Instrumental Bias Research Articles

Different glucose analyzers report different glucose concentration values in term newborns

BackgroundThe American Academy of Pediatrics and Pediatric Endocrine Society neonatal hypoglycemia guidelines based their glucose concentration treatment thresholds on studies that predominantly used Beckman and Yellow Springs Glucose Oxidase Analyzers. Currently, a majority (76%) of U.S. hospital laboratories utilizing glucose oxidase methodology use Vitros® Glucose Analyzers. However, a bias of ~+5% between glucose concentrations from Beckman vs. Vitros Glucose Analyzers has been reported; this could have a clinically significant effect when using published guideline treatment thresholds.MethodsTo determine if there is similar instrument bias between Beckman and Vitros Analyzers in reported glucose concentrations from term newborns, we compared plasma glucose concentrations measured within the first 3 h after birth by Beckman vs. Vitros Analyzers in a total of 1,987 newborns (Beckman n = 904, Vitros n = 1,083). Data were fit using nonlinear cubic spline models between collection time and glucose concentration.ResultsThe non-linear patterns of initial glucose concentrations (during the first 3 h after birth) as measured by Beckman and Vitros Analyzers paralleled each other with no overlap of the fit spline curve 95% confidence intervals, with an approximate +5 mg/dL constant bias. Additionally, in method comparison studies performed in the Chemistry Laboratory on adult samples, there was a +4.2-7.4 mg/dL measured glucose bias for the Beckman vs. Vitros Analyzer.ConclusionGlucose concentrations from term, appropriate size for gestational age newborns were about 5 mg/dL higher when measured by Beckman vs. Vitros Analyzers. Perhaps, concentrations of 45 mg/dL reported from Beckman Analyzers may be equivalent to 40 mg/dL from Vitros Analyzers. When managing neonatal hypoglycemia, it is important to know which analyzer was used and whether adjusting for potential instrument bias is necessary when following published guidelines.

Geostationary operational environmental satellite-R advanced baseline imager reflective solar band absolute validation using Sonoran desert scenes

The advanced baseline imagers (ABIs) on board the geostationary operational environmental satellite (GOES)-R series, GOES-16 and GOES-17 satellites, have accumulated long data series that have been updated throughout their missions to enhance their utility for imaging the Earth’s weather, oceans, and environment. In preparing for a reprocessing effort aimed at improving the consistency and image quality and reducing radiometric uncertainties necessary for some Earth science applications, we developed a vicarious validation technique for five of the six reflective solar bands. This technique uses Sonoran desert surface reflectance data derived from the moderate resolution imaging spectrometer bidirectional reflectance distribution function parameters product along with other atmospheric products to generate a predicted at-sensor radiance for both GOES-16 and GOES-17 for comparison with ABI observations and to enable ABI intercomparisons. This technique identified known instrument biases and demonstrated absolute validation over the course of a year, showing its capability to detect changes, monitor stability, and assess radiometric uncertainties for operational data applications and future reprocessed data sets.

Improved in situ analysis of lead isotopes in low-Pb melt inclusions using laser ablation-multi-collector-inductively coupled plasma-mass spectrometry.

In situ Pb isotope analyses of tiny melt inclusions using laser ablation-multi-collector-inductively coupled plasma-mass spectrometry (LA-MC-ICP-MS) are crucial for exploring the origins of mafic lavas. However, quantitative use of this technique with low-Pb (<10ppm) melt inclusions is difficult due to their low 204 Pb content and 204 Hg interference. Pb isotopic ratios of various reference glasses and olivine-hosted melt inclusions were determined using LA-MC-ICP-MS. Multiple ion counters were used to simultaneously determine signal intensities of all Pb isotopes and 202 Hg. An Hg signal-removal smoothing device reduced its signal in the gas blank by >80%. Instrumental mass bias was corrected using the standard-sample bracketing method. With 24-90 μm diameter laser spots, 2-4Hz repetition rates, and 2.5-4J cm-2 energy fluence, the analytical precisions of 20x Pb/204 Pb ratios (x = 6, 7, 8) for standards BHVO-2G, ML3B-G, NIST 614, NKT-1G, T1-G, GOR132-G, and StHs6/80-G were <1.0% (2RSD) when 208 Pb signals >100 000 cps. The Wangjiadashan melt inclusions have 206 Pb/204 Pb = 17.14-18.44, 207 Pb/204 Pb = 15.28-15.66, and 208 Pb/204 Pb = 37.12-38.68. The described method improves the precision and accuracy of in situ Pb isotope analysis in low-Pb melt inclusions using LA-MC-ICP-MS. The Pb isotopic compositions of the Wangjiadashan melt inclusions indicate the coexistence of LoMu and EMII+young HIMU components in the mantle source of weakly alkaline basalts.

Inflammation and heart failure: a two-sample Mendelian randomization study.

It is hypothesized that inflammation leads to heart failure. Results from observational studies thus far have been inconsistent and it is unclear whether inflammation is causally associated with new-onset heart failure. Mendelian randomization analyses are less prone to biases common in observational studies such as reverse causation and unmeasured confounding. The aim of this study was to investigate the causal relation between various inflammatory biomarkers with risk of new-onset heart failure by using a two-sample Mendelian randomization approach. Ten inflammatory biomarkers with available genome-wide association studies (GWAS) among individuals of European ancestry were identified and included C-reactive protein (CRP), immunoglobulin E, tumour necrosis factor (TNF), toll-like receptor 4, interleukin 1 receptor antagonist, interleukin 2 receptor subunit α, interleukin 6 receptor subunit α, interleukin 16, 17 and 18. For the associations between the identified SNPs and heart failure, we used the largest GWAS meta-analysis performed by the Heart Failure Molecular Epidemiology for Therapeutic Targets Consortium with 47 309 participants with heart failure and 930 014 controls. For our main analyses, we used the inverse-variance weighted method. We included 63 SNPs. CRP, TNF, interleukin 2, 16 and 18 were not associated with heart failure with odds ratios (ORs) of 1.01 [95% confidence interval (95% CI: 0.94-1.09), 1.11 (95% CI: 0.80-1.48), 0.97 (95% CI: 0.93-1.02), 0.99 (95% CI: 0.96-1.03) and 1.01 (95% CI: 0.97-1.06), respectively. The other biomarkers were also not associated with the risk of heart failure and suffered from weak instrument bias. This Mendelian randomization study could not determine a causal relationship between inflammation and risk of heart failure. However, some biomarkers suffered from weak instrument bias.

Evaluation of Seasonal Variability of First-Order Ionospheric Delay Correction at L5 and S1 Frequencies Using Dual-Frequency NavIC System

For the precise positioning applications it is important to determine and eliminate the positioning error introduced by various sources such as the ionosphere. To develop a standalone precise navigation system, India has launched the seven satellite constellations for NavIC (Navigation with Indian Constellation) system which can provide precision positioning over India and surrounded landmass. Since the ionospheric delay depends on the frequency of the satellite signal and NavIC systems work at different frequencies L5 and S1 than Global Positioning System (GPS) at L1 and L2, it is not possible to use the GPS data-driven study for NavIC based location calculations directly. Thus there is a need for a specialized ionospheric study for NavIC systems. In addition, the ionospheric delay is directly proportional to Slant Total Electron Content (STEC) which is dependent upon diurnal and seasonal solar activity. To achieve accurate positioning facilities, there is also a need for evaluation for seasonal variability of ionospheric delay correction for NavIC receivers. This paper deals with the STEC estimation; it's smoothing, and removal of instrumental biases from STEC. The determined true STEC has been used to determine first-order ionospheric delay correction at L5 and S1 frequencies. The delay correction at S1 has been found less (2–7 m) as compared to L5 (10–30 m). Furthermore, the seasonal variability of ionospheric delay has been analyzed using about 19 months of data (from June 2017 to December 2018) and found that the ionospheric delay follows unique seasonal characteristics which can be utilized for delay modeling. It has been also observed that the geostationary satellites of the NavIC system are more appropriate than geosynchronous satellites for ionospheric related studies.

Impairment of kidney function and kidney cancer: A bidirectional Mendelian randomization study.

Many observational epidemiology studies discovered that kidney cancer and impaired kidney function have a bidirectional relationship. However, it remains unclear whether these two kinds of traits are causally linked. In this study, we aimed to investigate the bidirectional causal relation between kidney cancer and kidney function biomarkers (creatinine-based estimated glomerular filtration rate (eGFRcrea), cystatin C-based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), serum urate, and urinary albumin-to-creatinine ratio (UACR)). For both directions, single-nucleotide polymorphisms (SNPs), as genetic instruments, for the five kidney function traits were selected from up to 1,004,040 individuals, and SNPs for kidney cancer were from 408,786 participants(1338 cases). In the main analysis, we applied two state-of-the-art MR methods, namely, contamination mixture and Robust Adjusted Profile Score to downweight the effect of weak instrument bias, pleiotropy, and extreme outliers. We additionally conducted traditional MR analyses as sensitivity analyses. Summary-level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Kaiser Permanente. Based on 99 SNPs, we found that the eGFRcrea had a significant negative causal effect on the risk of kidney cancer (OR=0.007, 95% CI:2.6 × 10-4 -0.569, p=0.041). After adjusting for body composition or diabetes, urate had a significant negative causal effect on kidney cancer (OR <1, p < 0.05). For UACR, it showed a strong causal effect on kidney cancer, after adjusting for body composition (OR=14.503, 95% CI: 2.546-96.001, p=0.032). Due to lacking significant signals and effect power for the reverse MR, further investigations are warranted. Our study suggested a potential causal effect of damaged kidney function on kidney cancer. EGFRcrea and UACR might be causally associated with kidney cancer, especially when patients were comorbid with obesity or diabetes. We called for larger sample-size studies to further unravel the underlying causal relationship and the exact mechanism.

Cross-fitted instrument: A blueprint for one-sample Mendelian randomization.

Bias from weak instruments may undermine the ability to estimate causal effects in instrumental variable regression (IVR). We present here a new approach to handling weak instrument bias through the application of a new type of instrumental variable coined ‘Cross-Fitted Instrument’ (CFI). CFI splits the data at random and estimates the impact of the instrument on the exposure in each partition. These estimates are then used to perform an IVR on each partition. We adapt CFI to the Mendelian randomization (MR) setting and term this adaptation ‘Cross-Fitting for Mendelian Randomization’ (CFMR). We show that, even when using weak instruments, CFMR is, at worst, biased towards the null, which makes it a conservative one-sample MR approach. In particular, CFMR remains conservative even when the two samples used to perform the MR analysis completely overlap, whereas current state-of-the-art approaches (e.g., MR RAPS) display substantial bias in this setting. Another major advantage of CFMR lies in its use of all of the available data to select genetic instruments, which maximizes statistical power, as opposed to traditional two-sample MR where only part of the data is used to select the instrument. Consequently, CFMR is able to enhance statistical power in consortia-led meta-analyses by enabling a conservative one-sample MR to be performed in each cohort prior to a meta-analysis of the results across all the cohorts. In addition, CFMR enables a cross-ethnic MR analysis by accounting for ethnic heterogeneity, which is particularly important in meta-analyses where the participating cohorts may have different ethnicities. To our knowledge, none of the current MR approaches can account for such heterogeneity. Finally, CFMR enables the application of MR to exposures that are either rare or difficult to measure, which would normally preclude their analysis in the regular two-sample MR setting.

High-precision attitude determination using spaceborne gravity gradiometer and gyroscope

This study investigates the application of a spaceborne gravity gradiometer to spacecraft attitude determination. Considering that the gradiometer raw measurements are influenced by angular rotation, a gyroscope is integrated to provide angular velocity information. To deal with unknown biases in both gradiometer and gyroscope measurements, a multiplicative extended Kalman filter (MEKF) is developed to estimate the attitude states and the instrument biases simultaneously. In addition, the cross-correlation between gyroscope measurements and gyroscope-compensated gradiometer measurements is analyzed. The MEKF algorithm is modified accordingly to cope with the correlation problem. Simulation scenarios with two different attitude modes are built to test the algorithm. With a gradiometer of 0.1 E (1 E = 10−9 s−2) accuracy and a navigation-grade gyroscope, attitude determination accuracy of several arcsecs is obtained. Real data from the GOCE (gravity field and steady-state ocean circulation explorer) spacecraft are also used to test the algorithm. Yaw, pitch, and roll angle errors of 2.8 arcsec, 20.9 arcsec, and 11.3 arcsec are achieved, respectively. The method can directly estimate a spacecraft's attitude relative to the Earth-centered Earth-fixed (ECEF) frame and is promising for high-precision spacecraft attitude determination in Earth-oriented missions.

Association of sedentary and physical activity behaviours with body composition: a genome-wide association and Mendelian randomisation study

ObjectivesStudies suggest that body composition can be independently improved through physical activity (PA). We performed a Mendelian randomisation (MR) study to test the incremental benefits of sedentary behaviour and various...

Broad band flux-density monitoring of radio sources with the Onsala twin telescopes

The Onsala twin telescopes (OTT) are two 13 m telescopes located at the Onsala Space Observatory in Sweden. With dual linear polarized broad-band (3-14 GHz) receivers, they are part of the next generation Very Long Baseline Interferometry (VLBI) Global Observing System (VGOS) for geodesy and astrometry. In addition to purely geodetic data products, VGOS will regularly produce full-polarisation images of hundreds of radio sources. These rich monitoring data will be valuable for both astronomy and geodesy. In this pilot study we aimed at monitoring ten bright radio sources to search for flares or similar activity, and at testing the instrument calibration on long (months) and short (hours) time scales. Using the OTT as a standalone instrument, we observed and analysed 91 short (<30 min) sessions spanning seven months. We monitored seven potentially variable radio sources (0059+581, 0552+398, 1144+402, 1156+295, 1617+229, 3C418, OJ287) and three reference calibrators (3C147, 3C286, 3C295). We used the Common Astronomy Software Applications (CASA) package to fringe-fit, bandpass-correct and scale the data to obtain flux densities in the four standard VGOS bands: 3.0-3.5 GHz (band 1), 5.2-5.7 GHz (band 2), 6.3-6.8 GHz (band 3), and 10.2-10.7 GHz (band 4). We obtained simultaneous multi-frequency light curves for ten radio sources. A bright multi-frequency flare is observed in the radio source 0059+581. OJ287 and 1156+295 show significant long-term variability in their light curves. After correcting for instrumental biases, we determine the empirical flux density uncertainty as sim5 %.

Anti-Müllerian Hormone and Cardiometabolic Disease in Women: A Two-Sample Mendelian Randomization Study.

Higher age-specific circulating anti-Müllerian hormone (AMH) levels have been linked to a lower risk of cardiometabolic outcomes. However, whether AMH has a casual role in the etiology of these diseases is unknown. The objective of this study was therefore to explore if circulating AMH levels have a causal effect on risk of coronary artery disease (CAD), ischemic stroke and type 2 diabetes (T2D) in women, using a two-sample Mendelian randomization (MR) approach. We used four single nucleotide polymorphisms (SNPs) from the most recent AMH GWAS meta-analysis as instrumental variables. Summary-level data for CAD (n = 149,752; 11,802 cases), ischemic stroke (n = 17,541; 4678 cases) and T2D (n = 464,389; 30,052 cases) were extracted from the UK Biobank, the Stroke Genetics Network, and DIAMANTE consortia, respectively. To assess the presence of potential pleiotropy we tested the association of the four AMH SNPs, both individually and combined in a weighted genetic risk score, with a range of cardiovascular risk factors and intermediate traits using UK Biobank data. MR estimates, i.e., inverse variance-weighted odds ratios ( ), did not support a causal effect of circulating AMH levels on CAD ( = 1.13, 95% CI: 0.95-1.35), ischemic stroke ( = 1.11, 95% CI: 0.83-1.49), and T2D ( = 0.98, 95% CI: 0.87-1.10). After adjustment for multiple testing, we observed associations between genetically predicted AMH and age at menopause, and age at menarche, but not with intermediate traits on the causal pathway between AMH and cardiometabolic health, such as atherosclerosis or glucose levels. This study does not provide evidence for a causal effect of circulating AMH levels on CAD, ischemic stroke and T2D in women, although weak instrument bias cannot be excluded.

SIMS matrix effects in oxygen isotope analysis of olivine and pyroxene: Application to Acfer 094 chondrite chondrules and reconsideration of the primitive chondrule minerals (PCM) line

The instrumental bias (here expressed as bias*, the difference relative to San Carlos Olivine, SC-Ol) of oxygen isotopes in secondary ion mass spectrometry (SIMS) analyses of olivine and pyroxene were investigated. Sixteen olivine (Fo0–100), nine orthopyroxene (En70–100Wo0–3), and three clinopyroxene (En28-49Wo45–50) reference materials (RMs) were utilized. The values of bias* are nearly invariant (within 0 ± 0.5‰) among magnesian olivine (Fo ≥60) RMs but decrease systematically with increasing Fe molar fraction down to ~ −10‰ (Fo0). The session-to-session variability of bias* for Fo ≥60 olivines is ≤0.3‰ but becomes slightly larger for more Fe-rich compositions (≤1.5‰). Orthopyroxene RMs have a narrow range of bias* values (−1.7‰ to −2.6‰) that show session-to-session variability ≤0.3‰; correspondingly, the sputter rates are similarly low and resemble those of Fo ≥60 olivines. Clinopyroxene RMs bias* values (−0.2‰ to +1.2‰) are more variable and have larger session-to-session variability (≤0.8‰), which appear to be independent of sputter rates. Bias* of the same RMs change slightly from session to session with different analytical settings (≤0.6‰ for Fo ≥60 and as much as 2‰ for fayalite) so that equations of bias* as a function of Fo, En, and Wo should be determined for each SIMS session by the analyses of multiple RMs.The new suite of olivine and pyroxene RMs with expanded composition range were used to correct the instrumental biases during oxygen three-isotope analysis of olivine and low-Ca pyroxene in chondrules of the ungrouped Acfer 094 chondrite, from which the primitive chondrule minerals (PCM, δ18O vs. δ17O) line was originally derived. The PCM line is considered to be a mixing trend of two extreme primary oxygen isotope reservoirs of solids in the early solar system. However, this new dataset, with better analytical precision and instrumental bias correction, allows two oxygen isotope trends to be clearly identified. One is represented by chondrules that plot on or above the PCM line, likely linked to ordinary chondrite (OC)-like materials. A second trend is represented by the major chondrule population in this chondrite that defines a regression line of δ17O = (0.968 ± 0.022) × δ18O − (3.46 ± 0.10) (MSWD = 2.0), consistent with recent oxygen isotope data of chondrules in carbonaceous chondrites (i.e., CV, CK, CO, and CM). We propose that this regression line represents a mixing of two oxygen isotope reservoirs (possibly 16O-rich solids and 16O-poor H2O ice) in the outer solar system and likely resulting from the separate evolutions of isotope reservoirs after the “Jupiter divide” built up.

Causality of anthropometric markers associated with polycystic ovarian syndrome: Findings of a Mendelian randomization study.

Using body mass index (BMI) as a proxy, previous Mendelian randomization (MR) studies found total causal effects of general obesity on polycystic ovarian syndrome (PCOS). Hitherto, total and direct causal effects of general- and central obesity on PCOS have not been comprehensively analyzed. To investigate the causality of central- and general obesity on PCOS using surrogate anthropometric markers. Summary GWAS data of female-only, large-sample cohorts of European ancestry were retrieved for anthropometric markers of central obesity (waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR)) and general obesity (BMI and its constituent variables-weight and height), from the IEU Open GWAS Project. As the outcome, we acquired summary data from a large-sample GWAS (118870 samples; 642 cases and 118228 controls) within the FinnGen cohort. Total causal effects were assessed via univariable two-sample Mendelian randomization (2SMR). Genetic architectures underlying causal associations were explored. Direct causal effects were analyzed by multivariable MR modelling. Instrumental variables demonstrated no weak instrument bias (F > 10). Four anthropometric exposures, namely, weight (2.69-77.05), BMI (OR: 2.90-4.06), WC (OR: 6.22-20.27), and HC (OR: 6.22-20.27) demonstrated total causal effects as per univariable 2SMR models. We uncovered shared and non-shared genetic architectures underlying causal associations. Direct causal effects of WC and HC on PCOS were revealed by two multivariable MR models containing exclusively the anthropometric markers of central obesity. Other multivariable MR models containing anthropometric markers of both central- and general obesity showed no direct causal effects on PCOS. Both and general- and central obesity yield total causal effects on PCOS. Findings also indicated potential direct causal effects of normal weight-central obesity and more complex causal mechanisms when both central- and general obesity are present. Results underscore the importance of addressing both central- and general obesity for optimizing PCOS care.

Precise measurements of δ88/86Sr for twenty geological reference materials by double-spike MC-ICP-MS

Analytical method using double-spike and MC-ICP-MS can provide high efficiency of measurement for stable Sr isotopic compositions (δ88/86Sr). Here we report a method for high precision measurement of δ88/86Sr using MC-ICP-MS. A84Sr–87Sr double-spike was used to correct instrumental mass bias of stable Sr isotopes. Strontium was purified by a cation exchange resin (AG50W-X12, 200–400 mesh), and for samples with high Er, Yb, Lu, and Hf contents, an additional chromatographic purification procedure was applied. The potential effects of doubly charged ion isobaric inferences and different measurement conditions were rigorously evaluated to improve the analytical precision. Data quality was monitored by measuring three USGS reference materials (BHVO-2, AGV-2, and G-2) and two in-house reference materials, giving the long-term precision of 0.03‰ (2SD) for δ88/86Sr. Twenty reference materials, including nine igneous rocks, four sedimentary rocks, two sediments, and five soils, have δ88/86Sr values range from −0.06‰ to 0.35‰, showing resolvable isotope fractionation during magmatic and supergene processes. This study provides a useful standard dataset for inter-laboratory comparison of stable Sr isotope studies.

Mechanisms of Inequity: The Impact of Instrumental Biases in the Child Protection System

The structural risk perspective conceptualizes the causes of inequities in child protection system contact as unequal exposure to the structural causes of child abuse risk, combined with biases in the responses of child welfare workers and reporters. This conceptual article proposes a third mechanism of inequity: instrumental biases. It is proposed that instrumental biases operate as a third group of mechanisms that inequitably increase the involvement of some groups and not others. Instrumental biases operate through institutional structures, interpretive concepts and risk proxies that affect how risk is coded and becomes attached to particular people. Against the background of the notify-investigate model that creates poor conditions for decision making, and shapes institutional structures, instrumental biases include the miscalibration of the demand and supply of services (an institutional cause); family-specific surveillance bias and a reliance on prior case histories (a risk proxy cause); widening legal definitions of serious harm (an interpretive concept cause); and complex responses to intimate partner violence that minimize theories of IPV and the social context it occurs within (concept and risk proxy causes). It is argued that within the decision-making context of the child protection system, how services are structured and risk becomes codified has disproportionate impacts on some communities compared to others. Examples from Aotearoa New Zealand, with reference to Māori and people living in high-deprivation areas, are used to illustrate these concepts.

Adjusting for collider bias in genetic association studies using instrumental variable methods.

Genome‐wide association studies have provided many genetic markers that can be used as instrumental variables to adjust for confounding in epidemiological studies. Recently, the principle has been applied to other forms of bias in observational studies, especially collider bias that arises when conditioning or stratifying on a variable that is associated with the outcome of interest. An important case is in studies of disease progression and survival. Here, we clarify the links between the genetic instrumental variable methods proposed for this problem and the established methods of Mendelian randomisation developed to account for confounding. We highlight the critical importance of weak instrument bias in this context and describe a corrected weighted least‐squares procedure as a simple approach to reduce this bias. We illustrate the range of available methods on two data examples. The first, waist–hip ratio adjusted for body‐mass index, entails statistical adjustment for a quantitative trait. The second, smoking cessation, is a stratified analysis conditional on having initiated smoking. In both cases, we find little effect of collider bias on the primary association results, but this may propagate into more substantial effects on further analyses such as polygenic risk scoring and Mendelian randomisation.

Investigating the Association Between Seven Sleep Traits and Nonalcoholic Fatty Liver Disease: Observational and Mendelian Randomization Study.

Background and Aim: Aberrant sleep parameters are associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, existing information is inconsistent among studies and involves reverse causation. Therefore, we aimed to investigate the observational associations and causations between sleep traits and NAFLD. Methods: We performed multivariable regression to assess observational associations of seven sleep traits (sleep duration, easiness of getting up in the morning, chronotype, nap during day, snoring, insomnia, and narcolepsy), and NAFLD in the UK Biobank (1,029 NAFLD). The Cox proportional hazards model was applied to derive hazard ratios and 95% confidence intervals (CIs). Furthermore, a bidirectional two-sample Mendelian randomization (MR) approach was used to explore the causal relationships between sleep traits and NAFLD. Results: In the multivariable regression model adjusted for potential confounders, getting up in the morning not at all easy (HR, 1.51; 95% CI, 1.27–1.78) and usually insomnia (HR, 1.46; 95% CI, 1.21–1.75) were associated with the risk of NAFLD. Furthermore, the easiness of getting up in the morning and insomnia showed a dose–response association with NAFLD (Ptrend <0.05). MR analysis found consistent causal effects of NAFLD on easiness of getting up in the morning (OR, 0.995; 95% CI, 0.990–0.999; p = 0.033) and insomnia (OR, 1.006; 95% CI, 1.001–1.011; p = 0.024). These results were robust to weak instrument bias, pleiotropy, and heterogeneity. Conclusions: Findings showed consistent evidence of observational analyses and MR analyses that trouble getting up in the morning and insomnia were associated with an increased risk of NAFLD. Bidirectional MR demonstrated causal effects of NAFLD on sleep traits.

An improved calibrated mass spectrometry for absolute copper isotope-ratio measurement using two strategies for mass bias correction factor

Modern advances in multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS) have greatly promoted the investigation of copper isotopes in various research fields. To meet the demand, an improved calibrated mass spectrometry for the absolute determination of copper isotopic composition was developed in this study. The method has made progress in the investigation of instrumental mass bias correction factor for copper isotopic analysis using MC-ICPMS through employing two independent strategies. One is the conventional mathematical iterative method based on the MC-ICPMS measurement data; the other one is direct calculation using the absolute copper isotopic compositions in isotopically enriched 63Cu and 65Cu materials by developing a TE-TIMS method. The results of Kiter = 0.95563(16)k = 1 and KTE = 0.95551(17)k = 1 were consistent in their standard uncertainties, demonstrated the first cross-validation of these two strategies. Thereafter, the proposed calibrated mass spectrometry were applied to re-measure the copper isotope amount ratios in three isotopic reference materials, resulted in RNIST SRM 97665/63 = 0.44547(16)k = 2, RERM®−AE63365/63 = 0.44549(16)k = 2, and RERM®−AE64765/63 = 0.44557(16)k = 2, respectively. These expended uncertainties were only one third or one fifth of the stated uncertainties in their certificates. Furthermore, the absolute copper isotopic compositions in four natural-abundance samples and a new copper isotopic reference material GBW04624 were determined, given an average atomic weight of copper as Ar(Cu) = 63.5456(4)k = 2. The δ65Cu values of GBW04624 relative to NIST SRM 976, ERM®-AE633 and ERM®-AE647 were also applied by implementing the C-SSBIN calibration model. This provides an additional independently certified and SI-traceable copper isotopic reference material, in support of various scientific researches.

Titanium Isotope Analysis of Igneous Reference Materials using a Double‐spike MC‐ICP‐MS Method

AbstractTi separation was achieved by ion‐exchange chromatography using Bio‐Rad AG 1‐X8 anion‐exchange and DGA resins. For high‐Fe/Ti and high‐Mg/Ti igneous samples, a three‐column procedure was required, whereas a two‐column procedure was used for low‐Fe/Ti and low‐Mg/Ti igneous samples. The Ti isotopes were analysed by MC‐ICP‐MS, and instrumental mass bias was corrected using a 47Ti‐49Ti double‐spike technique. The 47Ti‐49Ti double‐spike and SRM 3162a were calibrated using SRM 979‐Cr, certificated value 53Cr/52Crtrue = 0.11339. Isobaric interference was evaluated by analysing Alfa‐Ti doped with Na, Mg, Ca, and Mo, and results indicate that high concentrations of Na and Mg have no significant effect on Ti isotope analyses; however, Ca and Mo interferences lead to erroneous δ49/47Ti values when Ca/Ti and Mo/Ti ratios exceed 0.01 and 0.1, respectively. Titanium isotopic compositions were determined for 12 igneous reference materials, BCR‐2, BHVO‐2, GBW07105, AGV‐1, AGV‐2, W‐2, GBW07123, GBW07126, GBW07127, GBW07101, JP‐1, and DTS‐2b. Samples yield δ49/47Ti (‰) of −0.035 ± 0.022, −0.038 ± 0.031, 0.031 ± 0.022, 0.059 ± 0.038, 0.044 ± 0.037, 0.000 ± 0.015, 0.154 ± 0.044, −0.044 ± 0.018, 0.010 ± 0.022, 0.064 ± 0.043, 0.169 ± 0.034, and −0.047 ± 0.025 (relative to OL‐Ti, ±2SD), respectively; of which isotopic compositions of DTS‐2b, JP‐1, GBW07101, GBW07105, GBW07123, GBW07126, and GBW07127 are reported for the first time. Standard Alfa‐Ti was analysed repeatedly over a ten‐month period, indicating a reproducibility of ±0.047 (2SD) for δ49/47Ti, similar to the precisions obtained for geochemical reference materials.

Optimizing 40Ar/39Ar analyses using an Isotopx NGX-600 mass spectrometer

40Ar/39Ar geochronology relies on magnetic sector mass spectrometers to determine relative isotopic abundances. Ongoing technological developments within noble gas mass spectrometers over the last decade have led to analysis of increasingly smaller samples and higher precision, but also result in more complex data correction and interpretation. We describe a new multi-collector noble gas spectrometer, the Isotopx NGX-600, that is configured to optimize 40Ar/39Ar measurements. The NGX-600 is equipped with 9 Faraday collectors and one ion counting electron multiplier. Each Faraday is equipped with Isotopx ATONA® amplifier technology, enabling measurements spanning a dynamic range of amplified beam current from below 10−16 A to above 10−9 A. The performance of the NGX-600 is evaluated using both a conventional Nier-type ion source, and a next generation low temperature ion source, which allows for trap current variation from 200 μA to 1000 μA. We have performed over 3000 analyses of atmospheric argon to: (1) assess optimal measurement and integration times for blanks, baselines, and air aliquots of various ion intensities, (2) quantify the sensitivity via measurements of first principles 40Ar/39Ar standards, (3) compare the sensitivity between the conventional and new low temperature Nier-type ion sources, and (4) evaluate corrections associated with inter-Faraday biases, instrumental mass bias, and Faraday-multiplier gain. In addition to optimization experiments, we report a comparative analysis of both single crystal fusion and incremental heating data from Quaternary volcanic rocks obtained using both the 5-collector Nu Instruments Noblesse and the NGX-600 spectrometers.