980 resultados para Clermont, Marie-Anne de Bourbon-Condé, mademoiselle de, 1697-1741
Resumo:
Although there is a substantial body of work on desistance from crime in general, comparatively little is known about desistance from sexual crime. The broad aim of this paper is to provide an overview of the research methodology and preliminary findings from a recent empirical study on desistance from sexual offending conducted by the authors. Such findings have potentially important implications for policy and practice concerning sex offender risk assessment, treatment and management.
Resumo:
This chapter examines who and what brought about the transformation in the criminal justice system of Northern Ireland between 1998 and 2015, seeking to pinpoint the critical moments which stimulated the reforms, how they were delivered, and through what processes they are now being maintained. It seeks to identify the key agents of change and considers whether it is possible to generalise from Northern Ireland’s experience so that other conflicted societies might benefit from the lessons learned.
Resumo:
In this study, a comparison of different methods to predict drug−polymer solubility was carried out on binary systems consisting of five model drugs (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios. The drug−polymer solubility at 25 °C was predicted using the Flory−Huggins model, from data obtained at elevated temperature using thermal analysis methods based on the recrystallization of a supersaturated amorphous solid dispersion and two variations of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate). The predicted solubilities at 25 °C varied considerably depending on the method used. However, the three thermal analysis methods ranked the predicted solubilities in the same order, except for the felodipine−PVP system. Furthermore, the magnitude of the predicted solubilities from the recrystallization method and melting point depression method correlated well with the estimates based on the solubility in the liquid analogues, which suggests that this method can be used as an initial screening tool if a liquid analogue is available. The learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug−polymer solubility.
Resumo:
Objectives: Amorphous drug forms provide a useful method of enhancing the dissolution performance of poorly water-soluble drugs; however, they are inherently unstable. In this article, we have used Flory–Huggins theory to predict drug solubility and miscibility in polymer candidates, and used this information to compare spray drying and melt extrusion as processes to manufacture solid dispersions.
Method: Solid dispersions were characterised using a combination of thermal (thermogravimetric analysis and differential scanning calorimetry) and spectroscopic (Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction methods.
Key Findings: Spray drying permitted generation of amorphous solid dispersions to be produced across a wider drug concentration than melt extrusion. Melt extrusion provided sufficient energy for more intimate mixing to be achieved between drug and polymer, which may improve physical stability. It was also confirmed that stronger drug–polymer interactions might be generated through melt extrusion. Remixing and dissolution of recrystallised felodipine into the polymeric matrices did occur during the modulated differential scanning calorimetry analysis, but the complementary information provided from FTIR confirms that all freshly prepared spray-dried samples were amorphous with the existence of amorphous drug domains within high drug-loaded samples.
Conclusion: Using temperature–composition phase diagrams to probe the relevance of temperature and drug composition in specific polymer candidates facilitates polymer screening for the purpose of formulating solid dispersions.
Resumo:
Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled-Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC-3 cells with 5-Aza-CdR reactivated 39 genes (≥ 2-fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.
Resumo:
Ballykinler / Ballykinlar, on the Co. Down coastline with the Mourne Mountains as a backdrop is a village of 250 inhabitants, beside a British army base with 1500 inhabitants. It is a complex situation with a troubled and contested history, reflected by the two different spellings on the village road signs. The village is viewed as having low levels of community capacity and longstanding sectarian problems.
PS2 has been working with the artist, Anne Marie Dillon and the local community of Ballykinler / Ballykinlar since April 2009, facilitating and curating a range of ‘live’ projects that address the lack of shared community and cultural space. A series of projects has modestly advanced the village’s ambition- realising alternative cultural centres.
1. Bus Stop (April 2009)
www.pssquared.org/Ballykinler.php
2. Rhyzom Network Workshop (June 2010)
www.pssquared.org/research.php
3. Beach Huts (March 2011)
www.pssquared.org/beachhuts.php
4. Up Down (May 2011) (included village fair)
www.pssquared.org/UP-Down.php villageworks.org.uk/wp/
5. Transfer Tests (March 2012)
www.pssquared.org/streesociety2012.php
6. Links Community Gardens (May 2012)
www.pssquared.org/LinksGardens.php
Resumo:
There is ample evidence that young people engage in grooming and harmful sexual behaviour (HSB) using social media with enough frequency to make those behaviours important con-cerns for both society and care providers. This article provides a critical overview of the con-ceptual and empirical foundations of peer-to-peer grooming and the use of social media with-in the context of HSB. Based on this learning, it ultimately introduces a new model of inter-vention and of professional practice, which provides the standards for micro-level decision-making about goals, methods and assessment tailored to this specific offending context.
Resumo:
Taking as its case study Anne Cuneo’s autopathography, Une cuillerée de bleu (1979), and supported by a phenomenological reading of the subjective realities of illness, including feelings of alienation, fragmentation, and passivity, this article considers how the experience of cancer affects the patient’s perception of her body, self, and world.