Determining the Degree of Perceptible Static Eyelid Asymmetry and Effect of Face Inversion: A Cross-sectional Pilot Study.

Purpose: To determine the degree of static eyelid asymmetry required to be perceptible and whether this is affected by image inversion.

Methods: Images of 3 volunteers were digitally manipulated to have eyelid asymmetry of 0.5 mm, 1 mm, or 1.

An Industry Proposal for a Cell and Gene Therapy Safety Data Sheet.

Introduction: A safety data sheet (SDS) is an established hazard communication tool for chemicals, for which no comparable document exists in the biotherapeutics industry. As the cell and gene therapy (CGT) field expands, industry leaders have identified a growing need to address this gap in communication of the unique occupational health and safety risks posed by CGT materials and products.

Methods: Following the sections of a traditional chemical SDS, information was modified by industry subject matter experts, relevant to CGT biological materials.

Environmental Health and Safety Offers a Biosafety Risk Assessment for a Theoretical Model of a Gene Therapy Process Transfer from Research and Development to Large-Scale Manufacturing.

Introduction: This article provides a strategy by which a manufacturing process with a Biosafety Level 2 (BL2) designation can be downgraded to Biosafety Level 1 (BL1). The principles of the downgrading process are based on the robust contamination controls in clinical and commercial manufacturing, which typically are not part of Research and Development processes. These strict requirements along with the application of current Good Manufacturing Practice (cGMP) principles provide a framework by which processes can be suitably managed and controlled to mitigate biohazard risk, specifically for cell lines that may be contaminated with human pathogenic viral agents.

All-cause mortality and cardiovascular outcomes with sodium-glucose Co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and with combination therapy in people with type 2 diabetes.

Aim: To assess the relationship of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor analogues (GLP-1RA) and their combination (SGLT2i + GLP-1RA) with 5-year risk of all-cause mortality, hospitalization and cardiovascular/macrovascular disease in people with type 2 diabetes.

Materials And Methods: Retrospective cohort analysis of 2.2 million people with type 2 diabetes receiving insulin across 85 health care organizations using a global federated health research network.

Evolutionary history of the extinct wolf population from France in the context of global phylogeographic changes throughout the Holocene.

Phylogeographic patterns in large mammals result from natural environmental factors and anthropogenic effects, which in some cases include domestication. The grey wolf was once widely distributed across the Holarctic, but experienced phylogeographic shifts and demographic declines during the Holocene. In the 19th-20th centuries, the species became extirpated from large parts of Europe due to direct extermination and habitat loss.

Painful Diabetic Peripheral Neuropathy: Practical Guidance and Challenges for Clinical Management.

Painful diabetic peripheral neuropathy (PDPN) is present in nearly a quarter of people with diabetes. It is estimated to affect over 100 million people worldwide. PDPN is associated with impaired daily functioning, depression, sleep disturbance, financial instability, and a decreased quality of life.

Artificial Intelligence Based Analysis of Corneal Confocal Microscopy Images for Diagnosing Peripheral Neuropathy: A Binary Classification Model.

Diabetic peripheral neuropathy (DPN) is the leading cause of neuropathy worldwide resulting in excess morbidity and mortality. We aimed to develop an artificial intelligence deep learning algorithm to classify the presence or absence of peripheral neuropathy (PN) in participants with diabetes or pre-diabetes using corneal confocal microscopy (CCM) images of the sub-basal nerve plexus. A modified ResNet-50 model was trained to perform the binary classification of PN (PN+) versus no PN (PN-) based on the Toronto consensus criteria.

Artificial Intelligence and Corneal Confocal Microscopy: The Start of a Beautiful Relationship.

Corneal confocal microscopy (CCM) is a rapid non-invasive in vivo ophthalmic imaging technique that images the cornea. Historically, it was utilised in the diagnosis and clinical management of corneal epithelial and stromal disorders. However, over the past 20 years, CCM has been increasingly used to image sub-basal small nerve fibres in a variety of peripheral neuropathies and central neurodegenerative diseases.

Informed Consent In Facial Photograph Publishing: A Cross-sectional Pilot Study To Determine The Effectiveness Of Deidentification Methods.

This study determined the effectiveness of three deidentification methods: use of a) a black box to obscure facial landmarks, b) a letterbox view to display restricted facial landmarks and c) a half letterbox view. Facial images of well-known celebrities were used to create a series of decreasingly deidentified images and displayed to participants in a structured interview session. 55.

Artificial intelligence utilising corneal confocal microscopy for the diagnosis of peripheral neuropathy in diabetes mellitus and prediabetes.

Aims/hypothesis: We aimed to develop an artificial intelligence (AI)-based deep learning algorithm (DLA) applying attribution methods without image segmentation to corneal confocal microscopy images and to accurately classify peripheral neuropathy (or lack of).

Methods: The AI-based DLA utilised convolutional neural networks with data augmentation to increase the algorithm's generalisability. The algorithm was trained using a high-end graphics processor for 300 epochs on 329 corneal nerve images and tested on 40 images (1 image/participant).

Environmental Health and Biosafety Risk Assessment Guidance for Commercial-Scale Cell and Gene Therapy Manufacturing.

Introduction: This article aims to identify best practices, improve risk controls, and aid regulatory agencies in developing guidance for environmental and biosafety risk assessment for commercial-scale cell and gene therapy manufacturing.

Methods: A cross-functional team should start with hazard classification and testing requirements for materials used or generated by the process and process hazard characterization.

Results: The team develops a safety profile of the process to mitigate risks, including: product biological contamination risk and process controls, including raw materials, facilities, operator and environmental controls, and method of detection;a technical review of the process to evaluate the operational and engineering controls;monitoring systems to mitigate the risk of failure and/or breach of the system, preventing the release of material to the facility or operator exposure;site sanitization strategy and facility containment measures, including engineering designs, air handling systems, spill containment measures, surface cleanability, waste flows, and decontamination practices;a review of site practices, including process, employee, material and waste flows, staff training, controlled access, operator gowning, and emergency response plans/measures.

Increased Early Sensitivity to Eyes in Mouthless Faces: In Support of the LIFTED Model of Early Face Processing.

The N170 ERP component is a central neural marker of early face perception usually thought to reflect holistic processing. However, it is also highly sensitive to eyes presented in isolation and to fixation on the eyes within a full face. The lateral inhibition face template and eye detector (LIFTED) model (Nemrodov et al.

Effects of acute chemotherapy-induced mucositis on spontaneous behaviour and the grimace scale in laboratory rats.

Intestinal mucositis is a frequent side-effect of chemotherapy treatment. Many oncological research programs aim to identify novel treatments for this distressing condition, and these programs frequently use rat models. Little is known about the presence and progression of pain in these models and how this can best be treated by analgesic therapy.

Stability of coagulation proteins in lyophilized plasma.

Introduction: External quality assessment (EQA) is an important component of quality assurance for laboratory tests of haemostasis. Lyophilization of plasma confers stability of labile clotting factors, allowing valid comparison of results between participating centres. However, elevated ambient temperatures in some geographical areas could affect the stability of lyophilized samples in transit.

Vocational rehabilitation in early psychosis: cluster randomised trial.

Background: Individual placement and support (IPS) is effective in helping patients return to work but is poorly implemented because of clinical ambivalence and fears of relapse.

Aims: To assess whether a motivational intervention (motivational interviewing) directed at clinical staff to address ambivalence about employment improved patients' occupational outcomes.

Method: Two of four early intervention teams that already provided IPS were randomised to receive motivational interviewing training for clinicians, focused on attitudinal barriers to employment.

Viral and host factors determine innate immune responses in airway epithelial cells from children with wheeze and atopy.

Background: Airway epithelial cells (AEC) from patients with asthma, appear to have an impaired interferon (IFN)-β and -λ response to infection with rhinovirus.

Objectives: To determine if impaired IFN responses can be identified in young children at risk of developing asthma due to atopy and/or early life wheeze, and if the site of infection or the infecting virus influence the antiviral response.

Methods: Nasal (N) and tracheal (T) epithelial cells (EC) were collected from children categorised with atopy and/or wheeze based on specific IgE to locally common aeroallergens and a questionnaire concerning respiratory health.

Early sensitivity for eyes within faces: a new neuronal account of holistic and featural processing.

Eyes are central to face processing however their role in early face encoding as reflected by the N170 ERP component is unclear. Using eye tracking to enforce fixation on specific facial features, we found that the N170 was larger for fixation on the eyes compared to fixation on the forehead, nasion, nose or mouth, which all yielded similar amplitudes. This eye sensitivity was seen in both upright and inverted faces and was lost in eyeless faces, demonstrating it was due to the presence of eyes at fovea.

Long-term working memory deficits after concussion: electrophysiological evidence.

Background: Persistent complaints of lingering memory and concentration difficulties are common following a concussion, although the brain basis of these is unknown. Some suggest abnormalities can be found on the P300 event-related potential component, recorded using electroencephalography (EEG), despite unobservable cognitive impairments.

Objective: To examine the P300 and cognitive performance following a remote concussion during an n-back task that varies in working memory load.

Type-specific prevalence of human papillomavirus in women screened for cervical cancer in Labrador, Canada.

Background: A higher incidence of cervical cancer and human papillomavirus (HPV) infection has been reported in northern Canada and in First Nation, Métis and Inuit women, with some evidence to suggest that the HPV type distribution in these populations may be different from the rest of Canada.

Objective: The objective of this study was to measure the HPV type prevalence in Labrador women to determine if significant differences in HPV types could reduce the effectiveness of HPV vaccination.

Design: The prevalence of HPV types was determined in 1,370 women presenting for routine pap screening in Labrador between February and November 2010.

Home enteral tube feeding in children with inherited metabolic disorders: a review of long-term carer knowledge and technique.

Background: Home enteral tube feeding (HETF) is commonly used in children with inherited metabolic disorders (IMD). It is unclear how caregiver knowledge and their safety in using tube feeding techniques changes over time.

Methods: Caregivers of children with IMD on HETF from one UK IMD centre had annual interviews over 3 years using a structured questionnaire and observation to assess HETF knowledge and safety techniques.

siRNA against the G gene of human metapneumovirus.

Background: Human metapneumovirus (hMPV) is a significant viral respiratory pathogen of infants and children, the elderly and immunocompromised individuals. Disease associated with hMPV infection resembles that of human respiratory syncytial virus (RSV) and includes bronchiolitis and pneumonia. The glycosylated G attachment protein of hMPV is required for viral entry in vivo and has also been identified as an inhibitor of innate immune responses.

Mutation of the elongin C binding domain of human respiratory syncytial virus non-structural protein 1 (NS1) results in degradation of NS1 and attenuation of the virus.

Background: Human respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in the paediatic population, immunocompromised individuals and the elderly worldwide. However, despite global efforts over the past several decades there are no commercially available vaccines. RSV encodes 2 non-structural proteins, NS1 and NS2, that are type I interferon antagonists.

Accuracy of home enteral feed preparation for children with inherited metabolic disorders.

Background: Many children with rare chronic disorders require home enteral tube feeds (HETF) consisting of multiple modular ingredients. Feeds are often complex and the risk of errors during their preparation is high. The consequences of over- or under-concentration can be critical.