Multiple stressors alter greenhouse gas concentrations in streams through local and distal processes.

Streams are significant contributors of greenhouse gases (GHG) to the atmosphere, and the increasing number of stressors degrading freshwaters may exacerbate this process, posing a threat to climatic stability. However, it is unclear whether the influence of multiple stressors on GHG concentrations in streams results from increases of in-situ metabolism (i.e., local processes) or from changes in upstream and terrestrial GHG production (i.e., distal processes). Here, we hypothesize that the mechanisms controlling multiple stressor effects vary between carbon dioxide (CO2) and methane (CH4), with the latter being more influenced by changes in local stream metabolism, and the former mainly responding to distal processes. To test this hypothesis, we measured stream metabolism and the concentrations of CO2 (pCO2) and CH4 (pCH4) in 50 stream sites that encompass gradients of nutrient enrichment, oxygen depletion, thermal stress, riparian degradation and discharge. Our results indicate that these stressors had additive effects on stream metabolism and GHG concentrations, with stressor interactions explaining limited variance. Nutrient enrichment was associated with higher stream heterotrophy and pCO2, whereas pCH4 increased with oxygen depletion and water temperature. Discharge was positively linked to primary production, respiration and heterotrophy but correlated negatively with pCO2. Our models indicate that CO2-equivalent concentrations can more than double in streams that experience high nutrient enrichment and oxygen depletion, compared to those with oligotrophic and oxic conditions. Structural equation models revealed that the effects of nutrient enrichment and discharge on pCO2 were related to distal processes rather than local metabolism. In contrast, pCH4 responses to nutrient enrichment, discharge and temperature were related to both local metabolism and distal processes. Collectively, our study illustrates potential climatic feedbacks resulting from freshwater degradation and provides insight into the processes mediating stressor impacts on the production of GHG in streams.

Os rios são grandes emissores de gases com efeito de estufa (GEE) para a atmosfera, e o crescente número de agentes de stress que degradam os rios pode exacerbar este processo, e constituir uma ameaça à estabilidade climática. No entanto, não é claro se o efeito dos impactos humanos nas concentrações de GEE na água está associado ao aumento do metabolismo local do rio (processos locais) ou ao aumento da produção de GEE nas zonas a montante dos rios ou nas zonas terrestres adjacentes (processos distais). A nossa hipótese é que os mecanismos que controlam os efeitos dos impactos humanos na emissão de GEE variam entre o dióxido de carbono (CO2) e o metano (CH4). A nossa previsão é que o CO2 responde principalmente a processos distais, enquanto o CH4 é mais influenciado por alterações no metabolismo local dos cursos de água. Para avaliar esta hipótese, medimos o metabolismo aquático e as concentrações de CO2 (pCO2) e CH4 (pCH4) em 50 rios que abrangem gradientes de enriquecimento em nutrientes, depleção de oxigénio, stress térmico, degradação da zona ribeirinha e caudal. Os nossos resultados indicam que estes agentes de stress tiveram efeitos aditivos no metabolismo e nas concentrações de GEE nos rios, e que as interações entre os agentes de stress tiveram pouca capacidade preditiva. O enriquecimento em nutrientes foi associado a um aumento da heterotrofia e pCO2, enquanto o pCH4 aumentou com a depleção de oxigénio e com a temperatura da água. O caudal estava positivamente correlacionado com a produção primária, a respiração e a heterotrofia, mas negativamente correlacionado com o pCO2. Os nossos modelos indicam que as concentrações equivalentes de CO2 podem duplicar em rios eutrofizados e com baixa concentração de oxigénio, em comparação com os rios oligotróficos e com águas bem oxigenadas. A aplicação de modelos de equações estruturais mostrou que os efeitos do enriquecimento em nutrientes e do caudal no pCO2 estavam relacionados com processos distais e não com o metabolismo local. Em contrapartida, as respostas do pCH4 ao enriquecimento de nutrientes, ao caudal e à temperatura estavam relacionadas tanto com o metabolismo local como com processos distais. O nosso estudo demonstra que a degradação dos rios e dos ecossistemas ribeirinhos pode ter efeitos negativos na estabilidade climática e fornece informação relevante sobre os processos biogeoquímicos que medeiam os impactos humanos na produção de GEE nos rios.

Feature-specific quantile normalization and feature-specific mean-variance normalization deliver robust bi-directional classification and feature selection performance between microarray and RNAseq data.

BACKGROUND: Cross-platform normalization seeks to minimize technological bias between microarray and RNAseq whole-transcriptome data. Incorporating multiple gene expression platforms permits external validation of experimental findings, and augments training sets for machine learning models. Here, we compare the performance of Feature Specific Quantile Normalization (FSQN) to a previously used but unvalidated and uncharacterized method we label as Feature Specific Mean Variance Normalization (FSMVN). We evaluate the performance of these methods for bidirectional normalization in the context of nested feature selection. RESULTS: FSQN and FSMVN provided clinically equivalent bidirectional model performance with and without feature selection for colon CMS and breast PAM50 classification. Using principal component analysis, we determine that these methods eliminate batch effects related to technological platforms. Without feature selection, no statistical difference was identified between the performance of FSQN and FSMVN of cross-platform data compared to within-platform distributions. Under optimal feature selection conditions, balanced accuracy was FSQN and FSMVN were statistically equivalent to the within-platform distribution performance in multivariable linear regression analysis. FSQN and FSMVN also provided similar performance to within-platform distributions as the number of selected genes used to create models decreases. CONCLUSIONS: In the context of generating supervised machine learning classifiers for molecular subtypes, FSQN and FSMVN are equally effective. Under optimal modeling conditions, FSQN and FSMVN provide equivalent model accuracy performance on cross-platform normalization data compared to within-platform data. Using cross-platform data should still be approached with caution as subtle performance differences may exist depending on the classification problem, training, and testing distributions.

Individual Survival Distributions Generated by Multi-Task Logistic Regression Yield a New Perspective on Molecular and Clinical Prognostic Factors in Gastric Adenocarcinoma.

Recent advances in our understanding of gastric cancer biology have prompted a shift towards more personalized therapy. However, results are based on population-based survival analyses, which evaluate the average survival effects of entire treatment groups or single prognostic variables. This study uses a personalized survival modelling approach called individual survival distributions (ISDs) with the multi-task logistic regression (MTLR) model to provide novel insight into personalized survival in gastric adenocarcinoma. We performed a pooled analysis using 1043 patients from a previously characterized database annotated with molecular subtypes from the Cancer Genome Atlas, Asian Cancer Research Group, and tumour microenvironment (TME) score. The MTLR model achieved a 5-fold cross-validated concordance index of 72.1 ± 3.3%. This model found that the TME score and chemotherapy had similar survival effects over the entire study time. The TME score provided the greatest survival benefit beyond a 5-year follow-up. Stage III and Stage IV disease contributed the greatest negative effect on survival. The MTLR model weights were significantly correlated with the Cox model coefficients (Pearson coefficient = 0.86, p < 0.0001). We illustrate how ISDs can accurately predict the survival time for each patient, which is especially relevant in cases of molecular subtype heterogeneity. This study provides evidence that the TME score is principally associated with long-term survival in gastric adenocarcinoma. Additional external validation and investigation into the clinical utility of this ISD model in gastric cancer is an area of future research.

Treated and highly diluted, but wastewater still impacts diversity and energy fluxes of freshwater food webs.

Wastewater treatment plants (WWTPs) have greatly improved water quality globally. However, treated effluents still contain a complex cocktail of pollutants whose environmental effects might go unnoticed, masked by additional stressors in the receiving waters or by spatiotemporal variability. We conducted a BACI (Before-After/Control-Impact) ecosystem manipulation experiment, where we diverted part of the effluent of a large tertiary WWTP into a small, unpolluted stream to assess the effects of a well-treated and highly diluted effluent on riverine diversity and food web dynamics. We sampled basal food resources, benthic invertebrates and fish to search for changes on the structure and energy transfer of the food web with the effluent. Although effluent toxicity was low, it reduced diversity, increased primary production and herbivory, and reduced energy fluxes associated to terrestrial inputs. Altogether, the effluent decreased total energy fluxes in stream food webs, showing that treated wastewater can lead to important ecosystem-level changes, affecting the structure and functioning of stream communities even at high dilution rates. The present study shows that current procedures to treat wastewater can still affect freshwater ecosystems and highlights the need for further efforts to treat polluted waters to conserve aquatic food webs.

Increased CD4/CD8 Lymphocyte ratio predicts favourable neoadjuvant treatment response in gastric cancer: A prospective pilot study.

BACKGROUND: Despite optimal neoadjuvant chemotherapy only 40% of gastric cancer tumours achieve complete or partial treatment response. In the absence of treatment response, neoadjuvant chemotherapy in gastric cancer contributes to adverse events without additional survival benefit compared to adjuvant treatment or surgery alone. Additional strategies and methods are required to optimize the allocation of existing treatment regimens such as FLOT chemotherapy (5-Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel). Predictive biomarkers detected using immunohistochemistry (IHC) methods may provide useful data regarding treatment response. AIM: To investigate the utility of CD4, CD8, Galectin-3 and E-cadherin in predicting neoadjuvant FLOT chemotherapy tumour response in gastric adenocarcinoma. METHODS: Forty-three adult patients with gastric adenocarcinoma, of which 18 underwent neoadjuvant chemotherapy, were included in a prospective clinical cohort. Endoscopic biopsies were obtained from gastric cancer and normal adjacent gastric mucosa. Differences in expression of Galectin-3, E-cadherin, CD4+ and CD8+ molecules between tumours with and without treatment response to neoadjuvant chemotherapy were assessed with IHC. Treatment response was graded by clinical pathologists using the Tumour Regression Score according to the College of American Pathologists criteria. Treatment response was defined as complete or near complete tumour response, whereas partial or poor/no response was defined as incomplete. Digital IHC images were annotated and quantitatively assessed using QuPath 0.3.1. Biomarker expression between responsive and incomplete response tumours was assessed using a two-sided Wilcoxon test. Biomarker expression was also compared between normal and cancer tissue and between 15 paired tumour samples before and after chemotherapy. We performed a preliminary multivariate analysis and power analysis to guide future study. Statistical analyses were completed using R 4.1.2. RESULTS: The ratio between CD4+ and CD8+ lymphocytes was significantly greater in treatment responsive tumours (Wilcoxon, P = 0.03). In univariate models, CD4+/CD8+ ratio was the only biomarker that significantly predicted favourable treatment response (Accuracy 86%, P < 0.001). Using a glmnet multivariate model, high CD4+/CD8+ ratio and low Galectin-3 expression were the most influential variables in predicting a favourable treatment response. Analyses of paired samples found that FLOT chemotherapy also results in increased expression of CD4+ and CD8+ tumour infiltrating lymphocytes (Paired Wilcoxon, P = 0.002 and P = 0.008, respectively). Our power analysis suggests future study requires at least 35 patients in each treatment response group for CD8 and Galectin-3 molecules, whereas 80 patients in each treatment response group are required to assess CD4 and E-cadherin biomarkers. CONCLUSION: We demonstrate that an elevated CD4+/CD8+ Ratio is a promising IHC-based biomarker to predict favourable treatment response to FLOT neoadjuvant chemotherapy in locally advanced gastric cancer.

A global synthesis of human impacts on the multifunctionality of streams and rivers.

Human impacts, particularly nutrient pollution and land-use change, have caused significant declines in the quality and quantity of freshwater resources. Most global assessments have concentrated on species diversity and composition, but effects on the multifunctionality of streams and rivers remain unclear. Here, we analyse the most comprehensive compilation of stream ecosystem functions to date to provide an overview of the responses of nutrient uptake, leaf litter decomposition, ecosystem productivity, and food web complexity to six globally pervasive human stressors. We show that human stressors inhibited ecosystem functioning for most stressor-function pairs. Nitrate uptake efficiency was most affected and was inhibited by 347% due to agriculture. However, concomitant negative and positive effects were common even within a given stressor-function pair. Some part of this variability in effect direction could be explained by the structural heterogeneity of the landscape and latitudinal position of the streams. Ranking human stressors by their absolute effects on ecosystem multifunctionality revealed significant effects for all studied stressors, with wastewater effluents (194%), agriculture (148%), and urban land use (137%) having the strongest effects. Our results demonstrate that we are at risk of losing the functional backbone of streams and rivers if human stressors persist in contemporary intensity, and that freshwaters are losing critical ecosystem services that humans rely on. We advocate for more studies on the effects of multiple stressors on ecosystem multifunctionality to improve the functional understanding of human impacts. Finally, freshwater management must shift its focus toward an ecological function-based approach and needs to develop strategies for maintaining or restoring ecosystem functioning of streams and rivers.

Yield of routine staging laparoscopy in patients with gastric cancer in Alberta, Canada.

BACKGROUND: Despite guidelines recommending diagnostic laparoscopy in patients with gastric cancer, implementation is low. We aimed to explore trends in the use of laparoscopy for staging of gastric cancer in Alberta, Canada, determine the rate of positive findings and identify factors predictive of positive staging laparoscopy (SL) findings in this patient population. METHODS: In August 2018, we sent a survey to all general surgeons in Alberta who were members of the Alberta Association of General Surgeons to identify those treating gastric cancer. The survey inquired about type of practice (academic or community), gastric cancer case volume, routine versus selective use of SL and, if selective use of SL, criteria used to select cases. Participants were also asked to provide data from their SL cases from July 2007 to February 2019. We double-checked surgeon records with chart review. The primary outcome was evidence of metastatic disease on SL or cytologic examination or both. We performed logistic regression analysis to identify factors predictive of positive laparoscopy findings. RESULTS: The survey was completed by 41 of 127 surgeons (response rate 32.3%). We reviewed 116 cases from 5 surgeons at 4 centres. Gross metastatic disease or positive findings on cytologic examination or both were identified in 37 patients (31.9%). On univariate analysis, the following were associated with an increased risk of identification of metastatic disease at laparoscopy: visualization of the primary tumour on computed tomography (CT) (odds ratio [OR] 9.8, 95% confidence interval [CI] 1.2-76.5), presence of abdominal lymphadenopathy greater than 1 cm (OR 2.4, 95% CI 1.1-5.4) and presence of ascites (OR 19.1, 95% CI 2.2-161.8). Visualization of the primary tumour on CT (OR 8.4, 95% CI 1.0-68.3) and the presence of ascites (OR 15.9, 95% CI 1.8-137.0) remained statistically significant predictors on multivariate analysis. CONCLUSION: Metastatic disease was identified at SL in almost one-third of cases, which suggests that SL should still be used routinely in gastric cancer staging in Canadian centres. Our study identified several preoperative imaging findings associated with evidence of metastatic disease on laparoscopy; however, further studies are needed to establish robust predictors of positive findings before advocating for a selective SL approach.

Water diversion and pollution interactively shape freshwater food webs through bottom-up mechanisms.

Water diversion and pollution are two pervasive stressors in river ecosystems that often co-occur. Individual effects of both stressors on basal resources available to stream communities have been described, with diversion reducing detritus standing stocks and pollution increasing biomass of primary producers. However, interactive effects of both stressors on the structure and trophic basis of food webs remain unknown. We hypothesized that the interaction between both stressors increases the contribution of the green pathway in stream food webs. Given the key role of the high-quality, but less abundant, primary producers, we also hypothesized an increase in food web complexity with larger trophic diversity in the presence of water diversion and pollution. To test these hypotheses, we selected four rivers in a range of pollution subject to similar water diversion schemes, and we compared food webs upstream and downstream of the diversion. We characterized food webs by means of stable isotope analysis. Both stressors directly changed the availability of basal resources, with water diversion affecting the brown food web by decreasing detritus stocks, and pollution enhancing the green food web by promoting biofilm production. The propagation of the effects at the base of the food web to higher trophic levels differed between stressors. Water diversion had little effect on the structure of food webs, but pollution increased food chain length and trophic diversity, and reduced trophic redundancy. The effects at higher trophic levels were exacerbated when combining both stressors, as the relative contribution of biofilm to the stock of basal resources increased even further. Overall, we conclude that moderate pollution increases food web complexity and that the interaction with water abstraction seems to amplify this effect. Our study shows the importance of assessing the interaction between stressors to create predictive tools for a proper management of ecosystems.

Cross-continental importance of CH4 emissions from dry inland-waters.

Despite substantial advances in quantifying greenhouse gas (GHG) emissions from dry inland waters, existing estimates mainly consist of carbon dioxide (CO2) emissions. However, methane (CH4) may also be relevant due to its higher Global Warming Potential (GWP). We report CH4 emissions from dry inland water sediments to i) provide a cross-continental estimate of such emissions for different types of aquatic systems (i.e., lakes, ponds, reservoirs, and streams) and climate zones (i.e., tropical, continental, and temperate); and ii) determine the environmental factors that control these emissions. CH4 emissions from dry inland waters were consistently higher than emissions observed in adjacent uphill soils, across climate zones and in all aquatic systems except for streams. However, the CH4 contribution (normalized to CO2 equivalents; CO2-eq) to the total GHG emissions of dry inland waters was similar for all types of aquatic systems and varied from 10 to 21%. Although we discuss multiple controlling factors, dry inland water CH4 emissions were most strongly related to sediment organic matter content and moisture. Summing CO2 and CH4 emissions revealed a cross-continental average emission of 9.6 ± 17.4 g CO2-eq m-2 d-1 from dry inland waters. We argue that increasing droughts likely expand the worldwide surface area of atmosphere-exposed aquatic sediments, thereby increasing global dry inland water CH4 emissions. Hence, CH4 cannot be ignored if we want to fully understand the carbon (C) cycle of dry sediments.

Anti-tumor immunity in mismatch repair-deficient colorectal cancers requires type I IFN-driven CCL5 and CXCL10.

Colorectal cancers (CRCs) deficient in DNA mismatch repair (dMMR) contain abundant CD8+ tumor-infiltrating lymphocytes (TILs) responding to the abundant neoantigens from their unstable genomes. Priming of such tumor-targeted TILs first requires recruitment of CD8+ T cells into the tumors, implying that this is an essential prerequisite of successful dMMR anti-tumor immunity. We have discovered that selective recruitment and activation of systemic CD8+ T cells into dMMR CRCs strictly depend on overexpression of CCL5 and CXCL10 due to endogenous activation of cGAS/STING and type I IFN signaling by damaged DNA. TIL infiltration into orthotopic dMMR CRCs is neoantigen-independent and followed by induction of a resident memory-like phenotype key to the anti-tumor response. CCL5 and CXCL10 could be up-regulated by common chemotherapies in all CRCs, indicating that facilitating CD8+ T cell recruitment underlies their efficacy. Induction of CCL5 and CXCL10 thus represents a tractable therapeutic strategy to induce TIL recruitment into CRCs, where local priming can be maximized even in neoantigen-poor CRCs.

Interactive effects of discharge reduction and fine sediments on stream biofilm metabolism.

Discharge reduction, as caused by water diversion for hydropower, and fine sediments deposition, are prevalent stressors that may affect multiple ecosystem functions in streams. Periphytic biofilms play a key role in stream ecosystem functioning and are potentially affected by these stressors and their interaction. We experimentally assessed the interactive effects of discharge and fine sediments on biofilm metabolism in artificial indoor channels using a factorial split-plot design with two explanatory variables: water discharge (20, 39, 62, 141 and 174 cm3 s-1) and fine sediments (no sediment or 1100 mg L-1 of sediments). We incubated artificial tiles for 25 days in an unpolluted stream to allow biofilm colonization, and then placed them into the indoor channels for acclimation for 18 days. Subsequently, we manipulated water discharge and fine sediments and, after 17 days, we measured biofilm chlorophyll-a concentration and metabolism. Water velocity (range, 0.5 to 3.0 cm s-1) and sediment deposition (range, 6.1 to 16.6 mg cm-2) increased with discharge, the latter showing that the effect of increased inputs prevailed over sloughing. In the no-sediment treatments, discharge did not affect biofilm metabolism, but reduced chlorophyll-a. Sediments, probably as a consequence of nutrients released, promoted metabolism of biofilm and chlorophyll-a, which became independent of water discharge. Our results indicate that pulses of fine sediments can promote biofilm algal biomass and metabolism, but show interactive effects with discharge. Although discharge reduction can affect the abundance of basal resources for food webs, its complex interactions with fine sediments make it difficult to forecast the extent and direction of the changes.

Combined effects of urban pollution and hydrological stress on ecosystem functions of Mediterranean streams.

Urban pollution and hydrological stress are common stressors of stream ecosystems, but their combined effects on ecosystem functioning are still unclear. We measured a set of functional processes and accompanying environmental variables in locations upstream and downstream of urban sewage inputs in 13 streams covering a wide range of water pollution levels and hydrological variability. Sewage inputs seriously impaired stream chemical characteristics and led to complex effects on ecosystem functioning. Biofilm biomass accrual, whole-reach nutrient uptake and metabolism (ecosystem respiration) were generally subsidized, whereas organic matter decomposition and biofilm phosphorus uptake capacity decreased with increasing pollutant concentrations. Hydrological stress affected stream ecosystem functioning but its effect was minor compared to the effects of urban pollution, due to the large inter-site variability of the streams. Changes appeared mainly linked to the concentration of pharmaceutically active compounds, followed by other chemical characteristics and by hydrology. The results point to the need to further improve sewage treatment, especially as climate change will stress riverine organisms and reduce the dilution capacity of the receiving streams.

Evaluating the utility of computed tomography of the chest for gastric cancer staging

Background: International guidelines recommend routine computed tomography (CT) of the chest for gastric cancer staging. In Asian countries, where the incidence of pulmonary metastases is less than 1%, some guidelines recommend chest CT only for gastroesophageal junction cancers. If the incidence of pulmonary metastases is also low in Canada, routine chest CT may not be beneficial. Methods: We performed a retrospective review of patients in northern Alberta with newly diagnosed gastric cancer from January 2010 to July 2016. The primary aim of the study was to determine the incidence of pulmonary metastases at the time of diagnosis in this population. A secondary aim was to identify potential predictors of pulmonary metastases. We reviewed CT reports for pulmonary metastases. Imaging data also included liver metastases, abdominal lymphadenopathy (> 1 cm), ascites and omental or peritoneal nodules. Other data recorded were age, sex, primary tumour location, histologic type and tumour grade. Results: Four hundred and sixty-two patients (311 men, 151 women) were included in the analysis. Pulmonary metastases were identified in 25 patients (5.4%) overall and in 11 of 299 patients (3.7%) whose primary cancer was not in the cardia. On univariate analysis the presence of liver metastases (odds ratio [OR] 7.72, 95% confidence interval [CI] 3.24­18.37, p < 0.001) and abdominal lymphadenopathy (OR 3.30, 95% CI 1.29­8.48, p = 0.01) was associated with an increased risk of pulmonary metastases. Liver metastases retained statistical significance on multivariate analysis (OR 6.17, 95% CI 2.53­15.03, p < 0.001). Conclusion: The incidence of pulmonary metastases at the time of gastric cancer diagnosis is higher in northern Alberta than previously reported in Asian studies. Abdominal lymphadenopathy and liver metastases confer an elevated risk of pulmonary metastases.

Contexte: Les lignes directrices internationales recommandent une tomodensitométrie (TDM) thoracique de routine pour la stadification du cancer de l'estomac. Dans les pays asiatiques, où l'incidence des métastases pulmonaires est inférieure à 1 %, certaines lignes directrices recommandent la TMD thoracique seulement dans les cancers de la jonction gastro-oesophagienne. Si l'incidence des métastases pulmonaires est également faible au Canada, la TDM thoracique de routine pourrait ne pas être bénéfique. Méthodes: Nous avons procédé à une analyse rétrospective des patients du Nord de l'Alberta ayant reçu un diagnostic de cancer de l'estomac entre janvier 2010 et juillet 2016. L'objectif principal de l'étude était de déterminer l'incidence des métastases pulmonaires au moment du diagnostic chez cette population. Un objectif secondaire consistait à identifier les prédicteurs potentiels des métastases pulmonaires. Les rapports de TDM ont été passés en revue pour ce qui est des métastases pulmonaires. Les données provenant des épreuves d'imagerie incluaient aussi les métastases hépatiques, la lymphadénopathie abdominale (> 1 cm), l'ascite et les nodules épiploïques ou péritonéaux. Parmi les autres données consignées, mentionnons l'âge, le sexe, de même que la localisation, le type histologique et le grade de la tumeur principale. Résultats: Quatre cent soixante-deux patients (311 hommes, 151 femmes) ont été inclus dans l'analyse. Globalement, des métastases pulmonaires ont été observées chez 25 patients (5,4 %), et chez 11 patients sur 299 (3,7 %) dont le cancer principal ne se situait pas dans le cardia. À l'analyse univariée, la présence de métastases hépatiques (rapport des cotes [RC] 7,72, intervalle de confiance [IC] de 95 % de 3,24 à 18,37, p < 0,001) et de lymphadénopathie abdominale (RC 3,30, IC de 95 %, de 1,29 à 8,48, p = 0,01) a été associée à un risque accru de métastases pulmonaires. Les métastases hépatiques ont conservé leur portée statistique lors de l'analyse multivariée (RC 6,17, IC de 95 % de 2,53 à 15,03, p < 0,001). Conclusion: L'incidence des métastases pulmonaires au moment où un diagnostic de cancer de l'estomac est posé s'est révélée plus élevée dans le Nord de l'Alberta que dans les rapports d'études asiatiques précédentes. La lymphadénopathie abdominale et les métastases hépatiques confèrent un risque élevé de métastases pulmonaires.

Impact of wastewater effluent pollution on stream functioning: A whole-ecosystem manipulation experiment.

The ecological effects of wastewater treatment plant (WWTP) effluents on stream ecosystems cause growing concern. However, it is difficult to assess these effects as most streams receiving WWTP effluents are also affected by other stressors. We performed a whole-ecosystem manipulation experiment following a BACI design (Before-After/Control-Impact) in order to exclude the influence of other potentially confounding factors. We diverted part of the effluent of a large tertiary urban WWTP into a small, unpolluted stream, and studied its effects on ecosystem structure and functioning over two years (i.e., one year before and one year after the effluent diversion). Although highly diluted (final concentration in the receiving stream averaged 3%), the effluent promoted biofilm chlorophyll-a and biomass (2.3 and 2.1 times, respectively), exo-enzymatic activities (phosphatase 2.2 and glucosidase 4.2 times) and invertebrate-mediated organic matter decomposition (1.4 times), but reduced phosphorus uptake capacity of the epilithic biofilm down to 0.5 of the initial values. Biofilm metabolism, reach-scale nutrient uptake and microbially-mediated organic matter decomposition were not affected. Our results indicate that even well treated and highly diluted WWTP effluents can also affect the structure of the biofilm community and stream ecosystem functioning.

Simulating rewetting events in intermittent rivers and ephemeral streams: A global analysis of leached nutrients and organic matter.

Climate change and human pressures are changing the global distribution and the extent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico-chemical changes (preconditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experimentally simulated, under standard laboratory conditions, rewetting of leaves, riverbed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative characteristics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dissolved substances during rewetting events (56%-98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contributed most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental variables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached substances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying events.

Immediate and legacy effects of urban pollution on river ecosystem functioning: A mesocosm experiment.

Effluents from urban wastewater treatment plants (WWTP) consist of complex mixtures of substances that can affect processes in the receiving ecosystems. Some of these substances (toxic contaminants) stress biological activity at all concentrations, while others (e.g., nutrients) subsidize it at low concentrations and stress it above a threshold, causing subsidy-stress responses. Thus, the overall effects of WWTP effluents depend mostly on their composition and the dilution capacity of the receiving water bodies. We assessed the immediate and legacy effects of WWTP effluents in artificial streams, where we measured the uptake of soluble reactive phosphorus (SRP) by the biofilm, biomass accrual, benthic metabolism and organic matter decomposition (OMD). In a first phase (32 d), the channels were subjected to a gradient of effluent contribution, from pure stream water to pure effluent. WWTP effluent affected the ecosystem processes we measured, although we found no clear subsidy-stress patterns except for biofilm biomass accrual. Instead, most of the processes were subsidized, although they showed complex and process-specific patterns. Benthic metabolism and OMD were subsidized without saturation, as they peaked at medium and high levels of pollution, respectively, but they never fell below control levels. SRP uptake was the only process that decreased with increasing effluent concentration. In a second phase of the experiment (23 d), all channels were kept on pure stream water to analyse the legacy effects of the effluent. For most of the processes, there were clear legacy effects, which followed either subsidy, stress, or subsidy-stress patterns. SRP uptake capacity was stressed with increasing pollution legacy, whereas algal accrual and benthic metabolism continued being subsidized. Conversely, biofilm biomass accrual and OMD showed no legacy effects. Overall, the WWTP effluent caused complex and process-specific responses in our experiment, mainly driven by the mixed contribution of subsidizers and stressors. These results help improving our understanding of the effects of urban pollution on stream ecosystem functioning.

Multiple stressor effects on biodiversity and ecosystem functioning in a Mediterranean temporary river.

The hydrological and biological complexity of temporary rivers as well as their importance in providing goods and services is increasingly recognized, as much as it is the vulnerability of the biotic communities in view of climate change and increased anthropogenic pressures. However, the effects of flow intermittency (resulting from both seasonal variations and rising hydrological pressure) and pollution on biodiversity and ecosystem functioning have been overlooked in these ecosystems. We explore the way multiple stressors affect biodiversity and ecosystem functioning, as well as the biodiversity-ecosystem functioning (B-EF) relationship in a Mediterranean temporary river. We measured diversity of benthic communities (i.e. diatoms and macroinvertebrates) and related ecosystem processes (i.e. resource use efficiency-RUE and organic matter breakdown-OMB) across a pollution and flow intermittency gradient. Our results showed decreases in macroinvertebrate diversity and the opposite trend in diatom assemblages, whereas ecosystem functioning was negatively affected by both pollution and flow intermittency. The explored B-EF relationships showed contrasting results: RUE decreased with higher diatom diversity, whereas OMB increased with increased macroinvertebrate diversity. The different responses suggest contrasting operating mechanisms, selection effects possibly driving the B-EF relationship in diatoms and complementarity effects driving the B-EF relationship in macroinvertebrates. The understanding of multiple stressor effects on diversity and ecosystem functioning, as well as the B-EF relationship in temporary rivers could provide insights on the risks affecting ecosystem functioning under global change.

Surgical excision versus observation as initial management of desmoid tumors: A population based study.

SYNOPSIS: Desmoid tumors can be safely managed with watchful waiting, including either observation alone or tamoxifen/NSAIDs. Surgery at first presentation can be associated with significant treatment burden. BACKGROUND: Immediate surgery was historically recommended for desmoid tumors. Recently, watchful waiting, (tamoxifen/NSAIDs or observation alone), has been advocated. METHODS: All diagnoses of desmoid tumor within the Alberta Cancer Registry from August 2004 to September 2015 were identified. Patients with FAP were excluded. Demographics, tumor characteristics and treatment and outcome data were collected. Outcomes were compared between immediate surgery and watchful waiting. The effect of abdominal wall site on progression and recurrence and the effect of microscopic margin on recurrence were assessed with Fisher's exact test. RESULTS: We identified 111 non-FAP patients. Median follow-up was 35 months from diagnosis. 74% were female. Mean age was 42. Fifty (45%) underwent watchful waiting, of whom 21(42%) progressed, with median PFS of 10 months. Fifty-three (48%) underwent resection at presentation, of whom 8 (15%) recurred, with median disease-free survival of 22 months. Abdominal wall lesions were equally represented in both groups, and equally likely to progress on watchful waiting (50% vs 39%, p = 0.53), but there was a trend toward decreased recurrence after surgery. (5% vs 23%, p = 0.08). Microscopic margin had no effect on recurrence (14% of margin negative vs 20% of margin positive, p = 1.0). CONCLUSIONS: Watchful waiting was successful in 58% of patients, and a further 28% only required one aggressive treatment thereafter, for a total of 86%. Surgery had a favorable recurrence rate (15%), but some recurrences were associated with significant treatment burden. Treatment should be tailored to individual patients in a multidisciplinary setting. A trial of observation appears warranted in most patients. Recurrence rate was not affected by positive margins.

Drying and Rainfall Shape the Structure and Functioning of Nitrifying Microbial Communities in Riverbed Sediments.

Non-flow periods in fluvial ecosystems are a global phenomenon. Streambed drying and rewetting by sporadic rainfalls could drive considerable changes in the microbial communities that govern stream nitrogen (N) availability at different temporal and spatial scales. We performed a microcosm-based experiment to investigate how dry period duration (DPD) (0, 3, 6, and 9 weeks) and magnitude of sporadic rewetting by rainfall (0, 4, and 21 mm applied at end of dry period) affected stocks of N in riverbed sediments, ammonia-oxidizing bacteria (AOB) and archaea (AOA) and rates of ammonia oxidation (AO), and emissions of nitrous oxide (N2O) to the atmosphere. While ammonium (NH4 +) pool size decreased, nitrate (NO3 -) pool size increased in sediments with progressive drying. Concomitantly, the relative and absolute abundance of AOB and, especially, AOA (assessed by 16S rRNA gene sequencing and quantitative PCR of ammonia monooxygenase genes) increased, despite an apparent decrease of AO rates with drying. An increase of N2O emissions occurred at early drying before substantially dropping until the end of the experiment. Strong rainfall of 21 mm increased AO rates and NH4 + in sediments, whereas modest rainfall of 4 mm triggered a notable increase of N2O fluxes. Interestingly, such responses were detected only after 6 and 9 weeks of drying. Our results demonstrate that progressive drying drives considerable changes in in-stream N cycling and the associated nitrifying microbial communities, and that sporadic rainfall can modulate these effects. Our findings are particularly relevant for N processing and transport in rivers with alternating dry and wet phases - a hydrological scenario expected to become more important in the future.

Testing wastewater treatment plant effluent effects on microbial and detritivore performance: A combined field and laboratory experiment.

The amount of pollutants and nutrients entering rivers via point sources is increasing along with human population and activity. Although wastewater treatment plants (WWTPs) greatly reduce pollutant loads into the environment, excess nutrient loading is a problem in many streams. Using a Community and Ecosystem Function (CEF) approach, we quantified the effects of WWTP effluent on the performance of microbes and detritivores associated to organic matter decomposition, a key ecosystem process. We measured organic matter breakdown rates, respiration rates and exo-enzymatic activities of aquatic microbes. We also measured food consumption and growth rates and RNA to body-mass ratios (RNA:BM) of a dominant amphipod Echinogammarus berilloni. We predicted responses to follow a subsidy-stress pattern and differences between treatments to increase over time. To examine temporal effects of effluent, we performed a laboratory microcosm experiment under a range of effluent concentrations (0, 20, 40, 60, 80 and 100%), taking samples over time (days 8, 15 and 30; 4 and 10 replicates to assess microbe and detritivore performance respectively, per treatment and day). This experiment was combined with a field in situ Before-After Control-Impact Paired (BACIP) experiment whereby we added WWTP effluent poured (10 L s-1 during 20-40 min every 2 h) into a stream and collected microbial and detritivore samples at days 8 and 15 (5 and 15 replicates to assess the microbe and detritivore performance respectively, per period, reach and sampling day). Responses were clearer in the laboratory experiment, where the effluent caused a general subsidy response. Field measures did not show any significant response, probably because of the high dilution of the effluent in stream water (average of 1.6%). None of the measured variables in any of the experiments followed the predicted subsidy-stress response. Microbial breakdown, respiration rates, exo-enzymatic activities and invertebrate RNA:BM increased with effluent concentrations. Differences in microbial respiration and exo-enzymatic activities among effluent treatments increased with incubation time, whereas microbial breakdown rates and RNA:BM were consistent over time. At the end of the laboratory experiment, microbial respiration rates increased 156% and RN:BM 115% at 100% effluent concentration. Detritivore consumption and growth rates increased asymptotically, and both responses increased with by incubation time. Our results indicate that WWTP effluent stimulates microbial activities and alters detritivore performance, and stream water dilution may mitigate these effects.