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Enhancing neonatal immune responses with different vaccination strategies: Novel adjuvants and mucosal immunization.
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2026-10) Molina Estupiñan, Jenny Lorena; Stefanía P. Bjarnarson and Ingileif Jónsdóttir; Faculty of Medicine (UI); Læknadeild (HÍ); School of Health Sciences (UI); Heilbrigðisvísindasvið (HÍ)
Vaccination remains a cornerstone of global public health, significantly reducing mortality rates in infants and children. Despite substantial progress, infectious diseases continue to be a leading cause of death for children under five years of age, with 2.3 million fatalities occurring globally in the first month of life in 2022 alone. Many of these infections peak in incidence and severity during early infancy, before routine immunizations are initiated or can provide sufficient protection, highlighting the need for more effective preventive strategies in early life. Neonatal vaccination offers a promising approach by inducing immunity from birth and shortening this vulnerable period, supported by universal healthcare contact at delivery and thus high potential vaccination coverage, particularly in resource-limited settings. An ideal neonatal vaccine would offer a single-dose, needle-free immunization, eliciting immediate and long-lasting protection against multiple diseases. However, neonatal vaccination is challenged by the immaturity of the immune system, characterized by dampened innate responses, a Th2-biased T cell response profile, impaired germinal center (GC) formation, limited plasma cell survival and transient antibody (Ab) production, often resulting in suboptimal and short-lived immunity. Overcoming these limitations could be done with the development of safe and effective adjuvants and optimized immunization routes capable of inducing rapid and durable protective immune responses in early life. The overall aim of this thesis was to investigate how the route of immunization influences neonatal immune responses, with particular emphasis on intranasal (i.n.) versus subcutaneous (s.c.) vaccination, and how novel adjuvants modulate these responses to improve vaccine efficacy. Using a neonatal mouse model, we compared the effects of i.n. and s.c. administration with either mmCT or dmLT formulated with a pneumococcal conjugate vaccine, Pn1-CRM197, on serum Ab levels and Ab-secreting cells (ASCs) in the spleen and bone marrow (BM). Furthermore, we assessed the effects of immunization route, parenteral or mucosal administration, on the induction of B cell survival and activation receptors in the spleen, as well as plasma cell survival factors in the BM. Finally, we evaluated the dose-sparing capacity of the novel adjuvants mmCT, dmLT, CAF01 and CAF08b in comparison with the conventional adjuvant alum (aluminum hydroxide). Our focus was on primary neonatal Ab response, the persistence of ASCs and the protective capacity against two respiratory pathogens, Streptococcus pneumoniae and influenza virus. The results demonstrate that the route of immunization differentially shaped the kinetics of neonatal B cell activation and survival signaling. I.n. immunization induced earlier upregulation of BAFF-R, whereas s.c. immunization promoted earlier TACI expression and BAFF production which occurred at later time point following i.n. immunization, indicating distinct sequential programming of B cell survival and activation pathways. Despite these differences, i.n. and s.c. immunization with Pn1-CRM197 and mmCT or dmLT enhanced GC responses and persistence of vaccine-specific ASCs in BM. Notably, i.n. immunization accelerated plasmablast/plasma cell differentiation, increased BCMA expression, promoted earlier establishment of APRIL-rich BM plasma cell survival niches and enhanced the accumulation of vaccine-specific ASCs in the BM. Thus, these mechanistic changes translated into accelerated and sustained systemic and mucosal Ab responses, including persistent IgA production, while maintaining systemic IgG responses comparable to those induced by s.c. immunization. Together, these findings demonstrate that mucosal immunization accelerates neonatal B cell maturation and the establishment of long-lived humoral immunity by promoting the timely acquisition of key survival signals required for plasma cell differentiation and maintenance. In addition, the novel adjuvants mmCT, dmLT, CAF01 and CAF08b enabled substantial antigen dose sparing while maintaining protective immune responses against both pneumococcal and influenza antigens, although the magnitude of this effect depended on the vaccine. Collectively, this work demonstrates that rational selection of immunization routes and adjuvants can overcome key developmental limitations of neonatal immunity by promoting rapid B cell activation, durable plasma cell survival and long-lasting protective humoral immunity. In particular, i.n. immunization with Pn1-CRM197 and mmCT or dmLT enhanced systemic and mucosal humoral immune responses in the neonatal mouse model, highlighting the potential of mucosal vaccination with appropriate adjuvants as a promising strategy for accelerating protective immune responses early in life while simultaneously inducing systemic and mucosal immunity, providing important mechanistic and translational insights for the development of nextgeneration pediatric vaccines.
Verk
Advice to patients undergoing stem cell transplant : Content analysis of survivor peer support narratives
(2018-05-01) Symes, Yael R.; Barrington, Clare; Austin, Jane; Wu, Lisa M.; Fisher, Edwin B.; Rini, Christine; Department of Psychology
Hematopoietic stem cell transplant survivors often share advice with patients undergoing this difficult treatment. We content analyzed narratives written by 59 transplant survivors given the opportunity to share advice with patients. Analyses described categories of advice they shared and evaluated their perceptions of the helpfulness of advice they had received. We found nine advice categories and evidence for variation in their perceived helpfulness, especially for advice to “be your own advocate,” “have someone you can rely on,” and “think positive.” Findings suggest the need to investigate how seemingly innocuous advice can be unhelpful and potentially distressing to some patients.
Verk
Changes in Brain Structural Networks and Cognitive Functions in Testicular Cancer Patients Receiving Cisplatin-Based Chemotherapy
(2017-12-01) Amidi, Ali; Hosseini, S. M.Hadi; Leemans, Alexander; Kesler, Shelli R.; Agerbæk, Mads; Wu, Lisa M.; Zachariae, Robert; Department of Psychology
Background: Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore whether possible changes are related to decline in cognitive functioning. Methods: Sixty-four newly orchiectomized TC patients underwent structural magnetic resonance imaging (T1-weighted and diffusion-weighted imaging) and cognitive testing at baseline prior to further treatment and again at a six-month follow-up. At follow-up, 22 participants had received cisplatin-based chemotherapy (CT) while 42 were in active surveillance (S). Brain structural networks were constructed for each participant, and network properties were investigated using graph theory and longitudinally compared across groups. Cognitive functioning was evaluated using standardized neuropsychological tests. All statistical tests were two-sided. Results: Compared with the S group, the CT group demonstrated altered global and local brain network properties from baseline to follow-up as evidenced by decreases in important brain network properties such as small-worldness (P =.04), network clustering (P =.04), and local efficiency (P =.02). In the CT group, poorer overall cognitive performance was associated with decreased small-worldness (r = -0.46, P =.04) and local efficiency (r = -0.51, P =.02), and verbal fluency was associated with decreased local efficiency (r = -0.55, P =.008). Conclusions: Brain structural networks may be disrupted following treatment with cisplatin-based chemotherapy. Impaired brain networks may underlie poorer performance over time on both specific and nonspecific cognitive functions in patients undergoing chemotherapy. To the best of our knowledge, this is the first study to longitudinally investigate changes in structural brain networks in a cancer population, providing novel insights regarding the neurobiological mechanisms of cancer-related cognitive impairment.
Verk
Advancing Land-Cover and Land-Use Classification with Semantically Consistent and Data-Efficient Deep Learning on Multi-Source Earth Observation Data
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Industrial Engineering, Mechanical Engineering and Computer Science, 2026-10) Sharma, Surbhi; Prof. Dr. Morris Riedel; Faculty of Industrial Engineering, Mechanical Engineering and Computer Science (UI); Iðnaðarverkfræði-, vélaverkfræði- og tölvunarfræðideild (HÍ); School of Engineering and Natural Sciences (UI); Verkfræði- og náttúruvísindasvið (HÍ)
Land-use and Land-cover (LULC) mapping from Earth Observation (EO) imagery plays a fundamental role in environmental monitoring, urban planning, agricultural management, and climate change assessment. Recent advances in satellite missions, Machine Learning (ML), Deep Learning (DL), and foundation models have significantly improved large-scale mapping capabilities. However, important challenges remain, including semantic inconsistencies between satellite imagery and in-situ observations, the lack of large-scale benchmark datasets with detailed LULC information for training and evaluating advanced DL models, heterogeneous data sources, mixed pixel effects, limited availability of annotated training data, and the need for computationally scalable processing frameworks. Addressing these challenges requires methodologies that integrate multiple data modalities while improving semantic consistency, data efficiency, and spatial representation. This thesis presents a comprehensive framework for advancing satellite-based LULC mapping through four complementary research directions. First, it investigates the semantic relationship between satellite observations and in-situ field data by leveraging geo-tagged field photographs as an intermediate observational layer. The analysis demonstrates that apparent disagreements between satellite-derived and field-based information often arise not only from limitations of satellite observations but also from ambiguities in field interpretation and inconsistencies in land-cover (LC) taxonomies. Second, the thesis produces the Sen4Map, a large-scale benchmark dataset, integrating Sentinel-2 imagery with harmonized Land Use/Cover Area Frame Survey (LUCAS) field observations and ancillary information. The benchmark provides semantically rich annotations designed to support the development and evaluation of robust DL models for LULC mapping. Third, the thesis develops methods for sub-pixel LULC estimation to capture fine-scale landscape heterogeneity beyond the native spatial resolution of satellite imagery. As a proof of concept, the proposed framework estimates built-up fractions from Sentinel-2 imagery using geospatial foundation model embeddings, demonstrating the potential of pretrained spectral-spatial representations for sub-pixel characterization. And finally, the thesis explores data-efficient learning strategies for EO by investigating few-shot learning with meta-learning on publicly available Remote Sensing (RS) benchmark datasets. These approaches demonstrate improved generalization under limited annotation availability, reducing the dependence on extensive labeled datasets while maintaining competitive mapping performance across diverse environments. Beyond methodological advances, the thesis also contributes scalable computational iii solutions through a Hierarchical Data Format, version 5 (HDF5)-based data architecture optimized for High-Performance Computing (HPC) environments, enabling efficient storage, access, and processing of large multi-source EO datasets. Collectively, the proposed methodologies contribute toward more semantically consistent, data-efficient, and scalable satellite-based LULC mapping systems. As EO transitions toward foundation models, unified embedding representations, and agentic geospatial intelligence, the contributions presented in this thesis establish the datasets, semantic frameworks, and embedding-centric methodologies required to support the next generation of LULC mapping.
Verk
Evaluating the Validity of PHQ-9 Scores: A Multi-Method Psychometric Investigation of Sources of Variance Beyond Depression Severity
(University of Iceland, School of Health Sciences, Faculty of Psychology, 2026-10-07) Kristófersdóttir, Kristín Hulda; Fanney Þórsdóttir; Faculty of Psychology (UI); Sálfræðideild (HÍ); School of Health Sciences (UI); Heilbrigðisvísindasvið (HÍ)
The Patient Health Questionnaire-9 (PHQ-9) is one of the most widely used self-report measures of depressive symptoms in clinical practice and research. Its scores are often interpreted as indicators of depression severity, yet this interpretation depends on the extent to which responses reflect depressive symptomatology rather than other influences. The aim of this thesis was to evaluate the validity of PHQ-9 scores by examining sources of variance beyond depression severity that may influence item responses. The thesis comprised four interrelated studies conducted with Icelandic samples. Paper I examined the psychometric properties of an existing Icelandic translation of the PHQ-9 using Mokken scale analysis (MSA) and used cognitive interviews to investigate possible sources of weak item functioning. Paper II introduced a revised Icelandic translation of the PHQ-9 and evaluated its psychometric properties using MSA. Paper III used the method of paired comparisons to examine whether PHQ-9 items differ in their perceived sensitivity, that is, the extent to which respondents experience them as uncomfortable to disclose. Paper IV modeled socially desirable responding as a measured cause of method variance in the PHQ-9 to examine whether it systematically influences item responses and whether that influence varies with item sensitivity. The findings showed that the original Icelandic PHQ-9 had suboptimal scalability and that this was associated with several problems, including translation errors, ambiguous wording, multi-barreled item content, symptom overlap, and other response-process issues. The revised Icelandic translation performed better psychometrically, with stronger scalability and a more coherent ordering of respondents along a depression severity continuum. However, not all problems identified in the original version were resolved. The results further showed that PHQ-9 items differ systematically in perceived sensitivity. Items typically grouped as cognitive/affective were generally judged more uncomfortable to disclose than items grouped as somatic. Finally, socially desirable responding was a source of method variance in PHQ-9 responses, systematically lowering symptom reporting while accounting for considerably less variance than depression severity. This method effect varied across items but did not correspond to their perceived sensitivity. In sum, the findings suggest that PHQ-9 scores may reflect more than depression severity alone. The results support a cautious and context-sensitive interpretation of PHQ-9 sum scores. The PHQ-9 may still be useful as a brief indicator of depressive symptoms, particularly in its revised Icelandic form, but its scores should not be treated as fully transparent or pure measures of depression severity. The thesis underscores the importance of examining how instrument design, item content, translation, and response processes shape the meaning of psychological measurement scores.

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