Regression Slope Research Articles

Using Bland-Altman plot-based harmonization algorithm to optimize the harmonization for immunoassays.

Harmonization has been recommended by theInternational Organization for Standard (ISO) to achieve equivalent results across invitro diagnostic measurement devices (IVD-MDs). We aim to evaluate the effectiveness of Bland-Altman plot-based harmonization algorithm (BA-BHA) created in this study and compare it with weighted Deming regression-based harmonization algorithm (WD-BHA) proposed in ISO 21151:2020. Eighty patient sera were used as the harmonization reference material (HRM) to develop IVD-MD-specific harmonization algorithms. Another panel of 40 patient sera was used to validate the effectiveness of harmonization algorithms. We compared regression slopes, intercepts, Bland-Altman plot layouts, percent differences, limits of agreement (LoAs), between-method coefficients of variation (CV) before and after harmonization. After harmonization by WD-BHA, acceptable slopes and intercepts between measured values and HRM targets were observed in weighted Deming regression, but not in Passing-Bablok analysis. Mean differences were-5.5 to 5.0 % and differences at specific levels were-33.9 to 23.9 %. LoAs were-64.6 to 74.6 %. Between-method CV was 22.9 % (±12.9 %). However, after harmonization by BA-BHA, both weighted Deming and Passing-Bablok regressions equations presented harmonized results. Mean differences were-0.3 to 0.2 % and differences at specific levels were-1.1 to 1.6 %. LoAs were-23.3 to 23.2 %. Between-method CV was 8.4 % (±4.0 %). The data points were evenly distributed at both sides of the mean in Bland-Altman plots. The inequivalence of test results between different methods can be improved but unacceptable analytical differences at specific levels may be hidden in terms of an acceptable slope and intercept on WD-BHA. The new protocol BA-BHA may be a viable alternative to optimize the harmonization for immunoassays.

Respiratory Trajectories and Correlation with Serum Biochemical Indices in Spinal and Bulbar Muscular Atrophy

Background/Objectives: The primary life-threatening complication in spinal–bulbar muscular atrophy (SBMA) is ventilatory failure. The present study analyzes the longitudinal patterns of respiratory function tests over a follow-up of 11 years. Methods: We collected data from 9 genetically confirmed SBMA patients. Spirometric measurements [maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and forced vital capacity (FVC)], serum biochemical indices and SBMA functional rating scale (SBMAFRS) were collected every 6 months for 11 years. An average time curve was utilized to assess the changes in both pulmonary tests and serum biochemical indices of the patients. One-way repeated-measures ANOVA was applied to assess statistical differences. The Spearman’s rank correlation coefficient was utilized to evaluate the correlations between the respiratory function tests and serum biochemical and clinical indices. Results: A progressive decrease was observed in the respiratory function tests; the slope of the linear regression was significantly non-zero (p < 0.0001) for all three time curves. A major decrease was observed for MEP (52%) and MIP (42%), while this was minor for FVC (25%). SBMAFRS score correlated with FVC (r = 0.27), MIP (r = 0.53) and MEP (r = 0.51). MIP and MEP correlated with creatine phosphokinase (r = 0.3, r = 0.25, respectively) and MIP with creatinine levels (r = 0.31). Conclusions: This longitudinal study shows a progressive decline of spirometric data throughout life in SBMA patients. The decline appears to be related to clinical deterioration and muscle denervation. Spirometric measures relative to maximal strength of the respiratory muscles (MIP and MEP) may have a better predictive value for pulmonary and muscular decline than FVC.

Online application of the periodic linear regression method for daily monitoring of photovoltaic systems performance

This paper presents an analysis of the performance of photovoltaic (PV) systems using daily applications of the periodic linear regression method to the performance indicators Final Yield (YF) and Reference Yield (YR). The research was conducted on PV systems installed on rooftops and ground at the Federal Institute of Education, Science, and Technology of Goiás (IFG), Itumbiara Campus, from July 2022 to August 2023. The Energy Monitoring and Management Software (SMGE) was developed to calculate the performance indicators and perform linear regression to analyze the performance of the systems. The results demonstrate that the efficiency of the systems can be monitored by analyzing variations in the slopes of the linear regression lines. An increase in energy conversion efficiency was observed following the cleaning of the PV panels, as reflected in significant changes in the regression slopes. Additionally, natural events, such as rainfall, positively impacted system efficiency. These findings highlight the importance of proper maintenance of PV panels, whether through scheduled cleaning or natural events like rain.

A-316 A quantitative gas chromatography tandem mass spectrometry method for metabolic profiling of urine organic acids and acylglycines

Abstract Background The analysis of urine organic acids (UOA) and acylglycines (UAG) are an essential investigation for the diagnosis inborn errors of metabolism (IEMs). The vast majority of methods for these analytes use gas chromatography mass spectrometry (GC-MS) and are only qualitative. Gas chromatography tandem mass spectrometry (GC-MS/MS) offers greater sensitivity and selectivity and enables the combination of qualitative screening with quantitative analysis. We describe the development and validation results of a quantitative GC-MS/MS method. Methods Urine creatinine concentrations were measured (CobasPro, Roche Diagnostics) and normalized to 1.25 mmol/L. After internal standard addition, each urine specimen, calibration standard and QC were incubated with a hydroxylamine solution followed by a liquid-liquid extraction. Further sample concentration permitted the isolated UOA and UAG to be derivatized using N,O-bis(trimethylsilyl)trifluoroacetamine (BSTFA) with 1% chlorotrimethylsilane (TMCS) prior to injection. GC-MS/MS analysis was performed using a GC-MS-TQ8050 triple quadrupole system (Shimadzu) with a 30 m DB-5MS (Agilent J&W) capillary column (0.25 mm, ID of 0.25 µm). Split injection mode was deployed with an initial column temperature of 70°C. The mass spectrometer was operated in electron ionization (EI) and multiple reaction monitoring (MRM) modes. Results The optimal temperature gradient for high-resolution UOA and UAG separations was derived and their respective retention times determined. MS/MS detection parameters were optimized to permit the identification of precursor and production ions for all (N=36) derivatized analytes. Total analysis time was 33.8 min per injection. This method permits the measurement of 11 samples in one batch and is highly linear for all analytes (R^2 >0.99 and average slope 1.04). The limit of quantification (LOQ) was established and ranged from <0.05 to 2.1 µmol/mmol creatinine. Intra- and inter-day imprecision (CV%) was determined using matrix-matched abnormal and normal QC. Intra-day imprecision (N=10) ranged from 1.3% (2-ketoglutaric acid) to 9.7% (3-hydroxybutyric acid). Inter-day imprecision (N=30 over 15 days) ranged from 2.2% (ethylmalonic acid and methylmalonic acid) to 20.5% (3-hydroxy-3-methylglutaric acid). The method had an average accuracy of 113±14% for analytes included in the ERNDiM quantitative organic acids (urine) external quality assurance program. For analytes not included in this proficiency testing, the method showed good agreement when compared to a national reference laboratory, with average Deming correlation coefficients and regression slopes being 0.9944 and 1.1, respectively. No interferences were detected when monitoring the analyte quantifier and qualifier ion ratios in patient urine. Conclusions The devised GC-MS/MS protocol permits the unbiased identification and quantification of UOA and UAG used to investigate IEMs. The method has acceptable sensitivity, specificity, precision and accuracy for clinical routine clinical testing.

A-110 Analytical Performance Evaluation of Vitros® Immunodiagnostic Products Intact PTH II Assay

Abstract Background Intact parathyroid hormone (iPTH) is indicated to aid in the diagnosis of hyperparathyroidism, hypoparathyroidism, differential diagnosis of hypocalcemia or hypercalcemia and for intraoperative measurement of iPTH levels. Studies were conducted to evaluate the analytical performance of the Vitros Immunodiagnostic Products Intact PTH II (Vitros iPTH II) assay by determining limit of detection (LoD), limit of quantitation (LoQ), and precision. A method comparison of the Vitros iPTH II assay against the Roche Elecsys PTH assay was also conducted. Methods The LoD and LoQ were determined consistent with CLSI EP17. Precision was evaluated consistent with CLSI EP05 using six patient pools for 20 days. Repeatability was determined using two replicates per run. Within-lab precision was determined using a single reagent lot and a single calibration. A quantitative comparison between the Vitros iPTH II assay on a Vitros 3600 system and the Roche Elecsys PTH assay on a Roche Cobas 8000 system was conducted in accordance with CLSI guideline EP09 using 206 endogenous patient samples. Samples were selected to cover the full measuring interval and were tested over a total of six non-consecutive days. Results The LoD for the Vitros iPTH II assay was determined to be 1.7 pg/mL. The claimed LoQ was determined using a precision profile approach with a %CV limit of 20% and set at 1.7 pg/mL. For mean parathyroid hormone (PTH) concentrations ranging from 15.9 to 4656 pg/mL, repeatability (within-run) percent coefficient of variation (%CV) ranged from 0.8% to 1.4% and within-lab %CV ranged from 1.5% to 3.0%. The method comparison of the Vitros iPTH II assay versus the Roche Elecsys PTH assay yielded a correlation coefficient of 0.991 and a Passing-Bablok regression slope of 1.01 and intercept of 0.3. Conclusions The Vitros iPTH II assay demonstrated acceptable analytical performance in these studies, with high correlation and close agreement to the Roche Elecsys PTH assay.

B-153 Improving Accuracy of IgG subclasses Quantitation in Serum Using Liquid Chromatography - Tandem Mass Spectrometry (LC-MS/MS) on SCIEX 7500

Abstract Background Serum IgG subclasses (IgGSC) are most often measured for identification of selective immunodeficiency disease and IgG4-related disease (IgG4RD). Traditional nephelometric (IN) assays suffer from errors related to antigen excess and cross-reactivity that can impact the accuracy of results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been the routine testing methodology for serum IgG subclasses at St. Paul’s Hospital since 2015 due to the simplicity and freedom from inter-subclass cross-reactivity problems. In brief, 20 μL of serum sample is denatured, reduced, alkylated and digested, processed semi-automatically on Hamilton Starlet liquid handler. This is followed by analysis on a SCIEX 5500 QTRAP LC-MS/MS. However, when the method was migrated to the SCIEX 7500, it suffered from calibration curve splitting and poor between-device comparability. It was hypothesized that this could be caused by detuning of some high concentration analytes, suboptimal internal standard (IS) concentrations and, suboptimal IS multiple reaction monitoring (MRM) transition choices, and matrix effects from artificial calibrators. Methods Several modifications were made to improve accuracy and robustness: 1) new in-house calibrators were prepared using patient sample pool instead of using Binding Site IgG Subclass Kit calibrators. 2) More IS MRM transitions were added to the method with each analyte MRM quantitated using its own IS MRM using the same fragment ion. The IS concentration was also increased 5-fold for IgG1 and Total IgG. 3) To avoid problems arising from selectively ion detuning, the injection volume was reduced from 10 μL to 1 μL which permitted collision energies (CEs) to be normalized for each analyte/IS MRM pair. Results The new SCIEX 7500 method compares well with the original method (N=168) with Passing Bablok regression slopes of 0.94, 1.1, 1.0, 0.98, and 0.98 for IgG1-4 and IgG total respectively with corresponding intercepts of 0.3, -0.1, 0.0, 0.0, and 0.41 g/L and R^2 of 0.96, 0.95, 0.99, 0.98, and 0.95. Median differences were -1.76%, 1.07%, 1.06%, 6.13% and 1.91%. In a typical batch of 90 patient samples and four sets of calibrators, the calibration curves overlap well. Use of patient-based calibrators allowed calibration values to be centered in the range of typical patient sample values, particularly for IgG4, where the calibration curve was extended to 3.46 g/L compared with the previous high calibrator value of 0.48 g/L. Conclusions The new IgG subclass quantitation method on SCEIX 7500 LC-MS/MS system is robust with excellent reproducibility and between-device comparability.

B-021 Impact of Assay Conditions on FT4 Measurement Accuracy of Equilibrium Dialysis LC/MS/MS Clinical Assay

Abstract Background Reliable FT4 measurements are vital for accurate diagnosis and effective management of thyroid disorders. However, currently used FT4 immunoassays (IAs) lack standardization, leading to significant variations between platforms. Equilibrium dialysis (ED) coupled with LC-MS/MS analysis, considered the gold standard for FT4 measurement, has been adopted as a reference measurement procedure (RMP) for IA standardization. This study aimed to establish a high-throughput version of the routine clinical FT4 assay based on ED-LC/MS/MS technology and assess the impact of altered assay conditions on measurement accuracy. Methods A commercially available micro-ED plate was employed for ED-LC/MS/MS analysis. FT4 extraction from the dialysate was performed by utilizing a 96-well C18 SPE plate, followed by FT4 quantitation via LC-MS/MS in positive ion mode. Certified primary reference material was used to calibrate the assay. To evaluate assay robustness, the effects of minor method modifications were studied, including incubation time of ED, serum/buffer ratios in ED inserts, ED incubation temperature, shaker speed during ED, serum sample dilution ratio, and dialysate sample dilution ratio. Additionally, short-term and long-term stability of serum FT4 were assessed. Results The developed ED-LC/MS/MS assay successfully resolved T4, T3, reverse triiodothyronine (rT3), and other interferences within 4 minutes using C18 chromatography. The assay's linear range (0.5-100 pg/mL) encompassed clinically relevant FT4 concentrations across hypo- and hyperthyroid patient samples. Excellent agreement was observed between the routine assay based on ED-LC/MS/MS and CDC RMP with a Deming regression slope near 1 (95%CI: 0.87-1.06). Furthermore, serum/buffer ratios from 1:1 to 1:2.5 in ED inserts, shaker speeds from 75 to 150 rpm, and ED incubation times from 16 to 20 hours did not significantly affect FT4 measurement. However, elevated ED temperature (38°C) led to a more than 10% increase in FT4 values. Serum FT4 remained stable when exposed to room temperature for 12 hours, five freeze-thaw cycles, and -70°C storage for 1.5 years. Additionally, dilution of sera by up to 3-fold before ED did not alter FT4 measurement results. Diluting dialysate samples at least 3 times prior to SPE extraction proved accurate for samples exceeding the calibration curve range. Conclusions In conclusion, we successfully developed a routine clinical FT4 assay based on ED-LC/MS/MS that generates data comparable to the RMP. The assay exhibits robustness, with several altered conditions not significantly impacting measurement accuracy. This high-throughput and accurate assay demonstrates suitability for both clinical laboratories and large-scale epidemiological studies. Disclaimer: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Public Health Service, and the US Department of Health and Human Services.

B-267 Validation of the Newly Developed Fully Automated Chemiluminescent Enzyme Immunoassay (CLEIA) Reagent for Measurement of Cyclosporine in the Blood

Abstract Background Cyclosporine (CsA) is an immunosuppressive drug requiring therapeutic drug monitoring (TDM) for its narrow-ranged medication level. Approximately 60% of CsA in the blood exist as molecular complexes with proteins like cyclophilin in lymphocytes and erythrocytes. Measurement of CsA in the blood by immunoassay or liquid chromatography-tandem mass spectrometry (LC-MS/MS) requires an extraction process for CsA from the whole blood specimen, which is often manual complicated and time-consuming process causing a risk of variation in the measurement values among different operators. In addition, the small (cyclic polypeptide composed of 11 amino acids) and hydrophobic property of CsA, make it difficult to establish antibodies for a sandwich immunoassay. In this study, we have validated a novel fully automated sandwich immunoassay reagent for measurement of blood CsA that used a combination of newly-established CsA antibodies and iTACT® (immunoassay for total antigen including complex via pretreatment) technology. Methods The reagent was developed and validated on a fully automated immunoassay system, LUMIPULSE® L2400 (FUJIREBIO INC). Twenty uL whole blood specimens are sampled after mixed with suction/discharge stirring to prevent that blood cells settle to the bottom of a container on the analyzer, and then treated with a pretreatment solution to obtain free CsA. The treated samples are assayed by a two-step sandwich immunoassay. Limit of Detection (LoD), Limit of Quantitation (LoQ), within-laboratory precision, linearity, no interference, and the correlation of this assay and LC-MS/MS were validated, following the current CLSI guidelines protocols. Data were analyzed using Microsoft Excel statistical tool Analyse-it. Results The LoD and the LoQ were 2.7 ng/mL and 10.8 ng/mL respectively. The within-laboratory precision showed CV 1.6-2.9 %. Linearity was demonstrated over the range 13.1-2381.5 ng/mL. No interference was observed with unconjugated (≤19.7 mg/dL) or conjugated bilirubin (≤20.1 mg/dL), chyle (≤1480 FTU), RF (rheumatoid factor, ≤1000 IU/mL), and HAMA (human anti-mouse antibody, ≤1010 ng/mL). The correlation coefficient and the regression slope of this assay and LC-MS/MS were 1.0 and 1.0, respectively (N=120). Conclusions The performance of our novel CsA assay, which use LUMIPULSE L2400, was satisfactory for routine analysis. A unique fully-automated process, including the pretreatment process of whole blood specimens, for measurement would contribute the low LoQ and the low Within-laboratory CV. In addition, the results are obtained in 35-minute. We expect this novel immunoassay could reduce the burden on operators and turnaround time.

A-318 Validation of umbilical cord blood as an alternate sample type for quantitative in vitro detection of glucose-6-phosphate dehydrogenase in neonates

Abstract Background Detection of glucose-6-phosphate dehydrogenase (G6PD) deficiency provides important information for neonatal clinical management. G6PD newborn screening is recommended using umbilical cord blood specimens in vulnerable patient populations.1 Also, cord blood is used by many clinicians instead of peripheral blood for neonatal screening of G6PD.2 Use of cord blood is a modification to the FDA-approved Pointe Scientific G6PD kinetic-340 nm assay. The aim of this study was to validate cord blood as an alternate specimen type for the Pointe Scientific G6PD assay. Methods Hemoglobin (Hgb) results are from Sysmex XN 9100™ analyzers that use SLS methodology with photometric detection. G6PD results are from Roche cobas® c502 analyzers with Pointe Scientific kinetic method and spectrophotometric detection of activity, expressed as U/g Hgb. Neonatal blood specimens were obtained as paired samples from heel sticks and umbilical cord collected in EDTA lavender top tubes. Accuracy acceptance criteria was defined as Deming regression slope between 0.90 and 1.10, r-value of >0.90 and bias ±15% and mixing study recovery of ±10%. Precision (intra-assay and inter-assay), reportable range and linearity, carryover, and stability were established using cord blood samples or control materials sourced from Thermo Fisher Scientific or Sysmex. Reference intervals3, analytical sensitivity, specificity, and clinical validity were transferred to cord blood due to comparability with whole blood FDA-approved method. EP Evaluator software by Data Innovations® was used for calculations. Results Direct comparison of G6PD results (U/g Hgb) from 125 paired samples yielded a 0.9025 correlation coefficient, 1.024 Deming slope, and -0.25% bias. Mixing and recovery of admixed samples gave % recoveries of 102, 103, 101, 102, 100, and 100 for G6PD (U/g Hgb), and 102, 102, 101, 104, 99, and 105 for Hgb (g/dL). Intra-assay precision results were 2.4, 0.6, 0.8, 0.5, 0.4 % CV for G6PD and Hgb, respectively. Inter-assay precision results were 3.1, 3.3, 0.7, 0.7, 0.5 % CV for G6PD and Hgb, respectively. Reportable range and linearity evaluation resulted in a maximum deviation from target recovery of 4%, and a slope of 0.979 for a range of 50 - 2740 U/L, and reportable range for Hgb was confirmed as 0.1 - 26.0 g/dL using controls (1% maximum deviation and 0.991 slope). Carryover was -5.8 (mean concentration) for G6PD and 0% for Hgb after testing 21 replicates of pooled high and low samples in a defined order. Testing 3 samples in 3 replicates at each defined time interval defined stability as 1 week refrigerated or 72 hours room temperature for G6PD, and 3 days refrigerated or 1 day room temperature for Hgb. Conclusions Regression statistics and mixing-recovery studies demonstrated accuracy for detecting G6PD (U/g Hgb) and Hgb (g/dL) from EDTA cord blood. Additional performance characteristics were transferrable for this specimen type from the FDA-approved method for whole blood. Umbilical cord blood is an acceptable alternate specimen type for quantitative detection of G6PD (U/g Hgb) using Pointe Scientific with Sysmex XN-9100™ and Roche cobas® c502 instrumentation.

Vortex Trapping of Suspended Sand Grains Over Ripples

AbstractCoastal hydrodynamics and morphodynamics integrate the effects of small‐scale fluid‐sediment interactions; yet, these small‐scale processes are not well understood. To investigate sediment trapping by turbulent coherent structures or vortices, the transport of coarse sand over ripples was analyzed in a small‐oscillatory flow tunnel with phase‐separated Particle Image and Tracking Velocimetry. Results from one of the first direct measurements of vortex‐trapped sand grains under oscillatory flows are presented. The vortices mobilized sand grains along the ripple slopes just prior to flow reversal and transported the suspended sediment grains. During several flow cycles, some sand grains were temporarily trapped in the vortex, prescribing semi‐circular trajectories off‐center from the vortex core in quadrants of the vortex that were closest to the ripple slope, as illustrated by Nielsen (1992, https://doi.org/10.1142/1269). Comparisons of the horizontal sediment grain velocity with the horizontal fluid velocity yielded a linear relationship with a slope of 0.87. The vertical grain velocities also varied linearly with the vertical fluid velocity with a slope of approximately 1 and an offset of −0.08 m . The offset is close to the still water settling velocity for coarse sand grains, as hypothesized during vortex trapping. Additionally, estimates of the off‐center distance, between the centers of the semi‐circular sediment paths and vortex cores, compared well with the ratio of the settling velocity to the radian frequency of the vortex yielding a linear regression slope of 0.99. Improved understanding of vortex trapping effects on sediment dynamics may decrease uncertainty in model predictions of large‐scale coastal hydrodynamics and sediment transport.

Collaborations in publications on pediatric anesthesiology in the D-A-CH countries

Collaborations are an essential element of scientific activity and particularly important in fields such as pediatric anesthesiology, where the evidence base in general is relatively limited. Arecent scientometric analysis revealed ageographic diversification of publication activity in pediatric anesthesiology within the last two decades, accompanied by asurge in international collaborations. Given the hypothesis of asimilar growth in the activity and dynamics of publications in pediatric anesthesiology, the objective of this scientometric study was to analyze the publication activity and collaboration habits in research in pediatric anesthesiology from Germany, Austria and Switzerland (D-A-CH). This secondary analysis identified all publications on pediatric anesthesiology with an affiliation from the D‑A-CH countries between 2001 and 2020 from PubMed and Web of Science. The query parameters included the timeframe 2001-2020, authors' affiliations tied to anesthesiology departments (using various forms of the term "anesthesia"), and the mention of pediatric interest in titles or abstracts. The data underwent standardization to account for linguistic variations. The publications were assigned to astate, city and institution based on the correspondence address, to ayear based on the publication date and to asource based on the journal. The primary endpoint was publication activity and dynamics, represented by the number of publications and the respective growth rates (calculated as the linear regression slope). Secondary endpoints included the share of collaborations within and outside the D‑A-CH region (at the country and institutional level), the distribution of publication activity and the most prominent sources of publications. Between 2001 and 2020 atotal of 3406 publications on pediatric anesthesiology involving authors from the D‑A-CH countries were identified. Of these 2807 (82.4%) had acorrespondence address in D‑A-CH. The average annual growth rate of publications with acorrespondence address was + 2.9% for the D‑A-CH countries and + 7.7% for publications with collaborations. The number of publications in which an institution from D‑A-CH was named as acoauthor from acorrespondence address outside D‑A-CH also increased by an average of 7.4% per year during the study period. The majority of collaborations occurred between institutions within the D‑A-CH region, although Swiss institutions exhibited amuch higher proportion of collaborations outside the region. Of all publications with acorrespondence address 90% originated from 46cities. The most prominent source was Die Anästhesiologie for publications from Germany, and Pediatric Anesthesia for publications from Austria and Switzerland. The number of publications in pediatric anesthesiology from the D‑A-CH countries has increased over the past two decades, accompanied by asurge in collaborations. It is hoped that increased collaboration will contribute to ahigher level of evidence in pediatric anesthesiology care.

Intercomparison of sensible and latent heat flux measurements from combined eddy covariance, energy balance, and Bowen ratio methods above a grassland prairie

We present a comparison of four different methods of measuring sensible (H) and latent (LE) heat fluxes for a year over a mixed grass prairie ecosystem in the Nebraska SandHills [eddy covariance (EC), energy balance/Bowen ratio (EBBR), residual energy (RES), modified Bowen ratio (MBR) methods]. Additionally, we developed a set of quality control criteria for each method and present a simplification to the traditional EBBR setup. Using EC as reference, all methods yielded similar estimates of yearly H (regression slopes (m) ~ 2% from unity; HEC > HEBBR, HRES, and HMBR). For yearly LE, EBBR and RES yielded similar estimates with EC (m ~ 2% from unity; LEEC < LEEBBR and LERES), while a larger bias was found from MBR (m ~ 8% from unity; LEEC > LEMBR). At shorter time scales (~ hourly), moderate scatter was found about linear regression fits for H between EBBR and EC (R2 = 0.81), with smaller scatter between RES and MBR, and EC (R2 = 0.91). For LE, smaller scatter was also measured between EC, and EBBR and RES (R2 = 0.89 and 0.87, respectively), with the larger scatter between EC and MBR (R2 = 0.65). This suggests methods other than EC may be well suited to longer-term applications (≥ yearly), but have larger uncertainty on individual measurements.

Elevated preoperative lower esophageal sphincter pressure predicts improved clinical outcomes after per oral endoscopic myotomy (POEM).

Although per oral endoscopic myotomy (POEM) has shown to be beneficial forthe treatment ofachalasia, it can be difficult to predict who will have a robust and long-lasting response. Historically, it hasbeen shownthat higher lower esophageal sphincter pressures havebeen associatedwith poorer responses to alternative endoscopic therapies such as Botox therapy and pneumatic dilation. This studywas designedto evaluate if modern preoperative manometric data could similarly predict response totherapyafter POEM. This was a retrospective study of 237 patients who underwent POEM at a single institution over a period of 13years (2011-2023) and who had a high-resolution manometry performed preoperativelyandan Eckardt symptom score performed both preoperative and postoperatively. The achalasia type and integrated relaxation pressures (IRP) were tested for potential correlation with the need for any further achalasia interventions postoperativelyaswell asthe degree of Eckardt score reduction using a linear regression model. The Achalasia type on preoperative manometry was not predictive for further interventions or degree of Eckardt score reduction (p = 0.76 and 0.43, respectively). A higher IRP was not predictive of the need forfurtherinterventions, however, it was predictive of agreaterreduction in postoperative Eckardt scores (p = 0.03)asshown by the non-zero regression slope. In this study, achalasia type was not a predictive factor in the need for further interventions or the degree of symptom relief.Although IRPwas not predictive ofthe need for further interventions, a higher IRPdid predictbetter symptomatic relief postoperatively.This result is opposite that of other endoscopic treatment modalities (Botox and pneumatic dilation). Therefore, patients with higher IRP on preoperative high-resolution manometry would likely benefit from POEMwhichprovides significant symptomatic relief postoperatively.

Causal interpretations of family GWAS in the presence of heterogeneous effects

Family-based genome-wide association studies (GWASs) are often claimed to provide an unbiased estimate of the average causal effects (or average treatment effects; ATEs) of alleles, on the basis of an analogy between the random transmission of alleles from parents to children and a randomized controlled trial. We show that this claim does not hold in general. Because Mendelian segregation only randomizes alleles among children of heterozygotes, the effects of alleles in the children of homozygotes are not observable. This feature will matter if an allele has different average effects in the children of homozygotes and heterozygotes, as can arise in the presence of gene-by-environment interactions, gene-by-gene interactions, or differences in linkage disequilibrium patterns. At a single locus, family-based GWAS can be thought of as providing an unbiased estimate of the average effect in the children of heterozygotes (i.e., a local average treatment effect; LATE). This interpretation does not extend to polygenic scores (PGSs), however, because different sets of SNPs are heterozygous in each family. Therefore, other than under specific conditions, the within-family regression slope of a PGS cannot be assumed to provide an unbiased estimate of the LATE for any subset or weighted average of families. In practice, the potential biases of a family-based GWAS are likely smaller than those that can arise from confounding in a standard, population-based GWAS, and so family studies remain important for the dissection of genetic contributions to phenotypic variation. Nonetheless, their causal interpretation is less straightforward than has been widely appreciated.

Evaluation of the quality of life and the incidence of stress urinary incontinence in nulliparous women training selected sports: a cross-sectional survey pilot study

IntroductionThe number of women suffering from urinary incontinence is increasing every year. The most common type of this condition is stress urinary incontinence. Involuntary leakage of urine occurs when sneezing, coughing, laughing, and standing up, as well as during physical activity. The problem of urinary incontinence is very embarrassing for athletes and affects their sports performance. The aim of the study was to assess the occurrence of urinary incontinence symptoms in women regularly training in selected sports.Methods64 women athletes were selected for the study. This pilot study involved women training in athletics (short-distance running, long-distance running, hurdles and jumping (high jump, long jump, triple jump, pole vault), basketball, volleyball, or strength sports). Women were selected based on sample size calculation from those training in specified clubs. Women who had given birth were excluded from the study. The subjects completed a proprietary questionnaire consisting of 8 questions. They also completed the Urinary Distress Inventory, Short Form (UDI-6SF) questionnaire and the Incontinence Impact Questionnaire, Short Form (IIQ-7).ResultsIn this study, 43% of women who trained had symptoms of urinary incontinence. Regression analysis results with UDI-6SF and IIQ-7 total scores as dependent variables and age as an independent variable showed that the slopes of regression were not statistically significantly different (&lt;i&gt;p&lt;/i&gt;-value &gt; 0.05). The results of the analysis of the correlation between SUI (stress urinary incontinence) and age (&lt;i&gt;p&lt;/i&gt; = 0.0247) and practiced sport (&lt;i&gt;p&lt;/i&gt; = 0.0476) turned out to be statistically significant.ConclusionsThe type of sport practiced affects the occurrence of UI (urinary incontinence) symptoms in women. In this study, female athletes practicing strength sports had the greatest predisposition to the occurrence of UI symptoms. The occurrence of UI symptoms has little impact on the deterioration of the quality of life among women practicing selected sports.

Machine learning models for daily net radiation prediction across different climatic zones of China

Net radiation (Rn), a critical component in land surface energy cycling, is calculated as the difference between net shortwave radiation and longwave radiation at the Earth’s surface and holds significant importance in crop models for precision agriculture management. In this study, we examined the performance of four machine learning models, including extreme learning machine (ELM), hybrid artificial neural networks with genetic algorithm models (GANN), generalized regression neural networks (GRNN), and random forests (RF), in estimating daily Rn at four representative sites across different climatic zones of China. The input variables included common meteorological factors such as minimum and maximum temperature, relative humidity, sunshine duration, and shortwave solar radiation. Model performance was assessed and compared using statistical parameters such as the correlation coefficient (R2), root mean square errors (RMSE), mean absolute errors (MAE), and Nash–Sutcliffe coefficient (NS). The results indicated that all models slightly underestimated actual Rn, with linear regression slopes ranging from 0.810 to 0.870 across different zones. The estimated Rn was found to be comparable to observed values in terms of data distribution characteristics. Among the models, the ELM and GANN demonstrated higher consistency with observed values, exhibiting R2 values ranging from 0.838 to 0.963 and 0.836 to 0.963, respectively, across varying climatic zones. These values surpassed those of the RF (0.809–0.959) and GRNN (0.812–0.949) models. Additionally, the ELM and GANN models showed smaller simulation errors in terms of RMSE, MAE, and NS across the four climatic zones compared to the RF and GRNN models. Overall, the ELM and GANN models outperformed the RF and GRNN models. Notably, the ELM model's faster computational speed makes it a strong recommendation for Rn estimates across different climatic zones of China.

A Statistical Analysis of Drought and Fire Weather Indicators in the Context of Climate Change: The Case of the Attica Region, Greece

As warmer and drier conditions associated with global warming are projected to increase in southern Europe, the Mediterranean countries are currently the most prone to wildfire danger. In the present study, we investigated the statistical relationship between drought and fire weather risks in the context of climate change using drought index and fire weather-related indicators. We focused on the vulnerable and long-suffering area of the Attica region using high-resolution gridded climate datasets. Concerning fire weather components and fire hazard days, the majority of Attica consistently produced values that were moderately to highly anti-correlated (−0.5 to −0.9). This suggests that drier circumstances raise the risk of fires. Additionally, it was shown that the spatial dependence of each variable on the 6-months scale Standardized Precipitation Evapotranspiration Index (SPEI6), varied based on the period and climate scenario. Under both scenarios, an increasing rate of change between the drought index and fire indicators was calculated over future periods versus the historical period. In the case of mean and 95th percentiles of FWI with SPEI6, abrupt changes in linear regression slope values were observed, shifting from lower in the past to higher values in the future periods. Finally, the fire indicators’ future projections demonstrated a tendency towards an increasing fire weather risk for the region’s non-urban (forested and agricultural) areas. This increase was evident from the probability distributions shifting to higher mean and even more extreme values in future periods and scenarios. The study demonstrated the region’s growing vulnerability to future fire incidents in the context of climate change.

Sound Localization in Active Transcutaneous Bone Conduction Implant Users with Single-Sided Deafness.

Evaluate sound localization accuracy of subjects with single-sided deafness (SSD) with active transcutaneous bone conduction implants (atBCIs). Prospective case-control study. Tertiary referral center. Ten SSD patients (with ATBCIS) and 10 controls. Localization was assessed in a semianechoic chamber using a 24-speaker array. Stimuli included broadband noise (BBN) and narrowband noise (NBN). Perceived stimulus angle was recorded and compared with presented location. Statistical analyses were performed using ANOVA and Wilcoxon rank sum tests. The primary outcome measures were as follows: 1) mean angular error (MAE) error (°) and regression slope and 2) subjective benefit assessment (Speech Spatial Qualities questionnaire). Subjects with SSD demonstrated worse localization by MAE and regression slope compared with controls for both broadband noise (p < 0.0001) and narrowband noise at 500 Hz and 1000 kHz (p < 0.0001). There was no statistically significant difference (p = 0.1090) in slope between all groups at 4000 Hz. There was no significant difference in slope or MAE aided compared with unaided. Localization ability varied widely within the SSD cohort, with some individuals showing some ability in the unaided condition, best at 4000 Hz. Although SSQ confirmed particular difficulty in the spatial hearing domain, all domains improved with device use. Localization ability for individuals with SSD falls into a somewhat bimodal distribution. Some have fair localization, particularly at high frequencies, that is preserved but not improved with the atBCI. Others have minimal to no localization ability at any frequency, with no apparent device benefit.

The Relationship Between Anxiety, Depression and Cognitive Functioning in Older Adults: An Exploratory Cross‐Sectional Analysis of Wave 1 Lothian Birth Cohort 1936 Data

ABSTRACTObjectivesTo explore the strength of the association between cognitive functioning and depression and anxiety in older people without dementia.MethodsAn exploratory, cross‐sectional analysis of Wave 1 (2004–2007) data from the Lothian Birth Cohort 1936 dataset. Three subgroups were based on Hospital Anxiety and Depression Scale (HADS) subscales: no probable anxiety or depression (N = 592), probable anxiety no depression (N = 122), probable depression with/without anxiety (depression) (N = 30). Regression analyses determined relationships between subgroups and identified cognitive test variables.ResultsParticipants were 744 individuals (male = 385 [51.5%]; mean [M] age = 69.5 years [Standard deviation = 0.83]); characteristics for subgroups were similar. Participants with probable depression had slower simple reaction time scores than those with no anxiety or depression (regression slope [β] on the log10 scale = 0.05, 95% Confidence Interval [0.03, 0.08], p ≤ 0.001). Those with probable anxiety had significantly worse scores on other tests: Spatial span (β = −0.80 [−1.36, −0.25], p ≤ 0.005), Symbol Search (β = −1.67 [−2.90, −0.45], p ≤ 0.01), Matrix Reasoning (β = −1.58 [−2.55, −0.60], p ≤ 0.005) and Block Design (β = −3.33 [−5.29, −1.37], p ≤ 0.001), than those without probable anxiety or depression.ConclusionProbable depression and anxiety were found to be associated with lower cognitive function in those without evidence of dementia. People with probable anxiety showed poorer performance in tests that concerned making decisions. People with probable depression showed slower processing speed.

Auditory Localization Performance in Cochlear Implant Recipients With Single-Sided Deafness: The Challenges and Limitations of Current Outcome Metrics.

Acoustic localization accuracy metrics currently employed in clinical literature both overestimate and underestimate performance benefit of cochlear implantation (CI) for single-sided deafness (SSD). Although localization in SSD with CI has been investigated, performance characterization has relied heavily on average error. Although attractively concise, this measure may misrepresent performance. Here, we characterize frequency-specific localization on a granular level in subjects with CI for SSD as a critical analysis of localization outcome metrics. Eight CI recipients with SSD were recruited. Stimuli of broadband (BBN) and narrowband noise (NBN) at low (500 Hz), mid (1000 Hz), and high (4000 Hz) frequencies were presented in a semianechoic chamber. Localization accuracy was quantified in mean angular error (MAE) and linear regression slope. Use of a CI for SSD subjects improved localization performance by slope for all stimuli ( p ≤ 0.0033) to a level that was equal to normal-hearing controls at 1 and 4 kHz ( p ≥ 0.2281). MAE was also significantly improved for SSD subjects using CI for BBN stimuli ( p ≪ 0.0001); however, no statistically significant improvement in MAE was seen for NBN ( p ≥ 0.5773) with CI use. Descriptive analysis of individual subject performance highlights the reasons for contradictory results. There is inherent challenge in characterizing localization benefit for individuals with CI for SSD. Our data demonstrate the limitations of utilization of average error as the sole metric for outcome benefit. We emphasize the importance of continued research investigating alternative outcome measures as we work toward a more refined understanding of the potential benefits and limitations of cochlear implantation for SSD.