Inaugural Lecture by Prof.dr. Nadine N.W. Akkerman on the acceptance of her position as professor of Early Modern Literature & Culture at Leiden University on Friday 3 May 2024
Oratie uitgesproken door Prof.dr. Nadine N.W. Akkerman bij de aanvaarding van het ambt van hoogleraar Vroegmoderne Literatuur en Cultuur aan de Universiteit Leiden op vrijdag 3 mei 2024
Security is something that people tend to care about. But is it also something that they should care about? To explore this question, this dissertation first develops a new conceptual framework of... Show moreSecurity is something that people tend to care about. But is it also something that they should care about? To explore this question, this dissertation first develops a new conceptual framework of security. Next, it analyses how security relates to some key values for liberal democratic societies. The first of these is well-being. It is argued that there are important ways in which security can contribute to somebody’s well-being – but there are also ways in which security may hamper a person’s flourishing. The second value is freedom. It is shown that in public decision-making freedom and security may come at each other’s cost – yet there are also ways in which the two can work to each other’s benefit. The third value is equality. It is demonstrated that in order for a society to meet the demands of equality it must provide its members with a particular set of securities – while at the same time the pursuit of equality puts another set of securities out of reach. Ultimately, this dissertation finds no reason for considering security to be good for its own sake, but it argues that security can be good for the sake of well-being, freedom, and equality. Show less
Human vocal communication and music perception represent advanced cognitive skills, seemingly innate and universal. These faculties encompass a range of perceptual and cognitive abilities. Cross... Show moreHuman vocal communication and music perception represent advanced cognitive skills, seemingly innate and universal. These faculties encompass a range of perceptual and cognitive abilities. Cross-species research sheds light on the origins of musicality by investigating whether these traits are shared by nonhuman species. Songbirds, notably zebra finches, serve as valuable models due to their complex vocalizations and similarities to humans in auditory perception. My thesis explored zebra finches' sensitivity to spectral and temporal sound features. Chapter 2 examines the influence of song duration and spectral characteristics on song discrimination, while Chapter 3 tests song preferences. Chapter 4 investigates sequential and spectral feature recognition. Chapter 5 focuses on melody recognition. Zebra finches demonstrate perceptual flexibility, adapting focus based on stimulus characteristics. These findings underscore the importance of training conditions and stimulus nature in shaping auditory perception. Overall, my thesis enhances understanding of auditory cognition and cognitive flexibility among songbirds. Show less
This dissertation explores the impact of international cultural heritage law on individuals and local communities, particularly through the lens of cultural heritage law's use of universalising... Show moreThis dissertation explores the impact of international cultural heritage law on individuals and local communities, particularly through the lens of cultural heritage law's use of universalising language such as the ‘cultural heritage of mankind’. It argues that this rhetoric empowers states to prioritise purportedly common interests over local ones, potentially erasing living heritage value in the process. The dissertation places cultural heritage law in the context of broader international legal trends, in particular the tension between the pursuit of common interests through international law and the enduring influence of state sovereignty as a structuring principle of that law. It argues that contemporary cultural heritage law often fails to effectively limit state powers or protect the interests of individuals and local communities. It thus calls for stronger guarantees of participation within cultural heritage law, drawing upon legal standards developed within environmental law and human rights law. The dissertation suggests a rethinking the concept of ‘universal interest’ in heritage law to qualify the operation of state sovereignty and to better accommodate the interests of individuals and local communities, emphasizing their role as central actors and the need to bridge the gap between local and global interests in cultural heritage protection. Show less
In this reflective chapter, we examine the structural biases and empirical challenges underlying human trafficking ‘indicators’ (especially problem, risk and performance indicators) that are... Show moreIn this reflective chapter, we examine the structural biases and empirical challenges underlying human trafficking ‘indicators’ (especially problem, risk and performance indicators) that are routinely used to describe and measure human trafficking, assess risk, identify abuses, evaluate responses, and encourage accountability. While frequently used, such indicators can give an undue illusion of objectivity and reliability when they are neither neutral nor unskewed. In fact, numerous factors affect which elements are privileged as ‘indicators’ and which are obscured. We therefore examine here the selectivity, politics, racialized and gendered concerns that relate to the production and use of human trafficking indicators. Since human trafficking is a complex, highly-contested, and multi-faceted practice, it is not easily reduced to the crude generalizations upon which many indicators rest. We explore how the uncritical use of indicators can both contribute to stereotypical and unachievable ideals of victimhood and engender undue criminalization or withholding of victim support. In doing so, we disentangle some paradoxes around who is deemed ‘vulnerable’, ‘at risk’, ‘worthy of support’ and requiring ‘protection’. We highlight the – routinely overlooked – weak empirical basis and other limitations of many commonplace ‘indicators’ and challenges in building empirically-stronger and more robust indicators. The chapter concludes with overall implications of these critical reflections for policy, interventions, and research. Show less
AimsCustom triflange acetabular components (CTACs) play an important role in reconstructive orthopaedic surgery, particularly in revision total hip arthroplasty (rTHA) and pelvic tumour resection... Show moreAimsCustom triflange acetabular components (CTACs) play an important role in reconstructive orthopaedic surgery, particularly in revision total hip arthroplasty (rTHA) and pelvic tumour resection procedures. Accurate CTAC positioning is essential to successful surgical outcomes. While prior studies have explored CTAC positioning in rTHA, research focusing on tumour cases and implant flange positioning precision remains limited. Additionally, the impact of intraoperative navigation on positioning accuracy warrants further investigation. This study assesses CTAC positioning accuracy in tumour resection and rTHA cases, focusing on the differences between preoperative planning and postoperative implant positions.MethodsA multicentre observational cohort study in Australia between February 2017 and March 2021 included consecutive patients undergoing acetabular reconstruction with CTACs in rTHA (Paprosky 3A/3B defects) or tumour resection (including Enneking P2 peri-acetabular area). Of 103 eligible patients (104 hips), 34 patients (35 hips) were analyzed.ResultsCTAC positioning was generally accurate, with minor deviations in cup inclination (mean 2.7°; SD 2.84°), anteversion (mean 3.6°; SD 5.04°), and rotation (mean 2.1°; SD 2.47°). Deviation of the hip centre of rotation (COR) showed a mean vector length of 5.9 mm (SD 7.24). Flange positions showed small deviations, with the ischial flange exhibiting the largest deviation (mean vector length of 7.0 mm; SD 8.65). Overall, 83% of the implants were accurately positioned, with 17% exceeding malpositioning thresholds. CTACs used in tumour resections exhibited higher positioning accuracy than rTHA cases, with significant differences in inclination (1.5° for tumour vs 3.4° for rTHA) and rotation (1.3° for tumour vs 2.4° for rTHA). The use of intraoperative navigation appeared to enhance positioning accuracy, but this did not reach statistical significance.ConclusionThis study demonstrates favourable CTAC positioning accuracy, with potential for improved accuracy through intraoperative navigation. Further research is needed to understand the implications of positioning accuracy on implant performance and long-term survival. Show less
Objectives To compare the effectiveness of longstanding (>52 weeks), supervised exercise therapy with usual care in adults with rheumatoid arthritis (RA) and severe functional limitations.Methods P... Show moreObjectives To compare the effectiveness of longstanding (>52 weeks), supervised exercise therapy with usual care in adults with rheumatoid arthritis (RA) and severe functional limitations.Methods Participants were randomised 1:1 to the intervention (individualised goal-setting, active exercises, education and self-management regarding physical activity) or usual care. Primary endpoint was the change in the Patient-Specific Complaints activity ranked 1 (PSC1, 0–10) at 52 weeks. Secondary endpoints included the PSC activities ranked 2 and 3 (PSC2, PSC3), Health Assessment Questionnaire-Disability Index (HAQ-DI), Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL), 6-minute walk test (6MWT), Patient Reported Outcome Measurement Information System Physical Function-10 (PROMIS PF-10) and the Short Form-36 Physical and Mental Component Summary Scales (SF-36 PCS and MCS). (Serious) Adverse events (AEs) were recorded. Measurements were done by blinded assessors. Analyses at 52 weeks were based on the intention-to-treat principle.Results In total, 217 people (90% female, age 58.8 (SD 12.9) years) were randomised (n=104 intervention, n=98 usual care available for analyses). At 52 weeks, the improvement of the PSC1 was significantly larger in the intervention group (mean difference (95% CI) −1.7 (−2.4, –1.0)). Except for the SF-36 MCS, all secondary outcomes showed significantly greater improvements favouring the intervention (PSC2 −1.8 (−2.4, –1.1), PSC3 −1.7 (−2.4, −1.0), PROMIS PF-10 +3.09 (1.80, 4.38), HAQ-DI −0.17 (−0.29, –0.06), RAQoL −2.03 (−3.39, –0.69), SF-36 PCS +3.83 (1.49, 6.17) and 6MWT +56 (38, 75) m). One mild, transient AE occurred in the intervention group.Conclusion Longstanding, supervised exercise therapy was more effective than usual care in people with RA and severe functional limitations. Show less
This thesis summarizes a PhD research project, in which we successfully developed and tested a smartphone-based version of the AAT. We used the mobile AAT to show that approach-avoidance tendencies... Show moreThis thesis summarizes a PhD research project, in which we successfully developed and tested a smartphone-based version of the AAT. We used the mobile AAT to show that approach-avoidance tendencies can undergo substantial state-like changes. We further demonstrate how these changes can be systematically related to other state-variables and how important health-related outcomes such as overweight and obesity, can be explained by disruptions of these dynamics. Our findings have broad implications for approach-avoidance research and task-based research in general, as they reveal how smartphones can be used to get insights into the dynamic nature of task outcomes and how (disruptions of) these dynamics can have important real-life consequences. Show less
Thyroid cancer is a rare cancer with an excellent prognosis with standard care (including surgery and radioactive iodine therapy). However, a minority may show progression to refractory status.... Show moreThyroid cancer is a rare cancer with an excellent prognosis with standard care (including surgery and radioactive iodine therapy). However, a minority may show progression to refractory status. These advanced radioactive iodine-refractory thyroid cancer patients often have an aggressive disease course and poor prognosis. Unfortunately, no good treatment options are available for these patients.The registered drugs for this purpose include molecularly targeted therapy with the tyrosine kinase inhibitors (TKIs) lenvatinib, sorafenib, and as second-line cabozantinib. These agents were shown to delay progressive disease in clinical trials, but not overall survival. Moreover, the setting of a clinical trial is often stricter than real-life, as reflected by less favorable outcomes in real-world data. Furthermore, these drugs frequently have (intolerable) adverse events. When the limited treatment options for refractory thyroid cancer have been exhausted, inclusion in clinical trials is often recommended by international guidelines.More recent ‘basket trials’ also study tumor type-agnostic prescription of drugs based on molecular tumor profiling; e.g. an ALK TKI in presence of an ALK gene fusion. The molecular characterization of neoplasms may also improve diagnosis and/or help direct the further management strategy; e.g. in indeterminate thyroid cytopathology, or in specific cases of Multi-UniFocality in contrast to multifocality. Show less
ALK-positive NSCLC patients demonstrate initial responses to ALK tyrosine kinase inhibitor (TKI) treatments, but eventually develop resistance, causing rapid tumor relapse and poor survival rates.... Show moreALK-positive NSCLC patients demonstrate initial responses to ALK tyrosine kinase inhibitor (TKI) treatments, but eventually develop resistance, causing rapid tumor relapse and poor survival rates. Growing evidence suggests that the combination of drug and immune therapies greatly improves patient survival; however, due to the low immunogenicity of the tumors, ALK-positive patients do not respond to currently available immunotherapies. Tumor-associated macrophages (TAMs) play a crucial role in facilitating lung cancer growth by suppressing tumoricidal immune activation and absorbing chemotherapeutics. However, they can also be programmed toward a pro-inflammatory tumor suppressive phenotype, which represents a highly active area of therapy development. Iron loading of TAMs can achieve such reprogramming correlating with an improved prognosis in lung cancer patients. We previously showed that superparamagnetic iron oxide nanoparticles containing core-cross-linked polymer micelles (SPION-CCPMs) target macrophages and stimulate pro-inflammatory activation. Here, we show that SPION-CCPMs stimulate TAMs to secrete reactive nitrogen species and cytokines that exert tumoricidal activity. We further show that SPION-CCPMs reshape the immunosuppressive Eml4-Alk lung tumor microenvironment (TME) toward a cytotoxic profile hallmarked by the recruitment of CD8+ T cells, suggesting a multifactorial benefit of SPION-CCPM application. When intratracheally instilled into lung cancer-bearing mice, SPION-CCPMs delay tumor growth and, after first line therapy with a TKI, halt the regrowth of relapsing tumors. These findings identify SPIONs-CCPMs as an adjuvant therapy, which remodels the TME, resulting in a delay in the appearance of resistant tumors. Show less
This thesis explores ancient Egyptian descriptions of sicknesses of the inner body, the concepts used to understand them, and the trends in associated therapeutic applications for healing. It... Show moreThis thesis explores ancient Egyptian descriptions of sicknesses of the inner body, the concepts used to understand them, and the trends in associated therapeutic applications for healing. It concludes that the ancient Egyptian system of understanding recorded in writings—while somewhat obscured as the surviving texts were never intended to be descriptive of ideas—can be compared to other ways of thinking and categorising sickness experiences as found in other written cultures. Especially in terms of how such ideas are constructed and how therapies are associated with such concepts. Similarities can be observed in terms of core concepts and associated therapeutic applications recorded in cuneiform compendia of comparable age from Mesopotamia. Rather than using these observations as evidence of an influence of one culture over another, it is argued that these writings include practices and ideas which can instead be considered common to this region of the world, rather than as exclusive and invariably peculiar either the Egyptian and/or Mesopotamian cultures. Show less
Dijk, B.T. van; Boeren, A.M.P.; Khidir, S.J.H.; Hollander, N.K. den; Helm-van Mil, A.H.M. van der 2024
Objectives Rheumatoid arthritis (RA) mainly affects small joints. Despite the mechanical function of joints, the role of mechanical stress in the development of arthritis is insufficiently... Show moreObjectives Rheumatoid arthritis (RA) mainly affects small joints. Despite the mechanical function of joints, the role of mechanical stress in the development of arthritis is insufficiently understood. We hypothesised that mechanical stress/physical strain is a risk factor for joint inflammation in RA. Therefore, we studied work-related physical strain in subjects with clinically suspected arthralgia (CSA) as a risk factor for the presence of imaging-detected subclinical joint inflammation and the development of clinical arthritis/RA. Methods In 501 CSA patients and 155 symptom-free persons’ occupation-related physical strain was quantified using the International Standard Classification of Occupations. Contrastenhanced hand-MRIs were made and evaluated for joint inflammation (sum of synovitis/tenosynovitis/osteitis). CSA patients were followed on RA development. Age relationship was studied using an interaction term of physical strain with age. Results The degree of physical strain in CSA is associated with the severity of joint inflammation, independent of educational-level/BMI/smoking (interaction physical strain-age p=0.007; indicating a stronger association with increasing age). Physical strain is associated with higher tenosynovitis scores, in particular. In symptom-free persons, physical strain was not associated with imaging-detected joint inflammation. Higher degrees of physical strain also associated with higher risks for RA development in an age-dependent manner (HR=1.20 (1.06–1.37)/10-year increase in age), independent of educational-level/BMI/smoking. This association was partly mediated by an effect via subclinical joint inflammation. Conclusions Work-related physical strain increases the risk of subclinical joint inflammation and of developing RA. The age relationship suggests an effect of long-term stress or that tenosynovium is more sensitive to stress at older age. Together, the data indicate that mechanical stress contributes to the development of arthritis in RA. Show less
Oratie uitgesproken door Prof. mr. dr. drs. Mirjam P. Sombroek-van Doorm bij de aanvaarding van het ambt van hoogleraar Recht en Gezondheid aan de Universiteit Leiden op vrijdag 26 april 2024.
By the early eighteenth century Edo (present-day Tokyo) was one of the largest cities in the world. Sex and erotic allure could be found in many guises in this commercialized urban setting, both in... Show moreBy the early eighteenth century Edo (present-day Tokyo) was one of the largest cities in the world. Sex and erotic allure could be found in many guises in this commercialized urban setting, both in the city’s streets and in print. This chapter sets out to argue that sex assumed a multiplicity of meanings in this context that ranged from pleasure and procreation to potential pathology. To this purpose, it begins by tracing various discourses surrounding the three phenomena that have arguably received the most sustained attention in research to date, namely the sex trade, male same-sex desire, and the erotically explicit materials known as ‘spring pictures’ (Japanese shunga 春画/ shunpon 春本). The final sections aim to move beyond the standard narrative of the Edo period’s flourishing erotic culture by focusing on the female reproductive body, as well as medical and health discourses, thus aspiring to unsettle the paradigmatic character of this (male) pleasure-centred mode of sex and repudiate the monolithic view of early modern Japanese sexuality as unregulated. Show less
