Segregation analysis identifies specific alpha-defensin (DEFA1A3) SNP–CNV haplotypes in predisposition to IgA nephropathy

BACKGROUND: Immunoglobulin A (IgA) nephropathy is a disorder of the immune system affecting kidney function, and genome-wide association studies (GWAS) have defined numerous loci with associated variation, all implicating components of innate or adaptive immunity. Among these, single nucleotide polymorphisms (SNPs) in a region including the multiallelic copy number variation (CNV) of DEFA1A3 are associated with IgA nephropathy in both European and Asian populations. At present, the precise factors underlying the observed associations at DEFA1A3 have not been defined, although the key alleles differ between Asian and European populations, and multiple independent factors may be involved even within a single population. METHODS: In this study, we measured DEFA1A3 copy number in UK family trios with an offspring affected by IgA nephropathy, used the population distributions of joint SNP-CNV haplotypes to infer the likely segregation in trios, and applied transmission disequilibrium tests (TDT) to examine joint SNP-CNV haplotypes for over- or undertransmission into affected offspring from heterozygous parents. RESULTS AND CONCLUSIONS: We observed overtransmission of 3-copy class 2 haplotypes (raw p = 0.029) and some evidence for under-transmission of 3-copy class 1 haplotypes (raw p = 0.051), although these apparent effects were not statistically significant after correction for testing of multiple haplotypes

High sensitivity measurement of implanted As in the presence of Ge in GexSi1−x/Si layered alloys using trace element accelerator mass spectrometry

This article discusses high sensitivity measurement of implanted As in the presence of Ge in Ge(x)Si(1-x)/Si layered alloys using trace element accelerator mass spectrometry

Non-invasive carbon dioxide monitoring in a porcine model of acute lung injury due to smoke inhalation and burns

In critically ill intubated patients, assessment of adequacy of ventilation relies on measuring partial pressure of arterial carbon dioxide (PaCO2), which requires invasive arterial blood gas analysis. Alternative noninvasive technologies include transcutaneous CO2 (tPCO2) and end-tidal CO2 (EtCO2) monitoring. We evaluated accuracy of tPCO2 and EtCO2 monitoring in a porcine model of acute lung injury (ALI) due to smoke inhalation and burns. Eight anesthetized Yorkshire pigs underwent mechanical ventilation, wood-bark smoke inhalation injury, and 40% total body surface area thermal injury. tPCO2 was measured with a SenTec system (SenTec AG, Therwil, Switzerland) and EtCO2 with a Capnostream-20 (Oridion Medical, Jerusalem, Israel). These values were compared with PaCO2 measurements from an arterial blood gas analyzer. Paired measurements of EtCO2-PaCO2 (n = 276) and tPCO2-PaCO2 (n = 250) were recorded in the PaCO2 range of 25 to 85 mmHg. Overlapping data sets were analyzed based on respiratory and hemodynamic status of animals. Acute lung injury was defined as PaO2/FIO2 64 300 mmHg; hemodynamic instability was defined as mean arterial pressure 64 60 mmHg. Before ALI, EtCO2 demonstrated moderate correlation with PaCO2 (R = 0.45; P < 0.0001), which deteriorated after onset of ALI (R = 0.12; P < 0.0001). Before ALI, tPCO2 demonstrated moderate correlation (R = 0.51, P < 0.0001), which was sustained after onset of ALI (R = 0.78; P < 0.0001). During hemodynamic stability, EtCO2 demonstrated moderate correlation with PaCO2 (R = 0.44; P < 0.0001). During hemodynamic instability, EtCO2 did not correlate with PaCO2 (R = 0.03; P = 0.29). tPCO2 monitoring demonstrated strong correlation with PaCO2 during hemodynamic stability (R = 0.80, P < 0.0001), which deteriorated under hemodynamically unstable conditions (R = 0.39; P < 0.0001). Noninvasive carbon dioxide monitors are acceptable for monitoring trends in PaCO2 under conditions of hemodynamic and pulmonary stability. Under unstable conditions, reevaluation of patient status and increased caution in the interpretation of results are required

High Sensitivity Measurement of Implanted as in the Presence of Ge in Ge(x)Si(1-x)/Si Layered Alloys Using Trace Element Accelerator Mass Spectrometry

This article discusses high sensitivity measurement of implanted As in the presence of Ge in Ge(x)Si(1-x)/Si layered alloys using trace element accelerator mass spectrometry

1H-NMR Metabolomics Identifies Significant Changes in Metabolism over Time in a Porcine Model of Severe Burn and Smoke Inhalation

Burn injury initiates a hypermetabolic response leading to muscle catabolism and organ dysfunction but has not been well-characterized by high-throughput metabolomics. We examined changes in metabolism over the first 72 h post-burn using proton nuclear magnetic resonance (1H-NMR) spectroscopy and serum from a porcine model of severe burn injury. We sought to quantify the changes in metabolism that occur over time in response to severe burn and smoke inhalation in this preliminary study. Fifteen pigs received 40% total body surface area (TBSA) burns with additional pine bark smoke inhalation. Arterial blood was drawn at baseline (pre-burn) and every 24 h until 72 h post-injury or death. The aqueous portion of each serum sample was analyzed using 1H-NMR spectroscopy and metabolite concentrations were used for principal component analysis (PCA). Thirty-eight metabolites were quantified in 39 samples. Of these, 31 showed significant concentration changes over time (p &lt; 0.05). PCA revealed clustering of samples by time point on a 2D scores plot. The first 48 h post-burn were characterized by high concentrations of histamine, alanine, phenylalanine, and tyrosine. Later timepoints were characterized by rising concentrations of 2-hydroxybutyrate, 3-hydroxybutyrate, acetoacetate, and isovalerate. No significant differences in metabolism related to mortality were observed. Our work highlights the accumulation of organic acids resulting from fatty acid catabolism and oxidative stress. Further studies will be required to relate accumulation of the four organic carboxylates identified in this analysis to outcomes from burn injury

Recent circum-Arctic ice-wedge degradation and its hydrological impacts

Ice-wedges are common permafrost features formed over hundreds to thousands of years of repeated frost cracking and ice vein growth. We used field and remote sensing observations to assess changes in areas dominated by ice-wedges, and we simulated the effects of those changes on watershed-scale hydrology. We show that top melting of ice-wedges and subsequent ground subsidence has occurred at multiple sites in the North American and Russian Arctic. At most sites, melting ice-wedges have initially resulted in increased wetness contrast across the landscape, evident as increased surface water in the ice-wedge polygon troughs and somewhat drier polygon centers. Most areas are becoming more heterogeneous with wetter troughs, more small ponds (themokarst pits forming initially at ice-wedge intersections and then spreading along the troughs) and drier polygon centers. Some areas with initial good drainage, such as near creeks, lake margins, and in hilly terrain, high-centered polygons form an overall landscape drying due to a drying of both polygon centers and troughs. Unlike the multi-decadal warming observed in permafrost temperatures, the ice-wedge melting that we observed appeared as a sub-decadal response, even at locations with low mean annual permafrost temperatures (down to −14 °C). Gradual long-term air and permafrost warming combined with anomalously warm summers or deep snow winters preceded the onset of the ice-wedge melting. To assess hydrological impacts of ice-wedge melting, we simulated tundra water balance before and after melting. Our coupled hydrological and thermal model experiments applied over hypothetical polygon surfaces suggest that (1) ice-wedge melting that produces a connected trough-network reduces inundation and increases runoff, and that (2) changing patterns of snow distribution due to differential ground subsidence has a major control on ice-wedge polygon tundra water balance despite an identical snow water equivalent at the landscape-scale. These decimeter-scale geomorphic changes are expected to continue in permafrost regions dominated by ice-wedge polygons, with implications for land-atmosphere and land-ocean fluxes of water, carbon, and energy