Differential expression of CCR2 and CX3CR1 on CD16+ monocyte subsets is associated with asthma severity

Funding Reem Al-Rashoudi was funded as part of the Saudi Arabian Cultural Bureau, External Joint Supervision Program (EJSP) to do a PhD degree jointly between Aberdeen University, UK and King Saud University, SA. The funding body played no part in the preparation of the data or the manuscript. Acknowledgments This work was supported by a grant from ‘Research Center, Center for Female Scientific and Medical Colleges, Deanship of Scientific Research, King Saud University. Support from the Saudi Arabian Cultural Bureau and External Joint Supervision Program (EJSP) is also gratefully acknowledged. Professor Graeme Devereux (Liverpool School of Tropical Medicine) provided helpful discussion on asthma. Dr. Raif Yuecel and Amer Al-Mazrou provided expertise for flow cytometry and analysis.Peer reviewedPublisher PD

Hydrodynamic coupling in microbially mediated fracture mineralization : formation of self-organized groundwater flow channels

Evidence of fossilized microorganisms embedded within mineral veins and mineral-filled fractures has been observed in a wide range of geological environments. Microorganisms can act as sites for mineral nucleation and also contribute to mineral precipitation by inducing local geochemical changes. In this study, we explore fundamental controls on microbially induced mineralization in rock fractures. Specifically, we systematically investigate the influence of hydrodynamics (velocity, flow rate, aperture) on microbially mediated calcite precipitation. Our experimental results demonstrate that a feedback mechanism exists between the gradual reduction in fracture aperture due to precipitation, and its effect on the local fluid velocity. This feedback results in mineral fill distributions that focus flow into a small number of self-organizing channels that remain open, ultimately controlling the final aperture profile that governs flow within the fracture. This hydrodynamic coupling can explain field observations of discrete groundwater flow channeling within fracture-fill mineral geometries where strong evidence of microbial activity is reported

Altered Chromosomal Positioning, Compaction, and Gene Expression with a Lamin A/C Gene Mutation

Lamins A and C, encoded by the LMNA gene, are filamentous proteins that form the core scaffold of the nuclear lamina. Dominant LMNA gene mutations cause multiple human diseases including cardiac and skeletal myopathies. The nuclear lamina is thought to regulate gene expression by its direct interaction with chromatin. LMNA gene mutations may mediate disease by disrupting normal gene expression.To investigate the hypothesis that mutant lamin A/C changes the lamina's ability to interact with chromatin, we studied gene misexpression resulting from the cardiomyopathic LMNA E161K mutation and correlated this with changes in chromosome positioning. We identified clusters of misexpressed genes and examined the nuclear positioning of two such genomic clusters, each harboring genes relevant to striated muscle disease including LMO7 and MBNL2. Both gene clusters were found to be more centrally positioned in LMNA-mutant nuclei. Additionally, these loci were less compacted. In LMNA mutant heart and fibroblasts, we found that chromosome 13 had a disproportionately high fraction of misexpressed genes. Using three-dimensional fluorescence in situ hybridization we found that the entire territory of chromosome 13 was displaced towards the center of the nucleus in LMNA mutant fibroblasts. Additional cardiomyopathic LMNA gene mutations were also shown to have abnormal positioning of chromosome 13, although in the opposite direction.These data support a model in which LMNA mutations perturb the intranuclear positioning and compaction of chromosomal domains and provide a mechanism by which gene expression may be altered

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Modelling fault zone evolution : the effect of heterogeneity

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Simulating brittle fault evolution from networks of pre-existing joints within crystalline rock

Many faults grow by linkage of smaller structures, and damage zones along faults may arise as a result of this linkage process. In this paper we present the first numerical simulations of the temporal and spatial evolution of fault linkage structures from more than 20 pre-existing joints, the initial positions of which are based on field observation. We show how the constantly evolving geometry and local stress field contribute to fault zone evolution. Markedly different fault zone trace geometries are predicted when the joints are at different angles to the maximum compressive far field stress ranging from evolving smooth linear structures to producing complex 'stepped' fault zone trace geometries. We show that evolution of the complex fault zone geometry is governed by 1) the strong local variations in the stress field due to complex interactions between neighbouring joints and 2) the orientation of the initial joint pattern with respect to the far field stress

Distant off-fault damage and gold mineralization : the impact of rock heterogeneity

Field observations have established that fault-related damage can occur at locations, far from the principal slip surface, which are well outside the fractured region currently predicted by models of fault damage. We use a finite element model to simulate fracture initiation due to fault linkage and show how variations in rock properties allow off-fault damage to develop at surprisingly large distances away from the main fault. Off-fault damage continues to grow even after two adjacent, closely spaced fault segments have interacted and linked. We demonstrate that this process was important for the formation of fracture-hosted gold deposits in the Mount Pleasant goldfield, Western Australia. The strength of lithological contacts also has a significant impact on off-fault damage location and intensity. Our approach may go some way to explaining the non-intuitive distribution of mineralization in certain mineral systems, as well as being applicable to predict subsurface fracturing and fluid flow in hydrothermal/geothermal reservoirs

Organization Development in Health Care :High Impact Practices for a Complex and Changing Environment

https://aura.antioch.edu/stubooks/1004/thumbnail.jp