strictures and iatrogenic lesions: studies on early diagnosis and treatment.

Aims: This study was carried out to investigate the role of common liver function tests, and the degree of common bile duct dilatation in the differential diagnosis of extrahepatic cholestasis, as well as the occurrence, diagnosis and treatment of iatrogenic bile duct injuries. In bile duct injuries, special attention was paid to gender and severity distribution and long-term results. Patients and methods: All consecutive patients with diagnosed common bile duct stones or malignant strictures in ERCP between August 2000 and November 2003. Common liver function tests were measured in the morning before ERCP on all of these 212 patients, and their common bile duct diameter was measured from ERCP films. Between January 1995 and April 2002, 3736 laparoscopic cholecystectomies were performed and a total of 32 bile duct injuries were diagnosed. All pre-, per-, and postoperative data were collected retrospectively; and the patients were also interviewed by phone. Results: Plasma bilirubin proved to be the best discriminator between CBD stones and malignant strictures (p≤0.001 compared to other liver function tests and degree of common bile duct dilatation). The same effect was seen in Receiver Operating Characteristics curves (AUC 0.867). With a plasma bilirubin cut-off value of 145 μmol/l, four out of five patients could be classified correctly. The degree of common bile duct dilatation proved to be worthless in differential diagnostics. After laparoscopic cholecystectomy the total risk for bile duct injury was 0.86%, including cystic duct leaks. 86% of severe injuries and 88% of injuries requiring operative treatment were diagnosed in females. All the cystic duct leakages and 87% of the strictures were treated endoscopically. Good long-term results were seen in 84% of the whole study population. Conclusions: Plasma bilirubin is the most effective liver function test in differential diagnosis between CBD stones and malignant strictures. The only value of common bile duct dilatation is its ability to verify the presence of extrahepatic cholestasis. Female gender was associated with higher number of iatrogenic bile duct injuries, and in particular, most of the major complications occur in females. Most of the cystic duct leaks and common bile duct strictures can be treated endoscopically. The long-term results in our institution are at an internationally acceptable level.

Gender diversity and innovation in manufacturing and service firms

Traditionally, researchers have considered the innovation process as being gender neutral. However, recently some studies have begun to take gender diversity into account as a determinant of firms’ innovation. This paper aims to analyse how the effect of gender diversity on innovation output at firm level is sensitive to team size. Using the Spanish PITEC (Panel de Innovación Tecnológica) from 2007 to 2012 for innovative manufacturing and service firms, we estimate a multivariate probit model to analyse how gender diversity both in R&D teams and in the total workforce affect product, process, marketing and organizational innovations. Our results show that gender-diverse teams increase the probability of innovating, and this capacity is positively related team size. Gender diversity, in both the R&D department and the total workforce, has a larger positive impact on the probability of carrying out product and organizational innovations in larger teams than it does in smaller teams. This effect is less clear-cut in the case of marketing and process innovation, where the impact is only significant for micro and small firms. Finally, size effects are of greater importance when we distinguish between the manufacturing and service sectors. JEL Code: O30, O31, J16

Percepció i coneixements dels estudiants d'infermeria sobre la violència en la parella

Les últimes dades de l'estudi europeu del 2014, sobre la violència de parella indiquen que gairebé 62 milions de dones europees, havien sofert actes de violència de gènere, entre els quals es destaca els relacionats amb la violència de parella (VP). Els maltractaments constitueixen un problema molt greu que genera al nostre país cada vegada més alarma social i més actuacions legals i professionals per fer-li front. El sistema de salut és, amb freqüència, el primer lloc al que les víctimes de violència domèstica acudeixen a la recerca d'assessorament i ajuda, sent aquest el motiu pel qual els professionals de la salut tenen un paper central per a la seva assistència. Aquests formen part implicada en el sistema de detecció, atenció i actuació. Per això, els plans d'estudi de Grau d'Infermeria recullen en el BOE la formació en VP des de l’àmbit universitari. L’objectiu del nostre estudi consisteix en la identificació de la percepció i dels coneixements en relació a la violència de parella dels estudiants del Grau d’Infermeria de la Universitat de Girona durant el curs acadèmic 2012-2013. Per a dur-lo a terme es va realitzar un anàlisi quantitatiu dels resultats a través de l’administració d’una enquesta sobre sis aspectes de la VP, l’enquesta incloïa el perfil demogràfic (sexe, edat i anys d'estudi) dels estudiants i les declaracions relatives a les seves percepcions i coneixements sobre la VP: causes d'abús; la identificació de les dones objecte de VP i del seus autors; creences de les infermeres; funcions perceptibles; i la preparació educativa. Els estudiants del Grau d’Infermeria mostren tenir un bon coneixement sobre les causes del abús en VP, així com una formació adequada. També cal destacar que un 54,42% dels alumnes enquestats es veuen capacitats per afrontar un cas de VP com a infermer/a. S’observa una millora de la formació educativa en el transcurs acadèmic. En 1r curs un 40,09% té una bona formació, aquest valor augmenta fins a un 56,58% a tercer curs, baixant lleugerament fins un 44,27% a 4rt curs. Els resultats obtinguts són semblats a estudis de mostres similars en estudiants d'infermeria de Memphis (EUA) i de la University of Southern Queensland (Austràlia) quant a coneixements i percepció sobre la VP. Encara que els resultats mostren un coneixement i una percepció sobre la VP adequada, destaquem que això no succeeix en gairebé un 40% dels enquestats. La introducció de matèries específiques sobre igualtat i sobre violència contra la dona en els plans d’estudis, pot esdevenir una mesura preventiva per revisar i corregir possibles mites i creences en VP. Per tant, és necessari millorar la formació del currículum en estudiants d'infermeria per la importància d'aquest greu problema de salut pública, donant major èmfasis en la satisfacció de les necessitats emocionals i en la comprensió dels diferents enfocaments en VP, especialment en mesures de prevenció i educació

Patriarchal hauntings : re-reading villainy and gender in Daphne du Maurier’s 'Rebecca'

Daphne du Maurier’s popular classic Rebecca (1938) was traditionally marketed as a Gothic romance in which two lovers conquered the evil women that separated them. In more recent years, some feminist critics have provided a very different view of the story as a Gothic narrative about the dangers women suffer under patriarchal control. In this thesis, I propose, through a Gothic Studies and a Gender Studies reading, that the victim/abuser statuses in du Maurier’s novel cannot be equated to femininity and masculinity, respectively. Instead, I argue that villainy in Rebecca comes from being in a powerful position within patriarchy—a position that is occupied by both male and female characters

A Case-based reasoning approach to validate grammatical gender and number agreement in Spanish language

Across Latin America 420 indigenous languages are spoken. Spanish is considered a second language in indigenous communities and is progressively introduced in education. However, most of the tools to support teaching processes of a second language have been developed for the most common languages such as English, French, German, Italian, etc. As a result, only a small amount of learning objects and authoring tools have been developed for indigenous people considering the specific needs of their population. This paper introduces Multilingual–Tiny as a web authoring tool to support the virtual experience of indigenous students and teachers when they are creating learning objects in indigenous languages or in Spanish language, in particular, when they have to deal with the grammatical structures of Spanish. Multilingual–Tiny has a module based on the Case-based Reasoning technique to provide recommendations in real time when teachers and students write texts in Spanish. An experiment was performed in order to compare some local similarity functions to retrieve cases from the case library taking into account the grammatical structures. As a result we found the similarity function with the best performance

Probiotic lactobacilli and bifidobacteria in the mouth – in vitro studies on saliva-mediated functions and acid production

Probiotic lactobacilli and bifidobacteria in the mouth – in vitro studies on saliva-mediated functions and acid production Probiotics are viable bacteria which, when used in adequate amounts, are beneficial to the health of the host. Although most often related to intestinal health, probiotic bacteria can be found also in the mouth after consumption of products that contain them. This study aimed at evaluating the oral effects of probiotic bacteria already in commercial use. In a series of in vitro studies, the oral colonisation potential of different probiotic bacteria, their acid production and potential saliva-mediated effects on oral microbial ecology were investigated. The latter included effects on the salivary pellicle, the adhesion of other bacteria, and the activation of the peroxidase system. Streptococcus mutans, Streptococcus gordonii, Aggregatibacter actinomycetemcomitans and Helicobacter pylori were used as bacterial indicators of the studied phenomena. There were significant differences between the probiotic strains in their colonisation potential. They all were acidogenic, although using different sugars and sugar alcohols. However, their acid production could be inhibited by the peroxidase system. Based on the results, it can be suggested that probiotic bacteria might influence the oral microbiota by different, partly species or strain-specific means. These include the inhibition of bacterial adhesion, modification of the enamel pellicle, antimicrobial activity, and activation of the peroxidase system. To conclude, probiotic strains differed from each other in their colonisation potential and other oral effects as evaluated in vitro. Both positive and potentially harmful effects were observed, but the significance of the perceived results needs to be further evaluated in vivo.

The Importance of Semantics: Visual World Studies on Drawing Inferences and Resolving Anaphors

The present thesis investigated the importance of semantics in generating inferences during discourse processing. Three aspects of semantics, gender stereotypes, implicit causality information and proto-role properties, were used to investigate whether semantics is activated elaboratively during discourse comprehension and what its relative importance is in backward inferencing compared to discourse/structural cues. Visual world eye-tracking studies revealed that semantics plays an important role in both backward and forward inferencing: Gender stereotypes and implicit causality information is activated elaboratively during online discourse comprehension. Moreover, gender stereotypes, implicit causality and proto-role properties of verbs are all used in backward inferencing. Importantly, the studies demonstrated that semantic cues are weighed against discourse/structural cues. When the structural cues consist of a combination of cues that have been independently shown to be important in backward inferencing, semantic effects may be masked, whereas when the structural cues consist of a combination of fewer prominent cues, semantics can have an earlier effect than structural factors in pronoun resolution. In addition, the type of inference matters, too: During anaphoric inferencing semantics has a prominent role, while discourse/structural salience attains more prominence during non-anaphoric inferencing. Finally, semantics exhibits a strong role in inviting new inferences to revise earlier made inferences even in the case the additional inference is not needed to establish coherence in discourse. The findings are generally in line with the Mental Model approaches. Two extended model versions are presented that incorporate the current findings into the earlier literature. These models allow both forward and backward inferencing to occur at any given moment during the course of processing; they also allow semantic and discourse/structural cues to contribute to both of these processes. However, while the Mental Model 1 does not assume interactions between semantic and discourse/structural factors in forward inferencing, the Mental Model 2 does assume such a link.

Targeting striatal metabotropic glutamate receptor type 5 in Parkinson's disease: bridging molecular studies and clinical trials

Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors expressed primarily on neurons and glial cells modulating the effects of glutamatergic neurotransmission. The pharmacological manipulation of these receptors has been postulated to be valuable in the management of some neurological disorders. Accordingly, the targeting of mGlu5 receptors as a therapeutic approach for Parkinson's disease (PD) has been proposed, especially to manage the adverse symptoms associated to chronic treatment with classical PD drugs. Thus, the specific pharmacological blocking of mGlu5 receptors constitutes one of the most attractive non-dopaminergic-based strategies for PD management in general and for the L-DOPA-induced diskynesia (LID) in particular. Overall, we provide here an update of the current state of the art of these mGlu5 receptor-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.

Determination of phenobarbital in human plasma by a specific liquid chromatography method: application to a bioequivalence study

A liquid chromatography method was developed and validated for the determination of phenobarbital in human plasma using phenytoin as internal standard. The drugs were extracted from plasma by liquid-liquid extraction and separated isocratically on a C12 analytical column, maintained at 35 ºC, with water:acetonitrile:methanol (58.8:15.2:26, v/v/v) as mobile phase, run at a flow rate of 1.2 mL/min with detection at 205 nm. The method was linear in the range of 0.1-4 μg/mL (r²=0.9999) and demonstrated acceptable results for the precision, accuracy and stability studies. The method was successfully applied for the bioequivalence study of two tablet formulations (test and reference) of phenobarbital 100 mg after single oral dose administration to healthy human volunteers.

Electrometric studies on uranyl molybdates as a function of pH

The formation and composition of uranyl molybdates obtained by the interaction of uranyl acetate and sodium molybdate at specific pH levels 7.6, 5.5 and 4.1 have been studied by employing electrometric techniques involving pH and conductometric titrations. The results provide cogent evidence for the formation of three uranyl molybdates having the molecular formulae UO2O.MoO3, 3UO2O.7MoO3 and 2UO2O.8MoO3 in the vicinity of pH 5.7, 4.6 and 3.8, respectively. Analytical investigations of the compounds have also been carried out which substantiate the results of electrometric study.

Electrometric studies on formation of cerium vanadates as a function of pH

The precise nature of the reaction between nitric acid and sodium ortho-vanadate solutions has been studied by means of electrometric techniques involving potentiometric and conductometric titrations. The well defined inflections and breaks in the titration curves confirm the existence of the anions, pyro-V2O7(4-), meta-VO3- and poly-H2V10O28(4-) corresponding to the ratios of VO4(3-):H+ as 1:1, 1:2 and 1:2.6 in the neighborhood of pH 10.5, 7.4 and 3.6, respectively. The interaction of cerium(III) nitrate with sodium vanadate solutions, at specific pH levels 12.4, 10.5, 7.4 and 3.6 was also studied by potentiometric and conductometric titrations between the reactants. The end-points obtained from the sharp inflections in the titration curves provide definite evidence for the formation and precipitation of cerium ortho-Ce2O3.V2O5, pyro-2Ce2O3.3V2O5 and meta-Ce2O3.3V2O5 vanadates in the neighborhood of pH 7.4, 6.2 and 4.8, respectively. Analytical investigations on the precipitates formed confirm the results of the electrometric study.