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Spatial properties of tumour growth have profound implications for cancer progression, therapeutic resistance and metastasis. Yet, how spatial position governs tumour cell division remains difficult to evaluate in clinical tumours. Here, we demonstrate that faster division on the tumour periphery leaves characteristic genetic patterns, which become evident when a phylogenetic tree is reconstructed from spatially sampled cells. Namely, rapidly dividing peripheral lineages branch more extensively and acquire more mutations than slower-dividing centre lineages. We develop a Bayesian state-dependent evolutionary phylodynamic model (SDevo) that quantifies these patterns to infer the differential division rates between peripheral and central cells. We demonstrate that this approach accurately infers spatially varying birth rates of simulated tumours across a range of growth conditions and sampling strategies. We then show that SDevo outperforms state-of-the-art, non-cancer multi-state phylodynamic methods that ignore differential sequence evolution. Finally, we apply SDevo to single-time-point, multi-region sequencing data from clinical hepatocellular carcinomas and find evidence of a three- to six-times-higher division rate on the tumour edge. With the increasing availability of high-resolution, multi-region sequencing, we anticipate that SDevo will be useful in interrogating spatial growth restrictions and could be extended to model non-spatial factors that influence tumour progression.

Introduction: Due to occupational stress, nurses are often exposed to the risk of suffering musculoskeletal disorders in the course of their work. This results in increased absenteeism due to chronic back pain. This leads to the need to find alternatives to reduce occupational stress, not only for the caregivers concerned but also in view of the existing nursing shortage. One possibility here could be the use of an exoskeleton to support professional caregivers in their everyday care. Methods: In a first pilot project, nursing experts were asked in a workshop about the use of an exoskeleton in nursing settings with regard to the prerequisites, user settings and acceptance by means of a questionnaire. This was followed by a practical test in which caregivers wore the exoskeleton while carrying out their original daily nursing tasks. Here, results were generated by means of observation and questions on a questionnaire. Results: Seven questionnaires were evaluated, which were collected in the course of three field tests. The results show a benefit in care settings that are time-consuming and physically demanding for caregivers. According to the results, exoskeletons should be used especially in the care of obese, bariatric and mobility-impaired patients. Discussion: Successful use in everyday care requires an exoskeleton adapted to the daily care routine. In addition, repeated training and close support are necessary for improved acceptance. In addition, the implementation of the use of an exoskeleton should be implemented in care standards in order to achieve the highest possible acceptance. Keywords: exoskeleton, caregivers, musculoskeletal disorders, care situations

What, if anything, is the import of Hayek to epistemic democracy? Although Hayek is revered by epistemic democrats for his insights into the epistemic aspects of the market sphere, it is generally believed that his theory is moot with respect to democratic reason. This paper aims to challenge this verdict. I argue that a Hayekian analysis of inclusive public deliberation contributes at least three valuable lessons: (1) Hayek makes the case that under certain conditions even unbiased deliberators are permanently unable to converge on the best available policy option. Call this the problem of ‘persistent hidden policy champions’. (2) He demonstrates that to unlock hidden policy champions, reasonable minority factions need the opportunity to act on their own evidential standards. (3) He challenges epistemic democrats to think more carefully about how to design the “epistemic basic structure” (Kurtulmus and Irzik 2017) of society in order to account for persistent hidden policy champions.

Zusammenfassung Auf Grundlage sozialempirisch erhobener Primärdaten – gewonnen aus den militärischen Personalakten – werden in dieser Dokumentation anhand von Schaubildern, Diagrammen und Tabellen sozialstatistische Befunde für die Spitzen der Luftwaffen und Marinen beider deutscher Staaten der Forschung zur Verfügung gestellt. Je nach Erkenntnisinteresse und Fragestellung können die vorliegenden Daten als Bezugswerte einer umfassenden Deutung zugeführt werden. Um sie in ihren militärgeschichtlichen Kontext einzuordnen, wird das historiografische Konzept des »Primats der sozialen Herkunft« skizziert, die zugrundliegenden Quellen und die Methode vorgestellt, das Erkenntnispotenzial der Daten angedeutet und abschließend weiterführende Perspektiven für die Militärgeschichtsschreibung aufgezeigt. Verbunden ist die Dokumentation mit der Forderung, deutsches Militär im 19. und 20. Jahrhundert nicht mehr ausschließlich aus einer sozialdeterministischen Perspektive zu betrachten, sondern es vielmehr als Profession zu begreifen.

Fibroblast growth factor-23 (FGF-23) is a phosphaturic hormone used to monitor chronic kidney disease (CKD) in humans. The aim of this pilot study was to compare three diagnostic assays and to assess how the results correlate with parameters of renal dysfunction in cats. Four groups of 10 cats each were formed retrospectively according to creatinine, based on IRIS staging. FGF-23 was measured using two different ELISAs (MyBioSource and Kainos ELISA FGF-23 Kit) and an automated assay on the DiaSorin Liaison platform. Measurements were performed in 40 cats. Spearman’s rank correlation coefficient showed a strong correlation between the Kainos and DiaSorin assays (ρ = 0.742/p < 0.001) and a low correlation (ρ = 0.443/p = 0.005) between the Kainos and MyBioSource assays. The measurements with the Kainos assay strongly correlated with urea (ρ = 0.835/p < 0.001) and creatinine (ρ = 0.764/p < 0.001), and moderately correlated with SDMA (ρ = 0.580/p < 0.001) and phosphorus (ρ = 0.532/p < 0.001). The results of the MyBioSource and DiaSorin assays only showed a moderate correlation with urea (ρ = 0.624/0.572) and creatinine (ρ = 0.622/0.510) concentrations (p = 0.001 each). The Kainos assay showed the strongest correlation (ρ = 0.806) with the various creatinine concentrations according to the IRIS, followed by the MyBioSource (ρ = 0.663/p < 0.001) and DiaSorin assays (ρ = 0.580/p < 0.001). Overall, the Kainos assay demonstrated the best correlations with both biomarkers and various creatinine concentrations according to the IRIS. Individual assay-based reference values should be established to make a reliable interpretation of FGF-23 levels possible to diagnose or monitor feline CKD.

Millions of people displaced by conflicts have found refuge in water-scarce countries, where their perceived effect on water availability has shaped local water security discourses. Using an annual global data set, we explain the effects of refugee migrations on the host countries’ water stress through the food demand displaced by refugees and the water necessary to produce that food. The water footprint of refugee displacement increased by nearly 75% globally between 2005 and 2016. Although minimal in most countries, implications can be severe in countries already facing severe water stress. For example, refugees may have contributed up to 75 percentage points to water stress in Jordan. While water considerations should not, alone, determine trade and migration policy, we find that small changes to current international food supply flows and refugee resettlement procedures can potentially ease the effect of refugee displacement on water stress in water-vulnerable countries.

Multi-channel casing (MC) shows promising results in controlling the performance of the radial turbines. It has neither movable parts nor complicated control mechanisms therefore it withstands higher thermal loads compared to the commonly used control systems such as the Variable Geometry Turbine (VGT). This advantage makes the MC applicable for a wider range of applications which is difficult to be covered with the common control systems. Replacing the traditional spiral casing with the MC affects the blade's vibration behavior. First, a 3D unsteady computational fluid dynamic (CFD) simulation is performed to investigate the influence of using MC on the turbine flow field for both full and partial admission operation. Second, a forced response analysis is performed based on the CFD result to calculate the blade vibration amplitude at different resonance crossings. Finally, an MC is manufactured and tested experimentally to validate the numerical study. The results show that ignoring the casing replacement effect on the blade vibration during the MC design phase led to a high vibration amplitude and consequently causes high cycle fatigue.

Bayesian phylogeographic inference is a powerful tool in molecular epidemiological studies, which enables reconstruction of the origin and subsequent geographic spread of pathogens. Such inference is, however, potentially affected by geographic sampling bias. Here, we investigated the impact of sampling bias on the spatiotemporal reconstruction of viral epidemics using Bayesian discrete phylogeographic models and explored different operational strategies to mitigate this impact. We considered the continuous-time Markov chain (CTMC) model and two structured coalescent approximations (Bayesian structured coalescent approximation [BASTA] and marginal approximation of the structured coalescent [MASCOT]). For each approach, we compared the estimated and simulated spatiotemporal histories in biased and unbiased conditions based on the simulated epidemics of rabies virus (RABV) in dogs in Morocco. While the reconstructed spatiotemporal histories were impacted by sampling bias for the three approaches, BASTA and MASCOT reconstructions were also biased when employing unbiased samples. Increasing the number of analyzed genomes led to more robust estimates at low sampling bias for the CTMC model. Alternative sampling strategies that maximize the spatiotemporal coverage greatly improved the inference at intermediate sampling bias for the CTMC model, and to a lesser extent, for BASTA and MASCOT. In contrast, allowing for time-varying population sizes in MASCOT resulted in robust inference. We further applied these approaches to two empirical datasets: a RABV dataset from the Philippines and a SARS-CoV-2 dataset describing its early spread across the world. In conclusion, sampling biases are ubiquitous in phylogeographic analyses but may be accommodated by increasing the sample size, balancing spatial and temporal composition in the samples, and informing structured coalescent models with reliable case count data. ispartof: VIRUS EVOLUTION vol:9 issue:1 ispartof: location:England status: published

Private water supply systems consisting of a domestic well and septic system are used throughout the world where households lack access to public water supply and sewers. In residential areas with a high housing density, septic contamination of private wells is common and associated with multiple health concerns. This situation can give rise to social dilemmas, where individual costs de-incentivize homeowners from investing in enhanced septic systems that would reduce well contamination and bring communal benefits. We combine a stylized game theoretical model with a probabilistic groundwater model to characterize how economic and hydrogeological conditions interact to produce misaligned incentives conducive to social dilemmas. The occurrence of social dilemmas depends on the relative costs of well contamination versus the cost of installing an enhanced septic treatment system and the relative probabilities of cross-contamination versus self-contamination. The game reveals three types of social dilemmas that occur in such systems, with each calling for distinct policy solutions. We demonstrate how the model can be applied to existing systems, using a case study of St. Joseph County, Indiana, where high nitrate contamination rates have raised public health concerns. This analysis represents a step towards identifying alternative policy solutions for a problem that has remained difficult to address for decades.

American cutaneous leishmaniasis (ACL) is one of the most complex parasitic diseases from a clinical-immunopathological point of view due to the great heterogeneity of Leishmania species responsible for the disease. Currently, fifteen Leishmania species of the subgenera Leishmania, Viannia and Mundinia may give rise to ACL in Latin America. In Brazil, seven species are associated to the disease, but L. (V.) braziliensis and L. (L.) amazonensis stand out for producing the broadest clinical-immunopathological spectrum: localized cutaneous leishmaniasis [LCL: DTH+/++], borderline disseminated cutaneous leishmaniasis [BDCL: DTH+/−], mucocutaneous or mucosal leishmaniasis [MCL/ML: DTH++++], and anergic diffuse cutaneous leishmaniasis [ADCL: DTH−]. Although human genetic profile plays important factor in the immunopathogenesis of ACL, it deserves to be highlighted the crucial role of species-specific antigens of L. (V.) braziliensis and L. (L.) amazonensis [lipophosphoglycans, phosphatidylserine, proteophosphoglycans, glycoprotein-63 and CD200 – a macrophage activation inhibitor molecule] in the modulation of T-cell immune response (CD4+/CD8+) that will define the infection evolution.

Background Culture of Neisseria gonorrhoeae is essential for surveillance of complete antimicrobial susceptibility profiles. In 2014, the culture success rate of N. gonorrhoeae from samples taken at the clinic for sexually transmitted infections (STI clinic), Oslo University Hospital, Norway, was only 20%. The present study aimed to improve gonococcal culture rates using bedside inoculation of patient samples on gonococcal agar plates and incubation at the STI clinic. Methods This prospective quality improvement study was conducted by the STI clinic and the Department of Microbiology at Oslo University Hospital from May 2016 - October 2017. When culture of N. gonorrhoeae was clinically indicated, we introduced a parallel ‘bedside culture’ at the STI clinic and compared results with the standard culture at the microbiology department. Samples were taken from urethra, anorectum, pharynx and cervix. Culture rates were compared across symptomatic and asymptomatic anatomical sites. Results From 596 gonococcal-positive PCR samples, bedside culture had a significantly higher success rate of 57% compared to 41% with standard culture (p v. 45% from asymptomatic sites. The culture rates from different anatomical sites were as follows: urethra 93%, anorectum 64%, pharynx 28% and cervix 70%. Bedside culture significantly (p Conclusions Where feasible, bedside inoculation on gonococcal agar plates and incubation of samples from patients with gonorrhoea is recommended. This will improve the culture diagnostics and provide additional gonococcal isolates for antimicrobial resistance surveillance.

We present the first global glyoxal (CHOCHO) tropospheric column product derived from the TROPOspheric Monitoring Instrument (TROPOMI) on board the Sentinel-5 Precursor satellite. Atmospheric glyoxal results from the oxidation of other non-methane volatile organic compounds (NMVOCs) and from direct emissions caused by combustion processes. Therefore, this product is a useful indicator of VOC emissions. It is generated with an improved version of the BIRA-IASB scientific retrieval algorithm relying on the differential optical absorption spectroscopy (DOAS) approach. Among the algorithmic updates, the DOAS fit now includes corrections to mitigate the impact of spectral misfits caused by scene brightness inhomogeneity and strong NO2 absorption. The product comes along with a full error characterization, which allows for providing random and systematic error estimates for every observation. Systematic errors are typically in the range of 1 ×1014–3 ×1014 molec. cm−2 (∼30 %–70 % in emission regimes) and originate mostly from a priori data uncertainties and spectral interferences with other absorbing species. The latter may be at the origin, at least partly, of an enhanced glyoxal signal over equatorial oceans, and further investigation is needed to mitigate them. Random errors are large (>6×1014 molec. cm−2) but can be reduced by averaging observations in space and/or time. Benefiting from a high signal-to-noise ratio and a large number of small-size observations, TROPOMI provides glyoxal tropospheric column fields with an unprecedented level of detail. Using the same retrieval algorithmic baseline, glyoxal column data sets are also generated from the Ozone Monitoring Instrument (OMI) on Aura and from the Global Ozone Monitoring Experiment-2 (GOME-2) on board Metop-A and Metop-B. Those four data sets are intercompared over large-scale regions worldwide and show a high level of consistency. The satellite glyoxal columns are also compared to glyoxal columns retrieved from ground-based Multi-AXis DOAS (MAX-DOAS) instruments at nine stations in Asia and Europe. In general, the satellite and MAX-DOAS instruments provide consistent glyoxal columns both in terms of absolute values and variability. Correlation coefficients between TROPOMI and MAX-DOAS glyoxal columns range between 0.61 and 0.87. The correlation is only poorer at one mid-latitude station, where satellite data appear to be biased low during wintertime. The mean absolute glyoxal columns from satellite and MAX-DOAS generally agree well for low/moderate columns with differences of less than 1×1014 molec. cm−2. A larger bias is identified at two sites where the MAX-DOAS columns are very large. Despite this systematic bias, the consistency of the satellite and MAX-DOAS glyoxal seasonal variability is high.