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The radical character of molecules exhibiting singlet fission is related to the energy level matching relationships that facilitate this process. Using a linear H4model molecule, we employ quantum chemical topology descriptors based on full configuration interaction calculations to rationalize singlet fission. In this context, the influence of the closed-shell to diradical and diradical to tetraradical character on the singlet fission energy matching conditions is analyzed. We find that in the diradical limit the singlet fission efficiency can be manipulated considering the active molecule coupled to an excited diradical, while in the diradical to tetraradical limit, the efficiency is dependent only on the gap between the lowest-lying excited singlet and triplet state. Furthermore, our results reveal possible design strategies for molecules with radical character exhibiting efficient singlet fission.

This paper presents a novel approach for sensor fusion of robotic total station (RTS) and inertial navigation system (INS) to enable 6-degree-of-freedom (6DoF) pose estimation. Tight coupling of a spherical measurement model for RTS is developed, providing advantages over the traditional cartesian 3D-position measurement model, including supporting INS solution when distance measurements are unavailable and performing outlier detection in spherical observation space. Simulation studies demonstrate that replacing Global Navigation Satellite Systems (GNSS) with RTS for fusion with INS is beneficial in any environment (given line-of-sight (LOS) availability), even under ideal GNSS conditions. Furthermore, investigations on measurement models and failure identification over the entire range of RTS measurements reveal that the spherical model is advantageous over the cartesian model in certain regions. The developed methods are validated in a practical application for tilt compensation of an RTS pole, indicating a base 2D-RMSE of 3.8 mm for almost static and almost vertical poles, increasing with tilt and velocity.

Data-driven business models imply the inter-organisational exchange of data or similar value objects. Data science methods enable organisations to discover patterns and eventually knowledge from data. Further, by training machine learning models, knowledge is materialised in those models. Thus, organisations might risk the exposure of competitive knowledge by sharing data-related value objects, such as data, models or predictions. Although knowledge risks have been studied in traditional business models, little research has been conducted in the direction of data-driven business models. In this explorative qualitative study, we conducted 28 expert interviews in three rounds (two exploratory and one evaluatory) and identified five types of risks along the three basic types of value objects: data, models and predictions. These risks depend on the context, i.e., when competitive knowledge could be discovered from shared value objects. We found that those risks can be mitigated by technology, contractual regulations, trusted relationships, and adjusting the business model design. In this study, we show that the risk of knowledge leakage is a relevant risk factor in data-driven business models. Overall, knowledge risks should be considered already during business model design, and their management requires an interdisciplinary approach via a balanced assessment. The level of knowledge protection from a technology perspective highly depends on computer science innovations and thus is a moving target. As an outlook, we suggest that knowledge risk will become even more relevant with the extensive usage of machine learning and artificial intelligence in data-driven business models.

Recurrence of paroxysmal atrial fibrillation (AF) following pulmonary vein isolation (PVI) is presumably caused by pulmonary vein (PV) reconnections. However, there is little data available on the durability of PVI and incidence of arrhythmia recurrence in patients with persistent AF.

Der intermittierende Selbstkatheterismus (ISK) ist der Goldstandard für Patientinnen und Patienten mit funktionellen, neurogenen oder obstruktiven Blasenentleerungsstörungen, bei denen keine operative Therapieoption besteht. Diese schmerzlose Therapie wird ärztlich verordnet, und die Patientinnen und Patienten werden durch spezialisiertes, diplomiertes Pflegepersonal darin geschult. Die Betroffenen erlernen den ISK in der Regel rasch, integrieren ihn in ihr tägliches Leben und gewinnen dadurch meistens an Lebensqualität und Unabhängigkeit. Seit 2016 bietet die Universitätsklinik für Urologie am Inselspital Bern ein durch die Pflegeexpertin geleitetes Schulungsprogramm für ISK an. In den letzten 4 Jahren wurde bei 177 Frauen und 253 Männer die Indikation zum ISK gestellt, und die 430 Patientinnen und Patienten wurden erstmals ambulant dazu beraten und geschult. Beim telefonischen Follow-up nach 1 Woche fühlten sich 75 % der befragten Personen bei der Durchführung des ISK immer sicher und weitere 20 % meistens sicher. Alle Patientinnen und Patienten schätzten es sehr, dass sie für die Schulung nicht stationär aufgenommen wurden.

The incidence of Alzheimer’s disease (AD), the leading cause of dementia, increases rapidly with age, but why age constitutes the main risk factor is still poorly understood. Brain ageing affects oligodendrocytes and the structural integrity of myelin sheaths1, the latter of which is associated with secondary neuroinflammation2,3. As oligodendrocytes support axonal energy metabolism and neuronal health4–7, we hypothesized that loss of myelin integrity could be an upstream risk factor for neuronal amyloid-β (Aβ) deposition, the central neuropathological hallmark of AD. Here we identify genetic pathways of myelin dysfunction and demyelinating injuries as potent drivers of amyloid deposition in mouse models of AD. Mechanistically, myelin dysfunction causes the accumulation of the Aβ-producing machinery within axonal swellings and increases the cleavage of cortical amyloid precursor protein. Suprisingly, AD mice with dysfunctional myelin lack plaque-corralling microglia despite an overall increase in their numbers. Bulk and single-cell transcriptomics of AD mouse models with myelin defects show that there is a concomitant induction of highly similar but distinct disease-associated microglia signatures specific to myelin damage and amyloid plaques, respectively. Despite successful induction, amyloid disease-associated microglia (DAM) that usually clear amyloid plaques are apparently distracted to nearby myelin damage. Our data suggest a working model whereby age-dependent structural defects of myelin promote Aβ plaque formation directly and indirectly and are therefore an upstream AD risk factor. Improving oligodendrocyte health and myelin integrity could be a promising target to delay development and slow progression of AD.

ObjectiveTo estimate the extent of suboptimal statin use for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD) at different stages of the treatment pathway and identify patient groups at risk of suboptimal treatment.MethodsNational retrospective cohort study using linked National Health Service Scotland administrative data of adults hospitalised for an ASCVD event (n=167 978) from 2009 to 2017. Proportions of patients initiating, adhering to, discontinuing and reinitiating statins were calculated. We separately examined treatment following myocardial infarction (MI), ischaemic stroke and peripheral arterial disease (PAD) hospitalisations. Multivariable logistic regression and Cox proportional hazards models were used to assess the roles of patient characteristics in the likelihood of initiating and discontinuing statins.ResultsOf patients hospitalised with ASCVD, only 81% initiated statin therapy, 40% of whom used high-intensity statin. Characteristics associated with lower odds of initiation included female sex (28% less likely than men), age below 50 years or above 70 years (<50 year-olds 26% less likely, and 70–79, 80–89 and ≥90 year-olds 22%, 49% and 77% less likely, respectively, than 60–69 year-olds), living in the most deprived areas and history of mental health-related hospital admission. Following MI, 88% of patients initiated therapy compared with 81% following ischaemic stroke and 75% following PAD events. Of statin-treated individuals, 24% discontinued treatment. Characteristics associated with discontinuation were similar to those related to non-initiation.ConclusionsStatin use remains suboptimal for the secondary ASCVD prevention, particularly in women and older patients, and following ischaemic stroke and PAD hospitalisations. Improving this would offer substantial benefits to population health at low cost.

Die Inzidenz des Nierenkarzinoms ist aufgrund häufig eingesetzter bildgebender Verfahren gestiegen, ebenso die Anzahl der Behandlungsvarianten von Nierenrundherden. Neben der klassischen radikalen Nephrektomie haben sich die partielle Nephrektomie sowie auch lokal ablative Verfahren und die „active surveillance“ in Studien behauptet. Es gilt, bei jedem Fall die patientenspezifischen Komorbiditäten und die therapiespezifischen Risiken sowie auch das karzinomspezifische Mortalitätsrisiko gegeneinander abzuwägen.

Flexure pivots, which are widely used for precision mechanisms, generally have the drawback of presenting parasitic shifts accompanying their rotation. The known solutions for canceling these undesirable parasitic translations usually induce a loss in radial stiffness, a reduction of the angular stroke, and nonlinear moment–angle characteristics. This article introduces a novel family of kinematic structures based on coupled n-RRR planar parallel mechanisms, which presents exact zero parasitic shifts while alleviating the drawbacks of some known pivoting structures. Based on this invention, three symmetrical architectures have been designed and implemented as flexure-based pivots. The performance of the newly introduced pivots has been compared with two known planar flexure pivots having theoretically zero parasitic shift via Finite Element models and experiments performed on plastic mockups. The results show that the newly introduced flexure pivots are an order of magnitude radially stiffer than the considered pivots from the state-of-the-art while having equivalent angular strokes. To experimentally evaluate the parasitic shift of the novel pivots, one of the architectures was manufactured in titanium alloy using wire-cut electrical discharge machining. This prototype exhibits a parasitic shift under 1.5 µm over a rotation stroke of ±15 deg, validating the near-zero parasitic shift properties of the presented designs. These advantages are key to applications such as mechanical time bases, surgical robotics, or optomechanical mechanisms.

Intravesical therapy with the recombinant bacillus Calmette-Guérin (BCG) strain VPM1102BC is safe and well tolerated and maintains quality of life in 70% of patients. Of patients who had received previous standard BCG induction with or without BCG maintenance therapy, more than 49% and 43% remained without recurrence after 1 and 3 yr, respectively.

Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population.

Purpose: Artificial intelligence (AI) is currently one of the most disruptive technologies and can be applied in many different use cases. However, applying AI in regulated environments is challenging, as it is currently not clear how to achieve and assess the fairness, accountability and transparency (FAT) of AI. Documentation is one promising governance mechanism to ensure that AI is FAT when it is applied in practice. However, due to the nature of AI, documentation standards from software engineering are not suitable to collect the required evidence. Even though FAT AI is called for by lawmakers, academics and practitioners, suitable guidelines on how to document AI are not available. This interview study aims to investigate the requirements for AI documentations. Design/methodology/approach: A total of 16 interviews were conducted with senior employees from companies in the banking and IT industry as well as with consultants. The interviews were then analyzed using an informed-inductive coding approach. Findings: The authors found five requirements for AI documentation, taking the specific nature of AI into account. The interviews show that documenting AI is not a purely technical task, but also requires engineers to present information on how the AI is understandably integrated into the business process. Originality/value: This paper benefits from the unique insights of senior employees into the documentation of AI.

This article devises a photograph-based monitoring model to estimate the real-time PM2.5 concentrations, overcoming currently popular electrochemical sensor-based PM2.5 monitoring methods’ shortcomings such as low-density spatial distribution and time delay. Combining the proposed monitoring model, the photographs taken by various camera devices (e.g., surveillance camera, automobile data recorder, and mobile phone) can widely monitor PM2.5 concentration in megacities. This is beneficial to offering helpful decision-making information for atmospheric forecast and control, thus reducing the epidemic of COVID-19. To specify, the proposed model fuses Information Abundance measurement and Wide and Deep learning, dubbed as IAWD, for PM2.5 monitoring. First, our model extracts two categories of features in a newly proposed DS transform space to measure the information abundance (IA) of a given photograph since the growth of PM2.5 concentration decreases its IA. Second, to simultaneously possess the advantages of memorization and generalization, a new wide and deep neural network is devised to learn a nonlinear mapping between the above-mentioned extracted features and the groundtruth PM2.5 concentration. Experiments on two recently established datasets totally including more than 100 000 photographs demonstrate the effectiveness of our extracted features and the superiority of our proposed IAWD model as compared to state-of-the-art relevant computing techniques.

Glucan phosphatases are members of a functionally diverse family of dual-specificity phosphatase (DSP) enzymes. The plant glucan phosphatase Starch Excess4 (SEX4) binds and dephosphorylates glucans, contributing to processive starch degradation in the chloroplast at night. Little is known about the complex kinetics of SEX4 when acting on its complex physiologically relevant glucan substrate. Therefore, we explored the kinetics of SEX4 against both insoluble starch and soluble amylopectin glucan substrates. SEX4 displays robust activity and a unique sigmoidal kinetic response to amylopectin, characterized by a Hill coefficient of 2.77 ± 0.63, a signature feature of cooperativity. We investigated the basis for this positive kinetic cooperativity and determined that the SEX4 carbohydrate-binding module (CBM) dramatically influences the binding cooperativity and substrate transformation rates. These findings provide insights into a previously unknown but important regulatory role for SEX4 in reversible starch phosphorylation and further advances our understanding of atypical kinetic mechanisms.

In patients with non-invasive urothelial carcinoma of the prostatic urethra (PUC), treatment with Bacillus Calmette-Guérin (BCG) could be beneficial. To assess the response rates to BCG in the different tumor stages, to describe the clinical impact of transurethral resection of the prostate (TURP) before BCG treatment, and to review the side effects of BCG treatment for PUC. A systematic search was conducted using the PubMed database to identify original studies between 1977 and 2019 reporting on PUC and BCG. Of a total of 865 studies, ten were considered for evidence synthesis. An indication for BCG treatment was found in non-stromal invasive stages (Tis pu, Tis pd) and in stromal infiltrating cases (T1) of primary and secondary PUC when transitional cell carcinoma was the histology of origin. Studies including patients treated with TURP before BCG showed a better local response in the prostatic urethra with a higher disease free survival (DFS) (80–100% vs. 63–89%) and progression free survival (PFS) (90–100% vs. 75–94%) than patients in studies in which no TURP was performed. However, this difference in recurrence and progression in the prostate neither affected the total PFS (57–75% vs. 58–93%), nor the disease specific survival (70–100% vs. 66–100%). The use of resection loop biopsies of the prostatic urethra in appropriate cases during the primary work-up for suspected PUC, as well as the use of the current TNM classification for PUC, need to be improved. BCG therapy for non-stromal invasive stages of PUC show a good local response. Local response is further improved by a TURP before BCG therapy, although the overall prognosis does not seem to be affected. Further evidence for BCG treatment in the rare cases of stromal invasive PUC is needed. Specific side effects of BCG treatment for PUC are not reported.

Hip fracture caused by fall is a common injury of the elderly. The risk of sustaining a contralateral hip fracture has been reported to be 5–10%. Aging society heightens the need of efficient prevention tools. To be able to cope with this demand, understanding of biomechanics of hip fractures are mandatory. Previous studies suggest that geometry of the proximal femur could play an important role for fracture probability and fracture type. Thus, analysis of hip geometry could play an important role in the prediction and prevention of bilateral hip fractures. Aim of this study was to elucidate the influence of caput collum diaphyseal angle on the fracture type of proximal femur.

There is growing body of evidence from retrospective studies that renin-angiotensin system (RAS) blockade is associated with improved outcome after transcatheter aortic valve replacement (TAVR). However, it remains unknown whether the effect of RAS blockade is dose dependent. The current study sought to assess the dose-dependent effect of RAS blockade on survival and left-ventricular (LV) remodelling after TAVR.

Die Geschichte des Instituts für Informationswissenschaft an der Universität Graz in Österreich von seiner Gründung 1987 bis zur Fusionierung mit anderen Instituten im Jahr 2020 wird beschrieben und mit Daten aus bibliometrischen Analysen der Publikationen ergänzt. Abschließend wird ein Ausblick auf die Einbindung der Informationswissenschaft in neue Studienangebote gegeben.

Supported lipid bilayers (SLBs) are a very popular system for the study of biomimetic membranes. Understanding of the interactions between the solid substrate and the lipid membrane opens pathways to the design of new materials with fine-tunable properties. While it is possible to study SLBs via molecular dynamics (MD) simulations, difficulties still remain for these strategies; in particular, the confined water layer thickness and structure are difficult to reproduce in simulations. We have explored different coarse-grained (CG) models for the membrane/support interaction, and their impact on the substrate hydration level. Our results highlight the relevance of including long-range interactions in CG-MD simulations of fluid SLBs. Modeled neutron reflectivity curves are deduced from the structures obtained by molecular simulations, and substrate parameters are optimized to match the experimental and modeled reflectivity curves. We expect our coarse-grained approach to open new perspectives for the simulations of SLBs of increasing complexity, including lipid layers of complex compositions, or adsorbed lipidic layers on patterned surfaces.

Contrast-enhanced ultrasound (CEUS) has the potential to be a valuable alternative to contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMR), the current gold standards in characterisation of renal masses.

Primary urethral carcinoma (PUC) is a rare cancer accounting for <1% of all genitourinary malignancies.

Juvenile steelhead Oncorhynchus mykissenter the northern California Current ecosystem from the Columbia River and other Pacific Northwest coastal rivers and include several populations that are listed under the U.S. Endangered Species Act. However, relatively little is known about the response of these populations to interannual variability in ocean conditions. In 2015 and 2016, anomalous ocean conditions, called the warm “Blob,” persisted in the northern California Current, increasing ocean temperatures by over 2.5°C. To determine how steelhead respond to such major shifts in temperature, we compared diet composition, stomach fullness, size, and body condition of juvenile steelhead collected in 2015 and 2016 to those of a subset of steelhead collected in previous surveys (2001, 2002, 2004, and 2006–2011) that included warm, cool, and neutral ocean years. In addition, we used bioenergetics models to assess the importance of the marine environment in contributing to changes in steelhead condition under different ocean temperature scenarios. Steelhead from 2015 and 2016 exhibited some of the poorest body condition values but were the largest sizes across all years evaluated. Steelhead diet composition varied between warm and cold years and between warm and average years, with steelhead consuming more insects, juvenile rockfishes, and rare and unidentified fish in warm years. Unusual taxa, including gelatinous salps (2015 and 2016) and juvenile smelts (2016), were consumed during Blob‐influenced years. Bioenergetics models indicated that interannual variability in growth was influenced by changes in temperature and feeding conditions in the marine environment, with significant differences in growth between warm and cold ocean years apparent as early as day 2 of the simulated marine residence. These findings highlight the potential for warm ocean years to influence the diet composition and morphology of Columbia River steelhead populations and may lead to a better understanding of factors influencing survival of juvenile steelhead during early marine residence.

In bladder cancer patients treated with radical cystectomy (RC), controversy exists regarding the impact of the annual hospital volume (HV) and/or surgeon volume (SV) on oncological outcomes and quality of care.

When organizations create new knowledge and work practices as a reaction to challenges they face, they often have difficulty to adopt these new practices “on the ground”. One of the reasons is that in these cases, individual informal learning and collective knowledge creation are often insufficiently connected. In this paper, we investigate knowledge practices that explain how new knowledge generated in the process of creating and adapting new practices is applied in work situations. We conducted 30 semi-structured interviews in five networks of organizations focusing on knowledge sharing in the German construction industry. Through a qualitative content analysis, we first identified five patterns of situations where individual and collective knowledge interact to implement new work practices. We detail these patterns with four knowledge maturation practices that explain how individuals contribute to collective knowledge development, and three scaffolding practices that explain how individual learning processes are facilitated through help seeking and guiding. Four practices of knowledge appropriation explain how knowledge is adapted and validated in concrete work situations. We combine scaffolding, maturation and appropriation practices into a model of knowledge appropriation that extends workplace learning research by offering a distinctive perspective on the practices that shape the interaction between knowledge creation and individual learning.

Background: Although reported results on short stems sound very promising, the occurrence of distal femoral cortical hypertrophy is often observed. The aim of the present study was to report 5-year survival data of a commercially available trochanter sparing short stem and investigate the clinical impact of distal femoral cortical hypertrophy on the outcome.Methods: 123 total hip arthroplasties were performed on 120 patients from April 2008 to May 2010 (mean age 62, range 29–89 years; 71 hips from male patients, 58%). Clinical and radiological data were collected preoperative, at 6 weeks, 1, 2, 3, and 5 years postoperative to assess the outcome. Radiographs taken immediately postoperative as well as 1 and 5 years postoperative were used to identify and assess cortical hypertrophy.Results: 1 stem had to be revised due to aseptic loosening, resulting in a Kaplan-Meier survival analysis with endpoint for stem revision of 99.2% (95% Confidence Interval 94.1–99.9) at 5 years. 96 radiological and 95 clinical follow-ups were analysed 5 years postoperative. 68 (71%) hips showed distal femoral cortical hypertrophy after 5 years. The average Harris Hip Score and Oxford Hip Score improved 33 (standard deviation (SD) 15.1, range 2–70), 18 (SD 12.1, range -10–43) points, respectively. Overall 16% of the patients reported thigh pain, unrelated to the presence of cortical hypertrophy.Discussion: This short stem shows an excellent 5-year survival rate and good clinical outcome despite a high incidence of cortical hypertrophy. However, the question of the mechanism of load transfer arises.

Research in behavioral and experimental finance becomes more multifaceted and the analysis of data from speech interactions more important. This raises the need for technical support for researchers using qualitative data generated from speech interactions. aTrain serves this need and is an open-source, offline transcription tool with a graphical interface for audio data in multiple languages. It requires no programming skills, runs on most computers, operates without internet, and ensures data is not uploaded to external servers. aTrain combines OpenAI’s Whisper transcription models with speaker recognition and provides output that integrates with MAXQDA and ATLAS.ti. Available on the Microsoft Store for easy installation, its source code is also accessible on GitHub. aTrain, designed for speed on local computers, transcribes audio files at 2-3 times the audio duration on mobile CPUs using the highest-accuracy Whisper transcription models. With an entry-level graphics card, this speed improves to 30% of the audio duration.

Metastasis is a main cause of death in prostate cancer (PCa). To dissect the molecular cues from cancer cell–microenvironment interaction that drive metastatic cascade, bone metastatic PCa cells were intravenously implanted into zebrafish embryos and mice tibia forming metastatic lesions. Transcriptomic analysis showed an elevated expression of stemness genes, pro-inflammatory cytokines and TGF-β family member Activin A in the cancer cells at metastatic onset in both animal models. Consistently, analysis of clinical datasets revealed that the expression of Activin A is specifically elevated in metastases and correlates with poor prognosis in stratified high-risk PCa patients. It is further unveiled that the microenvironment induced Activin A expression by NF-κB activation. The elevated level of Activin A enhanced the invasive ALDHhiCSC-like phenotypes and PCa proliferation by activation of Smad and ERK1/2 signaling driving metastasis. Suppression of Activin A or Activin receptor significantly reduced the CSC-like subpopulation, invasion, metastatic growth, and bone lesion formation in zebrafish and mice xenografts, suggesting a functional role of NF-κB-dependent Activin A in PCa metastasis. Overall, our study demonstrates that human PCa cells can display a comparable response with the microenvironment in zebrafish and mice xenografts. Combining both animal models, we uncovered the microenvironment-dependent activin signaling as an essential driver in PCa metastasis with therapeutic potential.

Das „akute Skrotum“ ist ein Sammelbegriff für verschiedene Erkrankungen der Skrotalregion. Definierend sind plötzlich auftretende Schmerzen, Rötung und Schwellung im Bereich des Skrotums, meist einseitig. Zudem können die lokalen Beschwerden von Allgemeinsymptomen wie Übelkeit und Erbrechen begleitet sein. Als Ursache können mechanische, entzündliche, tumoröse oder traumatische Prozesse in Frage kommen. Es gilt, rasch adäquate diagnostische Abklärungen einzuleiten, um eine klinische Abwägung der Differenzialdiagnosen vornehmen zu können. Aufgrund der drohenden irreversiblen Parenchymschäden bei kurzer Ischämietoleranz muss insbesondere eine Hodentorsion ausgeschlossen werden. Im Zweifelsfall ist eine operative Freilegung des betroffenen Hodens einzuleiten. Das akute Skrotum ist deshalb immer als Notfall zu betrachten. Ziel dieses Artikels ist es, einen Überblick über die möglichen zugrunde liegenden Ätiologien zu vermitteln, um das diagnostische und therapeutische Vorgehen beim akuten Skrotum in der Hausarztpraxis zu strukturieren.

Starting out with a brief overview of recent TV series that feature complex and complicated female characters – or, as we call them, ‘difficult women’ – this introduction investigates the changing manner in which women have been represented on TV in previous decades. Demonstrating that especially TV shows of the 2010s undermine and work against traditional and stereotypical portrayals of women on TV and instead establish feminist discourses, we argue that this time period can be defined as a pivotal moment with regard to changing representations of women on TV. Using Netflix’s Orange Is the New Blackas an example, we also show that TV series that feature difficult women make use of the very techniques and conventions of what Jason Mittell has described as ‘Complex TV’ in order to consciously engage with questions of female representation on TV and to create a feminist discourse that works against sexist tropes and stereotypes.

Nebenniereninzidentalome sind insgesamt seltene Befunde, welche je nach initialem Befund (Hounsfield-Einheiten, Größe) weitergehende Abklärungen brauchen oder nicht. Bei einer Größe <4 cm und <10 Hounsfield-Einheiten in der nativen Computertomographie (CT) ist eine weitergehende Abklärung oder Nachsorge nicht notwendig. Alle anderen Befunde brauchen eine weitergehende Abklärung, welche je nach klinischer Präsentation auch die Abklärung der endokrinologischen Aktivität beinhaltet. Patienten sollten einem Dexamethasone-Supressionstest, einer Metanephrin- und Katecholaminbestimmung im Plasma oder Urin und Patienten mit einer arteriellen Hypertonie einem Aldosteron-Renin-Quotienten unterzogen werden. Ist die Bildgebung nicht konklusiv, ist eine weitergehende Abklärung mittels Kontrastmittel-CT, Magnetresonanztomographie oder PET-CT zu erwägen. Anhand der dann vorliegenden Untersuchungsresultate sollte die weitere Behandlung/Therapie an einem interdisziplinären Tumorboard besprochen und festgelegt werden. Les incidentalomes surrénaliens sont globalement rares et peuvent exiger ou non des investigations plus poussées après les constats initiaux (unités Hounsfield, dimensions de la tumeur). Une tumeur de <4 cm avec une densité de <10 unités Hounsfield n’exige ni des investigations plus approfondies, ni des examens de suivi. Tous les autres constats exigent des investigations approfondies comprenant aussi, selon les constats cliniques, une vérification de l’activité endocrinologique. Il faut soumettre les patients à une épreuve de suppression à la dexaméthasone, déterminer leurs taux de métanéphrines et de catécholamines dans le plasma ou l’urine et, chez les patients présentant une hypertension artérielle, déterminer le quotient aldostérone-rénine. Si l’imagerie n’est pas concluante, on envisagera des examens plus poussés par tomodensitométrie avec produit de contraste, par IRM ou par TEP-TDM. Dans le cadre d’un tumorboard interdisciplinaire, les résultats d’examen obtenus doivent alors servir de base à la discussion et définition de la marche à suivre pour le traitement.

We investigate the consequences of lipid peroxidation on the permeation properties of membranes comprising unsaturated lipid molecules by means of coarse-grained molecular simulations. After discussion on the impact of peroxidation on the properties of lipid bilayers such as stretching modulus, area per lipid, water permeation, and the distributions of various lipid components across the membrane, we focus in particular on the effect of peroxidation on the passive translocation of small nanoparticles of varying hydrophobicity across lipid bilayers. We consider two types of oxidized lipid bilayers which differ in their degree of peroxidation using a schematic model for the oxidized beads. Consistently with our previous work for nonoxidized lipid bilayers, we find a narrow window of translocation of the nanoparticles when their hydrophobicity is varied. Our studies suggest that oxidized lipid bilayers feature a more hydrophilic environment and strongly enhance the translocation rate of small nanoparticles without the formation of pores. Furthermore, an optimal permeation rate is found for peroxidized membranes, associated with more hydrophilic nanoparticles than that in the case of nonoxidized lipid bilayers. Strategies for targeting peroxidized lipid membranes in a more specific way are discussed in the light of our findings.