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De aanmaning voor de naheffingsaanslag parkeerbelasting is terecht. Dat belanghebbende de elektronische bekendmaking in de berichtenbox van MijnOverheid heeft gemist komt voor zijn rekening.
No full textIn de annotatie ga ik in op de omstandigheid dat mensen door het missen van aanmaningen in financiële problemen kunnen komen. Ook ga ik in op de ontwikkelingen die gaande zijn om kosteloze betalingsherinneringen te sturen voor (overheids)vorderingen
FIGNL1 inhibits homologous recombination in BRCA2 deficient cells by dissociating RAD51 filaments
No full textHomologous recombination (Hr) deficiency upon breast cancer Gene 2 (brcA2) loss arises from defects in the formation of rAD51 nucleoprotein filaments. We demonstrate that loss of the anti-recombinase Fidgetin Like 1 (FIGNL1) retains rAD51 loading at DNA double-stranded breaks (DSbs) in brcA2-deficient cells, leading to genome stability, Hr proficiency, and viability of brcA2-deficient mouse embryonic stem cells. Mechanistically, we demonstrate that strand invasion and subsequent Hr defects upon brcA2 loss primarily arise from the unrestricted removal of rAD51 from DSb sites by FIGNL1, rather than from defective rAD51 loading. Furthermore, we identify that the MMS22L-tONSL complex interacts with FIGNL1 and is critical for Hr in brcA2/FIGNL1 double-deficient cells. these findings identify a pathway for tightly regulating rAD51 activity to promote efficient Hr, offering insights into mechanisms of chemoresistance in brcA2-deficient tumors.</p
Excluding Investment Arbitration through Double Tax Agreements with a New Article 25 of the UN Model:A Feasible Way Forward?
No full textThis article assesses the consequences of potential amendments to article 25 of the United Nations Model Tax Convention. The new article 25 of the UN Model and the new Commentary on that article deal with arbitration under tax treaties and essentially aim to restrict the scope of international trade and investment arbitration when dealing with tax matters. The question is whether that can effectively be achieved by revising article 25 of the UN Model. This article will first assess the practical application of the new rule in the situations it seems to be intended for. For the legal aspects, the article will treat the subject matter as an episode of fragmentation and see what rules of international law have earlier proven useful in similar situations. The Vienna Convention on the Law of Treaties from 1969 will be the background to the discussion. The conclusion is that the road to a practical application has uncertainties still unresolved. If the provision makes it into tax treaties in relationships where it was intended, it is not certain that it would fulfil its objectives
Investors’ Quantitative Disclosure:Target Prices by Short Sellers
No full textWhile few market participants besides sell-side analysts publicly disclose target prices, we examine a growing trend where activist short sellers provide target prices to support their short theses. We find that short sellers’ target prices are informative in predicting future returns. We argue that their decision to disclose target prices reflects a trade-off between three factors: the speed of price adjustment, the exacerbation of certain risks, and reputation considerations. We find supporting evidence: target price disclosures are positively associated with price adjustment speed, the challenges and retaliation from shareholders and sell-side analysts, and proxies of short sellers’ information precision (which contributes to their reputation). We further argue and find evidence that the salience and quantitative nature of target prices contribute to the accelerated price adjustment by reducing investors’ processing costs. Overall, our study sheds light on the economic tradeoffs arising when investors decide to disclose quantitative information
Corrigendum to “The role of testosterone in odor-based perceptions of social status” [Evolution and Human Behavior, Volume 46 (2025) 106752]. (Evolution and Human Behavior (2025) 46(6), (S1090513825001011), (10.1016/j.evolhumbehav.2025.106752))
No full textThe authors regret incorrectly listing the university at which recruitment took place in the original version. This corrigendum corrects this mistake. The authors would like to apologise for any inconvenience caused.</p
EEG, machine learning, and prognostication after pediatric cardiac arrest:moving from promise to practice
No full textEORTC 1417 - REACTION:A phase II study of etoposide and cis/carboplatin with or without pembrolizumab in untreated extensive small cell lung cancer
No full textBackground Anti-PD-L1 antibodies with platinum-etoposide extend overall survival (OS) of extensive disease Small Cell Lung Cancer (ED-SCLC) patients. We evaluated the benefit of first-line pembrolizumab with platinum-etoposide in chemo-sensitive ED-SCLC. Methods REACTION is a multicenter, open-label, randomized phase II trial. Eligible patients (responders after 2 cycles of platinum-etoposide) were randomized 1:1 to experimental arm pembrolizumab in combination with 4 cycles of platinum-etoposide then pembrolizumab vs platinum-etoposide in the control arm. The primary endpoint was progression free survival (PFS). Circulating tumour cells (CTCs) were enumerated and their association with PFS and OS was investigated. Results Between Feb 7, 2018 and Oct 31, 2019, 125 patients were recruited (61 vs 64 experimental and control arms respectively) with 119 (58 vs 61) eligible and receiving at least one dose of treatment. Baseline characteristics were median age 65 vs 63.5 years, PS 1 (62 vs 60 %), and brain metastases (8 vs 11 %), in the experimental and control arms respectively. Amongst 124 patients who started treatment, 46 (37 %) experienced adverse events grade ≥ 3 for pembrolizumab arm vs 26 % in the control arm. Response rate was 61 % (67 vs 56 %). Median PFS (95 % CI) was 4.7 months (4.2, 5.6) vs 5.4 (4.7, 5.6), HR (80 % CI) = 0.84 (0.65, 1.09) and 1-sided p = 0.194. Median OS (95 % CI) was 12.3 months (8.9, 14.8) vs 10.4 (8.2, 12.2), HR (80 % CI) = 0.73 (0.54, 1.0) and 1-sided p = 0.097. CTC count per 7.5 ml blood at randomization was associated significantly with both PFS and OS regardless of treatment arms. Conclusions Pembrolizumab added to platinum-etoposide did not improve PFS over platinum-etoposide alone in chemo-sensitive patients with ED.</p
Timescapes of brand co-creation:A time-based multi-stakeholder place branding framework
No full textBrands are not static and evolve over time, yet the critical role of time in brand dynamics remains under-theorised. This paper proposes a time-based framework for place brand co-creation. It examines how time explains three key components of multi-stakeholder branding: participation, leadership, and the co-created brand. By introducing the concepts of timeframe, temporality, timing, tempo, duration, sequence, and time modalities and discussing them in place branding, this paper conceptualises the timescape of brand co-creation. The planned and emergent timescapes are introduced as two extreme ideal types of a time-based brand co-creation continuum, providing a time sensitive foundation for future theoretical and empirical studies on brand co-creation.</p
Anatomical progression of genetic frontotemporal lobar degeneration across the lifespan
No full textThe recent development of brain charts for the human lifespan offers an ideal modelling framework for pathologies such as genetic frontotemporal lobar degeneration (FTLD) which likely involve both neurodevelopmental and neurodegenerative processes over a lifetime. We have therefore combined this new methodological approach with MRI data from asymptomatic and symptomatic subjects, carrying C9orf72, MAPT or GRN mutations from the Genetic FTD Initiative (GENFI) and the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study. We analysed 37 532 MRIs from control subjects covering the entire lifespan and a total of 1341 MRIs from subjects with a pathogenic FTLD mutation, aged from 18 to 86 years old. We detected the first significant regional brain volume differences on average at 27 years old in C9orf72 and MAPT mutation carriers, and at 42 years old in GRN mutation carriers. The delay between the onset of anatomical changes and the average age of symptom onset (i.e. the presymptomatic phase) was 13 years for MAPT, 17 years for GRN and 34 years for C9orf72 mutation carriers. In terms of effect size, cumulative atrophy over the lifespan was twice as severe in affected brain regions in MAPT than in GRN or C9orf72 mutation carriers. However, the neurodegenerative process was spatially more extensive in C9orf72 (35 brain regions affected out of the 61 tested) compared with GRN or MAPT mutation carriers (25 and 18 regions, respectively). Schematically, the chronological staging of atrophy progression showed an initial involvement of the thalamus in C9orf72 expansion carriers, followed by the fronto-temporo-insular regions, the striatum and the amygdala. In GRN mutation carriers, atrophy began in fronto-insular areas, before progressing toward subcortical structures. In MAPT mutation carriers, atrophy affected the anterior temporal pole with the amygdala and hippocampus, before progressing to fronto-insular regions and the striatum. Our results using brain charts for the human lifespan show that C9orf72 is the most diffuse but also the slowest to emerge among genetic FTLD. MAPT FTLD is more aggressive and focal, while GRN FTLD is also rapidly progressive but with a later onset of the presymptomatic phase. Beyond quantification of the anatomical progression of genetic FTLD over the lifespan, these results may help determine the best timing to model and test disease-modifying strategies in FTLD, and monitor their effect in future clinical trials.</p