The sociology of consumer behaviour and men.

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Quantitative Analysis of the MGMT Methylation Status of Glioblastomas in Light of the 2021 WHO Classification.

Glioblastomas with methylation of the promoter region of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene exhibit increased sensitivity to alkylating chemotherapy. Quantitative assessment of the MGMT promoter methylation status might provide additional prognostic information. The aim of our study was to determine a quantitative methylation threshold for better survival among patients with glioblastomas. We included consecutive patients ≥18 years treated at our department between 11/2010 and 08/2018 for a glioblastoma, IDH wildtype, undergoing quantitative MGMT promoter methylation analysis. The primary endpoint was overall survival. A total of 321 patients were included. Median overall survival was 12.6 months. Kaplan-Meier and adjusted Cox regression analysis showed better survival for the groups with 16-30%, 31-60%, and 61-100% methylation. In contrast, survival in the group with 1-15% methylation was similar to those with unmethylated promoter regions. A secondary analysis confirmed this threshold. Better survival is observed in patients with glioblastomas with ≥16% methylation of the MGMT promoter region than with <16% methylation. Survival with tumors with 1-15% methylation is similar to with unmethylated tumors. Above 16% methylation, we found no additional benefit with increasing methylation

Advancing synoptic cancer reports beyond English: the University of Bern/PathoLink approach.

Synoptic reporting (SR) increases completeness and improves the understanding of pathology reports for tumours as compared to the more traditional “narrative” style. Furthermore, it is an important step towards higher levels of structured data capture [1]. SR is defined by a set of required data elements (RDE) specific for each tumour type and a characteristic paired format of RDE and response. The College of American Pathologists (CAP) requires accredited pathology laboratories to report many cancer types in a synoptic format and for this purpose publishes a comprehensive set of protocols [2]. More recently, the International Collaboration for Cancer Reporting (ICCR)—sponsored amongst others by the European Society of Pathology—has started to publish synoptic protocols with the aim to “produce internationally standardised and evidence-based datasets for the pathology reporting of cance

Prime beef cuts : culinary images for thinking 'men'

The paper contributes to scholarship theorising the sociality of the brand in terms of subject positions it makes possible through drawing upon the generative context of circulating discourses, in this case of masculinity, cuisine and celebrity. Specifically, it discusses masculinity as a socially constructed gender practice (Bristor and Fischer, 1993), examining materialisations of such practice in the form of visualisations of social relations as resources for 'thinking gender' or 'doing gender'. The transformative potential of the visualisations is illuminated by exploring the narrative content choreographed within a series of photographic images positioning the market appeal of a celebrity chef through the medium of a contemporary lifestyle cookery book. We consider how images of men 'doing masculinity'are not only channelled into reproducing existing gender hierarchy and compulsory heterosexuality in the service of commercial ends, but also into disrupting such enduring stereotyping through subtle reframing. We acknowledge that masculinity is already inscribed within conventionalised representations of culinary culture. In this case we consider how traces of masculinity are exploited and reinscribed through contemporary images that generate resources for rethinking masculine roles and identities, especially when viewed through the lens of stereotypically feminised pursuits such as shopping, food preparation, cooking, and the communal intimacy of food sharing. We identify unsettling tensions within the compositions, arguing that they relate to discursive spaces between the gendered positions written into the images and the popular imagination they feed off. Set against landscapes of culinary culture, we argue that the images invoke a brand of naively roughish "laddishness" or "blokishness", rendering it in domesticated form not only as benign and containable, but fashionable, pliable and, importantly, desirable. We conclude that although the images draw on stereotypical premeditated notions of a feral, boisterous and untamed heterosexual masculinity, they also set in motion gender-blending narratives

DNA adducts in human urinary bladder and other tissues.

Tobacco smoking is associated with an increased risk of cancer in a number of organs, including bladder and lung. Tobacco smoke contains at least 50 known chemical carcinogens that exert their biological effects through their covalent binding to cellular DNA. Examining human DNA for the presence of altered nucleotides is a means of monitoring exposure to genotoxic chemicals. DNA isolated from 73 human bladder biopsies has been analyzed by 32P-postlabeling for the presence of aromatic/hydrophobic adducts. Butanol extraction of DNA digests resulted in up to a 3-fold greater recovery of adducts than nuclease P1 digestion. Among 16 nonsmokers, adduct levels were in the range 3.2-20.8/10(8) nucleotides (mean 9.7). Eight ex-smokers had values in the range 2.6-12.3 (mean 7.1). Thirteen smokers had adduct levels between 1.3 and 26.7 adducts/10(8) nucleotides (mean 9.5, not different from nonsmokers). Six cigar smokers had higher levels of adducts (mean 12.1, range 7.3-15.0), but pipe smokers did not (five samples, mean 8.6, range 2.9-12.7). A further 8 samples from nonsmokers and 17 from smokers were examined in more detail. Although most of the DNA binding appears not to be smoking related, the levels of one adduct were found to be on average 2-fold higher in smokers (p < 0.005, one-tailed t test). Studies on tissues of the respiratory tract demonstrate a correlation between DNA adduct levels and exposure to tobacco smoke. Evidence to date on the influence of smoking on adducts in peripheral blood cells is equivocal; some studies demonstrate a significant effect, whereas others do not.(ABSTRACT TRUNCATED AT 250 WORDS

Effects of formalin fixation on polarimetric properties of brain tissue: fresh or fixed?

Imaging Mueller polarimetry (IMP) appears as a promising technique for real-time delineation of healthy and neoplastic tissue during neurosurgery. The training of machine learning algorithms used for the image post-processing requires large data sets typically derived from the measurements of formalin-fixed brain sections. However, the success of the transfer of such algorithms from fixed to fresh brain tissue depends on the degree of alterations of polarimetric properties induced by formalin fixation (FF). Comprehensive studies were performed on the FF induced changes in fresh pig brain tissue polarimetric properties. Polarimetric properties of pig brain were assessed in 30 coronal thick sections before and after FF using a wide-field IMP system. The width of the uncertainty region between gray and white matter was also estimated. The depolarization increased by 5% in gray matter and remained constant in white matter following FF, whereas the linear retardance decreased by 27% in gray matter and by 28% in white matter after FF. The visual contrast between gray and white matter and fiber tracking remained preserved after FF. Tissue shrinkage induced by FF did not have a significant effect on the uncertainty region width. Similar polarimetric properties were observed in both fresh and fixed brain tissues, indicating a high potential for transfer learning

Screening of the NIH Clinical Collection for inhibitors of HIV-1 integrase activity

Drug repurposing offers a validated approach to reduce drug attrition within the drug discovery and development pipeline through the application of known drugs and drug candidates to treat new indications. Full exploitation of this strategy necessitates the screening of a vast number of molecules against an extensive number of diseases of high burden or unmet need and the subsequent dissemination of the findings. In order to contribute to endeavours within this field, we screened the 727 compounds comprising the US National Institutes of Health (NIH) Clinical Collection through an HIV-1 (human immunodeficiency virus type 1) integrase stand transfer inhibition assay on an automated scintillation proximity assay platform. Only two compounds were identified within the initial screen, with cefixime trihydrate and epigallocatechin gallate found to reduce integrase strand transfer activity at IC50 values of 6.03±1.29 ?M and 9.57±1.62 ?M, respectively. However, both cefixime trihydrate and epigallocatechin gallate retained their low micromolar inhibitory activity when tested against a raltegravir-resistant integrase double mutant (FCIC50 values of 0.83 and 0.06, respectively), were ineffective in an orthogonal strand transfer ELISA (<30% inhibition at 100 ?M) and produced negligible selectivity index values (<1) in vitro. While no useful inhibitors of HIV-1 integrase strand transfer activity were found within the NIH Clinical Collection, the identification of two assay-disrupting molecules demonstrates the importance of consideration of non-specific inhibitors in drug repurposing screens. Significance: • This study is the first to screen the US NIH Clinical Collection for potential HIV-1 integrase inhibitors. • The pervasive nature of promiscuous inhibitors is emphasised

Idoxifene is equipotent to tamoxifen in inhibiting mammary carcinogenesis but forms lower levels of hepatic DNA adducts

Tamoxifen is an effective agent preventing mammary carcinogenesis in rats but causing liver tumours. Idoxifene is a more potent antioestrogen and is effective in patients with advanced breast cancer. We therefore compared the effects of idoxifene with tamoxifen on mammary carcinogenesis and hepatic DNA adduct formation. To do this, we undertook a study designed to compare tamoxifen with idoxifene as a chemopreventive agent in rats inoculated with N-methylnitrosourea (MNU) and also measured hepatic adduct formation. We examined the time to mammary tumour development in 272 female Ludwig/Wistar/Olac rats treated with MNU followed by tamoxifen (5 mg kg(-1)), equimolar idoxifene or vehicle three times a week for up to 24 weeks. To determine duration of effect, a second study was carried out whereby all of the 129 animals surviving at the end of treatment were entered into a surveillance programme for 27 weeks after the end of the administration period. Hepatic DNA adduct formation was examined by 32P-postlabelling in a group of rats after 24 weeks' treatment. In the first study, both idoxifene and tamoxifen were effective in preventing tumour growth as only 2 out of 21 (10%) MNU and vehicle-treated animals were alive and tumour free after 24 weeks compared with 13 out of 22 (59%) animals receiving MNU followed by idoxifene or tamoxifen (P < 0.001). The second study showed that, in both idoxifene- and tamoxifen-treated animals, a progressive regrowth of tumours occurred after cessation of therapy, as by the end of the observation period only four idoxifene-treated animals and one tamoxifen-treated animal were free from disease. In the subset of animals tested, tamoxifen-treated animals had approximately 100 times higher levels of DNA hepatic adducts than idoxifene-treated animals. Adducts were not seen in the control group. These results indicate that idoxifene is as effective a chemopreventive agent as tamoxifen in the rat while causing only very low levels of DNA adducts in liver tissue and suggest that idoxifene may be a well-tolerated chemopreventive agent in women who are at increased risk of breast cancer

Optimization viewpoint on Kalman smoothing, with applications to robust and sparse estimation

In this paper, we present the optimization formulation of the Kalman filtering and smoothing problems, and use this perspective to develop a variety of extensions and applications. We first formulate classic Kalman smoothing as a least squares problem, highlight special structure, and show that the classic filtering and smoothing algorithms are equivalent to a particular algorithm for solving this problem. Once this equivalence is established, we present extensions of Kalman smoothing to systems with nonlinear process and measurement models, systems with linear and nonlinear inequality constraints, systems with outliers in the measurements or sudden changes in the state, and systems where the sparsity of the state sequence must be accounted for. All extensions preserve the computational efficiency of the classic algorithms, and most of the extensions are illustrated with numerical examples, which are part of an open source Kalman smoothing Matlab/Octave package.Comment: 46 pages, 11 figure

Task design for audiographic conferencing: promoting beginner oral interaction in distance language learning

This paper presents the challenges involved in designing a full set of online tutorial materials for a beginners' Spanish course for distance language learners utilising an online audiographic conferencing VLE for synchronous oral interaction. Although much has been written about task design and task-based learning and teaching (TBLT) in language learning (Johnson, 2003; Klapper, 2003; Ellis, 2000; Nunan, 1989, among others), the shift to an audiographic Computer Mediated Communication (CMC) medium presents a number of challenges to task design which are only just beginning to be documented (Hampel 2003, Hampel & Baber 2003, Hampel & Hauck 2004). Here we will discuss what the challenges are for the design and implementation of activities suited to the development of oral skills in a foreign language in such an environment in the light of current theories of SLA (Skehan, 2003; Doughty & Long, 2003; Doughty, 2000; Long, 1996), task design, and CALL (Warschauer, 1997; Chapelle 1998) and how those challenges were met for the production of a full set of materials for a beginners' Spanish distance learning course at the Open University using a tool that had been deemed unsuitable for that level (Kötter, 2001). We will also present the findings of the developmental testing of a sample of these activities and recommend a model for tasks in an audiographic VLE to promote oral interaction at beginner level