Cardiovascular disease risk in the offspring of diabetic women: the impact of the intrauterine environment

The incidence of gestational diabetes is increasing worldwide, exposing large numbers of infants to hyperglycaemia whilst in utero. This exposure may have a long-term negative impact on the cardiovascular health of the offspring. Novel methods to assess cardiovascular status in the neonatal period are now available—including measuring arterial intima-media thickness and retinal photography. These measures will allow researchers to assess the relative impact of intrauterine exposures, distinguishing these from genetic or postnatal environmental factors. Understanding the long-term impact of the intrauterine environment should allow the development of more effective health policy and interventions to decrease the future burden of cardiovascular disease. Initiating disease prevention aimed at the developing fetus during the antenatal period may optimise community health outcomes

MoSS: Monocular Shape Sensing for Continuum Robots

Continuum robots are promising candidates for interactive tasks in medical and industrial applications due to their unique shape, compliance, and miniaturization capability. Accurate and real-time shape sensing is essential for such tasks yet remains a challenge. Embedded shape sensing has high hardware complexity and cost, while vision-based methods require stereo setup and struggle to achieve real-time performance. This paper proposes the first eye-to-hand monocular approach to continuum robot shape sensing. Utilizing a deep encoder-decoder network, our method, MoSSNet, eliminates the computation cost of stereo matching and reduces requirements on sensing hardware. In particular, MoSSNet comprises an encoder and three parallel decoders to uncover spatial, length, and contour information from a single RGB image, and then obtains the 3D shape through curve fitting. A two-segment tendon-driven continuum robot is used for data collection and testing, demonstrating accurate (mean shape error of 0.91 mm, or 0.36% of robot length) and real-time (70 fps) shape sensing on real-world data. Additionally, the method is optimized end-to-end and does not require fiducial markers, manual segmentation, or camera calibration. Code and datasets will be made available at https://github.com/ContinuumRoboticsLab/MoSSNet.Comment: 8 pages, 6 figures, submitted to RA-

Utilising surface-level data to explore surface, tooth, individual and family influence on the aetiology of hypomineralised second primary molars

OBJECTIVES: Hypomineralised second primary molars (HSPM) are common developmental enamel defects. The aims of this study were to use surface-level data to explore the clustering of HSPM at four levels (family, child, tooth, surface). METHODS: This study of 172 twin pairs was nested within the Peri/postnatal Epigenetic Twin Study. HSPM was measured by standardised oral examinations at age 6 years. Multilevel logistic regression models were fitted to assess the correlation structure of surface level data and variation in HSPM. The associations between surface level risk factors and HSPM were then explored using the multilevel logistic regression model using the best fitting correlation structure. RESULTS: The prevalence of HSPM was 68 (19.8%) children, with a total of 141 (10.3%) teeth and 264 tooth surfaces (6.3%) affected. Multilevel models revealed that a hierarchical structure accounting for correlation at the family, child and tooth level best accounted for the variation in HSPM. The estimated variances from the best fitting model (Model 3) were largest at the family level (12.27, 95% CI 6.68, 22.51) compared with 5.23 at the child level and 1.93 at the tooth level. Application of regression analysis utilising this three-level correlation structure identified tooth/surface level factors in addition to the previously identified familial and individual risk factors for HSPM. CONCLUSION: In addition to familial (environmental and genetic) and unique child-level factors, the aetiology of HSPM is likely to be influenced by local tooth-level factors

Randomised controlled trial comparing daily VerSus depot vitamin D3 therapy in 0-16-year-old newly settled refugees in Western Australia over a period of 40 weeks

Vitamin D deficiency is highly prevalent in newly settled refugees in Western Australia (WA). If adherence to daily vitamin D therapy is problematic, depot therapy is a therapeutic alternative. The aim of this studywas to compare daily versus depot treatment and factors influencing the therapeutic outcome. Newly settled refugees (n = 151) with 25(OH)D levels less than 78 nmol/L were randomised to receive daily or depot vitamin D therapy with eight weekly interval follow up to 40 weeks. Biochemical and clinical parameters were collected at each visit. Generalized LinearMixedModels (GLMM) examined the longitudinal changes over time controlling for confounders including age, gender, treatment arm, season, country of refuge/origin and sun exposure score. Participants were aged 5.5 months to 16.0 years (75 males, 83 females). Both treatment groups achieved vitamin D sufficiency. The daily treatment group had significantly higher 25(OH)D levels at each visit post baseline and a higher proportion of participants with levels above 50 nmol/L at all time points. Time, treatment group, calcium and sun exposure score were significant predictors of 25(OH)D serum levels. Depot vitamin D therapy is an alternative to daily treatment in this at-risk group of children and adolescents in whom treatment adherence is problemati

The PIRO concept: P is for predisposition

SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Etablierung eines revers–genetischen Systems für feline Coronaviren

Im Rahmen dieser Arbeit erfolgte die Etablierung eines revers-genetischen Systems für ein Serotyp I felines Coronavirus (FCoV). Dabei wurden folgende Ergebnisse erzielt: 1) Als Grundlage für die Etablierung des Systems wurde die komplette Genomsequenz des FCoV Stammes Black bestimmt und anhand dieser Sequenz der Genomaufbau ermittelt. Es ließ sich der für Coronaviren typische Genomaufbau nachweisen. 2) Die Herstellung eines infektiösen Klons beinhaltete die Integration einer kompletten cDNA Kopie des FCoV Stammes Black in das Vaccinia Virus Genom, welches als Vektor diente. Die coronavirale cDNA wurde in vitro transkribiert und die synthetische RNA in Zellen elektroporiert. Rekombinante FCoV ließen sich nachweisen und somit war die synthetische RNA infektiös, also in der Lage, den coronaviralen Replikationszyklus zu initiieren und zu durchlaufen. Die Analyse der gewonnenen rekombinanten Viren erfolgte nach Infektion feliner Zellkulturen mit verschiedenen Ansätzen. Dabei konnte festgestellt werden, dass die rekombinanten Viren die gleichen Eigenschaften wie der ursprüngliche FCoV Stamm Black besitzen. 3) In nachfolgenden Versuchen erfolgte die Herstellung zweier Reportergenexprimierender FCoV mit dem etablierten revers-genetischen System. Dabei wurden im FCoV Stamm Black Genom die akzessorischen Gene 3abc durch das „green fluorescent protein“ (GFP) oder Renilla Luciferase ersetzt. Die stabile Expression der Reportergene konnte in felinen Zellkulturen nachgewiesen werden. 4) Feline Monozyten, Makrophagen und dendritische Zellen (DCs), die als Zielzellen sowohl von FCoV als auch von anderen Coronaviren gelten, wurden mit Wildtyp und den Reportergen-exprimierenden FCoV in vitro infiziert. Die Infektion von monozytären Zellen konnte ausschließlich mit Hilfe der GFP exprimierenden Mutanten nachgewiesen werden.In this study a reverse genetic system for a serotype I feline coronavirus was established. The following results were obtained: 1) As basis for the establishment of a reverse genetic system the complete genomic sequence of FCoV strain Black was determined. The sequence analysis revealed the typical genome organization for coronavirus. 2) For the generation of an infectious clone the full-length FCoV strain Black cDNA was introduced into vaccinia virus as cloning vector. The FCoV cDNA was used for in vitro transcription and the synthesized RNA electroporated into cells. Recombinant FCoV could be detected which showed that the in vitro transcribed RNA was infectious and could initiate the coronavirus replication cycle. The resulting recombinant virus was analyzed in feline cell culture using different approaches. It could be demonstrated that the properties of the recombinant virus are indistinguishable from those of FCoV wild type virus strain Black. 3) In subsequent experiments based on the newly established reverse genetic system, two reporter gene expressing recombinant FCoV were generated. The accessory genes 3abc were replaced by genes encoding the green fluorescent protein (GFP) and Renilla luciferase. The stable expression of these reporter genes was demonstrated in feline cell culture. 4) Feline monocytes, macrophages and dendritic cells (DCs) which are considered to be important target cells for FCoV and other coronaviruses were infected with the wildtype and the reporter gene expressing FCoV. The infection of the monocytic cells was exclusively shown with the GFP expressing mutant

Causal inference in multi-cohort studies using the target trial approach

Longitudinal cohort studies provide the opportunity to examine causal effects of complex exposures on long-term health outcomes. Utilizing data from multiple cohorts has the potential to add further benefit by improving precision of estimates through data pooling and allowing examination of effect heterogeneity across contexts. However, the interpretation of findings can be complicated by biases that may be compounded when pooling data or may contribute to discrepant findings when analyses are replicated across cohorts. Here we extend the target trial framework, already well established as a powerful tool for causal inference in single-cohort studies, to address the specific challenges that can arise in the multi-cohort setting. The approach considers the target trial as a central point of reference, as opposed to comparing one study to another. This enables clear definition of the target estimand and systematic consideration of sources of bias within each cohort and additional sources of bias arising from data pooling. Consequently, analyses can be designed to reduce these biases and the resulting findings appropriately interpreted. We use a case study to demonstrate the approach and its potential to strengthen causal inference in multi-cohort studies through improved analysis design and clarity in the interpretation of findings.Comment: 34 pages, 3 figure