Some thoughts about matrix coordinate transformations

Matrix coordinate transformations are defined as substitution operators without requiring an ordering prescription or an inclusion function from the Abelian coordinate transformations. We construct transforming objects mimicking most of the properties of tensors. We point out some problems with the matrix generalization of contravariant vectors. We suggest to use the substitution operators to search for an inclusion function.Comment: LaTeX, 12 page

Factors Associated With Glaucoma Surgery in Pediatric Non-Infectious Uveitis

Purpose: To identify factors associated with glaucoma surgery in pediatric uveitis. Methods: Patients diagnosed with uveitis before their 18th birthday and with an observation period of at least one year were included in a retrospective case-control study. Results: A total of 185 patients were included, 84 of whom had undergone glaucoma surgery. Juvenile idiopathic arthritis (JIA)-related uveitis was associated with undergoing glaucoma surgery (p = .002). In the JIA-subgroup, the presence of anterior segment complications (OR 3.1 (95% CI 1.0 to 9.6); P = .045) and an IOP &gt; 21 mmHg during the first uveitis remission (OR 4.5 (95% CI 1.3 to 15.2); P = .015) were associated with an increased risk of glaucoma surgery. Sixty-eight percent of the cases needed glaucoma surgery within one year after they started IOP-lowering triple therapy. Conclusion: The risk profile for undergoing glaucoma surgery as outlined in this study is a valuable help to recognize and treat secondary glaucoma in a timely manner.</p

Cytokines and chemokines involved in acute retinal necrosis

PURPOSE. To investigate which cytokines and chemokines are involved in the immunopatho-genesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. METHODS. Serum and aqueous humor (AH) samples of 19 patients with ARN were analyzed by multiplex immunoassay. Infectious controls consisted of 18 patients with rubella virus– associated Fuchs’ uveitis and 20 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. The control group consisted of seven paired AH and serum samples from seven noninflammatory control patients with age-related cataract. In each sample, 4 anti-inflammatory, 12 proinflammatory, 2 vascular, and 4 other immune mediators were measured. In addition, various clinical characteristics were assessed. RESULTS. In ARN, 10 of the 22 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-18, MIF, MCP-1, Eotaxin, IP-10, IL-15, sICAM-1, and sVCAM-1, were significantly elevated when compared to all controls. In addition, one anti-inflammatory mediator (IL-10) was significantly elevated in ARN as compared to the controls. No association was found between the time of sampling and the extent and leve

Impact of digital interdisciplinary consultation on secondary care referrals by general practitioners:a protocol for a stepped-wedge cluster randomised controlled trial

INTRODUCTION: Optimal collaboration between general practice and hospital care is crucial to maintain affordable and sustainable access to healthcare for the entire population. General practitioners (GPs) are the gatekeepers to specialist care and patients will visit hospitals mostly only after referral. However, a substantial part of these referrals may be inappropriate, as communication between GPs and medical specialists can be challenging and referring patients may be the most obvious action for a GP to perform.A new digital platform (Prisma) connects GPs and specialists in interdisciplinary groups and facilitates asynchronous, accessible and fast teleconsultation within the group. No previous research has been done to evaluate the impact of this new platform on the referral rates to the hospital. METHODS AND ANALYSIS: A stepped-wedge randomised controlled trial (RCT) will be performed in Zwolle region in the Netherlands to analyse the effect of introduction of the platform on rate of inappropriate referrals to orthopaedic surgery. In four steps, GPs in the region will be given access to the platform. GPs will be part of the control condition until randomisation to the intervention. According to our sample size calculation, we need to include 18 practices with 1008 patients presenting with hip and knee symptoms. Routine care data of hospital registrations will be analysed to calculate the rate of inappropriate referrals (primary outcome). Secondary outcome are costs, primary and secondary care workload, posted cases and user satisfaction. Alongside this quantitative analysis, we will evaluate patient experience, facilitators and barriers for use of the platform. ETHICS AND DISSEMINATION: The medical ethics review board of University Medical Center Groningen (UMCG), the Netherlands (METc-number: 2021/288) has confirmed that the Medical Research Involving Human Subjects Act (WMO) does not apply to the process evaluation because the study does not involve randomisation of patients or different medical treatments (letter number: M21.275351). TRIAL REGISTRATION NUMBER: NL9704

Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease-associated genetic variants

Purpose: Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are neurotropic human alphaherpesviruses endemic worldwide. Upon primary infection, both viruses establish lifelong latency in neurons and reactivate intermittently to cause a variety of mild to severe diseases. Acute retinal necrosis (ARN) is a rare, sight-threatening eye disease induced by ocular VZV or HSV infection. The virus and host factors involved in ARN pathogenesis remain incompletely described. We hypothesize an underlying genetic defect in at least part of ARN cases. Methods: We collected blood from 17 patients with HSV-or VZV-induced ARN, isolated DNA and performed Whole Exome Sequencing by Illumina followed by analysis in Varseq with criteria of CADD score &gt; 15 and frequency in GnomAD &lt; 0.1% combined with biological filters. Gene modifications relative to healthy control genomes were filtered according to high quality and read-depth, low frequency, high deleteriousness predictions and biological relevance. Results: We identified a total of 50 potentially disease-causing genetic variants, including missense, frameshift and splice site variants and on in-frame deletion in 16 of the 17 patients. The vast majority of these genes are involved in innate immunity, followed by adaptive immunity, autophagy, and apoptosis; in several instances variants within a given gene or pathway was identified in several patients.Discussion: We propose that the identified variants may contribute to insufficient viral control and increased necrosis ocular disease presentation in the patients and serve as a knowledge base and starting point for the development of improved diagnostic, prophylactic, and therapeutic applications.</p

Methods to assess the effect of meat processing on viability of Toxoplasma gondii: towards replacement of mouse bioassay by in vitro testing

Consumption of meat containing viable tissue cysts is considered one of the main sources of human infection with Toxoplasma gondii. In contrast to fresh meat, raw meat products usually undergo processing, including salting and mixing with other additives such as sodium acetate and sodium lactate, which affects the viability of T. gondii. However, the experiments described in the literature are not always performed in line with the current processing methods applied in industry. It was our goal to study the effect of salting and additives according to the recipes used by industrial producers. Mouse or cat bioassay is the ‘gold standard’ to demonstrate the presence of viable T. gondii. However, it is costly, time consuming and for ethical reasons not preferred for large-scale studies. Therefore, we first aimed to develop an alternative for mouse bioassay that can be used to determine the effect of processing on the viability of T. gondii tissue cysts. The assays studied were (i) a cell culture method to determine the parasite’s ability to multiply, and (ii) a propidium monoazide (PMA) dye-based assay to selectively detect DNA from intact parasites. Processing experiments were performed with minced meat incubated for 20 h with low concentrations of NaCl, sodium lactate and sodium acetate. NaCl appeared to be the most effective ingredient with only one or two out of eight mice infected after inoculation with pepsin-digest of portions processed with 1.0, 1.2 and 1.6% NaCl. Results of preliminary experiments with the PMA-based method were inconsistent and did not sufficiently discriminate between live and dead parasites. In contrast, the cell culture method showed promising results, but further optimization is needed before it can replace or reduce the number of mouse bioassays needed. In future, standardised in vitro methods are necessary to allow more extensive testing of product-specific processing methods, thereby providing a better indication of the risk of T. gondii infection for consumers

Identification of Risk Factors for Dupilumab-associated OculaSurface Disease in Patients with Atopic Dermatitis

This study identified risk factors for the development of dupilumab-associated ocular surface disease in patients with moderate-to-severe atopic dermatitis in a large prospective daily practice cohort. Data from the Dutch BioDay Registry were used to assess the risk of developing dupilumab-associated ocular surface di-sease, by performing univariate and multivariate logistic regression analyses. A total of 469 patients were included, of which 152/469 (32.4%) developed dupi-lumab-associated ocular surface disease. Multivariate analysis showed a statistically significant association of the development of dupilumab-associated ocular surface disease with a history of any eye disease (his-tory of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at the start of dupilumab (odds ratio 5.16, 95% confidence interval 2.30–11.56, p < 0.001). In conclusion, a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis ex-cluded) combined with the use of ophthalmic medication at baseline was associated with the development of dupilumab-associated ocular surface disease in patients with atopic dermatitis

Development and clinical evaluation of a 3-step modified manipulation protocol for MRI-guided high-intensity focused ultrasound of uterine fibroids

__Objectives:__ The clinical applicability of magnetic resonance image−guided high-intensity focused ultrasound (MR-HIFU) treatment of uterine fibroids is often limited due to inaccessible fibroids or bowel interference. The aim of this study was to implement a newly developed 3-step modified manipulation protocol and to evaluate its influence on the number of eligible women and treatment fai