Showing papers by "Linköping University published in 2023"

Moderate alcohol consumption is associated with significant fibrosis progression in NAFLD

Abstract: The effect of moderate alcohol consumption on NAFLD histology is disputed. Assessment of alcohol consumption is commonly performed with interview or questionnaires. Phosphatidylethanol (PEth) in blood is a highly sensitive and specific alcohol biomarker, which only forms in the presence of ethanol. PEth has hitherto not been evaluated in longitudinal NAFLD studies. This study aimed to examine the impact of moderate alcohol consumption on histologic progression and evaluate the utility of PEth in NAFLD. NAFLD patients with serial biopsies were reviewed for inclusion in the study. At baseline, all patients reported alcohol consumption <140 g/week. Anthropometric and biochemical measurements were performed at baseline and follow-up. Alcohol consumption was assessed thoroughly at follow-up with clinical interview, the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) questionnaire, and analysis of PEth in whole blood. Eighty-two patients were included. Mean follow-up time was 17.2 years (SD±6.0). Patients with significant fibrosis progression (defined as progression of ≥2 stages or development of cirrhosis-related complications) reported higher alcohol consumption and had significantly higher PEth. Consumption >66-96 g/week (but <140 g) (i.e. moderate alcohol consumption) was associated with increased risk of significant fibrosis progression compared with no or low consumption. PEth ≥48 ng/mL and binge drinking showed the highest risk for significant fibrosis progression (aOR: 5.9; 95% CI: 1.6-21.4) and aOR: 5.1; 95% CI: 1.4-18.1, respectively). NAFLD patients consuming moderate amounts of alcohol are at increased risk for significant fibrosis progression and development of cirrhosis-related complications. PEth is a potential biomarker to assess harmful alcohol consumption in NAFLD. Patients reporting moderate consumption or exhibiting PEth ≥48 ng/mL should be advised to reduce alcohol consumption.

Sounding others’ sensations in interaction

Abstract: This study investigates the practice of “sounding for others,” wherein one person vocalizes to enact someone else’s putatively ongoing bodily sensation. We argue that it constitutes a collaborative way of performing sensorial experiences. Examples include producing cries with others’ strain or pain and parents sounding an mmm of gustatory pleasure on their infant’s behalf. Vocal sounds, their loudness, and duration are specifically deployed for instructing bodily experiences during novices’ real-time performance of various activities, such as tasting food for the first time or straining during a Pilates exercise. Vocalizations that are indexically tied to the body provide immediate displays of understanding and empathy that may be explicated further through lexicon. The existence of this practice challenges the conceptualization of communication as a transfer of information from an individual agent – even regarding assumedly individual body sensations – instead providing evidence of the joint nature of action and supporting dialogic theories of communication, including when language-marginal vocalizations are used.

Role of ventral subiculum neuronal ensembles in incubation of oxycodone craving after electric barrier–induced voluntary abstinence

Abstract: High relapse rate is a key feature of opioid addiction. In humans, abstinence is often voluntary due to negative consequences of opioid seeking. To mimic this human condition, we recently introduced a rat model of incubation of oxycodone craving after electric barrier–induced voluntary abstinence. Incubation of drug craving refers to time-dependent increases in drug seeking after cessation of drug self-administration. Here, we used the activity marker Fos, muscimol-baclofen (GABAa + GABAb receptor agonists) global inactivation, Daun02-selective inactivation of putative relapse-associated neuronal ensembles, and fluorescence-activated cell sorting of Fos-positive cells and quantitative polymerase chain reaction to demonstrate a key role of vSub neuronal ensembles in incubation of oxycodone craving after voluntary abstinence, but not homecage forced abstinence. We also used a longitudinal functional magnetic resonance imaging method and showed that functional connectivity changes in vSub-related circuits predict opioid relapse after abstinence induced by adverse consequences of opioid seeking.

Speed-resolved perfusion imaging using multi-exposure laser speckle contrast imaging and machine learning

Abstract: Laser speckle contrast imaging (LSCI) gives a relative measure of microcirculatory perfusion. However, due to the limited information in single-exposure LSCI, models are inaccurate for skin tissue due to complex effects from e.g. static and dynamic scatterers, multiple Doppler shifts, and the speed-distribution of blood. It has been demonstrated how to account for these effects in laser Doppler flowmetry (LDF) using inverse Monte Carlo (MC) algorithms. This allows for a speed-resolved perfusion measure in absolute units %RBC × mm/s, improving the physiological interpretation of the data. Until now, this has been limited to a single-point LDF technique but recent advances in multi-exposure LSCI (MELSCI) enable the analysis in an imaging modality.To present a method for speed-resolved perfusion imaging in absolute units %RBC × mm/s, computed from multi-exposure speckle contrast images.An artificial neural network (ANN) was trained on a large simulated dataset of multi-exposure contrast values and corresponding speed-resolved perfusion. The dataset was generated using MC simulations of photon transport in randomized skin models covering a wide range of physiologically relevant geometrical and optical tissue properties. The ANN was evaluated on in vivo data sets captured during an occlusion provocation.Speed-resolved perfusion was estimated in the three speed intervals 0 to 1 mm/s , 1 to 10 mm/s , and >10 mm/s , with relative errors 9.8%, 12%, and 19%, respectively. The perfusion had a linear response to changes in both blood tissue fraction and blood flow speed and was less affected by tissue properties compared with single-exposure LSCI. The image quality was subjectively higher compared with LSCI, revealing previously unseen macro- and microvascular structures.The ANN, trained on modeled data, calculates speed-resolved perfusion in absolute units from multi-exposure speckle contrast. This method facilitates the physiological interpretation of measurements using MELSCI and may increase the clinical impact of the technique.

Leadership and well-being of employees in the Nordic countries: A literature review

Abstract: There is a need for more knowledge regarding the importance of managerial leadership for fostering well-being in the workplace and how context has been accounted for in previous research.To carry out a literature review of previous research that empirically examines the importance of leadership for well-being in a Nordic working life context.A rapid literature review was conducted with narrative analysis in 5 steps: establish focus, research questions, and inclusion criteria; literature search; relevance screening; quality assessment; data analysis. The search identified 4566 unique studies where 35 quantitative and five qualitative met the relevance and quality criteria.Findings from quantitative and qualitative studies are presented. Transformational and supportive leadership are recurrently associated with employee well-being, although the qualitative studies also highlight adaptive leadership and leaders being available and providing space. Some connections are made to the Nordic context in the reviewed studies, but these connections are not fully elaborated.Leadership is related to employee well-being, although this relationship seems to be indirect, mediated by other factors in the working environment. The review identifies the need for more well-designed studies addressing the contextual factors of this relationship, and how leadership should be exercised in practice.

Social Touch Reduces Pain Perception—An fMRI Study of Cortical Mechanisms

Abstract: Unmyelinated low-threshold mechanoreceptors (C-tactile, CT) in the human skin are important for signaling information about hedonic aspects of touch. We have previously reported that CT-targeted brush stroking by means of a robot reduces experimental mechanical pain. To improve the ecological validity of the stimulation, we developed standardized human–human touch gestures for signaling attention and calming. The attention gesture is characterized by tapping of the skin and is perceived as neither pleasant nor unpleasant, i.e., neutral. The calming gesture is characterized by slow stroking of the skin and is perceived as moderately to very pleasant. Furthermore, the attention (tapping) gesture is ineffective, whereas the calming (stroking) gesture is effective in activating CT-afferents. We conducted an fMRI study (n = 32) and capitalized on the previous development of touch gestures. We also developed an MR compatible stimulator for high-precision mechanical pain stimulation of the thenar region of the hand. Skin-to-skin touching (stroking or tapping) was applied and was followed by low and high pain. When the stroking gesture preceded pain, the pain was rated as less intense. When the tapping gesture preceded the pain, the pain was rated as more intense. Individual pain perception related to insula activation, but the activation was not higher for stroking than for tapping in any brain area during the stimulation period. However, during the evaluation period, stronger activation in the periaqueductal gray matter was observed after calming touch compared to after tapping touch. This finding invites speculation that human–human gentle skin stroking, effective in activating CT-afferents, reduced pain through neural processes involving CT-afferents and the descending pain pathway.

Raw or Cooked? Object Detection on RAW Images

Abstract: Images fed to a deep neural network have in general undergone several handcrafted image signal processing (ISP) operations, all of which have been optimized to produce visually pleasing images. In this work, we investigate the hypothesis that the intermediate representation of visually pleasing images is sub-optimal for downstream computer vision tasks compared to the RAW image representation. We suggest that the operations of the ISP instead should be optimized towards the end task, by learning the parameters of the operations jointly during training. We extend previous works on this topic and propose a new learnable operation that enables an object detector to achieve superior performance when compared to both previous works and traditional RGB images. In experiments on the open PASCALRAW dataset, we empirically confirm our hypothesis.

The importance of neighborhood size for the study of white Flight and ethnic residential segregation

Abstract: The concept of “neighborhood” is crucial for ethnic residential segregation, but it is highly unclear what spatial unit the concept refers to when studying white flight. This paper asks at what distance from home in the neighborhood ethnic minorities prompt white flight. Based on Swedish registry data for Stockholm County (1998-2017), I find that white flight is mostly observed following growth in minorities’ presence within 300 meters from home, and that growth occurring farther prompt virtually no out-mobility. I show that white flight dynamics are abruptly more likely to occur once minorities’ share in the residential area most proximate to home surpasses 10%, reaching a maximum when the share is between 15-20%.

Improved Multimer Prediction using Massive Sampling with AlphaFold in CASP15

Abstract: AlphaFold has transformed structure prediction by enabling highly accurate predictions on par with experimentally determined structures. Still, for difficult cases, in particular, multimers, there is still room for improvement. Important for the success of AlphaFold is its ability to assess its own predictions. The basic idea for the Wallner group in CASP15 was to exploit the excellent ranking score in AlphaFold by massive sampling. To this end, we ran AlphaFold using six different settings, with and without templates, and with an increased number of recycles using both multimer v1 and v2 weights. In all cases, the dropout layers were enabled at inference to sample the uncertainty and increase the diversity of the generated models. A median of 4,810 models per target was generated and almost all (35/38) received a ranking_confidence > 0.7. Compared to other groups in CASP15, Wallner obtained the highest sum of Z-scores based on the DockQ score, 40.8 compared to 26.3 for the second highest, much higher than -0.2 achieved by the AlphaFold baseline method, NBIS-AF2-multimer. The improvement over the baseline is substantial with the mean DockQ increasing from 0.43 to 0.56, with several targets showing a DockQ score increase by +0.6 units. Remarkable, considering Wallner and NBIS-AF2-multimer were using identical input data. The reason for the success can be attributed to the diversified sampling using dropout with different settings and, in particular, the use of multimer v1, which seems to be much more susceptible to sampling compared to v2. The method is available here: http://wallnerlab.org/AFsample/.

Lifelong Learning, Migration, and Conditions for Inclusion

Abstract: In this chapter, we focus on the role of lifelong learning for the inclusion of migrants. We are specifically interested to understand how a country such as Sweden, with a long tradition of lifelong learning, creates conditions for inclusion of migrants at a time when major policy changes seriously challenge the historical foundations of the system itself. Our results indicate that a strong will for inclusion among participants and a strong will among teachers and circle leaders to support such wishes are important conditions for the inclusion of migrants. At the same time, there are conditions hindering inclusion such as overly-strong demands for the level of language knowledge needed, the responsibilization of migrants in terms of learning the language, participants’ previous educational and social background, as well as the challenges for migrants to get to know Swedes. These findings are discussed in relation to policy changes in Sweden as well as the other Nordic countries, where there has been a move toward more restrictive migration politics as well as increased market orientation of adult education. We argue that the historical legacy of adult education in Sweden and the current strong state support are important factors that manage to partly counter the current policy shifts.

Limited Association between Antibodies to Oxidized Low-Density Lipoprotein and Vascular Affection in Patients with Established Systemic Lupus Erythematosus

Abstract: Patients with systemic lupus erythematosus (SLE) are at an increased risk of cardiovascular disease. We aimed to evaluate whether antibodies to oxidized low-density lipoprotein (anti-oxLDL) were associated with subclinical atherosclerosis in patients with different SLE phenotypes (lupus nephritis, antiphospholipid syndrome, and skin and joint involvement). Anti-oxLDL was measured by enzyme-linked immunosorbent assay in 60 patients with SLE, 60 healthy controls (HCs) and 30 subjects with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Intima-media thickness (IMT) assessment of vessel walls and plaque occurrence were recorded using high-frequency ultrasound. In the SLE cohort, anti-oxLDL was again assessed in 57 of the 60 individuals approximately 3 years later. The levels of anti-oxLDL in the SLE group (median 5829 U/mL) were not significantly different from those in the HCs group (median 4568 U/mL), while patients with AAV showed significantly higher levels (median 7817 U/mL). The levels did not differ between the SLE subgroups. A significant correlation was found with IMT in the common femoral artery in the SLE cohort, but no association with plaque occurrence was observed. The levels of anti-oxLDL antibodies in the SLE group were significantly higher at inclusion compared to 3 years later (median 5707 versus 1503 U/mL, p < 0.0001). Overall, we found no convincing support for strong associations between vascular affection and anti-oxLDL antibodies in SLE.

Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation

Abstract: Childhood maltreatment (CM) is a risk factor for substance use disorders (SUD) in adulthood. Understanding the mechanisms by which people are susceptible or resilient to developing SUD after exposure to CM is important for improving intervention. This case-control study investigated the impact of prospectively assessed CM on biomarkers of endocannabinoid function and emotion regulation in relation to the susceptibility or resilience to developing SUD. Four groups were defined across the dimensions of CM and lifetime SUD (N = 101 in total). After screening, participants completed two experimental sessions on separate days, aimed at assessing the behavioral, physiological, and neural mechanisms involved in emotion regulation. In the first session, participants engaged in tasks assessing biochemical (i.e., cortisol, endocannabinoids), behavioral, and psychophysiological indices of stress and affective reactivity. During the second session, the behavioral and brain mechanisms associated with emotion regulation and negative affect were investigated using magnetic resonance imaging. CM-exposed adults who did not develop SUD, operationally defined as resilient to developing SUD, had higher peripheral levels of the endocannabinoid anandamide at baseline and during stress exposure, compared to controls. Similarly, this group had increased activity in salience and emotion regulation regions in task-based measures of emotion regulation compared to controls, and CM-exposed adults with lifetime SUD. At rest, the resilient group also showed significantly greater negative connectivity between ventromedial prefrontal cortex and anterior insula compared to controls and CM-exposed adults with lifetime SUD. Collectively, these peripheral and central findings point to mechanisms of potential resilience to developing SUD after documented CM exposure.

Camera Calibration Without Camera Access - A Robust Validation Technique for Extended PnP Methods

Abstract: A challenge in image based metrology and forensics is intrinsic camera calibration when the used camera is unavailable. The unavailability raises two questions. The first question is how to find the projection model that describes the camera, and the second is to detect incorrect models. In this work, we use off-the-shelf extended PnP-methods to find the model from 2D-3D correspondences, and propose a method for model validation. The most common strategy for evaluating a projection model is comparing different models’ residual variances—however, this naive strategy cannot distinguish whether the projection model is potentially underfitted or overfitted. To this end, we model the residual errors for each correspondence, individually scale all residuals using a predicted variance and test if the new residuals are drawn from a standard normal distribution. We demonstrate the effectiveness of our proposed validation in experiments on synthetic data, simulating 2D detection and Lidar measurements. Additionally, we provide experiments using data from an actual scene and compare non-camera access and camera access calibrations. Last, we use our method to validate annotations in MegaDepth.

Agent-Based Simulation and Ontology Integration for System-of-System Exploration

Abstract: The increasing interest in System-of-Systems (SoS) for engineering applications are introducing new challenges that must be overcome at an early design stage. One of these is the integration of different tools that can be used to make predictions about a system under development and how these together can be used to predict SoS performances by comparison of parameter spaces. The purpose of this paper is therefore to illustrate how different SoS architectures can be modeled, simulated, and evaluated throughout different scenarios by different teams of researchers following a common workflow. An ontology is used as an overarching knowledge base where information about entities, such as scenario details, can be extracted and used for the setup of Agent-based Simulations (ABS) through a tool integration software acting as master that controls the correct execution of the defined workflow. The tool integration software also enables additional modelling capabilities, such as a Design of Experiments (DOE) definition for design space explorations, an Optimizer with different algorithms, user-defined Python scripts, etc.

Measuring intestinal permeability in celiac disease ex vivo, using Ussing chambers

Abstract: Multicellular organisms need epithelial barriers to remain compartmentalized and protected from external influences. Although much progress has been made in understanding barrier integrity disruption in Celiac disease (CD), the regulatory and genetic mechanisms underlying the increased intestinal epithelial flux are still unknown. As we learn more about the regulation of permeability in homeostasis and pathogenesis, we will be able to develop strategies to strengthen the epithelial barrier function in intestinal disorders, including CD. For this purpose, Ussing chambers are increasingly used in native tissue, such as gut mucosa or cell monolayers, to assess the integrity of the barrier. In particular, the Ussing chambers allow the measurement of paracellular and transcellular parameters of CD small intestinal biopsies under physiologically specific conditions. In diverse types of diseases, this method is commonly used to determine epithelial barrier defects, but its application to CD has not yet been widely expanded. To provide a great model of barrier ex vivo studies in CD, we facilitate a standard protocol to measure paracellular and transcellular permeability using the Ussing chamber.

Investigating the agreement between methods of different precision

Abstract: Abstract Background Agreement between measurement methods is commonly investigated by a so-called Bland-Altman plot which, among other things, shows if the difference between the methods is independent of the size of the measurement. However, such analysis assumes that both methods have the same precision. If not, the plot may show a false trend caused by the difference in precision and not by an actual dependence on the size of the measurement. To solve this problem, we suggest a modification of the Bland-Altman plot such that the differences are plotted against an inverse-variance weighted average of the measurements rather than their mean. Methods We show analytically that the proposed modification indeed removes the linear bias component caused by differences in within-subject variance between the methods. We also illustrate the effects of true linear dependency and differences in precision on Bland-Altman plots of synthetic data with and without the proposed modification. Finally, we show the effect of this modification on real data with a significant difference in within-subject variance between the methods. Results In contrast to the standard Bland-Altman analysis, the slope of the bias in the synthetic data was correctly estimated by the proposed method. On real data, the linear trend observed in the standard Bland-Altman plot was almost completely removed with the proposed method. Conclusions This study shows that the proposed modification of the Bland-Altman analysis removes the false trends caused by differences in precision between the two methods when investigating their agreement.

AI for Climate Adaptation?

Abstract: In October 2021, the Swedish Meteorological and Hydrological Institute launched a novel national system for impact-based weather warnings, moving from the traditional format for meteorological, hydrological, and oceanographic warnings towards an assessment process that includes collaboration and consultation with regional stakeholders on the impacts that certain weather events would have for a specific geographic area and time frame. As part of this new system, local and regional administrative efforts are made to create assessment-support documentation drawing on local knowledge and providing support ahead of and during extreme weather events. We present initial results from the ongoing research project &#8216;AI4ClimateAdaptation&#8217; (https://liu.se/en/research/ai4climateadaptation), which explores the potential of employing AI-based image and text analysis to support the process and evaluate the precision of impact-based weather warnings. The project collects image and text data appropriate for subsequent use in AI-based analysis from citizen science campaigns and social media. The presentation focuses on the concept of integrating AI-based text and image analysis with the processes of the warning system, as well as the barriers and enablers that are identified by local, regional, and national stakeholders related to the role of AI in weather warning systems. We further discuss to what extent data and knowledge on historical extreme weather events can be integrated with local and regional climate adaptation efforts, and whether these efforts could bridge the divide between long-term adaptation strategies and short-term response measures related to extreme weather events. The results of this study are expected to contribute to the national system for impact-based weather warnings and to increase resilience to extreme climate-related weather events.

Multi‐Source Mapping of Peatland Types Using Sentinel‐1, Sentinel‐2, and Terrain Derivatives—A Comparison Between Five High‐Latitude Landscapes

Abstract: Mapping wetland types in northern-latitude regions with Earth Observation (EO) data is important for several practical and scientific applications, but at the same time challenging due to the variability and dynamic nature in wetland features introduced by differences in geophysical conditions. The objective of this study was to better understand the ability of Sentinel-1 radar data, Sentinel-2 optical data and terrain derivatives derived from Copernicus DEM to distinguish three main peatland types, two upland classes, and surface water, in five contrasting landscapes located in the northern parts of Alaska, Canada and Scandinavia. The study also investigated the potential benefits for classification accuracy of using regional classification models constructed from region-specific training data compared to a global classification model based on pooled reference data from all five sites. Overall, the results show high promise for classifying peatland types and the three other land cover classes using the fusion approach that combined all three EO data sources (Sentinel-1, Sentinel-2 and terrain derivatives). Overall accuracy for the individual sites ranged between 79.7% to 90.3%. Class specific accuracies for the peatland types were also high overall but differed between the five sites as well as between the three classes bog, fen and swamp. A key finding is that regional classification models consistently outperformed the global classification model by producing significantly higher classification accuracies for all five sites. This suggests for progress in identifying effective approaches for continental scale peatland mapping to improve scaling of e.g., hydrological- and greenhouse gas-related processes in Earth system models.

Transformations, trajectories and similarities of national production structures: a comparative fingerprinting approach

Abstract: This article proposes a network-analytical framework for the comparative study of national production structures in global production networks. Conceptualizing such structures as the networks of sectorial flows in nationally delineated components of multiregional input-output tables, the proposed heuristic extracts a structural profile that captures the up- and downstream prominence of economic sectors for a particular country and year. These ‘fingerprints’ of national production structures can subsequently be compared on a pairwise basis, providing novel ways to determine and compare the structural similarities, transformations, and trajectories of national economies in the global production regime.Two case studies exemplify the heuristic. The first applies clustering methods to explore spatiotemporal similarities for 40 countries over the 1995-2011 period. Based on such similarities, an analytically useful classification into 12 structural types is proposed. The second study addresses structural transformations and trajectories during EU’s eastern enlargement, finding significant structural change, yet minuscule East-West convergence.

The Mother Figure in the Surrealist Novel

Abstract: In the surrealist revolt against the state, the Church, and the family, the mother figure became a key target, both as custodian of bourgeois-patriarchal values and as symbol of Catholic doctrine. In works such as Georges Bataille’s Story of the Eye (1928), Salvador Dalí and Luis Buñuel’s L’age d’or (1930), and Joyce Mansour’s Jules César (1955), mothers are attacked and violated, suffering a fate similar to those of the detested mother figures in the fiction of the Marquis de Sade. Yet not all mothers in surrealist art and literature are portrayed in such unequivocally negative terms. Focusing on Leonor Fini’s Mourmour, conte pour enfants velus (1976) and Dorothea Tanning’s Chasm: A Weekend (2004), this chapter traces an alternative history of surrealist representations of the mother, one in which this figure is rendered more ambiguous and at times even invested with revolutionary potential. These novels, the chapter suggests, elaborate representations of maternity in critical dialogue with Freudian and Lacanian psychoanalysis. As such they resonate to some extent with the (largely contemporaneous) work of French feminist theorists such as Julia Kristeva, Luce Irigaray, and Hélène Cixous, in which the concept of maternity becomes configured as an alternative to the phallocentric symbolic order.

Ritande kan stödja barns och elevers lärande i naturvetenskap

Abstract: Att rita kan hjälpa barn att lära sig naturvetenskap och om hur bilder används inom naturvetenskapen. Forskare har undersökt hur lärare genomför aktiviteter där barn och elever i yngre åldrar får rita i den naturvetenskapliga undervisningen. Resultaten visar hur upplägget påverkar vilket lärande som blir möjligt. Att lärarens syfte, normer och det material som finns tillgängligt samspelar har betydelse för barns och elevers lärande.

Data from Fulvestrant-Mediated Attenuation of the Innate Immune Response Decreases ER&lt;sup&gt;+&lt;/sup&gt; Breast Cancer Growth &lt;i&gt;In Vivo&lt;/i&gt; More Effectively than Tamoxifen

Abstract: <div>Abstract<p>Although blocking estrogen-dependent signaling is a cornerstone of adjuvant treatment for breast cancer, 25% of patients experience recurrent disease. Stroma events including innate immune responses are key in cancer progression. How different estrogen receptor (ER)–targeting therapies, including the partial agonist tamoxifen and the pure antagonist fulvestrant, affect the tumor stroma has not yet been elucidated. Fulvestrant is used in only postmenopausal patients, and its effects in the presence of estradiol remain undetermined. Here we observe that fulvestrant decreases ER⁺ breast cancer growth compared with tamoxifen in the presence of physiologic levels of estradiol in human breast cancer in nude mice and in murine breast cancer in immune-competent mice. Fulvestrant significantly inhibited macrophage and neutrophil infiltration in both models. These effects were corroborated in a zebrafish model where fulvestrant inhibited neutrophil- and macrophage-dependent cancer cell dissemination more effectively than tamoxifen. A comprehensive analysis of 234 human proteins released into the cancer microenvironment by the cancer cells sampled via microdialysis <i>in vivo</i> revealed that 38 proteins were altered following both treatments; 25 of these proteins were associated with immune response and were altered by fulvestrant only. Compared with tamoxifen, fulvestrant significantly affected inflammatory proteins released by murine stroma cells. Importantly, <i>in vivo</i> microdialysis of human ER⁺ breast cancer revealed that the majority of affected proteins in murine models were upregulated in patients. Together, these results suggest that fulvestrant targets ER⁺ breast cancer more effectively than tamoxifen even in the presence of estradiol, mainly by attenuation of the innate immune response.</p>Significance:<p>These findings demonstrate novel effects of the pure antiestrogen fulvestrant in ER⁺ breast cancer and evaluate its effects under physiologic levels of estradiol, representative of premenopausal patients.</p></div>

A Figure of Merit for the Assessment of Electrification in Transport and Vehicle Applications

Abstract: The purpose of this study is to give an overview of the feasibility of electrification in different domains of vehicles for transportation and construction at a vehicle level. To achieve this an analytical framework for estimating the requirement domain in which a technology combination can be used in a system. Looking at key properties of technologies such as specific energy and power. This results in the definition of a figure of merit in the relationship between performance and cost. In this paper it is used on electric aircraft technologies, i.e., battery electric and hydrogen fuel cell aircraft, on heavy road vehicles and on work machines.