Transparente Verhaltensentscheidungen automatisierter Fahrzeuge – Sensitivitätsanalyse von Planungsalgorithmen

Im automatisierten Fahren arbeiten verschiedene Algorithmen zusammen, die Informationen übergeben, z. B. von der Wahrnehmung an die Planung. Dabei können sich Unsicherheiten fortpflanzen, die die Entscheidung des Planungsalgorithmus stark beeinflussen und möglicherweise zu Kollisionen führen, falls sie vom Planer nicht angemessen berücksichtigt werden. Aus diesem Grund wird die Qualität eines Planers häufig mit dem Auftreten von Kollisionen quantifiziert. Nutzer werden jedoch nicht nur ein sicheres, sondern aber auch ein ruhiges Fahrverhalten erwarten. Daher definiert diese Arbeit ein Maß für zulässige Planungsentscheidungen, das Schwankungen zwischen Planungsergebnissen betrachtet. Dies trägt dazu bei, dass unerwartete Fahrentscheidungen vermieden werden. In dieser Arbeit wird die Sensitivitätsanalyse nach Morris verwendet, um den Einfluss von Unsicherheiten in der Wahrnehmung auf Planungsentscheidungen zu untersuchen. Morris’ Analyse unterscheidet zwischen Inputs, die für die Planungsentscheidung relevant waren, und Inputs, die die Entscheidung nicht beeinflusst haben. Daraus wird abgeleitet, welcher Input zu unsicher war und welche Konsequenzen gezogen werden müssen: Einerseits sollte die Wahrnehmung speziell für diesen Input genauer arbeiten, andererseits sollte der Planer robuster gegenüber Unsicherheiten dieser Art werden. Aus diesen Ergebnissen kann leider noch nicht gefolgert werden, welche Menge an Wahrnehmungsunsicherheiten akzeptabel wäre. Dafür definiert ein stochastisches Optimierungsproblem die maximalen Unsicherheiten, die gerade noch zu Planungsergebnissen führen, die nicht stärker als ein Grenzwert schwanken. Dieses Vorgehen bietet für verschiedene Verkehrsszenarien die Möglichkeit, die Anforderungen an die Wahrnehmung genau mit den Voraussetzungen der Planung abzustimmen. Zusammengefasst können sowohl die Sensitivitätsanalyse als auch das stochastische Optimierungsproblem den Entwicklungsprozess unterstützen, indem sie z. B. beim Debugging helfen. Diese neuen Ansätze tragen dazu bei, die Verarbeitung der unsicherheitsbehafteten Informationen nachvollziehbarer zu gestalten und die Entwicklung automatisierter Fahrzeuge zu unterstützen. Im automatisierten Fahren betrifft Nachvollziehbarkeit aber nicht nur den Entwicklungsprozess, sondern auch den Endnutzer der Fahrfunktion. Die aktuelle Forschung erwartet, dass die Skepsis, die in großen Teilen der Bevölkerung gegenüber dem automatisierten Fahren herrscht, u. a. durch das Aufbauen von angemessenem Vertrauen abgebaut werden kann. Eine Möglichkeit, um Vertrauen bei Nutzern aufzubauen, sind Erklärungen, die das Verständnis der Nutzer verbessern. Bevor angemessene Erklärungen vom automatisierten Fahrzeug bereit gestellt werden können, sind zunächst Informationen nötig, die für die Beantwortung möglicher Fragen notwendig sind. Dafür wird zunächst das umfangreiche Wissen von Entwicklern als Ausgangspunkt verwendet. Daher wird zunächst mithilfe von Fokusgruppen untersucht, welche Fragen die Experten zu Fahrentscheidungen stellen, die sie während Testfahrten im Realverkehr als unerwartet wahrnahmen. Die Ergebnisse deuten darauf hin, dass vorrangig unerwartete laterale Bewegungen erklärt werden sollten. Um derartige unerwartete Fahrentscheidungen auch für Nutzer ohne detailliertes Fachwissen zu erklären, wird erneut die Sensitivitätsanalyse verwendet: Mit ihrer Hilfe werden die Informationen, die für zentrale Entscheidungen des automatisierten Fahrzeugs relevant sind, identifiziert. Anschließend werden diese interpretiert und in Zusammenhang mit der Umgebung sowie den geltenden Verkehrsregeln gesetzt. Das Ergebnis sind automatisch generierte, textbasierte Beschreibungen, die das Verhalten des automatisierten Fahrzeugs in leicht verständlicher Sprache wiedergeben und die nicht von menschlichen Fehlinterpretationen beeinflusst sind. Die Ergebnisse einer weiteren Studie zeigen, dass die generierten Sätze zwar derzeit noch als zu lang wahrgenommen werden und daher noch nicht als Nutzeranzeigen im Realverkehr verwendet werden können. Dennoch sind sie ein wichtiger und vielversprechender Schritt, um die technischen Voraussetzungen für zukünftige, informationsreiche und leicht verständliche Nutzeranzeigen zu erfüllen, die die Nachvollziehbarkeit von automatisierten Verhaltensentscheidungen erhöhen

Anatomical Reconstruction and Functional Imaging Reveal an Ordered Array of Skylight Polarization Detectors in Drosophila

Many insects exploit skylight polarization as a compass cue for orientation and navigation. In the fruit fly, Drosophila melanogaster, photoreceptors R7 and R8 in the dorsal rim area (DRA) of the compound eye are specialized to detect the electric vector (e-vector) of linearly polarized light. These photoreceptors are arranged in stacked pairs with identical fields of view and spectral sensitivities, but mutually orthogonal microvillar orientations. As in larger flies, we found that the microvillar orientation of the distal photoreceptor R7 changes in a fan-like fashion along the DRA. This anatomical arrangement suggests that the DRA constitutes a detector for skylight polarization, in which different e-vectors maximally excite different positions in the array. To test our hypothesis, we measured responses to polarized light of varying e-vector angles in the terminals of R7/8 cells using genetically encoded calcium indicators. Our data confirm a progression of preferred e-vector angles from anterior to posterior in the DRA, and a strict orthogonality between the e-vector preferences of paired R7/8 cells. We observed decreased activity in photoreceptors in response to flashes of light polarized orthogonally to their preferred e-vector angle, suggesting reciprocal inhibition between photoreceptors in the same medullar column, which may serve to increase polarization contrast. Together, our results indicate that the polarization-vision system relies on a spatial map of preferred e-vector angles at the earliest stage of sensory processing

What are the needs in oral antitumor therapy? An analysis of patients’ and practitioners’ preferences

BackgroundSince the European approval of CDK4/6 inhibitors in 2016, the treatment of patients with hormone-receptor-positive, HER2-negative metastatic breast cancer has changed significantly. Compared with chemotherapy, endocrine-based therapy has different treatment regimens and is associated with new side effects. Oral therapy aims for optimal drug efficacy and long treatment times while maintaining maximum independence and quality of life resulting in the conservation of medical staff resources.MethodsA monocentric analysis of therapy preferences of practitioners (25 nurses and physicians) and patients (11 on endocrine monotherapy, 17 on endocrine-based therapy, and 14 on intravenous chemotherapy) was performed using specific questionnaires. Preferences were assessed using a four-point Likert scale or bidirectional response options.ResultsAll patients were highly supportive of oral therapy (mean agreement score on the Likert scale 1.3, p < 0.001 vs. all other options) and a consultation interval of 4 weeks (2.0, p = 0.015 vs. 3 weeks). Practitioners also preferred oral therapy (1.4) and visits every 4 weeks (1.6). In general, patients on oral therapies reported higher compatibility of their therapy with daily life than patients on chemotherapy (1.6 and 1.7 vs. 2.6, p = 0.006). Outpatient oncology is the main source of information for all patients, mainly in case of side effects (2.0) and open questions (1.8). Regarding oral antitumor therapy regimens, patients do not show a significant preference for a specific regimen, while practitioners prefer a continuous regimen (1.6) over a 21/7 regimen (21 days on and 7 days off therapy, 2.5). Patients are likely to accept mild side effects (e.g., neutropenia, diarrhea, polyneuropathy, fatigue) and would still adhere to their initial choice of regimen (continuous or 21/7). Only when side effects occur with a severity of CTCAE grade 3 do patients prefer the regimen in which the side effects occur for a shorter period of time.ConclusionPatients and practitioners prefer oral antitumor therapy—both continuous and 21/7 regimens—over other application forms. Patient education and proper therapy management, supported by additional tools, contribute to the specific management of side effects and high adherence. This allows quality of life to be maintained during long-term therapy with CDK4/6 inhibitors in patients with metastatic breast cancer

Isotopic measurements in water vapor, precipitation, and seawater during EUREC4^4A

n early 2020, an international team set out to investigate trade-wind cumulus clouds and their coupling to the large-scale circulation through the field campaign EUREC$^4$A: ElUcidating the RolE of Clouds-Circulation Coupling in ClimAte. Focused on the western tropical Atlantic near Barbados, EUREC$^4$A deployed a number of innovative observational strategies, including a large network of water isotopic measurements collectively known as EUREC$^4$A-iso, to study the tropical shallow convective environment. The goal of the isotopic measurements was to elucidate processes that regulate the hydroclimate state – for example, by identifying moisture sources, quantifying mixing between atmospheric layers, characterizing the microphysics that influence the formation and persistence of clouds and precipitation, and providing an extra constraint in the evaluation of numerical simulations. During the field experiment, researchers deployed seven water vapor isotopic analyzers on two aircraft, on three ships, and at the Barbados Cloud Observatory (BCO). Precipitation was collected for isotopic analysis at the BCO and from aboard four ships. In addition, three ships collected seawater for isotopic analysis. All told, the in situ data span the period 5 January–22 February 2020 and cover the approximate area 6 to 16° N and 50 to 60° W, with water vapor isotope ratios measured from a few meters above sea level to the mid-free troposphere and seawater samples spanning the ocean surface to several kilometers depth. This paper describes the full EUREC$^4$A isotopic in situ data collection – providing extensive information about sampling strategies and data uncertainties – and also guides readers to complementary remotely sensed water vapor isotope ratios. All field data have been made publicly available even if they are affected by known biases, as is the case for high-altitude aircraft measurements, one of the two BCO ground-based water vapor time series, and select rain and seawater samples from the ships. Publication of these data reflects a desire to promote dialogue around improving water isotope measurement strategies for the future. The remaining, high-quality data create unprecedented opportunities to close water isotopic budgets and evaluate water fluxes and their influence on cloudiness in the trade-wind environment. The full list of dataset DOIs and notes on data quality flags are provided in Table 3 of Sect. 5 (“Data availability”)

SARS-CoV-2 omicron (B.1.1.529)-related COVID-19 sequelae in vaccinated and unvaccinated patients with cancer: results from the OnCovid registry

Background COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2. Methods OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death. We evaluated the prevalence of COVID-19 sequelae in patients who survived COVID-19 and underwent a formal clinical reassessment, categorising infection according to the date of diagnosis as the omicron (B.1.1.529) phase from Dec 15, 2021, to Jan 31, 2022; the alpha (B.1.1.7)-delta (B.1.617.2) phase from Dec 1, 2020, to Dec 14, 2021; and the pre-vaccination phase from Feb 27 to Nov 30, 2020. The prevalence of overall COVID-19 sequelae was compared according to SARS-CoV-2 immunisation status and in relation to post-COVID-19 survival and resumption of systemic anticancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974. Findings At the follow-up update on June 20, 2022, 1909 eligible patients, evaluated after a median of 39 days (IQR 24-68) from COVID-19 diagnosis, were included (964 [ 50 center dot 7%] of 1902 patients with sex data were female and 938 [49 center dot 3%] were male). Overall, 317 (16 center dot 6%; 95% CI 14 center dot 8-18 center dot 5) of 1909 patients had at least one sequela from COVID-19 at the first oncological reassessment. The prevalence of COVID-19 sequelae was highest in the prevaccination phase (191 [19 center dot 1%; 95% CI 16 center dot 4-22 center dot 0] of 1000 patients). The prevalence was similar in the alpha-delta phase (110 [16 center dot 8%; 13 center dot 8- 20 center dot 3] of 653 patients, p=0 center dot 24), but significantly lower in the omicron phase (16 [6 center dot 2%; 3 center dot 5-10 center dot 2] of 256 patients, p<0 center dot 0001). In the alpha- delta phase, 84 (18 center dot 3%; 95% CI 14 center dot 6-22 center dot 7) of 458 unvaccinated patients and three (9 center dot 4%; 1 center dot 9- 27 center dot 3) of 32 unvaccinated patients in the omicron phase had sequelae. Patients who received a booster and those who received two vaccine doses had a significantly lower prevalence of overall COVID-19 sequelae than unvaccinated or partially vaccinated patients (ten [7 center dot 4%; 95% CI 3 center dot 5-13 center dot 5] of 136 boosted patients, 18 [9 center dot 8%; 5 center dot 8-15 center dot 5] of 183 patients who had two vaccine doses vs 277 [ 18 center dot 5%; 16 center dot 5-20 center dot 9] of 1489 unvaccinated patients, p=0 center dot 0001), respiratory sequelae (six [4 center dot 4%; 1 center dot 6-9 center dot 6], 11 [6 center dot 0%; 3 center dot 0-10 center dot 7] vs 148 [9 center dot 9%; 8 center dot 4- 11 center dot 6], p= 0 center dot 030), and prolonged fatigue (three [2 center dot 2%; 0 center dot 1-6 center dot 4], ten [5 center dot 4%; 2 center dot 6-10 center dot 0] vs 115 [7 center dot 7%; 6 center dot 3-9 center dot 3], p=0 center dot 037)

SARS-CoV-2 omicron (B.1.1.529)-related COVID-19 sequelae in vaccinated and unvaccinated patients with cancer: results from the OnCovid registry

Background COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2. Methods OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death. We evaluated the prevalence of COVID-19 sequelae in patients who survived COVID-19 and underwent a formal clinical reassessment, categorising infection according to the date of diagnosis as the omicron (B.1.1.529) phase from Dec 15, 2021, to Jan 31, 2022; the alpha (B.1.1.7)-delta (B.1.617.2) phase from Dec 1, 2020, to Dec 14, 2021; and the pre-vaccination phase from Feb 27 to Nov 30, 2020. The prevalence of overall COVID-19 sequelae was compared according to SARS-CoV-2 immunisation status and in relation to post-COVID-19 survival and resumption of systemic anticancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974. Findings At the follow-up update on June 20, 2022, 1909 eligible patients, evaluated after a median of 39 days (IQR 24-68) from COVID-19 diagnosis, were included (964 [ 50 center dot 7%] of 1902 patients with sex data were female and 938 [49 center dot 3%] were male). Overall, 317 (16 center dot 6%; 95% CI 14 center dot 8-18 center dot 5) of 1909 patients had at least one sequela from COVID-19 at the first oncological reassessment. The prevalence of COVID-19 sequelae was highest in the prevaccination phase (191 [19 center dot 1%; 95% CI 16 center dot 4-22 center dot 0] of 1000 patients). The prevalence was similar in the alpha-delta phase (110 [16 center dot 8%; 13 center dot 8- 20 center dot 3] of 653 patients, p=0 center dot 24), but significantly lower in the omicron phase (16 [6 center dot 2%; 3 center dot 5-10 center dot 2] of 256 patients, p<0 center dot 0001). In the alpha- delta phase, 84 (18 center dot 3%; 95% CI 14 center dot 6-22 center dot 7) of 458 unvaccinated patients and three (9 center dot 4%; 1 center dot 9- 27 center dot 3) of 32 unvaccinated patients in the omicron phase had sequelae. Patients who received a booster and those who received two vaccine doses had a significantly lower prevalence of overall COVID-19 sequelae than unvaccinated or partially vaccinated patients (ten [7 center dot 4%; 95% CI 3 center dot 5-13 center dot 5] of 136 boosted patients, 18 [9 center dot 8%; 5 center dot 8-15 center dot 5] of 183 patients who had two vaccine doses vs 277 [ 18 center dot 5%; 16 center dot 5-20 center dot 9] of 1489 unvaccinated patients, p=0 center dot 0001), respiratory sequelae (six [4 center dot 4%; 1 center dot 6-9 center dot 6], 11 [6 center dot 0%; 3 center dot 0-10 center dot 7] vs 148 [9 center dot 9%; 8 center dot 4- 11 center dot 6], p= 0 center dot 030), and prolonged fatigue (three [2 center dot 2%; 0 center dot 1-6 center dot 4], ten [5 center dot 4%; 2 center dot 6-10 center dot 0] vs 115 [7 center dot 7%; 6 center dot 3-9 center dot 3], p=0 center dot 037)

Retrieving H2O/HDO columns over cloudy and clear-sky scenes from the Tropospheric Monitoring Instrument (TROPOMI)

This paper presents an extended scientific HDO/H2O total column data product from short-wave infrared (SWIR) measurements by the Tropospheric Monitoring Instrument (TROPOMI) including clear-sky and cloudy scenes. The retrieval employs a forward model which accounts for scattering, and the algorithm infers the trace gas column information, surface properties, and effective cloud parameters from the observations. Compared to the previous clear-sky-only data product, coverage is greatly enhanced by including scenes over low clouds, particularly enabling data over oceans as the albedo of water in the SWIR spectral range is too low to retrieve under cloud-free conditions. The new dataset is validated against co-located ground-based Fourier transform infrared (FTIR) observations by the Total Carbon Column Observing Network (TCCON). The median bias for clear-sky scenes is 1.4 x 10(21) molec cm(-2) (2.9 %) in H2O columns and 1.1 x 10(17) molec cm(-2) (-0.3 %) in HDO columns, which corresponds to -17 parts per thousand (9.9 %) in a posteriori delta D. The bias for cloudy scenes is 4.9 x 10(21) molec cm(-2) (11 %) in H2O, 1.1 x 10(18) molec cm(-2) (7.9 %) in HDO, and -20 parts per thousand (9.7 %) in a posteriori delta D. At low-altitude stations, the bias is small at low and middle latitudes and has a larger value at high latitudes. At high-altitude stations, an altitude correction is required to compensate for different partial columns seen by the station and the satellite. The bias in a posteriori delta D after altitude correction depends on sensitivity due to shielding by clouds and on realistic a priori profile shapes for both isotopologues. Cloudy scenes generally involve low sensitivity below the clouds, and since the information is filled up by the prior, a realistic shape of the prior is important for realistic total column estimation in these cases. Over oceans, aircraft measurements with the Water Isotope System for Precipitation and Entrainment Research (WISPER) instrument from a field campaign in 2018 are used for validation, yielding biases of -3.9 % in H2O and -3 parts per thousand in delta D over clouds. To demonstrate the added value of the new dataset, a short case study of a cold air outbreak over the Atlantic Ocean in January 2020 is presented, showing the daily evolution of the event with single-overpass results.ISSN:1867-1381ISSN:1867-854

Loss of PHD3 allows tumours to overcome hypoxic growth inhibition and sustain proliferation through EGFR

Solid tumours are exposed to microenvironmental factors such as hypoxia that normally inhibit cell growth. However, tumour cells are capable of counteracting these signals through mechanisms that are largely unknown. Here we show that the prolyl hydroxylase PHD3 restrains tumour growth in response to microenvironmental cues through the control of EGFR. PHD3 silencing in human gliomas or genetic deletion in a murine high-grade astrocytoma model markedly promotes tumour growth and the ability of tumours to continue growing under unfavourable conditions. The growth-suppressive function of PHD3 is independent of the established PHD3 targets HIF and NF-κB and its hydroxylase activity. Instead, loss of PHD3 results in hyperphosphorylation of epidermal growth factor receptor (EGFR). Importantly, epigenetic/genetic silencing of PHD3 preferentially occurs in gliomas without EGFR amplification. Our findings reveal that PHD3 inactivation provides an alternative route of EGFR activation through which tumour cells sustain proliferative signalling even under conditions of limited oxygen availability.Deutsche KrebshilfeGerman Ministry of Education and ResearchNational Genome NetworkBrain Tumour NetworkBehring-Roentgen FoundationKFO210LOEWE-OSFGutenberg Research CollegeJohannes Gutenberg University MainzClusters of Excellence ‘Cardio-Pulmonary System (ECCPS)’Universities of Giessen and FrankfurtDepto. de Bioquímica y Biología MolecularFac. de FarmaciaTRUEpu

The impact of nutritional counseling on thyroid disorders in head and neck cancer patients after (chemo)radiotherapy: results from a prospective interventional trial

Objective!#!To analyze the impact of nutritional counseling on the development of hypothyroidism after (chemo)radiotherapy in head and neck cancer patients to propose a new normal tissue complication probability (NTCP) model.!##!Materials and methods!#!At baseline, at the end of (chemo)radiotherapy, and during follow-up, thyroid-stimulating hormone (TSH) with free thyroxin (fT3 and fT4), nutritional status, and nutrient intake were prospectively analyzed in 46 out of 220 screened patients. Patients received (chemo)radiotherapy within an intervention (individual nutritional counseling every 2 weeks during therapy) and a control group (no nutritional counseling).!##!Results!#!Overall median follow-up was 16.5 [IQR: 12; 22] months. Fourteen patients (30.4%) presented with hypothyroidism after 13.5 [8.8; 17] months. During (chemo)radiotherapy, nutritional status worsened in the entire cohort: body mass index (p &amp;lt; 0.001) and fat-free mass index (p &amp;lt; 0.001) decreased, calorie deficit (p = 0.02) increased, and the baseline protein intake dropped (p = 0.028). The baseline selenium intake (p = 0.002) increased until the end of therapy. Application of the NTCP models by Rønjom, Cella, and Boomsma et al. resulted in good performance of all three models, with an AUC ranging from 0.76 to 0.78. Our newly developed NTCP model was based on baseline TSH and baseline ferritin. Model performance was good, receiving an AUC of 0.76 (95% CI: 0.61-0.87), with a sensitivity of 57.1% and specificity of 96.9% calculated for a Youden index of 0.73 (p = 0.004; area = 0.5).!##!Conclusion!#!Baseline TSH and ferritin act as independent predictors for radiotherapy-associated hypothyroidism. The exclusion of such laboratory chemistry parameters in future NTCP models may result in poor model performance