Derivatives. Replication and (auto)plagiarism in the social sciences

This working paper reports on the travelling exhibition “Derivatives”. This exhibition investigates the issue of originality in the context of (self) plagiarism and replication. The different views in the Arts and the scientific discourse form the point of departure for discovering how ideas that are identical can still be completely different and new, but also that ‘original’ works of art can be repetitive reproduction

Car Driving Performance in Hemianopia:An On-Road Driving Study

PURPOSE. To study driving performance in people with homonymous hemianopia (HH) assessed in the official on-road test of practical fitness to drive by the Dutch driver's licensing authority (CBR).METHODS. Data were collected from a cohort (January 2010-July 2012) of all people with HH following the official relicensure trajectory at Royal Dutch Visio and the CBR in the Netherlands. Driving performance during the official on-road tests of practical fitness to drive was scored by professional experts on practical fitness to drive, using the visual impairments protocol and a standardized scoring of visual, tactical and operational aspects. Age ranged from 27 to 72 years (mean = 52, SD = 11.7) and time since onset of the visual field defect ranged from 6 to 41 months (mean = 15, SD = 7.5).RESULTS. Fourteen (54%) participants were judged as fit to drive. Besides poor visual scanning during driving, specific tactical, and operational weaknesses were observed in people with HH that were evaluated as unfit to drive. Results suggest that judgement on practical fitness to drive cannot be based on solely the visual field size. Visual scanning and operational handling of the car were found to be more impaired with longer time not driven, while such an effect was not found for tactical choices during driving.CONCLUSIONS. Training programs aimed at improving practical fitness to drive in people with HH should focus on improving both visual scanning, as well as driving aspects such as steering stability, speed adaptation, and anticipating environmental changes.</p

Confirmatory factor analysis of the Dutch Screening Visual Complaints questionnaire in people with multiple sclerosis

BACKGROUND: Visual complaints among people with multiple sclerosis (pwMS) are common, but often difficult to recognize. The Screening Visual Complaints questionnaire (SVCq) has been developed to screen for visual complaints in people with a neurodegenerative disease, including multiple sclerosis (MS). A previous study performed a factor analysis in a normal population which revealed an acceptable one-factor model, a three-factor model and a five-factor model within the SVCq. To increase the usability of the SVCq in people with MS, the purpose of the current study was to investigate the fit of the three models in a cohort of pwMS. RESULTS: The confirmatory factor analysis on the SVCq in 493 people with MS showed good fit for all the models. The three-factor model (diminished visual perception, altered visual perception and ocular discomfort) outperformed the one-factor model. The five-factor model outperformed both models, which showed that dividing the first factor (diminished visual perception) into three more factors (function-related, luminance-related and task-related) has merit. CONCLUSIONS: All models may be useful in clinical care for pwMS. The one-factor model may give a quick overview of the presence and severity of visual complaints in general. The individual factors, of either the three- or the five factor models, may contribute to a better recognition of the nature of visual complaints in pwMS and may guide further steps in rehabilitation for pwMS with visual complaints

Direct Binding of Bovine IgG-Containing Immune Complexes to Human Monocytes and Their Putative Role in Innate Immune Training

Bovine milk IgG (bIgG) was shown to bind to and neutralize the human respiratory synovial virus (RSV). In animal models, adding bIgG prevented experimental RSV infection and increased the number of activated T cells. This enhanced activation of RSV-specific T cells may be explained by receptor-mediated uptake and antigen presentation after binding of bIgG-RSV immune complexes (ICs) with FcγRs (primarily CD32) on human immune cells. This indirect effect of bIgG ICs on activation of RSV-specific T cells was confirmed previously in human T cell cultures. However, the direct binding of ICs to antigen-presenting cells has not been addressed. As bovine IgG can induce innate immune training, we hypothesized that this effect could be caused more efficiently by ICs. Therefore, we characterized the expression of CD16, CD32, and CD64 on (peripheral blood mononuclear cells (PBMCs), determined the optimal conditions to form ICs of bIgG with the RSV preF protein, and demonstrated the direct binding of these ICs to human CD14 + monocytes. Similarly, bIgG complexed with a murine anti-bIgG mAb also bound efficiently to the monocytes. To evaluate whether the ICs could induce innate immune training more efficiently than bIgG itself, the resulted ICs, as well as bIgG, were used in an in vitro innate immune training model. Training with the ICs containing bIgG and RSV preF protein-but not the bIgG alone-induced significantly higher TNF-α production upon LPS and R848 stimulation. However, the preF protein itself nonsignificantly increased cytokine production as well. This may be explained by its tropism to the insulin-like growth factor receptor 1 (IGFR1), as IGF has been reported to induce innate immune training. Even so, these data suggest a role for IgG-containing ICs in inducing innate immune training after re-exposure to pathogens. However, as ICs of bIgG with a mouse anti-bIgG mAb did not induce this effect, further research is needed to confirm the putative role of bIgG ICs in enhancing innate immune responses in vivo

Familial hemiplegic migraine locus on 19p13 is involved in the common forms of migraine with and without aura

Migraine is a common neurological disease of two main types: migraine with aura and migraine without aura. Familial clustering suggests that genetic factors are involved in the etiology of migraine. Recently, a gene for familial hemiplegic migraine, a rare autosomal dominant subtype of migraine with aura, was mapped to chromosome 19p13. We tested the involvement of this chromosomal region in 28 unrelated families with the common forms of migraine with and without aura, by following the transmission of the highly informative marker D19S394. Sibpair analysis showed that affected sibs shared the same marker allele more frequently than expected by chance. Our findings thus also suggest the involvement of a gene on 19p13 in the etiology of the common forms of migraine

P-Glycoprotein Acts as an Immunomodulator during Neuroinflammation

Background: Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system in which autoreactive myelin-specific T cells cause extensive tissue damage, resulting in neurological deficits. In the disease process, T cells are primed in the periphery by antigen presenting dendritic cells (DCs). DCs are considered to be crucial regulators of specific immune responses and molecules or proteins that regulate DC function are therefore under extensive investigation. We here investigated the potential immunomodulatory capacity of the ATP binding cassette transporter P-glycoprotein (Pgp). P-gp generally drives cellular efflux of a variety of compounds and is thought to be involved in excretion of inflammatory agents from immune cells, like DCs. So far, the immunomodulatory role of these ABC transporters is unknown. Methods and Findings: Here we demonstrate that P-gp acts as a key modulator of adaptive immunity during an in vivo model for neuroinflammation. The function of the DC is severely impaired in P-gp knockout mice (Mdr1a/1b-/-), since both DC maturation and T cell stimulatory capacity is significantly decreased. Consequently, Mdr1a/1b-/- mice develop decreased clinical signs of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Reduced clinical signs coincided with impaired T cell responses and T cell-specific brain inflammation. We here describe the underlying molecular mechanism and demonstrate that P-gp is crucial for the secretion of pro-inflammatory cytokines such as TNF-alpha and IFN-gamma. Importantly, the defect in DC function can be restored by exogenous addition of these cytokines. Conclusions: Our data demonstrate that P-gp downmodulates DC function through the regulation of pro-inflammatory cytokine secretion, resulting in an impaired immune response. Taken together, our work highlights a new physiological role for P-gp as an immunomodulatory molecule and reveals a possible new target for immunotherap

Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4

Genes for familial hemiplegic migraine (FHM) and episodic ataxia type-2 (EA-2) have been mapped to chromosome 19p13. We characterized a brain- specific P/Q-type Ca2+ channel α1-subunit gene, CACNLIA4, covering 300 kb with 47 exons. Sequencing of all exons and their surroundings revealed polymorphic variations, including a (CA)(n)-repeat (D19S1150), a (CAG)(n)- repeat in the 3'-UTR, and different types of deleterious mutations in FHM and EA-2. In FHM, we found four different missense mutations in conserved functional domains. One mutation has occurred on two different haplotypes in unrelated FHM families. In EA-2, we found two mutations disrupting the reading frame. Thus, FHM and EA-2 can be considered as allelic channelopathies. A similar etiology may be involved in common types of migraine

The structure of the tetrasialoganglioside from human brain

Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle- age onset. In nine families, we identified heterozygous C- terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias

Twelve-year outcomes of watchful waiting versus surgery of mildly symptomatic or asymptomatic inguinal hernia in men aged 50 years and older:a randomised controlled trial

Background: Inguinal hernia belongs to the most common surgical pathology worldwide. Approximately, one third is asymptomatic. The value of watchful waiting (WW) in patients with asymptomatic or mildly symptomatic inguinal hernia has been established in a few randomised controlled trials (RCTs). The aim of this study was to assess long-term outcomes of a RCT comparing WW and elective surgery.Methods: In the original study, men aged ≥50 years with an asymptomatic or mildly symptomatic inguinal hernia were randomly assigned to WW or elective repair. In the present study, the primary outcome was the 12-year crossover rate to surgery, secondary outcomes were time-to-crossover, patient regret, pain, quality of life and incarceration. Dutch Trial Registry: NTR629. Findings: Out of 496 originally analysed patients, 488 (98.4%) were evaluable for chart review (WW: n = 258, surgery: n = 230), and 200 (41.0%) for telephone contact (WW: n = 106, surgery: n = 94) between November 2021 and March 2022 with a median 12 years follow-up (IQR 9–14). After 12 years, the estimated cumulative crossover rate to surgery was 64.2%, which was higher in mildly symptomatic than in asymptomatic patients (71.7% versus 60.4%, HR 1.451, 95% CI: 1.064–1.979). Time-to-crossover was longer in asymptomatic patients (50% after 6.0 years versus 2.0 years, p = 0.019). Patient regret was higher in the WW group (37.7 versus 18.0%, p = 0.002), as well as pain/discomfort (p = 0.031). Quality of life did not differ (p = 0.737). In the WW group, incarceration occurred in 10/255 patients (3.9%). Interpretation: During 12-year follow-up, most WW patients crossed over to surgery, significantly earlier with mildly symptomatic hernia. Considering the relatively low incarceration rate, WW might still be an option in asymptomatic patients with a clear preference and being well-informed about pros and cons.</p