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Genomic characterization and preclinical model development. To expand the therapeutic options for Epithelioid Hemangioendothelioma
No full textEpithelioid hemangioendothelioma (EHE) is an ultra-rare vascular sarcoma marked by TAZ-CAMTA1 (~90%) or YAP-TFE3 (~5%) fusion, leading to Hippo pathway dysregulation. EHE clinical behavior ranges from indolent to highly aggressive, but no biomarkers are known to predict clinical outcome at disease onset. Conventional chemotherapy has limited effectiveness and new treatment options are needed, as well as novel biomarkers of aggressiveness. This PhD project was part of a more extended project focused on preclinical investigations on EHE and involved three tasks:
i) Model generation: 3D spheroids were successfully generated from an already available patient-derived EHE cell line, both in monoculture and in co-culture with fibroblasts, revealing novel insights into the poorly understood interplay between EHE cells and stromal components, as well as providing a platform for future pharmacological and functional studies.
ii) Investigation of novel biomarkers: analysis of two independent patient series revealed a statistically significant correlation between circulating levels of Growth/differentiation factor 15 (GDF-15) and EHE aggressiveness, supporting its potential role as prognostic biomarker. Preclinical data demonstrated that GDF-15 is secreted by EHE cells and its levels are reduced following sirolimus treatment, through a mechanism involving 4E eIF4E binding protein 1 (4E-BP1) and Activating Transcription Factor 4 and 5 (ATF4/5). Additionally, microRNA (miRNA) sequencing (miRNA-seq) analysis, validated by a custom-developed digital droplet PCR (ddPCR) workflow, identified distinct alterations in circulating miRNA profiles of EHE patients, particularly in higher aggressive cases, with the clinical potential to improve risk stratification at diagnosis.
iii) Design and preclinical evaluation of novel therapeutic strategies: in vitro pharmacological investigations uncovered novel potential therapeutic vulnerabilities of EHE, particularly involving the Hippo and mitogen-activated protein kinase (MAPK) signaling axes, their reciprocal interplay and their cross-talk with the mammalian or mechanistic target of rapamycin (mTOR) pathway
Making Sense of Loss
No full textThe concluding chapter pulls together the various forms of loss outlined throughout the book and the key themes emerging from the different authors’ interpretations of their significance and symbolism. Split into four thematic sections – loss as a motivator; loss as an obligatory component of the research process; loss as symbolic; and loss as legacy – it considers how loss is integral to criminology. Criminology is a discipline which ultimately has loss located at its philosophical and practical core – and how we therefore interpret and negotiate loss is of crucial importance, whether that be as students, academics and/or researchers. Yet loss also represents a vital aspect of the commodified criminological academic complex, and how we respond to the ethical challenges that this raises is equally important. The purpose of the book was to offer a voice to the voiceless and ensure their stories are told. In doing so we also made sure our own voices were not lost. Centring loss within theoretical and methodological conceptions, however, also offers a small opportunity to unite the criminological (sociological, anthropological, psychological and legal) community(s) which transcends the litany of theoretical differences and juxtapositions within the discipline(s)
‘The Cheese that Tastes Good and Does Good’: Corporate Social Responsibility and National Belonging in ICA’s Folke Cheese Initiative
No full textThis paper critically examines the Folke Initiative, a corporate social responsibility project launched by the Swedish supermarket retailer ICA in 2017 and linked to its hard cheese brand, Folke. Using a historical-archival approach to multimodal critical discourse analysis, the study traces the Initiative’s evolution across product development, launch and promotion, call to action, and impact, analysing social media campaigns, promotional videos, packaging, and websites. The analysis demonstrates how ICA constructs Folke as a symbol of national identity, embedding banal nationalist cues, familiar landscapes, and rural imagery, while linking consumption to collective responsibility and social good. While the Initiative foregrounds community engagement, sustainability, and national cohesion, it offers limited solutions to structural social and economic inequalities. Folke, thus, exemplifies how food packaging—and its associated promotional materials—can function as strategic instruments, aligning with Swedish social-democratic values while extending corporate influence over local communities. By presenting everyday consumption as a contribution to society, ICA positions itself as a socially responsible actor, even as the long-term efficacy of the Initiative remains uncertain. Overall, this case contributes new insights into the temporal evolution of CSR discourse, the multimodal construction of product-based social responsibility, and the national specificity of sustainability practices in the Swedish food retail sector
The problem of free will is child's play
No full textI argue that the essence of ‘free will’ is control, the ability to do otherwise and that this ability is an acquired skill: We can and do see people acquire it, as for example small children learn to play and to do all the other things that human agents characteristically do
High-throughput nuclear morphometric analysis for pig sperm quality assessment
No full textArtificial insemination (AI) is commonplace in commercial pig breeding, and as such, ensuring sperm sample quality is of utmost importance to avoid reduced farrowing rates and litter sizes. Here, we have used high-throughput nuclear morphometric analysis to compare pig sperm samples categorised as meeting the AI standard (AIS) or not meeting the AI standard (N-AIS) (50 vs. 44 samples from unique boars, respectively). We show that pig sperm nuclei are asymmetric, that samples contain phenotypic shape abnormalities that show continuous variation and that samples classed as N-AIS have more abnormally shaped sperm than AIS samples. This variation is not detected in conventional analysis. The specific phenotypes identified suggest the disruption of key aspects of spermiogenesis and indicate future avenues for improving pig sperm quality. Additionally, we find that the distribution and severity of abnormal sperm phenotypes were significantly associated with the day of semen collection, indicating that environmental factors may influence sperm morphology. High-throughput nuclear morphometric analysis therefore reveals significant differences in sperm head morphology between AIS and N-AIS pig sperm samples and has the potential to be further developed as a tool for sperm assessment both in the pig breeding industry and in other species
The ‘forum effect’: how does participation in online forums affect student retention and academic performance at a distance learning university?
No full textDistance learning universities use online asynchronous forums to engage students in course content and build student academic communities. This research uses a mixed-methods approach to provide new empirical and qualitative evidence on the impact of online forum participation on student retention and academic performance on an undergraduate Economics course at a distance learning university. Using inferential logit regression models, we find forum participation has a positive impact on the pass/distinction boundary but not on the pass/fail-resit boundary. Moreover, this study provides evidence of a significant positive effect of forum participation on retention. Encouraging students to post is important because there is a positive ‘forum effect’ regardless of whether the student initiates the post. We also find that the marginal benefit of forum posting is diminishing, implying that ‘nudging’ a student to post even a few times can have a positive impact on their retention, with the first post being most critical. Qualitative evidence from student interviewees suggests that the nature of the forum activities and time aspects are important factors influencing student motivation to participate. Based on these findings we create an ‘ideal recipe’ for forum activities that is most likely to elicit student participation and thus aid student retention
Molecular and pore-scale structure evolution in amorphous solid water
No full textThe pore structure of vapour deposited amorphous solid water (ASW) is of both fundamental interest and astrophysical importance, where the system's properties are believed to play a major role in processes such as star and planetary body formation. Here we report a comprehensive characterisation of D2O ASW in the temperature range of 20 to 180 K, using combined total and small-angle neutron scattering. Significant changes to the ice morphology are observed across the temperature range 100 to 150 K, whereby there is a significant loss of specific surface area and porosity; the transition of 3D to 2D dominated pore shapes and a general compaction of the ice. The initial structure of nanometer scale microporous islands with voids between them at low temperature evolves with annealing into compact islands with larger voids. Even past crystallisation, there is still porosity present until desorption due to persisting void volume
Prevalence and risk factors of early gestational diabetes mellitus (EGDM) in Indians: The STRiDE study
No full textAim
Gestational diabetes mellitus (GDM) is usually diagnosed between 24–28 weeks (late GDM, LGDM). When diagnosed before 20 weeks, it is termed early GDM (EGDM). This study aimed to assess the prevalence and risk factors of EGDM compared to LGDM in Asian Indian women.
Methods
STratification of Risk of Diabetes in Early pregnancy (STRiDE), a prospective cohort study recruited 3,070 pregnant women before 16 weeks gestation across seven antenatal clinics in South India. Of these, 2,703 underwent early screening using fasting plasma glucose (FPG). Women with normal FPG underwent an oral glucose tolerance test (OGTT) at 24–28 weeks. Participants were classified into EGDM (FPG 92–125 mg/dL), LGDM (FPG < 92 mg/dL and abnormal OGTT), and normal glucose tolerance (NGT). Prevalence and risk factors were analyzed using logistic regression.
Results
Prevalence of EGDM and LGDM were 21.5 % and 19.5 %, respectively. Compared to LGDM, EGDM women had higher early pregnancy weight (63.9 vs. 61.2 kg), BMI (25.8 vs. 25.0 kg/m2), HbA1c (5.3 % vs. 5.1 %), and previous history of GDM (8.5 % vs. 5.3 %). Previous history of GDM was associated with EGDM, whereas family history of diabetes was associated with LGDM risk.
Conclusions
Women with EGDM have a unique metabolic profile and different risk factors compared to those with LGDM
Aging-independent decrease of complex multi-spine boutons in hippocampal area CA1 after contextual fear conditioning
No full textLong-lasting synaptic changes enable memory storage and regulate recall in the brain. Our previous work established that generation of multi-innervated dendritic spines (MISs), spines with typically two excitatory presynaptic inputs, underlies hippocampal memory formation in aged, but not young mice. The identification of MIS generation was done by ultrastructural analysis in hippocampal CA1 stratum radiatum 24 h after contextual fear conditioning (CFC). However, our analysis did not consider multi-spine boutons (MSBs), which were recently shown to increase in complexity (complex MSBs are pre-synaptic boutons connecting with more than two post-synapses) at a later time point after CFC in young age. Therefore, we re-analyzed our three-dimensional electron microscopy images and show that, unexpectedly, MSB complexity, decreases in CA1 stratum radiatum 24 h after CFC. The decrease in MSB complexity occurred both in young and aged mice, indicating that aging has no impact on this synaptic change. Considering that complex MSBs link the activity of multiple postsynaptic neurons, we suggest that after CFC a decrease in MSB complexity may be required for specific memory recall
Human-centric security for smart homes: A scoping review
No full textSmart home technologies, like cameras, door locks, and speakers, are increasingly used in our everyday lives. However, their continuous data collection and internet connectivity pose various security risks. While research on smart home security has mainly focused on technological aspects, human experience and societal factors also play a crucial role. Various human and social factors, such as user experience with smart home devices, security design processes, and government regulations, are intertwined and influence each other, affecting smart home security. It is therefore important to understand and consider these interconnected factors in technology design to secure homes that contain increasingly connected devices. This scoping review provides an overview of current human-centered studies (N=102) on smart home security, which aims to help researchers and practitioners better navigate this field. We present a conceptual framework that outlines key challenges in ensuring smart home security with a synthesis of insights on contributing human factors. We then summarize general security design principles and map existing user-centred security approaches in smart homes, and highlight research directions for future investigation. Beyond mapping existing studies, the review reveals a growing emphasis on engaging multiple stakeholders, especially smart home users, in shaping human-centered security