Design of the ExCersion-VCI study: The effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment

There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination ≥22 and Clinical Dementia Rating ≤0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Interplay between gene-expression profiling and adjuvant systemic treatment decision-making in early stage breast cancer patients

Adjuvant systemic treatment (AST) has improved outcome for breast cancer patients. However, not every breast cancer patient benefits from AST. Therefore, clinical treatment guidelines have been developed to distinguish those patients in whom the benefits of AST outweigh the negative effects based on their clinicopathological profile. In the first part of this thesis we describe the increased use of AST in Dutch early stage breast cancer patients on a nation-wide level under the influence of evolving clinical treatment guidelines. Furthermore, we demonstrate that guidelines are not always followed and that especially undertreatment (i.e. not receiving AST despite a guideline recommendation) is common. Clinicopathological factors do not always accurately identify those patients in whom AST is beneficial. In recent years gene-expression profiles (GEPs) have been developed to better identify those patients in whom AST is beneficial. In the second part of this thesis we describe how GEPs are currently deployed, the impact on the administration of adjuvant chemotherapy and chemotherapy decision-making in early stage breast cancer patients on a nationwide level. Concurrent with the introduction of GEPs in clinical practice, four molecular subtypes of breast cancer were identified which are associated with breast cancer outcome. These subtypes are increasingly used in the AST decision-making process. Pathological assessment of hormone receptor status, Ki67 status and Her2-Neu status can be used as a surrogate to distinguish between these molecular subtypes. In the last part of this thesis reveal a high discrepancy between molecular subtyping based on pathological assessment or a gene-expression test

Interplay between gene-expression profiling and adjuvant systemic treatment decision-making in early stage breast cancer patients

Adjuvant systemic treatment (AST) has improved outcome for breast cancer patients. However, not every breast cancer patient benefits from AST. Therefore, clinical treatment guidelines have been developed to distinguish those patients in whom the benefits of AST outweigh the negative effects based on their clinicopathological profile. In the first part of this thesis we describe the increased use of AST in Dutch early stage breast cancer patients on a nation-wide level under the influence of evolving clinical treatment guidelines. Furthermore, we demonstrate that guidelines are not always followed and that especially undertreatment (i.e. not receiving AST despite a guideline recommendation) is common. Clinicopathological factors do not always accurately identify those patients in whom AST is beneficial. In recent years gene-expression profiles (GEPs) have been developed to better identify those patients in whom AST is beneficial. In the second part of this thesis we describe how GEPs are currently deployed, the impact on the administration of adjuvant chemotherapy and chemotherapy decision-making in early stage breast cancer patients on a nationwide level. Concurrent with the introduction of GEPs in clinical practice, four molecular subtypes of breast cancer were identified which are associated with breast cancer outcome. These subtypes are increasingly used in the AST decision-making process. Pathological assessment of hormone receptor status, Ki67 status and Her2-Neu status can be used as a surrogate to distinguish between these molecular subtypes. In the last part of this thesis reveal a high discrepancy between molecular subtyping based on pathological assessment or a gene-expression test

Use and Impact of the 21-Gene Recurrence Score in Relation to the Clinical Risk of Developing Metastases in Early Breast Cancer Patients in the Netherlands

Background: The nationwide use of the 21-gene recurrence score (21-RS) and implications regarding chemotherapy administration in relation to clinical risk in early breast cancer patients are investigated. Methods: Breast cancer patients surgically treated between 2014 and 2016 were selected from the Netherlands Cancer Registry and categorized as having a clinical low, intermediate, or high risk of developing metastases. Deployment of the 21-RS is advocated in patients with an intermediate risk of developing metastases. The use and impact of the 21-RS test result on chemotherapy administration were assessed in relation to the clinical risk as well as patient and tumor characteristics; χ2 tests were used for analysis. Results: Of all patients, 20,488 were considered as clinical low-, 4,309 as intermediate-, and 15,266 as high-risk patients. The 21-RS was deployed in 0.1% (n = 23), 3.2% (n = 137), and 0.6% (n = 90) of these categories, respectively. In the clinical intermediate-risk group, the 21-RS assigned 73.7, 13.1, and 13.1% of patients to the genomic low-, intermediate-, and high-risk category, respectively. Adherence to the 21-RS was 95.6% in these patients. Conclusion: In the Netherlands, the 21-RS test is applied both inside and outside the guideline-directed area. In case of discordance between the genomic and clinical risk, patients were treated in line with the result of the 21-RS