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PURPOSE: Falls have significant financial impact. Proton pump inhibitor (PPI) therapy is associated with an increased risk of falls and fractures. Exercise programs have been shown to decrease risk of falls in the elderly population and are recommended by the U.S. Preventive Services Task Force for patients over age 65 to reduce falls. Our study aimed to explore the potential financial benefit of implementing three different Centers for Disease Control and Prevention-recommended exercise-based interventions for fall prevention (Tai Chi, Stepping On, and Otago Exercise Program) in ≥65-year-old patients on PPI therapy. METHODS: A Markov model was developed to predict the financial implications of fall-related outcomes in the study population. Net cost of the intervention was deducted from the financial savings predicted for fall avoidance relative to the fall reduction conferred by the intervention. Sensitivity analysis was performed on a range of odds ratios between falling and PPI use. RESULTS: Exercise-based interventions were found to offer financial savings when fall reduction rates exceeded 5%, irrespective of variable odds ratios between PPI use and fall rate. Hypothetical implementation of an exercise-based intervention for PPI users ≥65 years of age was estimated to result in annual fall- and fracture-related savings ranging from $10,317.35 to $18,766.28 per individual. Findings suggested an estimated annual reduction in U.S. health care costs of $18 billion to $85 billion. CONCLUSIONS: Implementing an exercise-based fall prevention program for elderly PPI users represents a possible strategy to mitigate health care costs in the United States. Future prospective studies are recommended.

The chemical composition of aerosol particles is a key parameter for human health and climate effects. Single-particle mass spectrometry (SPMS) has evolved to a mature technology with unique chemical coverage and the capability to analyze the distribution of aerosol components in the particle ensemble in real-time. With the fully automated characterization of the chemical profile of the aerosol particles, selective real-time monitoring of air quality could be performed e.g. for urgent risk assessments due to particularly harmful pollutants. For aerosol particle classification, mostly unsupervised clustering algorithms (ART-2a, K-means and their derivatives) are used, which require manual post-processing. In this work, we focus on supervised algorithms to tackle the problem of automatic classification of large amounts of aerosol particle data. Supervised learning requires data with labels to train a predictive model. Therefore, we created a labeled benchmark dataset containing ~24,000 particles with eight different coarse categories that were highly abundant at a measurement in summer in Central Europe: Elemental Carbon (EC), Organic Carbon and Elemental Carbon (OC-EC), Potassium-rich (K-rich), Calcium-rich (Ca-rich), Iron-rich (Fe-rich), Vanadium-rich (V-rich), Magnesium-rich (Mg-rich) and Sodium-rich (Na-rich). Using the chemical features of particles the performance of the following classical supervised algorithms was tested: K-nearest neighbors, support vector machine, decision tree, random forest and multi-layer perceptron. This work shows that despite the entrenched position of unsupervised clustering algorithms in the field, the use of supervised algorithms has the potential to replace the manual step of clustering algorithms in many applications, where real-time data analysis is essential. For the classification of the eight classes, the prediction accuracy of several supervised algorithms exceeded 97 %. The trained model was used to classify ~49,000 particles from a blind dataset in 0.2 seconds, taking into account also a class of “unclassified” particles. The predictions are highly consistent with the results obtained in a previous study using ART-2a.

Let $G$ be a simple algebraic group of exceptional type over an algebraically closed field of characteristic $p > 0$. This paper continues a long-standing effort to classify the connected reductive subgroups of $G$. Having previously completed the classification when $p$ is sufficiently large, we focus here on the case that $p$ is bad for $G$. We classify the connected reductive subgroups of $G$ which are not $G$-completely reducible, whose simple components have rank at least $3$. For each such subgroup $X$, we determine the action of $X$ on the adjoint module $L(G)$ and on a minimal non-trivial $G$-module, and the connected centraliser of $X$ in $G$. As corollaries we obtain information on: subgroups which are maximal among connected reductive subgroups; products of commuting $G$-completely reducible subgroups; subgroups with trivial connected centraliser; and subgroups which act indecomposably on an adjoint or minimal module for $G$., 41 pages, comments welcome

Air pollution by fine particles represents a severe environmental health-risk. The particle’s content of toxic compounds, such as polycyclic aromatic hydrocarbons (PAH), elemental carbon/soot or redox-active transition metals (e.g. Fe), is highly relevant for their toxicity. The particulate matter (PM) composition can be determined by chemical analysis of PM-loaded filter samples but no information on the mixing state of toxicants, i.e. the distribution of toxicants within the particle ensemble, is obtainable by this approach. The mixing state, however, is a crucial parameter to assess health effects as the toxicants may either be equally distributed over many particles (internally mixed) or could be highly concentrated within a small particle sub-population (externally mixed). In the latter case, the few particles with a very high concentration of toxicants can induce stronger cellular effects at the lung-deposition site. A new approach is based on single particle mass spectrometry (SPMS) but introduces a novel, tailored laser ionisation process. Aerosol particles are on-line sampled from the air and size-characterized by laser velocimetry. The organic coating of individual particles is desorbed by intense IR-laser pulses and subsequently the relevant toxicants (transition metals, PAH and soot) are ionized and MS-detected particle-by-particle, using a novel combined UV-laser ionization scheme (Schade et al. Anal., Chem. 2019; Passig et al. ACP 2022). The novel SPMS system offers the characterisation of the most relevant PM-toxicants (soot, metals, PAH) on a sized-resolved, single particle-basis and gives insight into their mixing state. First SPMS-ambient air monitoring results for PAH or metals show that, depending on conditions, the toxicants indeed either are concentrated on a very small fraction of the particle-ensemble or are rather uniformly distributed over all particles. Future application concepts of the new SPMS-technology in air monitoring and environmental health research are discussed.

Current regulations of particulate matter (PM) based on ambient mass concentrations does not encompass source dependent variation in toxicity or the impact of high numbers of ultrafine PM (UFPs) which contribute little to total PM mass. UFPs may pose risks due to their small size and high number/surface area concentrations and propensity to penetrate tissue barriers and reach the circulation and secondary target organs. ULTRHAS (2021-2025) is a project funded under the EU’s Research and Innovation program Horizon 2020 (Grant Agreement No. 955390). The project will specifically address (i) the impact of different transport modes, fuel technologies and wear components, including atmospheric ageing processes, on the physicochemical characteristics of particulate and gaseous emissions; and how these processes and characteristics affects (ii) the biological responses leading to harmful effects in the lung and beyond by applying state-of-the-art emission measurement, exposure and toxicity-testing approaches under highly controlled laboratory conditions. ULTRHAS will (iii) rank the health hazards of different transport mode emissions and (iv) apply an advanced health impact assessment framework incorporating burden of disease methods to quantify baseline and policy scenario impacts for development and prioritization of mitigation measures; and (v) evaluate the future impact and acceptance of new policies on public health, taking into account social aspects. ULTRHAS aims to provide enhanced understanding of health threats posed by nanoparticles from different transport modes; optimize a framework for toxicity and hazard assessment of aerosols; provide guidance for prioritization of mitigation measures for future legislation on air pollutants.

Herpes simplex esophagitis (HSE) represents a rare entity in immunocompetent patients and has infrequently been described in association with eosinophilic esophagitis (EoE). Causality in this rare association remains a debated topic. We present a case of HSE occurring in an immunocompetent adult with EoE and review the literature in support of EoE induced mucosal disruption predisposing to increased risk of HSE.

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged)., Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editing

The “Mental Health Impact of COVID-19 Pandemic on NIMH Patients and Volunteers” study was a longitudinal study launched in spring 2020 by researchers at NIMH, to investigate the effect of the emerging COVID-19 pandemic on mental health. For each participant, the study collected personal characteristics, such as demographics, psychological traits, and clinical history, together with personal circumstances at regular intervals during their enrollment in the study. In November of 2022, we submitted a preprint (https://doi.org/10.31234/osf.io/7enqw, attached as 10.31234psyarxiv_preprint.pdf), in which we examined the degree to which a variety of mental health outcomes over time for an individual can be predicted from personal characteristics and their changing circumstances, using regression models trained on other study participants. We found that it is possible to predict the variation of a participant’s mental health outcomes from time point to time point, for most of the outcomes we consider. This capability is dominated by information about outcome at the point of enrollment in the study, but can be improved by considering personal characteristics and circumstances. In this pre-registration we formalize our hypotheses before applying the model we developed to the final held out dataset. All numbered references below ( § sections, figures, tables, and reference articles) refer to the preprint.

The comprehensive chemical description of air pollution is a prerequisite for understanding atmospheric transformation processes and effects on climate and environmental health. In this study, a prototype vacuum photoionization Orbitrap mass spectrometer was evaluated for field-suitability by an online on-site investigation of emissions from a ship diesel engine. Despite remote measurements in a challenging environment, the mass spectrometric performance could fully be exploited. Due to the high resolution and mass accuracy in combination with resonance-enhanced multiphoton ionization, the aromatic hydrocarbon profile could selectively and sensitively be analyzed. Limitations from commonly deployed time-of-flight platforms could be overcome, allowing to unraveling the oxygen- and sulfur-containing compounds. Scan-by-scan evaluation of the online data revealed no shift in exact m/z, assignment statistics with root mean square error (RMSE) below 0.2 ppm, continuous high-resolution capabilities, and good isotopic profile matches. Emissions from three different feed fuels were investigated, namely, diesel, heavy fuel oil (HFO), and very low sulfur fuel oil (VLSFO). Regulations mainly concern the fuel sulfur content, and thus, exhaust gas treatment or new emerging fuels, such as the cycle-oil-based VLSFO, can legally be applied. Unfortunately, despite lower CHS-class emissions, a substantial amount of PAHs is emitted by the VLSFO with higher aromaticity compared to the HFO. Hence, legislative measures might need to take further chemical criteria into account.

This study aimed to evaluate the levels and phenomenology of equivalent black carbon (eBC) at the city center of Augsburg, Germany (01/2018 to 12/2020). Furthermore, the potential health risk of eBC based on equivalent numbers of passively smoked cigarettes (PSC) was also evaluated, with special emphasis on the impact caused by the COVID19 lockdown restriction measures. As it could be expected, peak concentrations of eBC were commonly recorded in morning (06:00-8:00 LT) and night (19:00-22:00 LT) in all seasons, coinciding with traffic rush hours and atmospheric stagnation. The variability of eBC was highly influenced by diurnal variations in traffic and meteorology (air temperature (T), mixing-layer height (MLH), wind speed (WS)) across days and seasons. Furthermore, a marked "weekend effect" was evidenced, with an average eBC decrease of ∼35% due to lower traffic flow. During the COVID19 lockdown period, an average ∼60% reduction of the traffic flow resulted in ∼30% eBC decrease, as the health risks of eBC exposure was markedly reduced during this period. The implementation of a multilinear regression analysis allowed to explain for 53% of the variability in measured eBC, indicating that the several factors (e.g., traffic and meteorology) may contribute simultaneously to this proportion. Overall, this study will provide valuable input to the policy makers to mitigate eBC pollutant and its adverse effect on environment and human health., The work is funded by National Natural Science Foundation of China (42101470), Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan (CIT&TCD201904037), the RI-URBANS project (Research Infrastructures Services Reinforcing Air Quality Monitoring Capacities in European Urban & Industrial Areas, European Union's Horizon 2020 research and innovation program, Green Deal, European Commission, contract 101036245), the dtec.bw -Digitalization and Technology Research Center of the Bundeswehr (project MORE), and Peiyang Future Scholar Scholarship (6120000246). We would like to thank to the Administration of Augsburg City for giving access to the traffic data (Tiefbauamt, Markus Furnier). We also would like to thank Prof. Dr. Stefan Emeis from Institute of Meteorology and Climate Research - Atmospheric Environmental Research (IMK-IFU) of Karlsruhe Institute of Technology for providing a ceilometer.

This survey article has two components. The first part gives a gentle introduction to Serre's notion of $G$-complete reducibility, where $G$ is a connected reductive algebraic group defined over an algebraically closed field. The second part concerns consequences of this theory when $G$ is simple of exceptional type, specifically its role in elucidating the subgroup structure of $G$. The latter subject has a history going back about sixty years. We give an overview of what is known, up to the present day. We also take the opportunity to offer several corrections to the literature., 42 pages

An exact computational replication of Smith et al. 2015 using HCP 500 data, and an extended analysis using HCP 1200 data.

In this conceptual replication, we apply the methodology of Smith et al. 2015 (https://doi.org/10.1038/nn.4125), which found a significant mode of covariance between subject characteristics and connectomes of subjects in the Human Connectome Project, to pre-adolescent data from the Adolescent Brain Cognitive Development (ABCD) study. Information about an exact computational replication of Smith et al. 2015 can be found at our other OSF project page (https://osf.io/qm49a/) and in our bioRxiv pre-print (https://doi.org/10.1101/2020.04.23.058313).

Introduction A wide array of alternative nicotine delivery devices (ANDD) has been developed and they are often described as less harmful than combustible cigarettes. This work compares the chemical emissions of three ANDD in comparison to cigarette smoke. All the tested ANDD are characterized by not involving combustion of tobacco. Aims and Methods Single-photon ionization time-of-flight mass spectrometry (SPI-TOFMS) is coupled to a linear smoking machine, which allows a comprehensive, online analysis of the gaseous phase of the ANDD aerosol and the conventional cigarette (CC) smoke. The following devices were investigated in this study: a tobacco cigarette with a glowing piece of coal as a heating source, an electric device for heating tobacco, and a first-generation electronic cigarette. Data obtained from a standard 2R4F research cigarette are taken as a reference. Results The puff-by-puff profile of all products was recorded. The ANDD show a substantial reduction or complete absence of known harmful and potentially harmful substances compared with the CC. In addition, tar substances (i.e. semivolatile and low volatile aromatic and phenolic compounds) are formed to a much lower extent. Nicotine, however, is supplied in comparable amounts except for the investigated electronic cigarette. Conclusions The data show that consumers switching from CC to ANDD are exposed to lower concentrations of harmful and potentially harmful substances. However, toxicological and epidemiological studies must deliver conclusive results if these reduced exposures are beneficial for users. Implications The comparison of puff-resolved profiles of emissions from different tobacco products, traditional and alternative, may help users switch to lower emission products. Puff-resolved comparison overcomes technical changes, use modes between products and may help in their regulation.

Microbial colonization of the human intestine impacts host metabolism and immunity; however, exactly when colonization occurs is unclear. Although many studies have reported bacterial DNA in first-pass meconium samples, these samples are typically collected hours to days after birth. Here, we investigated whether bacteria could be detected in meconium before birth. Fetal meconium (n = 20) was collected by rectal swab during elective breech caesarean deliveries without labour and before antibiotics and compared to technical and procedural controls (n = 5), first-pass meconium (neonatal meconium; n = 14) and infant stool (n = 25). Unlike first-pass meconium, no microbial signal distinct from negative controls was detected in fetal meconium by 16S ribosomal RNA gene sequencing. Additionally, positive aerobic (n = 10 of 20) and anaerobic (n = 12 of 20) clinical cultures of fetal meconium (13 of 20 samples positive in at least one culture) were identified as likely skin contaminants, most frequently Staphylococcus epidermidis, and not detected by sequencing in most samples (same genera detected by culture and sequencing in 2 of 13 samples with positive culture). We conclude that fetal gut colonization of healthy term infants does not occur before birth and that microbial profiles of neonatal meconium reflect populations acquired during and after birth. Fetal meconium does not have a detectable microbiota, as shown using 16S rRNA sequencing and culture of rectal swabs collected during elective breech caesarean sections without labour and before antibiotics, indicating that colonization occurs during and after birth.

To evaluate the visual and refractive outcomes for presbyopia and myopia treatment using the Teneo 317 M2 platform and the myopic SUPRACOR algorithm.Percy Military Hospital and private Laser Victor Hugo Center, France.Observational retrospective nonrandomized study.Fifty eyes (25 patients) treated with bilateral myopic SUPRACOR and micromonovision using the Teneo 317 M2 platform and followed up for 12 months. Study outcomes included binocular and monocular visual acuities (without correction for distance and near vision), the spherical equivalent, predictability, stability, safety, optical aberrations and complications.The mean age was 50.6 ± 2.7 years and the mean preoperative spherical equivalent was -2.6 ± 1.4 diopters. At 12 months postoperatively, the mean binocular UDVA was 0.02 ± 0.03 logMAR and 24 patients (96%) achieved an acuity of 20/25 or better. Binocular UNVA was equal to Jaeger 1 in 18 patients (72%), and Jaeger 2 or better in 23 patients (92%). Twelve eyes (24%) had lost 1 Snellen line and 1 eye (2%) had lost 2 Snellen lines of monocular CDVA. No cases required retreatment; however, one eye (2%) underwent revision surgery, due to diffuse lamellar keratitis.Our study suggests that SUPRACOR using the Teneo 317 M2 platform is a safe and effective technique for myopia and presbyopia treatment. SUPRACOR is therefore a viable alternative to monovision for presbyopia and myopia. However, a careful patient selection is essential to satisfy realistic expectations.

Let G be a finite primitive permutation group on a set Ω with nontrivial point stabilizer Gα⁠. We say that G is extremely primitive if Gα acts primitively on each of its orbits in Ω∖{α}⁠. These groups arise naturally in several different contexts, and their study can be traced back to work of Manning in the 1920s. In this paper, we determine the almost simple extremely primitive groups with socle an exceptional group of Lie type. By combining this result with earlier work of Burness, Praeger, and Seress, this completes the classification of the almost simple extremely primitive groups. Moreover, in view of results by Mann, Praeger, and Seress, our main theorem gives a complete classification of all finite extremely primitive groups, up to finitely many affine exceptions (and it is conjectured that there are no exceptions). Along the way, we also establish several new results on base sizes for primitive actions of exceptional groups, which may be of independent interest.\ud \ud

Ocean warming is increasing the incidence, scale, and severity of global-scale coral bleaching and mortality, culminating in the third global coral bleaching event that occurred during record marine heatwaves of 2014-2017. While local effects of these events have been widely reported, the global implications remain unknown. Analysis of 15,066 reef surveys during 2014-2017 revealed that 80% of surveyed reefs experienced significant coral bleaching and 35% experienced significant coral mortality. The global extent of significant coral bleaching and mortality was assessed by extrapolating results from reef surveys using comprehensive remote-sensing data of regional heat stress. This model predicted that 51% of the world’s coral reefs suffered significant bleaching and 15% significant mortality, surpassing damage from any prior global bleaching event. These observations demonstrate that global warming’s widespread damage to coral reefs is accelerating and underscores the threat anthropogenic climate change poses for the irreversible transformation of these essential ecosystems.

The emissions of marine diesel engines have gained both global and regional attentions because of their impact on human health and climate change. To reduce ship emissions, the International Maritime Organization capped the fuel sulfur content of marine fuels. Consequently, either low-sulfur fuels or additional exhaust gas cleaning devices for the reduction in sulfur dioxide (SO2) emissions became mandatory. Although a wet scrubber reduces the amount of SO2 significantly, there is still a need to consider the reduction in particle emissions directly. We present data on the particle removal efficiency of a scrubber regarding particle number and mass concentration with different marine fuel types, marine gas oil, and two heavy fuel oils (HFOs). An open-loop sulfur scrubber was installed in the exhaust line of a marine diesel test engine. Fine particulate matter was comprehensively characterized in terms of its physical and chemical properties. The wet scrubber led up to a 40% reduction in particle number, whereas a reduction in particle mass emissions was not generally determined. We observed a shift in the size distribution by the scrubber to larger particle diameters when the engine was operated on conventional HFOs. The reduction in particle number concentrations and shift in particle size were caused by the coagulation of soot particles and formation/growing of sulfur-containing particles. Combining the scrubber with a wet electrostatic precipitator as an additional abatement system showed a reduction in particle number and mass emission factors by >98%. Therefore, the application of a wet scrubber for the after-treatment of marine fuel oil combustion will reduce SO2 emissions, but it does not substantially affect the number and mass concentration of respirable particulate matters. To reduce particle emission, the scrubber should be combined with additional abatement systems.

Background: Surgical site infections are among the most common healthcare-associated infections, especially in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this retrospective study was to examine postoperative infectious complications according to preoperative screening findings of nasal and rectal swabs. Methods: Two hundred four consecutive patients received nasal and rectal swab examination for multidrug-resistant (MDR) bacteria within 30 days before the operation in patients where CRS and HIPEC were planned. Inclusion criteria were as follows: confirmed peritoneal metastases (histologically and/or cytologically); age under 85 years; adequate renal, liver, and bone marrow function; no sign of infection preoperatively; resectable disease; and CRS and HIPEC procedure. If surgical site infection occurred, the microbial spectrum of the site was assessed. One hundred twenty-one patients (63 female [52.1%] and 58 male [47.9%]) met the criteria and were further analyzed retrospectively. Statistical correlations between postoperative complications and risk factors were investigated by univariate and multivariate analysis. Results: Postoperative complications in total were observed in 57 patients (47.1%) with major complications (Clavien-Dindo grades 3–4) in 15 patients (12.4%) and infectious complications in 37 (30.6%) patients. The overall prevalence of nasal MRSA carriage was 3.28%, and the overall prevalence of rectal MDR bacteria carriage was 10.7%. In propensity score analysis, colonized patients compared to noncolonized patients showed increased total complications (CD1–5, p = 0.025), infectious complications (p = 0.028), surgical site infections (p = 0.022) as well as pneumonia (p = 0.016). Multivariate analysis showed that in addition to preoperative rectal colonization, American Society of Anesthesiologists score was a risk factor for postoperative complications. Conclusions: Preoperative 3-MRGN and vancomycin-resistant enterococcus colonization were associated with increased complications and surgical site infections. Special antimicrobial treatment pathways are necessary for these patients to reduce postoperative complications due to colonization.

BACKGROUND: Secondary organic aerosols (SOAs) formed from anthropogenic or biogenic gaseous precursors in the atmosphere substantially contribute to the ambient fine particulate matter [PM ≤2.5μm in aerodynamic diameter (PM2.5)] burden, which has been associated with adverse human health effects. However, there is only limited evidence on their differential toxicological impact. OBJECTIVES: We aimed to discriminate toxicological effects of aerosols generated by atmospheric aging on combustion soot particles (SPs) of gaseous biogenic (β-pinene) or anthropogenic (naphthalene) precursors in two different lung cell models exposed at the air-liquid interface (ALI). METHODS: Mono- or cocultures of lung epithelial cells (A549) and endothelial cells (EA.hy926) were exposed at the ALI for 4 h to different aerosol concentrations of a photochemically aged mixture of primary combustion SP and β-pinene (SOAβPIN-SP) or naphthalene (SOANAP-SP). The internally mixed soot/SOA particles were comprehensively characterized in terms of their physical and chemical properties. We conducted toxicity tests to determine cytotoxicity, intracellular oxidative stress, primary and secondary genotoxicity, as well as inflammatory and angiogenic effects. RESULTS: We observed considerable toxicity-related outcomes in cells treated with either SOA type. Greater adverse effects were measured for SOANAP-SP compared with SOAβPIN-SP in both cell models, whereas the nano-sized soot cores alone showed only minor effects. At the functional level, we found that SOANAP-SP augmented the secretion of malondialdehyde and interleukin-8 and may have induced the activation of endothelial cells in the coculture system. This activation was confirmed by comet assay, suggesting secondary genotoxicity and greater angiogenic potential. Chemical characterization of PM revealed distinct qualitative differences in the composition of the two secondary aerosol types. DISCUSSION: In this study using A549 and EA.hy926 cells exposed at ALI, SOA compounds had greater toxicity than primary SPs. Photochemical aging of naphthalene was associated with the formation of more oxidized, more aromatic SOAs with a higher oxidative potential and toxicity compared with β-pinene. Thus, we conclude that the influence of atmospheric chemistry on the chemical PM composition plays a crucial role for the adverse health outcome of emissions. https://doi.org/10.1289/EHP9413.

585 Background: The approval of atezolizumab + bevacizumab for untreated advanced HCC was a significant benefit for patients, but with an increased risk of potentially severe bleeding complications. Tivozanib (a selective VEGFR 1, 2, & 3 tyrosine kinase inhibitor [TKI]) has been combined with durvalumab in the DEDUCTIVE study; preliminary results presented in January 2022 showed that this combination was well tolerated with comparable efficacy to other immune checkpoint and VEGF containing regimens in patients with previously untreated HCC ( J Clin Oncol 40, no. 4 suppl 462-462). We now report the final results of this cohort (cohort A) of patients as well as those with previously treated HCC, including safety results for all the patients. Methods: Major eligibility criteria included age >18 yrs with documented advanced HCC, Child-Pugh Class A, ECOG 0 or 1, and creatinine clearance >40 ml/min. Major exclusion criteria included co-infection with HBV and HCV and significant organ dysfunction. Patients were treated with 0.89 mg tivozanib p.o., 21 days on followed by 7 days off and 1500 mg durvalumab i.v. every 28 days. The primary objective was to determine the safety and tolerability of this combination in patients with advanced HCC; secondary objectives included assessing objective response rate (ORR), progression free survival, and overall survival (OS). The study was amended in 2021 to include a cohort of patients previously treated with atezolizumab and bevacizumab (cohort B). Results: 21 patients were enrolled in cohort A and 6 in cohort B; the median age was 67, 88% of patients were male, and 24% were Asian. The median follow-up time was 13.2 mos and 3.4 mos for cohorts A and B, respectively. Data were available for 25 of the 27 patients enrolled. For cohort A, the ORR was 25% (5/20) and 1-year OS was 76%. For safety analysis, 24 (96%) patients had at least 1 treatment-emergent adverse event (TEAE); 92% were attributed possibly to either tivozanib or durvalumab; 32% were serious TEAEs and there was 1 TEAE leading to death (unrelated). Of the 8 (32%) serious TEAE, 2 were coronavirus infection. 2 patients had serious (grade 3) treatment-related AEs: 1 pneumonitis and 1 with gastrointestinal hemorrhage and anemia. There were no grade 4 or 5 treatment-related AEs. Conclusions: Treatment with the combination of tivozanib and durvalumab in patients with either untreated advanced HCC or those previously treated with atezolizumab and bevacizumab was well tolerated; no severe bleeding events occurred in this study. Efficacy outcomes were comparable to other IO-TKI combinations in HCC. Data for PDL1 status, HBV/HCV status was collected and will be presented along with final safety and efficacy results for both cohorts. Clinical trial information: NCT03970616 .

Purpose Corticosteroids, in particular dexamethasone, are one of the primary treatment options for critically ill COVID-19 patients. However, there are a growing number of cases that involve COVID-19-associated pulmonary aspergillosis (CAPA), and it is unclear whether dexamethasone represents a risk factor for CAPA. Our aim was to investigate a possible association of the recommended dexamethasone therapy with a risk of CAPA. Methods We performed a study based on a cohort of COVID-19 patients treated in 2020 in our 13 intensive care units at Charité Universitätsmedizin Berlin. We used ECMM/ISHM criteria for the CAPA diagnosis and performed univariate and multivariable analyses of clinical parameters to identify risk factors that could result in a diagnosis of CAPA. Results Altogether, among the n = 522 intensive care patients analyzed, n = 47 (9%) patients developed CAPA. CAPA patients had a higher simplified acute physiology score (SAPS) (64 vs. 53, p p p = 0.024), renal replacement therapy (60% vs. 41%, p = 0.024), and they were more likely to die (64% vs. 48%, p = 0.049). The multivariable analysis showed dexamethasone (OR 3.110, CI95 1.112–8.697) and SAPS (OR 1.063, CI95 1.028–1.098) to be independent risk factors for CAPA. Conclusion In our study, dexamethasone therapy as recommended for COVID-19 was associated with a significant three times increase in the risk of CAPA. Trial registration Registration number DRKS00024578, Date of registration March 3rd, 2021.

In this study, the exposure to ambient particulate matter metrics (PM1, PM2.5, PM10, black carbon (BC), brown carbon (BrC), ultraviolet particulate matter (UVPM), particle number concentration (PNC), and lung deposited surface area (LDSA)) were measured along a fixed walking route with specific focus on three typical micro-environments (park, central business district (CBD), and traffic) in different time of day during the non-heating (May–Oct.) and heating (Nov.–Apr.2nd year) periods from 2018 to 2020 in the downtown Augsburg, Germany. The spatio-temporal exposure to ambient PM metrics exhibited substantial heterogeneity during the observation period, with park environment having lowest exposure and traffic area having the highest exposure. Generally, the higher LDSA concentrations were found in traffic area and CBD during the observation periods, while the lower concentrations were found in the park, which is similar with other ambient PM metrics (PMX, eUVPM, eBC, and PNC). The correlations between LDSA and other ambient PM metrics were higher during the heating than non-heating period in most of investigated environments, indicating the different PM sources. Overall, this study provides a comprehensive assessment of personal exposure that complements fixed-site ambient PM metrics measurements in the context of health risk assessment and epidemiological studies., The work is funded by National Natural Science Foundation of China (42101470), the Research Project of the Ministry of Science and Technology of China (2019YFC0507800), the Germany Federal Ministry of Transport and Digital Infrastructure (BMVI) as part of SmartAQnet (19F2003B), the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five - year Plan (CIT&TCD201904037), and the China Scholarship Council (CSC) under the State Scholarship Fund (201706860028), and Peiyang Future Scholar Scholarship (6120000246).

The health effects of exposure to secondary organic aerosols (SOAs) are still limited. Here, we investigated and compared the toxicities of soot particles (SP) coated with β-pinene SOA (SOA(βPin)-SP) and SP coated with naphthalene SOA (SOA(Nap)-SP) in a human bronchial epithelial cell line (BEAS-2B) residing at the air-liquid interface. SOA(βPin)-SP mostly contained oxygenated aliphatic compounds from β-pinene photooxidation, whereas SOA(Nap)-SP contained a significant fraction of oxygenated aromatic products under similar conditions. Following exposure, genome-wide transcriptome responses showed an Nrf2 oxidative stress response, particularly for SOA(Nap)-SP. Other signaling pathways, such as redox signaling, inflammatory signaling, and the involvement of matrix metalloproteinase, were identified to have a stronger impact following exposure to SOA(Nap)-SP. SOA(Nap)-SP also induced a stronger genotoxicity response than that of SOA(βPin)-SP. This study elucidated the mechanisms that govern SOA toxicity and showed that, compared to SOAs derived from a typical biogenic precursor, SOAs from a typical anthropogenic precursor have higher toxicological potency, which was accompanied with the activation of varied cellular mechanisms, such as aryl hydrocarbon receptor. This can be attributed to the difference in chemical composition; specifically, the aromatic compounds in the naphthalene-derived SOA had higher cytotoxic potential than that of the β-pinene-derived SOA.

Supplemental Material for “I’ve been cheated, been mistreated, when will I be loved”: Two decades of infidelity research through an intersectional lens by Dana A Weiser, M Rosie Shrout, Adam V Thomas, Adrienne L Edwards and Jaclyn Cravens Pickens in Journal of Social and Personal Relationships

Figures for Modes 3 & 4, Unthresholded positive-negative axis, and details on the HCP-trained ICA-FIX pipeline.

Thomas Adam, Thomas Moos und Rolf Schmitt (Hrsg.) Oppenheimer. Eine jüdische Familie aus Bruchsal. Spuren – Geschichte – Begegnungen. (Veröffentlichungen zur Geschichte der Stadt Bruchsal, Band 25). Verlag regionalkultur Ubstadt-Weiher 2012. 327 Seiten mit zahlreichen Abbildungen. Fester Einband €22,80. ISBN 978-3-89735-747-1

We show that the categories of compact Lie groups and complex reductive groups (not necessarily connected) are homotopy equivalent topological categories. In other words, the corresponding categories enriched in the homotopy category of topological spaces are equivalent. This can also be interpreted as an equivalence of infinity categories., 11 pages. Version 2: minor edits. Version 3: the final journal version with minor edits

Adverse health effects driven by airborne particulate matter (PM) are mainly associated with reactive oxygen species formation, pro-inflammatory effects, and genome instability. Therefore, a better understanding of the underlying mechanisms is needed to evaluate health risks caused by exposure to PM. The aim of this study was to compare the genotoxic effects of two oxidizing agents (menadione and 3-chloro-1,2-propanediol) with three different reference PM (fine dust ERM-CZ100, urban dust SRM1649, and diesel PM SRM2975) on monocytic THP-1 and alveolar epithelial A549 cells. We assessed DNA oxidation by measuring the oxidized derivative 8-hydroxy-2'-deoxyguanosine (8-OHdG) following short and long exposure times to evaluate the persistency of oxidative DNA damage. Cytokinesis-block micronucleus cytome assay was performed to assess chromosomal instability, cytostasis, and cytotoxicity. Particles were characterized by inductively coupled plasma mass spectrometry in terms of selected elemental content, the release of ions in cell medium and the cellular uptake of metals. PM deposition and cellular dose were investigated by a spectrophotometric method on adherent A549 cells. The level of lipid peroxidation was evaluated via malondialdehyde concentration measurement. Despite differences in the tested concentrations, deposition efficiency, and lipid peroxidation levels, all reference PM samples caused oxidative DNA damage to a similar extent as the two oxidizers in terms of magnitude but with different oxidative DNA damage persistence. Diesel SRM2975 were more effective in inducing chromosomal instability with respect to fine and urban dust highlighting the role of polycyclic aromatic hydrocarbons derivatives on chromosomal instability. The persistence of 8-OHdG lesions strongly correlated with different types of chromosomal damage and revealed distinguishing sensitivity of cell types as well as specific features of particles versus oxidizing agent effects. In conclusion, this study revealed that an interplay between DNA oxidation persistence and chromosomal damage is driving particulate matter-induced genome instability.

In the complex situation with the plurality of emissions, the important research task of assessing the air quality and potential sources through aerosol composition analyses remains for Moscow’s megacity environment. The light absorption, PM10 mass concentration, aerosol composition, and meteorological parameters in this urban background were measured during spring 2017, a period characterized by significant changes in the air temperature, mass advection, and solar radiation. The organic and elemental carbon (OC and EC) and 76 organic compounds, e.g., alkanes, polycyclic aromatic hydrocarbons (PAHs), oxidized PAHs, hopanes, anhydrosugars, polyols, primary and secondary saccharides, and HULIS, as well as 13 ions, including K+, a marker of biomass burning, have been quantified to determine the carbonaceous and inorganic chemical profiles of the aerosol. The correlation between the absorption Angstrom exponent (AAE) and the levoglucosan concentration reveals the relative contributions of agricultural fires and residential biomass burning (BB) nearby to the urban aerosol composition. Combining detailed analytical and statistical approaches, we have identified and analyzed the specific chemical compounds that most accurately represent the variability of the aerosol composition. Principal component analysis (PCA) highlights the main factors for marker species related to gasoline/diesel traffic, BB, biogenic activity, and secondary formation in the atmosphere. Distinguishing the BB-affected periods allows us to evaluate daily changes in the aerosol composition in relation to the transported air masses and detected fires in the areas surrounding Moscow.

BACKGROUND Jaundice or preoperative cholestasis (PC) are typical symptoms of pancreatic masses. Approximately 50% of patients undergo preoperative biliary drainage (PBD) placement. PBD is a common cause of bacterobilia (BB) and is a known surgical site infection risk factor. An adjustment of preoperative antibiotic prophylaxis (PAP) may be reasonable according to the profile of BB. For this, we examined the microbiological findings in routine series of patients. AIM To investigate the incidence and profile of biliary bacterial colonization in patients undergoing pancreatic head resections. METHODS In the period from January 2009 to December 2015, 285 consecutive pancreatic head resections were performed. Indications for surgery were malignancy (71%), chronic pancreatitis (18%), and others (11%). A PBD was in 51% and PC was in 42%. The standard PAP was ampicillin/sulbactam. Intraoperatively, a smear was taken from the hepatic duct. An analysis of the isolated species and resistograms was performed. Patients were categorized according to the presence or absence of PC (PC+/PC-) and PBD (PBD+/PBD-) into four groups. Antibiotic efficiency was analyzed for standard PAP and possible alternatives. RESULTS BB was present in 150 patients (53%). BB was significantly more frequent in PBD+ (n =120) than in PBD- (n = 30), P < 0.01. BB was present both in patients with PC and without PC: (PBD-/PC-: 18%, PBD-/PC+: 30%, PBD+/PC-: 88%, PBD+/PC+: 80%). BB was more frequent in malignancy (56%) than in chronic pancreatitis (45%). PBD, however, was the only independent risk factor in multivariate analysis. In total, 357 pathogens (342 bacteria and 15 fungi) were detected. The five most common groups (n = 256, 74.8%) were Enterococcus spp. (28.4%), Streptococcus spp. (16.9%), Klebsiella spp. (12.6%), Escherichia coli (10.5%), and Enterobacter spp. (6.4%). A polymicrobial BB (PBD+: 77% vs PBD-: 40%, P < 0.01) and a more frequent detection of Enterococcus (P < 0.05) was significantly associated with PBD+. In PBD+, the efficiency of imipenem and piperacillin/tazobactam was significantly higher than that of the standard PAP (P < 0.01). CONCLUSION PBD-/PC- and PBD-/PC+ were associated with a low rate of BB, while PBD+ was always associated with a high rate of BB. In PBD+ patients, BB was polymicrobial and more often associated with Enterococcus. In PBD+, the spectrum of potential bacteria may not be covered by standard PAP. A more potent alternative for prophylactic application, however, was not found.

The notion that civil society and democracy go hand in hand has been a cornerstone of modernization theory. The formation of civil society, so the argument went, contributed to the democratization of society and provided the backbone of democracy. If one follows such an interpretation of modernization and of modern society, monarchic systems should be void of civil society. And yet, the case of Germany shows that civil society developed and even flourished within a monarchic society. The Kingdom of Prussia in 1865 was the home to an extensive network of civil society organizations that included associations, endowments, and foundations. These organizations provided services in the fields of education, social welfare, and supported all kinds of cultural institutions. These organizations were essential for the functioning of Prussia’s public institutions. Donors who created these institutions had a voice in the shaping of monarchic society, and the visions of donors often coincided with the visions put forward by monarchical rulers. The number of Prussians involved in giving, the number of organizations created, and the amount of money given were truly astonishing. Between 2 and 3% of Prussia’s population was involved in civil society organizations. The funds provided by these organizations accounted for 20–30% of public-school funding. And the number of organizations created a tight network that spanned across the entire country. Nineteenth-century monarchic Prussia was not void of civil society as it should have been if American social scientists are correct. Instead, Prussia provided the home to a vibrant civil society. Civil society emerges when societies move from an agrarian and organized system of social hierarchies to an industrial, and traditional social hierarchies destroying system. The destruction of established social hierarchies, the creation and accumulation of wealth, and the emergence of social inequality provided powerful incentives for the formation of civil society. Since this economic modernization and transformation occurred not only within democratic societies such as the USA but also within monarchic societies such as Prussia, civil society developed in both types of political system

We present the calibration strategy for the 20 kton liquid scintillator central detector of the Jiangmen Underground Neutrino Observatory (JUNO). By utilizing a comprehensive multiple-source and multiple-positional calibration program, in combination with a novel dual calorimetry technique exploiting two independent photosensors and readout systems, we demonstrate that the JUNO central detector can achieve a better than 1% energy linearity and a 3% effective energy resolution, required by the neutrino mass ordering determination. [Figure not available: see fulltext.], 0, info:eu-repo/semantics/published

Microbial colonization of the human intestine impacts host metabolism and immunity, however when colonization occurs is unclear. Although numerous studies have reported bacterial DNA in first-pass meconium samples, these samples are collected hours to days after birth. We investigated whether bacteria could be detected in meconium prior to birth. Fetal meconium (n = 20) was collected by rectal swab during elective breech Cesarean sections without labour prior to antibiotics and compared to technical and procedural controls (n = 5), first-pass meconium (neonatal meconium; n = 14), and infant stool (n = 25). Unlike first-pass meconium, no microbial signal distinct from negative controls was detected in fetal meconium by 16S rRNA gene sequencing. Additionally, positive aerobic (n = 10 of 20) and anaerobic (n = 12 of 20) clinical cultures of fetal meconium (13 of 20 samples positive in at least one culture) were identified as likely skin contaminants, most frequently Staphylococcus epidermidis, and not detected by sequencing in most samples (same genera detected by culture and sequencing in 2 of 13 samples with positive culture). We conclude that fetal gut colonization does not occur before birth, and that microbial profiles of neonatal meconium reflect populations acquired during and after birth.

4009 Background: Survival outcomes are historically poor in patients (pts) with advanced/metastatic iCCA, with median overall survival (mOS) times of approximately 1 year with first-line gemcitabine plus cisplatin and approximately 6 months with second-line chemotherapy. Futibatinib, a highly selective, irreversible FGFR1–4 inhibitor, demonstrated efficacy with durable responses in pts with iCCA harboring FGFR2 fusion/rearrangements in the pivotal FOENIX-CCA2 phase 2 study (NCT02052778). At the primary analysis of this trial (data cutoff: October 1, 2020), an objective response rate (ORR) of 41.7% was observed, with a median duration of response (mDOR) of 9.7 mo. Here, we report updated efficacy (including mature OS data) and safety data from the final analysis with an additional 8 mo of follow-up. Methods: FOENIX-CCA2 was a single-arm phase 2 study that enrolled pts with advanced/metastatic iCCA with FGFR2 fusion/rearrangement and progressive disease (PD) after ≥1 prior treatment (tx; including gemcitabine plus platinum-based chemotherapy). Pts received futibatinib 20 mg once daily until PD/intolerability. The primary endpoint was ORR per RECIST v1.1 by independent central review. Secondary endpoints were DOR, disease control rate (DCR), progression-free survival (PFS), OS, safety, and patient-reported outcomes. Results: At the time of the final data cutoff (May 29, 2021), median follow-up was 25.0 mo, and 96/103 pts (93%) had discontinued tx. The median number of tx cycles was 13.0 for a median tx duration of 9.1 mo. The confirmed ORR was 41.7% (43/103) and thereby the same as of the primary analysis, as was the DCR (at 82.5%). The ORR was consistent across pt subgroups. The mDOR was 9.5 mo, and 74% of responses lasted ≥6 mo. mPFS was 8.9 mo, with a 12-mo PFS rate of 35.4%. Mature mOS was 20.0 mo, with a 12-mo OS rate of 73.1% . No new safety signals were identified. Common tx-related adverse events (TRAEs) included hyperphosphatemia (85%), alopecia (33%), dry mouth (30%), diarrhea (28%), dry skin (27%), and fatigue (25%). TRAEs resulted in tx discontinuation in 4 pts (4%). No tx-related deaths occurred. Quality of life was maintained from baseline to tx cycle 13. Conclusions: Findings from the final analysis of FOENIX-CCA2 confirm the results of the primary analysis and reinforce the durable efficacy and continued tolerability of futibatinib in previously treated pts with advanced/metastatic iCCA harboring FGFR2 fusion/rearrangements. Mature OS data were consistent with data from the primary analysis and far exceed historical data in this patient population. Clinical trial information: NCT02052778.

Ships are main contributors to global air pollution with substantial impacts on climate and public health. To improve air quality in densely populated coastal areas and to protect sensitive ecosystems, sulfur emission control areas (SECA) were established in many regions of the world. Ships in SECAs operate with low-sulfur fuels, typically distillate fractions such as marine gas oil (MGO). Alternatively, exhaust gas cleaning devices (scrubbers) can be implemented to remove SO2 from the exhaust, thus allowing the use of cheap high-sulfur residual fuels. Compliance monitoring is established in harbors, but difficult in open water because of high costs and technical limitations. Here we present the first experiments to detect individual ship plumes from distances of several kilometers by single-particle mass spectrometry (SPMS). In contrast to most monitoring approaches that evaluate the gaseous emissions, such as manned or unmanned surveillance flights, sniffer technologies and remote sensing, we analyze the chemical composition of the particulate phase that is transported by the wind over long distances. We optimized SPMS technology for the evaluation of residual fuel emissions and demonstrate their detection in a SECA. Our experiments show that ships with installed scrubbers can emit PM emissions with health-relevant metals in quantities high enough to be detected from more than 10 km distance, emphasizing the importance of novel exhaust cleaning technologies and cleaner fuels. Because of the unique and stable metal signatures, our method is not affected by urban background. With this study, we establish a route towards a novel monitoring protocol for ship emissions. Therefore, we present and discuss mass spectral signatures that indicate the particle age, and thus the distance to the source. By matching ship transponder data, measured wind data and air mass back trajectories, we show, how real-time SPMS data can be evaluated to assign distant ship passages.