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Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients.
Methods and results
This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman’s Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6–33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (−0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (−0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63–0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].
Conclusions
Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.
Imprinting control regions (ICRs) play a fundamental role in establishing and maintaining the non-random monoallelic expression of certain genes, via common regulatory elements such as non-coding RNAs and differentially methylated regions (DMRs) of DNA. We recently surveyed DNA methylation levels within four ICRs (H19-ICR, IGF2-DMR, KvDMR, and NESPAS-ICR) in whole-blood genomic DNA from 128 monozygotic (MZ) and 128 dizygotic (DZ) human twin pairs. Our analyses revealed high individual variation and intra-domain covariation in methylation levels across CpGs and emphasized the interaction between epigenetic variation and the underlying genetic sequence in a parent-of-origin fashion. Here, we extend our analysis to conduct two genome-wide screenings of single nucleotide polymorphisms (SNPs) underlying either intra-domain covariation or parent-of-origin-dependent association with methylation status at individual CpG sites located within ICRs. Although genome-wide significance was not surpassed due to sample size limitations, the most significantly associated SNPs found through multiple-trait genome-wide association (MQFAM) included the previously described rs10732516, which is located in the vicinity of the H19-ICR. Similarly, we identified an association between rs965808 and methylation status within the NESPAS-ICR. This SNP is positioned within an intronic region of the overlapping genes GNAS and GNAS-AS1, which are imprinted genes regulated by the NESPAS-ICR. Sixteen other SNPs located in regions apart from the analyzed regions displayed suggestive association with intra-domain methylation. Additionally, we identified 13 SNPs displaying parent-of-origin association with individual methylation sites through family-based association testing. In this exploratory study, we show the value and feasibility of using alternative GWAS approaches in the study of the interaction between epigenetic state and genetic sequence within imprinting regulatory domains. Despite the relatively small sample size, we identified a number of SNPs displaying suggestive association either in a domain-wide or in a parent-of-origin fashion. Nevertheless, these associations will require future experimental validation or replication in larger and independent samples.
Extreme impacts can result from extreme weather and climate events, but can also occur without extreme events. This chapter examines two broad categories of impacts on human and ecological systems, both of which are influenced by changes in climate, vulnerability, and exposure: first, the chapter primarily focuses on impacts that result from extreme weather and climate events, and second, it also considers extreme impacts that are triggered by less-than-extreme weather or climate events. These two categories of impacts are examined across sectors, systems, and regions. Extreme events can have positive as well as negative impacts on ecosystems and human activities.
Economic losses from weather- and climate-related disasters have increased, but with large spatial and interannual variability (high confidence, based on high agreement, medium evidence). Global weather- and climate-related disaster losses reported over the last few decades reflect mainly monetized direct damages to assets, and are unequally distributed. Estimates of annual losses have ranged since 1980 from a few US$ billion to above 200 billion (in 2010 dollars), with the highest value for 2005 (the year of Hurricane Katrina). In the period 2000 to 2008, Asia experienced the highest number of weather- and climate-related disasters. The Americas suffered the most economic loss, accounting for the highest proportion (54.6%) of total loss, followed by Asia (27.5%) and Europe (15.9%). Africa accounted for only 0.6% of global economic losses. Loss estimates are lower bound estimates because many impacts, such as loss of human lives, cultural heritage, and ecosystem services, are difficult to value and monetize, and thus they are poorly reflected in estimates of losses. [4.5.1, 4.5.3.3, 4.5.4.1]
Edited by
Alex S. Evers, Washington University School of Medicine, St Louis,Mervyn Maze, University of California, San Francisco,Evan D. Kharasch, Washington University School of Medicine, St Louis
Healthcare data suggest that the incidence and severity of Clostridium difficile infection (CDI) in hospitals are increasing. However, the overall burden of disease and the mortality rate associated with CDI, including the contribution from cases of infection that occur in nursing homes, are poorly understood.
Objective.
To describe the epidemiology, disease burden, and mortality rate of healthcare-onset CDI.
Methods.
In 2006, active public reporting of healthcare-onset CDI, using standardized case definitions, was mandated for all Ohio hospitals and nursing homes. Incidence rates were determined and stratified according to healthcare facility characteristics. Death certificates that listed CDI were analyzed for trends.
Results.
There were 14,329 CDI cases reported, including 6,376 cases at 210 hospitals (5,217 initial cases [ie, cases identified more than 48 hours after admission to a healthcare facility in patients who had not had CDI during the previous 6 months] and 1,159 recurrent cases [ie, cases involving patients who had had CDI during the previous 6 months]) and 7,953 cases at 955 nursing homes (4,880 initial and 3,073 recurrent cases). After adjusting for missing data, the estimated total was 18,200 cases of CDI, which included 7,000 hospital cases (5,700 initial and 1,300 recurrent cases) and 11,200 nursing homes cases (6,900 initial and 4,300 recurrent cases). The rate for initial cases was 6.4-7.9 cases/10,000 patient-days for hospitals and 1.7-2.9 cases/10,000 patient-days for nursing homes. The rate for initial cases in nursing homes decreased during the study (P < .001). Nonpediatric hospital status (P = .011), a smaller number of beds (P = .003), and location in the eastern or northeastern region of the state (P = .011) were each independently associated with a higher rate of initial cases in hospitals. Death certificates for 2006 listed CDI among the causes of death for 893 Ohio residents; between 2000 and 2006, this number increased more than 4-fold.
Conclusion.
Healthcare-onset CDI represents a major public health threat that, when considered in the context of an increasing mortality rate, should justify a major focus on prevention efforts.
In reviewing the tectonic features of a portion of Portuguese East Africa, south of the Zambezi, one of the present writers alone (2), and also in conjunction with Capt. R. C. Wilson (1), advanced the view that the surface topography had to some extent been affected by the same movements which were associated farther north with the Rift Zone period of Eastern Africa. This opinion was arrived at from the consideration of the physiography, the observation of definite faulting in places, especially in western Sheringoma on an extension of the Nyasa-Shire line, and also of volcanic occurrences elsewhere in significant positions.
The “bluestone” which is found in the central parts of some of the concretions associated with the large spiral bodies described by Mr. B. B. Woodward is found, on microscopical examination, to be a calcareous sandstone. Sabangular grains of quartz, averaging 0·04 mm. in diameter, constitute over 50 per cent of the rock, and are set in a cement of carbonates which have crystallized in plates very much as in the Fontainebleau sandstone. These plates are sometimes 3 cm. across, and give a characteristic lustre to the stone. The quartz-grains are evenly distributed through the plates of crystalline carbonate, and are so closely packed as to be almost in contact. It is easy to imagine that with the complete removal of the carbonates by solution there would remain a friable sandstone, very porous, but still occupying almost the same volume as the bluestone.
The alkaline volcanic rocks of the Lupata Gorge were described in 1915 by E. O. Teale and R. C. Wilson, and in 1922 F. P. Mennell showed that at the entrance to the gorge these rocks were preceded by a sheet of columnar rhyolite intercalated between two series of sediments, for which he proposed the name of the Upper and Lower Lupata Sandstones respectively; the Lower series rested on Karroo basalts, and these upon Karroo sandstones. In 1923, E. O. Teale and W. Campbell Smith gave a detailed petro-graphical description of certain of the alkaline lavas and of the intrusive olivine-nephelinite (nepheline-basalt) of Sena Hill on the south side of the Zambezi.
The peculiar garnetiferous rock occurring to the east of Loch Borolan seems to have been first noted by Dr. Callaway in 1883, and is described by Dr. Bonney in an appendix to Dr. Callaway's paper.
IN the course of a journey from El Obeid to Jebel Marra, in Darfur, Captain Hubert Lynes collected a number of the rocks from the volcano of Dereiba and from various other points on the route, shown in the map (Fig. 1). The rocks of this area have not been described hitherto. The following notes give a brief description of the nature of the country, with petrological details of the rocks collected.
Increasing MOSFET performance requires scaling, the systematic reduction in device dimensions. Tunneling leakage, however, provides an absolute scaling limit for SiO2of about 1.5 nm. Power limitations and device reliability are likely to pose softer limits slightly above 2 nm. We have investigated the use of high permittivity materials such as TiO2, ZrO2, and their silicates as potential replacements for SiO2. We have synthesized titanium nitrate (Ti(NO3)4or TN), zirconium nitrate (Zr(NO3)4or ZrN), and hafnium nitrate (Hf(NO3)4or HfN) as hydrogen and carbon free deposition precursors. Several problems arise in the use of these films including the formation of an amorphous low permittivity interfacial layer. For TiO2this layer is formed by silicon up diffusion. Surface nitridation retards the formation of the interfacial layer. We discuss the effects of both thermal and remote plasma surface nitridation treatments on the properties of the film stack. ZrO2and HfO2appear to form a thermal layer of silicon oxide between the high permittivity film and the silicon and have excess oxygen in the bulk of the film.
It is well known that some giant extragalactic star-forming regions contain WR stars. D'Odorico, Massey, Rosa and coworkers found many examples in nearby galaxies of giant HII regions whose spectra show that they contain WN, and occasionally, WC stars. The dwarf emission-line galaxies He 2–10 (Allen et al. 1976) and Tol 3 (Kunth & Sargent 1981) have a strong broad emission feature near HeII 4686Å; in the latter object ∼150 WN stars are required to explain the observed equivalent width.