Situs inversus abdominalis and duodenal atresia

Fewer than 20 patients born with situs inversus and duodenal atresia have been reported in the literature. We present a patient with this condition. A newborn baby presented shortly after birth with persistent bilious vomiting. An abdominal radiograph showed a right-sided stomach bubble and a second bubble on the left - typical of duodenal atresia but with mirror image configuration. Laparotomy confirmed the diagnosis of situs inversus abdominalis, which was also demonstrated by contrast studies and ultrasound. Duodenoduodenostomy was performed and the patient discharged on day 8 postoperatively. Situs inversus is associated with other congenital malformations including splenic malformations, left-sided liver and cardiac abnormalities; it is rarely associated with duodenal atresia. Duodenal obstruction in the presence of situs inversus has been described, including obstruction due to a web, stenosis, pre-duodenal portal vein and complete atresia. The patient presented in this paper had a duodenal web in the second part of the duodenum. Before undertaking surgery it is important to establish the presence of associated gastrointestinal and cardiac abnormalities

Single unconfined compression of cellular dense collagen scaffolds for cartilage and bone tissue engineering

Cell seeded collagen matrix scaffolds have been extensively evaluated recently as potential systems for de-novo tissue regeneration and repair for a variety of tissue types. While collagen gels are biologically excellent as starting point scaffold materials, their use is limited by the lack of cohesive structure and inherently weak mechanical properties due to a high liquid content (>99%). An ingenious method of combining unconfined plastic compression (PC) with capillary action has shown that these scaffolds can be rapidly processed into tissue like structures, which can be immediately implanted into the host[1]. It has been shown that the rapid increase in fibrillar collagen density dramatically enhanced the mechanical properties of such scaffolds thus potentially eliminating the need for long term cellular action. This simple project investigated the effect of single unconfined compression on cartilage-cell seeded collagen matrices in terms of cell viability, proliferation and oxygen consumption

Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease.

Mitochondria abnormalities in skeletal muscle may contribute to frailty and sarcopenia, commonly present in patients with chronic kidney disease (CKD). Dysfunctional mitochondria are also a major source of oxidative stress and may contribute to cardiovascular disease in CKD We tested the hypothesis that mitochondrial structure and function worsens with the severity of CKD Mitochondrial volume density, mitochondrial DNA (mtDNA) copy number, BNIP3, and PGC1α protein expression were evaluated in skeletal muscle biopsies obtained from 27 subjects (17 controls and 10 with CKD stage 5 on hemodialysis). We also measured mtDNA copy number in peripheral blood mononuclear cells (PBMCs), plasma isofurans, and plasma F2-isoprostanes in 208 subjects divided into three groups: non-CKD (eGFR>60 mL/min), CKD stage 3-4 (eGFR 60-15 mL/min), and CKD stage 5 (on hemodialysis). Muscle biopsies from patients with CKD stage 5 revealed lower mitochondrial volume density, lower mtDNA copy number, and higher BNIP3 content than controls. mtDNA copy number in PBMCs was decreased with increasing severity of CKD: non-CKD (6.48, 95% CI 4.49-8.46), CKD stage 3-4 (3.30, 95% CI 0.85-5.75, P = 0.048 vs. non-CKD), and CKD stage 5 (1.93, 95% CI 0.27-3.59, P = 0.001 vs. non-CKD). Isofurans were higher in patients with CKD stage 5 (median 59.21 pg/mL, IQR 41.76-95.36) compared to patients with non-CKD (median 49.95 pg/mL, IQR 27.88-83.46, P = 0.001), whereas F2-isoprostanes did not differ among groups. Severity of CKD is associated with mitochondrial dysfunction and markers of oxidative stress. Mitochondrial abnormalities, which are common in skeletal muscle from patients with CKD stage 5, may explain the muscle dysfunction associated with frailty and sarcopenia in CKD Further studies are required to evaluate mitochondrial function in vivo in patients with different CKD stages

Perfusion of oxygen in 3D plastic compressed collagen constructs

The development of 3D connective tissues in vitro is heavily dependent upon remodelling of the matrix, in particular collagen, by resident cells. We have developed a novel plastic compression (PC) technique, for the fabrication of dense cell-collagen based bio-mimetic tissues (Brown et al. 2005). Cell survival in these PC collagen constructs is critical for successful tissue modelling and so the aim here is to understand, quantitatively their dynamic perfusion. This is important for the development of tissue bioreactors for the culture of PC constructs. We have used a fibre-optic oxygen sensor to measure changing oxygen levels in the core of such constructs. This effectively measures O2 consumption by cells, and by extrapolation, gradients and diffusion properties in the model tissues, which can be correlated with cell death

Toward Performance-Portable PETSc for GPU-based Exascale Systems

The Portable Extensible Toolkit for Scientific computation (PETSc) library delivers scalable solvers for nonlinear time-dependent differential and algebraic equations and for numerical optimization.The PETSc design for performance portability addresses fundamental GPU accelerator challenges and stresses flexibility and extensibility by separating the programming model used by the application from that used by the library, and it enables application developers to use their preferred programming model, such as Kokkos, RAJA, SYCL, HIP, CUDA, or OpenCL, on upcoming exascale systems. A blueprint for using GPUs from PETSc-based codes is provided, and case studies emphasize the flexibility and high performance achieved on current GPU-based systems.Comment: 15 pages, 10 figures, 2 table

Measuring velocity of sound with nuclear resonant inelastic x-ray scattering

Nuclear resonant inelastic x-ray scattering is used to measure the projected partial phonon density of states of materials. A relationship is derived between the low-energy part of this frequency distribution function and the sound velocity of materials. Our derivation is valid for harmonic solids with Debye-like low-frequency dynamics. This method of sound velocity determination is applied to elemental, composite, and impurity samples which are representative of a wide variety of both crystalline and noncrystalline materials. Advantages and limitations of this method are elucidated

Large-scale sequencing of SARS-CoV-2 genomes from one region allows detailed epidemiology and enables local outbreak management.

The COVID-19 pandemic has spread rapidly throughout the world. In the UK, the initial peak was in April 2020; in the county of Norfolk (UK) and surrounding areas, which has a stable, low-density population, over 3200 cases were reported between March and August 2020. As part of the activities of the national COVID-19 Genomics Consortium (COG-UK) we undertook whole genome sequencing of the SARS-CoV-2 genomes present in positive clinical samples from the Norfolk region. These samples were collected by four major hospitals, multiple minor hospitals, care facilities and community organizations within Norfolk and surrounding areas. We combined clinical metadata with the sequencing data from regional SARS-CoV-2 genomes to understand the origins, genetic variation, transmission and expansion (spread) of the virus within the region and provide context nationally. Data were fed back into the national effort for pandemic management, whilst simultaneously being used to assist local outbreak analyses. Overall, 1565 positive samples (172 per 100 000 population) from 1376 cases were evaluated; for 140 cases between two and six samples were available providing longitudinal data. This represented 42.6 % of all positive samples identified by hospital testing in the region and encompassed those with clinical need, and health and care workers and their families. In total, 1035 cases had genome sequences of sufficient quality to provide phylogenetic lineages. These genomes belonged to 26 distinct global lineages, indicating that there were multiple separate introductions into the region. Furthermore, 100 genetically distinct UK lineages were detected demonstrating local evolution, at a rate of ~2 SNPs per month, and multiple co-occurring lineages as the pandemic progressed. Our analysis: identified a discrete sublineage associated with six care facilities; found no evidence of reinfection in longitudinal samples; ruled out a nosocomial outbreak; identified 16 lineages in key workers which were not in patients, indicating infection control measures were effective; and found the D614G spike protein mutation which is linked to increased transmissibility dominates the samples and rapidly confirmed relatedness of cases in an outbreak at a food processing facility. The large-scale genome sequencing of SARS-CoV-2-positive samples has provided valuable additional data for public health epidemiology in the Norfolk region, and will continue to help identify and untangle hidden transmission chains as the pandemic evolves.The sequencing costs were funded by the COVID-19 Genomics UK (COG-UK) Consortium which is supported by funding from the Medical Research Council (MRC) part of UK Research and Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute