Molecular epidemiology of SARS-CoV-2: a regional to global perspective

Background After a year of the global SARS-CoV-2 pandemic, a highly dynamic genetic diversity is surfacing. Among nearly 1000 reported virus lineages, dominant lineages such as B.1.1.7 or B.1.351 attract media attention with questions regarding vaccine efficiency and transmission potential. In response to the pandemic, the Jena University Hospital began sequencing SARS-CoV-2 samples in Thuringia in early 2020.Methods Viral RNA was sequenced in tiled amplicons using Nanopore sequencing. Subsequently, bioinformatic workflows were used to process the generated data. As a genomic background, 9,642 representative SARS-CoV-2 genomes (1,917 of German origin) were extracted from more than 300.000 genomes.Results In a comprehensive bioinformatics analysis, we have set Thuringian isolates in the German, European and global context. In Thuringia, a largely rural German region without an international airport and a population density below the German average, we discovered many of the common “EU lineages”. German samples are scattered across eight major clades, and Thuringian samples occupy four of them.Conclusion The rapid emergence and spread of novel variants are of great concern as these lineages could transmit more efficiently, evade current vaccine efforts or undermine diagnostic test accuracy. To anticipate and mitigate these threats, a continuous molecular surveillance is essential.Key messagesBioinformatics analysis of 1,917, 4,251, and 3,474 SARS-CoV-2 genomes from Germany, the EU (except Germany), and non-EU, respectively, subsampled from more than 300,000 public genomes and placed in the context of Thuringian sequencesConstant antigenic drift for SARS-CoV-2 and no clear pattern or clustering is visible in Thuringia based on the current number of samplesCurrently over 100 described lineages are identified in Germany and only a subset (9) are detected in Thuringia so far, most likely due to genetic undersamplingFrom a national perspective, it is likely that high-frequency lineages, which are currently spreading throughout Europe, will eventually also reach ThuringiaSystematic and dense molecular surveillance via whole-genome sequencing is needed to detect concerning new lineages early, limit spread and adjust vaccines if necessaryCompeting Interest StatementThe authors have declared no competing interest.Funding StatementThe work is funded by the German Ministry of Education and Research (BMBF), grant number 01KX2021, and the Thuringian Region Government, grant number TZUZI82094.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:not applicableAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data is available on GISAID.Introduction Methods - Nanopore sequencing and genome reconstruction - Time tree creation Results - Most highly prevalent SARS-CoV-2 lineages in Germany detected in Thuringia - Genetic divergence and current lineage distribution Discussio

Irinotecan in patients with relapsed or cisplatin-refractory germ cell cancer: a phase II study of the German Testicular Cancer Study Group

Despite generally high cure rates in patients with metastatic germ cell cancer, patients with progressive disease on first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. Irinotecan has shown antitumour activity in human testicular tumour xenografts in nude mice. We have performed a phase II study examining the single agent activity of irinotecan in patients with metastatic relapsed or cisplatin-refractory germ cell cancer. Refractory disease was defined as progression or relapse within 4 weeks after cisplatin-based chemotherapy or relapse after salvage high-dose chemotherapy with autologous stem cell support. Irinotecan was administered at a dose of 300 (−350) mg m−2 every 3 weeks. Response was evaluated every 4 weeks. Fifteen patients have been enrolled. Median age was 35 (19–53) years. Primary tumour localisation was gonadal/mediastinal in 12/3 patients. Patients had been pretreated with a median of six (4–12) cisplatin-containing cycles and 13 out of 15 patients had previously failed high-dose chemotherapy with blood stem cell support. Median number of irinotecan applications was two (1–3). Fourteen patients are assessable for response and all for toxicity. In one patient, no adequate response evaluation was performed. Toxicity was generally acceptable and consisted mainly of haematological side effects with common toxicity criteria 3° anaemia (two patients), common toxicity criteria 3° leukocytopenia (one patient) and common toxicity criteria 3° thrombocytopenia (three patients). Common toxicity criteria 3/4° non-haematological toxicity occurred in five patients (33%): 1×diarrhoea, 2×alopecia, 1×fever and in one patient worsening of pre-existing peripheral polyneuropathy from 1° to 4°. No response was observed to irinotecan therapy. Currently, 13 patients have died of the disease and two patients are alive with the disease. The patients included in our study exhibit similar prognostic characteristics as patients treated in previous trials evaluating new drugs in this setting. Irinotecan at a dose of 300–350 mg m−2 every 3 weeks appears to have no antitumour activity in patients with cisplatin-refractory germ cell cancer and, thus, further investigation in this disease is not justified

Heavy metal content of soils and sediments of the river Elbe in selected parts of East Germany

The former German Democratic Republic (GDR), now the five eastern states of Germany, had an intensive livestock and crop production characterized by wide application of agrochemicals and organic manure. This contributed to the contamination of the river Elbe which is known as one of the most polluted rivers in Europe. Consequently, it was assumed that the flood plains of the river Elbe which are used as grassland (nearly 85.680 hectares in the eastern states) are also polluted. First results of our research on heavy metal pollution of arable soils, high flood sediments, and flood plains will be presented and discussed. (orig.)SIGLEAvailable from TIB Hannover: RA 3251(94/E/4) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Die Auswirkungen der Naehrstoffe (Stickstoff und Phosphor) auf die Gewaesserbeschaffenheit der Stromelbe unter sich veraendernden Belastungsbedingungen Abschlussbericht

There is a research deficit on the effects of nutrients on the biological water quality in rivers, specially in regards to the relationship between the input of nutrients in river basins and the measured load in the rivers. Considerable differences exist in the nutrient budgets due to loss and retention of the nutrients during their transport from basin to river outlet. The objective of the project was to investigate processes which influence the eutrophication in the Elbe in order to determine new water quality targets needed to decrese the algae growth. Sampling was carried out during varios times of the year via boat cruises along the Elbe from Schmilka to Neu Darchau (532 km). The chlorophyll content increased 3 to 6 fold accompanied by a reduction in concentrations of soluble phosphorus and silicate. Up to 20% of the nitrogen was eliminated by denitrification. 10-12% of the total annual load of phosphorus was transported out of the river by dredging and high flooding events. An effective suppression of the eutrophication is not yet possible, because the SPR concentr. are still above the threshold values 1-15 #mu#g/P/1. (orig.)SIGLEAvailable from TIB Hannover: F00B473 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Zusammenstellung, Auswertung und Bewertung des vorhandenen Datenmaterials ueber die stoffliche Belastung der Gewaesserguete der Mittelelbe nach einheitlichen gemeinsamen Kriterien (Vorstudie). Bd. 2

Vol. 2 is a supplement to Vol. 1, which contained the text. Vol. 2 presents the data measured between 1985 and 1989 in the form of tables. (BBR)Der Band 2 ist die Anlage zum Textband 1 und enthaelt die Messdaten von 1985 bis 1989 in Form von Tabellen. (BBR)SIGLEAvailable from TIB Hannover: RA 3251(93/E/18),2 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Umwelt, Naturschutz und Reaktorsicherheit, Bonn (Germany); Umweltbundesamt, Berlin (Germany)DEGerman

Multi-Spectral Quantum Cascade Lasers on Silicon With Integrated Multiplexers

Multi-spectral midwave-infrared (mid-IR) lasers are demonstrated by directly bonding quantum cascade epitaxial gain layers to silicon-on-insulator (SOI) waveguides with arrayed waveguide grating (AWG) multiplexers. Arrays of distributed feedback (DFB) and distributed Bragg-reflection (DBR) quantum cascade lasers (QCLs) emitting at ∼4.7 µm wavelength are coupled to AWGs on the same chip. Low-loss spectral beam combining allows for brightness scaling by coupling the light generated by multiple input QCLs into the fundamental mode of a single output waveguide. Promising results are demonstrated and further improvements are in progress. This device can lead to compact and sensitive chemical detection systems using absorption spectroscopy across a broad spectral range in the mid-IR as well as a high-brightness multi-spectral source for power scaling