Bias factor, maximum bias and the E-value: insight and extended applications

Background Unmeasured confounding can bias the relationship between exposure and outcome. Sensitivity analyses generate bias-adjusted measures but these are not much used; this may change with the availability of the E-value (for evidence for causality in observational studies), appealing for its ease of calculation. However, as currently proposed, the E-value has some practical limitations that may reduce its use. Methods We first provide some insight into the relationship between two established measures for unmeasured confounding: ‘the bias factor’ and the maximum value this bias factor can take (‘the B bias’). These measures are the statistical foundation for the E-value. We use them to develop new E-value formulas for situations when it is not currently applicable such as e.g. when, not unusually, a negative relation between unmeasured confounder and outcome and a positive one with exposure are postulated. We also provide E-values on the odds ratio scale because, currently, even when using the odds ratio as the study measure in the calculation of E-value, the result is to be interpreted as a relative risk, which is somewhat inconvenient. Results The additional formulas for the E-value measure make it applicable in all possible scenarios defined by the combined directions between unmeasured confounder and both the exposure and outcome. In addition, E-value measures can now be interpreted as odds ratios if the observed results are reported on the same scale. Conclusions The E-value is part of newer sensitivity analyses methods for unmeasured confounding. We provide insight into its structure, underscoring its advantages and limitations, and expand its applications.

Validation of temperature data from the RAman Lidar for Meteorological Observations (RALMO) at Payerne. An application to liquid cloud supersaturation

The RAman Lidar for Meteorological Observations (RALMO) is operated at the MeteoSwiss station of Payerne (Switzerland) and provides, amongst other products, continuous measurements of temperature since 2010. The temperature profiles are retrieved from the pure rotational Raman (PRR) signals detected around the 355-nm Cabannes line. The transmitter-receiver system of RALMO is described in detail and the reception and acquisition units of the PRR channels are thoroughly characterized. The FastCom P7888 card used to acquire the PRR signal, the calculation of the dead-time and the desaturation procedure are also presented. The temperature profiles retrieved from RALMO data during the period going from July 2017 to the end of December 2018 have been validated against two reference operational radiosounding systems (ORS) co-located with RALMO, i.e. the Meteolabor SRS-C50 and the Vaisala RS41. These radiosondes have also been used to perform seven calibrations during the validation period. The maximum bias (ΔTmax), mean bias (μ) and mean standard deviation (σ) of RALMO temperature Tral with respect to the reference ORS Tors are used to characterize the accuracy and precision of Tral in the troposphere. The ΔTmax, μ and σ of the daytime differences ΔT=Tral−Tors in the lower troposphere are 0.28 K, 0.02±0.1 K and 0.62±0.03 K, respectively. The nighttime differences suffer a mean bias of μ = 0.05±0.34 K, a mean standard deviation σ=0.66±0.06 , and a maximum bias ΔTmax=0.29 K over the whole troposphere. The small ΔTmax, μ and σ values obtained for both daytime and nighttime comparisons indicate the high stability of RALMO that has been calibrated only seven times over 18 months. The retrieval method can correct for the largest sources of correlated and uncorrelated errors, e.g. signal noise, dead-time of the acquisition system and solar background. Especially the solar radiation (scattered into the field of view from the Zenith angle Phi affects the quality of PRR signals and represents a source of systematic error for the retrieved temperature. An imperfect subtraction of the background from the daytime PRR profiles induces a bias of up to 2 K at all heights. An empirical correction f(Φ) ranging from 0.99 to 1, has therefore been applied to the mean background of the PRR signals to remove the bias. The correction function f(Φ) has been validated against the numerical weather prediction model COSMO suggesting that f(Φ) does not introduce any additional source of systematic or random error to Tral. A seasonality study has been performed to help understanding if the overall daytime and nighttime zero-bias hides seasonal non-zero biases that cancel out when combined in the full dataset. Finally, the validated RALMO temperature has been used in combination with the humidity profiles retrieved from RALMO to calculate the relative humidity and to perform a qualitative study of supersaturation occurring in liquid stratus clouds.

Validation of a Video-Based Performance Analysis System (Mediacoach®) to Analyze the Physical Demands during Matches in LaLiga

The aim of the present study was to assess the accuracy of a multi-camera tracking system (Mediacoach®) to track elite football players’ movements in real time. A total of 207 observations of 38 official matches from Liga 1, 2, 3™ (2nd Spanish Division, season 2017/18) were included in the study (88 defenders, 84 midfielders, and 35 attackers of the same team). Total distance (TD, m) distance in zone 4 (DZ4) at a speed of 14–21 km/h, distance in zone 5 (DZ5) at a speed of 21–24 km/h (DZ5), distance in zone 6 (DZ6) at a speed of ≥24 km/h, maximum speed (km/h), and number of sprints (actions above 24 km/h) were registered with the Apex® GPS system (STATSports™, Newry, N. Ireland) and Mediacoach® semi-automatic tracking system (LaLiga™, Madrid, Spain). The level of agreement between variables estimated by the two systems was analyzed. Bias was also calculated by deducting the GPS estimated value from the video estimated value, and then dividing the difference score by the GPS estimated value. All variables showed high ICC values (>0.75) and very large correlations (r > 0.70). However the video-based performance analysis system overestimated the results obtained in the different speed zones (DZ5: +16.59 ± 62.29 m; LOA95%: −105.49 to 138.68; DZ6: +93.26 ± 67.76 m; LOA95%: −39.55 to 226.07), the number of sprints (+2.27 ± 2.94; LOA95%: −3.49 to 8.02), and the maximum speed (+0.32 ± 1.25 km/h; LOA95%: −2.13 to 2.77). The maximum bias was found in DZ6 (47%). This demonstrates that Mediacoach® is as accurate as a GPS system to obtain objective data in real time, adapted to physical and movement demands of elite football, especially for total distance and distances traveled at medium speeds.

Impact of filtration artifacts on the seasonality of river waters chemical composition

The difference in concentration of filterable trace metals, macro ions, nitrate and dissolved organic carbon (DOC) after capsule and membrane 0.45 µm filters was studied at the seasonal sampling of the typical medium size boreal Razdolnaya River, Far East of Russia. Trace metals showed notable decrease after membrane filtration compared with capsules, though concentrations of macro ions, nitrates and DOC were equal. Clogging of membranes with subsequent retention of coarse colloids was suggested as a reason for this difference. In summer the dissimilarity in concentration grew in order Cu < Zn < Ni, Cd < Mn < Fe reflecting a significant role of coarse colloids in the pool of filterable forms for Fe and Mn. In winter, retention of Mn was declined due to input of ionic forms from redox cycle. Floods are the periods with the most notable increase of coarse colloids content and maximum bias in the determination of filterable trace metals if frontal membrane filtration is being used.

Gender-partitioned patient medians of serum albumin requested by general practitioners for the assessment of analytical stability

Background:Recently, the use of separate gender-partitioned patient medians of serum sodium has revealed potential for monitoring analytical stability within the optimum analytical performance specifications for laboratory medicine. The serum albumin concentration depends on whether a patient is sitting or recumbent during phlebotomy. We therefore investigated only examinations requested by general practitioners (GPs) to provide data from sitting patients.Methods:Weekly and monthly patient medians of serum albumin requested by GP for both male and female patients were calculated from the raw data obtained from three analysers in the hospital laboratory on examination of samples from those >18 years. The half-range of medians were applied as an estimate of the maximum bias. Further, the ratios between the two medians were calculated (females/males).Results:The medians for male and female patients were closely related despite considerable variation due to the current analytical variation. This relationship was confirmed by the calculated half-range for the monthly ratio between the genders of 0.44%, which surpasses the optimum analytical performance specification for bias of serum albumin (0.72%). The weekly ratio had a half-range of 1.83%, which surpasses the minimum analytical performance specifications of 2.15%.Conclusions:Monthly gender-partitioned patient medians of serum albumin are useful for monitoring of long-term analytical stability, where the gender medians are two independent estimates of changes in (delta) bias: only results requested by GP are of value in this application to ensure that all patients are sitting during phlebotomy.

Separate patient serum sodium medians from males and females provide independent information on analytical bias

Background:During monitoring of monthly medians of results from patients undertaken to assess analytical stability in routine laboratory performance, the medians for serum sodium for male and female patients were found to be significantly related.Methods:Daily, weekly and monthly patient medians of serum sodium for both male and female patients were calculated from results obtained on samples from the population >18 years on three analysers in the hospital laboratory. The half-range of medians was applied as an estimate of the maximum bias. Further, the ratios between the two medians were calculated.Results:The medians of both genders demonstrated dispersions over time, but they were closely connected in like patterns, which were confirmed by the half-range of the ratios of medians for males and females that varied from 0.36% for daily, 0.14% for weekly and 0.036% for monthly ratios over all instruments.Conclusions:The tight relationship between the gender medians for serum sodium is only possible when raw laboratory data are used for calculation. The two patient medians can be used to confirm both and are useful as independent estimates of analytical bias during constant calibration periods. In contrast to the gender combined median, the estimate of analytical bias can be confirmed further by calculation of the ratios of medians for males and females.

Quality Control of Structural Parameters (CELL POPULATION DATA) of Sysmex XN Series

INTRODUCTION: Cell population data (CPD) measured by hematology analyzers (HA) describe morphological parameters of white blood cell (WBC) subpopulations and are reported to be as useful parameters in the screening of several hematological and non-hematological diseases. The Sysmex XN is an HA that uses fluorescence flow cytometry for WBC differential, combining forward scatter (FSC), side scatter (SSC) and fluorescence intensity (SFL) to identify WBC populations. These three measures, along with their Distribution Width (DW), are used to provide CPD of Neutrophils (NE), Lymphocytes (LY) and Monocytes (MO). Recent articles have shown that neutrophils CPD parameters (NE-SSC, NE-SFL) may be useful in the diagnosis of myelodysplastic syndromes [1,2] and sepsis [3]. However, little is known on their analytical quality specification, as the comparability of CPD between instruments and laboratories. The aim of the study was to evaluate the between-analyzers consistency of CPD provided by Sysmex XN comparing the results obtained in five different XN modules installed in the same laboratory. Here we present the results for NE-SSC and NE- SFL, the CPD parameters mainly used to support the diagnosis of suspected sepsis and myelodysplasia M&M Peripheral blood samples collected in K3EDTA tubes (Becton Dickinson, NJ) in three different days from 30 healthy blood donors (HBD, 10 samples/daily) were analyzed within 30 minutes on each XN module. Additionally, all normal samples analyzed by the lab were selected from the routine workload of one month (November 2015) consisting of a total of 35.500 samples. The inclusion criteria (that led to a selection of 6,702 normal routine samples, NRS) were as follows: no morphological flags, WBC from 4.0 to 10.0 x 109/L; Hgb from 120 to 170 g/L; MCV from 84 to 98 fL, PLT from 150 to 450 x 109/L; RDW-CV < 14.0%; NRBC=0.00 x 109/L; NE from 2.00 to 5.60 x 109/L, LY from 1.50 to 3.50 x 109/L, MO from 0.30 to 0.80 x 109/L, EOS from 0.10 to 0.60 x 109/L, BASO <0.20 x 109/L. Finally, the daily results of XN-Chex control blood (Normal level) were included in the evaluation. For each group of samples (HBD, NRS, XN-Check) we compared the median values of CPD parameter obtained on each XN modules. The between-analyzers consistency of CPD parameter was assessed calculating the percentage of Bias (Bias%) between the median value of each XN module and the overall median value of all the five analyzers. To evaluate the stability over the time of CPD parameters, the same study on 30 HBD, 6,690 NRS and XN-Chex control blood was repeated after two months (January 2016). RESULTS The median values of NE-SSC and NE-SFL obtained in each group of samples are shown in Table 1. The results highlight a good agreement between analyzers, with a maximum Bias of -3.85%. Interestingly, the median values of NE-SSC and NE-SFL were practically the same in HBD and NRS while, as expected, they were significantly different on XN-Chex (due to the presence of stabilized cells). However, the Bias observed for each module XN on control blood was similar to that observed on fresh blood (HBS and NRS groups). Median values of NE-SSC and NE-SFL were practically the same after two months both in HBD and NRS, proving that CPD parameters are stable over the time. Similar results were obtained on all the other CPD parameters provided by Sysmex XN (data not shown) CONCLUSIONS CPD parameters are stable over the time and their inclusion on the automated QC of the analyzer based on the moving average of normal may be a reliable and inexpensive method to assess the between-analyzers consistency of CPD parameters. Providing the expected values of CPD parameters, XN-Check could be useful for the daily QC, to assess the need of calibration and to improve the inter-laboratory comparability being the Neutrophils the best WBC population to control using XN-Check control blood. The moving average can be used too as a way to monitor the calibration and to decide what to do when the QC materials give a result out of range (moving average).The results of this study show the possibility to calibrate the CPD parameters. The availability of a calibration material also for CPD parameters would guarantee a further improvement of standardization and their use as reportable diagnostic parameters. 1. Le Roux G, Vlad A, Eclache V et al. Int J Lab Hematol 2010;32:237-243 2. Furundarena JR, Araiz M, Uranga M et al. Int J Lab Hematol 2010;32:360-366 3. Park SH, Park CJ, Lee BR et al. Int J Lab Hematol 2014;37 Table 1 Table 1. Disclosures Simon-Lopez: Sysmex Corporation: Consultancy, Honoraria. Buoro:Sysmex EMEA: Research Funding. Pacioni:DASIT Diagnostica SpA: Employment, Other: Scientific Manager of DASIT (Distributor of Sysmex in Italy). Seghezzi:Sysmex EMEA: Research Funding. Manenti:Sysmex EMEA: Research Funding.

A chironomid-based mean July temperature inference model from the south-east margin of the Tibetan Plateau, China

Chironomid based calibration training sets comprised of 100 lakes from southwestern China and a subset of 47 lakes from Yunnan Province were established. Multivariate ordination analyses were used to investigate the relationship between the distribution of chironomid species and 15 environmental variables from these lakes. Canonical correspondence analyses (CCAs) and partial CCAs showed that mean July temperature is the sole independent and significant (p < 0.05) variable that explains 16 % of the variance in the chironomid data from the 47 Yunnan lakes. Mean July temperature remains one of the independent and significant variables explaining the second largest amount of variance after potassium ions (K+) in the 100 south-western Chinese lakes. Quantitative transfer functions were created using the chironomid assemblages for both calibration data sets. The first component of the weighted average partial least square (WA-PLS) model based on the 47 lakes training set produced a coefficient of determination (r2jack) of 0.83, maximum bias (jackknifed) of 3.15 and root mean squared error of prediction (RMSEP) of 1.72 °C. The two-component WA-PLS model for the 100 lakes training set produced an r2bootstrap of 0.63, maximum bias (bootstrapped) of 5.16 and RMSEP of 2.31 °C. We applied both transfer functions to a 150-year chironomid record from Tiancai Lake (26°38′3.8 N, 99°43’E, 3898 m a.s.l), Yunnan, China to obtain mean July temperature inferences. The reconstructed results based on both models showed remarkable similarity to each other in terms of pattern. We validated these results by applying several reconstruction diagnostics and comparing them to a 50-year instrumental record from the nearest weather station (26°51'29.22"N, 100°14'2.34"E, 2390 m a.s.l). Both transfer functions perform well in this comparison. We argue that the large training set is also suitable for reconstruction work despite the low explanatory power of MJT because it contains a more complete range of modern temperature and environmental data for the chironomid taxa observed and is therefore more robust.

Effect of the Glonass-Specific Receiver Antenna Phase Center Corrections on the Results of European Regional GNSS Network

ABSTRACT In the paper I investigated the effect of the GLONASS-specific receiver antenna phase center corrections on the results of a regional permanent GNSS network. I made analysis, using Bernese GPS Software 5.0, of GPS-only and GPS-GLONASS (GNSS) observations collected at permanent sites in Europe. Two types of GNSS solutions were computed: with GPS phase center corrections used for observations of both systems, and with the system specific corrections for observations of the respective system. The Bernese software was modified accordingly to use GLONASS specific corrections for GLONASS measurements. The results, i.e., coordinates and tropospheric zenith delays were analyzed and compared between computed solutions. Introducing GLONASS-specific receiver antenna phase center corrections did not improve the repeatability of the GNSS coordinate time series. Differences of coordinates between the two GNSS solutions were highly repeatable but offsets (biases) were observed; maximum bias for horizontal component was 1 mm and 4 mm for up component. Similar biases were observed for stations with the same antenna models. Periodic signal with a period of 1/3-year was found in difference time series between GPS and GNSS solutions for north component with a maximum peak-to-peak amplitude 2.8 mm. The periodic signal was attributed to GLONASS.