Target Product Profile for a Machine Learning-Automated Retinal Imaging Analysis Software for Use in English Diabetic Eye Screening: Protocol for a Mixed Methods Study.

Background: Diabetic eye screening (DES) represents a significant opportunity for the application of machine learning (ML) technologies, which may improve clinical and service outcomes. However, successful integration of ML into DES requires careful product development, evaluation, and implementation. Target product profiles (TPPs) summarize the requirements necessary for successful implementation so these can guide product development and evaluation.

European Society for Organ Transplantation (ESOT) Consensus Statement on the Role of Pancreas Machine Perfusion to Increase the Donor Pool for Beta Cell Replacement Therapy.

The advent of Machine Perfusion (MP) as a superior form of preservation and assessment for cold storage of both high-risk kidney's and the liver presents opportunities in the field of beta-cell replacement. It is yet unknown whether such techniques, when applied to the pancreas, can increase the pool of suitable donor organs as well as ameliorating the effects of ischemia incurred during the retrieval process. Recent experimental models of pancreatic MP appear promising.

Commentary: Patient Perspectives on Artificial Intelligence; What have We Learned and How Should We Move Forward?

Artificial intelligence (AI) in healthcare has now begun to make its contributions to real-world patient care with varying degrees of both public and clinical acceptability around it. The heavy investment from governments, industry and academia needed to reach this point has helped to surface different perspectives on AI. As clinical AI applications become a reality, however, there is an increasing need to harness and integrate patient perspectives, which address the distinct needs of different populations, healthcare systems and clinical problems more closely.

An observational clinical study of the influence of phacoemulsification on choroidal neovascular membrane activity in age related macular degeneration.

Background: Thousands of phacoemulsification surgeries are performed on eyes with age-related macular degeneration (AMD) complicated by choroidal neovascular membrane (CNV) in the United Kingdom each year. As populations age this number is expected to rise. Controversy over phacoemulsification's influence on CNV activity limits the information which clinicians and these patients use to decide on surgery.

New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases.

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed.

A non-randomised trial of video and written educational adjuncts in undergraduate ophthalmology.

Background: Provision of relevant pre-learning materials has been shown to increase student engagement and improve outcomes in medical education. This non-randomised study attempts to quantify the educational gains, and relative efficacy of video and written pre-learning materials, in ophthalmology undergraduate teaching.

Methods: Ninety-eight final year medical students were contacted prior to their three-day ophthalmology placements at a British tertiary ophthalmology unit.

10-year trends in English primary care glaucoma prescribing.

Background: In 2018 NHS prescriptions in England cost £8.83 billion. Within ophthalmic prescribing, glaucoma is the most costly indication.

Stenotrophomonas maltophilia-A Case Series of a Rare Keratitis Affecting Patients With Bandage Contact Lens.

Objectives: Stenotrophomonas maltophilia is an opportunistic pathogen known to form biofilms on contact lens and case surfaces that may result in permanent visual loss in cases of microbial keratitis. Because of its multiple drug resistance and extremely low incidence, there is little consensus on treatment. We investigated the predisposing factors, management, and visual outcomes in a small case series of patients to better inform the management of this rarely reported keratitis.

An investigation of the genetic basis of increased susceptibility to neutralization by anti-fusion glycoprotein antibody arising on passage of human respiratory syncytial virus in cell culture.

Human respiratory syncytial virus isolates have previously been shown to exhibit resistance to neutralization by anti-fusion glycoprotein antibodies that is lost on passage in cell culture. Early passage resistant and late passage susceptible stocks of two virus isolates from different epidemics were cloned by plaque purification. Early passage stocks of both isolates yielded predominantly neutralization resistant clones while late passage stocks yielded predominantly susceptible clones.

A high-throughput fluorescence anisotropy-based assay for human topoisomerase II β-catalyzed ATP-dependent supercoiled DNA relaxation.

Because of their essentiality for DNA replication, transcription, and repair, type II topoisomerases are targets for antibacterial and anticancer drugs. There are two type II topoisomerases in humans, topoisomerase IIα (TOP2A) and topoisomerase IIβ (TOP2B), and two in bacteria, gyrase and topoisomerase IV. Inhibition of one or both of the human type II topoisomerases by antibacterial compounds targeting their bacterial counterparts could result in toxicity.

Immunogenicity in mice of human metapneumovirus with a truncated SH glycoprotein.

The SH glycoprotein of human metapneumovirus (HMPV) is twice the size of that of human respiratory syncytial virus and possesses a large, hydrophilic luminal domain. The glycoprotein is located on the surface of the virion and of virus infected cells and, if immunogenic, might be expected to play a role in anti-viral immunity. Initial attempts to study anti-SH antibody immunogenicity were thwarted by the instability of the SH gene on passage both in human bronchial epithelial cells and in mice.

The impact of aluminium smelter shut-down on the concentration of fluoride in vegetation and soils.

Although a great deal is known about the deposition of fluoride on vegetation, and the hazards associated with uptake by grazing herbivores, little is known about what happens to the concentration of fluoride in vegetation and soil at polluted sites once deposition ceases. The closure of Anglesey Aluminium Metals Ltd smelter, in September 2009, provided a unique opportunity to study fluoride loading once deposition stopped. Fluoride was monitored in plants and soil within 1 km of the former emission source.

The European Market for Animal-Friendly Products in a Societal Context.

This article takes a future focus on the direction in which social forces develop the market for animal-friendly products in Europe. On the basis of qualitative data gathered in the context of the European EconWelfare project, the differences across eight European countries are studied. The findings suggest that, given international trade barriers that prevent an improvement of animal welfare through legislation, many stakeholders believe that the market is the most viable direction to improve farm animal welfare.

The characterization of monoclonal antibodies to human metapneumovirus and the detection of multiple forms of the virus nucleoprotein and phosphoprotein.

Little is known of the proteome of human metapneumovirus (HMPV). In this study a panel of monoclonal antibodies to the virus have been characterized and used to identify viral proteins present in infected cell lysates. Of thirteen anti-HMPV monoclonal antibodies four reacted with recombinant fusion glycoprotein and one with recombinant G glycoprotein by immunofuorescence but not in western blots suggesting that they recognize conformation dependent epitopes.

Stretch independent regulation of prostaglandin E(2) production within the isolated guinea-pig lamina propria.

Objective: To use an isolated preparation of the guinea-pig bladder lamina propria (LP) to investigate the effects of adenosine tri-phosphate (ATP) and nitric oxide (NO) on the release of prostaglandin E(2) (PGE(2)).

Materials And Methods: The bladders of female guinea-pigs (200-400 g) were isolated and opened to expose the urothelial surface. The LP was dissected free of the underlying detrusor muscle and cut into strips from the dome to base.

Systemic effects on leaf glutathione metabolism and defence protein expression caused by esca infection in grapevines.

Esca is a devastating disease of Vitis vinifera L., caused by fungal pathogen(s) inhabiting the wood. The pathogens induce symptoms in the foliage, which are associated with structural and biochemical changes in leaves.

A generic expression system to produce proteins that co-assemble with alkane thiol SAM.

Surface biology aims to observe and control biological processes by combining bio-, surface, and physical chemistry. Self-assembled monolayers (SAM) on gold surfaces have provided excellent methods for nanoscale surface preparation for such studies. However, extension of this work requires the specific immobilization of whole protein domains and the direct incorporation of recombinant proteins into SAM is still problematic.

Outcome and toxicity of an Ifosfamide-based soft tissue sarcoma treatment protocol in children. The importance of local therapy.

Background. Although the survival of children with soft tissue sarcoma (STS) has improved considerably, the outcome of patients with metastatic disease, and those with primary tumours of the extremities or parameningeal sites remains disappointing. We describe the clinical outcome of an ifosfamide-based regimen with local therapy directed only to children who failed to achieve a complete response to initial chemotherapy.

The impact of the human DNA topoisomerase II C-terminal domain on activity.

Background: Type II DNA topoisomerases (topos) are essential enzymes needed for the resolution of topological problems that occur during DNA metabolic processes. Topos carry out an ATP-dependent strand passage reaction whereby one double helix is passed through a transient break in another. Humans have two topoII isoforms, alpha and beta, which while enzymatically similar are differentially expressed and regulated, and are thought to have different cellular roles.

Purification of human respiratory syncytial virus by ultracentrifugation in iodixanol density gradient.

Ultracentrifugation in sucrose density gradient remains the most commonly used technique for hRSV purification. However, the high viscosity and hyper-osmotic property of sucrose can cause damage to the extremely labile virus leading to loss of infectivity. To overcome these limitations, an alternative purification technique was developed using iodixanol as gradient medium, incorporating MgSO(4) as a stabilizing agent and EDTA to disaggregate the virus prior to infectivity assay.

Characterization of a double dockerin from the cellulosome of the anaerobic fungus Piromyces equi.

The assembly into supramolecular complexes of proteins having complementary activities is central to cellular function. One such complex of considerable biological and industrial significance is the plant cell wall-degrading apparatus of anaerobic microorganisms, termed the cellulosome. A central feature of bacterial cellulosomes is a large non-catalytic protein, the scaffoldin, which contains multiple cohesin domains.

Diagnosis of human metapneumovirus by immunofluorescence staining with monoclonal antibodies in the North-East of England.

Background: Since its discovery in 2001 human metapneumovirus (hMPV) has been shown to be a significant cause of human respiratory disease, responsible for 5-8% of respiratory infections in hospitalised children. Diagnosis hitherto has been largely carried out by reverse tanscriptase polymerase chain reaction (RT-PCR) but immunofluorescence staining of cells from nasopharyngeal secretions (IF) offers advantages for some laboratories and may produce a more rapid result in urgent cases. We have recently demonstrated that IF with a rabbit antiserum gave sensitivity equal to that of RT-PCR.

Adaxial/abaxial specification in the regulation of photosynthesis and stomatal opening with respect to light orientation and growth with CO2 enrichment in the C4 species Paspalum dilatatum.

Whole-plant morphology, leaf structure and composition were studied together with the effects of light orientation on the dorso-ventral regulation of photosynthesis and stomatal conductance in Paspalum dilatatum cv. Raki plants grown for 6 wk at either 350 or 700 microl l(-1) CO(2). Plant biomass was doubled as a result of growth at high CO(2) and the shoot:root ratio was decreased.

MDM2 RNA binding is blocked by novel monoclonal antibody h-MDM2-F4-14.

Amplification of MDM2 has been described in a variety of human cancers. Prognostic studies have revealed that abnormal MDM2 expression correlates with poor prognosis. Many of the consequences of mdm2/p53 interactions have been investigated, and mdm2-p53 dependent events characterized.