Estimates of the number of vascular plant species currently under threat of extinction are shockingly high, with the highest extinction rates reported for narrow-range, woody plants, especially in... Show moreEstimates of the number of vascular plant species currently under threat of extinction are shockingly high, with the highest extinction rates reported for narrow-range, woody plants, especially in biodiversity hotspots with Mediterranean and tropical climates. The large genus Erica is a prime example, as a large proportion of its 851 species, all shrubs or small trees, are endemic to the Cape Floristic Region (CFR) of South Africa. Almost two hundred are known to be threatened and a further hundred are ‘Data Deficient’. We need to target conservation efforts and research to fill the most problematic knowledge gaps. This can be especially challenging in large genera, such as Erica, with numerous threatened species that are closely related. One approach involves combining knowledge of phylogenetic diversity with that of IUCN threat status to identify the most Evolutionarily Distinct and Globally Endangered (EDGE) species. We present an expanded and improved phylogenetic hypothesis for Erica (representing 65% of described species diversity) and combine this with available threat and distribution data to identify species and geographic areas that could be targeted for conservation effort to maximise preservation of phylogenetic diversity (PD). The resulting 39 EDGE taxa include 35 from the CFR. A further 32 high PD, data deficient taxa are mostly from outside the CFR, reflecting the low proportion of assessed taxa outside South Africa. The most taxon-rich areas are found in the south-western CFR. They are not the most phylogenetically diverse, but do include the most threatened PD. These results can be cross-referenced to existing living and seed-banked ex situ collections and used to target new and updated threat assessments and conservation action. Show less
This paper looks at the complex manner in which children were documented in Ottoman Egypt and their access to citizenship later in postcolonial Egypt. It discusses the making of social and... Show moreThis paper looks at the complex manner in which children were documented in Ottoman Egypt and their access to citizenship later in postcolonial Egypt. It discusses the making of social and political categories, like citizenship and statelessness, and how Greeks moved through those categories. This paper also analyzes how these categories were imposed, first by the Ottoman Empire and then by the Egyptian nation-state. The end of the Ottoman Empire in 1922, and the declaration of the Egyptian Republic in 1953, the Suez Crisis in 1956, the Arab-Israeli Wars in 1967 and 1973, and the new labor laws of the 1950s and 1960s, among other events, impacted Greeks and others who lived in Egypt at that time. The impact among Greeks in Suez Canal cities was particularly evident in the community’s cohesion, as most evacuated the cities in 1967 with almost everyone else following in 1973. These economic and political factors, and the social processes the community underwent, defined Greek children’s relation with the Egyptian postcolonial state. Show less
Aims: To evaluate the prognostic implications of the left atrial reservoir strain–defined diastolic dysfunction (LARS-DD) grade in patients undergoing transcatheter aortic valve implantation (TAVI)... Show moreAims: To evaluate the prognostic implications of the left atrial reservoir strain–defined diastolic dysfunction (LARS-DD) grade in patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) and to determine whether post-TAVI LARS was more closely associated with new-onset atrial fibrillation than pre-TAVI LARS. Methods and results: Pre-TAVI LARS-DD was evaluated by speckle-tracking echocardiography and was assigned as Grade 0 to 1 (LARS ≥24%), Grade 2 (LARS 19–24%), and Grade 3 (LARS <19%). Patients were followed up for the primary endpoint of all-cause mortality from the date of TAVI. For the secondary endpoint, patients with pre- and post-TAVI LARS measurements and no history of atrial fibrillation were evaluated for the occurrence of new-onset atrial fibrillation. A total of 601 patients [median age 81 (76–85) years, 53% males] were included. Overall, 169 patients (28%) were LARS-DD Grade 0/1, 96 patients (16%) were LARS-DD Grade 2, and 336 (56%) were LARS-DD Grade 3. Over a median follow-up of 40 (interquartile range 26–58) months, a total of 258 (43%) patients died. In a comprehensive multivariable Cox regression model, the LARS-DD grade was independently associated with all-cause mortality [adjusted hazard ratio (HR) 1.28 per one-grade increase, 95% confidence interval (CI) 1.07–1.53, P = 0.007]. For the secondary endpoint of new-onset atrial fibrillation, a total of 285 patients were evaluated. Post-TAVI LARS (subdistributional HR 1.14 per 1% <20%, 95% CI 1.05–1.23, P = 0.0009), but not pre-TAVI LARS (P = 0.93), was independently associated with new-onset atrial fibrillation. Conclusion: An increased LARS-DD grade was independently associated with long-term post-TAVI survival in patients with severe AS. Post-TAVI LARS was closely related to the occurrence of new-onset atrial fibrillation. Show less
Nădăban, A.; Frame, C.O.; El Yachioui, D.; Gooris, G.S.; Dalgliesh, R.M.; Malfois, M.; ... ; Bouwstra, J.A. 2024
The lipids located in the outermost layer of the skin, the stratum corneum (SC), play a crucial role in maintaining the skin barrier function. The primary components of the SC lipid matrix are... Show moreThe lipids located in the outermost layer of the skin, the stratum corneum (SC), play a crucial role in maintaining the skin barrier function. The primary components of the SC lipid matrix are ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFAs). They form two crystalline lamellar phases: the long periodicity phase (LPP) and the short periodicity phase (SPP). In inflammatory skin conditions like atopic dermatitis and psoriasis, there are changes in the SC CER composition, such as an increased concentration of a sphingosine-based CER (CER NS) and a reduced concentration of a phytosphingosine-based CER (CER NP). In the present study, a lipid model was created exclusively forming the SPP, to examine whether alterations in the CER NS:CER NP molar ratio would affect the lipid organization. Experimental data were combined with molecular dynamics simulations of lipid models containing CER NS:CER NP at ratios of 1:2 (mimicking a healthy SC ratio) and 2:1 (observed in inflammatory skin diseases), mixed with CHOL and lignoceric acid as the FFA. The experimental findings show that the acyl chains of CER NS and CER NP and the FFA are in close proximity within the SPP unit cell, indicating that CER NS and CER NP adopt a linear conformation, similarly as observed for the LPP. Both the experiments and simulations indicate that the lamellar organization is the same for the two CER NS:CER NP ratios while the SPP NS:NP 1:2 model had a slightly denser hydrogen bonding network than the SPP NS:NP 2:1 model. The simulations show that this might be attributed to intermolecular hydrogen bonding with the additional hydroxide group on the headgroup of CER NP compared with CER NS. Show less
Nimphy C.A., Elzinga B.M., Does A.J.W. van der; Bockstaele B. van; Pérez-Edgar K., Westenberg M, Aktar E. 2024
INTRODUCTION\nMETHODS\nRESULTS\nCONCLUSION\nThe epidermal inflammation associated with psoriasis drives skin barrier perturbations. The skin barrier is primarily located in stratum corneum (SC).... Show moreINTRODUCTION\nMETHODS\nRESULTS\nCONCLUSION\nThe epidermal inflammation associated with psoriasis drives skin barrier perturbations. The skin barrier is primarily located in stratum corneum (SC). Its function depends on the SC lipid matrix of which ceramides constitute important components. Changes in the ceramide profile directly correlate to barrier function. In this study, we characterized the dynamics of the barrier function and ceramide profile of psoriatic skin during anti-Interleukin-23 therapy with guselkumab.\nWe conducted a double-blind, randomized controlled trial in which 26 mild-to-severe plaque psoriasis patients were randomization 3:1 to 100mg guselkumab or placebo for 16 weeks and barrier dynamics monitored throughout. Barrier function was measured by trans-epidermal Water loss measurements. Untargeted ceramide profiling was performed using liquid chromatography-mass spectrometry after SC was harvested using tape-stripping.\nThe barrier function and ceramide profile of lesional skin normalized to that of controls during treatment with guselkumab, but not placebo. This resulted in significant differences compared to placebo at the end of treatment. Changes in the lesional ceramide profile during treatment correlated with barrier function and target lesion severity. Non-lesional skin remained similar throughout treatment.\nGuselkumab therapy restored the skin barrier in psoriasis. Concomitant correlations between skin barrier function, the ceramide profile and disease severity demonstrate their interdependency. Show less
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
