Проблематика переходу до інформаційного суспільства

Аналізуються фундаментальні передумови, що є первинними в процесі творення інформаційного суспільства. Обґрунтовується теза, що електронна готовність та електронне залучення є основоположними факторами переходу суспільства від індустріального до інформаційного устрою. Подано основні характеристики цих понять та наголошено на їх значенні

Leber's hereditary optic neuropathy like disease in MT-ATP6 variant m.8969G>A

Purpose: To describe a case with Leber's hereditary optic neuropathy (LHON) like optic atrophy in the presence of MT-ATP6 gene variant m.8969G > A. Observations: A 20-year-old patient with a history of mild developmental delay, mild cognitive impairment, and positional tremor presented with subacute painless visual loss over a few weeks. Mitochondrial genome sequencing revealed a variant in MT-ATP6, m.8969G > A (p.Ser148Asn). This variant was previously reported in association with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) and with nephropathy, followed by brain atrophy, muscle weakness and arrhythmias, but not with optic atrophy. Conclusions and importance: Rare variants in MT-ATP6 can also cause LHON like optic atrophy. It is important to perform further genetic analysis of mitochondrial DNA in genetically unsolved cases suspected of Leber's hereditary optic neuropathy to confirm the clinical diagnosis

Bimanual performance in children with unilateral perinatal arterial ischaemic stroke or periventricular haemorrhagic infarction

Background: Long term outcome data on bimanual performance in children with perinatal arterial ischaemic stroke (PAIS) and periventricular haemorrhagic infarction (PVHI) with and without unilateral spastic cerebral palsy (USCP) is sparse. Aims: To assess bimanual performance in children with PAIS or PVHI with and without USCP and to explore the relationship with unilateral hand function and full-scale IQ (FSIQ) in a cross-sectional study. Methods: Fifty-two children with PAIS (n = 27) or PVHI (n = 25) participated at a median age of 12 years and 1 month (range 6–20 years). The Bruininks Oseretsky Test of Motor Proficiency-2 (bimanual precision and dexterity subtest), Assisting Hand Assessment, Purdue Pegboard Test and Wechsler Intelligence scale were administered. Results: Bimanual dexterity was worse in children with USCP (p < 0.02) without a difference for the pathology groups. In children without USCP (n = 21), those with PAIS showed a better bimanual precision compared to children with PVHI (p < 0.04). The AHA score and the Purdue Pegboard score of the dominant hand explained 51% of the variance in bimanual precision and dexterity in children with USCP. In absence of USCP, FSIQ together with AHA scores explained 66% of the variance in bimanual precision and FSIQ together with the Purdue Pegboard Test score of the dominant hand, 71% of the variance in bimanual dexterity. Conclusions: Children with PAIS without USCP have a more favourable bimanual hand function compared to children with PVHI. This difference appears to be associated with a preserved FSIQ

Quality of life in patients with CRB1-associated retinal dystrophies:A longitudinal study

Purpose: To assess the longitudinal vision-related quality of life among patients with CRB1-associated inherited retinal dystrophies. Methods: A longitudinal questionnaire study included 22 patients with pathogenic CRB1 variants. The National Eye Institute Visual Function Questionnaire (39 items, NEI VFQ-39) was applied at baseline, two-year follow-up, and 4-year follow-up. Classical test theory was performed to obtain subdomain scores and in particular ‘near activities’ and ‘total composite’ scores. The Rasch analysis based on previous calibrations of the NEI VFQ-25 was applied to create visual functioning and socio-emotional subscales. Results:In total, 22 patients with pathogenic CRB1 variants were included, with a median age of 25.0 years (IQR: 13–31 years) at baseline and mean follow-up of 4.0 ± 0.3 years. A significant decline at 4 years was observed for ‘near activities’ (51.0 ± 23.8 vs 35.4 ± 14.7, p = 0.004) and ‘total composite’ (63.0 ± 13.1 vs 52.0 ± 12.1, p = 0.001) subdomain scores. For the Rasch-scaled scores, the ‘visual functioning’ scale significantly decreased after 4 years (−0.89 logits; p = 0.012), but not at 4-year follow-up (+0.01 logits; p = 0.975). The ‘socio-emotional’ scale also showed a significant decline after 2 years (−0.78 logits, p = 0.033) and 4 years (−0.83 logits, p = 0.021). Conclusion: In the absence of an intervention, a decline in vision-related quality of life is present in patients with pathogenic CRB1 variants at 4-year follow-up. Patient-reported outcome measures should be included in future clinical trials, as they can be a potential indicator of disease progression and treatment efficacy.</p

A disastrous project: C. P. Keller and the fortification (plans) of Bimilipatnam

Leiden University Libraries has two remarkable fortification plans in its collections. They depict the village of Bimilipatnam under VOC rule. After a ransack by plundering Maratha troops in 1754, the local Mughal-regent allowed the Dutch to construct a stronghold in the village. VOC-authorities commissioned military engineer Coenraad Pieter Keller to survey the plot of land allocated to them and deliver plans and a proposal how this fortification could be constructed. The eventual fort was poorly constructed and collapsed two times. Keller was scapegoated by his superiors. He did not let the allegations pass and defended himself at Batavia. His written apologia has been preserved and provides unique insights in the career of a hybrid mapmaker in colonial service. By careful archival research we can reconstruct the context in which the plans were produced, interpreted by their intended audience and circulated until it was acquired by Leiden UniversityLibraries.UBL - Publicaties niet-programma gebonde

Frequency and Genetic Spectrum of Inherited Retinal Dystrophies in a Large Dutch Pediatric Cohort:The RD5000 Consortium

Purpose: Gene-based therapies for inherited retinal dystrophies (IRDs) are upcoming. Treatment before substantial vision loss will optimize outcomes. It is crucial to identify common phenotypes and causative genes in children. This study investigated the frequency of these in pediatric IRD with the aim of highlighting relevant groups for future therapy. Methods:Diagnostic, genetic, and demographic data, collected from medical charts of patients with IRD aged up to 20 years (n = 624, 63% male), registered in the Dutch RD5000 database, were analyzed to determine frequencies of phenotypes and genetic causes. Phenotypes were categorized as nonsyndromic (progressive and stationary IRD) and syndromic IRD. Genetic causes, mostly determined by whole-exome sequencing (WES), were examined. Additionally, we investigated the utility of periodic reanalysis of WES data in genetically unresolved cases.Results: Median age at registration was 13 years (interquartile range, 9-16). Retinitis pigmentosa (RP; n = 123, 20%), Leber congenital amaurosis (LCA; n = 97, 16%), X-linked retinoschisis (n = 64, 10%), and achromatopsia (n = 63, 10%) were the most frequent phenotypes. The genetic cause was identified in 76% of the genetically examined patients (n = 473). The most frequently disease-causing genes were RS1 (n = 32, 9%), CEP290 (n = 28, 8%), CNGB3 (n = 21, 6%), and CRB1 (n = 17, 5%). Diagnostic yield after reanalysis of genetic data increased by 7%. Conclusions: As in most countries, RP and LCA are the most prominent pediatric IRDs in the Netherlands, and variants in RS1 and CEP290 were the most prominent IRD genotypes. Our findings can guide therapy development to target the diseases and genes with the greatest needs in young patients.</p

Intraoperative electrocorticography using high-frequency oscillations or spikes to tailor epilepsy surgery in the Netherlands (the HFO trial): a randomised, single-blind, adaptive non-inferiority trial

Background Intraoperative electrocorticography is used to tailor epilepsy surgery by analysing interictal spikes or spike patterns that can delineate epileptogenic tissue. High-frequency oscillations (HFOs) on intraoperative electrocorticography have been proposed as a new biomarker of epileptogenic tissue, with higher specificity than spikes. We prospectively tested the non-inferiority of HFO-guided tailoring of epilepsy surgery to spike-guided tailoring on seizure freedom at 1 year.Methods The HFO trial was a randomised, single-blind, adaptive non-inferiority trial at an epilepsy surgery centre (UMC Utrecht) in the Netherlands. We recruited children and adults (no age limits) who had been referred for intraoperative electrocorticography-tailored epilepsy surgery. Participants were randomly allocated (1:1) to either HFO-guided or spike-guided tailoring, using an online randomisation scheme with permuted blocks generated by an independent data manager, stratified by epilepsy type. Treatment allocation was masked to participants and clinicians who documented seizure outcome, but not to the study team or neurosurgeon. Ictiform spike patterns were always considered in surgical decision making. The primary endpoint was seizure outcome after 1 year (dichotomised as seizure freedom [defined as Engel 1A-11 vs seizure recurrence [Engel 1C-4]). We predefined a non-inferiority margin of 10% risk difference. Analysis was by intention to treat, with prespecified subgroup analyses by epilepsy type and for confounders. This completed trial is registered with the Dutch Trial Register, Toetsingonline ABR.NL44527.041.13, and ClinicalTrials.gov, NCT02207673.Findings Between Oct 10, 2014, and Jan 31,2020,78 individuals were enrolled to the study and randomly assigned (39 to HFO-guided tailoring and 39 to spike-guided tailoring). There was no loss to follow-up. Seizure freedom at 1 year occurred in 26 (67%) of 39 participants in the HFO-guided group and 35 (90%) of 39 in the spike-guided group (risk difference -23.5%, 90% CI -39.1 to -7.9; for the 48 patients with temporal lobe epilepsy, the risk difference was -25.5%, -45.1 to -6.0, and for the 30 patients with extratemporal lobe epilepsy it was -20.3%, -46.0 to 5.4). Pathology associated with poor prognosis was identified as a confounding factor, with an adjusted risk difference of-7.9% (90% CI -20.7 to 4.9; adjusted risk difference -12.5%, -31.0 to 5.9, for temporal lobe epilepsy and 5.8%, -7.7 to 19.5, for extratemporal lobe epilepsy). We recorded eight serious adverse events (five in the HFO-guided group and three in the spike-guided group) requiring hospitalisation. No patients died.Interpretation HFO-guided tailoring of epilepsy surgery was not non-inferior to spike-guided tailoring on intraoperative electrocorticography. After adjustment for confounders, HFOs show non-inferiority in extratemporal lobe epilepsy. This trial challenges the clinical value of HFOs as an epilepsy biomarker, especially in temporal lobe epilepsy. Further research is needed to establish whether HFO-guided intraoperative electrocorticography holds promise in extratemporal lobe epilepsy. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd

The Perplexing Problem of Persistently PCR-Positive Personnel

Early in the coronavirus disease 2019 (COVID-19) pandemic, the Centers for Disease Control and Prevention (CDC) published return-to-work criteria for healthcare personnel who had recovered from severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection. These criteria were most recently updated on April 3, 2020.1 The CDC has endorsed 2 different approaches to allow staff to return to work: a symptom or time-based strategy and a test-based strategy. Many institutions initially adopted the test-based strategy, in part because CDC initially recommended it as the preferred option (but no longer does so) and, in part, because it seemed the more definitive or conservative of the 2 CDC options

Mammillary body atrophy and other MRI correlates of school-age outcome following neonatal hypoxic-ischemic encephalopathy

The mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). The aim of this study was to assess neurodevelopmental outcome in 10-year-old children with HIE with and without therapeutic hypothermia. Additional aims were to assess the associations between MB atrophy, brain volumes (including the hippocampi), white matter microstructure and neurodevelopmental outcome at school-age. Ten-year-old children with HIE were included, who were treated with therapeutic hypothermia (n = 22) or would have qualified but were born before this became standard of care (n = 28). Children completed a neuropsychological and motor assessment and MRI. Mammillary bodies were scored as normal or atrophic at 10 years. Brain volumes were segmented on childhood MRI and DTI scans were analysed using tract-based spatial statistics. Children with HIE suffered from neurocognitive and memory problems at school-age, irrespective of hypothermia. Hippocampal volumes and MB atrophy were associated with total and performance IQ, processing speed and episodic memory in both groups. Normal MB and larger hippocampi were positively associated with global fractional anisotropy. In conclusion, injury to the MB and hippocampi was associated with neurocognition and memory at school-age in HIE and might be an early biomarker for neurocognitive and memory problems

Oxygen binding to cobalt and iron phthalocyanines as determined from in situ X-ray absorption spectroscopy

Cobalt phthalocyanine (CoPc) and iron phthalocyanine (FePc) are possible oxygen reduction catalysts in fuel cells, but the exact functioning and deactivation of these catalysts is unknown. The electronic structure of the CoPc and FePc has been studied in situ under hydrogen and oxygen atmospheres by a combination of ambient-pressure X-ray photoelectron spectroscopy and X-ray absorption spectroscopy. The results show that when oxygen is introduced, the iron changes oxidation state while the cobalt does not. The data show that oxygen binds in an end-on configuration in CoPc, while for FePc side-on binding is most likely