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Background: Regular physical activity during childhood and adolescence can positively affect overall cardiometabolic health, fundamental motor skill development, bone density, quality of life, and psychological well-being. Research on physical activity in children is growing continuously, and one area is focused on assessing children's physical activity. Advances in wearable technology have provided more reliable tools for assessing physical activity, particularly in young children. These wearables must be calibrated to age-specific groups, body positions, and epoch times. Furthermore, muscle strength is an important health indicator in children; however, little is known about how muscle strength is influenced by age, maturity, hormones, and cytokines in pediatric populations. This thesis aimed to examine methods to estimate physical activity in children, understand which factors are associated with muscular strength in trained male children, and increase our understanding of how exercise-related hormones and proinflammatory cytokines (IL-6 and TNF-α) adapt to acute and long-term training. 

Methods: This thesis included four studies. Paper I aimed to calibrate two accelerometer devices, MotionWatch 8 (MW8) and ActiGraph GT3X ( GT3X), worn on the hip and wrist (n = 30), and to develop age-specific cut-offs for physical activity intensities in 3-year-old children. Paper II was a cross-sectional study that examined the associations of muscular strength measures with anthropometric factors, chronological age, maturation, and training experience in trained prepubertal and pubertal males (n = 41). Another aim of Paper II was to examine whether a handgrip strength test can predict the total muscle strength assessed with whole-body free-weight exercises. Paper III was an intervention study that examined acute hormonal and cytokine responses to free-weight resistance training in trained prepubertal and pubertal male children (n = 41). Paper IV was a systematic review and meta-analysis that assessed the evidence of the effects of exercise training and training type on hormone and cytokine adaptations in children and adolescents. 

Results: There was a strong correlation between MW8 and the GT3X device (counts/30 s) at both hip and wrist levels (Paper I). The devices' cut-off scores for physical activity levels were classified with outstanding and excellent accuracy (Paper I). The cross-sectional study showed that muscular strength tests in trained male children are mostly associated with anthropometric factors, which differ depending on the exercise test chosen (Paper II). Furthermore, the handgrip strength test was strongly associated with total muscle strength in trained male children (Paper II). A single resistance training session induced greater acute post-exercise testosterone and IGF-I levels in pubertal children than in prepubertal male children (Paper III). Post-exercise IL-6 levels were significantly increased only in the prepubertal group. Lastly, the systematic review and meta-analysis showed that long-term exercise training had a small effect on resting hormonal concentrations. Resistance training, but not endurance training, increased resting testosterone levels in healthy children and adolescents (Paper IV). 

Conclusions: Measuring and classifying physical activity levels in preschoolers can be achieved accurately using MW8 or the GT3X device (Paper I). Another finding was that anthropometric measures such as body mass and fat-free mass are important factors associated with muscle strength, and they may be used to scale muscle strength scores to provide a fair interpretation across children of different body sizes (Paper II). A simple handgrip strength test could be a quick and effective screening tool for practitioners and researchers to estimate total muscle strength in trained male children (Paper II). Furthermore, pubertal children were stronger than prepubertal children and had greater post-exercise IGF-I and testosterone responses following a single resistance training session (Paper III). Finally, the systematic review and meta-analysis suggested that exercise training had a small effect on hormonal concentrations in healthy children and adolescents (Paper IV). 

In this thesis globalisation is explored from both a temporal and spatial perspective, focusing on the role of global advanced producer service (APS) companies. These firms, recognised in the literature as key agents of globalisation, facilitate international outreach for other companies. The research spans three papers focusing on two areas: the former Soviet Union and Sweden. In both territories, it demonstrates how global APS companies adapt their location strategies to local contexts. In Sweden, the research further explores the role of global APS companies in shaping localised labour demand, highlighting their position in the competition within various job categories. In order to provide a comprehensive understanding of global APS firms’ business strategies, the thesis employs a range of methodologies, including network analysis, modelling, machine learning and text analysis.

The findings uncover the dual nature of global APS companies, which simultaneously follow planetary trends while swiftly responding to changes in local conditions for doing business. Consequently, the complex and fragmented nature of globalisation is revealed. The temporal dimension plays a crucial role in the analysis, showcasing the diversity of spatial and labour market strategies of global APS companies over time. Additionally, the research highlights the influence of companies’ sectorial specialisations regarding business strategies and responsiveness to local contexts. This illustrates how companies within the same sector may adopt different approaches to location and hiring principles depending on specific local conditions.

The thesis advocates for a multi-scalar approach to globalisation research, emphasising the importance of scale in methodological considerations. It underscores how the choice of scale impacts research findings, demonstrating that globalisation manifests differently at various levels of analysis. This insight reinforces the need for reflection on scale as a key element in the design and interpretation of globalisation studies. This nuanced approach challenges universal narratives of globalisation, advocating for more contextualised and scale-sensitive research frameworks.

Smart and autonomous earthmoving equipment enhances energy efficiency,productivity, and safety at construction sites and mines. The innovations provide means to reach high-set sustainability goals and be profitable despite increasing labor shortages. In addition, recent technological breakthroughs in artificial intelligence highlight the potential of superhuman capabilities to further enhance operations. This thesis presents a computational approach to end-to-end optimization of autonomous wheel loaders operating in a dynamic environment. Wheel loaders are mainly used for repeatedly loading material and carrying it to load receivers in quarries and mines. The difficulty lies in that each loading action alters the state of the material pile. The resulting state affects the possible outcomes of the subsequent loading process and, ultimately, the total performance. Thus, the challenge is to achieve both autonomous and high-performance wheel loading over a sequence of tasks. Achieving this requires the ability to predict future outcomes and account for the cumulative effect of loading actions. The thesis constructs a real-time wheel loader simulator, develops world models for sequential loading actions with evolving pile states, formulates the end-to-end optimization problem, and introduces a look-ahead tree search method to solve the problem. These contributions provide insights into utilizing physics-based simulation in combination with machine learning to further improve sustainability in mining and construction.

Background/aim: Acromegaly is a rare disease caused by a pituitary tumor secreting excess growth hormone, which leads to acral growth, organ enlargement, and facial changes. Patients with acromegaly have an increased risk of type 2 diabetes, cardiovascular disease, and arthropathy. Due to the rarity and slow progression of the disease, there is a considerable diagnostic delay (5–8 years), which contributes to increased morbidity and mortality. This thesis is based on four studies aimed at investigating the presentation of sleep apnea and carpal tunnel syndrome (CTS) in patients with acromegaly and the potential for digital analysis of voice and face to identify patients with acromegaly. 

Methods and results: Paper I was a cross-sectional, multicenter study of 259 patients with acromegaly: 29% of the patients were previously diagnosed with sleep apnea, with more than half (57%) of these diagnosed prior to the diagnosis of acromegaly. Another 8% of this cohort were found to have undiagnosed sleep apnea by targeted clinical assessment and sleep investigation. Paper II was a retrospective, national registry-based study of 556 patients with a diagnosis of acromegaly from the National Patient Registry. It found a 6-fold higher incidence of CTS diagnosis and surgery prior to acromegaly diagnosis compared to the general population. The risk of CTS was higher in women with acromegaly, and 84% of patients with CTS were diagnosed and surgically treated before the diagnosis of acromegaly. The potential window of opportunity to diagnose acromegaly earlier led us to investigate new non-invasive screening tools. In Paper III, a multicenter cohort study, we collected voice recordings from 151 patients with acromegaly (23% biochemically active) and 139 matched controls to create a machine learning algorithm, which identified the voice of patients with acromegaly at higher accuracy than experienced endocrinologists (ROC AUC 0.84 vs 0.69). Both biochemically active and controlled patients with acromegaly reported increased voice impairment (Voice Handicap Index) compared to controls. In Paper IV, we used facial images from 155 patients and 153 controls from the same cohort and machine learning algorithms for face analysis to train several machine learning models. The best model matched the accuracy of the compound assessment of 12 experienced endocrinologists (ROC AUC 0.85 vs 0.89) in acromegaly prediction while showing a higher sensitivity (0.82 vs 0.66). 

Conclusions: The diagnostic delay in acromegaly leads to the presence of comorbidities long before the disease is recognized. In this time window, non-invasive screening tools based on facial and voice analysis may improve the chances for earlier diagnosis. 

The Swedish income tax system is dependent on the taxation of income deriving from employment. Simultaneously, taxation posits questions on power, fiscal policy as well as who should be taxed, and why. However, the research on various aspects of how the Swedish tax subject is produced in its legal and historical context is limited. In adherence to the dissertation’s objective, that is, to investigate and analyse the production of the working tax subject, the analysis indicates that the discussions prevalent in the empirical material can be interpreted as underpinned by an economic rationality, positioning the tax subject as an economically rational, self-serving and moral actor. The analysis further indicates that the legislator has proposed different tax techniques such as tax reductions, tax deductions, tax exemptions as well as limitations of legal capacity to structure and inform the conduct of the tax subject.

The findings especially suggest that the tax subject and the proposed changes in legislation have been and still are gendered in relation to work and tax morality. Furthermore, the findings suggest that the Swedish working tax subject is a subject always in motion, never fully determined but always intertwined with economy, morality, and history.

The thesis employs a thematic analysis in order to examine preparatory works connected to the Swedish taxation of income deriving from employment, starting with the Swedish Municipal Income Tax Act (1928:370), ending with the Swedish Income Tax Act (1999:1229) of today. The thesis also analyses the empirical material through a theoretical framework developed around questions of subject positions, gender, class, and Foucauldian governmentality.

In the last several decades, European party systems have seen the entry of ‘new’ parties, such as green parties and radical right parties, competing on novel issues largely unrelated to the dominant economic left-right dimension of conflict. Alongside the development of an multidimensional arena for ideological conflict between parties, matters of affect between voters and parties have also come to the fore, where not only disagreement over policy but also dislike towards other parties and partisans may influence party behavior. At the same time, coalition governments continue to be the predominate form of government across Europe, and by their very nature necessitate compromises between different parties to form, govern, and remain in office. With [JH1] ‘new’ issues in play along more dimensions and inter-party hostilities, this may have adverse consequences for the functioning of coalition governments.

In this thesis, I set out to study how multidimensional ideological polarization, focusing on the two dominant dimensions of economic policy and sociocultural policy, in concert with affective polarization among political elites affect party positioning, government formation, coalition governance, and government termination. The potential impact of multidimensional polarization has received little empirical attention in the literature on coalition governments, and this thesis aims to remedy this deficiency by showing how greater levels of multidimensional ideological and affective polarization create a more complex bargaining environment which ought to have several impacts on the life cycle of governments, from their formation until their demise. I pursue the topic in five papers which cover party strategic positioning in a multidimensional space (Paper 1), assessing the impact of different operationalizations of policy space on the predictive capabilities of empirical models of government formation (Paper 2), the effects of elite affective polarization on which government forms (Paper 3), what mechanisms variously polarized coalition governments use to resolve conflicts (Paper 4), and how ideological polarization in the opposition impacts the survival of minority governments (Paper 5).

The results from the papers point in a mixed direction. While parties behave in a way that is consistent with them exploiting the multidimensional character of modern politics in their positioning, there are few predictive gains to be made in modeling policy space as consisting of more than a general left-right ‘super dimension’. Still, the sociocultural dimension does seem to affect which government forms. The role of elite affective polarization receives considerable support, indicating that how party elites feel about their potential coalition partners matters as much — if not more — than any ideological disagreements. Finally, minority governments facing a divided opposition fare better in terms of survival than minority governments facing a united opposition. On the whole, the results indicate that while multidimensional conflict structures do matter, it is not to the degree that it upends the functioning of government by coalition.

Alterations in 3D chromatin organization and epigenetic regulation drivecancer progression. Here I use glioblastoma (GB) as a model to understandthe broad impact of epigenetic changes on tumour biology. By mapping the promoter-enhancer interactome and chromatin states in GB, we uncovered extensive rewiring of chromatin architecture that leads to the activation of gene networks associated with synaptic communication, axonogenesis, axon guidance, and chromatin remodelling. Central to these networks are transcription factors (TFs) such as SMAD3 and PITX1, identified as keyplayers in gene regulatory networks (GRNs) mediating neuron-to-gliomasynaptic communication. Moreover, we showed that tumour growth can be affected by modulating the activity of TFs, such as SMAD3, which mediates neuron-to-glioma synapses. These findings highlight how epigenetic changes and reorganization of 3D genome topology enable GB cells to integrate neural signals and translate them into a proliferative response.

Through epigenetic perturbation of novel EGFR (Epidermal Growth Factor Receptor) enhancers, we observed a reduction in GB cell proliferation and invasion, alongside increased sensitivity to the chemotherapeutic agent temozolomide (TMZ). Therefore, targeting specific regulatory regions canalso influence tumour cell behaviour, though to a lower extent than targeting complete GRNs via TF modulation.

Additionally, using Multi-Omics Binary Integration via Lasso Ensembles (MOBILE), a Machine Learning (ML)-based tool, we identified novel GRNs impacted by the rewiring of GB’s epigenetic landscape and critical for GB pathogenesis. Among them, GABA signalling emerged as a previously unrecognized driver of GB tumour progression. 

In summary, this work advances our understanding of how epigenetic regulation and 3D chromatin architecture shape the gene expression landscape of glioblastoma tumours. It paves the way for novel therapeutic strategies targeting chromatin regulators and GRNs to tackle difficult-to-treat cancers, such as glioblastoma.

Aim: This thesis aimed to identify potential targets that can be leveraged to enhance vaccination coverage and urban-rural equity, and to evaluate the impact of large-scale interventions on coverage and urban-rural equity in The Gambia.

Methods: This study consists of four quantitative substudies. The data sources used were The Gambian Demographic and Health Survey (2013: n = 1,660; 2020: n = 1,456); an electronic register (n = 41,720 from 2019 to 2020); and a paper-based register (n = 16,972 from 2019 to 2020 and n = 61,839 from 2021 to 2022). The main outcome variables were full basic vaccination and Hepatitis B birth dose timeliness among children aged 12–23 months. The analysis methods used were counterfactual, decomposition, multilevel, difference-in-differences, and controlled interrupted time series analysis.

Findings: Potential targets: missed vaccination opportunities lowered vaccination by more than 10% and explained almost all (95%) of the urban-rural inequity among children who had missed opportunities. Children with delayed or non-vaccinated history, due for vaccination in the third quarter, or vaccinated in private facilities had higher odds of under-vaccination while those vaccinated in more than facility or in facilities with a birth dose-to-health worker ratio of 100–299 had lower odds. Impact of interventions: vaccination coverage improvement was lower (12%) but inequity decreased more in regions that implemented the pay-for-performance scheme. The Hepatitis B birth dose intervention led to a small (2.1%) improvement in timely Hepatitis B vaccination at birth, especially in facilities with the worst performance at baseline.

Conclusions: This thesis has identified several potential targets for improving the vaccination gap. Intervening in the identified factors with consideration for their differential impact in urban and rural areas could improve vaccination coverage and equity in The Gambia and contribute to achieving global vaccination goals. The thesis highlighted the impact of two interventions. However, it does not attribute the improvements in coverage to the pay-for-performance scheme but suggests that it might have contributed to reducing urban-rural inequity. Given the intervention’s impact, the Hepatitis B birth dose intervention alone is insufficient to drive timeliness to the desired 90% coverage for elimination.

Background: Standardized cancer patient pathways (CPP) have been adopted as a new policy in several countries, including Sweden. CPPs aim to facilitate patients' trajectories within the health system and improve the timely diagnosis and treatment of cancer. In Sweden, the adoption of CPPs entailed a decision made by decision-makers at the top of the health system; this mandated the use of CPPs by primary and secondary healthcare professionals when assessing patients and addressing their symptoms. Typically, primary healthcare (PHC) is the first point of contact for patients in Sweden seeking care for symptoms that indicate serious illnesses such as cancer. This raises the question of how the adoption of CPPs influenced PHC. Given that the goal was for the policies to work as intended, i.e., to improve early diagnosis and treatment of cancer, understanding the influence of the adoption of CPPs on PHC and its professionals is needed.

Aim: To explore how the adoption of CPPs in northern Sweden influenced PHC organizations and provisions. 

Methods: Qualitative (studies I-III) and quantitative (study IV) methods were utilized. Data were collected using individual and group interviews with participants working in the health system (I–III), and from the National Cancer Register concerning patients diagnosed with colorectal cancer before and after the introduction of CPPs. Additionally, data from electronic health record reviews, from Statistics Sweden, and regarding distance to the hospital for each patient, measured using Google Maps, were collected (IV). The individual interviews comprised participants in national, regional, and local leadership positions (I). The group interviews encompassed nurses and physicians working at PHC in one region (I–III). Interview data were analyzed using the Grounded Theory Method. The quantitative data was analyzed using comparative descriptive statistics and logistic regression (IV).

Results: The actors that adopted CPPs along the cancer trajectory and across the different healthcare levels were not equally involved in developing CPPs. Specifically, actors in PHC, which is the main entrance into care, were barely involved. This might have impacted the initial adoption and subsequent processes. The adoption of CPPs within the Swedish health system involved actors at different organizational levels. Distinct strategies were used to achieve shared goals, although this resulted in insufficient collaboration between the actors at different levels (I). The insufficient involvement of PHC resulted in unintended consequences, such as PHC organizations adjusting routines by themselves. PHC professionals combined existing work as usual with new practices following CPPs to facilitate timely diagnosis and were learning by testing the new ways of working in their practices. Moreover, they continued to manage the unequal relationship to secondary healthcare (II). Applying CPPs in patient encounters entailed challenges for professionals. When determining the seriousness of symptoms, they either relied on their professional competencies or followed symptoms described as alarming by the CPPs. Physicians perceived CPP templates to be easy to apply when their clinical cancer suspicions matched the predetermined criteria; when they did not, a workaround was needed to refer patients to secondary healthcare. Nurses and physicians described sensitively telling patients about upcoming rapid investigation procedures as challenging; for example, they did not want to frighten patients and sometimes tried to safeguard them by not providing detailed information about CPPs (III). The time to diagnosis was reduced for patients with colorectal cancer after the introduction of CPPs, particularly for those who initiated their pathway in PHC. However, for patients with right-sided colon cancer (in the ascending colon), the time to diagnosis did not improve (IV). 

Conclusion: PHC is the entrance into healthcare and is important for early cancer diagnosis. Therefore, it is essential to integrate the perspectives of PHC, e.g., nurses and physicians, when developing and adopting new policies to improve the diagnostic process. Despite the improvement of diagnostic processes that resulted from the introduction of CPPs, challenges remain when specific cancer symptoms are lacking, and clinical suspicions do not always align with the CPP templates.

Introduction: Gender dysphoria describes the stress and discomfort that transgender and gender diverse (TGD) people may experience when their gender identity is not aligned with their birth-assigned sex. A mismatch between voice and gender identity, voice dysphoria, can be a prominent part of gender dysphoria and may lead to limited participation in social life. Gender-affirming voice training provided by speech and language pathologists (SLPs) aims to assist TGD voice clients to reach their preferred gender expression in voice. The training is mainly based on research on voice and speech features most influential for the perception of femininity and masculinity in cisgender naive listeners, that is, people whose gender identity aligns with their birth-assigned sex and who have no professional training in voice assessments. The overall purpose of this thesis was to adopt a client-centred perspective by focusing on TGD people’s perception of voices and voice modification.

Method: To increase the understanding of TGD people’s motives and perceived barriers to voice modification, semi-structured interviews were conducted with 15 TGD voice clients considering gender-affirming voice training (Study I). To explore TGD people’s perceptions of voices in relation to cisgender naive listeners and SLPs, a listening experiment was constructed in which 132 voices representing a variety of gender expressions were rated according to the degree of femininity and masculinity, respectively. (Study II). The listener ratings were combined with a comprehensive set of acoustic voice and speech features using a penalized regression model to identify the relative strength of acoustic features most salient for listeners’ perception of femininity and masculinity in voice (Study IV). A rating protocol for standardised auditory-perceptual assessment of voice and speech features influencing the perception of gender expression in voice was developed and evaluated regarding consistency and agreement in six SLP listeners (Study III).

Results: Study I: The interviews showed that the TGD voice clients’ expected gains of modifying the voice included increased well-being, participation in social life, and control over the voice. Anticipated barriers included fears of not reaching one’s set goals and that the modified voice would no longer be an efficient tool for communication. Study II: The results of the listening experiment indicated that while TGD and cisgender naive listeners did not differ in their perceptions of femininity and masculinity, SLPs rated the voices as less feminine, and less masculine compared to the other two groups. Study IV: The acoustic models that best predicted the listener ratings explained 89% and 86% of the variance of the rated femininity and masculinity in voices, respectively. While fundamental frequency was seen to be the single most influential acoustic feature, the results verified the co-contribution of 222 other acoustic properties of articulation, intonation and resonance. Study III: The evaluation of the auditory-perceptual rating protocol provided support for structured clinical ratings within gender-affirming voice training to be meaningful. The protocol items were rated overall in a consistent manner by the SLPs, but the level of agreement among SLPs was lower.

Conclusions: The project places the TGD voice client in focus, taking a stance on the importance of applying a client-centred approach in both voice training and research. The results showed the need to address motivational and constraining factors for voice modification as these may affect TGD clients’ adherence to voice training and their satisfaction with training results. SLPs should be attentive to how their professional training may influence their perception of voices and encourage explorations of the TGD voice client’s perceptions of femininity and masculinity to ensure that goal setting and evaluation of training outcomes reflect the perceptions of the client. The voice training should consider the combined influence of pitch, intonation, resonance and articulation to target the client’s preferred gender expression in voice, measures which are also possible to analyse acoustically. To promote consensus among SLPs when performing auditory-perceptual assessments of these voice and speech aspects, joint listener training is recommended on a regular basis.

The project provides methodological alternatives for how listener experiments can be conducted to lessen the impact of normative assumptions about gender expression in voice as binary and equalled with the gender categories man and woman. The project advocates for a non-binary presentation of femininity and masculinity to be considered in future research on the perception of voices.

This doctoral thesis focuses on Item Response Theory (IRT), a statistical method widely used in fields such as education and psychology to analyze response patterns on tests and surveys. In practice, IRT models are estimated using collected test data, which allows researchers to assess both how effectively each item measures the underlying trait—such as subject knowledge or personality characteristics—that the test aims to evaluate, and to estimate each individual's level of that trait. Unlike traditional methods that simply sum predetermined item scores, IRT accounts for the difficulty of each item and its ability to measure the intended trait.

The thesis consists of four research articles, each addressing different aspects of IRT and its applications. The first article focuses on test equating, ensuring that scores from different versions of a test are comparable. Equating methods with and without IRT are compared using simulations to explore the advantages and disadvantages of incorporating IRT into the kernel equating framework. The second and third articles introduce and compare different types of IRT models. Through simulations and real test data examples, these studies demonstrate that more flexible models can better capture the true relationships between test responses and the underlying traits being measured.

Finally, the IRTorch Python package is presented in the fourth study. IRTorch supports various IRT models and estimation methods and can be used to analyze data from different types of tests and surveys. In summary, the thesis demonstrates how IRT-based equating methods can serve as an alternative to traditional equating methods, how more flexible IRT models can improve the precision of test results, and how user-friendly software can make advanced statistical models accessible to a wider audience.