Disordini psichici e sociali. 'Il Diavolo Bianco' e 'La Duchessa di Amalfi' di Webster. [Mental and social disorders. 'The White Devil' and 'The Duchess of Malfi' by Webster]

In this essay, the authors explore the mental and social worlds depicted in Webster's two great Jacobean tragedies, The White Devil (1612) and The Duchess of Malfi. (1623). The authors particularly focus on the sibling relationships depicted in these plays, and explore how far the strengths or weakness of these relationships, their domination by the life or death drives, by emotions of love or hate, can be understood as a measure of the health of the social order in which these relationships are situate

Using serum CA125 to assess the activity of potential cytostatic agents in ovarian cancer

Objective: New strategies are required to rapidly identify novel cytostatic agents before embarking on large randomized trials. This study investigates whether a change in rate of rise (slope) of serum CA125 from before to after starting a novel agent could be used to identify cytostatic agents. Tamoxifen was used to validate this hypothesis. Methods: Asymptomatic patients with relapsed ovarian cancer who had responded to chemotherapy were enrolled and had CA125 measurements taken every 4 weeks, then more frequently when rising. Once levels reached 4 times the upper limit of normal or nadir, they started continuous tamoxifen 20 mg daily, as well as fortnightly CA125 measurements until symptomatic progression. Because of the potentially nonlinear relationship of CA125 over time, it was felt that to enable normal approximations to be utilized a natural logarithmic standard transformation [ln(CA125)] was the most suitable to improve linearity above the common logarithmic transformation to base 10. Results: From 235 recruited patients, 81 started tamoxifen and had at least 4 CA125 measurements taken before and 4 CA125 measurements taken after starting tamoxifen, respectively. The mean regression slopes from using at least 4 1n(CA125) measurements immediately before and after starting tamoxifen were 0I0149 and 0I0093 [ln(CA125)/d], respectively. This difference is statistically significant, P = 0I001. Therefore, in a future trial with a novel agent, at least as effective as tamoxifen, using this effect size, the number of evaluable patients needed, at significance level of 5% and power of 80%, is 56. Conclusions: Further validation of this methodology is required, but there is potential to use comparison of mean regression slopes of ln(CA125) as an interim analysis measure of efficacy for novel cytostatic agents in relapsed ovarian cancer.Peer reviewedFinal Accepted Versio

Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as 'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone

Exposure of a population of invasive wild pigs to simulated toxic bait containing biomarker: implications for population reduction

BACKGROUND: An international effort to develop an acute and humane toxic bait for invasive wild pigs (Sus scrofa) is underway to curtail their expansion. We evaluated the ability to expose a population of wild pigs to a simulated toxic bait (i.e., placebo bait containing a biomarker, rhodamine B, in lieu of the toxic ingredient) to gain insight on potential population reduction. We used 28 GPS-collars and sampled 428 wild pigs to examine their vibrissae for evidence of consuming the bait. RESULTS: We estimated that 91% of wild pigs within 0.75 km of bait sites (total area = 16.8 km2) consumed the simulated toxic bait, exposing them to possible lethal effects. Bait sites spaced 0.75–1.5 km apart achieved optimal delivery of the bait, but wild pigs ranging ≥ 3 km away were susceptible. Use of wild pig-specific bait stations resulted in no non-target species directly accessing the bait. CONCLUSION: Results demonstrate the potential for exposing a large proportion of wild pigs to a toxic bait in similar ecosystems. Toxic bait may be an effective tool for reducing wild pig populations especially if used as part of an integrated pest management strategy. Investigation of risks associated with a field-deployment of the toxic bait is needed

Seeing the way: visual sociology and the distance runner's perspective

Employing visual and autoethnographic data from a two‐year research project on distance runners, this article seeks to examine the activity of seeing in relation to the activity of distance running. One of its methodological aims is to develop the linkage between visual and autoethnographic data in combining an observation‐based narrative and sociological analysis with photographs. This combination aims to convey to the reader not only some of the specific subcultural knowledge and particular ways of seeing, but also something of the runner's embodied feelings and experience of momentum en route. Via the combination of narrative and photographs we seek a more effective way of communicating just how distance runners see and experience their training terrain. The importance of subjecting mundane everyday practices to detailed sociological analysis has been highlighted by many sociologists, including those of an ethnomethodological perspective. Indeed, without the competence of social actors in accomplishing these mundane, routine understandings and practices, it is argued, there would in fact be no social order

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

High-throughput genomic technology in research and clinical management of breast cancer. Plasma-based proteomics in early detection and therapy

Protein-based breast cancer biomarkers are a promising resource for breast cancer detection at the earliest and most treatable stages of the disease. Plasma is well suited to proteomic-based methods of biomarker discovery because it is easily obtained, is routinely used in the diagnosis of many diseases, and has a rich proteome. However, due to the vast dynamic range in protein concentration and the often uncertain tissue and cellular origin of plasma proteins, proteomic analysis of plasma requires special consideration compared with tissue and cultured cells. This review briefly touches on the search for plasma-based protein biomarkers for the early detection and treatment of breast cancer