External Precision Research Articles

The evolution of clinical trials: Can we address the challenges of the future?

The authors describe key challenges facing the clinical trials community and propose solutions to these issues, including the role the Clinical Trials Transformation Initiative can play in addressing these issues. Specifically, the authors reflect on clinical trial globalization and the harmonization of frameworks and requirements across regions; the challenges associated with balancing the desire for external validity, pragmatic trials, and precision medicine; clinical trial transparency; and operational complexity and the expense of clinical trials. By addressing these challenges, future clinical trials will be more feasible, relevant, and credible, and support both the continuing altruistic contributions of patients and the collection of more meaningful data.

High-precision determination of lithium and magnesium isotopes utilising single column separation and multi-collector inductively coupled plasma mass spectrometry.

RationaleLi and Mg isotopes are increasingly used as a combined tool within the geosciences. However, established methods require separate sample purification protocols utilising several column separation procedures. This study presents a single‐step cation‐exchange method for quantitative separation of trace levels of Li and Mg from multiple sample matrices.MethodsThe column method utilises the macro‐porous AGMP‐50 resin and a high‐aspect ratio column, allowing quantitative separation of Li and Mg from natural waters, sediments, rocks and carbonate matrices following the same elution protocol. High‐precision isotope determination was conducted by multi‐collector inductively coupled plasma mass spectrometry (MC‐ICPMS) on the Thermo Scientific™ NEPTUNE Plus™ fitted with 1013 Ω amplifiers which allow accurate and precise measurements at ion beams ≤0.51 V.ResultsSub‐nanogram Li samples (0.3–0.5 ng) were regularly separated (yielding Mg masses of 1–70 μg) using the presented column method. The total sample consumption during isotopic analysis is <0.5 ng Li and <115 ng Mg with long‐term external 2σ precisions of ±0.39‰ for δ7Li and ±0.07‰ for δ26Mg. The results for geological reference standards and seawater analysed by our method are in excellent agreement with published values despite the order of magnitude lower sample consumption.ConclusionsThe possibility of eluting small sample masses and the low analytical sample consumption make this method ideal for samples of limited mass or low Li concentration, such as foraminifera, mineral separates or dilute river waters.

Application of 1013 ohm Faraday cup current amplifiers for boron isotopic analyses by solution mode and laser ablation multicollector inductively coupled plasma mass spectrometry.

Boron isotope ratios (δ11 B values) are used as a proxy for seawater paleo-pH, amongst several other applications. The analytical precision can be limited by the detection of low intensity ion beams from limited sample amounts. High-gain amplifiers offer improvements in signal/noise ratio and can be used to increase measurement precision and reduce sample amounts. 1013 ohm amplifier technology has previously been applied to several radiogenic systems, but has thus far not been applied to non-traditional stable isotopes. Here we apply 1013 ohm amplifier technology for the measurement of boron isotope ratios using solution mode MC-ICP-MS and laser ablation mode (LA-)MC-ICP-MS techniques. Precision is shown for reference materials as well as for low-volume foraminifera samples. The baseline uncertainty for a 0.1 pA 10 B+ ion beam is reduced to <0.1 ‰ for a typical measurement period. The external precision is better than 0.2 ‰ (2SD) for δ11 B measurements for solution samples containing as little as 0.8 ng total boron. For in situ microanalyses with LA-MC-ICP-MS, the external precision of 11 B/10 B from an in-house calcite standard was 1 ‰ (2SD) for individual spot analyses, and 0.3 ‰ for the mean of ≥10 replicate spot analyses. 1013 ohm amplifier technology is demonstrated to offer advantages for the determination of δ11 B values by both MC-ICP-MS and LA-MC-ICP-MS for small samples of biogenic carbonates, such as foraminifera shells. 1013 ohm amplifier technology will also be of benefit to other non-traditional stable isotope measurements.

Precise carbon isotopic ratio analyses of micro amounts of carbonate and non-carbonate in basalt using continuous-flow isotope ratio mass spectrometry.

Continuous-flow isotope ratio mass spectrometry (CF-IRMS) is a specialized technique used to quickly analyze very small amounts of sample. We have used CF-IRMS to assess the influences of sample weight and relative carbon content on the accuracy and precision of the δ13 C values of micro amounts of carbonate and non-carbonate in silicate rocks. The analytical work was performed on a Gasbench II (GB) sample preparation device and on an Elemental Analyzer (EA), which were both interfaced to CF-IRMS instruments. Potential silicate matrix effects on the carbon isotopic analyses were investigated by measuring mixtures of calibrated carbon reference materials and quartz powder. The calibration lines, established by the measured raw values and the known values of three reference materials mixed with quartz powder, were used to calibrate the δ13 C values of basalt samples from eastern China. The δ13 C values measured by GB-CF-IRMS of one national carbonate reference material, GBW04416, deviate slightly from the known value for approximately 20-70μg of carbonate contained in 4.5-mL vials; the smaller the sample size, the lower the measured δ13 C values. External precision better than 0.1‰ (1σ, n=26) is achieved at a signal intensity for mass 44 of between 868 and 1614mV, corresponding to a sample weight of 30.8-50.2μg, whereas it is reduced to 0.27‰ (1σ, n=34) at a signal intensity between 519 and 1614mV, corresponding to a sample weight of 21.1-50.2μg. In the EA-CF-IRMS experiments for non-carbonate carbon, at high carbon concentration (greater than 800ppm) and at optimum sample weights, the accuracy and precision are both better than 0.2‰. For carbon concentrations less than 500ppm, the measured δ13 C values deviate from the average by up to -1.2‰ and the precision is 0.74‰. The measured δ13 C values decrease substantially at lower carbon concentration and higher sample weights, and poorer precision is obtained. Suggestions are made to measure repeatedly the same carbon concentration of sample and reference materials in order to obtain not only reproducible, but also accurate carbon isotope ratios.

Isotope analysis of nanogram to sub-nanogram sized Nd samples by total evaporation normalization thermal ionization mass spectrometry

This paper presents 143Nd/144Nd analysis of nanogram to sub-nanogram sized Nd samples using total evaporation normalization thermal ionization mass spectrometry (TEN-TIMS) with Nd+ ions. Total integration of high and stable Nd+ ion signals produced by dynamic filament-current control until sample burnout in combination with a long baseline measurement achieved reasonably high signal to noise ratios even for very small samples. Repeated analyses of an Nd isotopic reference material JNdi-1 with Nd sample sizes of 2, 1, 0.5, and 0.1ng all yielded consistent 143Nd/144Nd values with external precisions of 42, 62, 93, and 184ppm (2RSD), respectively. Errors were as small as analytical error limits defined by counting statistics. Repeated analyses of basalt (JB-2) and coral (JCp-1) samples with 0.6–1.2ng of Nd after processing with low-blank Nd separation chemistry designed for small samples also gave 143Nd/144Nd values consistent with those given by large-sized sample analyses, and the external precisions were comparable to the JNdi-1 analyses. The TEN-TIMS technique was capable of analyzing 143Nd/144Nd ratios of geological materials with sample sizes as small as 0.5ng of Nd with a precision of ±1 ε-unit or better.

An optical method for carbon dioxide isotopes and mole fractions in small gas samples: Tracing microbial respiration from soil, litter, and lignin.

Carbon dioxide isotope (δ13 C value) measurements enable quantification of the sources of soil microbial respiration, thus informing ecosystem C dynamics. Tunable diode lasers (TDLs) can precisely measure CO2 isotopes at low cost and high throughput, but are seldom used for small samples (≤5mL). We developed a TDL method for CO2 mole fraction ([CO2 ]) and δ13 C analysis of soil microcosms. Peaks in infrared absorbance following constant volume sample injection to a carrier were used to independently measure [12 CO2 ] and [13 CO2 ] for subsequent calculation of δ13 C values. Using parallel soil incubations receiving differing C substrates, we partitioned respiration from three sources using mixing models: native soil organic matter (SOM), added litter, and synthetic lignin containing a 13 C label at Cβ of the propyl side chain. Once-daily TDL calibration enabled accurate quantification of δ13 C values and [CO2 ] compared with isotope ratio mass spectrometry (IRMS), with long-term external precision of 0.17 and 0.31‰ for 5 and 1mL samples, respectively, and linear response between 400 and 5000μmol mol-1 CO2 . Production of CO2 from native soil C, added litter, and lignin Cβ varied over four orders of magnitude. Multiple-pool first-order decay models fitted to data (R2 >0.98) indicated substantially slower turnover for lignin Cβ (17years) than for the dominant pool of litter (1.3years) and primed soil C (3.9years). Our TDL method provides a flexible, precise, and high-throughput (60 samples h-1 ) alternative to IRMS for small samples. This enables the use of C isotopes in increasingly sophisticated experiments to test biogeochemical controversies, such as the fate of lignins in soil.

Petroleum generation and migration in the Cambro-Ordovician Laurentian margin succession of NW Scotland

Fluid inclusion and organic biomarker data show that there was formerly a hydrocarbon system in the Cambro-Ordovician Laurentian margin rocks of NW Scotland. Oil fluid inclusions occur in stylolitized Eriboll Formation sandstone, in K-feldspar cements with an 40 Ar/ 39 Ar age of 415 ± 5.5/5.8 Ma (2σ, analytical precision/full external precision). Organic extracts from Durness Group black limestones yield biomarker ratios characteristic of high thermal maturity. Organic maturation to yield oil probably occurred during orogenic deformation along the Moine Thrust Zone. The recognition of a hydrocarbon system in Scotland adds to a huge hydrocarbon province in Laurentian rocks including North America and Greenland. Supplementary material : Technical data for Ar-Ar dating are available at https://doi.org/10.6084/m9.figshare.c.3879616

Combination of terrestrial reference frames based on space geodetic techniques in SHAO: methodology and main issues

Based on years of input from the four geodetic techniques (SLR, GPS, VLBI and DORIS), the strategies of the combination were studied in SHAO to generate a new global terrestrial reference frame as the material realization of the ITRS defined in IERS Conventions. The main input includes the time series of weekly solutions (or fortnightly for SLR 1983–1993) of observational data for satellite techniques and session-wise normal equations for VLBI. The set of estimated unknowns includes 3-dimensional Cartesian coordinates at the reference epoch 2005.0 of the stations distributed globally and their rates as well as the time series of consistent Earth Orientation Parameters (EOPs) at the same epochs as the input. Besides the final solution, namely SOL-2, generated by using all the inputs before 2015.0 obtained from short-term observation processing, another reference solution, namely SOL-1, was also computed by using the input before 2009.0 based on the same combination of procedures for the purpose of comparison with ITRF2008 and DTRF2008 and for evaluating the effect of the latest six more years of data on the combined results. The estimated accuracy of the x-component and y-component of the SOL-1 TRF-origin was better than 0.1 mm at epoch 2005.0 and better than 0.3 mm yr−1 in time evolution, either compared with ITRF2008 or DTRF2008. However, the z-component of the translation parameters from SOL-1 to ITRF2008 and DTRF2008 were 3.4 mm and −1.0 mm, respectively. It seems that the z-component of the SOL-1 TRF-origin was much closer to the one in DTRF2008 than the one in ITRF2008. The translation parameters from SOL-2 to ITRF2014 were 2.2, −1.8 and 0.9 mm in the x-, y- and z-components respectively with rates smaller than 0.4 mm yr−1. Similarly, the scale factor transformed from SOL-1 to DTRF2008 was much smaller than that to ITRF2008. The scale parameter from SOL-2 to ITRF2014 was −0.31 ppb with a rate lower than 0.01 ppb yr−1. The external precision (WRMS) compared with IERS EOP 08 C04 of the combined EOP series was smaller than 0.06 mas for the polar motions, smaller than 0.01 ms for the UT1-UTC and smaller than 0.02 ms for the LODs. The precision of the EOPs in SOL-2 was slightly higher than that of SOL-1.

Improved analytical techniques of sulfur isotopic composition in nanomole quantities by MC-ICP-MS

We propose an improved method for precise sulfur isotopic measurements by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) in conjunction with a membrane desolvation nebulization system. The problems of sulfur loss through the membrane desolvation apparatus are carefully quantified and resolved. The method overcomes low intrinsic sulfur transmission through the instrument, which was initially 1% when operating at a desolvation temperature of 160 °C. Sulfur loss through the membrane desolvation apparatus was resolved by doping with sodium. A Na/S ratio of 2 mol mol−1 produced sulfur transmissions with 98% recovery. Samples of 3 nmol (100 ng) sulfur achieved an external precision of ±0.18‰ (2 SD) for δ34S and ±0.10‰ (2 SD) for Δ33S (uppercase delta expresses the extent of mass-independent isotopic fractionation). Measurements made on certified reference materials and in-house standards demonstrate analytical accuracy and reproducibility. We applied the method to examine microbial-induced sulfur transformation in marine sediment pore waters from the sulfate-methane transition zone. The technique is quite versatile, and can be applied to a range of materials, including natural waters and minerals.

Development of pressed sulfide powder tablets for in situ sulfur and lead isotope measurement using LA-MC-ICP-MS

Controlling the accuracy and precision of sulfur and lead isotopic compositions in natural sulfide minerals requires the use of well-characterized reference materials with matrices similar to those of the unknown samples being analyzed. However, it is often a challenge to prepare natural or synthetic reference materials with homogeneous isotope compositions on a micro-scale. Herein, we report a novel method to synthesize homogeneous sulfide reference materials in the form of nano-particulate pressed sulfide powder tablets (PSPTs). Non-matrix-matched external calibration was used to obtain accurate and precise lead isotopic ratios, while mass bias was corrected using a standard-sample bracketing method and a thallium standard solution doping process. In situ analysis of lead isotopic ratios of PSPTs using laser ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) yielded good external precisions of <0.026% for 207,208Pb/206Pb and <0.057% for 206,207,208Pb/204Pb (2RSD). Meanwhile, the standard deviations of results afforded by LA-MC-ICP-MS were better than 0.41‰ for 34S/32S (2SD). The in situ analytical results of PSPTs were consistent with the values obtained using solution nebulizer MC-ICP-MS, thus demonstrating the reliability and robustness of our analytical protocol. This method can also be used to synthesize different material matrices with homogeneous sulfur and lead isotopes to correct mass bias when using standard-sample bracketing for in situ analysis.

Three-Dimensional Adjustment of Precision Control Network Based on Independent Coordinate System

The control network measurement system based on Railway fixed pile can be used in the maintenance of ballasted track. However, how to evaluate the impact of the external observation precision of the control network on the relative position precision and the position precision of the control point does not have a final conclusion. This paper combines line field conditions of Railway line. We have proposed a net-shaped and analysis of field data collected on the basis of three-dimensional control point adjustment calculation. And then, we can get the relation among field observation precision of control point and relative positional precision and positional precision of the control point. The result shows that if the azimuth measurement accuracy is less than ±1¢¢ , the accuracy of the vertical measurement and the distance measurement are less than ±1¢¢ and ( ) 6 2 2 10 mm − ± + × , respectively. And then the relative position accuracy of control network will be less than ±4mm . The conclusion plays an important role in the ballasted track measurement standard and work.

Accurate and precise determination of lead isotope composition in selected geochemical reference materials

Lead (Pb) isotopes have been extensively employed in tracing sources of Pb and its transport pathways through the environment. However, Pb isotopic ratios in related geochemical reference materials are scarce. Here, we report high-precision Pb isotopic ratios measured by Nu Plasma II MC-ICP-MS using calibrated 205Tl/203Tl = 2.38865 (NIST SRM 997) for mass discrimination correction. The long-term external precision (2SD) for NIST SRM 981 of Pb, BCR-2, and BHVO-2 are 0.31‰ (n = 105), 0.42‰ (n = 11), and 0.25‰ (n = 5) for 208Pb/206Pb and 0.16‰, 0.53‰, and 0.07‰ for 206Pb/207Pb, both respectively, and their Pb isotopic ratios are in excellent agreement with the recommended values. Using this method, we report for the first time Pb isotopic compositions in shale SGR-1b (USGS); coal CLB-1 (USGS); stream sediments GSD-17, -21, and -23 (IGGE); soils GSS-12, -13, -14, -15, and -16 (IGGE); plants GSV-1, -2, and -3 (IGGE); and human hair GSH-1(IGGE).

Carbonate clumped isotope analyses with the long-integration dual-inlet (LIDI) workflow: scratching at the lower sample weight boundaries.

Clumped isotope analyses (Δ47 ) of carbonates by dual inlet (DI) mass spectrometry require long integration times to reach the necessary high precision due to the low abundance of the rare isotopologue 13 C18 O16 O. Traditional DI protocols reach this only with large amounts of sample and/or a large number of replicates as a large portion of the analyte gas is wasted. We tested an improved analytical workflow that significantly reduces the sample sizes and total analysis time per sample while preserving precision and accuracy. We implemented the LIDI (long-integration dual-inlet) protocol to measure carbonates in micro-volume mode using a Kiel IV carbonate device coupled to a Thermo Scientific 253 Plus isotope ratio mass spectrometer without the new 1013 ohm amplifier technology. The LIDI protocol includes a single measurement of the sample gas (600s integration) followed by a single measurement of the working gas (WG) with the same integration time. The Δ47 measurements of four calcite standards over a period of 5weeks demonstrate excellent long-term stability with a standard deviation of ±0.021 to ±0.025 ‰ for the final values of the individual aliquots. The Δ47 analyses of a coral, four foraminifera and a calcite precipitated in the laboratory demonstrate that 14 replicates of 90 to 120μg are sufficient to achieve an external precision of ±0.007 ‰ (1SE) or of ±0.013 ‰ at the 95% confidence level. This study demonstrates that by using a Kiel IV-253 Plus system with LIDI it is possible to achieve the same analytical precision as conventional DI measurements with at least a factor of 40 less sample material. With the new 1013 ohm resistor technology there is the potential to reduce the required sample material even more. This opens new avenues of research in paleoceanography, paleoclimatology, low-temperature diagenesis and other currently sample size limited applications. Copyright © 2017 John Wiley & Sons, Ltd.

A multiple ion counter total evaporation (MICTE) method for precise analysis of plutonium by thermal ionization mass spectrometry

This paper presents a total evaporation method for the analysis of sub-picogram quantities of Pu, utilizing an array of multiple ion counters. Data from three standards are presented to assess the utility of the technique. An external precision of 1.5% RSD (2σ) was achieved on aliquots approaching 100 fg for the minor 240Pu isotope. Accurate analysis of <1 femtogram of 240Pu, is achievable, with an external reproducibility of better than 10% RSD (2σ). This new technique represents a significant advance in the total evaporation method and will allow routine measurement of femtogram sized Pu samples by thermal ionization mass spectrometry.

Efficient simultaneous partial nitrification, anammox and denitrification (SNAD) system equipped with a real-time dissolved oxygen (DO) intelligent control system and microbial community shifts of different substrate concentrations

Simultaneous partial nitrification, anammox and denitrification (SNAD) process was studied in a sequencing batch biofilm reactor (SBBR) fed with synthetic wastewater in a range of 2200 mgN/L ∼ 50 mgN/L. Important was an external real-time precision dissolved oxygen (DO) intelligent control system that consisted of feed forward control system and feedback control system. This DO control system permitted close control of oxygen supply according to influent concentration, effluent quality and other environmental factors in the reactor. In this study the operation was divided into six phases according to influent nitrogen applied. SNAD system was successfully set up after adding COD into a CANON system. And the presence of COD enabled the survival of denitrifiers, and made Thauera and Pseudomonas predominant as functional denitrifiers in this system. Denaturing gradient gel electrophoresis (DGGE), fluorescence in situ hybridization (FISH) and 16S rRNA amplicon pyrosequencing were used to analyze the microbial variations of different substrate concentrations. Results indicated that the relative population of ammonia oxidizing bacteria (AOB) members decreased when influent ammonia concentration decreased from 2200 mg/L to 50 mg/L, while no dramatic drop of the percent of anammox bacteria was seen. And Nitrosomonas europaea was the predominant AOB in SNAD system treating sewage, while Candidatus Brocadia was the dominant anammox bacteria.

Precise Geoid Determination over Hong Kong from Heterogeneous Data Sets using a Hybrid Method

ABSTRACTThis study attempts to develop a methodology to construct a high-precision geoid model (HKGEOID-2016) over Hong Kong. To achieve this objective, a hybrid method is employed in this article. The proposed method involves three steps: the combination of multisource data; the construction of gravimetric geoid model using the remove-restore technique and Molodensky's theory; and the optimal combination of heterogeneous height data, improved by the evaluation of stochastic models through the variance component estimation method and assessment of the parametric model. The accuracy of the constructed geoid is evaluated with independent GNSS/leveling data. Numerical results indicate that external precision of 1.5 cm level is achievable. Furthermore, compared with the former geoid model HKGEOID-2000, the proposed procedure in this study improves the accuracy of the geoid significantly.

High-precision 40Ar/39Ar dating of pleistocene tuffs and temporal anchoring of the Matuyama-Brunhes boundary

Abstract High-precision 40 Ar/ 39 Ar ages for a series of proximal tuffs from the Toba super-volcano in Indonesia, and the Bishop Tuff and Lava Creek Tuff B in North America have been obtained. Core from Ocean Drilling Project Site 758 in the eastern equatorial Indian Ocean contains discrete tephra layers that we have geochemically correlated to the Young Toba Tuff (73.7 ± 0.3 ka), Middle Toba Tuff (502 ± 0.7 ka) and two eruptions (OTTA and OTTB) related to the Old Toba Tuff (792.4 ± 0.5 and 785.6 ± 0.7 ka, respectively) ( 40 Ar/ 39 Ar data reported as full external precision, 1 sigma). Within ODP 758 Termination IX is coincident with OTTB and hence this age tightly constrains the transition from Marine Isotope Stage 19–20 for the Indian Ocean. The core also preserves the location of the Australasian tektites, and the Matuyama-Brunhes boundary with Bayesian age-depth models used to determine the ages of these events, c. 786 and c. 784 ka, respectively. In North America, the Bishop Tuff (766.6 ± 0.4 ka) and Lava Creek Tuff B (627.0 ± 1.5 ka) have quantifiable stratigraphic relationships to the Matuyama-Brunhes boundary. Linear age-depth extrapolation, allowing for uncertainties associated with potential hiatuses in five different terrestrial sections, defines a geomagnetic reversal age of 789 ± 6 ka. Considering our data with respect to the previously published age data for the Matuyama-Brunhes boundary of Sagnotti et al. (2014), we suggest at the level of temporal resolution currently attainable using radioisotopic dating the last reversal of Earths geomagnetic field was isochronous. An overall Matuyama-Brunhes reversal age of 783.4 ± 0.6 ka is calculated, which allowing for inherent uncertainties in the astronomical dating approach, is indistinguishable from the LR04 stack age (780 ± 5 ka) for the geomagnetic boundary. Our high-precision age is 10 ± 2 ka older than the Matuyama-Brunhes boundary age of 773 ± 1 ka, as reported previously by Channell et al. (2010) for Atlantic Ocean records. As ODP 758 features in the LR04 marine stack, the high-precision 40 Ar/ 39 Ar ages determined here, as well as the Matuyama-Brunhes boundary age, can be used as temporally accurate and precise anchors for the Pleistocene time scale.

High-precision analysis of 182W/184W and 183W/184W by negative thermal ionization mass spectrometry: Per-integration oxide corrections using measured 18O/16O

Here we describe a new analytical technique for the high-precision measurement of 182W/184W and 183W/184W using negative thermal ionization mass spectrometry (N-TIMS). We improve on the recently reported method of Trinquier et al. (2016), which described using Faraday cup collectors coupled with amplifiers utilizing 1013Ω resistors to continuously monitor the 18O/16O of WO3− and make per-integration oxide corrections. In our study, we report and utilize a newly measured oxygen mass fractionation line, as well as average 17O/16O and 18O/16O, which allow for more accurate per-integration oxide interference corrections. We also report a Faraday cup and amplifier configuration that allows 18O/16O to be continuously monitored for WO3− and ReO3−, both of which are ionized during analyses of W using Re ribbon. The long-term external precision of 182W/184W is 5.7ppm and 3.7ppm (2SD) when mass bias corrected using 186W/184W and 186W/183W, respectively. For 183W/184W mass bias is corrected using 186W/184W, yielding a long-term external precision of 6.6ppm. An observed, correlated variation in 182W/184W and 183W/184W, when mass bias corrected using 186W/184W, is most likely the result of Faraday cup degradation over months-long intervals.

Reconstructing seasonality using d18O in incremental layers of human enamel: a test of the analytical protocol developed for SHRIMP IIe/MC ion microprobe

A number of recent studies dealing with palaeoclimate and environmental reconstruction include the measurement of oxygen isotope composition of mammalian teeth. Some of them analyse a temporal sequence of the changes recorded in bioapatite from enamel layers representing the whole period of tooth development. Enamel samples display large intra-tooth δ 18 O variations that may reflect a seasonal fluctuation in the δ 18 O of local palaeoclimate parameters. The present paper provides an effective analytical protocol for sequential δ 18 O analysis of human teeth using SHRIMP IIe/MC ion microprobe. It is possible to follow the inner enamel layer along enamel-dentine junction on a high spatial scale in a range about 0.02 mm of spot diameter and 0.12–0.14 mm of the distance between spots. Using the methodology described herein, we can achieve an external precision for δ 18 O analysis <0.2‰ (1σ). The number of 60 to 90 single analyses covering the enamel layer between the incisal and apical ends is enough to obtain temporal resolution of less than one month and to document precisely seasonal fluctuation caused by local environmental and climate factors. The methodology of δ 18 O in situ measurements has been tested on human teeth from Tell Majnuna, a 4th millennium BCE cemetery in Northern Mesopotamia, which is a relatively arid area with high seasonal differences in precipitation and temperature. Observed pattern of δ 18 O variations is consistent with expected seasonal fluctuations, although the overall effect is blurred by some inertia in the enamel maturation.

A SELF-CALIBRATION METHOD FOR ARTICULATED ARM COORDINATE MEASURING MACHINES

To improve the accuracy of articulated arm coordinate measuring machines (AACMM) and simplify the calibration process, an improved self-calibration method was proposed. Unlike the traditional calibration methods, which need external expensive precision instruments and elaborate setups, the proposed self-calibration method only requires a gauge to assist the data acquisition operation. By designing a movement trajectory of the AACMM, a series of joint angles can be obtained to form overdetermined equations based on the kinematic model of the AACMM. Therefore, the structural parameters of the AACMM can be obtained by solving the equations. Consequently, the calibration can be achieved by solving these equations. The coefficient matrix of the equations was further analyzed to simplify the equations, and a constructive method was presented to identify the structural parameters by solving the simplified equations with a modified simulated annealing algorithm, in which an optimized search strategy was applied to improve the robustness and efficiency. Experimental studies on an AACMM validate the convenience and effectiveness of the proposed AACMM self-calibration approach.