Global Distribution of Human-Associated Fecal Genetic Markers in Reference Samples from Six Continents

Numerous bacterial genetic markers are available for the molecular detection of human sources of fecal pollution in environmental waters. However, widespread application is hindered by a lack of knowledge regarding geographical stability, limiting implementation to a small number of well-characterized regions. This study investigates the geographic distribution of five human-associated genetic markers (HF183/BFDrev, HF183/BacR287, BacHum-UCD, BacH, and Lachno2) in municipal wastewaters (raw and treated) from 29 urban and rural wastewater treatment plants (750-4»400»000 population equivalents) from 13 countries spanning six continents. In addition, genetic markers were tested against 280 human and nonhuman fecal samples from domesticated, agricultural and wild animal sources. Findings revealed that all genetic markers are present in consistently high concentrations in raw (median log10 7.2-8.0 marker equivalents (ME) 100 mL-1) and biologically treated wastewater samples (median log10 4.6-6.0 ME 100 mL-1) regardless of location and population. The false positive rates of the various markers in nonhuman fecal samples ranged from 5% to 47%. Results suggest that several genetic markers have considerable potential for measuring human-associated contamination in polluted environmental waters. This will be helpful in water quality monitoring, pollution modeling and health risk assessment (as demonstrated by QMRAcatch) to guide target-oriented water safety management across the globe.Fil: Mayer, René E.. Vienna University of Technology; Austria. Interuniversity Cooperation Centre for Water and Health; AustriaFil: Reischer, Georg. Vienna University of Technology; AustriaFil: Ixenmaier, Simone K.. Vienna University of Technology; Austria. Interuniversity Cooperation Centre for Water and Health; AustriaFil: Derx, Julia. Vienna University of Technology; AustriaFil: Blaschke, Alfred Paul. Vienna University of Technology; AustriaFil: Ebdon, James E.. University of Brighton; Reino UnidoFil: Linke, Rita. Vienna University of Technology; Austria. Interuniversity Cooperation Centre Water And Health; AustriaFil: Egle, Lukas. Vienna University of Technology; AustriaFil: Ahmed, Warish. Csiro Land And Water; AustraliaFil: Blanch, Anicet R.. Universidad de Barcelona; EspañaFil: Byamukama, Denis. Makerere University; UgandaFil: Savill, Marion. Affordable Water Limited;Fil: Mushi, Douglas. Sokoine University Of Agriculture; TanzaniaFil: Cristobal, Hector Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones para la Industria Química. Universidad Nacional de Salta. Facultad de Ingeniería. Instituto de Investigaciones para la Industria Química; ArgentinaFil: Edge, Thomas A.. Canada Centre for Inland Waters. Environment and Climate Change Canada; CanadáFil: Schade, Margit A.. Bavarian Environment Agency; AlemaniaFil: Aslan, Asli. Georgia Southern University; Estados UnidosFil: Brooks, Yolanda M.. Michigan State University; Estados UnidosFil: Sommer, Regina. Interuniversity Cooperation Centre Water And Health; Austria. Medizinische Universitat Wien; AustriaFil: Masago, Yoshifumi. Tohoku University; JapónFil: Sato, Maria I.. Cia. Ambiental do Estado de Sao Paulo. Departamento de Análises Ambientais; BrasilFil: Taylor, Huw D.. University of Brighton; Reino UnidoFil: Rose, Joan B.. Michigan State University; Estados UnidosFil: Wuertz, Stefan. Nanyang Technological University. Singapore Centre for Environmental Life Sciences Engineering and School of Civil and Environmental Engineering; SingapurFil: Shanks, Orin. U.S. Environmental Protection Agency; Estados UnidosFil: Piringer, Harald. Vrvis Research Center; AustriaFil: Mach, Robert L.. Vienna University of Technology; AustriaFil: Savio, Domenico. Karl Landsteiner University of Health Sciences; AustriaFil: Zessner, Matthias. Vienna University of Technology; AustriaFil: Farnleitner, Andreas. Vienna University of Technology; Austria. Interuniversity Cooperation Centre Water And Health; Austria. Karl Landsteiner University of Health Sciences; Austri

Fludarabine modulates composition and function of the T cell pool in patients with chronic lymphocytic leukaemia

The combination of cytotoxic treatment with strategies for immune activation represents an attractive strategy for tumour therapy. Following reduction of high tumour burden by effective cytotoxic agents, two major immune-stimulating approaches are being pursued. First, innate immunity can be activated by monoclonal antibodies triggering antibody-dependent cellular cytotoxicity. Second, tumour-specific T cell responses can be generated by immunization of patients with peptides derived from tumour antigens and infused in soluble form or loaded onto dendritic cells. The choice of cytotoxic agents for such combinatory regimens is crucial since most substances such as fludarabine are considered immunosuppressive while others such as cyclophosphamide can have immunostimulatory activity. We tested in this study whether fludarabine and/or cyclophosphamide, which represent a very effective treatment regimen for chronic lymphocytic leukaemia, would interfere with a therapeutic strategy of T cell activation. Analysis of peripheral blood samples from patients prior and during fludarabine/cyclophosphamide therapy revealed rapid and sustained reduction of tumour cells but also of CD4+ and CD8+ T cells. This correlated with a significant cytotoxic activity of fludarabine/cyclophosphamide on T cells in vitro. Unexpectedly, T cells surviving fludarabine/cyclophosphamide treatment in vitro had a more mature phenotype, while fludarabine-treated T cells were significantly more responsive to mitogenic stimulation than their untreated counterparts and showed a shift towards TH1 cytokine secretion. In conclusion, fludarabine/cyclophosphamide therapy though inducing significant and relevant T cell depletion seems to generate a micromilieu suitable for subsequent T cell activation

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

die Österreichische Phosphorbilanz und die ganzheitliche und vergleichende Bewertung von Technologien zur Rückgewinnung von Phosphor aus dem kommunalen Abwasser

Zusammenfassung in deutscher SprachePhosphor (P) ist eine endliche und nicht substituierbare Ressource, essentiell für die hohen Erträge in der Landwirtschaft. Emissionen von Phosphor in die Gewässer können jedoch zu einer Überversorgung und erheblichen Gewässergüteproblemen durch Eutrophierung führen. Da Europa über keine nennenswerten P Rohphosphatlagerstätten verfügt, ist es folglich auf Importe angewiesen und abhängig von geopolitischen Entwicklungen sowie den aktuellen Rohstoffmärkten. Nationale P Bilanzen bestätigen auf der einen Seite die Abhängigkeit von mineralischen Düngern auf Rohphosphatbasis (~2 kg P pro Einwohner und Jahr), verdeutlichen jedoch gleichzeitig, dass kommunales Abwasser (~1 kg P E-1a-1) sowie weitere P haltige Abfälle, wie z.B. Tiermehle (~0.5-0.6 kg P E-1a-1), eine potentielle aber gegenwärtig zumeist ungenutzte P Ressource sind. Zahlreiche Technologien wurden in den letzten Jahren mit dem Ziel der P-Rückgewinnung aus verschiedenen Teilströmen einer Kläranlage (Ablauf, Schlammwasser, Faulschlamm) sowie von Klärschlammaschen entwickelt und teilweise bereits großtechnisch umgesetzt. Im Rahmen dieser Arbeit wurden 19 ausgewählte P-Rückgewinnungstechnologien nach einer eigens entwickelten Methodik zusammengefasst und nach technischen, ökologischen und ökonomischen Kriterien bewertet. Dabei wurden sowohl die P-Rückgewinnungstechnologien an sich, als auch in Bezug auf die gesamte Prozesskette - vom Kläranlagenzulauf bis hin zur fachgerechten Entsorger sämtlicher anfallender flüssiger und fester Reststoffe - betrachtet. Dies ermöglicht die Miteinbeziehung von Wechselwirkungen mit dem bestehenden Entsorgungssystem in Hinblick auf technische Anforderungen, Umweltauswirkungen und Kosten in der Bewertung. Die Ergebnisse liefern auch Grundlagen für Gesetzgeber und politischen Entscheidungsträger, die für Entwicklungen eines Konzeptes für ein zukünftiges optimiertes P-Management genutzt werden können. Ein wichtiger Aspekt der Ergebnisse ist, dass kein einzelner finaler Bewertungsindikator zur Bewertung der teils sehr komplexen und verschiedenen technologischen Ansätze sinnvoll ist. Vielmehr ergeben die zahlreichen ausgewählten Bewertungskriterien ein Gesamtbild, welches eine Rückgewinnungstechnologie und deren technische Ausgereiftheit, deren Umweltauswirkungen und Kosten ganzheitlich beschreibt. Diese Arbeit zeigt zum Beispiel, dass technisch bereits ausgereifte und vielfach bereits großtechnisch umgesetzte Methoden zur Rückgewinnung von P aus Schlammwasser, unter gewissen Voraussetzungen wirtschaftlich betrieben und gleichzeitig reine, sehr gut pflanzenverfügbare Endprodukte erzeugt werden können. Mit dem Ziel einer größtmöglichen Nutzung des abwasserbürtigen Phosphors wäre zukünftig jedoch eine Rückgewinnung aus Klärschlammaschen anzustreben. Bei der Verbrennung des Klärschlammes sollte dabei eine Vermischung mit P-armen und schadstoffhaltigen Brennstoffen vermieden werden. Die dafür notwendigen Strukturen wie z.B. Monoverbrennungsanlagen müsste dazu allerdings noch ausgebaut werden. Weitere Vorteile einer 'Monoverbrennungs-Strategie' sind zum einen die Möglichkeiten der Nutzung weiterer P-reicher Stoffströme (z.B. Tiermehl) und zum anderen die Möglichkeit einer Zwischenlagerung der Asche mit dem Ziel einer späteren Rückgewinnung (Aufbau einer österreichischen Phosphormine). Insgesamt ist nicht davon auszugehen, dass sich eine Implementierung von P-Recycling Technologien auf volkswirtschaftlicher Ebene finanziell rentieren würde. Die Kosten der eingesetzten Technologien werden dabei stark von den Anforderungen an Recyclingraten und Produktqualitäten bestimmt. So reicht die Spanne von Technologien, mit denen ein gut pflanzenverfügbares Produkt, mit sehr geringer Schwermetallbelastung, zu vergleichsweise höheren Kosten und mit geringer P-Rückgewinnung erzeugt werden kann, bis zu Technologien, bei denen mit im Vergleich zu einer Entsorgung der Klärschlammasche auf Deponien ohne oder mit nur geringen zusätzlichen Kosten, sehr hohen P-Recyclingraten, aber keiner Entfernung von Schwermetallen und geringer Verfügbarkeit des Phosphors zu rechnen ist. Welche Technologie(n) zur Behandlung der Klärschlammasche schlussendlich zum Einsatz kommen, wird von den (rechtlichen) Anforderungen an Recyclingraten und an die Produktqualität und von ökonomischen Anreizen durch die Verwaltung abhängen.Phosphorus (P) is a finite and non-substitutable resource, essential to sustain high levels of agricultural productivity. However, too high concentrations of P in ecosystems can cause eutrophication, an important environmental issue. Europe does not have noteworthy raw phosphate deposits and is therefore dependent on imports, the geopolitical situation, and raw material markets. The first aim of this Thesis was the development of a detailed and complete phosphorus budget for Austria based on the methodology of a material flow analysis (MFA). As a first result of an Austrian P budget assessment, the dependence on mineral P fertilizers application (2 kg P cap-1yr-1) was confirmed. In contrast to that, further analysis highlighted considerable, but often unexploited P-loads in municipal wastewater (~1 kg P cap-1yr-1) and animal by-products such as meat and bone meal (~0.5-0.6 kg P cap-1yr-1). Numerous recycling technologies have been developed and partially implemented over the past years to recover P from different sources of wastewater treatment plants (secondary treated effluent, digester supernatant, and (digested) sewage sludge) as well as from sewage sludge ashes. This work describes a methodology for a comparative technical, environmental and economic assessment of P-recycling and shows its applicability for 19 selected technologies. Out of this application, useful information for a possible future implementation can be derived for decision making. The recovery technologies have not only been assessed as stand-alone processes, but also with regard to the impact on the total process chain - from the wastewater treatment plant influent to the final disposal of all occurring liquid and solid wastes. With this methodological approach interplays on the whole process chain in respect to technological requirements, environmental impacts and costs are included into the assessment. The results show that there is not one final indicator based on which various technologies can be sufficiently compared and the best solution identified. The overall performance of a recycling technology under specific circumstances is described by the analysis of numerous assessment criteria. This work reveals for example, that technologies to recover P from digester supernatant are ready for application from a technical point of view. Consequently, there are already many cases where these technologies have been implemented on a full-scale, and in some cases, they even pay back economically. Simultaneously a clean and very good plant-available P rich material is produced. However, to achieve the greatest recovery of P from wastewater, sewage sludge ashes should be addressed. To enable P recovery from ashes, the co-incineration of combustibles low in P, as well as high ash and high heavy metal contents should be avoided. In this context, the necessary structures such as the mono-incineration of sewage sludge have to be increased in Austria as prerequisite of implementation of these technologies. Further advantages of a mono-incineration strategy include the potential of the combined usage of other P rich flows (e.g., meat and bone meal) and the possible temporal storage of the occurring ashes for a future P recovery (creation of an Austrian P-mine). On a national scale, the recovery of P from sewage sludge ash (SSA) will hardly pay back economically with costs being dependent on the required removal of pollutants and/or the quality of the recovered material or product. There is a wide range of available technologies for the production of P-fertilizers: Some fertilizers have very low heavy metal contents, a good P availability at relatively high costs, and moderate recycling rates. In contrast to that, a complete recycling of P in SSA would have moderate to no extra costs, compared to a reference system with ashes being put into landfills. However, this approach would result in a low P availability and would not include heavy metal depollution. Therefore, which technologies will finally be applied to recover P from SSA will depend on (legal) requirements on product quality and economic incentives from national authorities to support their implementation.19

Novel models for prediction of benefit and toxicity with FOLFIRINOX treatment of pancreatic cancer using clinically available parameters.

BACKGROUND:Despite modern chemotherapy regimens, survival of pancreatic cancer patients remains dismal. Toxicity is a major concern and it is a challenge to upfront identify patients with the highest benefit from aggressive polychemotherapy. We aimed to evaluate ORR and side effects of the FOLFIRINOX regimen, highlighting dose modification and to explore possible prognostic response factors as a clinical tool. METHODS:This retrospective study includes 123 patients with metastatic PC that were treated with FOLFIRINOX between the years 2007 to 2016 in a single academic institution. Survival rates were analysed using the Kaplan-Meier method. Prognostic models including laboratory and clinical parameters were calculated using Cox proportional models in univariate and multivariate analyses. RESULTS:Median age at diagnosis was 64 years (47-78 years), 71 (57, 7%) were male and the majority had an ECOG performance status of 0 or 1 (63 patients; 83.7%). After a median follow up of 17.8 months, median progression free survival (PFS) and overall survival (OS) were 5.7 (4.55-6.84; 95%CI) and 11.8 months (9.35-14.24; 95%CI) respectively. Overall response rate with FOLFIRINOX was 34.9% and stable disease rate was 21.9%. Regarding Grade 3/4 side effects, 62 events, were reported in 37 patients. Looking at risk factors e.g. patient characteristics, tumor marker, inflammatory markers and body composition multivariate analyses proved CEA >4 elevation and BMI > 25 at the time point before palliative chemotherapy to be independent negative prognostic factors for OS. Grouping patients with no risk factor, one or two of these risk factors we analyzed a median OS of 17.4 moths, 9.6 months and 6.7 months (p<0.001) respectively. In addition we identified thrombocytosis and low BMI as predictors of early toxicity. CONCLUSION:This study identifies two easily available factors influencing overall survival with FOLFIRINOX therapy. By combining these two factors to create a score for OS, we propose a prognostic tool for physicians to identify patients, who are unlikely to benefit more from FOLFIRINOX or likely to experience toxicity

C-Reactive Protein and Neutrophil/Lymphocytes Ratio: Prognostic Indicator for Doubling Overall Survival Prediction in Pancreatic Cancer Patients

Background: Despite modern chemotherapy regimens, survival of patients with locally advanced/metastatic pancreatic cancer remains dismal. Long-term survivors are rare and there are no prognostic scores to identify patients benefitting most from chemotherapy. Methods: This retrospective study includes 240 patients with pancreatic cancer who were treated in a primary palliative setting between the years 2007 to 2016 in a single academic institution. Survival rates were analyzed using the Kaplan&ndash;Meier method. Prognostic models including laboratory and clinical parameters were calculated using Cox proportional models in univariate and multivariate analyses. Results: Median age at diagnosis was 67 years (range 29&ndash;90 years), 52% were female and a majority had an ECOG performance status of 0 or 1. Locally advanced pancreatic cancer was diagnosed in 23.3% (n = 56) and primary metastatic disease in 76.7% (n = 184) of all patients. Median overall survival of the whole study cohort was 8.3 months. Investigating potential risk factors like patient characteristics, tumor marker or inflammatory markers, multivariate survival analysis found CRP (c-reactive protein) and NLR (neutrophil to lymphocyte ratio) elevation before the start of palliative chemotherapy to be independent negative prognostic factors for OS (overall survival) (p &lt; 0.001 and p &lt; 0.01). Grouping patients with no risk factor versus patients with one or two of the above mentioned two risk factors, we found a median OS of 16.8 months and 9.4 months (p &lt; 0.001) respectively. By combining these two factors, we were also able to identify pancreatic cancer patients that were more likely to receive any post first line therapy. These two risk factors are predictive for improved survival independent of disease stage (III or IV) and applied chemotherapy agents in first line. Conclusion: By combining these two factors, CRP and NLR, to create a score for OS, we propose a simple, new prognostic tool for OS prediction in pancreatic cancer

Environmental impacts of phosphorus recovery from municipal wastewater

Phosphorus mining from phosphate rock is associated with economic as well as environmental concerns. Through phosphorus recovery from municipal wastewater, countries could decrease their dependency on the global phosphate rock market, however, conceivably leading to an increase in environmental impacts from fertilizer production. In this work 18 phosphorus recovery technologies are evaluated in terms of cumulative energy demand, global warming potential and acidification potential with the methodology of life cycle analysis. These indicators are then contrasted with other environmental criteria, i.e. recovery potential, heavy metal and organic micropollutant decontamination potential and fertilizer efficiency, to determine their overall environmental performance. The LCA shows that a broad spectrum of changes in gaseous emissions and energy demand can be expected through the implementation of P recovery from wastewater. Linkage to further environmental performance results exposes certain trade-offs for the different technologies. Recovery from the liquid phase has mostly positive or comparably little impacts on emissions and energy demand but the low recovery potential contradicts the demand for efficient recycling rates. For recovery from sewage sludge, those technologies that already are or are close to being applied full-scale, are associated with comparatively high emissions and energy demand. Recovery from sewage sludge ash shows varying results, partly revealing trade-offs between heavy metal decontamination, emissions and energy demand. Nevertheless, recovery from ash is correlated with the highest potential for an efficient recycling of phosphorus. Further research should include implications of local infrastructures and legal frameworks to determine economically and environmentally optimised P recovery and recycling concepts.The Austrian Science Funds (FWF)1271391