Engaging stakeholders across a socio-environmentally diverse network of water research sites in North and South America

Maintaining and restoring freshwater ecosystem services in the face of local and global change requires adaptive research that effectively engages stakeholders. However, there is a lack of understanding and consensus in the research community regarding where, when, and which stakeholders should be engaged and what kind of researcher should do the engaging (e.g., physical, ecological, or social scientists). This paper explores stakeholder engagement across a developing network of aquatic research sites in North and South America with wide ranging cultural norms, social values, resource management paradigms, and eco-physical conditions. With seven sites in six countries, we found different degrees of engagement were explained by differences in the interests of the stakeholders given the history and perceived urgency of water resource problems as well as differences in the capacities of the site teams to effectively engage given their expertise and resources. We categorized engagement activities and applied Hurlbert and Gupta's split ladder of participation to better understand site differences and distill lessons learned for planning comparative socio-hydrological research and systematic evaluations of the effectiveness of stakeholder engagement approaches. We recommend research networks practice deliberate engagement of stakeholders that adaptively accounts for variations and changes in local socio-hydrologic conditions. This, in turn, requires further efforts to foster the development of well-integrated research teams that attract and retain researchers from multiple social science disciplines and enable training on effective engagement strategies for diverse conditions

Engaging stakeholders across a socio-environmentally diverse network of water research sites in North and South America

Maintaining and restoring freshwater ecosystem services in the face of local and global change requires adaptive research that effectively engages stakeholders. However, there is a lack of understanding and consensus in the research community regarding where, when, and which stakeholders should be engaged and what kind of researcher should do the engaging (e.g., physical, ecological, or social scientists). This paper explores stakeholder engagement across a developing network of aquatic research sites in North and South America with wide ranging cultural norms, social values, resource management paradigms, and eco-physical conditions. With seven sites in six countries, we found different degrees of engagement were explained by differences in the interests of the stakeholders given the history and perceived urgency of water resource problems as well as differences in the capacities of the site teams to effectively engage given their expertise and resources. We categorized engagement activities and applied Hurlbert and Gupta's split ladder of participation to better understand site differences and distill lessons learned for planning comparative socio-hydrological research and systematic evaluations of the effectiveness of stakeholder engagement approaches. We recommend research networks practice deliberate engagement of stakeholders that adaptively accounts for variations and changes in local socio-hydrologic conditions. This, in turn, requires further efforts to foster the development of well-integrated research teams that attract and retain researchers from multiple social science disciplines and enable training on effective engagement strategies for diverse conditions.Fil: Smyth, Robyn L.. Bard College; Estados UnidosFil: Fatima, Uroosa. Bard College; Estados UnidosFil: Segarra, Monique. Bard College; Estados UnidosFil: Borre, Lisa. Cary Institute of Ecosystem Studies; Estados UnidosFil: Zilio, Mariana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Económicas y Sociales del Sur. Universidad Nacional del Sur. Departamento de Economía. Instituto de Investigaciones Económicas y Sociales del Sur; ArgentinaFil: Reid, Brian. Universidad Austral de Chile; ChileFil: Pincetl, Stephanie. Institute of the Environment and Sustainability; Estados UnidosFil: Astorga, Anna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Económicas y Sociales del Sur. Universidad Nacional del Sur. Departamento de Economía. Instituto de Investigaciones Económicas y Sociales del Sur; ArgentinaFil: Huamantinco Cisneros, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Geografía y Turismo; ArgentinaFil: Conde, Sergio Daniel. Universidad de la República; UruguayFil: Harmon, Thomas Christopher. University of California Merced; Estados UnidosFil: Hoyos, Natalia. Universidad del Norte; ColombiaFil: Escobar, Jaime. Universidad del Norte; Colombia. Smithsonian Tropical Research Institute; PanamáFil: Lozoya, Juan Pablo. Universidad de la República; UruguayFil: Perillo, Gerardo Miguel E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Geología; ArgentinaFil: Piccolo, Maria Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Geografía y Turismo; ArgentinaFil: Rusak, James A.. Dorset Environmental Science Centre; Canadá. Queens University; CanadáFil: Velez, Maria I.. University of Regina; Canad

Fast and efficient QTL mapper for thousands of molecular phenotypes

In order to discover quantitative trait loci, multi-dimensional genomic datasets combining DNA-seq and ChiP-/RNA-seq require methods that rapidly correlate tens of thousands of molecular phenotypes with millions of genetic variants while appropriately controlling for multiple testing

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Docetaxel Versus Surveillance After Radical Prostatectomy for High-risk Prostate Cancer: Results from the Prospective Randomised, Open-label Phase 3 Scandinavian Prostate Cancer Group 12 Trial

To access publisher's full text version of this article click on the hyperlink belowBACKGROUND: Adjuvant chemotherapy is standard treatment for other solid tumours, but to date has not proven effective in prostate cancer. OBJECTIVE: o evaluate whether six cycles of docetaxel alone improve biochemical disease-free survival after radical prostatectomy for high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Open-label, randomised multinational phase 3 trial. Enrolment of 459 patients after prostatectomy. INCLUSION CRITERIA: high-risk pT2 margin positive or pT3a Gleason score ≥4+3, pT3b, or lymph node positive disease Gleason score ≥3+4. Patients assigned (1:1) to either six cycles of adjuvant docetaxel 75mg/m2 every 3 wk without daily prednisone (Arm A) or surveillance (Arm B) until endpoint was reached. Primary endpoint was prostate-specific antigen progression ≥0.5 ng/ml. INTERVENTION: Docetaxel treatment after prostatectomy. RESULTS AND LIMITATIONS: Median time to progression, death, or last follow-up was 56.8 mo. Primary endpoint was reached in 190/459 patients-the risk of progression at 5 yr being 41% (45% in Arm A and 38% in Arm B). There was evidence of nonproportional hazards in Kaplan-Meier analysis, so we used the difference in restricted mean survival time as the primary estimate of effect. Restricted mean survival time to endpoint was 43 mo in Arm A versus 46 mo in Arm B (p=0.06), a nonsignificant difference of 3.2 mo (95% confidence interval: 6.7 to -1.5 mo). A total of 116 serious adverse events were recorded in Arm A and 41 in Arm B with no treatment-related deaths. Not all patients received docetaxel by protocol. The endpoint is biochemical progression and some patients received radiation treatment before the endpoint. CONCLUSIONS: Docetaxel without hormonal therapy did not significantly improve biochemical disease-free survival after radical prostatectomy. PATIENT SUMMARY: In this randomised trial, we tested whether chemotherapy after surgery for high-risk prostate cancer decreases the risk of a rising prostate-specific antigen. We found no benefit from docetaxel given after radical prostatectomy.Sanof