A primer for microbiome time-series analysis

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Coenen, A. R., Hu, S. K., Luo, E., Muratore, D., & Weitz, J. S. A primer for microbiome time-series analysis. Frontiers in Genetics, 11, (2020): 310, doi:10.3389/fgene.2020.00310.Time-series can provide critical insights into the structure and function of microbial communities. The analysis of temporal data warrants statistical considerations, distinct from comparative microbiome studies, to address ecological questions. This primer identifies unique challenges and approaches for analyzing microbiome time-series. In doing so, we focus on (1) identifying compositionally similar samples, (2) inferring putative interactions among populations, and (3) detecting periodic signals. We connect theory, code and data via a series of hands-on modules with a motivating biological question centered on marine microbial ecology. The topics of the modules include characterizing shifts in community structure and activity, identifying expression levels with a diel periodic signal, and identifying putative interactions within a complex community. Modules are presented as self-contained, open-access, interactive tutorials in R and Matlab. Throughout, we highlight statistical considerations for dealing with autocorrelated and compositional data, with an eye to improving the robustness of inferences from microbiome time-series. In doing so, we hope that this primer helps to broaden the use of time-series analytic methods within the microbial ecology research community.This work was supported by the Simons Foundation (SCOPE award ID 329108) and the National Science Foundation (NSF Bio Oc 1829636)

Chemical vapor deposition and infiltration for the production of tungsten fiber reinforced tungsten composite material

Contribution submission to the conference Regensburg 2016Chemical vapor deposition and infiltration for the productionof tungsten fiber reinforced tungsten composite material —∙Martin Aumann1, Jan Willem Coenen1, Hanns Gietl2, TillHoeschen2, Johann Riesch2, Klaus Schmid2, Rudolf Neu2, andChristian Linsmeier1 — 1Forschungszentrum Juelich GmbH, Institutfür Energie- und Klimaforschung, 52425 Juelich — 2Max-Planck-Institut für Plasmaphysik, 85748 GarchingDue to its high melting point, high corrosion resistance and its preferableproperties in terms of hydrogen retention, tungsten is a promisingcandidate in future nuclear fusion devices. However, the mechanicalbehavior of tungsten is crucial, as it is inherently brittle at room temperature.As possibility to overcome this brittleness, a composite materialcan be formed, which shows pseudo-ductility and therefore avoidscatastrophic failure of the material. A possibility to produce such aWf/W-composite is chemical vapor deposition and chemical vapor infiltration,where tungsten is deposited on small tungsten wires throughthe reaction of WF6 and H2. With ongoing infiltration time, pores areformed between the fibers, which decrease in size through the chemicalreaction. For better process understanding, a pore model was established,which solves the mass balance inside the pore and the resultingpore diameter simultaneously. It shows a significant difference in diameterfor longer infiltration times. This behavior shall be proved inexperiments with an experimental pore, which is similar to the simulatedone. Furthermore also kinetic investigations on the chemicalsurface reaction are carried out to increase the process understanding.Part: MMType: Vortrag;TalkTopic: Transport (Diffusion, Leitfähigkeit,Wärme)/ Transport (Diffusion,conductivity, heat)Email: [email protected]

The Influence of Taxation on Small Enterprise Development in Russia

Formation of adequate conditions in Russia market economy model requires the creation of a sound financial base. An important place in the mobilization of financial resources of society plays a tax system with its characteristic features of each state and the specifics of the tasks performed at a certain stage. In recent years, the negative effects of the transition period is expected to overcome through the development of small businesses, which determines the possibility of self-realization of the population in achieving the established preferences and values, as well as through the optimization of the tax system and, in particular, strengthening and stimulating social functions taxes. Formation and development of a market economy based on private property, accompanied by an expansion of business and the creation of small businesses, the activation of various financial and credit institutions, thus increasing the number of actual taxpayers. In connection with this problem is exacerbated relations between the state in the face of tax structures and small businesses as taxpayers

Money in monetary policy design: monetary cross-checking in the New-Keynesian model

In the New-Keynesian model, optimal interest rate policy under uncertainty is formulated without reference to monetary aggregates as long as certain standard assumptions on the distributions of unobservables are satisfied. The model has been criticized for failing to explain common trends in money growth and inflation, and that therefore money should be used as a cross-check in policy formulation (see Lucas (2007)). We show that the New-Keynesian model can explain such trends if one allows for the possibility of persistent central bank misperceptions. Such misperceptions motivate the search for policies that include additional robustness checks. In earlier work, we proposed an interest rate rule that is near-optimal in normal times but includes a cross-check with monetary information. In case of unusual monetary trends, interest rates are adjusted. In this paper, we show in detail how to derive the appropriate magnitude of the interest rate adjustment following a significant cross-check with monetary information, when the New-Keynesian model is the central bank’s preferred model. The cross-check is shown to be effective in offsetting persistent deviations of inflation due to central bank misperceptions. Keywords: Monetary Policy, New-Keynesian Model, Money, Quantity Theory, European Central Bank, Policy Under Uncertaint

Metabolism of no-carrier-added 2-[18F]fluoro-L-tyrosine in rats

Background: Several fluorine-18 labelled fluoroamino acids have been evaluated as tracers for the quantitative assessment of cerebral protein synthesis in vivo by positron emission tomography (PET). Among these, 2-[18F]fluoro-L-tyrosine (2-[18F]Tyr) has been studied in mice at a low specific activity. Its incorporation into proteins is fast and metabolism via other pathways is limited. The present in vivo study was carried out in normal awake rats using no-carrier-added 2-[18F]Tyr. Under normal physiological conditions, we have studied the incorporation into proteins and the metabolism of the tracer in different brain areas. Methods: No-carrier-added 2-[18F]Tyr was administered to awake rats equipped with chronic arterial and venous catheters. The time course of the plasma activity was studied by arterial blood sampling. The biodistribution of the activity in the main organs was studied at the end of the experiment. The distribution of radioactive species in plasma and brain regions was studied by acidic precipitation of the proteins and HPLC analysis of the supernatant. Results: The absolute uptake of radioactivity in brain regions was homogenous. In awake rats, nocarrier-added 2-[18F]Tyr exhibits a fast and almost quantitative incorporation into the proteins fractions of cerebellum and cortex. In striatum, this incorporation into proteins and the unchanged fraction of the tracer detected by HPLC could be lower than in other brain regions. Conclusion: This study confirms the potential of 2-[18F]fluoro-L-tyrosine as a tracer for the assessment of the rate of protein synthesis by positron emission tomography. The observed metabolism suggests a need for a correction for the appearance of metabolites, at least in plasma

Influence of patient symptoms and physical findings on general practitioners' treatment of respiratory tract infections: a direct observation study

BACKGROUND: The high rate of antibiotic prescriptions general practitioners (GPs) make for respiratory tract infections (RTI) are often explained by non-medical reasons e.g. an effort to meet patient expectations. Additionally, it is known that GPs to some extent believe in the necessity of antibiotic treatment in patients with assumed bacterial infections and therefore attempt to distinguish between viral and bacterial infections by history taking and physical examination. The influence of patient complaints and physical examination findings on GPs' prescribing behaviour was mostly investigated by indirect methods such as questionnaires. METHODS: Direct, structured observation during a winter "cough an cold period" in 30 (single handed) general practices. All 273 patients with symptoms of RTI (age above 14, median 37 years, 51% female) were included. RESULTS: The most frequent diagnoses were 'uncomplicated upper RTI/common cold' (43%) followed by 'bronchitis' (26%). On average, 1.8 (95%-confidence interval (CI): 1.7–2.0) medicines per patient were prescribed (cough-and-cold preparations in 88% of the patients, antibiotics in 49%). Medical predictors of antibiotic prescribing were pathological findings in physical examination such as coated tonsils (odds ratio (OR) 15.4, 95%-CI: 3.6–66.2) and unspecific symptoms like fatigue (OR 3.1, 95%-CI 1.4–6.7), fever (OR 2.2, 95%-CI: 1.1–4.5) and yellow sputum (OR 2.1, 95%-CI: 1.1–4.1). Analysed predictors explained 70% of the variance of antibiotic prescribing (R(2 )= 0,696). Efforts to reduce antibiotic prescribing, e.g. recommendations for self-medication, counselling on home remedies or delayed antibiotic prescribing were rare. CONCLUSIONS: Patient complaints and pathological results in physical examination were strong predictors of antibiotic prescribing. Efforts to reduce antibiotic prescribing should account for GPs' beliefs in those (non evidence based) predictors. The method of direct observation was shown to be accepted both by patients and GPs and offered detailed insights into the GP-patient-interaction

The effects of new life-prolonging drugs for metastatic castration-resistant prostate cancer (mCRPC) patients in a real-world population

Item does not contain fulltextBACKGROUND: In 2004 docetaxel was the first life-prolonging drug (LPD) registered for metastatic castration-resistant prostate cancer (mCRPC) patients. Between 2011 and 2014 new LPDs for mCRPC (cabazitaxel, abiraterone, enzalutamide, and radium-223) were introduced in the Netherlands. The objective of this study is to assess the impact of the introduction of new LPDs on treatment patterns and overall survival (OS) over time. PATIENTS AND METHODS: CRPC patients diagnosed in the years 2010-2016 in the observational, retrospective CAPRI registry (20 hospitals) were included and followed up to 2018. Two subgroups were analyzed: treatment-naïve patients (subgroup 1, n = 3600) and post-docetaxel patients (subgroup 2, n = 1355). RESULTS: In both subgroups, the use of any LPD increased: from 57% (2010-2011) to 69% (2014-2015) in subgroup 1 and from 65% (2011-2012) to 79% (2015-2016) in subgroup 2. Chemotherapy as first mCRPC-treatment (i.e., docetaxel) and first post-docetaxel treatment (i.e., cabazitaxel or docetaxel rechallenge) decreased (46-29% and 20-9% in subgroup 1 and 2, respectively), while the use of androgen-receptor targeting treatments (ART) increased from 11% to 39% and 46% to 64% in subgroup 1 and 2, respectively. In subgroup 1, median OS (mOS) from diagnosis CRPC increased from 28.5 months to 31.0 months (p = 0.196). In subgroup 2, mOS from progression on docetaxel increased from 7.9 months to 12.5 months (p < 0.001). After multiple imputations of missing values, in multivariable cox-regression analysis with known prognostic parameters, the treatment period was independent significant for OS in subgroup 1 (2014-2015 vs. 2010-2011 with HR 0.749, p < 0.001) and subgroup 2 (2015-2016 vs. 2011-2012 with HR 0.811, p = 0.037). CONCLUSION: Since 2010, a larger proportion of mCRPC patients was treated with LPDs, which was related to an increased mOS

Greenhouse gas emissions in The Netherlands 1990-2012 : National Inventory Report 2014

In 2012 is de totale uitstoot van broeikasgassen van Nederland, zoals CO2, methaan en lachgas, met ongeveer 1,7 procent gedaald ten opzichte van 2011. Deze daling komt vooral door een lager brandstofgebruik in de energie- en transportsector. Dit lijkt een gevolg van de economische recessie, waardoor emissies door elektriciteitsproductie en het wegtransport in Nederland zijn afgenomen. Cijfers De totale broeikasgasemissie wordt uitgedrukt in CO2-equivalenten en bedraagt in 2012 191,7 teragram (megaton of miljard kilogram) . Ten opzichte van de uitstoot in het Kyoto-basisjaar (213,2 Tg CO2-equivalenten) is dit een afname van ongeveer 10 procent. Het basisjaar, dat afhankelijk van het broeikasgas 1990 of 1995 is, dient voor het Kyoto-protocol als referentie voor de uitstoot van broeikasgassen. De uitstoot van de overige broeikasgassen zoals lachgas en methaan is sinds het basisjaar met 51 procent afgenomen. De CO2-uitstoot daarentegen is in deze periode met 4 procent gestegen. Landen zijn voor het Kyoto-protocol verplicht om de totale uitstoot van broeikasgassen op twee manieren te rapporteren: met en zonder het soort landgebruik en de verandering daarin. Dit is namelijk van invloed op de uitstoot van broeikasgassen. Voorbeelden zijn natuurontwikkeling (dat CO2 bindt) of ontbossing (waardoor CO2 wordt uitgestoten). In bovengenoemde getallen zijn deze zogeheten LULUCF-emissies (Land Use, Land Use Change and Forestry) niet meegenomen. Overige onderdelen inventarisatie Het RIVM stelt jaarlijks op verzoek van het Ministerie van Infrastructuur en Milieu (IenM) de inventarisatie van broeikasgasemissies op. De inventarisatie bevat trendanalyses om ontwikkelingen in de uitstoot van broeikasgassen tussen 1990 en 2012 te verklaren, en een analyse van de onzekerheid in deze getallen. Ook is aangegeven welke bronnen het meest aan deze onzekerheid bijdragen. Daarnaast biedt de inventarisatie documentatie van de gebruikte berekeningsmethoden, databronnen en toegepaste emissiefactoren. Met deze inventarisatie voldoet Nederland aan de nationale rapportageverplichtingen voor 2012 van het Klimaatverdrag van de Verenigde Naties (UNFCCC), van het Kyoto-Protocol en van het Bewakingsmechanisme Broeikasgassen van de Europese Unie.Total greenhouse gas emissions from the Netherlands in 2012 decreased by approximately 1.7 per cent, compared with 2011 emissions. This decrease is mainly the result of decreased fuel combustion in the Energy sector (increased electricity import) and in road transport. In 2012, total direct greenhouse gas emissions (excluding emissions from LULUCF - land use, land use change and forestry) in the Netherlands amounted to 191.7 Tg CO2 eq. This is approximately 10 per cent below the emissions in the base year (213.2 Tg CO2 eq.). The 51% reduction in the non-CO2 emissions in this period is counterbalanced by 4 per cent increase in CO2 emissions since 1990. This report documents the Netherlands' 2014 annual submission of its greenhouse gas emissions inventory in accordance with the guidelines provided by the United Nations Framework Convention on Climate Change (UNFCCC), the Kyoto Protocol and the European Union's Greenhouse Gas Monitoring Mechanism. The report comprises explanations of observed trends in emissions; a description of an assessment of key sources and their uncertainty; documentation of methods, data sources and emission factors applied; and a description of the quality assurance system and the verification activities performed on the data.Ministerie van I&

Comparing nuclear power trajectories in Germany and the UK: from ‘regimes' to ‘democracies’ in sociotechnical transitions and Discontinuities

This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ‘nuclear renaissance’, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field of‘sustainability transitions’. To this end, an ‘abductive’ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are ‘internal’ and ‘external’ to the ‘focal regime configuration’ of nuclear power and associated ‘challenger technologies’ like renewables. It is ‘internal’ criteria that are emphasised in conventional sociotechnical regime theory, with ‘external’ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. ‘Internal’ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germany– the reverse of what is occurring. ‘External’ criteria are more aligned with observed dynamics –especially those relating to military nuclear commitments and broader ‘qualities of democracy’. Despite many differences of framing concerning exactly what constitutes ‘democracy’, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitments– whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio