Baby schema features are a specific set of physical features-including chubby cheeks, large, low-set eyes, and a large, round head-that have evolutionary adaptive value in their ability to trigger... Show moreBaby schema features are a specific set of physical features-including chubby cheeks, large, low-set eyes, and a large, round head-that have evolutionary adaptive value in their ability to trigger nurturant care. In this study among nulliparous women (N = 81; M age = 23.60, SD = 0.44), we examined how sensitivity to these baby schema features differs based on individual variations in nurturant care motivation and oxytocin system gene methylation. We integrated subjective ratings with measures of facial expressions and electroencephalography (EEG) in response to infant faces that were manipulated to contain more or less pronounced baby schema features. Linear mixed effects analyses demonstrated that infants with more pronounced baby schema features were rated as cuter and participants indicated greater motivation to take care of them. Furthermore, infants with more pronounced baby schema features elicited stronger smiling responses and enhanced P2 and LPP amplitudes compared to infants with less pronounced baby schema features. Importantly, individual differences significantly predicted baby schema effects. Specifically, women with low OXTR methylation and high nurturance motivation showed enhanced differentiation in automatic neurophysiological responses to infants with high and low levels of baby schema features. These findings highlight the importance of considering individual differences in continued research to further understand the complexities of sensitivity to child cues, including facial features, which will improve our understanding of the intricate neurobiological system that forms the basis of caregiving behavior. Show less
BackgroundBased on observational studies and randomised controlled trials (RCTs), the benefit–harm balance of antihypertensive treatment in older adults with dementia is unclear.ObjectiveTo assess... Show moreBackgroundBased on observational studies and randomised controlled trials (RCTs), the benefit–harm balance of antihypertensive treatment in older adults with dementia is unclear.ObjectiveTo assess whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPSs) and maintains quality of life (QoL) in nursing home residents with dementia.DesignOpen-label, blinded-outcome RCT. Randomisation 1:1, stratified by nursing home organisation and baseline NPS. Trial registration: NL7365.SubjectsDutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) ≤160 mmHg during antihypertensive treatment. Exclusion criteria included heart failure NYHA-class-III/IV, recent cardiovascular events/procedures or life expectancy <4 months (planned sample size n = 492).MeasurementsCo-primary outcomes NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16 weeks.ResultsFrom 9 November 2018 to 4 May 2021, 205 participants (median age 85.8 [IQR 79.6–89.5] years; 79.5% female; median SBP 134 [IQR 123–146] mmHg) were randomised to either antihypertensive treatment discontinuation (n = 101) or usual care (n = 104). Safety concerns, combined with lacking benefits, prompted the data safety and monitoring board to advice a premature cessation of randomisation. At 16-week follow-up, no significant differences were found between groups for NPI-NH (adjusted mean difference 1.6 [95% CI –2.3 to 5.6]; P = 0.42) or Qualidem (adjusted mean difference − 2.5 [95% CI –6.0 to 1.0]; P = 0.15). Serious adverse events (SAEs) occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95% CI 0.98–2.79]). All 32-week outcomes favoured usual care.ConclusionHalfway through this study, a non-significant increased SAE risk associated with discontinuing antihypertensive treatment was observed, and an associated interim analysis showed that significant worthwhile health gain for discontinuation of antihypertensive treatment was unlikely. This unbeneficial benefit–harm balance shows that discontinuation of antihypertensive treatment in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia. Show less
Background: Previous studies demonstrated the prognostic value of baseline cardiac damage staging as well as left ventricular global longitudinal strain (LVGLS) in patients undergoing transcatheter... Show moreBackground: Previous studies demonstrated the prognostic value of baseline cardiac damage staging as well as left ventricular global longitudinal strain (LVGLS) in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of the present study was to evaluate the changes in cardiac damage stage and LVGLS after TAVI and to investigate their prognostic values when integrated into the follow-up assessment. Methods: Patients with severe aortic stenosis undergoing TAVI were hierarchically classified into cardiac damage stages based on echocardiographic criteria before TAVI and at a 6-month follow-up. At the same time, LVGLS was measured. The staging system included stage 0 = no signs of cardiac damage; stage 1 = LV damage; stage 2 = mitral or left atrial damage; stage 3 = pulmonary vasculature or tricuspid damage; and stage 4 = right ventricular damage. The primary endpoint was all-cause mortality. Results: A total of 620 patients were included. At follow-up, LVGLS significantly improved, and the improvement was similar among each baseline cardiac damage stage. Follow-up LVGLS values were divided into quintiles, and each quintile was integrated into the cardiac damage staging, leading to a reclassification of 308 (50%) patients. At the time of a median follow-up at 48 (IQR 31–71) months starting from the 6-month follow-up after TAVI, 262 (38%) patients had died. A multivariable Cox regression model showed that LVGLS-integrated cardiac damage staging at follow-up had an incremental prognostic value over the baseline assessment (HR per 1-stage increase 1.384; 95% CI 1.152–1.663; p < 0.001). Conclusions: The integration of LVGLS with conventional echocardiographic parameters of cardiac damage at a 6-month follow-up after TAVI can improve patient risk-stratification. Show less
The reconstruction of the Proto-Berber light verbs (i.e. CCC, *ălməd ‘to learn’, VCC, *agəm ‘to draw water’, CC *ăǵən ‘to lie down’ and C̄C: *ăffəɣ ‘to go out’), has received considerable attention... Show moreThe reconstruction of the Proto-Berber light verbs (i.e. CCC, *ălməd ‘to learn’, VCC, *agəm ‘to draw water’, CC *ăǵən ‘to lie down’ and C̄C: *ăffəɣ ‘to go out’), has received considerable attention in Berber historical linguistics. But, verbs that have u in the second syllable such as Ghadamsi əmdu ‘to finish’ and əṭkur ‘to fill’ require further study. These verbs share several formal similarities with the regular light verb of the type *ălməd ‘to learn’, but they have not yet been integrated into a model of the Proto-Berber verbal system. This paper will propose a reconstruction of the Proto-Berber light verb, incorporating these verbs as a subclass of the light verb, whose difference in vocalisation is triggered by the presence of a plain vowel in the second syllable of the stem. Show less
This thesis is focused on the targeting of two antigens often expressed on the surface of cancer cells: MICA and HLA-E. Both antigens are members of the MHC-I family of proteins. They both act as... Show moreThis thesis is focused on the targeting of two antigens often expressed on the surface of cancer cells: MICA and HLA-E. Both antigens are members of the MHC-I family of proteins. They both act as ligands for the NK receptors on NK cells and CD8+ T cells. We target MICA using nanobodies, or VHHs, the small variable regions of camelid-derived heavy-chain only antibodies. The nanobodies are used as nanobody-drug conjugate, fused to the Mertansine-derivative DM1, or as the targeting domain of chimeric antigen receptors to create CAR NK cells. These nanobody-based immunotherapies selectively target and kill MICA-positive cancer cells. We target HLA-E with an antibody directed against a 13-amino acid epitope unique to the cytoplasmic tail of HLA-E. The antibody is specific to HLA-E and can be used for detection of HLA-E positive cells in flow cytometry and immunofluorescence and detection of HLA-E positive tumors in immunohistochemistry. Together with the epitope, the antibody can be used as a novel epitope tag for detection and purification of unrelated proteins. Show less
Holstein, Y. van; Mooijaart, S.P.; Oevelen, M. van; Deudekom, F.J. van; Vojinovic, D.; Bizzarri, D.; ... ; Trompet, S. 2024
Prognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality ... Show morePrognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality (MetaboHealth) and biological age (MetaboAge). This study aims to investigate the association of MetaboHealth and MetaboAge with 1-year mortality in older patients with solid tumors, and to study their predictive value for mortality in addition to established clinical predictors. This prospective cohort study included patients aged ≥ 70 years with a solid malignant tumor, who underwent blood sampling and a geriatric assessment before treatment initiation. The outcome was all-cause 1-year mortality. Of the 192 patients, the median age was 77 years. With each SD increase of MetaboHealth, patients had a 2.32 times increased risk of mortality (HR 2.32, 95% CI 1.59–3.39). With each year increase in MetaboAge, there was a 4% increased risk of mortality (HR 1.04, 1.01–1.07). MetaboHealth and MetaboAge showed an AUC of 0.66 (0.56–0.75) and 0.60 (0.51–0.68) for mortality prediction accuracy, respectively. The AUC of a predictive model containing age, primary tumor site, distant metastasis, comorbidity, and malnutrition was 0.76 (0.68–0.83). Addition of MetaboHealth increased AUC to 0.80 (0.74–0.87) (p = 0.09) and AUC did not change with MetaboAge (0.76 (0.69–0.83) (p = 0.89)). Higher MetaboHealth and MetaboAge scores were associated with 1-year mortality. The addition of MetaboHealth to established clinical predictors only marginally improved mortality prediction in this cohort with various types of tumors. MetaboHealth may potentially improve identification of older patients vulnerable for adverse events, but numbers were too small for definitive conclusions. The TENT study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22–10-2019. Show less
Big Science, commonly defined as conventional science made big in three dimensions, namely organizations, machines, and politics, brings a plethora of different stakeholders together, often for a... Show moreBig Science, commonly defined as conventional science made big in three dimensions, namely organizations, machines, and politics, brings a plethora of different stakeholders together, often for a long period of time. This includes policymakers, scientists, (scientific) managers as well as local “host” communities. Each group has considerable, though often different, stakes in Big Science. These diverging interests require stakeholders to negotiate and to compromise between and among one another. Using qualitative methods, this dissertation contributes to a deeper understanding of such processes in and around Big Science in two distinct ways. First, it sheds light on how different stakeholders pursue and negotiate their interests within and in relation to Big Science. In doing so, the thesis pays particular attention to non-Western and indigenous actors, two stakeholder groups that the existing literature on Big Science has so far largely neglected. Second, it theorizes how conflicts emerge and develop between and among stakeholders, thus advancing theory-building in the largely undertheorized literature on Big Science. Overall, the dissertation demonstrates that, in contrast to conventional science, Big Science carries significant symbolism for the involved stakeholders, which often impedes effective stakeholder and conflict management. Show less
This thesis explores the role of what has traditionally been considered as neural “noise”, specifically BOLD signal variability and aperiodic neural activity, in human cognitive functions,... Show moreThis thesis explores the role of what has traditionally been considered as neural “noise”, specifically BOLD signal variability and aperiodic neural activity, in human cognitive functions, particularly in metacontrol. The metacontrol model assumes that individuals vary in their cognitive styles between "persistence" and "flexibility." Persistence emphasizes focused goal pursuit, while flexibility allows for easy task switching and consideration of diverse possibilities. Through three empirical studies, this thesis investigates the relationship between two specific forms of neural "noise" – BOLD signal variability and aperiodic neural activity – and metacontrol biases (i.e., persistence vs. flexibility). Chapter 2 emphasizes the importance of resting-state BOLD signal variability in understanding individualized cognitive control styles. Chapter 3 highlights the importance of the aperiodic component of the EEG power spectrum in reflecting demand-specific metacontrol states. Notably, Chapter 4 illuminates the functional significance of aperiodic activity in creative thinking. Overall, the research presented in this thesis highlights the importance of resting-state BOLD signal variability and aperiodic activity in the EEG power spectrum for understanding the neural underpinnings of cognitive functions. Show less
In this thesis, rational points on K3 surfaces are studied. In the first part of Chapter 1 the Brauer group and the the Brauer-Manin obstruction are introduced. The second part of Chapter 1 is... Show moreIn this thesis, rational points on K3 surfaces are studied. In the first part of Chapter 1 the Brauer group and the the Brauer-Manin obstruction are introduced. The second part of Chapter 1 is devoted to the introduction of the refined Swan conductor and the link between the latter and the Brauer-Manin set. The aim of Chapter 2 is to give the first example of a K3 surface over a number field (in fact, over the rational numbers) for which a prime of good reduction is involved in the Brauer-Manin obstruction; this gives a negative answer to a question originally asked by Swinnerton-Dyer. In Chapter 3 the role of primes of good reduction in the Brauer-Manin obstruction is discussed, with a focus on K3 surfaces. Finally, in the last chapter, after introducing some techniques that can be used to compute the refined Swan conductor, several examples of Brauer-Manin obstruction on K3 surfaces are provided, with a focus on Kummer K3 surfaces. Show less
Deursen, L. van; Vaart, R. van der; Chavannes, N.H.; Aardoom, J.J. 2024
Introduction Cancer survivors face physical, lifestyle, psychological, and psychosocial challenges. Despite the availability of aftercare services, survivors still have unmet needs. Digital... Show moreIntroduction Cancer survivors face physical, lifestyle, psychological, and psychosocial challenges. Despite the availability of aftercare services, survivors still have unmet needs. Digital aftercare programs may ofer support, but their use is limited. This study aimed to examine what is needed to improve uptake and adoption of these programs. Additionally, it explored sociodemographic and clinical variables that may infuence these needs. Methods A mixed-methods approach was used, involving qualitative interviews and a questionnaire. The research was guided by the COM-B model of behaviour, which considers capability, opportunity, and motivation crucial for behaviour. Qualitative analysis was performed using the framework method. Statistical analyses involved descriptive statistics and regression analysis. Results Fourteen cancer survivors were interviewed, and 213 participants completed the questionnaire. Findings indicated that most respondents had a positive or neutral attitude towards digital aftercare programs, believing these could address their cancer-related challenges. Still, only a small percentage had experience with them, and most were unaware of their existence. Many expressed a desire to be informed about them. Some were uncertain about their efectiveness. Others were concerned about a lack of reimbursement. No signifcant infuence of the sociodemographic and clinical variables was found. Conclusion Cancer survivors are generally positive about digital aftercare programs but are often unaware of their availability. Raising awareness, clarifying their value, and providing support and reimbursement could enhance uptake and adoption. Implications for Cancer Survivors The current insights can help improve participation in digital aftercare programs, ultimately fostering health, well-being, and quality of life of cancer survivors. Show less
By discussing the bodily aspects of undersea immersion, this paper investigates the lived experiences of the photographer’s body in space. To do this, it draws on the work of phenomenological... Show moreBy discussing the bodily aspects of undersea immersion, this paper investigates the lived experiences of the photographer’s body in space. To do this, it draws on the work of phenomenological philosophers who have theorized the body, such as Edmund Husserl, Edward S. Casey, Maurice Merleau-Ponty, and Gaston Bachelard, showing how the body is simultaneously active and passive in its environs. To make this point tangible, it examines a recent photographic work by contemporary Dutch artist Roosmarijn Pallandt, who attempts to capture her bodily sensations by submerging herself underwater while taking photographs. The paper argues that her photographic practice augments the bilaterality of the phenomenal body: being both a physical body (Körper) that needs to hold together kinesthetically and a lived body (Leib) that can go further proprioceptively. Consequently, by employing phenomenology vis-à-vis Pallandt’s photographic practice, the author defines immersivity as being concurrently still and moving, static and dynamic, passive and active, that is: as being inactive in space. Following this line of argument, he puts forward that the bodily immersivity is an instance of sheer inactivity. Show less
In this dissertation I argue that the proto-daoist text the Zhuangzi and the ethical relation of Levinas are fruitful resources to reconsider the self-other relation in comparative philosophy.... Show moreIn this dissertation I argue that the proto-daoist text the Zhuangzi and the ethical relation of Levinas are fruitful resources to reconsider the self-other relation in comparative philosophy. Comparative philosophy is a hermeneutical practice in which the philosopher's assumptions, beliefs and emotional commitments influence and determine the comparative process. I argue that in order to overcome injustice and theoretical colonization of the cultural other, we need to adopt an ethical attiude in which we reside in the pivot and are willing to take the quesiton of social justice into account Show less
To cope with environmental changes, humans need to adjust their cognitive control states to meet different challenges. Two important cognitive control states are cognitive persistence and cognitive... Show moreTo cope with environmental changes, humans need to adjust their cognitive control states to meet different challenges. Two important cognitive control states are cognitive persistence and cognitive flexibility. Persistence is a state of maintaining stable attention, while flexibility is a state where attention can switch freely. These two states are antagonistic to each other; one cannot switch attention flexibly while being focused, and one cannot focus on a single stimulus while switching attention flexibly. Our understanding of the neural mechanisms underlying these cognitive control states is still limited. Therefore, in this dissertation, we used two brain science research techniques, EEG and fMRI, to study brain activities associated with these two states. To induce these states, the dissertation employed two creative thinking tasks, namely convergent thinking and divergent thinking, and two meditation techniques, focused attention meditation and open monitoring meditation. The results discuss EEG and fMRI indicators related to these states, providing preliminary evidence for research in this field. Show less
The main aim of the present thesis is to investigate the authoritative role of the ancestors in matters of social cohesion, succession, inheritance, property ownership and gender norms. In... Show moreThe main aim of the present thesis is to investigate the authoritative role of the ancestors in matters of social cohesion, succession, inheritance, property ownership and gender norms. In particular the purpose is to ascertain whether religious sources concerning the cult of the ancestors can provide concrete evidence on how justice was actually administrated in Ancient Egypt. The title – Only the dead can tell us – derived indeed from the idea that this core of religious beliefs, which also included necromantic practices, can be invaluable for better understanding Ancient Egyptian society and justice. Show less
The mucosal origin hypothesis of rheumatoid arthritis has renewed the interest in IgA autoantibodies, but their added value over IgG anti-citrullinated protein antibody (ACPA) and IgM rheumatoid... Show moreThe mucosal origin hypothesis of rheumatoid arthritis has renewed the interest in IgA autoantibodies, but their added value over IgG anti-citrullinated protein antibody (ACPA) and IgM rheumatoid factor (RF) for modern treatment outcomes remains unknown. We aimed to investigate the prognostic value of IgA-ACPA and IgA-RF for treatment outcomes in an early arthritis population. IgA-ACPA/RF isotypes were measured in baseline sera from 480 inflammatory arthritis (IA) patients, who were included in the treatment in the Rotterdam Early Arthritis Cohort trial (tREACH). The tREACH trial was a multicentre, stratified, single-blinded trial with a treat-to-target approach. The prognostic value of IgA-ACPA/RF was determined by evaluating differences in (1) quick-attained (< 6 months after diagnosis) and persistent remission rates, (2) DMARD-free remission and (3) biological use between IA patients with and without IgA-ACPA/RF over 3 years of follow-up. IgA-ACPA was present in 23% of patients and overlapped with IgG-ACPA positivity in 94%. Similarly, IgA-RF overlapped with IgM-RF in 90% of patients. IgA-ACPA positivity was associated with lower DFR rates and more biological use, but this effect was largely mediated by the presence of IgG-ACPA, since this effect disappeared after stratification for IgG-ACPA (HR 0.6, 95%CI 0.2-1.6 for DFR). No differences were observed in ‘quick-attained and persistent remission’ rates and for IgA-RF. Their seems to be no additional value of IgA-ACPA and IgA-RF for modern, long-term clinical outcomes. The effects of IgA-ACPA seen in our study are largely mediated by the presence of IgG-ACPA. Based on these results, there is no rationale for measuring these isotypes in daily practice. Show less
