Are Eye Clinics Safe For The Road? An Observational Report

We report an observational study, based on the examination of 319 medical records, identifying the proportion of patients whose driving status was documented on the first and subsequent glaucoma clinic visits. We also established the proportion of patients with documented Driving and Vehicle Licencing Agency (DVLA)-related advice when they did not meet driving standards based on their visual acuity and/or visual fields (VF). On presentation, driving status was assessed in 61% (n=195) patients. Of the remaining 124, 44% (n=55) had their driving status documented at a subsequent visit, on an average 8 years later. Of all patients (78%, n=250) whose driving status was assessed at some stage, 42% (n=134) were drivers. Of the 203 patients who were either drivers or whose driving status was unknown, 37% (n=75) were assessed as having a visual acuity or bilateral VF defect that was below the legal limit for driving, 39 of whom were known drivers. Only 13 were advised to inform the DVLA, and only 5 patients were advised to update their spectacles or listed for surgery to improve their vision. We therefore potentially failed to perform our DVLA duty in 76% (n=57) of patients. We have made suggestions for improving the current performance in this respect based on the findings of this study

Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8+ Suppressor T Cells

Human CD8+ regulatory T cells, particularly the CD8+CD28− T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their application in future clinical trials. In the current study, we develop a novel strategy that combines common gamma chain (γc) cytokines IL-2, IL-7 and IL-15 and donor antigen presenting cells (APCs) to stimulate full HLA-mismatched allogeneic human CD8+ T cells which results in significant expansions of donor-specific CD8+CD28− T suppressor cells in vitro. The expanded CD8+CD28− T cells exhibit increased expressions of CTLA-4, FoxP3, and CD25, while down-regulate expressions of CD56, CD57, CD127, and perforin. Furthermore, these cells suppress proliferation of CD4+ T cells in a contact-dependent and cytokine-independent manner. Interestingly, the specificity of suppression is restricted by the donor HLA class I antigens but promiscuous to HLA class II antigens, providing a potential mechanism for linked suppression. Taken together, our results demonstrate a novel role for common γc cytokines in combination with donor APCs in the expansion of donor-specific CD8+CD28− T suppressor cells, and represent a robust strategy for in vitro generation of such cells for adoptive cellular immunotherapy in transplantation

Database-driven High-Throughput Calculations and Machine Learning Models for Materials Design

This paper reviews past and ongoing efforts in using high-throughput ab-inito calculations in combination with machine learning models for materials design. The primary focus is on bulk materials, i.e., materials with fixed, ordered, crystal structures, although the methods naturally extend into more complicated configurations. Efficient and robust computational methods, computational power, and reliable methods for automated database-driven high-throughput computation are combined to produce high-quality data sets. This data can be used to train machine learning models for predicting the stability of bulk materials and their properties. The underlying computational methods and the tools for automated calculations are discussed in some detail. Various machine learning models and, in particular, descriptors for general use in materials design are also covered.Comment: 19 pages, 2 figure

Nac1 interacts with the POZ-domain transcription factor, Miz1

Nac1 (nucleus accumbens 1) is a POZ (poxvirus and zinc finger)-domain transcriptional repressor that is expressed at high levels in ovarian serous carcinoma. Here we identify Nac1 as a novel interacting partner of the POZ-domain transcriptional activator, Miz1 (Myc-interacting zinc-finger protein 1), and using chemical crosslinking we show that this association is mediated by a heterodimeric interaction of the Nac1 and Miz1 POZ domains. Nac1 is found in discrete bodies within the nucleus of mammalian cells, and we demonstrate the relocalization of Miz1 to these structures in transfected HeLa cells. We show that siRNA (small interfering RNA)-mediated knockdown of Nac1 in ovarian cancer cells results in increased levels of the Miz1 target gene product, p21Cip1. The interaction of Nac1 with Miz1 may thus be relevant to its mechanism of tumourigenesis in ovarian cancer

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Success of trabeculectomy surgery in relation to cataract surgery: 5-year outcomes

Aims: To compare success proportions at 5 years in three surgical groups: group 1, trabeculectomy alone; group 2, trabeculectomy followed by cataract surgery within 2 years; and group 3, trabeculectomy performed on a pseudophakic eye. Methods: A retrospective cohort study. 194 eyes of 194 patients were identified with at least 5 years’ follow-up post trabeculectomy (N=85, 60 and 49 in groups 1, 2 and 3, respectively). Main outcome measures: 1. Primary outcome measure: intraocular pressure (IOP) at 5 years post-trabeculectomy surgery, 2.Secondary outcome measure: change in visual acuity at 5 years. Results: At 5 years, the mean IOP (SD) was 12.9 (3.5), 12.5 (4.8) and 12.7 (4.8) mm Hg in groups 1, 2 and 3, respectively. Overall success was almost identical, 58%, 57% and 59% in groups 1, 2 and 3, respectively. There was no significant difference between the groups in terms of percentage IOP reduction, number of medications, proportion restarting medication and reoperation rates at 5 years. Logistic regression for an outcome of failure showed men to be at increased risk of failure OR 1.97 (95% CI 1.10 to 3.52, p=0.02). Nearly 80% of patients retained or improved their vision following their initial trabeculectomy. Conclusions: The sequence in which surgery is carried out does not appear to affect trabeculectomy function at 5 years, success being similar to trabeculectomy alone. In our study, men may be at increased risk of failure