Cancer risk is determined by a complex interplay of environmental and heritable factors. Polygenic risk scores (PRS) provide a personalized genetic susceptibility profile that may be leveraged for ...disease prediction. Using data from the UK Biobank (413,753 individuals; 22,755 incident cancer cases), we quantify the added predictive value of integrating cancer-specific PRS with family history and modifiable risk factors for 16 cancers. We show that incorporating PRS measurably improves prediction accuracy for most cancers, but the magnitude of this improvement varies substantially. We also demonstrate that stratifying on levels of PRS identifies significantly divergent 5-year risk trajectories after accounting for family history and modifiable risk factors. At the population level, the top 20% of the PRS distribution accounts for 4.0% to 30.3% of incident cancer cases, exceeding the impact of many lifestyle-related factors. In summary, this study illustrates the potential for improving cancer risk assessment by integrating genetic risk scores.
Systemic inflammation markers have been linked to increased cancer risk and mortality in a number of studies. However, few studies have estimated pre-diagnostic associations of systemic inflammation ...markers and cancer risk. Such markers could serve as biomarkers of cancer risk and aid in earlier identification of the disease. This study estimated associations between pre-diagnostic systemic inflammation markers and cancer risk in the prospective UK Biobank cohort of approximately 440,000 participants recruited between 2006 and 2010. We assessed associations between four immune-related markers based on blood cell counts: systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and risk for 17 cancer sites by estimating hazard ratios (HR) using flexible parametric survival models. We observed positive associations with risk for seven out of 17 cancers with SII, NLR, PLR, and negative associations with LMR. The strongest associations were observed for SII for colorectal and lung cancer risk, with associations increasing in magnitude for cases diagnosed within one year of recruitment. For instance, the HR for colorectal cancer per standard deviation increment in SII was estimated at 1.09 (95% CI 1.02–1.16) in blood drawn five years prior to diagnosis and 1.50 (95% CI 1.24–1.80) in blood drawn one month prior to diagnosis. We observed associations between systemic inflammation markers and risk for several cancers. The increase in risk the last year prior to diagnosis may reflect a systemic immune response to an already present, yet clinically undetected cancer. Blood cell ratios could serve as biomarkers of cancer incidence risk with potential for early identification of disease in the last year prior to clinical diagnosis.
The use and importance of reintroduction as a conservation tool to return a species to its historical range from which it has been extirpated will increase as climate change and human development ...accelerate habitat loss and population extinctions. Although the number of reintroduction attempts has increased rapidly over the past 2 decades, the success rate is generally low. As a result of population differences in fitness-related traits and divergent responses to environmental stresses, population performance upon reintroduction is highly variable, and it is generally agreed that selecting an appropriate source population is a critical component of a successful reintroduction. Conservation genomics is an emerging field that addresses long-standing challenges in conservation, and the potential for using novel molecular genetic approaches to inform and improve conservation efforts is high. Because the successful establishment and persistence of reintroduced populations is highly dependent on the functional genetic variation and environmental stress tolerance of the source population, we propose the application of conservation genomics and transcriptomics to guide reintroduction practices. Specifically, we propose using genome-wide functional loci to estimate genetic variation of source populations. This estimate can then be used to predict the potential for adaptation. We also propose using transcriptional profiling to measure the expression response of fitness-related genes to environmental stresses as a proxy for acclimation (tolerance) capacity. Appropriate application of conservation genomics and transcriptomics has the potential to dramatically enhance reintroduction success in a time of rapidly declining biodiversity and accelerating environmental change. El uso y la importancia de la reintroducción como herramienta de conservación para regresar a las especies a su extensión histórica de la que han sido extirpada incrementarán conforme el cambio climático y los establecimientos humanos aceleren la pérdida de bábitat y la extinción de poblaciones. Aunque el número de intentos de reintroducción ha incrementado en las últimas dos décadas, la tasa de éxitos es generalmente baja. Como resultado de las diferencias poblacionales en los caracteres relacionados con la adecuación y las respuestas divergentes a los estreses ambientales, el desempeño poblacional tras la reintroducción es altamente variable y es un acuerdo general que la selección de una población fuente adecuada es un componente crítico de la reintroducción exitosa. La genómica de la conservación es un campo emergente que se enfoca en los retos de larga duración que enfrenta la conservación. El potencial para utilizar estrategias novedosas de genética molecular para informar y mejorar los esfuerzos de conservación es alto. Ya que el establecimiento exitoso y la persistencia de las poblaciones reintroducidas es altamente dependiente de la variación genética funcional y la tolerancia al estrés ambiental de la población fuente, proponemos la aplicación de la genómica de la conservación y los transcriptomas para guiar las práticas de reintroducción. Específicamente, proponemos usar loci funcionales a nivel genoma para estimar la variación genética de las poblaciones fuente. Este estimado puede usarse para predecir el potencial de adaptación de la población. También proponemos usar evaluaciones por perfiles de transcripción para medir la respuesta de expresión a los estreses ambientales de los genes relacionados con la adecuación como sustitutos de la capacidad de aclimatación (tolerancia). La aplicación adecuada de la genómica de la conservación y los transcriptomas tiene el potencial de mejorar dramáticamente el éxito de reintroducción en tiempos de declinación crítica de la biodiversidad y de cambios ambientales acelerados.
In 2022, the 22nd International Conference on Aquatic Invasive Species returned to Europe as a hybrid event. The conference welcomed representatives from 41 countries, including the largest group of ...students and early career professionals of any ICAIS conference. The theme of the conference was "Global Climate Change Amplifies Aquatic Invasive Species Impacts." Keynote speakers discussed ongoing invasions and the damaging synergy between climate change and invasions, presented on the value of risk assessment, outreach, and education, highlighted new ways to estimate the economic costs of invasions, and told attendees about some of the work of NGOs in managing invasions. This special issue includes a selection of papers that were presented at the conference, along with a few related papers that were not presented which touch on the risk of specific vectors, improvements in survey techniques to detect new or spreading invaders, and advances in management approaches to control AIS.
Risk factors for pancreatic cancer include a cluster of metabolic conditions such as obesity, hypertension, dyslipidemia, insulin resistance, and type 2 diabetes. Given that these risk factors are ...correlated, separating out causal from confounded effects is challenging. Mendelian randomization (MR), or the use of genetic instrumental variables, may facilitate the identification of the metabolic drivers of pancreatic cancer.
We identified genetic instruments for obesity, body shape, dyslipidemia, insulin resistance, and type 2 diabetes in order to evaluate their causal role in pancreatic cancer etiology. These instruments were analyzed in relation to risk using a likelihood-based MR approach within a series of 7110 pancreatic cancer patients and 7264 control subjects using genome-wide data from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Potential unknown pleiotropic effects were assessed using a weighted median approach and MR-Egger sensitivity analyses.
Results indicated a robust causal association of increasing body mass index (BMI) with pancreatic cancer risk (odds ratio OR = 1.34, 95% confidence interval CI = 1.09 to 1.65, for each standard deviation increase in BMI 4.6 kg/m2). There was also evidence that genetically increased fasting insulin levels were causally associated with an increased risk of pancreatic cancer (OR = 1.66, 95% CI = 1.05 to 2.63, per SD 44.4 pmol/L). Notably, no evidence of a causal relationship was observed for type 2 diabetes, nor for dyslipidemia. Sensitivity analyses did not indicate that pleiotropy was an important source of bias.
Our results suggest a causal role of BMI and fasting insulin in pancreatic cancer etiology.
This paper presents the global project Network for Observation of Volcanic and Atmospheric Change (NOVAC), the aim of which is automatic gas emission monitoring at active volcanoes worldwide. Data ...from the network will be used primarily for volcanic risk assessment but also for geophysical research, studies of atmospheric change, and ground validation of satellite instruments. A novel type of instrument, the scanning miniaturized differential optical absorption spectroscopy (Mini‐DOAS) instrument, is applied in the network to measure volcanic gas emissions by UV absorption spectroscopy. The instrument is set up 5–10 km downwind of the volcano under study, and typically two to four instruments are deployed at each volcano in order to cover different wind directions and to facilitate measurements of plume height and plume direction. Two different versions of the instrument have been developed. Version I was designed to be a robust and simple instrument for measurement of volcanic SO2 emissions at high time resolution with minimal power consumption. Version II was designed to allow the best possible spectroscopy and enhanced flexibility in regard to measurement geometry at the cost of larger complexity, power consumption, and price. In this paper the project is described, as well as the developed software, the hardware of the two instrument versions, measurement strategies, data communication, and archiving routines. As of April 2009 a total of 46 instruments have been installed at 18 volcanoes worldwide. As a typical example, the installation at Tungurahua volcano in Ecuador is described, together with some results from the first 21 months of operation at this volcano.
Aim
Environmental DNA (eDNA)‐based techniques are useful tools in disciplines such as conservation biogeography at local to global scales since they provide promising methods to locate organisms at ...low abundance. Here, we raise a largely overlooked issue that the marker (primer pairs and/or probes) sensitivity of eDNA‐based detection should be optimized and reported to improve detection performance and result interpretation.
Location
Global.
Methods
We analysed 250 articles published between 2008 and 2019 that sought to detect animals from environmental water samples using species‐specific markers to identify effort required.
Results
Most (66.0%) studies used newly designed markers, and real‐time quantitative PCR dominated the studies (72.4% of articles). The use of quantitative PCR increased significantly over time (p = .016), while conventional PCR decreased significantly (p = .005). In 82.4% of studies using newly designed markers, researchers did not screen their chosen markers for sensitivity, and 46.7% of these studies did not report the limit of detection (LoD). Limited knowledge of sensitivity screening and LoD was also found among aquatic species on the list of the world's worst alien invasive species, and many studies used published markers without such knowledge, potentially propagating errors.
Main conclusions
The rapidly growing use of eDNA‐based detection of low‐abundance species requires well‐designed protocols to improve sensitivity. Knowledge of the limits of eDNA technology is imperative, particularly when applied to conservation biogeography studies for detecting non‐indigenous or endangered species. Our results highlight the currently inadequate sensitivity screening of genetic markers used in most studies, contrasting the transition to highly sensitive PCR methods. Along with ongoing calls for standardization in the eDNA methods, we add that newly designed markers be screened to determine and optimize sensitivity before use to reduce the uncertainty of detection and benefit future applications within or beyond areas of their development.
Abstract Background A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death. ...Objective To increase the specificity of screening for lethal PCa at an early stage. Design, setting, and participants We conducted a case–control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Västerbotten, Sweden. Of 40 379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12 542 men were followed for >15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis. Outcome measurements and statistical analysis Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers. Results and limitations Most metastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (≤0.6%). Among men with PSA >2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA >2 ng/ml were defined as low risk by this model and had a ≤1% 15-yr risk of metastasis. Conclusions Screening at ages 50–60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making. Patient summary For men in their fifties, screening should focus on those in the top 10% to 25% of PSA values because the majority of subsequent cases of distant metastasis are found among these men. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making.
Individuals abstaining from alcohol consumption frequently find themselves in contexts encouraging consumption, with limited alternative social interaction opportunities. Conscious clubbing events ...exclude alcohol and drugs, possibly providing valuable social connections, but little is known about event benefits. Twelve conscious clubbing event attendees and facilitators aged 25–55 from across Europe participated in semi-structured photo-elicitation interviews, which were analysed using thematic analysis. Findings suggested that conscious clubbing appears to enhance health, healing and growth, aiding recovery from substance dependency and trauma. Positioned as a modern ritual, symbolic and ritualistic preparations and experiences promoted storytelling and self-discovery. Connecting through synchronised but unchoreographed movement, participants engaged in powerful journeys and transformative experiences detached from life constraints. Inclusive digital and face-to-face conscious clubbing communities provided a sense of meaning and belonging away from substance use pressures and harms, particularly for those marginalised within society. Findings provide important and in-depth insights, including novel harm prevention implications. Future work should consider participatory barriers, event sustainability and misconceptions to increase event availability and participation.
Inbreeding depression is the loss of fitness resulting from the mating of genetically related individuals. Traditionally, the study of inbreeding depression focused on genetic effects, although ...recent research has identified DNA methylation as also having a role in inbreeding effects. Since inbreeding depression and DNA methylation change with age and environmental stress, DNA methylation is a likely candidate for the regulation of genes associated with inbreeding depression. Here, we use a targeted, multigene approach to assess methylation at 22 growth‐, metabolic‐, immune‐ and stress‐related genes. We developed PCR‐based DNA methylation assays to test the effects of intense inbreeding on intragenic gene‐specific methylation in inbred and outbred Chinook salmon. Inbred fish had altered methylation at three genes, CK‐1, GTIIBS and hsp70, suggesting that methylation changes associated with inbreeding depression are targeted to specific genes and are not whole‐genome effects. While we did not find a significant inbreeding by age interaction, we found that DNA methylation generally increases with age, although methylation decreased with age in five genes, CK‐1, IFN‐ɣ, HNRNPL, hsc71 and FSHb, potentially due to environmental context and sexual maturation. As expected, we found methylation patterns differed among tissue types, highlighting the need for careful selection of target tissue for methylation studies. This study provides insight into the role of epigenetic effects on ageing, environmental response and tissue function in Chinook salmon and shows that methylation is a targeted and regulated cellular process. We provide the first evidence of epigenetically based inbreeding depression in vertebrates.
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