Reliability of lithium dilution cardiac output in anaesthetized sheep

BACKGROUND: Cardiac output (CO) measurement with lithium dilution (COLD) has not been fully validated in sheep using precise ultrasonic flow probe technology (COUFP). Sheep generate important cardiovascular research models and the use of COLD has become more popular in experimental settings. METHODS: Ultrasonic transit-time perivascular flow probes were surgically implanted on the pulmonary artery of 13 sheep. Paired COLD readings were taken at six time points, before and after implantation of a left ventricular assist device (LVAD) and compared with COUFP recorded just after lithium injection. RESULTS: The mean COLD was 5.7 litre min(-1) (range 3.8-9.6 litre min(-1)) and mean COUFP 5.9 litre min(-1) (range 4.0-9.2 litre min(-1)). The bias (standard deviation) was 0.3 (1.0) litre min(-1) [5.1 (16.9)%] and limits of agreement (LOA) were -1.7 to 2.3 litre min(-1) (-28.8 to 39.0%) with a percentage error (PE) of 34.4%. Data to assess trending [rate (95% confidence intervals)] included a 78 (62-93)% concordance rate in the four-quadrant plot (n=27). In the half moon polar plot (n=19), the mean polar angle was +5°, the radial LOA were -49 to +35° and 68 (47-89)% of data points fell within 22.5° of the mean polar angle. Both tests indicated moderate to poor trending ability. CONCLUSION: COLD is not precise when evaluated against COUFP in sheep based on the statistical criteria set, but the results are comparable with previously published animal studies. KEYWORDS:

Dilution of candidates: the case of iron-related genes in restless legs syndrome

Restless legs syndrome (RLS) is a common multifactorial disease. Some genetic risk factors have been identified. RLS susceptibility also has been related to iron. We therefore asked whether known iron-related genes are candidates for association with RLS and, vice versa, whether known RLS-associated loci influence iron parameters in serum. RLS/control samples (n = 954/1814 in the discovery step, 735/736 in replication 1, and 736/735 in replication 2) were tested for association with SNPs located within 4 Mb intervals surrounding each gene from a list of 111 iron-related genes using a discovery threshold of P = 5 × 10(-4). Two population cohorts (KORA F3 and F4 with together n = 3447) were tested for association of six known RLS loci with iron, ferritin, transferrin, transferrin-saturation, and soluble transferrin receptor. Results were negative. None of the candidate SNPs at the iron-related gene loci was confirmed significantly. An intronic SNP, rs2576036, of KATNAL2 at 18q21.1 was significant in the first (P = 0.00085) but not in the second replication step (joint nominal P-value = 0.044). Especially, rs1800652 (C282Y) in the HFE gene did not associate with RLS. Moreover, SNPs at the known RLS loci did not significantly affect serum iron parameters in the KORA cohorts. In conclusion, the correlation between RLS and iron parameters in serum may be weaker than assumed. Moreover, in a general power analysis, we show that genetic effects are diluted if they are transmitted via an intermediate trait to an end-phenotype. Sample size formulas are provided for small effect sizes.

Chromosomal assignment of the canine melanophilin gene (MLPH): a candidate gene for coat color dilution in Pinschers

Pinschers affected by coat color dilution show a specific pigmentation phenotype. The dilute pigmentation phenotype leads to a silver-blue appearance of the eumelanin-containing fur and a pale sandy color of pheomelanin-containing fur. In Pinscher breeding, dilute black-and-tan dogs are called "blue," and dilute red or brown animals are termed "fawn" or "Isabella fawn." Coat color dilution in Pinschers is sometimes accompanied by hair loss and a recurrent infection of the hair follicles. In human and mice, several well-characterized genes are responsible for similar pigment variations. To investigate the genetic cause of the coat color dilution in Pinschers, we isolated BAC clones containing the canine ortholog of the known murine color dilution gene Mlph. RH mapping of the canine MLPH gene was performed using an STS marker derived from BAC sequences. Additionally, one MLPH BAC clone was used as probe for FISH mapping, and the canine MLPH gene was assigned to CFA25q24.

Nd and Sr isotopic compositions and isotope dilution trace element concentrations from 7 sediment cores along the southeast Greenland margin

The Nd and Sr isotopic compositions of Quaternary glacial and glacimarine siliciclastic sediments deposited along the margin of southeast Greenland were determined to assess the roles of the Greenland, Iceland, and more distal ice sheets in delivering detritus to this portion of the northern North Atlantic. The isotopic compositions of detritus generated by portions of the southern Greenland Ice Sheet were defined through measurements of till and trough mouth fan sediments. Massive diamicts from the Scoresby Sund trough mouth fan show a restricted range of e-Nd (-11.8 to -16.6) and 87Sr/86Sr (0.7192-0.7246) consistent with their derivation from mixtures of sediments derived from Paleoproterozoic and/or Caledonian basement and Tertiary Greenland basalts. Further south at Kangerlussuaq, till isotopic compositions covary with the underlying basement type, with low e-Nd values in the inner fiord (-18.1) reflecting the erosion of the local Precambrian gneisses, but with higher e-Nd values (-2.3 to 2.5) found where the trough crosses East Greenland Tertiary basalts. Fine-grained (< 63 µm) sediments deposited along the southeast Greenland margin also show regular spatial isotopic variations. Ambient sediments and ice-rafted detritus in the southern Irminger Basin trend towards low e-Nd values (to ~ -28) and 87Sr/86Sr ratios (~ 0.711 to ~ 0.715) and are likely derived from proximal Archean gneisses of SE Greenland. Further north in the northern Irminger and Blosseville Basins, sediments trend toward much higher e-Nd (> -4) and low 87Sr/86Sr (< 0.709) reflecting a component derived from the local Iceland volcanic rocks and/or the East Greenland Tertiary basalts. In all three regions, the locally-derived detritus is intermixed with sediment with an intermediate e-Nd value (~ -10) and 87Sr/86Sr (~ 0.718) that was likely delivered by icebergs emanating from the Eurasian Ice Sheets and not from eastern Greenland. Deposition of glacial sediments from both proximal and distal (Eurasian) sources occurred adjacent to SE Greenland throughout the past 50 Ka, with periodic increases in IRD deposition at various times including those of Heinrich events 1, 2 and 4. These results suggest that at least the southern portions of the Greenland Ice Sheet experienced periodic instabilities during the Last Glacial period.