Identification of microchip implantation events for dogs and cats in the VetCompass Australia database

In Australia, compulsory microchipping legislation requires that animals are microchipped before sale or prior to 3 months in the Australian Capital Territory, New South Wales, Queensland and Victoria, and by 6 months in Western Australia and Tasmania. Describing the implementation of microchipping in animals allows the data guardians to identify individual animals presenting to differing veterinary practices over their lifetimes, and to evaluate compliance with legislation. VetCompass Australia (VCA) collates electronic patient records from primary care veterinary practices into a database for epidemiological studies. VCA is the largest companion animal clinical data repository of its kind in Australia, and is therefore the ideal resource to analyse microchip data as a permanent unique identifier of an animal. The current study examined the free-text ‘examination record’ field in the electronic patient records of 1000 randomly selected dogs and cats in the VCA database. This field may allow identification of the date of microchip implantation, enabling comparison with other date fields in the database, such as date of birth. The study revealed that the median age at implantation for dogs presented as individual patients, rather than among litters, was 74.4 days, significantly lower than for cats (127.0 days, p = 0.003). Further exploration into reasons for later microchipping in cats may be useful in aligning common practice with legislative requirements

The impact of a standardised intramuscular sedation protocol for acute behavioural disturbance in the emergency department

Background: Acute behavioural disturbance (ABD) is an increasing problem in emergency departments. This study aimed to determine the impact of a structured intramuscular (IM) sedation protocol on the duration of ABD in the emergency department. Methods: A historical control study was undertaken comparing 58 patients who required physical restraint and parenteral sedation with the structured IM sedation protocol, to 73 historical controls treated predominantly by intravenous sedation, according to individual clinician preference. The primary outcome was the duration of the ABD defined as the time security staff were required. Secondary outcomes were the requirement for additional sedation, drug related-adverse effects and patient and staff injuries. Results: The median duration of the ABD in patients with the new sedation protocol was 21 minutes (IQR: 15 to 35 minutes; Range: 5 to 78 minutes) compared to a median duration of 30 minutes (IQR: 15 to 50 minutes; Range: 5 to 135 minutes) in the historical controls which was significantly different (p = 0.03). With IM sedation only 27 of 58 patients (47%; 95% CI: 34% to 60%) required further sedation compared to 64 of 73 historical controls (88%; 95%CI: 77% to 94%). There were six (10%) drug-related adverse events with the new IM protocol [oxygen desaturation (5), oxygen desaturation/airway obstruction (1)] compared to 10 (14%) in the historical controls [oxygen desaturation (5), hypoventilation (4) and aspiration (1)]. Injuries to staff occurred with three patients using the new sedation protocol and in seven of the historical controls. Two patients were injured during the new protocol and two of the historical controls. Conclusion: The use of a standardised IM sedation protocol was simple, more effective and as safe for management of ABD compared to predominantly intravenous sedation

Evolutionary Plasticity of Polycomb/Trithorax Response Elements in Drosophila Species

cis-Regulatory DNA elements contain multiple binding sites for activators and repressors of transcription. Among these elements are enhancers, which establish gene expression states, and Polycomb/Trithorax response elements (PREs), which take over from enhancers and maintain transcription states of several hundred developmentally important genes. PREs are essential to the correct identities of both stem cells and differentiated cells. Evolutionary differences in cis-regulatory elements are a rich source of phenotypic diversity, and functional binding sites within regulatory elements turn over rapidly in evolution. However, more radical evolutionary changes that go beyond motif turnover have been difficult to assess. We used a combination of genome-wide bioinformatic prediction and experimental validation at specific loci, to evaluate PRE evolution across four Drosophila species. Our results show that PRE evolution is extraordinarily dynamic. First, we show that the numbers of PREs differ dramatically between species. Second, we demonstrate that functional binding sites within PREs at conserved positions turn over rapidly in evolution, as has been observed for enhancer elements. Finally, although it is theoretically possible that new elements can arise out of nonfunctional sequence, evidence that they do so is lacking. We show here that functional PREs are found at nonorthologous sites in conserved gene loci. By demonstrating that PRE evolution is not limited to the adaptation of preexisting elements, these findings document a novel dimension of cis-regulatory evolution

Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis

Introduction: Psoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF) or interleukin-17A (IL-17A). About 50% of patients respond to each, but it is not currently possible to predict response for individual patients, necessitating sequential treatment steps. A recent proof of concept study in PsA suggested that using peripheral immunophenotype to choose therapy could improve time to treatment response. This study will test the hypothesis, within an open-label parallel-group biomarker-stratified multicentre randomised controlled trial, which the baseline proportion of CD4+T cells with an activated type 17 immunophenotype (Th17 levels) predicts response to IL-17A or TNF inhibitors in PsA. Additional analyses will identify if the model can be refined by combining additional clinical and immunophenotypic factors. Statistical modelling will be used to predict the likely effectiveness of these approaches compared with standard care. Methods and analysis: Patients with PsA eligible to start their first biologic as part of standard care are recruited and baseline blood tests are taken for immunophenotyping. Participants are stratified equally by Th17 levels and randomised 1:1 to receive either TNF (adalimumab) or IL-17A (secukinumab) inhibitors. The primary analysis will establish the interaction between baseline immunophenotype and treatment on the primary outcome (achievement of minimal disease activity criteria at week 24). In secondary analysis, modelling will identify if this prediction model can be optimised further by incorporating clinical phenotypes and additional immunophenotyping techniques. Ethics and dissemination: Ethical approval for the study was granted by the North West Preston Research Ethics Committee (ref 21/NW/0016). Dissemination will be via conference presentations and peer-reviewed publications, aiming to impact on treatment guidelines. Trial registration number ISRCTN17228602

Noncardiac genetic predisposition in sudden infant death syndrome.

PURPOSE: Sudden infant death syndrome (SIDS) is the commonest cause of sudden death of an infant; however, the genetic basis remains poorly understood. We aimed to identify noncardiac genes underpinning SIDS and determine their prevalence compared with ethnically matched controls. METHODS: Using exome sequencing we assessed the yield of ultrarare nonsynonymous variants (minor allele frequency [MAF] ≤0.00005, dominant model; MAF ≤0.01, recessive model) in 278 European SIDS cases (62% male; average age =2.7 ± 2 months) versus 973 European controls across 61 noncardiac SIDS-susceptibility genes. The variants were classified according to American College of Medical Genetics and Genomics criteria. Case-control, gene-collapsing analysis was performed in eight candidate biological pathways previously implicated in SIDS pathogenesis. RESULTS: Overall 43/278 SIDS cases harbored an ultrarare single-nucleotide variant compared with 114/973 controls (15.5 vs. 11.7%, p=0.10). Only 2/61 noncardiac genes were significantly overrepresented in cases compared with controls (ECE1, 3/278 [1%] vs. 1/973 [0.1%] p=0.036; SLC6A4, 2/278 [0.7%] vs. 1/973 [0.1%] p=0.049). There was no difference in yield of pathogenic or likely pathogenic variants between cases and controls (1/278 [0.36%] vs. 4/973 [0.41%]; p=1.0). Gene-collapsing analysis did not identify any specific biological pathways to be significantly associated with SIDS. CONCLUSIONS: A monogenic basis for SIDS amongst the previously implicated noncardiac genes and their encoded biological pathways is negligible

Decreased TNF-α synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging

Immunity declines during aging, however the mechanisms involved in this decline are not known. In this study, we show that cutaneous delayed type hypersensitivity (DTH) responses to recall antigens are significantly decreased in older individuals. However, this is not related to CC chemokine receptor 4, cutaneous lymphocyte-associated antigen, or CD11a expression by CD4+ T cells or their physical capacity for migration. Instead, there is defective activation of dermal blood vessels in older subject that results from decreased TNF-α secretion by macrophages. This prevents memory T cell entry into the skin after antigen challenge. However, isolated cutaneous macrophages from these subjects can be induced to secrete TNF-α after stimulation with Toll-like receptor (TLR) 1/2 or TLR 4 ligands in vitro, indicating that the defect is reversible. The decreased conditioning of tissue microenvironments by macrophage-derived cytokines may therefore lead to defective immunosurveillance by memory T cells. This may be a predisposing factor for the development of malignancy and infection in the skin during aging

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

Submission to the Discussion Paper Proposal to expand the scope of eligible containers in Queensland’s Container Refund Scheme – Containers for Change

We comment on the Queensland Government proposal to expand the scope of eligible containers in Queensland's Container Refund Scheme. We highlight that the scheme should be amended to shift from a littering prevention mechanism to a circular economy mechanism. While the scheme has been effective in reducing littering of drinking containers, the scheme is not encouraging circular economy practices. Given that the scheme increases the availability of quality materials, future reforms should be focused on enhancing re-use of these materials. A re-use scheme should be “place-based” encouraging the re-use of plastic and glass bottles around the current Container for Change collection sites and should be designed in consultation with university, industry, and community

The DNA Framework of Visualization

A comprehensive framework is presented for analyzing and specifying an extensive range of visualizations in terms of their fundamental ‘DNA’ building blocks of visual encoding and (de)composition

Target oxygen saturation range : 92-96% versus 94-98%

This scientific letter considers the rationale for the target oxygen saturation measured by pulse oximetry (SpO₂) range of 92–96% for oxygen therapy in adult patients without COPD or other conditions associated with chronic respiratory failure, recommended by the Thoracic Society of Australia and New Zealand, in contrast to the 94–98% target range recommended by the British Thoracic Society. We conclude from the available evidence that the SpO₂ target of 92–96% may be preferable to 94–98%.3 page(s