Burden of Glaucoma in the United Kingdom: A Multicenter Analysis of United Kingdom Glaucoma Services

OBJECTIVE: ,To determine the spectrum of glaucoma-associated health care resource utilization among outpatients attending National Health Service (NHS) hospital glaucoma clinics and the costs of managing glaucoma in this setting. DESIGN: Retrospective observational cohort study using electronic medical record data. SUBJECTS: Patients aged ≥ 18 years attending 5 NHS glaucoma clinics in the United Kingdom (2013‒2018) with ≥ 12 months of continuous electronic medical record data. METHODS: Deidentified Medisoft Ophthalmology electronic medical record data (January 2013‒December 2018) from 43 742 eligible patients were categorized by year of clinic visit. Extracted information included patient demographics, glaucoma diagnoses, topical glaucoma medication prescription start/stop dates, types/numbers of glaucoma clinic visits, glaucoma investigations (visual acuity, intraocular pressure, visual field, and OCT), and glaucoma procedures received over 12 months after the first (“index”) visit of the specified year. Direct glaucoma-related health care costs (clinic visits, investigations, procedures, and ongoing glaucoma medication initiated in the clinic) were estimated from event volumes and unit costs (UK national tariffs) and expressed from the direct-payer perspective. MAIN OUTCOME MEASURES: Glaucoma diagnoses and topical glaucoma medication use at the index clinic visit; numbers of glaucoma clinic visits, investigations and procedures; and glaucoma-related health care costs over 12 months postindex. RESULTS: For the 2016 cohort (n = 21 719), the estimated average total cost of NHS-provided glaucoma care over 12 months was £405 per patient (medical staff services £209, glaucoma investigations £126, glaucoma medication £40, glaucoma procedures £26). Among this cohort, 40.8% had ocular hypertension/suspected glaucoma, 70% had 0-to-mild visual field impairment, and 14% had undergone a glaucoma procedure. Over 12 months, patients received (mean) 2.0 glaucoma clinic visits and 1.5 visual field tests, and 7% underwent glaucoma procedure(s). Results were similar for the other years examined. CONCLUSIONS: Cost estimates for managing patients with glaucoma in the UK are required for effective service planning. Appreciable proportions of patients managed in NHS glaucoma clinics may be considered at low risk of blindness (glaucoma suspects and those with ocular hypertension with mild visual field loss) and may be more appropriately managed with alternative, more affordable models of care

Counting all dyons in N =4 string theory

For dyons in heterotic string theory compactified on a six-torus, with electric charge vector Q and magnetic charge vector P, the positive integer I = g.c.d.(Q \wedge P) is an invariant of the U-duality group. We propose the microscopic theory for computing the spectrum of all dyons for all values of I, generalizing earlier results that exist only for the simplest case of I=1. Our derivation uses a combination of arguments from duality, 4d-5d lift, and a careful analysis of fermionic zero modes. The resulting degeneracy agrees with the black hole degeneracy for large charges and with the degeneracy of field-theory dyons for small charges. It naturally satisfies several physical requirements including integrality and duality invariance. As a byproduct, we also derive the microscopic (0,4) superconformal field theory relevant for computing the spectrum of five-dimensional Strominger-Vafa black holes in ALE backgrounds and count the resulting degeneracies

Heart rate changes during partial seizures: A study amongst Singaporean patients

INTRODUCTION: Studies in Europe and America showed that tachycardia, less often bradycardia, frequently accompanied partial seizures in Caucasian patients. We determine frequency, magnitude and type of ictal heart rate changes during partial seizures in non-Caucasian patients in Singapore. METHODS: Partial seizures recorded during routine EEGs performed in a tertiary hospital between 1995 and 1999 were retrospectively reviewed. All routine EEGs had simultaneous ECG recording. Heart rate before and during seizures was determined and correlated with epileptogenic focus. Differences in heart rate before and during seizures were grouped into 4 types: (1) >10% decrease; (2) -10 to +20% change; (3) 20–50% increase; (3) >50% increase. RESULTS: Of the total of 37 partial seizures, 18 were left hemisphere (LH), 13 were right hemisphere (RH) and 6 were bilateral (BL) in onset. 51% of all seizures showed no significant change in heart rate (type 2), 22% had moderate sinus tachycardia (type 3), 11% showed severe sinus tachycardia (type 4), while 16% had sinus bradycardia (type 1). Asystole was recorded in one seizure. Apart from having more tachycardia in bilateral onset seizures, there was no correlation between side of ictal discharge and heart rate response. Compared to Caucasian patients, sinus tachycardia was considerably less frequent. Frequency of bradycardia was similar to those recorded in the literature. CONCLUSIONS: Significant heart rate changes during partial seizures were seen in half of Singaporean patients. Although sinus tachycardia was the most common heart rate change, the frequency was considerably lower compared to Caucasian patients. This might be due to methodological and ethnic differences. Rates of bradycardia are similar to those recorded in the literature

Derivation of marker gene signatures from human skin and their use in the interpretation trancriptional changes associated with dermatological disorders

Numerous studies have explored the altered transcriptional landscape associated with skin diseases to understand the nature of these disorders. However, data interpretation represents a significant challenge due to a lack of good maker sets for many of the specialised cell types that make up this tissue, whose composition may fundamentally alter during disease. Here we have sought to derive expression signatures that define the various cell types and structures that make up human skin, and demonstrate how they can be used to aid the interpretation of transcriptomic data derived from this organ. Two large normal skin transcriptomics datasets were identified, one RNA-seq (n = 578), the other microarray (n = 165), quality controlled and subjected separately to network-based analyses to identify clusters of robustly co-expressed genes. The biological significance of these clusters was then assigned using a combination of bioinformatics analyses, literature and expert review. After cross comparison between analyses, 20 gene signatures were defined. These include expression signatures for hair follicles, glands (sebaceous, sweat, apocrine), keratinocytes, melanocytes, endothelia, muscle, adipocytes, immune cells, and a number of pathway systems. Collectively we have named this resource SkinSig. SkinSig was then used in the analysis of transcriptomic datasets for 18 skin conditions, providing in-context interpretation of these data. For instance, conventional analysis has shown there to be a decrease in keratinisation and fatty metabolism with age; we more accurately define these changes to be due to loss of hair follicles and sebaceous glands. SkinSig also highlighted the over-/under-representation of various cell types in skin diseases, reflecting an influx in immune cells in inflammatory disorders and a relative reduction in other cell types. Overall, our analyses demonstrate the value of this new resource in defining the functional profile of skin cell types and appendages, and in improving the interpretation of disease data

Fatigue testing of three peristernal median sternotomy closure techniques

Failure of a sternotomy closure because of closure system fatigue is a complication that may result in dehiscence and put the individual at risk for serious complications. The purpose of this study was to assess the fatigue performance of three peristernal median sternotomy closure techniques (figure-of-eight stainless-steel wires, figure-of-eight stainless-steel cables, or Pectofix Dynamic Sternal Fixation [DSF] stainless-steel plates) in order to quantify the potential risk of fatigue failure of these devices when subject to cyclic loads in physiologically relevant loading directions

Apocrine Hidradenocarcinoma of the Scalp: A Classification Conundrum

Introduction The classification of malignant sweat gland lesions is complex. Traditionally, cutaneous sweat gland tumors have been classified by either eccrine or apocrine features. Methods A case report of a 33-year-old Hispanic man with a left scalp mass diagnosed as a malignancy of adnexal origin preoperatively is discussed. After presentation at our multidisciplinary tumor board, excision with ipsilateral neck dissection was undertaken. Results Final pathology revealed an apocrine hidradenocarcinoma. The classification and behavior of this entity are discussed in this report. Conclusion Apocrine hidradenocarcinoma can be viewed as an aggressive malignant lesion of cutaneous sweat glands on a spectrum that involves both eccrine and apoeccrine lesions

The genome and transcriptome of Trichormus sp NMC-1: insights into adaptation to extreme environments on the Qinghai-Tibet Plateau

The Qinghai-Tibet Plateau (QTP) has the highest biodiversity for an extreme environment worldwide, and provides an ideal natural laboratory to study adaptive evolution. In this study, we generated a draft genome sequence of cyanobacteria Trichormus sp. NMC-1 in the QTP and performed whole transcriptome sequencing under low temperature to investigate the genetic mechanism by which T. sp. NMC-1 adapted to the specific environment. Its genome sequence was 5.9 Mb with a G+C content of 39.2% and encompassed a total of 5362 CDS. A phylogenomic tree indicated that this strain belongs to the Trichormus and Anabaena cluster. Genome comparison between T. sp. NMC-1 and six relatives showed that functionally unknown genes occupied a much higher proportion (28.12%) of the T. sp. NMC-1 genome. In addition, functions of specific, significant positively selected, expanded orthogroups, and differentially expressed genes involved in signal transduction, cell wall/membrane biogenesis, secondary metabolite biosynthesis, and energy production and conversion were analyzed to elucidate specific adaptation traits. Further analyses showed that the CheY-like genes, extracellular polysaccharide and mycosporine-like amino acids might play major roles in adaptation to harsh environments. Our findings indicate that sophisticated genetic mechanisms are involved in cyanobacterial adaptation to the extreme environment of the QTP

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Two stage fracture of a polyethylene post in a 9-year-old posterior-stabilized knee prosthesis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Several cases of tibial post breakage are reported in the literature. To the best of our knowledge, only three cases of NexGen knee prosthesis (Zimmer, Warsaw, Indiana, USA) tibial post failure have been reported.</p> <p>Case presentation</p> <p>In November 1999, a 63-year-old Caucasian woman from Italy with a history of symptomatic left knee osteoarthritis underwent a total knee arthroplasty. In March 2008, while rising from a chair, she felt a sudden pain and instability in her left knee. She reported a fracture of the polyethylene post of the tibial insert. No malposition or malalignment of either the femoral or tibial components were identified. The polyethylene tibial insert was studied under light microscopy and scanning electron microscopy. The fracture was also noted to have occurred without any notable polyethylene wear.</p> <p>Conclusion</p> <p>Scanning electron microscopy revealed two different damage patterns that could be explained with a two-stage rupture of our patient's polyethylene post. This could have been caused by a non-optimal ligamentous balancing during first implant surgery. Her knee probably developed a varus instability that weakened the post, and then a posterior anterior stress finally broke the polyethylene.</p

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible