Methods to convert continuous outcomes into odds ratios of treatment response and numbers needed to treat: meta-epidemiological study

Clinicians find standardized mean differences (SMDs) calculated from continuous outcomes difficult to interpret. Our objective was to determine the performance of methods in converting SMDs or means to odds ratios of treatment response and numbers needed to treat (NNTs) as more intuitive measures of treatment effect.

Continuous measurements of methane mixing ratios from ice cores

This work presents a new, field-deployable technique for continuous, high-resolution measurements of methane mixing ratios from ice cores. The technique is based on a continuous flow analysis system, where ice core samples cut along the long axis of an ice core are melted continuously. The past atmospheric air contained in the ice is separated from the melt water stream via a system for continuous gas extraction. The extracted gas is dehumidified and then analyzed by a Wavelength Scanned-Cavity Ring Down Spectrometer for methane mixing ratios. We assess the performance of the new measurement technique in terms of precision (±0.8 ppbv, 1σ), accuracy (±8 ppbv), temporal (ca. 100 s), and spatial resolution (ca. 5 cm). Using a firn air transport model, we compare the resolution of the measurement technique to the resolution of the atmospheric methane signal as preserved in ice cores in Greenland. We conclude that our measurement technique can resolve all climatically relevant variations as preserved in the ice down to an ice depth of at least 1980 m (66 000 yr before present) in the North Greenland Eemian Ice Drilling ice core. Furthermore, we describe the modifications, which are necessary to make a commercially available spectrometer suitable for continuous methane mixing ratio measurements from ice cores.

Comparative study of biphasic calcium phosphates with different HA/TCP ratios in mandibular bone defects. A long-term histomorphometric study in minipigs

Three biphasic calcium phosphate (BCP) bone substitute materials with hydroxyapatite (HA)/tricalcium phosphate (TCP) ratios of 20/80, 60/40, and 80/20 were compared to coagulum, particulated autogenous bone, and deproteinized bovine bone mineral (DBBM) in membrane-protected bone defects. The defects were prepared in the mandibles of 24 minipigs that were divided into four groups of six with healing times of 4, 13, 26, and 52 weeks, respectively. The histologic and histomorphometric evaluation focused on differences in amount and pattern of bone formation, filler degradation, and the interface between bone and filler. Collapse of the expanded polytetrafluoroethylene barrier membrane into the coagulum defects underlined the necessity of a filler material to maintain the augmented volume. Quantitatively, BCP 20/80 showed bone formation and degradation of the filler material similar to autografts, whereas BCP 60/40 and BCP 80/20 rather equaled DBBM. Among the three BCP's, the amount of bone formation and degradation of filler material seemed to be inversely proportional to the HA/TCP ratio. The fraction of filler surface covered with bone was highest for autografts at all time points and was higher for DBBM than BCP 80/20 and 60/40 at the early healing phase. TRAP-positive multinucleated cells were identified on BCP and DBBM surfaces without showing typical signs of resorption lacunae.

Optimized Demineralization Technique for the Measurement of Stable Isotope Ratios of Nonexchangeable H in Soil Organic Matter

To make use of the isotope ratio of nonexchangeable hydrogen (δ2Hn (nonexchangeable)) of bulk soil organic matter (SOM), the mineral matrix (containing structural water of clay minerals) must be separated from SOM and samples need to be analyzed after H isotope equilibration. We present a novel technique for demineralization of soil samples with HF and dilute HCl and recovery of the SOM fraction solubilized in the HF demineralization solution via solid-phase extraction. Compared with existing techniques, organic C (Corg) and organic N (Norg) recovery of demineralized SOM concentrates was significantly increased (Corg recovery using existing techniques vs new demineralization method: 58% vs 78%; Norg recovery: 60% vs 78%). Chemicals used for the demineralization treatment did not affect δ2Hn values as revealed by spiking with deuterated water. The new demineralization method minimized organic matter losses and thus artificial H isotope fractionation, opening up the opportunity to use δ2Hn analyses of SOM as a new tool in paleoclimatology or geospatial forensics.

ROSINA/DFMS capabilities to measure isotopic ratios in water at comet 67P/Churyumov–Gerasimenko

The likelihood that comets may have delivered part of the water to Earth has been reinforced by the recent observation of the earth-like D/H ratio in Jupiter-family comet 103P/Hartley 2 by Hartogh et al. (2011). Prior to this observation, results from several Oort cloud comets indicated a factor of 2 enrichment of deuterium relative to the abundance at Earth. The European Space Agency’s Rosetta spacecraft will encounter comet 67P/Churyumov-Gerasimenko, another Jupiter-family comet of likely Kuiper belt origin, in 2014 and accompany it from almost aphelion to and past perihelion. Onboard Rosetta is the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) which consists of two mass spectrometers and a pressure sensor [Balsiger et al. 2007]. With its unprecedented mass resolution, for a space-borne instrument, the Double Focusing Mass Spectrometer (DFMS), one of the major subsystems of ROSINA, will be able to obtain unambiguously the ratios of the isotopes in water from in situ measurements in the coma around the comet. We will discuss the performance of this sensor on the basis of measurements of the terrestrial hydrogen and oxygen isotopic ratios performed with the flight spare instrument in the lab. We also show that the instrument on Rosetta is capable of measuring the D/H even in the very low density water background released by the spacecraft. This capability demonstrates that ROSINA should obtain very sensitive measurements of these ratios in the cometary environment. These measurements will allow detection of fractionation as function of the distance from the nucleus as well as fractionation due to mechanisms that are correlated with heliocentric distance.

Magma differentiation fractionates Mo isotope ratios: Evidence from the Kos Plateau Tuff (Aegean Arc)

We investigated high temperature Mo isotope fractionation in a hydrous supra-subduction volcano-plutonic system (Kos, Aegean Arc, Greece) in order to address the debate on the δ98/95Mo variability of the continental crust. In this igneous system, where differentiation is interpreted to be dominated by fractional crystallization, bulk rock data from olivine basalt to dacite show δ98/95Mo ratios increasing from +0.3 to +0.6‰ along with Mo concentrations increasing from 0.8 to 4.1 μg g−1. Data for hornblende and biotite mineral separates reveal the extraction of light Mo into crystallizing silicates, with minimum partition coefficients between hornblende- silicate melt and biotite-silicate melt of 0.6 and 0.4 δ98/95Mo, respectively. Our data document significant Mo isotope fractionation at magmatic temperatures, hence, the igneous contribution to continental runoff is variable, besides probable source-related variability. Based on these results and published data an average continental δ98/95Mo of +0.3 to +0.4‰ can be derived. This signature corresponds more closely to the average of published data of dissolved Mo loads of large rivers than previous estimates and is consistent with an upper limit of δ98/95Mo = 0.4‰ of the Earth's upper crust as derived from the analysis of molybdenites.

Diffusive equilibration of N2, O2 and CO2 mixing ratios in a 1.5-million-years-old ice core

In the framework of the International Partnerships in Ice Core Sciences, one of the most important targets is to retrieve an Antarctic ice core that extends over the last 1.5 million years (i.e. an ice core that enters the climate era when glacial–interglacial cycles followed the obliquity cycles of the earth). In such an ice core the annual layers of the oldest ice would be thinned by a factor of about 100 and the climatic information of a 10 000 yr interval would be contained in less than 1 m of ice. The gas record in such an Antarctic ice core can potentially reveal the role of greenhouse gas forcing on these 40 000 yr cycles. However, besides the extreme thinning of the annual layers, also the long residence time of the trapped air in the ice and the relatively high ice temperatures near the bedrock favour diffusive exchanges. To investigate the changes in the O2 / N2 ratio, as well as the trapped CO2 concentrations, we modelled the diffusive exchange of the trapped gases O2, N2 and CO2 along the vertical axis. However, the boundary conditions of a potential drilling site are not yet well constrained and the uncertainties in the permeation coefficients of the air constituents in the ice are large. In our simulations, we have set the drill site ice thickness at 2700 m and the bedrock ice temperature at 5–10 K below the ice pressure melting point. Using these conditions and including all further uncertainties associated with the drill site and the permeation coefficients, the results suggest that in the oldest ice the precessional variations in the O2 / N2 ratio will be damped by 50–100%, whereas CO2 concentration changes associated with glacial–interglacial variations will likely be conserved (simulated damping 5%). If the precessional O2 / N2 signal will have disappeared completely in this future ice core, orbital tuning of the ice-core age scale will be limited.

Partial volume correction incorporating Rb-82 positron range for quantitative myocardial perfusion PET based on systolic-diastolic activity ratios and phantom measurements.

BACKGROUND: Quantitative myocardial PET perfusion imaging requires partial volume corrections. METHODS: Patients underwent ECG-gated, rest-dipyridamole, myocardial perfusion PET using Rb-82 decay corrected in Bq/cc for diastolic, systolic, and combined whole cycle ungated images. Diastolic partial volume correction relative to systole was determined from the systolic/diastolic activity ratio, systolic partial volume correction from phantom dimensions comparable to systolic LV wall thicknesses and whole heart cycle partial volume correction for ungated images from fractional systolic-diastolic duration for systolic and diastolic partial volume corrections. RESULTS: For 264 PET perfusion images from 159 patients (105 rest-stress image pairs, 54 individual rest or stress images), average resting diastolic partial volume correction relative to systole was 1.14 ± 0.04, independent of heart rate and within ±1.8% of stress images (1.16 ± 0.04). Diastolic partial volume corrections combined with those for phantom dimensions comparable to systolic LV wall thickness gave an average whole heart cycle partial volume correction for ungated images of 1.23 for Rb-82 compared to 1.14 if positron range were negligible as for F-18. CONCLUSION: Quantitative myocardial PET perfusion imaging requires partial volume correction, herein demonstrated clinically from systolic/diastolic absolute activity ratios combined with phantom data accounting for Rb-82 positron range.

Estimation of male-to-female ratios of mutation rate in primates and rodents

Haldane (1935) developed a method for estimating the male-to-female ratio of mutation rate ($\alpha$) by using sex-linked recessive genetic disease, but in six different studies using hemophilia A data the estimates of $\alpha$ varied from 1.2 to 29.3. Direct genomic sequencing is a better approach, but it is laborious and not readily applicable to non-human organisms. To study the sex ratios of mutation rate in various mammals, I used an indirect method proposed by Miyata et al. (1987). This method takes advantage of the fact that different chromosomes segregate differently between males and females, and uses the ratios of mutation rate in sequences on different chromosomes to estimate the male-to-female ratio of mutation rate. I sequenced the last intron of ZFX and ZFY genes in 6 species of primates and 2 species of rodents; I also sequenced the partial genomic sequence of the Ube1x and Ube1y genes of mice and rats. The purposes of my study in addition to estimation of $\alpha$'s in different mammalian species, are to test the hypothesis that most mutations are replication dependent and to examine the generation-time effect on $\alpha$. The $\alpha$ value estimated from the ZFX and ZFY introns of the six primate specise is ${\sim}$6. This estimate is the same as an earlier estimate using only 4 species of primates, but the 95% confidence interval has been reduced from (2, 84) to (2, 33). The estimate of $\alpha$ in the rodents obtained from Zfx and Zfy introns is ${\sim}$1.9, and that deriving from Ube1x and Ube1y introns is ${\sim}$2. Both estimates have a 95% confidence interval from 1 to 3. These two estimates are very close to each other, but are only one-third of that of the primates, suggesting a generation-time effect on $\alpha$. An $\alpha$ of 6 in primates and 2 in rodents are close to the estimates of the male-to-female ratio of the number of germ-cell divisions per generation in humans and mice, which are 6 and 2, respectively, assuming the generation time in humans is 20 years and that in mice is 5 months. These findings suggest that errors during germ-cell DNA replication are the primary source of mutation and that $\alpha$ decreases with decreasing length of generation time. ^

Oxygen isotope ratios (18O/16O) of hemicellulose-derived sugar biomarkers in plants, soils and sediments as paleoclimate proxy II: insight from a climate transect study

The oxygen isotopic composition of precipitation (δ18Oprec) is well known to be a valuable (paleo-)climate proxy. Paleosols and sediments and hemicelluloses therein have the potential to serve as archives recording the isotopic composition of paleoprecipitation. In a companion paper (Zech et al., 2014) we investigated δ18Ohemicellulose values of plants grown under different climatic conditions in a climate chamber experiment. Here we present results of compound-specific δ18O analyses of arabinose, fucose and xylose extracted from modern topsoils (n = 56) along a large humid-arid climate transect in Argentina in order to answer the question whether hemicellulose biomarkers in soils reflect δ18Oprec. The results from the field replications indicate that the homogeneity of topsoils with regard to δ18Ohemicellulose is very high for most of the 20 sampling sites. Standard deviations for the field replications are 1.5‰, 2.2‰ and 1.7‰, for arabinose, fucose and xylose, respectively. Furthermore, all three hemicellulose biomarkers reveal systematic and similar trends along the climate gradient. However, the δ18Ohemicellulose values (mean of the three sugars) do not correlate positively with δ18Oprec (r = −0.54, p < 0.014, n = 20). By using a Péclet-modified Craig-Gordon (PMCG) model it can be shown that the δ18Ohemicellulose values correlate highly significantly with modeled δ18Oleaf water values (r = 0.81, p < 0.001, n = 20). This finding suggests that hemicellulose biomarkers in (paleo-)soils do not simply reflect δ18Oprec but rather δ18Oprec altered by evaporative 18O enrichment of leaf water due to evapotranspiration. According to the modeling results, evaporative 18O enrichment of leaf water is relatively low (∼10‰) in the humid northern part of the Argentinian transect and much higher (up to 19‰) in the arid middle and southern part of the transect. Model sensitivity tests corroborate that changes in relative air humidity exert a dominant control on evaporative 18O enrichment of leaf water and thus δ18Ohemicellulose, whereas the effect of temperature changes is of minor importance. While oxygen exchange and degradation effects seem to be negligible, further factors needing consideration when interpreting δ18Ohemicellulose values obtained from (paleo-)soils are evaporative 18O enrichment of soil water, seasonality effects, wind effects and in case of abundant stem/root-derived organic matter input a partial loss of the evaporative 18O enrichment of leaf water. Overall, our results prove that compound-specific δ18O analyses of hemicellulose biomarkers in soils and sediments are a promising tool for paleoclimate research. However, disentangling the two major factors influencing δ18Ohemicellulose, namely δ18Oprec and relative air humidity controlled evaporative 18O enrichment of leaf water, is challenging based on δ18O analyses alone.