Discrete element modeling of aeolian-like morphologies on comet 67P/Churyumov-Gerasimenko

Context: Even after the Rosetta mission, some of the mechanical parameters of comet 67P/Churyumov-Gerasimenko’s surface material are still not well constrained. They are needed to improve our understanding of cometary activity or for planning sample return procedures. Aims: We discuss the physical process dominating the formation of aeolian-like surface features in the form of moats and wind tail-like bedforms around obstacles and investigate the mechanical and geometrical parameters involved. Methods: By applying the discrete element method (DEM) in a low-gravity environment, we numerically simulated the dynamics of the surface layer particles and the particle stream involved in the formation of aeolian-like morphological features. The material is composed of polydisperse spherical particles that consist of a mixture of dust and water ice, with interparticle forces given by the Hertz contact model, cohesion, friction, and rolling friction. We determined a working set of parameters that enables simulations to be reasonably realistic and investigated morphological changes when modifying these parameters. Results: The aeolian-like surface features are reasonably well reproduced using model materials with a tensile strength on the order of 0.1–1 Pa. Stronger materials and obstacles with round shapes impede the formation of a moat and a wind tail. The integrated dust flux required for the formation of moats and wind tails is on the order of 100 kg^m−2, which, based on the timescale of morphological changes inferred from Rosetta images, translates to a near-surface particle density on the order of 10^−6–10^−4 kg m^−3. Conclusions: DEM modeling of the aeolian-like surface features reveals complex formation mechanisms that involve both deposition of ejected material and surface erosion. More numerical work and additional in situ measurements or sample return missions are needed to better investigate mechanical parameters of cometary surface material and to understand the mechanics of cometary activity

Discrete element modeling of boulder and cliff morphologies on comet 67P/Churyumov-Gerasimenko

Context. Even after the Rosetta mission, some of the mechanical parameters of comet 67P/Churyumov-Gerasimenko's surface material are not yet well constrained. These parameters are needed to improve our understanding of cometary activity or for planning sample return missions. Aims. We study some of the physical processes involved in the formation of selected surface features and investigate the mechanicaland geometrical parameters involved. Methods. Applying the discrete element method (DEM) in a low-gravity environment, we numerically simulated the surface layer particle dynamics involved in the formation of selected morphological features. The material considered is a mixture of polydisperse ice and dust spheres with inter-particle forces given by the Hertz contact model, translational friction, rolling friction, cohesion from unsintered contacts, and optionally due to bonds from ice sintering. We determined a working set of parameters that enables the simulations to be reasonably realistic and investigated morphological changes due to modifications thereof. Results. The selected morphological features are reasonably well reproduced using model materials with a tensile strength on the order of 1-10 Pa. Increasing the diameters of the spherical particles decreases the material strength, and increasing the friction leads to a more brittle but somewhat stronger material. High friction is required to make the material sufficiently brittle to match observations, which points to the presence of very rough, even angular particles. Reasonable seismic activity does not suffice to trigger the collapses of cliffs without material heterogeneities or structural defects. Conclusions. DEM modeling can be a powerful tool to investigate mechanical parameters of cometary surface material. However, many uncertainties arise from our limited understanding of particle shapes, spatial configurations, and size distributions, all on multiple length scales. Further numerical work, in situ measurements, and sample return missions are needed to better understand the mechanics of cometary material and cometary activity

Opportunities and challenges of Web 2.0 for vaccination decisions.

A growing number of people use the Internet to obtain health information, including information about vaccines. Websites that allow and promote interaction among users are an increasingly popular source of health information. Users of such so-called Web 2.0 applications (e.g. social media), while still in the minority, represent a growing proportion of online communicators, including vocal and active anti-vaccination groups as well as public health communicators. In this paper, the authors: define Web 2.0 and examine how it may influence vaccination decisions; discuss how anti-vaccination movements use Web 2.0 as well as the challenges Web 2.0 holds for public health communicators; describe the types of information used in these different settings; introduce the theoretical background that can be used to design effective vaccination communication in a Web 2.0 environment; make recommendations for practice and pose open questions for future research. The authors conclude that, as a result of the Internet and Web 2.0, private and public concerns surrounding vaccinations have the potential to virally spread across the globe in a quick, efficient and vivid manner. Web 2.0 may influence vaccination decisions by delivering information that alters the perceived personal risk of vaccine-preventable diseases or vaccination side-effects. It appears useful for public health officials to put effort into increasing the effectiveness of existing communication by implementing interactive, customized communication. A key step to providing successful public health communication is to identify those who are particularly vulnerable to finding and using unreliable and misleading information. Thus, it appears worthwhile that public health websites strive to be easy to find, easy to use, attractive in its presentation and readily provide the information, support and advice that the searcher is looking for. This holds especially when less knowledgeable individuals are in need of reliable information about vaccination risks and benefits

Brain metastasis and survival outcomes after first-line therapy in metastatic melanoma: a multicenter DeCOG study on 1704 patients from the prospective skin cancer registry ADOREG

Background Despite the availability of effective systemic therapies, a significant number of advanced melanoma patients develops brain metastases. This study investigated differences in incidence and time to diagnosis of brain metastasis and survival outcomes dependent on the type of first-line therapy.Methods Patients with metastatic, non-resectable melanoma (AJCCv8 stage IIIC–V) without brain metastasis at start of first-line therapy (1L-therapy) were identified from the prospective multicenter real-world skin cancer registry ADOREG. Study endpoints were incidence of brain metastasis, brain metastasis-free survival (BMFS), progression-free survival (PFS), and overall survival (OS).Results Of 1704 patients, 916 were BRAF wild-type (BRAFwt) and 788 were BRAF V600 mutant (BRAFmut). Median follow-up time after start of 1L-therapy was 40.4 months. BRAFwt patients received 1L-therapy with immune checkpoint inhibitors (ICI) against CTLA-4+PD-1 (n=281) or PD-1 (n=544). In BRAFmut patients, 1L-therapy was ICI in 415 patients (CTLA-4+PD-1, n=108; PD-1, n=264), and BRAF+MEK targeted therapy (TT) in 373 patients. After 24 months, 1L-therapy with BRAF+MEK resulted in a higher incidence of brain metastasis compared with PD-1±CTLA-4 (BRAF+MEK, 30.3%; CTLA-4+PD-1, 22.2%; PD-1, 14.0%). In multivariate analysis, BRAFmut patients developed brain metastases earlier on 1L-therapy with BRAF+MEK than with PD-1±CTLA-4 (CTLA-4+PD-1: HR 0.560, 95% CI 0.332 to 0.945, p=0.030; PD-1: HR 0.575, 95% CI 0.372 to 0.888, p=0.013). Type of 1L-therapy, tumor stage, and age were independent prognostic factors for BMFS in BRAFmut patients. In BRAFwt patients, tumor stage was independently associated with longer BMFS; ECOG Performance status (ECOG-PS), lactate dehydrogenase (LDH), and tumor stage with OS. CTLA-4+PD-1 did not result in better BMFS, PFS, or OS than PD-1 in BRAFwt patients. For BRAFmut patients, multivariate Cox regression revealed ECOG-PS, type of 1L-therapy, tumor stage, and LDH as independent prognostic factors for PFS and OS. 1L-therapy with CTLA-4+PD-1 led to longer OS than PD-1 (HR 1.97, 95% CI 1.122 to 3.455, p=0.018) or BRAF+MEK (HR 2.41, 95% CI 1.432 to 4.054, p=0.001), without PD-1 being superior to BRAF+MEK.Conclusions In BRAFmut patients 1L-therapy with PD-1±CTLA-4 ICI resulted in a delayed and less frequent development of brain metastasis compared with BRAF+MEK TT. 1L-therapy with CTLA-4+PD-1 showed superior OS compared with PD-1 and BRAF+MEK. In BRAFwt patients, no differences in brain metastasis and survival outcomes were detected for CTLA-4+PD-1 compared with PD-1

Real‐world outcomes using PD‐1 antibodies and BRAF + MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland

Abstract Background Programmed death‐1 (PD‐1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high‐risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real‐world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland. Methods Multicenter, retrospective study investigating stage III–IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib + trametinib (D + T) between 1/2017 and 10/2021. The primary endpoint was 12‐month recurrence‐free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear‐regression machine learning model to assess the risk of early melanoma recurrence. Results In total, 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analysed. The vast majority received anti PD‐1 therapies (n = 1003). Twelve‐month RFS for anti PD‐1 and BRAF + MEK inhibitor‐treated patients were 78.1% and 86.5%, respectively (hazard ratio [HR] 1.998 [95% CI 1.335–2.991]; p = 0.001). There was no statistically significant difference in overall survival (OS) in anti PD‐1 (95.8%) and BRAF + MEK inhibitor (96.9%) treated patients (p > 0.05) during the median follow‐up of 17 months. Data indicates that anti PD‐1 treated patients who develop immune‐related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95% CI 0.443–0.754], p = 0.001). BRAF mutation status did not affect overall efficacy of anti PD‐1 treatment (p > 0.05). In both, anti PD‐1 and BRAF + MEK inhibitor treated cohorts, data did not show any difference in 12‐month RFS and 12‐month OS comparing patients receiving total lymph node dissection (TLND) versus sentinel lymph node biopsy only (p > 0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC = 0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials. Conclusions Despite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that TLND does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk

Grade 4 Neutropenia Secondary to Immune Checkpoint Inhibition — A Descriptive Observational Retrospective Multicenter Analysis

Introduction Immune checkpoint inhibitors (ICI) are increasingly being used to treat numerous cancer types. Together with improved recognition of toxicities, this has led to more frequent identification of rare immune-related adverse events (irAE), for which specific treatment strategies are needed. Neutropenia is a rare hematological irAE that has a potential for a high mortality rate because of its associated risk of sepsis. Prompt recognition and timely treatment of this life-threatening irAE are therefore critical to the outcome of patients with immune-related neutropenia. Methods This multicenter international retrospective study was conducted at 17 melanoma centers to evaluate the clinical characteristics, diagnostics, treatment, and outcomes of melanoma patients with grade 4 neutropenia (<500 neutrophils/µl blood) treated with ICI between 2014 and 2020. Some of these patients received metamizole in addition to ICI (ICI+/met+). Bone marrow biopsies (BMB) of these patients were compared to BMB from non-ICI treated patients with metamizole-induced grade 4 neutropenia (ICI-/met+). Results In total, 10 patients (median age at neutropenia onset: 66 years; seven men) with neutropenia were identified, equating to an incidence of 0.14%. Median onset of neutropenia was 6.4 weeks after starting ICI (range 1.4–49.1 weeks). Six patients showed inflammatory symptoms, including fever (n=3), erysipelas (n=1), pharyngeal abscess (n=1), and mucositis (n=1). Neutropenia was diagnosed in all patients by a differential blood count and additionally performed procedures including BMB (n=5). Nine of 10 patients received granulocyte colony-stimulating factors (G-CSF) to treat their grade 4 neutropenia. Four patients received systemic steroids (including two in combination with G-CSF, and one in combination with G-CSF and additional ciclosporin A). Four patients were treated with one or more antibiotic treatment lines, two with antimycotic treatment, and one with additional antiviral therapy. Five patients received metamizole concomitantly with ICI. One fatal outcome was reported. BMB indicated a numerically lower CD4+ to CD8+ T cells ratio in patients with irNeutropenia than in those with metamizole-induced neutropenia. Conclusion Grade 4 neutropenia is a rare but potentially life-threatening side effect of ICI treatment. Most cases were sufficiently managed using G-CSF; however, adequate empiric antibiotic, antiviral, and antimycotic treatments should be administered if neutropenic infections are suspected. Immunosuppression using corticosteroids may be considered after other causes of neutropenia have been excluded

Investment Risk - The Perspective of Private Investors

Am Finanzmarkt wird in der Regel davon ausgegangen, dass Anlagerisiken quantifizierbar sind, z.B. als Beta oder Volatilität. Empirische Untersuchungen zeigen, dass das Risikourteil von Privatanlegern nicht nur auf quantitativen Merkmalen beruht. In dieser Arbeit wird untersucht, durch welche Aspekte das durch Finanzlaien wahrgenommene Anlagerisiko gekennzeichnet ist. In Studie 1 wurden 98 Probanden (Pbn) verschiedene Anlageformen vorgelegt, die sie hinsichtlich des mit ihnen verbundenen Risikos und weiterer qualitativer und quantitativer Merkmale, die sich in anderen Studien als relevant erwiesen hatten, auf fünfstufigen Ratingskalen beurteilten. Eine Regressionsanalyse erwies die Merkmale Sorge, Neuheit, Volatilität und Vorhersagbarkeit als erklärungsstärkste Prädiktoren des Risikourteils. In Studie 2 wurde mit einer internetbasierten Befragung (171 Pbn, methodisch wie in Studie 1) überprüft, ob Merkmale wie Geschlecht, Alter, Wissen und Erfahrung die Beurteilung der Risiken beeinflussen. Weder für die demografischen Merkmale noch für das Finanzwissen (erfasst über einen Wissenstest) und die Anlageerfahrung konnten Effekte auf das Risikourteil nachgewiesen werden. Außerdem wurde analysiert, ob sich die Anlageformen (z.B. Aktien, Rentenfonds, Sparbuch) hinsichtlich der Wahrnehmung ihrer Risiken unterscheiden. Eine Clusteranalyse erlaubte, die Anlageformen aufgrund ihrer Risikocharakteristika in drei Gruppen zu klassifizieren: risikoreiche Anlageformen mit hoher Liquidität, mittelmäßig riskante Anlageformen mit eingeschränkter Liquidität und risikoarme Anlageformen. Regressionsanalysen zeigten, dass bei den risikoreichen Anlageformen die Volatilität, bei den mittelmäßig riskanten Anlageformen die Sorge und bei den risikoarmen Anlageformen die Totalverlustwahrscheinlichkeit der erklärungsstärkste Prädiktor des Risikourteils ist. In zwei weiteren Studien wurde die Rolle spezifischer Merkmale spekulativer Anlageformen analysiert. In Studie 3 konnten 351 Pbn hypothetisch in einen Aktienfonds investieren, der in unterschiedlichem Ausmaß mit Ambiguität verbunden war, indem er entweder in inländische oder ausländische Aktien investierte bzw. in Aktien von Branchen, die entweder als sehr bekannt (Medien) oder sehr unbekannt (Maschinenbau) erlebt werden. Es zeigte sich erwartungsgemäß, dass inländische Produkte gegenüber ausländischen bei der Investition bevorzugt werden. Das Risikourteil unterschied sich jedoch nicht in Abhängigkeit vom Investitionsland. Hinsichtlich verschiedener Branchen konnte kein Effekt der mit ihnen verbundenen Ambiguität auf die Investitionsbereitschaft nachgewiesen werden. Überraschenderweise hielten Pbn das Risiko des Fonds, der in eine ambigue Branche investiert, für geringer als das Risiko des Fonds, der in eine gut bekannte Branche investiert. In Studie 4 konnten 131 Pbn hypothetisch in Fonds investieren, deren Branchen sich hinsichtlich ihres Images unterschieden. Ein Teil der Branchen war dabei mit besonders negativem Image verbunden (z.B. Rüstung), ein anderer Teil mit sehr positivem Image (z.B. Software). Einflüsse des Images auf das Risikourteil konnten nicht nachgewiesen werden. Zwischen der Investitionsbereitschaft und dem Branchenimage konnte jedoch ein Zusammenhang gezeigt werden: Pbn investierten umso mehr, je positiver das Image einer Branche war. In einer Regressionsanalyse erwies sich das Image als besserer Prädiktor für die Investitionsbereitschaft als die Risiko- und Renditemerkmale. Aus den Befunden wurden Empfehlungen für die Praxis der Anlageberatung abgeleitet. Diese sollen dazu beitragen, die Perspektive der Privatanleger bei der Risikoaufklärung verstärkt zu berücksichtigen und damit die gesetzliche Forderung nach einer anlegergerechten Beratung zu erfüllen.In financial markets, it is normally assumed that investment risk is quantifiable, e.g. as Beta or volatility. Empirical investigations have shown that the risk judgements of private investors are not only based on quantitative criteria. The aim of this research is to identify those aspects which determine laypeople´s perception of investment risk. In study 1, different investment forms were presented to 98 subjects (Ss). The risk along with other quantitative and qualitative features, which proved important in past studies, was rated on scales ranging from 1 to 5. A regression analysis showed the attributes worry, novelty, volatility and predictability as best predictors for explaining risk judgement. In study 2, the influence of features such as gender, age, knowledge and experience on judging risk was tested by an online survey (171 Ss, method equivalent to Study 1). Demographic features, financial knowledge (measured by a knowledge test) and investment experience did not affect risk judgement. It was then analyzed whether the type of investment (e.g. stocks, bond funds, savings) differ with regard to their perceived risks. A classification on the basis of risk characteristics via cluster analysis revealed three groups: high-risk investment forms with high liquidity, moderate risk investment forms with limited liquidity and low-risk investment forms. Regression analysis showed that risk judgement is best predicted by volatility for high-risk investment forms, by worry for moderate-risk investment forms and by probability of total loss for low-risk investment forms. In two further studies, the role of specific features of speculative investment forms was analyzed. In study 3, 351 Ss had to invest hypothetically in an equity fund which had varying degrees of ambiguity. Either it invested in domestic or foreign stocks in one case or in stocks of different industry groups perceived as well known (media) or unknown (machine construction) in the other case. As expected, investments in domestic funds were favoured compared to investments in foreign funds. Risk judgements did not differ depending on investment state. No effects of differences in ambiguity on the willingness to invest could be detected with regard to industry groups. Surprisingly, the risk of the fund investing in an ambiguous industry group was rated lower than the risk of the fund investing in a familiar industry group. In study 4, 131 Ss could invest hypothetically in equity funds investing in various industry groups differing with respect to image. Some of the industry groups had an extreme negative image (e.g. defence industry), others an extreme positive image (e.g. software industry). Effects of image on risk judgements could not be proven. However, a significant correlation between image and willingness to invest was detected: the more positive the image the more money Ss invested. In a regression analysis, image turned out to be a better predictor for willingness to invest than risk- and return-features. The results of these studies were used to make recommendations to investment consultants. The perspective of private investors should be considered more when educating about investment risk thereby fulfilling the legal obligation to properly inform investors as stated by German Securities Trading Act

Studying the boulder morphology on comet 67P using discrete element simulations

Our overall aim is to investigate the physics of volatile-related surface features on asteroids and comets. In the present work, we focus on studying the morphology of boulders and cliff collapses on comet 67P/Churyumov-Gerasimenko’s surface (Fig. 1). This study continues and complements previous work, where we have been investigating dynamical processes that are implied by surface features on comet 67P [1] and on asteroid Vesta[2]