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BACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHOD(S): The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3.0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This

We conducted a policy situation analysis in three Mekong region countries, focused on how the animal and human health systems interact to control avian influenza (AI). The study used scoping literature reviews aimed at establishing existing knowledge concerning the regulatory context. We then conducted a series of key informant interviews with national and sub-national government officials and representatives of producers and poultry farmers to understand their realities in managing the complex interface of the two sectors to control AI. We found signs of formal progress in establishing the policy and legislative frameworks needed to enable cooperation of the two sectors but a series of constraints that impede their effective operation. These included the competitive relationships involved, especially with budgetary allocations and mandates that can conflict with each other. Many local actors also view development partners (e.g., bilateral and multilateral donors) as having a dominant role in establishing these collaborations, limiting the extent to which there is local ownership of the agenda. The animal and human health sectors are not equally resourced, with the animal health sector disadvantaged in terms of surveillance and laboratory systems, human resources and financial allocations. Contrasting strategies for achieving objectives have also characterised the two sectors in recent decades, seeing a major shift towards the use of incentive-based approaches in the human health sector but very little parallel development in the animal health sector, largely dependent on command and control approaches. Successful future collaborations between the two sectors are likely to depend on better resourcing in the animal health sector, increasing local ownership of the agenda, and ensuring that both sectors can use the full range of regulatory strategies available to achieve objectives.

Poly ADP ribose polymerase (PARP) inhibitors offer a survival advantage to women with high-grade serous ovarian cancer who have a germline BRCA1/2 pathogenic variant (PV). Yet, rates of genetic testing among this population have remained persistently low. A national, centralized telephone genetic counseling service was established in January 2016 in Australia to improve access to genetic services and facilitate BRCA1/2 testing for this population to inform treatment. Medical oncologists can refer their patients with high-grade serous ovarian cancer to this service for genetic testing. This study aimed to explore oncologists’ experiences of using this telephone genetic counseling service for their patients with high-grade serous ovarian cancer. A qualitative approach using semi-structured telephone interviews was undertaken with Australian oncologists who had referred patients to the telephone genetic counseling service. Sixteen oncologists participated and described referring patients to the telephone genetic counseling service due to the timeliness of obtaining a genetic counseling appointment and BRCA1/2 test results. They also reported this service offered convenience for patients living in regional or rural areas who then did not have to travel for an appointment with a clinical genetics service. Many oncologists noted the importance of in-person genetic counseling for patients who received positive BRCA1/2 results. Areas for improvement identified by the oncologists related to communication issues between the service and the patient. Overall, findings suggest that oncologists perceived telephone genetic counseling as an acceptable and useful healthcare service for patients with high-grade serous ovarian cancer. Moreover, they perceived telephone genetic counseling to be efficient, delivering convenient genetic counseling to patients.

BACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHODS: The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3·0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This s

Biplots constructed from principal components of a compositional data set are an established means to explore its features. Principal Component Analysis (PCA) is also used to transform a set of spatial variables into spatially decorrelated factors. However, because no spatial structures are accounted for in the transformation the application of PCA is limited. In geostatistics and blind source separation a variety of different matrix diagonalization methods have been developed with the aim to provide spatially or temporally decorrelated factors. Just as PCA, many of these transformations are linear and so lend themselves to the construction of biplots. In this contribution we consider such biplots for a number of methods (MAF, UWEDGE and RJD transformations) and discuss how and if they can contribute to our understanding of relationships between the components of regionalized compositions. A comparison of the biplots with the PCA biplot commonly used in compositional data analysis for the case of data from the Northern Irish geochemical survey shows that the biplots from MAF and UWEDGE are comparable as are those from PCA and RJD. The biplots emphasize different aspects of the regionalized composition: for MAF and UWEDGE the focus is the spatial continuity, while for PCA and RJD it is variance explained. The results indicate that PCA and MAF combined provide adequate and complementary means for exploratory statistical analysis.

Biplots constructed from principal components of a compositional data set are an established means to explore its features. Principal Component Analysis (PCA) is also used to transform a set of spatial variables into spatially decorrelated factors. However, because no spatial structures are accounted for in the transformation the application of PCA is limited. In geostatistics and blind source separation a variety of different matrix diagonalization methods have been developed with the aim to provide spatially or temporally decorrelated factors. Just as PCA, many of these transformations are linear and so lend themselves to the construction of biplots. In this contribution we consider such biplots for a number of methods (MAF, UWEDGE and RJD transformations) and discuss how and if they can contribute to our understanding of relationships between the components of regionalized compositions. A comparison of the biplots with the PCA biplot commonly used in compositional data analysis for the case of data from the Northern Irish geochemical survey shows that the biplots from MAF and UWEDGE are comparable as are those from PCA and RJD. The biplots emphasize different aspects of the regionalized composition: for MAF and UWEDGE the focus is the spatial continuity, while for PCA and RJD it is variance explained. The results indicate that PCA and MAF combined provide adequate and complementary means for exploratory statistical analysis.