A Bayesian Belief Network learning tool integrates multi-scale effects of riparian buffers on stream invertebrates

Riparian forest buffers have multiple benefits for biodiversity and ecosystem services in both freshwater and terrestrial habitats but are rarely implemented in water ecosystem management, partly reflecting the lack of information on the effectiveness of this measure. In this context, social learning is valuable to inform stakeholders of the efficacy of riparian vegetation in mitigating stream degradation. We aim to develop a Bayesian belief network (BBN) model for application as a learning tool to simulate and assess the reach-and segment-scale effects of riparian vegetation properties and land use on instream invertebrates. We surveyed reach-scale riparian conditions, extracted segment-scale riparian and subcatchment land use information from geographic information system data, and collected macroinvertebrate samples from four catchments in Europe (Belgium, Norway, Romania, and Sweden). We modelled the ecological condition based on the Average Score Per Taxon (ASPT) index, a macroinvertebrate-based index widely used in European bioassessment, as a function of different riparian variables using the BBN modelling approach. The results of the model simulations provided insights into the usefulness of riparian vegetation attributes in enhancing the ecological condition, with reach-scale riparian vegetation quality associated with the strongest improvements in ecological status. Specifically, reach-scale buffer vegetation of score 3 (i.e. moderate quality) generally results in the highest probability of a good ASPT score (99-100%). In contrast, a site with a narrow width of riparian trees and a small area of trees with reach-scale buffer vegetation of score 1 (i.e. low quality) predicts a high probability of a bad ASPT score (74%). The strengths of the BBN model are the ease of interpretation, fast simulation, ability to explicitly indicate uncertainty in model outcomes, and interactivity. These merits point to the potential use of the BBN model in workshop activities to stimulate key learning processes that help inform the management of riparian zones

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

Novel therapeutic strategies targeting HIV integrase

Integration of the viral genome into host cell chromatin is a pivotal and unique step in the replication cycle of retroviruses, including HIV. Inhibiting HIV replication by specifically blocking the viral integrase enzyme that mediates this step is an obvious and attractive therapeutic strategy. After concerted efforts, the first viable integrase inhibitors were developed in the early 2000s, ultimately leading to the clinical licensure of the first integrase strand transfer inhibitor, raltegravir. Similarly structured compounds and derivative second generation integrase strand transfer inhibitors, such as elvitegravir and dolutegravir, are now in various stages of clinical development. Furthermore, other mechanisms aimed at the inhibition of viral integration are being explored in numerous preclinical studies, which include inhibition of 3' processing and chromatin targeting. The development of new clinically useful compounds will be aided by the characterization of the retroviral intasome crystal structure. This review considers the history of the clinical development of HIV integrase inhibitors, the development of antiviral drug resistance and the need for new antiviral compounds

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

The recovery of European freshwater biodiversity has come to a halt

Owing to a long history of anthropogenic pressures, freshwater ecosystems are among the most vulnerable to biodiversity loss1. Mitigation measures, including wastewater treatment and hydromorphological restoration, have aimed to improve environmental quality and foster the recovery of freshwater biodiversity2. Here, using 1,816 time series of freshwater invertebrate communities collected across 22 European countries between 1968 and 2020, we quantified temporal trends in taxonomic and functional diversity and their responses to environmental pressures and gradients. We observed overall increases in taxon richness (0.73% per year), functional richness (2.4% per year) and abundance (1.17% per year). However, these increases primarily occurred before the 2010s, and have since plateaued. Freshwater communities downstream of dams, urban areas and cropland were less likely to experience recovery. Communities at sites with faster rates of warming had fewer gains in taxon richness, functional richness and abundance. Although biodiversity gains in the 1990s and 2000s probably reflect the effectiveness of water-quality improvements and restoration projects, the decelerating trajectory in the 2010s suggests that the current measures offer diminishing returns. Given new and persistent pressures on freshwater ecosystems, including emerging pollutants, climate change and the spread of invasive species, we call for additional mitigation to revive the recovery of freshwater biodiversity.N. Kaffenberger helped with initial data compilation. Funding for authors and data collection and processing was provided by the EU Horizon 2020 project eLTER PLUS (grant agreement no. 871128); the German Federal Ministry of Education and Research (BMBF; 033W034A); the German Research Foundation (DFG FZT 118, 202548816); Czech Republic project no. P505-20-17305S; the Leibniz Competition (J45/2018, P74/2018); the Spanish Ministerio de Economía, Industria y Competitividad—Agencia Estatal de Investigación and the European Regional Development Fund (MECODISPER project CTM 2017-89295-P); Ramón y Cajal contracts and the project funded by the Spanish Ministry of Science and Innovation (RYC2019-027446-I, RYC2020-029829-I, PID2020-115830GB-100); the Danish Environment Agency; the Norwegian Environment Agency; SOMINCOR—Lundin mining & FCT—Fundação para a Ciência e Tecnologia, Portugal; the Swedish University of Agricultural Sciences; the Swiss National Science Foundation (grant PP00P3_179089); the EU LIFE programme (DIVAQUA project, LIFE18 NAT/ES/000121); the UK Natural Environment Research Council (GLiTRS project NE/V006886/1 and NE/R016429/1 as part of the UK-SCAPE programme); the Autonomous Province of Bolzano (Italy); and the Estonian Research Council (grant no. PRG1266), Estonian National Program ‘Humanitarian and natural science collections’. The Environment Agency of England, the Scottish Environmental Protection Agency and Natural Resources Wales provided publicly available data. We acknowledge the members of the Flanders Environment Agency for providing data. This article is a contribution of the Alliance for Freshwater Life (www.allianceforfreshwaterlife.org).Peer reviewe

Correction: Ho, L.T.; Goethals, P.L.M. Opportunities and Challenges for the Sustainability of Lakes and Reservoirs in Relation to the Sustainable Development Goals (SDGs). Water 2019, 11, 1462

In the original article [...

Model-based analysis of increased loads on the performance of activated sludge and waste stabilization ponds

In a way to counter criticism on low cost-effective conventional activated sludge (AS) technology, waste stabilization ponds (WSPs) offer a valid alternative for wastewater treatment due to their simple and inexpensive operation. To evaluate this alternative with respect to its robustness and resilience capacity, we perform in silico experiments of different peak-load scenarios in two mathematical models representing the two systems. A systematic process of quality assurance for these virtual experiments is implemented, including sensitivity and identifiability analysis, with non-linear error propagation. Moreover, model calibration of a 210-day real experiment with 31 days of increased load was added to the evaluation. Generally speaking, increased-load scenarios run in silico showed that WSP systems are more resilient towards intermediate disturbances, hence, are suitable to treat not only municipal wastewater, but also industrial wastewater, such as poultry wastewater, and paperboard wastewater. However, when disturbances are extreme (over 7000 mg COD·L-1), the common design of the natural system fails to perform better than AS. Besides, the application of sensitivity analysis reveals the most influential parameters on the performance of the two systems. In the AS system, parameters related to autotrophic bacteria have the highest influence on the dynamics of particulate organic matter, while nitrogen removal is largely driven by nitrification and denitrification. Conversely, with an insignificant contribution of heterotrophs, the nutrient removal in the pond system is mostly done by algal assimilation. Furthermore, this systematic model-based analysis proved to be a suitable means for investigating the maximum load of wastewater treatment systems, and from that avoiding environmental problems and high economic costs for cleaning surface waters after severe overload events

Assessment of Land-Use Impact on Macroinvertebrate Communities in the Zwalm River Basin (Flanders, Belgium) Using Multivariate Analysis and Geographic Information Systems

Relationships between land-use and river water quality assessed by means of biological and physical-chemical variables and habitat characteristics were analysed for the Zwalm River basin in Flanders (Belgium). The research focussed on three zones within this river basin, each characterized by different land uses, and consequently, different types of pollution, mainly of diffuse origin. Environmental data have been integrated within a Geographic Information System. Possible relationships between aquatic ecosystem and land-use variables were searched for by means of multivariate analysis