Qualitative analysis of how patients decide that they want risk-reducing mastectomy, and the implications for surgeons in responding to emotionally-motivated patient requests

Objective Contemporary approaches to medical decision-making advise that clinicians should respect patients’ decisions. However, patients’ decisions are often shaped by heuristics, such as being guided by emotion, rather than by objective risk and benefit. Risk-reducing mastectomy (RRM) decisions focus this dilemma sharply. RRM reduces breast cancer (BC) risk, but is invasive and can have iatrogenic consequences. Previous evidence suggests that emotion guides patients’ decision-making about RRM. We interviewed patients to better understand how they made decisions about RRM, using findings to consider how clinicians could ethically respond to their decisions. Methods Qualitative face-to-face interviews with 34 patients listed for RRM surgery and two who had decided against RRM. Results Patients generally did not use objective risk estimates or, indeed, consider risks and benefits of RRM. Instead emotions guided their decisions: they chose RRM because they feared BC and wanted to do ‘all they could’ to prevent it. Most therefore perceived RRM to be the ‘obvious’ option and made the decision easily. However, many recounted extensive post-decisional deliberation, generally directed towards justifying the original decision. A few patients deliberated before the decision because fears of surgery counterbalanced those of BC. Conclusion Patients seeking RRM were motivated by fear of BC, and the need to avoid potential regret for not doing all they could to prevent it. We suggest that choices such as that for RRM, which are made emotionally, can be respected as autonomous decisions, provided patients have considered risks and benefits. Drawing on psychological theory about how people do make decisions, as well as normative views of how they should, we propose that practitioners can guide consideration of risks and benefits even, where necessary, after patients have opted for surgery. This model of practice could be extended to other medical decisions that are influenced by patients’ emotions

Overexpression of leucocyte common antigen (LAR) P-subunit in thyroid carcinomas

Protein tyrosine phosphatase (PTPase) dephosphorylation and protein tyrosine kinase (PTKs) phosphorylation of key signal transduction proteins may be regulated by extracellular signals, making PTPases important in the regulation of cell proliferation. Leucocyte common antigen (LAR), a receptor-like PTPase, consists of E-subunit, containing the cell adhesion molecule-like receptor region, and P-subunit specific for a short segment of the extracellular region, the transmembrane peptide, and two cytoplasmic PTPase domains. We produced a monoclonal antibody against the LAR P-subunit for immunohistochemical screening of LAR expression in normal and tumourous tissues. Gliomas and gastric, colorectal, lung, breast and prostate cancers showed weak and relatively infrequent expression. Intense and diffuse expression, however, was detected in 95% (227 out of 239) of thyroid carcinomas, but only 12% (22 out of 128) of adenomas and no cases of benign thyroid disease were immunopositive. In contrast to broad staining in carcinomas, LAR expression in thyroid adenomas was often found in small focal or locally invasive areas. Western blot analysis similarly detected LAR P-subunit protein in thyroid carcinomas, but not in normal tissues. We believe this to be the first demonstration of LAR overexpression in thyroid carcinoma and may help to elucidate the role of PTPases in the development of malignancy

Evaluation of Candidate Stromal Epithelial Cross-Talk Genes Identifies Association between Risk of Serous Ovarian Cancer and TERT, a Cancer Susceptibility “Hot-Spot”

We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n = 675) and controls (n = 1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs—PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616—were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-allele<0.05 in the discovery stage were selected for replication in a subset of five OCAC studies (n = 1,233 serous invasive cases; n = 3,364 controls). The discovery stage associations in PODXL, ITGA6, and MMP3 were attenuated in the larger replication set (adj. Pper-allele≥0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele = 0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04–1.24) p = 0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus

Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis

Magnetism of U/Fe multilayers

Magnetic multilayers are known to have behaviour shaped by the intrinsic magnetic properties of their constituents and of their interactions. Multilayers composed of Uranium (5f electrons) and transition metal (3d electrons) provide the unique combination of a potentially large orbital moment with strong electronic hybridisation effects between the extended 5f states and the strongly magnetic 3d states. In this study U/Fe multilayers with layer thicknesses 20

Magnetism of uranium/iron multilayers: I. Fabrication and characterization

U/Fe multilayers constitute a magnetic system in which the 3d magnetism of the Fe layers will be modified by hybridization with the U 5f electrons. This paper describes a programme of measurements of the magnetic behaviour of these systems beginning with the fabrication and thorough characterization of the samples. Metallic U/Fe multilayers were prepared by DC sputtering in a UHV chamber. A range of samples with measured U thicknesses, t U, in the range 18-66 Å and Fe thicknesses, t Fe, from 7 to 108 Å was fabricated. X-ray and neutron reflectivity measurements showed strong peaks indicating good layer structure and gave a determination of the bilayer thickness. X-ray diffraction analysis showed crystalline α-U and α-Fe for layer thicknesses greater than about 20 Å. The α-Fe is strongly textured with (110) planes in the layer plane. The Fe lattice parameter is larger for the case of thin layers, but approaches the bulk value of 2.866 Å at t Fe ∼ 75 Å. Mössbauer spectra of α-Fe were obtained for t Fe ≥ 18 Å; a non-magnetic component of thickness ∼12 Å per layer is always present. The results from these different experimental techniques are combined to present a detailed description of these multilayer systems

Resonant magnetic reflectivity from U/Fe multilayers

U/Fe multilayers have been produced through dc sputtering. The high quality of these multilayers has been confirmed through x-ray reflectivity measurements and fitting to the resultant spectra. These samples are currently the subject of investigations using techniques including polarized neutron reflectivity, conversion electron Mossbauer spectroscopy, and magnetotransport and magneto-optic measurements. In this article, we report on results obtained from a [U 30 Angstrom/Fe 40 Angstrom]x30 multilayer through resonant magnetic scattering performed on the XMaS beamline at the European Synchrotron Radiation Facility. The asymmetry ratio is defined as (I+-I-)/(I++I-), where I+(I-) is the normalized intensity obtained with circular polarization and the applied field parallel (antiparallel) to the beam direction. Asymmetry data are presented as functions of both energy and momentum transfer. We have identified a Uranium moment with the use of resonant magnetic reflectivity at 12 K. Reversal of the polarity of the asymmetry ratio between the first and second superlattice peaks indicates a nonuniform moment distribution through the uranium layers. Temperature dependence measurements confirm that the moment also exists at room temperature. (C) 2003 American Institute of Physics

Finding the sweet spot: Can social marketing encourage cane farmers to change practices for water quality outcomes in the Great Barrier Reef Catchment?

The Great Barrier Reef is under increasing pressure from the cumulative effects of climate change, land-based runoff, coastal land-use change and direct use impacts. Many water quality behaviour change programs fail to achieve sustained change using traditional methods. NQ Dry Tropics received funding from the Queensland Government Reef Water Quality Program to trial methods with 14 farmers at two wetland sites, to achieve water quality outcomes in the sugarcane farming sector of the Lower Burdekin. These methods sought to increase the adoption of practice changes to reduce excess irrigation and nutrients in the fun off flowing into nearby wetlands using an adapted community-based social marketing methodology to understand an individual's perceived benefits and barriers to practice change, and create tailored extension, engagement, and communication tools. This paper will evaluate the effectives of using social marketing techniques to change the attitudes and behaviour of the sugarcane farmers