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Background: In 2019, new therapeutic recommendations for multidrug-resistant (MDR-) and extensively drug-resistant (XDR) tuberculosis (TB) were published by the WHO, advocating the use of oral drugs and stepwise composition of antibiotic regimens. To date, the economic consequences of those recommendations in low incidence settings have not been evaluated. Objective: To assess the costs of applying the new recommendations against a set of 86 MDR-TB/XDR-TB strains, each with individual phenotypic drug resistance patterns, identified in 2018/2019 by the German National Reference Center for Mycobacteria. Methods: Hospitalization costs as covered by German statutory health insurance and the loss of productivity due to illness were calculated using the most recent 2018 statistical data. Costs due to combining five agents in the intensive phase and costs of outpatient monitoring were determined by Monte-Carlo simulation covering all treatment options over an 18-month period. Drug costs were compared to those arising under the approach recommended by the WHO in 2016. Results: Hospitalization costs per MDR-TB patient were €30,152 and the mean costs of antimicrobials over a period of 18 months were €66,854 (range €20,671 to €187,444). Total treatment costs, including outpatient monitoring, were €73,551.56 per patient (range €30,114 to €145.878). In addition, we determined an average cost of €11,410.20 due to productivity loss over a period of 6 months sick leave. Despite a shortened minimum recommended treatment duration (18 versus 20 months), the estimated costs were 24.5% higher based on the 2019 recommendations as compared to the 2016 guideline version. Conclusion: Higher costs for treating MDR-TB/XDR-TB in Germany are to be expected under the new WHO regimens. However, it must be determined whether treatment duration and costs associated with sick leave may be further reduced in the future through shorter hospital stays and earlier culture conversion.

The formation of organic nitrates (ONs) in the gas phase and their impact on mass formation of secondary organic aerosol (SOA) was investigated in a laboratory study for α-pinene and β-pinene photooxidation. Focus was the elucidation of those mechanisms that cause the often observed suppression of SOA mass formation by NOx, and therein the role of highly oxygenated multifunctional molecules (HOMs). We observed that with increasing NOx concentration (a) the portion of HOM organic nitrates (HOM-ONs) increased, (b) the fraction of accretion products (HOM-ACCs) decreased, and (c) HOM-ACCs contained on average smaller carbon numbers. Specifically, we investigated HOM organic nitrates (HOM-ONs), arising from the termination reactions of HOM peroxy radicals with NOx, and HOM permutation products (HOM-PPs), such as ketones, alcohols, or hydroperoxides, formed by other termination reactions. Effective uptake coefficients γeff of HOMs on particles were determined. HOMs with more than six O atoms efficiently condensed on particles (γeff>0.5 on average), and for HOMs containing more than eight O atoms, every collision led to loss. There was no systematic difference in γeff for HOM-ONs and HOM-PPs arising from the same HOM peroxy radicals. This similarity is attributed to the multifunctional character of the HOMs: as functional groups in HOMs arising from the same precursor HOM peroxy radical are identical, vapor pressures should not strongly depend on the character of the final termination group. As a consequence, the suppressing effect of NOx on SOA formation cannot be simply explained by replacement of terminal functional groups by organic nitrate groups. According to their γeff all HOM-ONs with more than six O atoms will contribute to organic bound nitrate (OrgNO3) in the particulate phase. However, the fraction of OrgNO3 stored in condensable HOMs with molecular masses > 230 Da appeared to be substantially higher than the fraction of particulate OrgNO3 observed by aerosol mass spectrometry. This result suggests losses of OrgNO3 for organic nitrates in particles, probably due to hydrolysis of OrgNO3 that releases HNO3 into the gas phase but leaves behind the organic rest in the particulate phase. However, the loss of HNO3 alone could not explain the observed suppressing effect of NOx on particle mass formation from α-pinene and β-pinene. Instead we can attribute most of the reduction in SOA mass yields with increasing NOx to the significant suppression of gas phase HOM-ACCs, which have high molecular mass and are potentially important for SOA mass formation at low-NOx conditions.

Abstract In tribute to Dr. Robert N. Ginsburg (1925–2017), we examine his 1991 seminal paper Controversies about Stromatolites: Vices and Virtues, which summarized current ideas about stromatolites including controversies of definition, whether ancient stromatolites should be interpreted as sedimentary structures and mechanisms of carbonate fixation. The accepted model of stromatolite morphogenesis in 1991 was that biology controls microscale internal structure whereas environment controls macroscale morphology. Ginsburg, however, predicted that biology and environmental influences on stromatolite growth were closely coupled at macro, meso and micro scales. Recent research in Hamelin Pool and the Bahamas has advanced our understanding of the inherent duality of stromatolites and associated controversies. These studies suggest that at the macroscale, when physical forces are strong, the environment is the main control on the morphology; however, when physical forces are weak, biological communities become the main drivers of morphology. Therefore, stromatolites can be considered both as fossils and as sedimentary structures dependent on the energy in the environment of deposition. At the mesoscale, as predicted by Trompette, stromatolite fabrics are influenced equally by environment and biology. As the degree of lamination is often unknown or heterogeneous, a generic genetic term such as ‘microbialite’ is considered the most appropriate terminology for structures of probable microbial origin. At the microscale, stromatolite microfabrics reflect environmentally driven cycling of microbial communities, reflecting both biology and environment. With respect to carbonate fixation, research on modern stromatolites provides a model for biofilm precipitation of micritic laminae lacking microfossils in ancient stromatolites. As pointed out by Ginsburg, the inherent duality of environmental and biological controls of morphogenesis at all scales is at the root of many long‐standing controversies. Recent investigations corroborate the foresight of Ginsburg nearly 30 years ago, further confirming well‐preserved stromatolites can provide insight into both biology and environmental factors in ancient ecosystems.

Due to the potential hazard of diclofenac on aquatic organisms and the lack of higher-tier ecotoxicological studies, a long-term freshwater mesocosm experiment was set up to study the effects of this substance on primary producers and consumers at environmentally realistic nominal concentrations 0.1, 1 and 10 µg/L (average effective concentrations 0.041, 0.44 and 3.82 µg/L). During the six-month exposure period, the biovolume of two macrophyte species (Nasturtium officinale and Callitriche platycarpa) significantly decreased at the highest treatment level. Subsequently, a decrease in dissolved oxygen levels was observed. High mortality rates, effects on immunity, and high genotoxicity were found for encaged zebra mussels (Dreissena polymorpha) in all treatments. In the highest treatment level, one month after the beginning of the exposure, mortality of adult fish (Gasterosteus aculeatus) caused effects on the final population structure. Total abundance of fish and the percentage of juveniles decreased whereas the percentage of adults increased. This led to an overall shift in the length frequency distribution of the F1 generation compared to the control. Consequently, indirect effects on the community structure of zooplankton and macroinvertebrates were observed in the highest treatment level. The No Observed Effect Concentration (NOEC) value at the individual level was

Hydroxyl (OH) radical reactivity (kOH) has been measured for 18 years with different measurement techniques. In order to compare the performances of instruments deployed in the field, two campaigns were conducted performing experiments in the atmospheric simulation chamber SAPHIR at Forschungszentrum Jülich in October 2015 and April 2016. Chemical conditions were chosen either to be representative of the atmosphere or to test potential limitations of instruments. All types of instruments that are currently used for atmospheric measurements were used in one of the two campaigns. The results of these campaigns demonstrate that OH reactivity can be accurately measured for a wide range of atmospherically relevant chemical conditions (e.g. water vapour, nitrogen oxides, various organic compounds) by all instruments. The precision of the measurements (limit of detection −1 at a time resolution of 30 s to a few minutes) is higher for instruments directly detecting hydroxyl radicals, whereas the indirect comparative reactivity method (CRM) has a higher limit of detection of 2 s−1 at a time resolution of 10 to 15 min. The performances of the instruments were systematically tested by stepwise increasing, for example, the concentrations of carbon monoxide (CO), water vapour or nitric oxide (NO). In further experiments, mixtures of organic reactants were injected into the chamber to simulate urban and forested environments. Overall, the results show that the instruments are capable of measuring OH reactivity in the presence of CO, alkanes, alkenes and aromatic compounds. The transmission efficiency in Teflon inlet lines could have introduced systematic errors in measurements for low-volatile organic compounds in some instruments. CRM instruments exhibited a larger scatter in the data compared to the other instruments. The largest differences to reference measurements or to calculated reactivity were observed by CRM instruments in the presence of terpenes and oxygenated organic compounds (mixing ratio of OH reactants were up to 10 ppbv). In some of these experiments, only a small fraction of the reactivity is detected. The accuracy of CRM measurements is most likely limited by the corrections that need to be applied to account for known effects of, for example, deviations from pseudo first-order conditions, nitrogen oxides or water vapour on the measurement. Methods used to derive these corrections vary among the different CRM instruments. Measurements taken with a flow-tube instrument combined with the direct detection of OH by chemical ionisation mass spectrometry (CIMS) show limitations in cases of high reactivity and high NO concentrations but were accurate for low reactivity (−1) and low NO (

A new PLant chamber Unit for Simulation (PLUS) for use with the atmosphere simulation chamber SAPHIR (Simulation of Atmospheric PHotochemistry In a large Reaction Chamber) has been built and characterized at the Forschungszentrum Jülich GmbH, Germany. The PLUS chamber is an environmentally controlled flow-through plant chamber. Inside PLUS the natural blend of biogenic emissions of trees is mixed with synthetic air and transferred to the SAPHIR chamber, where the atmospheric chemistry and the impact of biogenic volatile organic compounds (BVOCs) can be studied in detail. In PLUS all important environmental parameters (e.g., temperature, photosynthetically active radiation (PAR), soil relative humidity (RH)) are well controlled. The gas exchange volume of 9.32 m3 which encloses the stem and the leaves of the plants is constructed such that gases are exposed to only fluorinated ethylene propylene (FEP) Teflon film and other Teflon surfaces to minimize any potential losses of BVOCs in the chamber. Solar radiation is simulated using 15 light-emitting diode (LED) panels, which have an emission strength up to 800 µmol m−2 s−1. Results of the initial characterization experiments are presented in detail. Background concentrations, mixing inside the gas exchange volume, and transfer rate of volatile organic compounds (VOCs) through PLUS under different humidity conditions are explored. Typical plant characteristics such as light- and temperature- dependent BVOC emissions are studied using six Quercus ilex trees and compared to previous studies. Results of an initial ozonolysis experiment of BVOC emissions from Quercus ilex at typical atmospheric concentrations inside SAPHIR are presented to demonstrate a typical experimental setup and the utility of the newly added plant chamber.

Impacts of soil moisture on de novo monoterpene (MT) emissions from Holm oak, European beech, Scots pine, and Norway spruce were studied in laboratory experiments. The volumetric water content of the soil, Θ, was used as the reference quantity to parameterize the dependency of MT emissions on soil moisture and to characterize the severity of the drought. When Θ dropped from 0.4 m3 × m−3 to ~0.2 m3 × m−3 slight increases of de novo MT emissions were observed but with further progressing drought the emissions decreased to almost zero. In most cases the increases of MT emissions observed under conditions of mild drought were explainable by increases of leaf temperature due to lowered transpirational cooling. When Θ fell below certain thresholds, MT emissions decreased simultaneously with Θ and the relationship between Θ and MT emissions was approximately linear. The thresholds of Θ (0.044–0.19 m3 × m−3) were determined, as well as other parameters required to describe the soil moisture dependence of de novo MT emissions for application in the Model of Emissions of Gases and Aerosols from Nature, MEGAN. A factorial approach was found appropriate to describe the impacts of Θ, temperature, and light. Temperature and Θ influenced the emissions largely independently from each other, and, in a similar manner, light intensity and Θ acted independently on de novo MT emissions. The use of Θ as the reference quantity in a factorial approach was tenable in predicting constitutive de novo MT emissions when Θ changed on a time scale of days. Empirical parameterization with Θ as a reference was only unsuccessful when soil moisture changed rapidly

Neural systems are characterized by their complex dynamics, reflected on signals produced by neurons and neuronal ensembles. This complexity exhibits specific features in health, disease and in different states of consciousness, and can be considered a hallmark of certain neurologic and neuropsychiatric conditions. To measure complexity from neurophysiologic signals, a number of different nonlinear tools of analysis are available. However, not all of these tools are easy to implement, or able to handle clinical data, often obtained in less than ideal conditions in comparison to laboratory or simulated data. Recently, the temporal structure function emerged as a powerful tool for the analysis of complex properties of neuronal activity. The temporal structure function is efficient computationally and it can be robustly estimated from short signals. However, the application of this tool to neuronal data is relatively new, making the interpretation of results difficult. In this methods paper we describe a step by step algorithm for the calculation and characterization of the structure function. We apply this algorithm to oscillatory, random and complex toy signals, and test the effect of added noise. We show that: (1) the mean slope of the structure function is zero in the case of random signals; (2) oscillations are reflected on the shape of the structure function, but they don't modify the mean slope if complex correlations are absent; (3) nonlinear systems produce structure functions with nonzero slope up to a critical point, where the function turns into a plateau. Two characteristic numbers can be extracted to quantify the behavior of the structure function in the case of nonlinear systems: (1). the point where the plateau starts (the inflection point, where the slope change occurs), and (2). the height of the plateau. While the inflection point is related to the scale where correlations weaken, the height of the plateau is related to the noise present in the signal. To exemplify our method we calculate structure functions of neuronal recordings from the basal ganglia of parkinsonian and healthy rats, and draw guidelines for their interpretation in light of the results obtained from our toy signals.

The impact of nitrogen oxides (NOx = NO + NO2) on new particle formation (NPF) and on photochemical ozone production from real plant volatile organic compound (BVOC) emissions was studied in a laboratory setup. At high NOx conditions ([BVOC] / [NOx] < 7, [NOx] > 23 ppb) new particle formation was suppressed. Instead, photochemical ozone formation was observed resulting in higher hydroxyl radical (OH) and lower nitrogen monoxide (NO) concentrations. When [NO] was reduced back to levels below 1 ppb by OH reactions, NPF was observed. Adding high amounts of NOx caused NPF to be slowed by orders of magnitude compared to analogous experiments at low NOx conditions ([NOx] ~300 ppt), although OH concentrations were higher. Varying NO2 photolysis enabled showing that NO was responsible for suppression of NPF. This suggests that peroxy radicals are involved in NPF. The rates of NPF and photochemical ozone production were related by power law dependence with an exponent approaching −2. This exponent indicated that the overall peroxy radical concentration must have been similar when NPF occurred. Thus, permutation reactions of first-generation peroxy radicals cannot be the rate limiting step in NPF from monoterpene oxidation. It was concluded that permutation reactions of higher generation peroxy-radical-like intermediates limit the rate of new particle formation. In contrast to the strong effects on the particle numbers, the formation of particle mass was substantially less sensitive to NOx concentrations. If at all, yields were reduced by about an order of magnitude only at very high NOx concentrations.

Atmospheric aerosols impact climate by scattering and absorbing solar radiation and by acting as ice and cloud condensation nuclei. Biogenic secondary organic aerosols (BSOAs) comprise an important component of atmospheric aerosols. Biogenic volatile organic compounds (BVOCs) emitted by vegetation are the source of BSOAs. Pathogens and insect attacks, heat waves and droughts can induce stress to plants that may impact their BVOC emissions, and hence the yield and type of formed BSOAs, and possibly their climatic effects. This raises questions of whether stress-induced changes in BSOA formation may attenuate or amplify effects of climate change. In this study we assess the potential impact of stress-induced BVOC emissions on BSOA formation for tree species typical for mixed deciduous and Boreal Eurasian forests. We studied the photochemical BSOA formation for plants infested by aphids in a laboratory setup under well-controlled conditions and applied in addition heat and drought stress. The results indicate that stress conditions substantially modify BSOA formation and yield. Stress-induced emissions of sesquiterpenes, methyl salicylate, and C17-BVOCs increase BSOA yields. Mixtures including these compounds exhibit BSOA yields between 17 and 33%, significantly higher than mixtures containing mainly monoterpenes (4–6% yield). Green leaf volatiles suppress SOA formation, presumably by scavenging OH, similar to isoprene. By classifying emission types, stressors and BSOA formation potential, we discuss possible climatic feedbacks regarding aerosol effects. We conclude that stress situations for plants due to climate change should be considered in climate–vegetation feedback mechanisms.

El intestino delgado es el segmento más difícil de evaluar del tubo digestivo. Con el desarrollo tecnológico, nuevas modalidades de imagen como la Enteroclisis por Tomografía Computada y por Resonancia Magnética han permitido un mejor rendimiento y resolución en la evaluación de patologías intestinales como enfermedad de Crohn, tumores de intestino delgado, estudio de hemorragia digestiva y obstrucción intestinal parcial, entre otras. En el presente artículo se presenta una revisión de las indicaciones, aspectos técnicos y una revisión pictográfica de las principales patologías que afectan este segmento.

Climate change will induce extended heat waves to parts of the vegetation more frequently. High temperatures may act as stress (thermal stress) on plants changing emissions of biogenic volatile organic compounds (BVOCs). As BVOCs impact the atmospheric oxidation cycle and aerosol formation, it is important to explore possible alterations of BVOC emissions under high temperature conditions. Applying heat to European beech, Palestine oak, Scots pine, and Norway spruce in a laboratory setup either caused the well-known exponential increases of BVOC emissions or induced irreversible changes of BVOC emissions. Considering only irreversible changes of BVOC emissions as stress impacts, we found that high temperatures decreased the de novo emissions of monoterpenes, sesquiterpenes and phenolic BVOC. This behaviour was independent of the tree species and whether the de novo emissions were constitutive or induced by biotic stress. In contrast, application of thermal stress to conifers amplified the release of monoterpenes stored in resin ducts of conifers and induced emissions of green leaf volatiles. In particular during insect attack on conifers, the plants showed de novo emissions of sesquiterpenes and phenolic BVOCs, which exceeded constitutive monoterpene emissions from pools. The heat-induced decrease of de novo emissions was larger than the increased monoterpene release caused by damage of resin ducts. For insect-infested conifers the net effect of thermal stress on BVOC emissions could be an overall decrease. Global change-induced heat waves may put hard thermal stress on plants. If so, we project that BVOC emissions increase is more than predicted by models only in areas predominantly covered with conifers that do not emit high amounts of sesquiterpenes and phenolic BVOCs. Otherwise overall effects of high temperature stress will be lower increases of BVOC emissions than predicted by algorithms that do not consider stress impacts.

Stress-induced volatile organic compound (VOC) emissions from transgenic Grey poplar modified in isoprene emission potential were used for the investigation of photochemical secondary organic aerosol (SOA) formation. In poplar, acute ozone stress induces the emission of a wide array of VOCs dominated by sesquiterpenes and aromatic VOCs. Constitutive light-dependent emission of isoprene ranged between 66 nmol m−2 s−1 in non-transgenic controls (wild type WT) and nearly zero (−2 s−1) in isoprene emission-repressed plants (line RA22), respectively. Nucleation rates of up to 3600 cm−3 s−1 were observed in our experiments. In the presence of isoprene new particle formation was suppressed compared to non-isoprene containing VOC mixtures. Compared to isoprene/monoterpene systems emitted from other plants the suppression of nucleation by isoprene was less effective for the VOC mixture emitted from stressed poplar. This is explained by the observed high efficiency of new particle formation for emissions from stressed poplar. Direct measurements of OH in the reaction chamber revealed that the steady state concentration of OH is lower in the presence of isoprene than in the absence of isoprene, supporting the hypothesis that isoprenes' suppressing effect on nucleation is related to radical chemistry. In order to test whether isoprene contributes to SOA mass formation, fully deuterated isoprene (C5D8) was added to the stress-induced emission profile of an isoprene free poplar mutant. Mass spectral analysis showed that, despite the isoprene-induced suppression of particle formation, fractions of deuterated isoprene were incorporated into the SOA. A fractional mass yield of 2.3% of isoprene was observed. Future emission changes due to land use and climate change may therefore affect both gas phase oxidation capacity and new particle number formation.

In many environments organic matter significantly contributes to the composition of atmospheric aerosol particles influencing its properties. Detailed chemical characterization of ambient aerosols is critical in order to understand the formation process, composition, and properties of aerosols and facilitates source identification and relative contributions from different types of sources to ambient aerosols in the atmosphere. However, current analytical methods are far from full speciation of organic aerosols and often require sampling times of up to one week. Offline methods are also subjected to artifacts during aerosol collection and storage. In the present work a new technique for quasi on-line compound specific measurements of organic aerosol particles was developed. The Aerosol Collection Module (ACM) focuses particles into a beam which is directed to a cooled sampling surface. The sampling takes place in a high vacuum environment where the gas phase from the sample volume is removed. After collection is completed volatile and semi-volatile compounds are evaporated from the collection surface through heating and transferred to a detector. For laboratory characterization the ACM was interfaced with a Gas Chromatograph Mass Spectrometer, Flame Ionization Detector system (GC/MS-FID), abbreviated as ACM GC-MS. The particle collection efficiency, gas phase transfer efficiency, and linearity of the ACM GC-MS were determined using laboratory generated octadecane aerosols. The ACM GC-MS is linear over the investigated mass range of 10 to 100 ng and a recovery rate of 100% was found for octadecane particles. The ACM GC-MS was applied to investigate secondary organic aerosol (SOA) formed from β-pinene oxidation. Nopinone, myrtanal, myrtenol, 1-hydroxynopinone, 3-oxonopinone, 3,7-dihydroxynopinone, and bicyclo[3,1,1]hept-3-ene-2-one were found as products in the SOA. The ACM GC-MS results are compared to quartz filter samples taken in parallel to the ACM GC-MS measurements. First measurements of ambient atmospheric aerosols are presented.

For the first time we have investigated the natural ecosystem engineering capacity of stromatolitic microbial assemblages. Stromatolites are laminated sedimentary structures formed by microbial activity and are considered to have dominated the shallows of the Precambrian oceans. Their fossilised remains are the most ancient unambiguous record of early life on earth. Stromatolites can therefore be considered as the first recognisable ecosystems on the planet. However, while many discussions have taken place over their structure and form, we have very little information on their functional ecology and how such assemblages persisted despite strong eternal forcing from wind and waves. The capture and binding of sediment is clearly a critical feature for the formation and persistence of stromatolite assemblages. Here, we investigated the ecosystem engineering capacity of stromatolitic microbial assemblages with respect to their ability to stabilise sediment using material from one of the few remaining living stromatolite systems (Highborne Cay, Bahamas). It was shown that the most effective assemblages could produce a rapid (12-24 h) and significant increase in sediment stability that continued in a linear fashion over the period of the experimentation (228 h). Importantly, it was also found that light was required for the assemblages to produce this stabilisation effect and that removal of assemblage into darkness could lead to a partial reversal of the stabilisation. This was attributed to the breakdown of extracellular polymeric substances under anaerobic conditions. These data were supported by microelectrode profiling of oxygen and calcium. The structure of the assemblages as they formed was visualised by low-temperature scanning electron microscopy and confocal laser microscopy. These results have implications for the understanding of early stromatolite development and highlight the potential importance of the evolution of photosynthesis in the mat forming process. The evolution of photosynthesis may have provided an important advance for the niche construction activity of microbial systems and the formation and persistence of the stromatolites which came to dominate shallow coastal environments for 80% of the biotic history of the earth.