The population-specific Thr44Met OCT3 coding variant affects metformin pharmacokinetics with subsequent effects on insulin sensitivity in C57Bl/6J mice.

Aims/hypothesis: Metformin is an important first-line treatment for type 2 diabetes and acts by increasing the body's ability to dispose of glucose. Metformin's efficacy can be affected by genetic variants in the transporters that regulate its uptake into cells. The SLC22A3 gene (also known as EMT; EMTH; OCT3) codes for organic cation transporter 3 (OCT3), which is a broad-specificity cation transporter that also transports metformin.

A Multivariate Statistical Approach to Wrinkling Detection in Composites.

Nondestructive inspection using ultrasound in materials such as carbon-fiber reinforced polymers (CFRPs) is challenging as the ultrasonic wave will scatter from each ply in the structure of the component. This may be improved using image processing algorithms such as the total focusing method (TFM); however, the high level of backscattering within the sample is very likely to obscure a signal arising from a flaw. Detection of wrinkling, or out-of-plane fiber waviness, is especially difficult to automate as no additional scattering is produced (as might be the case with delaminations).

Product Enhanced Reverse Transcriptase for assessing replication competent virus in vectors retroviral vectors pseudotyped with GALV and VSV-G envelopes.

We evaluated the use of the Product Enhanced Reverse Transcriptase (PERT) assay as a means of detecting virus in retroviral vectors products pseudotyped with Gibbon Ape Leukemia Virus (GALV) and Vesicular Stomatitis Virus G (VSVG) envelopes. PERT provides greater standardization than the S+/L- assay which has been used extensively in virus detection. A challenge is that PERT will also detect residual retroviral vectors as vector particles contain reverse transcriptase.

Stain-Free Approach to Determine and Monitor Cell Heath Using Supervised and Unsupervised Image-Based Deep Learning.

Cell-based medicinal products (CBMPs) are a growing class of therapeutics that promise new treatments for complex and rare diseases. Given the inherent complexity of the whole human cells comprising CBMPs, there is a need for robust and fast analytical methods for characterization, process monitoring, and quality control (QC) testing during their manufacture. Existing techniques to evaluate and monitor cell quality typically constitute labor-intensive, expensive, and highly specific staining assays.

'I think we just do it once and leave it …' The collection and utility of family health history in general practice in Aotearoa New Zealand: a qualitative study.

Introduction The value of family health history as a means to understanding health risk has been long known. Its value in a precision medicine context is also now becoming apparent. General practitioners (GPs) are considered to play a key role in the collection, and investigation, of family health history, but it remains widely reported as being both poorly and infrequently undertaken.

Impact of surgical lung biopsy on lung function and survival in patients with idiopathic pulmonary fibrosis in a multi-centre registry cohort.

Background And Objective: Establishing an accurate and timely diagnosis of idiopathic pulmonary fibrosis (IPF) is essential for appropriate management and prognostication. In some cases, surgical lung biopsy (SLB) is performed but carries non-negligible risk. The objective of this retrospective study was to determine if SLB is associated with accelerated lung function decline in patients with IPF using the Canadian Registry for Pulmonary Fibrosis.

Identifying Māori perspectives on gene editing in Aotearoa New Zealand.

Māori perspectives on gene technologies are evolving, and traditional cultural constructs continue to inform a wide diversity of views. Here we summarise a series of research activities aimed at identifying evolving Māori perspectives on gene editing and how these inform engagement at the co-innovation interface.

Finite element modelling strategy for determining directivity of thermoelastically generated laser ultrasound.

Laser ultrasound (LU) is a contactless and couplant-free remote non-destructive (NDE) technique, which uses lasers for ultrasonic generation and detection rather than conventional piezoelectric transducers. For a transducer, an important characteristic is the directivity, the angle-dependent amplitude of the ultrasonic waves generated in the material. In the non-destructive thermoelastic regime, LU source has been widely modelled as a surface force dipole.

Treatment of rheumatoid arthritis-associated interstitial lung disease in a multi-center registry cohort.

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is challenging to manage, with a paucity of robust data to guide treatment. Our aim was to characterize the pharmacologic treatment of RA-ILD utilizing a retrospective design in a national multi-center prospective cohort, and to identify associations between treatment and change in lung function and survival.

Methods: Patients with RA-ILD and a radiological pattern of non-specific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP) were included.

A Polynesianspecific missense CETP variant alters the lipid profile.

Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at associate with serum lipid profiles and cardiovascular disease. Here, sequencing of identified a missense variant rs1597000001 (p.

Genetic testing for misclassified monogenic diabetes in Māori and Pacific peoples in Aōtearoa New Zealand with early-onset type 2 diabetes.

Aims: Monogenic diabetes accounts for 1-2% of diabetes cases yet is often misdiagnosed as type 2 diabetes. The aim of this study was to examine in Māori and Pacific adults clinically diagnosed with type 2 diabetes within 40 years of age, (a) the prevalence of monogenic diabetes in this population (b) the prevalence of beta-cell autoantibodies and (c) the pre-test probability of monogenic diabetes.

Methods: Targeted sequencing data of 38 known monogenic diabetes genes was analyzed in 199 Māori and Pacific peoples with BMI of 37.

Circulating cytokine levels in systemic sclerosis related interstitial lung disease and idiopathic pulmonary fibrosis.

Exploration of cytokine levels in systemic sclerosis-associated interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF) is needed to find common and diverse biomolecular pathways. Circulating levels of 87 cytokines were compared amongst 19 healthy controls and consecutive patients with SSc-ILD (n = 39), SSc without ILD (n = 29), and IPF (n = 17) recruited from a Canadian centre using a log-linear model adjusted for age, sex, baseline forced vital capacity (FVC), and immunosuppressive or anti-fibrotic treatment at time of sampling. Also examined was annualized change in FVC.

Eligibility criteria from pharmaceutical randomised controlled trials of idiopathic pulmonary fibrosis: a registry-based study.

Background: Little is known about generalisability of randomised controlled trials (RCTs) for idiopathic pulmonary fibrosis (IPF). We evaluated eligibility criteria for phase III IPF RCTs to determine their representativeness in clinical registries, and calculated forced vital capacity (FVC) changes according to eligibility criteria.

Methods: Common eligibility criteria used in >60% of IPF RCTs were identified from a literature search and applied to patients with IPF from prospective Australian and Canadian registries.

Quantitative Raman Cross-Sections and Band Assignments for Fentanyl and Fentanyl Analogs.

Raman cross sections and spectra were measured for five synthetic opioid fentanyl analogs: fentanyl citrate, sufentanil citrate, alfentanil HCl, carfentanil oxalate, and remifentanil HCl. The measurements were performed with excitation wavelengths in the visible (532 nm) and near infrared (785 nm). In addition, density functional theory (DFT) calculations were employed to generate simulated spectra of the compounds and aid in identification of the observed spectral modes.

Diagnostic agreement among experts assessing adults presenting with possible cystic fibrosis: need for improvement and implications for patient care.

Background: Increasing awareness of milder presentations of cystic fibrosis (CF) and greater interest in non-CF bronchiectasis are likely to lead to more CF screening by respiratory clinicians. As a result, adults who may not strictly fulfil CF diagnostic criteria yet display evidence of abnormal CF transmembrane conductance regulator (CFTR) function are being identified. The degree of agreement on diagnosis and care needs in these cases between CF clinicians remains unknown, and has implications for patient care, including access to CFTR modulator therapies.

Pulmonary exacerbation inflammatory phenotypes in adults with cystic fibrosis.

Background: Adults with cystic fibrosis (CF) develop exuberant inflammatory responses during pulmonary exacerbations (PEx) but whether distinct systemic inflammatory profiles can be identified and whether these associate with disparate treatment outcomes are unclear. We conducted a pilot study to address this question and hypothesized that CF adults with a pauci-inflammatory phenotype might derive less clinical benefit from intravenous (IV) antibiotic treatment than patients with other systemic inflammatory phenotypes.

Methods: Six proteins reflective of systemic inflammation were examined in 37 PEx from 28 unique CF subjects.

Experience to date with CFTR modulators during pregnancy and breastfeeding in the British Columbia Cystic Fibrosis clinic.

The introduction and rapid uptake of CFTR modulator therapy, in addition to other treatments, has significantly increased life expectancy in CF and provided more women the opportunity to consider and successfully be managed throughout pregnancy. There is however limited evidence to guide patient management and enable informed decision making. Here we report the experience to date from a large multidisciplinary Cystic Fibrosis quaternary referral center in managing patients on CFTR modulators in the peri- and post-partum periods.