One of the most important correlation functions in physics, especially in cosmology, is the energy density, which describes how much energy is present at each point in spacetime due to matter... Show moreOne of the most important correlation functions in physics, especially in cosmology, is the energy density, which describes how much energy is present at each point in spacetime due to matter fields. A key contribution to the energy density of the primordial universe comes from gravitational waves (GWs), as they offer a way to study epochs inaccessible with electromagnetic signals. This thesis focuses on vacuum GWs, the tensorial counterpart of scalar quantum fluctuations that seeded galaxies. Their renormalized energy density connects to the observed abundance of the first light elements, providing a pathway to constrain vacuum GWs without direct detection. Careful renormalization of the divergences arising in computing the energy density of vacuum GWs reveals that they only renormalize background quantities and do not act as an additional radiation-like species. We stress that a fundamental role in reaching this conclusion is played by properly following through with the renormalization procedure, which is not a way to "sweep divergences under the rug" by introducing a hard cutoff in divergent integrals. Instead, it is a well-defined method to absorb UV-divergent contributions and extract meaningful physical predictions. Show less
Willemsen, R.F.; Versluis, A.; Aardoom, J.J.; Petrus, A.H.J.; Silven, A.V.; Chavannes, N.H.; Dijke, A. van 2024
Introduction: Depressive and anxiety disorders are common mental disorders ranking among the leading causes of global disease burden. Not all clients currently benefit from therapy and clients are... Show moreIntroduction: Depressive and anxiety disorders are common mental disorders ranking among the leading causes of global disease burden. Not all clients currently benefit from therapy and clients are looking for modern ways of therapy. Online psychotherapy is a promising option for better meeting clients’ needs. Recently, a new psychotherapy concept has emerged that combines videoconferencing sessions with support through a mobile application. The latter allows for ecological momentary assessments and interventions, facilitates communication between patients and therapists in between sessions through chat, and allows for incorporating feedbackinformed treatment principles. Material and methods: The study was a retrospective observational matched cohort study, comparing online psychotherapy with Therapy As Usual (TAU) for clients with depressive or anxiety disorders. Data were obtained via questionnaires, which are part of standard clinical care. Primary outcomes included general mental functioning, and symptoms of depression and anxiety. Secondary outcomes were efficiency, client satisfaction, and therapy costs. Primary endpoints were analyzed using linear mixed models analysis, with an interaction term between time and group. Secondary outcomes were analyzed using linear regression. Results: Larger improvements were observed in the online compared to the TAU group for general mental functioning and depressive disorder (i.e., General mental functioning: B = -8.50, 95 CI: − 15.01 − − 1.97, p = 0.011; Depressive disorder: B = − 3.66, 95 % CI: − 5.79 – -1.54p < 0.01). No significant differences in change over time between the two groups were observed for anxiety disorder (B = -3.64, 95 % CI: (− 13.10 – 5.82) p = 0.447). The total number of sessions was significantly higher in the online psychotherapy group than in TAU (B = 3.71, p < 0.01), although clients were matched on treatment time in weeks. Treatment session duration in minutes was comparable across the groups. Discussion: Online psychotherapy with app support showed to be a promising alternative to TAU for depressive and anxiety disorders. More research is needed to evaluate the effectiveness, cost-effectiveness and client satisfaction of online psychotherapy compared to TAU, such as randomized controlled trials or studies multiple baseline series designs, and in-depth qualitative research. Show less
This systematic review aims to summarize the currently available literature regarding the association of plasma metabolites and vitamins with the nutritional status in adult hospitalized patients.... Show moreThis systematic review aims to summarize the currently available literature regarding the association of plasma metabolites and vitamins with the nutritional status in adult hospitalized patients. A systematic literature search was performed in PubMed and EMBASE, and all studies comparing metabolite or vitamin levels in malnourished versus well-nourished hospitalized patients were included. Twenty-three studies were eligible for inclusion, representing 3803 hospitalized patients. Several metabolites involved in the metabolism of methionine, purine, glutathione, carnitine, phenylalanine, and tryptophan, as well as some vitamins, seem to be associated with malnutrition in hospitalized patients. These compounds can potentially be used to assess nutritional status. Show less
The on-going dialectic of Muslim desires regarding the rules of Islam ('Sharia'), followed by Western responses and, in turn, Muslim counter-responses, is what creates the dynamic that makes up ... Show moreThe on-going dialectic of Muslim desires regarding the rules of Islam ('Sharia'), followed by Western responses and, in turn, Muslim counter-responses, is what creates the dynamic that makes up ‘Sharia in the West’. This article discusses the third tier of the Sharia-dialectic, that is the manners in which Muslims respond (in terms of Sharia) to the Western responses regarding Sharia. It will be shown that the Muslim responses are quite diverse and at time squite innovative. This sheds a new light on our understanding of 'Sharia'. Show less
Background1H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and... Show moreBackground1H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals.MethodsLeveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by 1H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors.FindingsWe trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays. Interestingly, a previously reported multi-analyte score indicating mortality risk (MetaboHealth) could also be accurately reconstructed. Sixteen of our derived surrogates, including the MetaboHealth surrogate, showed significant associations with mortality, independent of relevant covariates.InterpretationThe addition of our metabolic analyte-derived surrogates to the well-established epigenetic clock GrimAge demonstrates that our surrogates potentially represent valuable mortality signal. Show less
BackgroundDepressive symptoms are associated with an increased risk of Alzheimer's disease (AD). There has been a recent emergence in plasma biomarkers for AD pathophysiology, such as amyloid-beta ... Show moreBackgroundDepressive symptoms are associated with an increased risk of Alzheimer's disease (AD). There has been a recent emergence in plasma biomarkers for AD pathophysiology, such as amyloid-beta (Aβ) and phosphorylated tau (p-tau), as well as for axonal damage (neurofilament light, NfL) and astrocytic activation (glial fibrillary acidic protein, GFAP). Hypothesizing that depressive symptoms may occur along the AD process, we investigated associations between plasma biomarkers of AD with depressive symptoms in individuals without dementia.MethodsA two-stage meta-analysis was performed on 2 clinic-based and 6 population-based cohorts (N = 7210) as part of the Netherlands Consortium of Dementia Cohorts. Plasma markers (Aβ42/40, p-tau181, NfL, and GFAP) were measured using Single Molecular Array (Simoa; Quanterix) assays. Depressive symptoms were measured with validated questionnaires. We estimated the cross-sectional association of each standardized plasma marker (determinants) with standardized depressive symptoms (outcome) using linear regressions, correcting for age, sex, education, and APOE ε4 allele presence, as well as subgrouping by sex and APOE ε4 allele. Effect estimates were entered into a random-effects meta-analysis.ResultsMean age of participants was 71 years. The prevalence of clinically relevant depressive symptoms ranged from 1% to 22%. None of the plasma markers were associated with depressive symptoms in the meta-analyses. However, NfL was associated with depressive symptoms only in APOE ε4 carriers (β 0.11; 95% CI: 0.05–0.17).ConclusionsLate-life depressive symptoms did not show an association to plasma biomarkers of AD pathology. However, in APOE ε4 allele carriers, a more profound role of neurodegeneration was suggested with depressive symptoms. Show less
COVID-19 has been associated with high mortality in patients treated with Chimeric Antigen Receptor (CAR) T-cell therapy for hematologic malignancies. Here, we investigated whether the outcome has... Show moreCOVID-19 has been associated with high mortality in patients treated with Chimeric Antigen Receptor (CAR) T-cell therapy for hematologic malignancies. Here, we investigated whether the outcome has improved over time with the primary objective of assessing COVID-19-attributable mortality in the Omicron period of 2022 compared to previous years. Data for this multicenter study were collected using the MED-A and COVID-19 report forms developed by the EBMT. One-hundred-eighty patients were included in the analysis, 39 diagnosed in 2020, 35 in 2021 and 106 in 2022. The median age was 58.9 years (min-max: 5.2–78.4). There was a successive decrease in COVID-19-related mortality over time (2020: 43.6%, 2021: 22.9%, 2022: 7.5%) and in multivariate analysis year of infection was the strongest predictor of survival (p = 0.0001). Comparing 2022 with 2020–2021, significantly fewer patients had lower respiratory symptoms (21.7% vs 37.8%, p = 0.01), needed oxygen support (25.5% vs 43.2%, p = 0.01), or were admitted to ICU (5.7% vs 33.8%, p = 0.0001). Although COVID-19-related mortality has decreased over time, CAR T-cell recipients remain at higher risk for complications than the general population. Consequently, vigilant monitoring for COVID-19 in patients undergoing B-cell-targeting CAR T-cell treatment is continuously recommended ensuring optimal prevention of infection and advanced state-of-the art treatment when needed. Show less
Kat, A.C. de; Roelofs, F.; Slagboom, P.E.; Broekmans, F.J.M.; Beekman, M.; Berg, N. van den 2024
Research questionAre age at last childbirth and number of children, as facets of female reproductive health, related to individual lifespan or familial longevity?DesignThis observational study... Show moreResearch questionAre age at last childbirth and number of children, as facets of female reproductive health, related to individual lifespan or familial longevity?DesignThis observational study included 10,255 female participants from a multigenerational historical cohort, the LINKing System for historical family reconstruction (LINKS), and 1258 female participants from 651 long-lived families in the Leiden Longevity Study (LLS). Age at last childbirth and number of children, as outcomes of reproductive success, were compared with individual and familial longevity using the LINKS dataset. In addition, the genetic predisposition in the form of a polygenic risk score (PRS) for age at menopause was studied in relation to familial longevity using the LLS dataset.ResultsFor each year increase in the age of the birth of the last child, a woman's lifespan increased by 0.06 years (22 days; P = 0.002). The yearly risk for having a last child was 9% lower in women who survived to the oldest 10% of their birth cohort (hazard ratio 0.91, 95% CI 0.86–0.95). Women who came from long-living families did not have a higher mean age of last childbirth. There was no significant association between familial longevity and genetic predisposition to age at menopause.ConclusionsFemale reproductive health associates with a longer lifespan. Familial longevity does not associate to extended reproductive health. Other factors in somatic maintenance that support a longer lifespan are likely to have an impact on reproductive health. Show less
Existing metabolomic clocks exhibit deficiencies in capturing the heterogeneous aging rates among individuals with the same chronological age. Yet, the modifiable and non-modifiable factors in... Show moreExisting metabolomic clocks exhibit deficiencies in capturing the heterogeneous aging rates among individuals with the same chronological age. Yet, the modifiable and non-modifiable factors in metabolomic aging have not been systematically studied. Here, a new aging measure—MetaboAgeMort—is developed using metabolomic profiles from 239,291 UK Biobank participants for 10-year all-cause mortality prediction. The MetaboAgeMort showed significant associations with all-cause mortality, cause-specific mortality, and diverse incident diseases. Adding MetaboAgeMort to a conventional risk factors model improved the predictive ability of 10-year mortality. A total of 99 modifiable factors across seven categories are identified for MetaboAgeMort. Among these, 16 factors representing pulmonary function, body composition, socioeconomic status, dietary quality, smoking status, alcohol intake, and disease status showed quantitatively stronger associations. The genetic analyses revealed 99 genomic risk loci and 271 genes associated with MetaboAgeMort. The tissue-enrichment analysis showed significant enrichment in liver. While the external validation of the MetaboAgeMort is required, this study illuminates heterogeneous metabolomic aging across the same age, providing avenues for identifying high-risk individuals, developing anti-aging therapies, and personalizing interventions, thus promoting healthy aging and longevity. Show less
This study explores Adzagbe, a youth language based on Ewe, spoken in Aflao, Ghana. It aims to uncover how this code is created and the reasons behind its development among Aflao's youth. Data was... Show moreThis study explores Adzagbe, a youth language based on Ewe, spoken in Aflao, Ghana. It aims to uncover how this code is created and the reasons behind its development among Aflao's youth. Data was collected through recorded conversations, interviews, and observations across four key zones of Adzagbe speakers: Zorokpome, Dekeme, Atisukorpe, and Border. Findings show that Adzagbe is formed through the manipulation of Ewe, combined with elements from some Ghanaian and West African languages, English and French, resulting in unique lexical items spanning nouns, verbs, adjectives, and adverbs. These manipulations include morphological changes like prefixation, suffixation, and reduplication, as well as phonological adjustments such as clipping and metathesis of word syllables. Semantic alterations involve metaphor, euphemism, and narrowing. Adzagbe idiomatic expressions are creative, often humorous, and rooted in Ewe, reflecting the speakers'identity, which is distinct from the older generation and mainstream Aflao culture. The language and associated culture are male-dominated, with practices like nicknaming, flamboyant fashion, and rebellious music. Displays of wealth, drug use, and attention-seeking behaviours such as hair dyeing and splurging on expensive vehicles are common in public settings. Adzagbe is also gendered and ageist, attracting criticism from the older generation, particularly towards its female speakers. Show less
Overall, the main objective of this thesis is to gain further insight in relevant outcome measures for older patients after breast cancer treatment. The specific aims of this thesis are threefold.... Show moreOverall, the main objective of this thesis is to gain further insight in relevant outcome measures for older patients after breast cancer treatment. The specific aims of this thesis are threefold. First, to improve breast cancer care for the older population by identifying patients who are likely to develop postoperative complications and side effects of therapy. Secondly, to investigate long-term effects of breast cancer treatment on quality of life and physical and psychological functioning. Third, to illustrate treatment patterns and survival of patients with HER2-overexpressing metastatic breast cancer in different age groups over time. Show less
This study examined to what extent current Dutch criminal justice practice complies with the rationale of the codification principle. It has emerged that within substantive special criminal law,... Show moreThis study examined to what extent current Dutch criminal justice practice complies with the rationale of the codification principle. It has emerged that within substantive special criminal law, the handling of the principle of legality and the principle of guilt regularly deviates from the general principles of substantive criminal law in the Dutch Criminal Code. In some instances, these deviations have been generalised, which has led to a movement that is not well compatible with the codification principle. This movement has been made visible in this study. The conclusions and recommendations that follow from this study aim to achieve a better coordination of special criminal law with the Criminal Code, and to a more adequate maintenance of substantive criminal law in the spirit of the codification principle. Show less
In the Autumn of 1962, a crew of twelve committed pacifists decided to sail into Soviet territory in order to protest against the resumption of nuclear testing at Novaya Zemlya. Without visas for... Show moreIn the Autumn of 1962, a crew of twelve committed pacifists decided to sail into Soviet territory in order to protest against the resumption of nuclear testing at Novaya Zemlya. Without visas for their final destination the voyage was, by the crew’s own admission, a study in ‘civil disobedience by boat’, meant to draw the eyes of the world to the dangers of nuclear weapons. With the assistance of European Quakers, Gandhians and other sympathisers at ports along the way, the voyage met with initial success. Hopes of global attention were dashed, however, when the Cuban missile crisis broke out just as Everyman III was detained by the Soviets at the port of Leningrad. Show less
Regulatory pressure causes hundreds of millions in economic damage each year and causes great social unrest. For decades, successive cabinets have had the ambition to reduce regulatory pressure.... Show moreRegulatory pressure causes hundreds of millions in economic damage each year and causes great social unrest. For decades, successive cabinets have had the ambition to reduce regulatory pressure. But despite all their diligence, all their efforts to involve all kinds of forces from society in regulations, all the research and the use of a variety of instruments, they have not succeeded in reducing the regulatory pressure as experienced by society. Regulatory pressure has so far mainly been approached from an economic-instrumental perspective. Within this perspective, citizens weigh the advantages of rules against the disadvantages. But is that the only way in which people experience regulatory pressure?Epstein's Cognitive-experiential self-theory shows that our brain has developed in the course of evolution in such a way that there are people who trust their reason more and that there are people who rely more intuitively on their experience. This dissertation shows that rational people deal with rules very differently than experience-oriented people and indicates the consequences this has for the experience of regulatory pressure. Regulators who want to direct behaviour in our society must balance a rational experience of rules with an experiential experience of rules. Show less
Organic amendments applied to agricultural fields can partially offset our carbon emissions to the atmosphere and improve the resilience of agriculture to the effects of climate change. Driving... Show moreOrganic amendments applied to agricultural fields can partially offset our carbon emissions to the atmosphere and improve the resilience of agriculture to the effects of climate change. Driving these benefits, however, are complex and poorly understood interactions between organic amendment properties, microbial communities and soil environmental conditions. In this thesis, I explore the impact of amendment decomposition on changes in soil microbial, chemical and physical properties to develop a better understanding of how different organic amendments can be utilized for sustainable soil management and climate-smart agriculture. Experimental results reveal a number of properties within amendments that are influential in driving efficient soil carbon accumulation, microbial biomass growth, and improving soil hydraulic and physical properties. We also demonstrate the impact of amendments on changes in the soil resilience to rapid temperature fluctuations and introduce the MiPrime model, a model for predicting soil carbon dynamics after applying organic amendments of different types. Through the work in this thesis, we hope to facilitate the design of more efficient and effective amendment application strategies. Show less
