Critical Value Research Articles

Fixed-point algorithms for solving the critical value and upper tail quantile of Kuiper's statistics

Kuiper's statistic is a good measure for the difference of ideal distribution and empirical distribution in the goodness-of-fit test. However, it is a challenging problem to solve the critical value and upper tail quantile, or simply Kuiper pair, of Kuiper's statistics due to the difficulties of solving the nonlinear equation and reasonable approximation of infinite series. In this work, the contributions lie in three perspectives: firstly, the second order approximation for the infinite series of the cumulative distribution of the critical value is used to achieve higher precision; secondly, the principles and fixed-point algorithms for solving the Kuiper pair are presented with details; finally, finally, a mistake about the critical value cnα for (α,n)=(0.01,30) in Kuiper's distribution table has been labeled and corrected where n is the sample capacity and α is the upper tail quantile. The algorithms are verified and validated by comparing with the table provided by Kuiper. The methods and algorithms proposed are enlightening and worth of introducing to the college students, computer programmers, engineers, experimental psychologists and so on.

Establishing and verifying the threshold value of HLA mixed antigen reagent screening test results

Objective: To establish the threshold value of human leukocyte antigen (HLA) mixed antigen reagent screening test results, and to verify it by HLA single antigen reagent confirmation test results. Methods: The results of 2 255 serum samples tested for HLA antibodies by HLA mixed antigen reagent in the department of HLA Laboratory, the First Affiliated Hospital of Soochow University from October 2017 to December 2021 were retrospectively analyzed. Among them, 1 139 samples were also tested by single antigen HLA Class-Ⅰ reagent and 1 116 samples were also tested by single antigen HLA Class-Ⅱ reagent. Based on the same antigens coated with both reagents, the Mean Fluorescence Intensity (MFI) and Nomalized Background ratio (NBG ratio) of 12 HLA Class-Ⅰ beads and 5 HLA Class-Ⅱ beads in the HLA mixed antigen reagent and the MFI of 77 anti-HLA class-Ⅰ antibodies and 35 anti-HLA class-Ⅱ antibodies detected by HLA single antigen reagent were recorded. The MFI and NBG ratio of HLA mixed antigen reagent beads in 1 139 or 1 116 samples were segmented according to the positive rate of antibodyies detected by the single antigen reagent corresponding to the antigens coated with each HLA mixed antigen reagent bead, and the results of the HLA mixed antigen screening test were verified by the HLA single antigen reagent confirmation test. Results: The threshold values of MFI and NBG ratio of HLA mixed antigen reagent's 17 beads were established. The MFI of No. 1 to No. 17 beads of HLA mixed antigen reagent ranged from 26.86 to 21 925.58, and the NBG ratio ranged from 0 to 434.65. According to the positive detection rate of HLA single antigen reagent corresponding to the coated antigens, the MFI and NBG ratio of the beads of HLA mixed antigen reagent were divided into positive interval, suspicious positive interval, suspicious negative interval and negative interval. The positive rates of anti-HLA class-Ⅰ antibodies by HLA mixed antigen reagent and single antigen HLA Class-Ⅰ reagent were 87.5% (997/1 139) and 66.3% (755/1 139). The positive rates of anti-HLA class-Ⅱ antibodies were 63.4% (707/1 116) and 44.9% (501/1 116). In the samples with suspicious negative, suspicious positive and positive results of HLA class-Ⅰ、Ⅱ antibodies detected by HLA mixed antigen reagent, the positive detection rates of single antigen HLA Class-Ⅰ reagent were 14.9% (17/114), 41.3% (145/351) and 91.3% (590/646), respectively. The positive detection rates of single antigen HLA Class-Ⅱ reagent were 15.5% (58/375), 26.5% (81/306) and 88.8% (356/401), respectively. Conclusions: In this study, the threshold values of MFI and NBG ratio of HLA mixed antigen reagent screening test are established, and the threshold values are verified by the results of HLA single antigen reagent confirmation test. HLA mixed reagent screening test can be used for screening of HLA antibodies, and if necessary, it should be combined with HLA single antigen confirmatory test for clinical detection of HLA antibodies.

Interview with James R. Kincaid, an English professor masquerading as an author (or the other way around)

ABSTRACT In this interview with a senior Victorianist, James R. Kincaid, Aerol Arnold Professor Emeritus of English at the University of Southern California, reflects on his life and what led him to a career as a professor of literature and the value and appeal of literary criticism. He comments on his major books, his other writing, and on authors Charles Dickens and Lewis Carroll as well as the academic world during his distinguished long career.

Prognostic Implications of Left Atrial Strain in Bicuspid Aortic Valve With Chronic Aortic Regurgitation.

Left atrial reservoir strain (LARS) is a novel imaging biomarker of left ventricular diastolic dysfunction. This study aimed to examine the prognostic implications of LARS in patients with bicuspid aortic valve and significant (moderate-severe to severe) aortic regurgitation. A total of 220 patients with bicuspid aortic valve and significant aortic regurgitation were prospectively enrolled in our study. LARS and left ventricular global longitudinal strain were derived from speckle-tracking echocardiography. The end point was a composite of all-cause mortality, heart failure hospitalization, and aortic valve repair or replacement. The threshold value of LARS <24% was used to identify impaired left atrial mechanics based on prior results. During a median follow-up of 364 (interquartile range, 294-752) days, 46 patients (20.9%) reached the composite end points. On multivariable Cox analysis, impaired LARS (adjusted hazard ratio, 2.08 [95% CI, 1.05-4.11]; P=0.036) was a statistically significant predictor of composite end points after adjustment for other statistically significant predictors. Finally, adding impaired LARS to other statistically significant predictors (New York Heart Association functional class and left ventricular global longitudinal strain) significantly improved the global χ2 (from 32.19 to 36.56; P=0.037) and reclassification (continuous net reclassification index=0.55; P<0.001) of the prediction model. In patients with bicuspid aortic valve and significant aortic regurgitation, the impairment of LARS is a strong independent prognostic predictor and confers incremental prognostic utility over clinical and other echocardiographic parameters. These findings suggest that LARS could be considered in risk stratification for such populations.

Factors Associated with Persistent Efficacy of Abrocitinib without Flare: A Multivariable Analysis of the JADE-REGIMEN Study

Introduction: JADE REGIMEN (NCT03627767) was conducted to evaluate the feasibility of continual, reduced dose or withdrawal of abrocitinib after induction of response in patients with moderate-to-severe atopic dermatitis (AD). This post hoc analysis evaluated patient factors associated with a higher probability of persistent clinical response with abrocitinib, without flare, during a 40-week maintenance period.Methods: Data were analyzed from patients who responded to abrocitinib 200 mg induction therapy (12 weeks) and were randomly assigned to receive abrocitinib (200 or 100 mg) or placebo in the maintenance period (40 weeks). A multivariable logistic regression model with fixed and random effects was fit to determine factors associated with not experiencing flare by week 52. Fixed effects (factors) considered were randomly allocated treatment, age (&lt;18 vs ≥18 years), race, weight, prior use of systemic agents, AD duration, onset of response in induction (early vs late), Investigator’s Global Assessment score at randomization, body surface area (BSA, ≤50% vs &gt;50%) at baseline, and percentage change in Eczema Area and Severity Index (EASI) at randomization. Backward elimination and stepwise model selection procedures were applied with entry and exit criteria based on a P value threshold of 5%.Results:1233 patients received abrocitinib 200 mg in the induction period. By week 12, 798 (64.7%) achieved a response and were randomly assigned to receive maintenance treatment for 40 weeks. In total, 356 patients (44.6%) experienced a protocol-defined flare: 16.5% (200 mg), 39.6% (100 mg), and 77.5% (placebo). After model selection, the analysis identified continuation of treatment with abrocitinib 200 mg (odds ratio [OR], 19.51; 95% CI, 11.28-33.75) or reduced-dose abrocitinib 100 mg (5.27; 3.29-8.46) as the greatest predictors of not experiencing flare during maintenance. Not having previously used systemic agents (OR, 1.53; 95% CI, 1.09-2.14), lower baseline BSA (1.55; 1.10-2.17), and greater percentage reduction of EASI during induction (1.35; 1.15-1.59) were also associated with not experiencing flare.Conclusions: Multivariable analysis of JADE REGIMEN indicated that maintenance treatment with abrocitinib in patients with AD reduced the risk for flare in a dose-dependent manner. Other factors associated with maintaining response to treatment without flare included no previous exposure to systemic agents, lower extent of BSA involvement at baseline, and greater percent change in EASI during induction. These findings may assist clinicians with abrocitinib dosing decisions in the future.

Predictive Value of Global Longitudinal Strain on the Recovery of Left Ventricular Function Following ST-Segment Elevation Myocardial Infarction

Background: Identifying reliable predictors for ventricular recovery at the outset is crucial for patients with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). Objectives: This study aimed to evaluate the role of baseline global longitudinal strain (GLS) in predicting myocardial recovery following an acute infarction. Methods: We enrolled 60 consecutive patients diagnosed with STEMI and admitted to Al-Zahra Hospital for PCI from March 2022 to March 2023. Echocardiography was performed on all patients within 48 hours after revascularization to measure baseline parameters, including left ventricular ejection fraction (LVEF) and GLS. Follow-up echocardiography was conducted 6 months later to reassess LVEF. Results: At the 6-month follow-up, 38 (63.3%) patients showed a ≥ 5% improvement in LVEF, indicating ventricular recovery. The change in GLS was significantly different between the groups (recovered: -4.72 ± 2.00, not recovered: -2.41 ± 2.15, P &lt; 0.001). A baseline GLS ≤ -4.5 and &gt; -14.8 was predictive of either failure to recover or successful recovery of LVEF with 100% negative and positive predictive values, respectively. Baseline GLS values &gt; -9.2 were predictive of LV recovery with 50% sensitivity and 83.3% specificity (P = 0.0002, AUC (95% confidence interval) = 0.697 (0.594, 0.799)). The type of revascularization was linked to better prediction outcomes, with patients undergoing primary and rescue PCIs more likely to recover during the follow-up period compared to those receiving deferred PCI after 24 hours (P = 0.032). Conclusions: While certain baseline GLS value thresholds may serve as predictors of LVEF recovery in patients with STEMI undergoing primary PCI, further prospective studies with larger cohorts are needed to establish more precise cut-off values.

Rayleigh–Bénard Convection With Multiple Solutions in Trapezoidal Closed Cavities

Abstract Rayleigh–Bénard convection (RBC) in symmetric trapezoidal closed cavities with cavity angle ϕ=70°−110°, filled with air, is studied using numerical simulations where inclined side walls are adiabatic. In contrast to rectangular cavities, where no flow exists below a threshold value, there is a weak convection even at a low Rayleigh number (Ra) due to the fact that there is a component of thermal gradient in the horizontal direction in these cavities. Interestingly, these cavities show sudden and significant jumps in the convection, similar to square cavities (Rac = 2585.02 for ϕ=90°), as Ra increases beyond a critical value (Rac). It is noted here that these Rac represent symmetry-breaking pitchfork bifurcations. These bifurcations are seen in both acute (Rac = 8000 for ϕ=70°) and obtuse (Rac = 2300 for ϕ=110°) angle trapezoidal cavities. Moreover, it is observed that multiple steady-state solutions (MSSS) exist as Ra is further increased. A forward and backward continuation approach for numerical simulations is used to track the co-existence of MSSS. These steady-states have co-existing one-roll and two-roll convective patterns beyond another threshold value of Ra. Here, two types of critical Ra have been identified for different cavity angles; one shows the sudden jump in the convection, and the other is the one beyond which MSSS co-exist. Furthermore, a codimension two bifurcation analysis is carried out with Ra and ϕ as two parameters. The bifurcation analysis divides the parameter space into different regions based on the multiplicity of the solutions.

Detection of SARS-CoV-2 variants distributed from March 2020 to May 2022 and their effect on the infection severity in Iraqi population

New SARS-CoV-2 variants appeared in late December 2020 as Mutations accumulated in the original virus. This study aimed to provide a local database about variants of COVID-19 circulating in the Iraqi population from 2020 to 2022 and the time of emergence of new strains each month since very few local studies have documented its existence in the country. Real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assays were employed to 319 collected and analyzed nasal swabs to determine whether an infection had occurred. A sophisticated diagnostic kit that sorted the distinctive mutations was implemented to evaluate the variants. Results showed Younger patients were more likely to be infected with the Alpha variant (66 patients) than older people (43 patients). Additionally, patients with wild-type infestations had more robust viral load and lower Ct threshold values, culminating in an increase in severity during infection with wild-type virus 26/32 (81.250). Meanwhile, 65/109(59.63%) of patients infected with the Alpha variant developed severe and critical illness and 51/84(60.71%)were infected with Delta or Delta plus variants. In conclusion, the Alpha variant had the highest infection percentage of 109(46.6%), followed by Delta or Delta plus variant 84(26.33%), Beta or Gamma variants 47(20.1%), Omicron variant 46(19.6%), and finally wild-type virus of 32(13.7%). February 2020 witnessed a preliminary finding of the wild-type, while the Alpha variant emerged in December 2020, Beta/Gamma variances were recognized in December 2020, Delta/Delta plus variances began in April 2021, and the Omicron variant debuted in March 2022. Keywords: SARS-CoV-2, Mutation, rRT-PCR, Coronavirus disease 2019, TaqPath, cycle threshold (Ct) value

Wavelength-induced shedding frequency modulation of seal whisker inspired cylinders

The spanwise undulated cylinder geometry inspired by seal whiskers has been shown to alter shedding frequency and reduce fluid forces significantly compared to smooth cylindrical geometry. Prior research has parameterized the whisker-inspired geometry and demonstrated the relevance of geometric variations on force reduction properties. Among the geometric parameters, undulation wavelength was identified as a significant contributor to forcing changes. To analyze the effect of undulation wavelength, a thorough investigation isolating changes in wavelength is performed to expand upon previous research that parameterized whisker-inspired geometry and the relevance of geometric variations on the force reduction properties. A set of five whisker-inspired models of varying wavelength are computationally simulated at a Reynolds number of 250 and compared with an equivalent aspect ratio smooth elliptical cylinder. Above a critical non-dimensional value, the undulation wavelength reduces the amplitude and frequency of vortex shedding accompanied by a reduction in oscillating lift force. Frequency shedding is tied to the creation of wavelength-dependent vortex structures which vary across the whisker span. These vortices produce distinct shedding modes in which the frequency and phase of downstream structures interact to decrease the oscillating lift forces on the whisker model with particular effectiveness around the wavelength values typically found in nature. The culmination of these location-based modes produces a complex and spanwise-dependent lift frequency spectra at those wavelengths exhibiting maximum force reduction. Understanding the mechanisms of unsteady force reduction and the relationship between undulation wavelength and frequency spectra is critical for the application of this geometry to vibration tuning and passive flow control for vortex-induced vibration (VIV) reduction.

Effect of Deformation Degree on Microstructure and Properties of Ni-Based Alloy Forgings

The primary objective of this paper is to investigate the influence of deformation degree on the microstructure and properties of a Ni-based superalloy. An upsetting experiment was conducted using a free-forging hammer to achieve a deformation degree ranging from 60% to 80%. The impact of the forging deformation degree on the hardness and high-temperature erosion performance was evaluated using the Rockwell hardness tester (HRC) and high-temperature erosion tester, respectively. The experimental results indicate that as the deformation degree increased, the hardness of the forged material progressively increased while the rate of high-temperature erosion gradually decreased. In order to comprehensively study the mechanism behind the variations in forging performance, optical microscopy (OM), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM) were employed. The findings reveal that as the deformation degree increased, the presence of small-angle grain boundaries and an increase in grain boundary area contributed to enhanced hardness in the alloy forgings. Furthermore, it was discovered that grain boundaries with twin orientation promoted dynamic recrystallization during deformation, specifically through a discontinuous dynamic recrystallization mechanism. Additionally, the precipitated γ′ phase in the alloy exhibited particle sizes ranging from 40 to 100 nm. This particle size range resulted in a higher critical shear stress value and a more pronounced strengthening effect on the alloy.

Correlation analysis between combined deflection angle and osteonecrosis of femoral head after femoral neck fracture

To evaluate the correlation between pelvic incidence (PI) angle, hip deflection angle (HDA), combined deflection angle (CDA) and osteonecrosis of the femoral head (ONFH) after femoral neck fracture, in order to explore early predictive indicators for ONFH occurrence after femoral neck fracture. A study was conducted on patients with femoral neck fractures who underwent cannulated screw internal fixation between December 2018 and December 2020. Among them, 208 patients met the selection criteria and were included in the study. According to the occurrence of ONFH, the patients were allocated into ONFH group and non-NOFH group. PI, HDA, and CDA were measured based on the anteroposterior X-ray films of pelvis and axial X-ray films of the affected hip joint before operation, and the differences between the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the value of the above imaging indicators in predicting the occurrence of ONFH. Among the 208 patients included in the study, 84 patients experienced ONFH during follow-up (ONFH group) and 124 patients did not experience ONFH (non-ONFH group). In the non-ONFH group, there were 59 males and 65 females, the age was 18-86 years (mean, 53.9 years), and the follow-up time was 18-50 months (mean, 33.2 months). In the ONFH group, there were 37 males and 47 females, the age was 18-76 years (mean, 51.6 years), and the follow-up time was 8-45 months (mean, 22.1 months). The PI, HDA, and CDA were significantly larger in the ONFH group than in the non-ONFH group ( P<0.05). ROC curve analysis showed that the critical value of PI was 19.82° (sensitivity of 40.5%, specificity of 86.3%, P<0.05); the critical value of HDA was 20.94° (sensitivity of 77.4%, specificity of 75.8%, P<0.05); and the critical value of CDA was 39.16° (sensitivity of 89.3%, specificity of 83.1%, P<0.05). There is a correlation between PI, HDA, CDA and the occurrence of ONFH after femoral neck fracture, in which CDA can be used as an important reference indicator. Patients with CDA≥39.16° have a higher risk of ONFH after femoral neck fracture.

The Physics behind Precipitation Onset Bias in CMIP6 Models: The Pseudo-Entrainment Diagnostic and Trade-Offs between Lapse Rate and Humidity

Abstract Conditional instability and the buoyancy of plumes drive moist convection but have a variety of representations in model convective schemes. Vertical thermodynamic structure information from Atmospheric Radiation Measurement (ARM) sites and reanalysis (ERA5), satellite-derived precipitation (TRMM3b42), and diagnostics relevant for plume buoyancy are used to assess climate models. Previous work has shown that CMIP6 models represent moist convective processes more accurately than their CMIP5 counterparts. However, certain biases in convective onset remain pervasive among generations of CMIP modeling efforts. We diagnose these biases in a cohort of nine CMIP6 models with subdaily output, assessing conditional instability in profiles of equivalent potential temperature, θe, and saturation equivalent potential temperature, θes, in comparison to a plume model with different mixing assumptions. Most models capture qualitative aspects of the θes vertical structure, including a substantial decrease with height in the lower free troposphere associated with the entrainment of subsaturated air. We define a “pseudo-entrainment” diagnostic that combines subsaturation and a θes measure of conditional instability similar to what entrainment would produce under the small-buoyancy approximation. This captures the trade-off between larger θes lapse rates (entrainment of dry air) and small subsaturation (permits positive buoyancy despite high entrainment). This pseudo-entrainment diagnostic is also a reasonable indicator of the critical value of integrated buoyancy for precipitation onset. Models with poor θe/θes structure (those using variants of the Tiedtke scheme) or low entrainment runs of CAM5, and models with low subsaturation, such as NASA-GISS, lie outside the observational range in this diagnostic.

Prognostic factors among patients with pathological Grade Group 5 prostate cancer based on robot-associated radical prostatectomy specimens from a large Japanese cohort (MSUG94).

There are no definitive prognostic factors for patients with pathological Grade Group 5 (pGG 5) prostate cancer (PCa) undergoing robot-associated radical prostatectomy (RARP). This study aimed to explore the prognostic factors among patients with pGG 5 PCa in a large Japanese cohort (MSUG94). This retrospective, multi-institutional cohort study was conducted between 2012 and 2021 at ten centers in Japan and included 3195 patients. Patients with clinically metastatic PCa (cN1 or cM1) and those receiving neoadjuvant and/or adjuvant therapy were excluded. Finally, 217 patients with pGG5 PCa were analyzed. The median follow-up period was 28.0months. The 3- and 5-year biochemical recurrence-free survival (BCRFS) rates of the overall population were 66.1% and 57.7%, respectively. The optimal threshold value (47.2%) for the percentage of positive cancer cores (PPCC) with any GG by systematic biopsy was chosen based on receiver operating characteristic curve analysis. Univariate analysis revealed that the prostate-specific antigen level at diagnosis, pT, pN, positive surgical margins (PSMs), lymphovascular invasion, and PPCC were independent prognostic factors for BCRFS. A multivariate analysis revealed that PSMs and PPCC were independent prognostic factors for BCRFS. Using these two predictors, we stratified BCRFS, metastasis-free survival (MFS), and castration-resistant PCa-free survival (CRPC-FS) among patients with pGG 5 PCa. The combination of PSMs and PPCC may be an important predictor of BCRFS, MFS, and CRPC-FS in patients with pGG 5 PCa undergoing RARP.

The timber complex of the Russian Federation: Formation of priority areas of import substitution

Subject. This article discusses the problems of development of the domestic market of forest products and technological modernization of timber complex enterprises. Objectives. The article aims to develop measures to reduce the dependence of Russian timber complex enterprises on imports. Methods. For the study, I used generalization, analogy, comparative and systems analyses. Results. The article finds that in 2023, the dependence of timber complex enterprises on imports has reached critical values and it proposes measures necessary to support the industry. Conclusions. Despite some positive trends related to meeting the needs of the domestic market for forest products, in the long term the industry will need to solve the problems caused by the technological lag behind developed countries.

The Size Differences of Breast Cancer and Benign Tumors Measured by Two-Dimensional Ultrasound and Contrast-Enhanced Ultrasound.

Ultrasound (US) imaging has been observed to underestimate tumor size in clinical practice. This study aims to compare the size measurements of breast cancer and benign tumors using two-dimensional ultrasound (2DUS) and contrast-enhanced ultrasound (CEUS). The study included 42 clinically confirmed breast cancer and 47 benign breast tumors. Two experienced physicians independently measured the maximal longitudinal and transverse diameters of the masses in 2DUS and CEUS. All analyses were performed in R (4.2.2) and GraphPad Prism 6. The maximal longitudinal and transverse diameters of breast cancer measured by CEUS were 26.61 ± 0.21% and 26.24 ± 0.19% larger compared with 2DUS, and benign breast tumors had an 11.74 ± 0.21% and 11.06 ± 0.14% increase in size compared with 2DUS. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) for the difference between 2DUS and CEUS was 0.870 for longitudinal diameters (95% CI: 0.795-0.945, sensitivity 0.842, specificity 0.783, threshold value 0.215), and 0.863 for transverse diameters (95% CI: 0.785-0.942, sensitivity 0.667, specificity 0.936, threshold value 0.203). The size measurements of both breast cancer and benign tumors were larger in CEUS compared with 2DUS, with CEUS measurements of breast cancer being more pronounced than those of benign breast tumors. These findings suggest that CEUS may provide a more precise assessment of tumor size, which is crucial for determining optimal treatment strategies and improving patient outcomes in breast cancer management.

Biomechanical Threshold Values for Identifying Clinically Significant Knee-Related Symptoms Six Months Following Anterior Cruciate Ligament Reconstruction.

Slower habitual walking speed and aberrant gait biomechanics are linked to clinically significant knee-related symptoms and articular cartilage composition changes linked to posttraumatic osteoarthritis (PTOA) following anterior cruciate ligament reconstruction (ACLR). To determine specific gait biomechanical variables that can accurately identify individuals with clinically significant knee-related symptoms post-ACLR, and the corresponding threshold values, sensitivity, specificity, and odds ratios for each biomechanical variable. Cross-sectional analysis. Laboratory. Seventy-one individuals (n=38 female; age=21±4 years; height=1.76±0.11 m; mass=75.38±13.79 kg) who were 6 months post-primary unilateral ACLR (6.2±0.4 months). 3D motion capture of 5 overground walking trials was used to calculate discrete gait biomechanical variables of interest during stance phase (1st and 2nd peak vertical ground reaction force [vGRF]; midstance minimum vGRF; peak internal knee abduction and extension moments; and peak knee flexion angle), along with habitual walking speed. Knee Injury and Osteoarthritis Outcome Scores (KOOS) was used to dichotomize patients as symptomatic (n=51) or asymptomatic (n=20) using the Englund et al. 2003 KOOS guidelines for defining clinically significant knee-related symptoms. Separate receiver operating characteristic (ROC) curves and respective areas under the curve (AUC) were used to evaluate the capability of each biomechanical variable of interest for identifying individuals with clinically significant knee-related symptoms. Habitual walking speed (AUC=0.66), vGRF at midstance (AUC=0.69), and 2nd peak vGRF (AUC=0.76), demonstrated low-to-moderate accuracy for identifying individuals with clinically significant knee-related symptoms. Individuals who exhibited habitual walking speeds ≤1.27 m/s, midstance vGRF ≥0.82 BW, and 2nd peak vGRF ≤1.11 BW, demonstrated 3.13, 6.36, and 9.57 times higher odds of experiencing clinically significant knee-related symptoms, respectively. Critical thresholds for gait variables may be utilized to identify individuals with increased odds of clinically significant knee-related symptoms and potential targets for future interventions.

PUM1 and PGK1 are Favorable Housekeeping Genes over Established Biodosimetry-related Housekeeping Genes such as HPRT1, ITFG1, DPM1, MRPS5, 18S rRNA and Others after Radiation Exposure.

In gene expression (GE) studies, housekeeping genes (HKGs) are required for normalization purposes. In large-scale inter-laboratory comparison studies, significant differences in dose estimates are reported and divergent HKGs are employed by the teams. Among them, the 18S rRNA HKG is known for its robustness. However, the high abundance of 18S rRNA copy numbers requires dilution, which is time-consuming and a possible source of errors. This study was conducted to identify the most promising HKGs showing the least radiation-induced GE variance after radiation exposure. In the screening stage of this study, 35 HKGs were analyzed. This included selected HKGs (ITFG1, MRPS5, and DPM1) used in large-scale biodosimetry studies which were not covered on an additionally employed pre-designed 96-well platform comprising another 32 HKGs used for different exposures. Altogether 41 samples were examined, including 27 ex vivo X-ray irradiated blood samples (0, 0.5, 4 Gy), six X-irradiated samples (0, 0.5, 5 Gy) from two cell lines (U118, A549), as well as eight non-irradiated tissue samples to encompass multiple biological entities. In the independent validation stage, the most suitable candidate genes were examined from another 257 blood samples, taking advantage of already stored material originating from three studies. These comprise 100 blood samples from ex vivo X-ray irradiated (0-4 Gy) healthy donors, 68 blood samples from 5.8 Gy irradiated (cobalt-60) Rhesus macaques (RM) (LD29/60) collected 0-60 days postirradiation, and 89 blood samples from chemotherapy-(CTx) treated breast tumor patients. CTx and radiation-induced GE changes in previous studies appeared comparable. RNA was isolated, converted into cDNA, and GE was quantified employing TaqMan assays and quantitative RT-PCR. We calculated the standard deviation (SD) and the interquartile range (IQR) as measures of GE variance using raw cycle threshold (Ct) values and ranked the HKGs accordingly. Dose, time, age, and sex-dependent GE changes were examined employing the parametrical t-test and non-parametrical Kruskal Wallis test, as well as linear regression analysis. Generally, similar ranking results evolved using either SD or IQR GE measures of variance, indicating a tight distribution of GE values. PUM1 and PGK1 showed the lowest variance among the first ten most suitable genes in the screening phase. MRPL19 revealed low variance among the first ten most suitable genes in the screening phase only for blood and cells, but certain comparisons indicated a weak association of MRPL19 with dose (P = 0.02-0.09). In the validation phase, these results could be confirmed. Here, IQR Ct values from, e.g., X-irradiated blood samples were 0.6 raw Ct values for PUM1 and PGK1, which is considered to represent GE differences as expected due to methodological variance. Overall, when compared, the GE variance of both genes was either comparable or lower compared to 18S rRNA. Compared with the IQR GE values of PUM1 and PGKI, twofold-fivefold increased values were calculated for the biodosimetry HKG HPRT1, and comparable values were calculated for biodosimetry HKGs ITFG1, MRPS5, and DPM1. Significant dose-dependent associations were found for ITFG1 and MRPS5 (P = 0.001-0.07) and widely absent or weak (P = 0.02-0.07) for HPRT1 and DPM1. In summary, PUM1 and PGK1 appeared most promising for radiation exposure studies among the 35 HKGs examined, considering GE variance and adverse associations of GE with dose.

Apparent diffusion coefficient values predict response to brachytherapy in bulky cervical cancer

BackgroundDiffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer.MethodsClinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden’s J statistic was used to identify a threshold value.ResultsAmong 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10− 3 mm2/s were 5.33 (95% CI, 1.35–24.4) times more likely to achieve CMR.ConclusionsClinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer.

Logistic analysis of delayed reporting of emergency blood potassium and comparison of improved outcomes

Potassium testing is an essential test in emergency medicine. Turnaround time (TAT) is the time between specimen receipt by the laboratory and the release of the test report. A brief in-laboratory TAT increases emergency department effectiveness. Optimizing processes to shorten TAT using other tools requires extensive time, resources, training, and support. Therefore, we aimed to find a convenient way to shorten TAT, identify risk factors affecting the timeliness of emergency potassium test reporting, and verify the intervention’s effects. The dependent variable was emergency potassium reporting time > 30 or < 30 min. Logistic analysis was performed on monitorable factors, such as sex, age, potassium results, number of items, specimen processing time (including centrifugation and time before specimen loading), critical value ratio, instrument status, shift where the report was issued, specimen status, and work experience, as independent variables. In the multivariate analysis, work experience, instrument failure rate, and specimen processing time were risk factors for emergency blood potassium reporting exceeding 30 min. Improvement measures were implemented, significantly decreasing the timeout rate for acute potassium reporting. Our study confirms the usefulness of logistics in reducing the time required to report potassium levels in the emergency department, providing a new perspective on quality management.

Programmable Threshold Logic Implementations in a Memristor Crossbar Array.

In this study, we demonstrate the implementation of programmable threshold logics using a 32 × 32 memristor crossbar array. Thanks to forming-free characteristics obtained by the annealing process, its accurate programming characteristics are presented by a 256-level grayscale image. By simultaneous subtraction between weighted sum and threshold values with a differential pair in an opposite way, 3-input and 4-input Boolean logics are implemented in the crossbar without additional reference bias. Also, we verify a full-adder circuit and analyze its fidelity, depending on the device programming accuracy. Lastly, we successfully implement a 4-bit ripple carry adder in the crossbar and achieve reliable operations by read-based logic operations. Compared to stateful logic driven by device switching, a 4-bit ripple carry adder on a memristor crossbar array can perform more reliably in fewer steps thanks to its read-based parallel logic operation.