Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility. Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry. Design, setting, and participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19 378 cases and 61 620 controls of African ancestry. Outcome measurements and statistical analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness. Results and limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40–60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10–1.38, p = 4.4 × 10–4). Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry. Patient summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease

MBL Agreement of Association

Document establishing the Marine Biological Laboratory as a Massachusetts corporationPurpose "to establish and maintain a laboratory or station for scientific study and investigation, and a school for instruction in biology and natural history"Correspondenc

Coronary artery calcium score: has anything changed?

Calcium deposition along the coronary artery walls is a surrogate biomarker for atherosclerosis, and its presence in the coronary arteries could reflect the severity of coronary artery disease (CAD). High coronary artery calcium score (CACS) correlates with advanced disease and a higher likelihood of coronary stenoses. Many studies have supported the role of CACS as a screening tool for CAD. Historically, CACS was introduced with electron beam computed tomography (EBCT), but in the last 30 years, many changes have occurred in CT, where the development of multidetector spiral technology has made reliable the noninvasive study of the heart and coronary arteries. Correlation studies with intravascular ultrasound (IVUS) and histology have demonstrated the capability of multidetector CT (MDCT) to provide information useful for characterising atherosclerotic plaque in a noninvasive manner. This has shifted the interest from heavily calcified deposits to plaque with a low-density core and small, superficial calcified nodules, features more frequently present in atherosclerotic plaque prone to rupture and responsible for acute coronary events (culprit lesions). The purpose of this review article is to summarise the recent evolution and revolution in the field of CT, strengthen the importance of a coronary CT study not limited to CACS evaluation and CAD grading but also used to obtain information about plaque composition, and to improve stratification of the patient at risk for acute coronary events

Adubação nitrogenada na aveia preta. I - Influência na produção de matéria seca e ciclagem de nutrientes sob sistema plantio direto Black oat biomass and nutrient cycling as affected by nitrogen fertilization in soil under no-tillage

O desempenho do sistema plantio direto está associado, dentre outros fatores, à quantidade e à qualidade dos resíduos aportados ao solo. A aveia preta é a principal cultura de cobertura utilizada na entressafra das culturas comerciais de verão. Em muitas situações, o desenvolvimento desta gramínea é limitado pela baixa disponibilidade de N do solo. Neste contexto, a adubação nitrogenada pode ser uma alternativa para aumentar a eficiência da aveia preta como cultura de cobertura no sistema plantio direto. O objetivo principal do presente estudo foi verificar a influência de doses de adubação nitrogenada sobre a produção de fitomassa, quantidade de nutrientes acumulados (N, P, K, Ca e Mg) e relação C/N dos resíduos produzidos pela cultura da aveia. O trabalho foi realizado durante os anos de 1998, 1999 e 2000, na área experimental do Departamento de Solos da UFSM, Santa Maria (RS), em um Argissolo Vermelho distrófico arênico com 19 g kg-1 de MO. O delineamento experimental foi de blocos ao acaso, com quatro repetições e sete tratamentos com aveia preta. Nestes, foram aplicadas as seguintes doses de N: 0, 40, 80, 120, 160, 200 e 240 kg ha-1. A fonte de N foi a uréia, aplicada parceladamente e a lanço na cultura da aveia. A adubação com P e K e a correção da acidez foram iguais em todos os tratamentos. A adubação nitrogenada ocasionou resposta quadrática na produção de matéria seca e na quantidade de nutrientes estocados na parte aérea da aveia, exceção ao N cuja resposta foi linear. A recuperação de N desta gramínea foi baixa, alcançando 33 %, na média dos três anos. Na maior dose de N aplicada, a ciclagem de P e K foi aumentada em, respectivamente, 70 e 88 % em relação ao tratamento sem adubação. Para o Ca, a dose estimada de 120 kg ha-1 de N promoveu incremento de 95 % no acúmulo deste nutriente, enquanto, para o Mg, levou a um aumento de 90 %, quando comparada ao tratamento sem adubação nitrogenada. A relação C/N dos resíduos produzidos diminuiu, aproximadamente, em uma unidade a cada 10 kg ha-1 de N aplicados na aveia. Portanto, a adubação nitrogenada, além de proporcionar maior ciclagem de nutrientes, foi uma eficiente estratégia para melhorar a quantidade e a qualidade dos resíduos de aveia preta aportados ao solo no sistema plantio direto.<br>The performance of no-tillage systems depends, among other factors, on the quantity and quality of residues added to the soil. In Southern Brazil, the main cover crop anteceding summer crops is black oat (Avena strigosa, Schieb). The growth of this grass is often limited by N deficiency. In this situation, nitrogen fertilization is a possible option to increase the efficiency of this cover crop in no-tillage systems. Main goal of this study was the evaluation of effects of N rates applied on black oat and biomass production, the amount of nutrient uptake (N, P, K, Ca, and Mg), as well as the C/N ratio in the produced residues. The experiment was carried out during 1998, 1999, and 2000 at the Federal University of Santa Maria, on the experimental area of the Soil Science Department, Santa Maria county, Rio Grande do Sul State, Brazil, on a typic Hapludalf with a sandy loam A horizon and 19 g kg-1 organic matter. The experimental layout was a completely randomized block design in four replicates, with treatments that consisted in seven N rates (0, 40, 80, 120, 160, 200, and 240 kg ha-1) applied to the black oat. Urea, used as N source, was spread out manually and in up to four split applications. Lime, P and K fertilization, based on crop needs, was applied at constant rates in all treatments. Nitrogen fertilization of black oat gave rise to a quadratic response in biomass production and nutrient contents stored in the oat shoots, while N responded linearly. The plant N recovery was low (around 33 % of the total N applied) in a three year average. Under the highest N dose, the amounts of recycled P and K was 70 and 88 % higher than in oat without N application. At the estimated N application rate of 120 kg ha-1, the amount of recycled Ca increased by 95 % and the recycled Mg by 90 %, compared to the treatment without nitrogen fertilizer. The C/N ratio of the produced residues decreased by about one unit for each 10 kg ha-1 of applied N. In conclusion, N fertilization is a viable alternative to increase the quality and quantity of black oat biomass added to soils in no-tillage systems; besides, it improves nutrient cycling

Genome-wide association study of prostate cancer-specific survival

Free to read\ud \ud BACKGROUND: \ud \ud Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical.\ud \ud METHODS: \ud \ud We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR).\ud \ud RESULTS: \ud \ud We observed no significant association between genetic variants and prostate cancer survival.\ud \ud CONCLUSIONS: \ud \ud Common genetic variants with large impact on prostate cancer survival were not observed in this study.\ud \ud IMPACT: \ud \ud Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes

The role of micro-organisms in the ecological connectivity of running waters

Pusch M, Fiebig D, Brettar I, et al. The role of micro-organisms in the ecological connectivity of running waters. Freshwater Biology. 1998;40(3):453-495