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The see-through brain: Changes in inhibition through space and time in a mouse model for Kleefstra Syndrome
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325474.pdf (Publisher’s version ) (Open Access)In my thesis entitled “The see-through brain: Changes in inhibition through space and time in a mouse model for Kleefstra Syndrome” I investigate the development of inhibitory neurons in a mouse model of Kleefstra Syndrome, a syndromic form of intellectual disability with strong autistic traits (Ehmt1+/- mouse).
We first investigated the impact of Ehmt1 haploinsufficiency on the maturation of Parvalbumin-positive GABAergic neurons during the critical periods for the auditory, somatosensory and visual cortices. We found that while PV+ neuron maturation was generally delayed in Ehmt1+/- mice, it eventually reached wild-type levels—except in layer 4 of the primary somatosensory cortex.
We then scaled up from single brain areas to the entire mouse brain. To this end we implemented whole-brain clearing and imaging using the iDISCO technique and developed a new data analysis pipeline, FriendlyClearmap. We validated this new pipeline by imaging the three largest groups of GABAergic interneurons in wild type mice: PV+, SST+, and VIP+.
When we used this pipeline on Ehmt1+/- mice, we discovered changes in all three main GABAergic cell classes, with VIP+ neurons being more abundant in the Ehmt1+/- cortex and SST+ neurons being less abundant in the Ehmt1+/- cortex and the amygdala. Most notably, we identified an early hypermaturation of PV+ neurons in the amygdala, which persisted into adulthood and leads to increased inhibitory transmission at the circuit level.
To conclude, with this thesis I show that Ehmt1+/- haploinsufficiency affects the entire inhibitory system of the mouse brain, but in a region- and cell-type specific way – we found both delays as well as speedups, overabundance as well as scarcity, depending on the time and place.Radboud University, 17 november 2025Promotores : Nadif Kasri, N., Bokhoven, J.H.L.M. van Co-promotor : Schubert, D.268 p
Disparities in cancer incidence and stage at diagnosis between male and female patients in the Netherlands
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325664.pdf (Publisher’s version ) (Closed access)9 p
The metallicity dependence of long-duration gamma-ray bursts
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326341.pdf (Publisher’s version ) (Open Access
Turning Chairs, Opening Minds: Redesigning Feedback in Medical Clerkships
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326073.pdf (Publisher’s version ) (Open Access)5 p
Joodse burgers in Hengelo. Onteigening en rechtsherstel
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Working to promote feelings of safety among individuals with mild intellectual disabilities or borderline intellectual functioning who display severe challenging behavior: A qualitative study within residential care
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322467.pdf (Publisher’s version ) (Open Access)Feeling safe is important but not self-evident for people with mild intellectual disabilities or borderline intellectual functioning who exhibit severe challenging behavior. The present study explores how organizations involved in the collaboration 'Pro' work to promote feelings of safety among their service users in residential care, with a focus on unconditionality, the context and service users' needs. Qualitative data from ethnographic longitudinal research, eight semi-structured interviews, and six focus groups were thematically analyzed. Data were primarily collected at three residential disability service organizations. Three themes were identified from the data: 1) All levels of the organization subscribe to the vision of providing unconditional support, 2) Providing stability in teams and support within a dynamic environment, 3) Striving to give service users as ordinary a life as possible. Working to promote service users' safety requires the active commitment of all professionals in the organization. Future research into the actual work done by organizations may provide valuable insights into how service users' safety may be enhanced.22 augustus 202527 p
From Planning to Presence: The Power of a ‘5-to-12 Death’ and the Emergence of Meaningful Rituals beyond the Euthanasia Day
No full textItem does not contain fulltext20 years of the Centre for Death & Society, 12 juni 202
A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis
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324621.pdf (Publisher’s version ) (Open Access)BACKGROUND: Giant-cell arteritis is a systemic vasculitis with limited treatment options. The efficacy and safety of upadacitinib - a selective Janus kinase (JAK) inhibitor that blocks the signaling of several cytokines, including interleukin-6 and interferon-γ - are unknown in patients with giant-cell arteritis. METHODS: We randomly assigned patients with new-onset or relapsing giant-cell arteritis, in a 2:1:1 ratio, to receive upadacitinib at a dose of 15 mg or 7.5 mg orally once daily plus a 26-week glucocorticoid taper or placebo plus a 52-week glucocorticoid taper. The primary end point was sustained remission at week 52, defined by the absence of signs or symptoms of giant-cell arteritis from week 12 through week 52 and adherence to the protocol-specified glucocorticoid taper. RESULTS: A total of 209 patients received upadacitinib at a dose of 15 mg, 107 received upadacitinib at a dose of 7.5 mg, and 112 received placebo; 70% of the patients had new-onset giant-cell arteritis. Upadacitinib at a dose of 15 mg showed superiority over placebo with respect to the primary end point (46.4% [95% confidence interval {CI}, 39.6 to 53.2] vs. 29.0% [95% CI, 20.6 to 37.5]; P = 0.002). Upadacitinib at a dose of 15 mg was superior to placebo in the analysis of the hierarchically prespecified and multiplicity-controlled key secondary end points of sustained complete remission, time to a disease flare, cumulative glucocorticoid exposure, and patient-reported outcomes. Upadacitinib at a dose of 7.5 mg was not superior to placebo with respect to the primary end point (41.1% [95% CI, 31.8 to 50.4]). Safety outcomes during the treatment period of 52 weeks were similar in the upadacitinib and placebo groups. Although cardiovascular risk is a potential concern with a JAK inhibitor, no major adverse cardiovascular events occurred in the upadacitinib groups. CONCLUSIONS: In patients with giant-cell arteritis, upadacitinib at a dose of 15 mg - but not 7.5 mg - with a 26-week glucocorticoid taper showed efficacy superior to that of placebo with a 52-week glucocorticoid taper. (Funded by AbbVie; SELECT-GCA ClinicalTrials.gov number, NCT03725202.)
Noot bij: EHRM 25 mei 2025, 2025, (SS e.a. t. Italië (EHRM, nr. 21660/18). ʻPullbacksʼ uitgevoerd door Libië dankzij Italiaanse ondersteuning vallen buiten rechtsmacht Italië)
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323882.pdf (Publisher’s version ) (Closed access)25 mei 202