Influence of common lighting conditions and time-of-day on the effort-related cardiac response

Melanopic stimuli trigger diverse non-image-forming effects. However, evidence of a melanopic contribution to acute effects on alertness and performance is inconclusive, especially under common lighting situations. Effects on cognitive performance are likely mediated by effort-related physiological changes. We assessed the acute effects of lighting in three scenarios, at two times of day, on effort-related changes to cardiac contraction as indexed by the cardiac pre-ejection period (PEP). In a within-subject design, twenty-seven participants performed a cognitive task thrice during a morning and a late-afternoon session. We set the lighting at 500 lux in all three lighting scenarios, measured horizontally at the desk level, but with 54 lux, 128 lux, or 241 lux melanopic equivalent daylight illuminance at the eye level. Impedance cardiography and electrocardiography measurements were used to calculate PEP, for the baseline and task period. A shorter PEP during the task represents a sympathetic heart activation and therefore increased effort. Data were analysed with linear mixed-effect models. PEP changes depended on both the light scene and time of day (p = 0.01 and p = 0.002, respectively). The highest change (sympathetic activation) occurred for the medium one of the three stimuli (128 lux) during the late-afternoon session. However, effect sizes for the singular effects were small, and only for the combined effect of light and time of day middle-sized. Performance scores or self-reported scores on alertness and task demand did not change with the light scene. In conclusion, participants reached the same performance most efficiently at both the highest and lowest melanopic setting, and during the morning session. The resulting U-shaped relation between melanopic stimulus intensity and PEP is likely not dependent solely on intrinsic ipRGC stimuli, and might be moderated by extrinsic cone input. Since lighting situations were modelled according to current integrative lighting strategies and real-life indoor light intensities, the result has implications for artificial lighting in a work environment

The magnetic fabrics of experimentally deformed artificial clay-water dispersions

The development of magnetic fabrics in artificial clay-water dispersions and natural, hematite-bearing mudstones is investigated in plane-strain pure shear laboratory experiments under strain rates of 1.6 x 10-5 and 2 x 10-4 s-1. The mixtures contain 0,15, 30 and 45% chlorite in an illite matrix, and 0, 1, 3, 6 and 8% magnetite in a kaolin matrix. Shortening up to 40% is imposed. The resulting fabrics show the following characteristics: (1) In the clay mixtures, the principal susceptibility axes (kmax >= kint >= kmin) rotate away from the well defined initial fabric orientations into the princip strain directions (e1 >= e2 >= e3) at strains > 30%. (2) Both mineralogical composition and initial magnetic fabric, but not the applied strain, influence the magnitudes of the principal susceptibility axes. (3) The illite-chlorite mixture series show an almost linear correlation between mineral concentration and susceptibility magnitudes. (4) Magnetite dominates the fabric of the magnetite-kaolin mixtures; the fabric is independent of the magnetite concentration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28975/1/0000002.pd

Index-antiguiding in narrow-ridge GaN-based laser diodes investigated by measurements of the current-dependent gain and index spectra and by self-consistent simulation

The threshold current density of narrow (1.5 {\mu}m) ridge-waveguide InGaN multi-quantum-well laser diodes, as well as the shape of their lateral far-field patterns, strongly depend on the etch depth of the ridge waveguide. Both effects can be attributed to strong index-antiguiding. A value of the antiguiding factor R = 10 is experimentally determined near threshold by measurements of the current-dependent gain and refractive index spectra. The device performances are simulated self-consistently solving the Schr\"odinger-Poisson equations and the equations for charge transport and waveguiding. Assuming a carrier-induced index change which matches the experimentally determined antiguiding factor, both the measured high threshold current and the shape of the far-field pattern of lasers with shallow ridges can be reproduced theoretically.Comment: This is an author-created, un-copyedited version of an article accepted for publication in the IEEE Journal of Quantum Electronics. IEEE is not responsible for any errors or omissions in this version of the manuscript or any version derived from i

Methodological studies of the Composite International Diagnostic Interview (CIDI) in the US national comorbidity survey (NCS)

This paper reports the results of methodological studies carried out in conjunction with the US National Comorbidity Survey (NCS) to evaluate Version 1.0 of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). These studies relied on recent survey data collection methodology literature to investigate problems regarding question comprehension, instruction comprehension, respondent motivation to report accurately, and regarding the limits of respondent ability to report accurately. Insights and strategies developed by survey methodologists were used to modify the CIDI in an effort to address these problems. The paper describes these strategies and methodological studies that evaluated their effects, including a clinical reappraisal study and a field experiment that evaluated the impact of question modifications on prevalence estimates. The paper closes with a discussion of remaining methodological problems with the CIDI and potentially useful future studies that might be able to develop solutions to these problems. Copyright © 1998 Whurr Publishers Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34217/1/33_ftp.pd

Disease Severity, Fever, Age, and Sex Correlate With SARS-CoV-2 Neutralizing Antibody Responses

Clinical trials on the use of COVID-19 convalescent plasma remain inconclusive. While data on safety is increasingly available, evidence for efficacy is still sparse. Subgroup analyses hint to a dose-response relationship between convalescent plasma neutralizing antibody levels and mortality. In particular, patients with primary and secondary antibody deficiency might benefit from this approach. However, testing of neutralizing antibodies is limited to specialized biosafety level 3 laboratories and is a time- and labor-intense procedure. In this single center study of 206 COVID-19 convalescent patients, clinical data, results of commercially available ELISA testing of SARS-CoV-2 spike-IgG and -IgA, and levels of neutralizing antibodies, determined by plaque reduction neutralization testing (PRNT), were analyzed. At a medium time point of 58 days after symptom onset, only 12.6% of potential plasma donors showed high levels of neutralizing antibodies (PRNT50 >= 1:320). Multivariable proportional odds logistic regression analysis revealed need for hospitalization due to COVID-19 (odds ratio 6.87; p-value 0.0004) and fever (odds ratio 3.00; p-value 0.0001) as leading factors affecting levels of SARS-CoV-2 neutralizing antibody titers in convalescent plasma donors. Using penalized estimation, a predictive proportional odds logistic regression model including the most important variables hospitalization, fever, age, sex, and anosmia or dysgeusia was developed. The predictive discrimination for PRNT50 >= 1:320 was reasonably good with AUC: 0.86 (with 95% CI: 0.79-0.92). Combining clinical and ELISA-based pre-screening, assessment of neutralizing antibodies could be spared in 75% of potential donors with a maximal loss of 10% of true positives (PRNT50 >= 1:320)

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous. Despite extensive clinical reports, underlying immunological mechanisms are poorly characterized and levels of T cellular and innate immunity in severe cases remain to be determined. In the present study, we report clinical and immunological findings of 5 PAD patients with severe and fatal COVID-19 and undetectable specific humoral immune response to SARS-CoV-2. Reactive T cells to SARS-CoV-2 spike (S) and nucleocapsid (NCAP) peptide pools were analyzed comparatively by flow cytometry in PAD patients, convalescents and naive healthy individuals. All examined PAD patients developed a robust T cell response. The presence of polyfunctional cytokine producing activated CD4(+) T cells indicates a memory-like phenotype. An analysis of innate immune response revealed elevated CD169 (SIGLEC1) expression on monocytes, a surrogate marker for type I interferon response, and presence of type I interferon autoantibodies was excluded. SARS-CoV-2 RNA was detectable in peripheral blood in three severe COVID-19 patients with PAD. Viral clearance in blood was observed after treatment with COVID-19 convalescent plasma/monoclonal antibody administration. However, prolonged mucosal viral shedding was observed in all patients (median 67 days) with maximum duration of 127 days. PAD patients without specific humoral SARS-CoV-2 immunity may suffer from severe or fatal COVID-19 despite robust T cell and normal innate immune response. Intensified monitoring for long persistence of SARS-CoV-2 viral shedding and (prophylactic) convalescent plasma/specific IgG as beneficial treatment option in severe cases with RNAemia should be considered in seronegative PAD patients

Microenvironment‐induced restoration of cohesive growth associated with focal activation of P ‐cadherin expression in lobular breast carcinoma metastatic to the colon

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E‐cadherin loss. Focal activation of P‐cadherin expression in tumor cells that are deficient for E‐cadherin occurs in a subset of ILCs. Switching from an E‐cadherin deficient to P‐cadherin proficient status (EPS) partially restores cell–cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52‐year‐old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E‐cadherin and P‐cadherin. CDH1 /E‐cadherin mutations were determined by next‐generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1 /E‐cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E‐cadherin‐negative and P‐cadherin‐negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter‐cryptal ILC cells switched to a P‐cadherin‐positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment‐induced EPS and conversion to cohesive growth

Overview: On the transport and transformation of pollutants in the outflow of major population centres – observational data from the EMeRGe European intensive operational period in summer 2017

Megacities and other major population centres (MPCs) worldwide are major sources of air pollution, both locally as well as downwind. The overall assessment and prediction of the impact of MPC pollution on tropospheric chemistry are challenging. The present work provides an overview of the highlights of a major new contribution to the understanding of this issue based on the data and analysis of the EMeRGe (Effect of Megacities on the transport and transformation of pollutants on the Regional to Global scales) international project. EMeRGe focuses on atmospheric chemistry, dynamics, and transport of local and regional pollution originating in MPCs. Airborne measurements, taking advantage of the long range capabilities of the High Altitude and LOng Range Research Aircraft (HALO, https://www.halo-spp.de, last access: 22 March 2022), are a central part of the project. The synergistic use and consistent interpretation of observational data sets of different spatial and temporal resolution (e.g. from ground-based networks, airborne campaigns, and satellite measurements) supported by modelling within EMeRGe provide unique insight to test the current understanding of MPC pollution outflows. In order to obtain an adequate set of measurements at different spatial scales, two field experiments were positioned in time and space to contrast situations when the photochemical transformation of plumes emerging from MPCs is large. These experiments were conducted in summer 2017 over Europe and in the inter-monsoon period over Asia in spring 2018. The intensive observational periods (IOPs) involved HALO airborne measurements of ozone and its precursors, volatile organic compounds, aerosol particles, and related species as well as coordinated ground-based ancillary observations at different sites. Perfluorocarbon (PFC) tracer releases and model forecasts supported the flight planning, the identification of pollution plumes, and the analysis of chemical transformations during transport. This paper describes the experimental deployment and scientific questions of the IOP in Europe. The MPC targets – London (United Kingdom; UK), the Benelux/Ruhr area (Belgium, the Netherlands, Luxembourg and Germany), Paris (France), Rome and the Po Valley (Italy), and Madrid and Barcelona (Spain) – were investigated during seven HALO research flights with an aircraft base in Germany for a total of 53 flight hours. An in-flight comparison of HALO with the collaborating UK-airborne platform Facility for Airborne Atmospheric Measurements (FAAM) took place to assure accuracy and comparability of the instrumentation on board. Overall, EMeRGe unites measurements of near- and far-field emissions and hence deals with complex air masses of local and distant sources. Regional transport of several European MPC outflows was successfully identified and measured. Chemical processing of the MPC emissions was inferred from airborne observations of primary and secondary pollutants and the ratios between species having different chemical lifetimes. Photochemical processing of aerosol and secondary formation or organic acids was evident during the transport of MPC plumes. Urban plumes mix efficiently with natural sources as mineral dust and with biomass burning emissions from vegetation and forest fires. This confirms the importance of wildland fire emissions in Europe and indicates an important but discontinuous contribution to the European emission budget that might be of relevance in the design of efficient mitigation strategies. The present work provides an overview of the most salient results in the European context, with these being addressed in more detail within additional dedicated EMeRGe studies. The deployment and results obtained in Asia will be the subject of separate publications

Welche Macht darf es denn Sein? Tracing ‘Power’ in German Foreign Policy Discourse

The relationship between ‘Germany’ and ‘power’ remains a sensitive issue. While observers tend to agree that Germany has regained the status of the most powerful country in Europe, there is debate whether that is to be welcomed or whether that is a problem. Underpinning this debate are views, both within Germany and amongst its neighbours, regarding the kind of power Germany has, or should (not) have. Against this backdrop, the article reviews the dominant role conceptions used in the expert discourse on German foreign policy since the Cold War that depict Germany as a particular type of ‘power’. Specifically, we sketch the evolution of three prominent conceptions (constrained power, civilian power, hegemonic power) and the recent emergence of a new one (shaping power). The article discusses how these labels have emerged to give meaning to Germany’s position in international relations, points to their normative and political function, and to the limited ability of such role images to tell us much about how Germany actually exercises power

Microenvironment-induced restoration of cohesive growth associated with focal activation of P-cadherin expression in lobular breast carcinoma metastatic to the colon

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E-cadherin loss. Focal activation of P-cadherin expression in tumor cells that are deficient for E-cadherin occurs in a subset of ILCs. Switching from an E-cadherin deficient to P-cadherin proficient status (EPS) partially restores cell–cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52-year-old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E-cadherin and P-cadherin. CDH1/E-cadherin mutations were determined by next-generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1/E-cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E-cadherin-negative and P-cadherin-negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter-cryptal ILC cells switched to a P-cadherin-positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment-induced EPS and conversion to cohesive growth