The tectonics of the western Ordos Plateau, Ningxia, China: Slip rates on the Luoshan and East Helanshan Faults

Analysis of the locus, style, and rate of faulting is fundamental to understanding the kinematics of continental deformation. The Ordos Plateau lies to the northeast of Tibet, within the India-Eurasia collision zone. Previous studies have suggested that it behaves rigidly and rotates anticlockwise within a large-scale zone of ENE-WSW left-lateral shearing. For this rotation to be accommodated, the eastern and western margins of the Ordos Plateau should be undergoing right-lateral shearing and yet the dominant faulting style appears to be extensional. We focus specifically on the kinematics of the faults bounding the western margin of the Ordos Plateau and make new slip rate estimates for two of the major faults in the region: the right-lateral strike-slip Luoshan Fault and the normal-slip East Helanshan Fault. We use a combination of infrared stimulated luminescence dating of offset landforms with high-resolution imagery and topography from the Pleiades satellites to determine an average right-lateral slip rate of 4.3 ± 0.4 mm/a (1σ uncertainty) on the Luoshan Fault. Similarly, we use 10Be exposure dating to determine a vertical throw rate on the East Helanshan Fault of <0.6 ± 0.1 mm/a, corresponding to an extension rate of <0.7 ± 0.1 mm/a (1σ uncertainty). Both of these results agree well with slip rates determined from the latest campaign GPS data. We therefore conclude that right-lateral shearing is the dominant motion occurring in the western Ordos region, supporting a kinematic model of large-scale anticlockwise rotation of the whole Ordos Plateau

Interstitial lung disease in children - genetic background and associated phenotypes

Interstitial lung disease in children represents a group of rare chronic respiratory disorders. There is growing evidence that mutations in the surfactant protein C gene play a role in the pathogenesis of certain forms of pediatric interstitial lung disease. Recently, mutations in the ABCA3 transporter were found as an underlying cause of fatal respiratory failure in neonates without surfactant protein B deficiency. Especially in familiar cases or in children of consanguineous parents, genetic diagnosis provides an useful tool to identify the underlying etiology of interstitial lung disease. The aim of this review is to summarize and to describe in detail the clinical features of hereditary interstitial lung disease in children. The knowledge of gene variants and associated phenotypes is crucial to identify relevant patients in clinical practice

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Gene expression analysis of children with acute hematogenous osteomyelitis caused by Methicillin-resistant Staphylococcus aureus: correlation with clinical severity of illness.

Children with acute hematogenous osteomyelitis (AHO) demonstrate a broad spectrum of clinical manifestations, ranging from mild to severe. Several advances have been achieved in the study of host immune response to acute invasive Staphylococcus aureus infections through gene expression analysis. However, previous research has neither attempted to evaluate the response of children with AHO specific to Methicillin-resistant Staphylococcus aureus (MRSA) nor to correlate gene expression with clinical phenotype. Study objective was to correlate gene expression of children with AHO due to MRSA with clinical severity of illness. Whole blood samples were obtained in Tempus tubes from 12 children with osteomyelitis once cultures obtained directly from the site of infection confirmed to be positive for MRSA. Using an Illumina platform and a systems-wide modular analysis, microarray findings from ten of these children were compared to that of nine healthy (age, ethnicity and gender) matched controls and correlated with clinical severity of illness. Children with AHO from MRSA demonstrated over-expression of innate immunity with respect to neutrophil activity, coagulation, inflammatory response, and erythrocyte development. Concurrently, these children demonstrated under-expression of adaptive immunity with respect to lymphocyte activation and activity of T-cell, cytotoxic or NK cell, and B-cell lines. Three over-expressed genes, P2RX1, SORT1, and RETN, and two under-expressed genes, LOC641788 and STAT 4, were significantly correlated with severity of illness. STAT 4 showed the strongest correlation (R2 = -0.83). STAT4 downregulation could potentially explain under-expression of genes related to adaptive immunity in this cohort of patients with AHO. This study identified specific genes which correspond to disease severity during the early hospitalization of children with AHO from MRSA. Pattern recognition of this combination of genes could help to identify in the future severe clinical phenotypes before the disease is fully manifest and direct appropriate attention and resources to those children

Genomic Heterogeneity of Methicillin Resistant Staphylococcus aureus Associated with Variation in Severity of Illness among Children with Acute Hematogenous Osteomyelitis.

IntroductionThe association between severity of illness of children with osteomyelitis caused by Methicillin-resistant Staphylococcus aureus (MRSA) and genomic variation of the causative organism has not been previously investigated. The purpose of this study is to assess genomic heterogeneity among MRSA isolates from children with osteomyelitis who have diverse severity of illness.Materials and methodsChildren with osteomyelitis were prospectively studied between 2010 and 2011. Severity of illness of the affected children was determined from clinical and laboratory parameters. MRSA isolates were analyzed with next generation sequencing (NGS) and optical mapping. Sequence data was used for multi-locus sequence typing (MLST), phylogenetic analysis by maximum likelihood (PAML), and identification of virulence genes and single nucleotide polymorphisms (SNP) relative to reference strains.ResultsThe twelve children studied demonstrated severity of illness scores ranging from 0 (mild) to 9 (severe). All isolates were USA300, ST 8, SCC mec IVa MRSA by MLST. The isolates differed from reference strains by 2 insertions (40 Kb each) and 2 deletions (10 and 25 Kb) but had no rearrangements or copy number variations. There was a higher occurrence of virulence genes among study isolates when compared to the reference strains (p = 0.0124). There were an average of 11 nonsynonymous SNPs per strain. PAML demonstrated heterogeneity of study isolates from each other and from the reference strains.DiscussionGenomic heterogeneity exists among MRSA isolates causing osteomyelitis among children in a single community. These variations may play a role in the pathogenesis of variation in clinical severity among these children

Module Analysis of Gene Expression Profile in Whole Blood From Patients with MRSA AHO.

<p>Gene expression in one of the subjects within the healthy control group revealed an unusual array of cellular expression. This subject was excluded and microarray statistical analysis was repeated without his information. Gene expression levels were compared between healthy controls and patients with MRSA AHO on a module by module analysis. Each column represents a subject and each row a cell type. Colored spots represent the percentage of significant over-expressed (red) or under expressed (blue) transcripts (Mann-Whitney p<0.05). The intensity of the color refers to the number of transcripts within each of the pre-selected modules not the actual fold change that is up or down regulated compared to healthy controls. Modular analysis identified that patients had upregulation of innate immunity and mild downregulation of adaptive immunity.</p

Clinical Characteristics of Children Hospitalized with MRSA AHO During Study Time Period.

<p>Subjects excluded from statistical analysis in bold.</p

Gene Expression Biosignature in Whole Blood From Healthy Controls and Patients With MRSA AHO.

<p>Statistical tests were used to compare the two study groups (Welch’s t-test, p<0.05 with Benjamini-Hochberg’s method). <b>A)</b> Analysis of the healthy control group with 9 subjects and the MRSA AHO group with 10 patients yielded 23,023 genes expressed at statistically different levels. Hierarchical clustering, used to organize those genes to reveal differential expression, supports that patients with MRSA AHO have unique signatures that classify them as different from controls. <b>B)</b> Further statistical analysis between the healthy controls and the MRSA AHO group yielded 269 genes expressed at different levels.</p

Module Analysis of Gene List Applied To an Independent Set of Patients Revealed The Same Modular Map.

<p>Average modular transcriptional fingerprint of patients with MRSA AHO showed that patients had upregulation of innate immunity including platelet, neutrophil and erythroid-related genes. Analysis also showed that patients had mild downregulation of adaptive immunity including B- cell, T-cell and NK cell-related genes. Interferon signature was not noted in this analysis.</p