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Campylobacter jejuni is one of the leading causes of foodborne illness worldwide. C. jejuni is commonly found in poultry. It is the most frequent cause of contamination and thus resulting in not only public health concerns but also economic impacts. To test for this bacterial contamination in food processing plants, this study attempted to employ a simple and rapid detection assay called loop-mediated isothermal amplification (LAMP). The best cutoff value for the positive determination of C. jejuni calculated using real-time LAMP quantification cycle (Cq) was derived from the receiver operating characteristic (ROC) curve modeling. The model showed an area under curve (AUC) of 0.936 (95% Wald CI: 0.903–0.970). Based on Youden's J statistic, the optimal cutoff value which had the highest sensitivity and specificity from the model was calculated as 18.07. The LAMP assay had 96.9% sensitivity, 95.8% specificity, and 93.9 and 97.9% positive and negative predictive values, respectively, compared to a standard culture approach for C. jejuni identification. Among all non-C. jejuni strains, the LAMP assay gave each of 12.5% false-positive results to C. coli and E. coli (1 out of 8 samples). The assay can detect C. jejuni at the lowest concentration of 103 CFU/mL. Our results suggest a preliminary indicator for the application of end-point LAMP assays, such as turbidity and UV fluorescence tests, to detect C. jejuni in field operations. The LAMP assay is an alternative screening test for C. jejuni contamination in food samples. The method provides a rapid detection, which requires only 9 min with a cutoff value of Cq. We performed the extraction of DNA from pure cultures and the detection of C. jejuni using the LAMP assay within 3 h. However, we were not able to reduce the time for the process of enrichment involved in our study. Therefore, we suggest that alternative enrichment media and rapid DNA extraction methods should be considered for further study. Compared to other traditional methods, our proposed assay requires less equipment and time, which is applicable at any processing steps in the food production chain. [ABSTRACT FROM AUTHOR]

In a recent breakthrough, Teyssier (Ann Probab 48(5):2323–2343, 2020) introduced a new method for approximating the distance from equilibrium of a random walk on a group. He used it to study the limit profile for the random transpositions card shuffle. His techniques were restricted to conjugacy-invariant random walks on groups; we derive similar approximation lemmas for random walks on homogeneous spaces and for general reversible Markov chains. We illustrate applications of these lemmas to some famous problems: the k-cycle shuffle, sharpening results of Hough (Probab Theory Relat Fields 165(1–2):447–482, 2016) and Berestycki, Schramm and Zeitouni (Ann Probab 39(5):1815–1843, 2011), the Ehrenfest urn diffusion with many urns, sharpening results of Ceccherini-Silberstein, Scarabotti and Tolli (J Math Sci 141(2):1182–1229, 2007), a Gibbs sampler, which is a fundamental tool in statistical physics, with Binomial prior and hypergeometric posterior, sharpening results of Diaconis, Khare and Saloff-Coste (Stat Sci 23(2):151–178, 2008). [ABSTRACT FROM AUTHOR]

We aimed to predict subsequent gestational diabetes mellitus (GDM) by fasting plasma glucose (FPG) in the first trimester. Healthy pregnant women who were screened for GDM at 24–28 gestational weeks and had FPG levels calculated during their first antenatal visit and less than 14 gestational weeks were included in this study. Of the 2605 women who were recruited for the study, 245 (9.4%) were diagnosed with GDM at weeks 24–28. The diagnostic accuracy for FPG predicting GDM was 66.5, 78.4, and 88.2 for the cutoff values of 87.5 mg/dl, 92 mg/dl, and 99.5 mg/dl, respectively. FPG values which are within the normoglycaemic range constitute an independent risk factor for the development of GDM. The threshold for gestational diabetes diagnosis must be revised. [ABSTRACT FROM AUTHOR]

The earliest formulation of the Higgs naturalness argument has been criticized on the grounds that it relies on a particular cutoff-based regularization scheme. One response to this criticism has been to circumvent the worry by reformulating the naturalness argument in terms of a renormalized, regulator-independent parametrization. An alternative response is to deny that regulator dependence poses a problem for the naturalness argument, because nature itself furnishes a particular, physically correct regulator for any effective field theory (EFT) in the form of that EFT’s physical cutoff, together with an associated set of bare parameters that constitute the unique physically preferred “fundamental parameters” of the EFT. Here, I argue that both lines of defense against the initial worry about regulator dependence are flawed. I argue that reformulation of the naturalness argument in terms of renormalized parameters simply trades dependence on a particular regularization scheme for dependence on a particular renormalization scheme, and that one or another form of scheme dependence afflicts all formulations of the Higgs naturalness argument. Concerning the second response, I argue that the grounds for suspending the principle of regularization or renormalization scheme independence in favor of a physically preferred parametrization are thin; the assumption of a physically preferred parametrization, whether in the form of bare “fundamental parameters” or renormalized “physical parameters,” constitutes a theoretical idle wheel in generating the confirmed predictions of established EFTs, which are invariably scheme-independent. I highlight certain features of the alternative understanding of EFTs, and the EFT-based approach to understanding the foundations of QFT, that emerges when one abandons the assumption of a physically preferred parametrization. I explain how this understanding departs from several dogmas concerning the mathematical formulation and physical interpretation of EFTs in high-energy physics. [ABSTRACT FROM AUTHOR]

Background: Fecal immunochemical testing (FIT) is an established method for colorectal cancer (CRC) screening. Measured FIT-concentrations are associated with both present and future risk of CRC, and may be used for personalized screening. However, evaluation of personalized screening is computationally challenging. In this study, a broadly applicable algorithm is presented to efficiently optimize personalized screening policies that prescribe screening intervals and FIT-cutoffs, based on age and FIT-history. Methods: We present a mathematical framework for personalized screening policies and a bi-objective evolutionary algorithm that identifies policies with minimal costs and maximal health benefits. The algorithm is combined with an established microsimulation model (MISCAN-Colon), to accurately estimate the costs and benefits of generated policies, without restrictive Markov assumptions. The performance of the algorithm is demonstrated in three experiments. Results: In Experiment 1, a relatively small benchmark problem, the optimal policies were known. The algorithm approached the maximum feasible benefits with a relative difference of 0.007%. Experiment 2 optimized both intervals and cutoffs, Experiment 3 optimized cutoffs only. Optimal policies in both experiments are unknown. Compared to policies recently evaluated for the USPSTF, personalized screening increased health benefits up to 14 and 4.3%, for Experiments 2 and 3, respectively, without adding costs. Generated policies have several features concordant with current screening recommendations. Discussion: The method presented in this paper is flexible and capable of optimizing personalized screening policies evaluated with computationally-intensive but established simulation models. It can be used to inform screening policies for CRC or other diseases. For CRC, more debate is needed on what features a policy needs to exhibit to make it suitable for implementation in practice. [ABSTRACT FROM AUTHOR]

Background: The electrocardiographic diagnosis of acute myocardial infarction (AMI) in the setting of cardiac pacing is often challenging. The original Sgarbossa criteria proposed in 1996 were demonstrated to be valid for diagnosis of AMI in both ventricular paced rhythm and left bundle branch block. To improve accuracy, the modified Sgarbossa criteria (MSC) were proposed.Case Presentation: We presented a case of electrocardiographic diagnosis of AMI in a pacemaker patient. The Electrocardiogram (ECG) was false negative by using the original Sgarbossa criteria, whereas true positive by the MSC at a ratio of - 0.20.Conclusions: The application of MSC using an appropriate ratio (- 0.20 or - 0.25) may facilitate a timely diagnosis of AMI. Physicians should carefully choose the appropriate cutoff in a case-by-case basis. [ABSTRACT FROM AUTHOR]

Human growth hormone (hGH) provocation test is an essential tool to assess growth hormone deficiency (GHD) in children and young adults. It is important to have a robust method to determine the hGH peak of stimulation. This work aimed to compare three common automated immunoassays for hGH quantification and to ascertain whether there are still result-related differences which can impact clinical decision. We analyzed the GH provocation test for 39 young subjects from pediatric department of Montpellier hospital, admitted for suspicion of growth hormone deficiency. The full range of measurements as well as the peak level of serum GH were compared using three automated immunoassays on three different immunoanalyzers: IDS-hGH on iSYS, LIAISON-hGH on Liaison XL and Elecsys ROCHE-hGH, on COBAS 8000. A good correlation was obtained between methods for all measurements (r2>0.99) by using Passing–Bablok regression analysis. Bland–Altman analysis showed the best agreement between IDS-hGH and LIAISON-hGH systems (bias=−14.5%) compared to Elecsys ROCHE-hGH (bias=28.3%). When considering stratification of the study population and a unique cutoff, there were some discrepancies in interpretation of the results especially concerning the more recent Elecsys ROCHE-hGH assay. Nevertheless, when the adequate cutoff for each method was taken into account results were well correlated for all systems. A cutoff for Elecsys Roche-hGH method was established to better explain the results. Clinician must be aware of the use of assay-specific cutoff to correctly integrate the results of GH tests in the GHD diagnosis. [ABSTRACT FROM AUTHOR]

Recently, the asymptotic mean value of the height for a birth-and-death process is given in Videla [Videla, L.A. (2020)]. We consider the asymptotic variance of the height in the case when the number of states tends to infinity. Further, we prove that the heights exhibit a cutoff phenomenon and that the normalized height converges to a degenerate distribution. [ABSTRACT FROM AUTHOR]

Cefquinome is the fourth generation of cephalosporin approved solely in animal usage. In order to slow down the resistance development of E. coli to cefquinome, and to protect and maintain the effectiveness of cefquinome, an ex vivo PK/PD modeling of cefquinome against E. coli in cows after intramammary infusion administration was conducted. The epidemiologic cutoff (ECOFF) and pharmacodynamic cutoff (COPD) of cefquinome against E. coli in lactation cows after intramammary infusion administration were recommended. The MICs of cefquinome against 1073 clinical E. coli isolates ranged from 0.015 to >64 μg/ml, and the ECOFF was defined as 0.125 μg/ml. The pharmacokinetic results showed that cefquinome maintained high concentration in milk for a long period with the T1/2β of 10.60 h after intramammary infusion in dairy cows. The drug concentration in skimmed milk was still as high as 0.15 mg/ml after 48 h. Cefquinome displayed bacterial killing effect at 2× MIC with the initial inoculum of 106 cfu/ml in vitro; however, the same effect was attained with a concentration as high as 32× MIC with the initial inoculum of 108 cfu/ml both in artificial medium and in skimmed milk. The initial inoculum is an important factor on time‐killing curve accounting for weakened killing pattern of cefquinome. The AUC0–24 h/MIC index correlated well with ex vivo efficacy. The AUC0–24 h/MIC values for bactericidal effect were 50, 016, and 67,644, respectively, for initial inoculum of 106 and 108 cfu/ml, indicating the bacterial loading or the severity of infection would infect the PK/PD modeling results. The ex vivo PK/PD‐based population dose prediction indicated a target attainment rate (TAR) at the existing daily dose (75 mg/udder) of 84.77% against E. coli. Thus, it was recommended as rational dosage. The COPD of cefquinome against E. coli was determined as 8 μg/ml at the dose of 75 mg/udder. The derived ECOFF, COPD, together with ex vivo PK/PD‐based population dose prediction served as important steps in the establishment of optimum dose regimen and provided a useful interpretative criterion to categorize the antimicrobial susceptibility testing results of cefquinome. [ABSTRACT FROM AUTHOR]

The Fredrickson-Andersen one spin facilitated model belongs to the class of Kinetically Constrained Spin Models. It is a non attractive process with positive spectral gap. In this paper we give a precise result on the relaxation for this process on an interval [1, L] starting from any initial configuration. A consequence of this result is that this process exhibits cutoff at time L/(2v) with window O(√L) for a certain positive constant v. The key ingredient is the study of the evolution of the leftmost empty site in a filled infinite half-line called the front. In the process of the proof, we improve recent results about the front motion by showing that it evolves at speed v according to a uniform central limit theorem. [ABSTRACT FROM AUTHOR]

Background and Purpose: Walking speed can be used to identify characteristics of frailty in older adults. It has a strong positive correlation with balance abilities. The Brief-Balance Evaluation Systems Test (Brief-BESTest) was developed to assess functions of the 6 balance control systems in a short time. However, for community-dwelling older adults, the relationship between walking speed and the Brief-BESTest needs to be clarified. Even the cutoff scores for each Brief-BESTest section should be indicated for physical therapists to effectively evaluate balance deficits. Our objective was to establish cutoff scores for individual Brief-BESTest sections, determine fast or slow walkers in community-dwelling older adults, and investigate the relationship between balance control systems and walking speed. Methods: In a cross-sectional study involving 55 participants 77 years and older, the Brief-BESTest was evaluated after grouping the participants based on their walking speeds in public community centers. We compared the age, history of falls, handgrip strength, quadriceps strength, appendicular skeletal muscle mass index, comfortable walking speeds, and the Brief-BESTest scores between the fast- and slow-walking groups by using the independent t test, Fisher exact test, or Mann-Whitney U test. We also determined the receiver operating characteristic curves, and calculated the cutoff, area under the curve (AUC), sensitivity, and specificity of each section. Results: All sections of the Brief-BESTest, except Section 1 (Biomechanical Constraints) were able to differentiate between fast and slow walkers in community-dwelling older women. Section VI (Stability in Gait) showed the highest AUC (0.83) and the cutoff score for the fast- and slow-walker groups was 3.0 points (sensitivity = 0.85, specificity = 0.81). Sections III, IV, and V (Anticipatory, Reactive, and Sensory Orientation, respectively) had moderate AUC (0.71-0.72). Sections I and II (Stability Limits) showed weak correlations with the walking speed. Conclusions: Three sections (III, anticipatory postural adjustments; IV, reactive postural responses; and VI, stability in gait) could differentiate between fast and slow walkers. Section VI was a particularly important balance function measurement that differentiated the walking speed with the highest accuracy. Therefore, it should be a primary focus when physical therapists treat community-dwelling older adults. [ABSTRACT FROM AUTHOR]

Chosen cutoff for cytokeratin 19 fragment antigen (CYFRA 21-1) as a tumor biomarker considerably influences its diagnostic and prognostic usefulness. The aim of the present study is to determine an optimal cutoff value for diagnostic validity of CYFRA 21-1 by Lumipulse ® technology in patients with suspected cancer and also to determine if CYFRA 21-1 levels provide prognostic value.

Cefquinome, the fourth-generation cephalosporin applied solely for veterinary medicine, is commonly used for bovine mastitis caused by Staphylococcus aureus. The present study aims to establish an optimal dose and provide a PK/PD Cutoff value (COPD) for cefquinome against S. aureus based on ex vivo pharmacokinetics and pharmacodynamics (PK/PD) integration. This study investigated the pharmacokinetics (PK) of cefquinome when administered as three consecutive intramammary (IMM) doses of cefquinome in three healthy dairy cows at 75 mg/gland. Drug concentration was determined by HPLC-MS/MS assay. The ex vivo pharmacodynamics (PD) of cefquinome were evaluated by using a milk sample from a PK experiment. The relationship between the AUC/ MIC of cefquinome and bacterial loading reduction was simulated using a Sigmoid Emax model. The cefquinome concentration in milk attained a maximum level of 1.55 ± 0.21 mg/mL at 1.8 h after the third administration. The mean value of the area under the concentration-time curve (AUC0−24) was 26.12 ± 2.42 mg·h/mL after the third administration. The elimination half-life was 10.6 h. For PD profile, the MICs of cefquinome in milk were 2–4 times higher than those in the broth. In vitro time-killing curve shows that initial bacterial concentration has a huge impact on antibacterial effect on three strains. The antibacterial effect was weakened with the initial bacterial concentration increasing from 106 to 108 CFU/mL. The AUC0−24h/MIC index correlated well with ex vivo efficacy both for the initial inoculum of 106 CFU/mL and 108 CFU/mL (R2 > 0.84). According to the inhibitory sigmoid Emax model analysis, the PK/PD surrogate (AUC0−24/MIC) values were 8,638, 1,397, and 3,851 for bactericidal effect (E = −3) with an initial inoculum of 106 CFU/mL, while the corresponding values were 12,266, 2,295, and 5,337, respectively, with the initial inoculum of 108 CFU/mL. The ex vivo PK/PD based population dose prediction indicated a target attainment rate (TAR) of 90% of 55 mg/gland/12 h. The COPD for cefquinome against S. aureus was 2 μg/mL under the recommended dose of 55 mg/gland/12 h. However, it should be validated in clinical practice in future investigations. These results contribute to the rational use of cefquinome for mastitis treatment in clinical veterinary medicine.

Danofloxacin is a synthetic fluoroquinolone with broad-spectrum activity developed for use in veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff values and the optimum doses of danofloxacin against P. multocida and H. parasuis in piglets. Single dose serum pharmacokinetics was determined in piglets after intravenous and intramuscular administration of 2.5 mg/kg. Danofloxacin was well absorbed and fully bioavailable (95.2%) after intramuscular administration of 2.5 mg/kg. The epidemiological cutoff (ECOFF) values of danofloxacin from 931 P. multocida isolates and 263 H. parasuis isolates were 0.03 and 4 mg/L, respectively. Danofloxacin MICs determined in porcine serum were markedly lower than those measured in artificial broth, with a broth/serum ratio of 4.33 for H. parasuis. Compared to P. multocida, danofloxacin exhibited significantly longer post-antibiotic effects (3.18–6.60 h) and post-antibiotic sub-MIC effects (7.02–9.94 h) against H. parasuis. The mean area under the concentration-time curve/MIC (AUC24h/MIC) targets of danofloxacin in serum associated with the static and bactericidal effects were 32 and 49.8, respectively, for P. multocida, whereas they were 14.6 and 37.8, respectively, for H. parasuis. Danofloxacin AUC24h/MIC targets for the same endpoints for P. multocida were higher than those for H. parasuis. At the current dose of 2.5 mg/kg, the PK/PD cutoff (COPD) values of danofloxacin against P. multocida and H. parasuis were calculated to be 0.125 and 0.5 mg/L, respectively, based on Monte Carlo simulations. The predicted optimum doses of danofloxacin for a probability of target attainment (PTA) of > 90% to cover the overall MIC population distributions of P. multocida and H. parasuis in this study were 2.38 and 13.36 mg/kg, respectively. These PK/PD-based results have potential relevance for the clinical dose optimization and evaluation of susceptibility breakpoints for danofloxacin in the treatment of swine respiratory tract infections involving these pathogens.

Objectives: Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl -1 /mIU∙l -1 . We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD)., Methods: Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995-1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl -1 /mIU∙l -1 ) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening., Results: In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19-1.86). In CONPASS, when compared to essential hypertension with ARR < 1.0, PA with ARR ≥ 1.0 carried a higher CVD risk (odds ratio 2.24, 95%CI 1.41-3.55), while essential hypertension with ARR ≥ 1.0 had an unchanged CVD risk (1.02, 0.62-1.68). Setting ARR cutoff at 2.4 ~ 4.9, 10% ~30% of PA subjects would be unrecognized although they carried a 2.45 ~ 2.58-fold higher CVD risk than essential hypertension., Conclusions: The CVD risk-based optimal ARR cutoff is 1.0 ng·dl -1 /mIU∙l -1 for PA screening. The current guideline-recommended ARR cutoff may miss patients with PA and high CVD risk., Clinical Trial Registration: ClinicalTrials.gov (NCT03224312).

BackgroundFecal immunochemical testing (FIT) is an established method for colorectal cancer (CRC) screening. Measured FIT-concentrations are associated with both present and future risk of CRC, and may be used for personalized screening. However, evaluation of personalized screening is computationally challenging. In this study, a broadly applicable algorithm is presented to efficiently optimize personalized screening policies that prescribe screening intervals and FIT-cutoffs, based on age and FIT-history.MethodsWe present a mathematical framework for personalized screening policies and a bi-objective evolutionary algorithm that identifies policies with minimal costs and maximal health benefits. The algorithm is combined with an established microsimulation model (MISCAN-Colon), to accurately estimate the costs and benefits of generated policies, without restrictive Markov assumptions. The performance of the algorithm is demonstrated in three experiments.ResultsIn Experiment 1, a relatively small benchmark problem, the optimal policies were known. The algorithm approached the maximum feasible benefits with a relative difference of 0.007%. Experiment 2 optimized both intervals and cutoffs, Experiment 3 optimized cutoffs only. Optimal policies in both experiments are unknown. Compared to policies recently evaluated for the USPSTF, personalized screening increased health benefits up to 14 and 4.3%, for Experiments 2 and 3, respectively, without adding costs. Generated policies have several features concordant with current screening recommendations.DiscussionThe method presented in this paper is flexible and capable of optimizing personalized screening policies evaluated with computationally-intensive but established simulation models. It can be used to inform screening policies for CRC or other diseases. For CRC, more debate is needed on what features a policy needs to exhibit to make it suitable for implementation in practice.

The accuracy of neuropsychological assessments relies on participants exhibiting their true abilities during administration. The Test of Memory Malingering (TOMM) is a popular performance validity test used to determine whether an individual is providing honest answers. While the TOMM has proven to be highly sensitive to those who are deliberately exaggerating their symptoms, there is a limited explanation regarding the significance of using 45 as a cutoff score. The present study aims to further investigate this question by examining TOMM scores obtained in a large sample of active-duty military personnel ( N  = 859, M  = 26 years, SD  = 6.14, 97.31% males, 72.44% white). Results indicated that no notable discrepancies existed between the frequency of participants who scored a 45 and those who scored slightly below a 45 on the TOMM. The sensitivity and specificity of the TOMM were derived using the forced-choice recognition (FCR) scores obtained by participants on the California Verbal Learning Test, Second Edition (CVLT-II). The sensitivity for each trial of the TOMM was 0.84, 0.55, and 0.63, respectively; the specificity for each trial of the TOMM was 0.69, 0.93, and 0.92, respectively. Because sensitivity and specificity rates are both of importance in this study, balanced accuracy scores were also reported. Results suggested that various alternative cutoff scores produced a more accurate classification compared to the traditional cutoff of 45. Further analyses using Fisher's exact test also indicated that there were no significant performance differences on the FCR of the CVLT-II between individuals who received a 44 and individuals who received a 45 on the TOMM. The current study provides evidence on why the traditional cutoff may not be the most effective score. Future research should consider employing alternative methods which do not rely on a single score.

Peak stimulated growth hormone (GH) levels are known to decrease with increasing body mass index (BMI), possibly leading to overdiagnosis of GH deficiency (GHD) in children with overweight and obesity. However, current guidelines do not guide how to interpret the peak GH values of these children. This systematic review and meta-analysis aimed to study the effect of the BMI standard deviation score (SDS) on stimulated peak GH values in children, to identify potential moderators of this association, and to quantify the extent to which peak GH values in children with obesity are decreased. This systematic review was performed by the PRISMA guidelines. Medline, Embase, Cochrane, Web of Science, and Google Scholar databases were searched for studies reporting the impact of weight status on peak GH in children. Where possible, individual participant data was extracted and/or obtained from authors. Quality and risk of bias were evaluated using the Scottish Intercollegiate Guidelines Network (SIGN) checklists. The primary outcome was the association between peak GH values and BMI SDS. The pooled correlation coefficient r, 95% confidence interval (CI), and heterogeneity statistic I2 were calculated under a multilevel, random-effects model. In addition, exploratory moderator analyses and meta-regressions were performed to investigate the effects of sex, pubertal status, presence of syndromic obesity, mean age and mean BMI SDS on the study level. For the individual participant dataset, linear mixed-models regression analysis was performed with BMI SDS as the predictor and ln(peak GH) as the outcome, accounting for the different studies and GH stimulation agents used. In total, 58 studies were included, providing data on n = 5135 children (576 with individual participant data). Thirty-six (62%) studies had high, 19 (33%) medium, and 3 (5%) low risks of bias. Across all studies, a pooled r of −0.32 (95% CI −0.41 to −0.23, n = 2434 patients from k = 29 subcohorts, I2 = 75.2%) was found. In meta-regressions, larger proportions of males included were associated with weaker negative correlations (p = 0.04). Pubertal status, presence of syndromic obesity, mean age, and mean BMI SDS did not moderate the pooled r (all p > 0.05). Individual participant data analysis revealed a beta of −0.123 (95% CI −0.160 to −0.086, p < 0.0001), i.e. per one-point increase in BMI SDS, peak GH decreases by 11.6% (95% CI 8.3–14.8%). To our knowledge, this is the first systematic review and meta-analysis to investigate the impact of BMI SDS on peak GH values in children. It showed a significant negative relationship. Importantly, this relationship was already present in the normal range of BMI SDS and could lead to overdiagnosis of GHD in children with overweight and obesity. With the ever-rising prevalence of pediatric obesity, there is a need for BMI (SDS)-specific cutoff values for GH stimulation tests in children. Based on the evidence from this meta-analysis, we suggest the following weight status-adjusted cutoffs for GH stimulation tests that have cutoffs for children with normal weight of 5, 7, 10, and 20 µg/L: for overweight children: 4.6, 6.5, 9.3, and 18.6 µg/L; and for children with obesity: 4.3, 6.0, 8.6, and 17.3 µg/L. [ABSTRACT FROM AUTHOR]

Sarcopenia is defined as a progressive and generalized skeletal muscle disorder that is associated with an increased likelihood of adverse outcomes, including mobility problems and mortality. To reach a global consensus for its standard definition and diagnosis, more recently, a revised EWGSOP consensus (EWGSOP2) has been published. In EWGSOP2 definition, sarcopenia has been regarded as skeletal muscle failure and low muscle strength has been put forward as its key defining characteristics. EWGSOP2 suggested the use of handgrip strength cutoff values calculated by mean minus 2.5 standard deviations of the young healthy population. In this report, following EWGSOP2ʼs suggestion, we aimed to outline the handgrip strength cutoffs derived from a young Turkish reference population, and compare them with the other population-specific reports. [ABSTRACT FROM AUTHOR]

Abstract Background Risk scores were mainly proved to predict undiagnosed type 2 diabetes mellitus (UT2DM) in a non-invasive manner and to guide earlier clinical treatment. The objective of the present study was to assess the performance of the Finnish Diabetes Risk Score (FINDRISC) for detecting three outcomes: UT2DM, prediabetes, and the metabolic syndrome (MS). Methods This was a prospective, cross-sectional study during which employees aged between 30 and 64, with no known diabetes and working within the faculties of the Lebanese University (LU) were conveniently recruited. Participants completed the FINDRISC questionnaire and their glucose levels were examined using both fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT). Furthermore, they underwent lipid profile tests with anthropometry. Results Of 713 subjects, 397 subjects (55.2% female; 44.8% male) completed the blood tests and thus were considered as the sample population. 7.6% had UT2DM, 22.9% prediabetes and 35.8% had MS, where men had higher prevalence than women for these 3 outcomes (P = 0.001, P = 0.003 and P = 0.001) respectively. The AUROC value with 95% Confidence Interval (CI) for detecting UT2DM was 0.795 (0.822 in men and 0.725 in women), 0.621(0.648 in men and 0.59 in women) for prediabetes and 0.710 (0.734 in men and 0.705 in women) for MS. The correspondent optimal cut-off point for UT2DM was 11.5 (sensitivity = 83.3% and specificity = 61.3%), 9.5 for prediabetes (sensitivity = 73.6% and specificity = 43.1%) and 10.5 (sensitivity = 69.7%; specificity = 56.5%) for MS. Conclusion The FINDRISC can be considered a simple, quick, inexpensive, and non-invasive instrument to use in a Lebanese community of working people who are unaware of their health status and who usually report being extremely busy because of their daily hectic work for the screening of UT2DM and MS. However, it poorly screens for prediabetes in this context.

Background: Necrotizing enterocolitis (NEC) is a lethal disease affecting newborns with significant morbidity and mortality rates. Moreover, it is the most eminent gastrointestinal threat affecting premature newborns. Unfortunately, early symptoms and signs are usually vague; therefore, there is a special demand for sensitive biomarkers in this regard. This study aimed to investigate the role of fecal calprotectin in stage I NEC and identify specific cut off value at this stage to differentiate stage I NEC from other gastrointestinal disorders.Methods: This cross-sectional study was conducted at New Children Hospital, Cairo University, Egypt. In total, 100 newborns were included in this study who were assigned to the patient group with stage I NEC (n=60) and control group (n=40)with age and gender-matched newborns.Fecal calprotectin level was assessed using an enzyme-linked immunosorbent assay in both groups. Follow up of the patient group was performed for the development of stage II or III NEC.Results: The patient group obtained significantly elevated levels of fecal calprotectin, compared to the control group (P=0.000). Within the patient group, 43 (71.66%) newborns developed stage II or III NEC, whereas 17 (28.33%) cases developed no NEC. In addition, the level of fecal calprotectin was significantly higher in the group who developed stage II or III NEC (P=0.001). According to the receiver operating characteristic (ROC) curve, the cutoff value of 109.5 μg/g feces showed 100% sensitivity and specificity, and the area under the ROC curvewas equal to 1 in differentiating NEC from other conditions.Conclusion: The study showed that fecal calprotectin can be used as a sensitive and specific marker for the early detection of necrotizing enterocolitis.

Abstract Background The infrared tympanic thermometer (IRTT) is a popular method for temperature screening in children, but it has been debated for the low accuracy and reproducibility compared with other measurements. This study was aimed to identify and quantify studies reporting the diagnostic accuracy of the new generation IRTT in children and to compare the sensitivity and specificity of IRTT under different cutoffs and give the optimal cutoff. Methods Articles were derived from a systematic search in PubMed, Web of Science Core Collection, and Embase, and were assessed for internal validity by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The figure of risk of bias was created by Review Manager 5.3 and data were synthesized by MetaDisc 1.4. Results Twelve diagnostic studies, involving 4639 pediatric patients, were included. The cut-offs varied from 37.0 °C to 38.0 °C among these studies. The cut-off 37.8 °C was with the highest sROC AUC (0.97) and Youden Index (0.83) and was deemed to be the optimal cutoff. Conclusion The optimal cutoff for infrared tympanic thermometers is 37.8 °C. New Generation Tympanic Thermometry is with high diagnostic accuracy in pediatric patients and can be an alternative for fever screening in children.

Abstract The present study investigates the effects of clay core thickness and cutoff wall depth on some of the design parameters in the Sabalan rock fill dam by the finite-element method using the SEEP/W software. Clay cores with various thicknesses and cutoff walls in different situations of dam foundations were tested. The results revealed that (1) the maximum hydraulic gradient in Sabalan dam foundation occurs in the cutoff wall; (2) the minimum hydraulic gradient can be found by changing the location of the cutoff wall, under the center of clay core; and (3) discharge reduction depends on the optimum position at heel of the core. As the permeability decreases and the depth of the cutoff wall increases, the hydraulic gradient in the cutoff wall increases. As the thickness of the clay core increases, hydraulic gradient and the seepage discharge decreases and the uplift pressure increases.

Jie Chen,1 Jingwen Luo,2 Xia He,3 Chenjing Zhu3 1Department of Oncology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Oncology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Radiation Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Xia He; Chenjing ZhuDepartment of Radiation Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Tel/Fax +86-28-85475576Email hexiabm@163.com; drchenjingzhu@gmail.comIntroduction: We performed this study to explore the diagnostic accuracies and cutoff values of contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) for the detection and diagnosis of metastatic retropharyngeal lymph nodes (RLNs) in patients with nasopharyngeal carcinoma (NPC).Methods: One hundred and twenty-eight patients with a total of 159 RLNs were included in the study. The sizes of maximal and minimal axial diameters of each node on both contrast-enhanced CT and MRI images were measured. The characteristics of the RLNs (malignant or benign), as well as the survival of patients, were classified based on the results of follow-up MRI.Results: RLN size cutoffs of 4– 11 mm for minimal axial diameter were used. We found that MRI showed higher sensitivity while CT demonstrated higher specificity. The reasonable criterion for the diagnosis of metastatic RLNs in MRI was a minimal axial diameter of ≥ 6 mm, which yielded a sensitivity, specificity and diagnostic odds ratio (DOR) of 0.71, 0.82 and 10.88.Conclusion: The radiologic criteria that should be used for the assessment of RLN metastases in NPC patients are nodes with a minimal axial diameter of ≥ 6 mm on MR images.Keywords: retropharyngeal lymph node, metastasis, nasopharyngeal carcinoma, cutoff, MRI

In clinical and epidemiological studies, biomarkers are associated with disease diagnosis and prognosis. Using biomarkers to classify subjects into groups, such as high-risk or low-risk, may help with the application of the most appropriate care or procedure within each group. In the case of a continuous biomarker, a cutoff value to define the groups should be determined. A widespread and straightforward method is to select a cutoff value that minimizes the P-value when comparing the outcomes between the two groups. However, a problem that arises with this procedure is that of multiple testing, which leads to an increase in false positive error rate, and thus the significance of the obtained cutoff value tends to be overestimated. In this article, we introduce several methods to correct the P-value for determining the statistical significance of an optimal cutoff value for a quantitatively measured biomarker with applications to clinical data.

Abstract Background As research in treatments for neurocognitive diseases progresses, there is an increasing need to identify cognitive decline in the earliest stages of disease for initiation of treatment in addition to determining the efficacy of treatment. For early identification, accurate cognitive tests cutoff values for cognitive impairment are essential. Methods We conducted a study on 297 cognitively healthy elderly people from the BioFINDER study and created subgroups excluding people with signs of underlying neuropathology, i.e., abnormal cerebrospinal fluid [CSF] β-amyloid or phosphorylated tau, CSF neurofilament light (neurodegeneration), or cerebrovascular pathology. We compared cognitive test results between groups and examined the age effect on cognitive test results. Results In our subcohort without any measurable pathology (n = 120), participants achieved better test scores and significantly stricter cutoffs for cognitive impairment for almost all the examined tests. The age effect in this subcohort disappeared for all cognitive tests, apart from some attention/executive tests, predominantly explained by the exclusion of cerebrovascular pathology. Conclusion Our study illustrates a new approach to establish normative data that could be useful to identify earlier cognitive changes in preclinical dementias. Future studies need to investigate if there is a genuine effect of healthy aging on cognitive tests or if this age effect is a proxy for higher prevalence of preclinical neurodegenerative diseases.

Abstract Background Gamithromycin is a macrolide approved for the treatment of bovine and swine respiratory diseases. Our study aims to establish the clinical breakpoint and optimum dose regimen for gamithromycin against Haemophilus parasuis in piglets. Results Gamithromycin was well absorbed and fully bioavailable (87.2–101%) after intramuscular and subcutaneous administrations. The MICs of gamithromycin for 192 clinical H. parasuis isolates ranged from 0.008 to 128 mg/L and the epidemiological cutoff (ECOFF) was calculated as 1.0 mg/L. A large potentiation effect of serum on in vitro susceptibility of gamithromycin was observed for H. parasuis, with broth/serum ratios of 8.93 for MICs and 4.46 for MBCs, respectively. The postantibiotic effects were 1.5 h (1 × MIC) and 2.4 h (4 × MIC), and the postantibiotic sub-MIC effects ranged from 2.7 to 4.3 h. Gamithromycin had rapid and concentration-dependent killing against H. parasuis, and the AUC24h/MIC ratio correlated well with ex vivo efficacy (R2 = 0.97). The AUC24h/MIC targets in serum associated with bacteriostatic, bactericidal and eradication activities were 15.8, 30.3 and 41.2, respectively. The PK/PD-based population dose prediction indicated a probability of target attainment (PTA) for the current marketed dose (6 mg/kg) of 88.9% against H. parasuis. The calculated gamithromycin dose for a PTA ≥ 90% was 6.55 mg/kg. Based on Monte Carlo simulations, the PK/PD cutoff (COPD) was determined to be 0.25 mg/L. Conclusion The determined cutoffs and PK/PD-based dose prediction will be of great importance in gamithromycin resistance surveillance and serve as an important step in the establishment of optimum dose regimen and clinical breakpoints.

Abstract Background Correcting anemia during pregnancy often requires integrating food and non-food-based approaches. Nonetheless, little is known about specific dietary diversity (DD) cutoff values predicting risk of anemia during the different trimesters of pregnancy. Objective We aimed to determine the lowest possible DD cutoff values associated with risk of maternal anemia at mid and term of pregnancy in a rural resource limited setting of Ethiopia. Design A multi-center prospective cohort study was conducted enrolling 432 eligible pregnant women from eight rural health centers selected from four districts in Arsi zone, Central Ethiopia. Women were classified into exposed (n = 216) and unexposed (n = 216) groups, based on Women’s Individual Dietary Diversity (WIDD) score, and were followed from mid to term of pregnancy. The cutoff values for WIDD corresponding to the lowest risk of anemia were defined by receiver operating characteristic (ROC) curve analysis. Logistic regressions were also fitted to identify food groups associated with low anemia risk during pregnancy. Results The overall prevalence of anemia increased from 28.6 to 32.4% between mid and term of pregnancy. Calculatedly, using the ROC curve analysis, the minimum WIDD score associated with lower risk of anemia was three and four respectively at these periods. Not consuming animal source foods [adjusted odds ratio (AOR), 2.36; 95% confidence interval (CI), 1.35–4.14], pre-existing anemia (AOR 28.56; 95% CI, 14.33, 56.79), and low DD during pregnancy (AOR, 2.22; 95% CI, 1.09–4.52) were associated with risk of anemia at term. Conclusion The cutoff for WIDD score predicting risk of anemia varied significantly, increasing from three to four, between mid and term of pregnancy. Additional population-based observational and experimental studies validating the metrics are needed before policy level recommendations. Trial registration This trial was registered at clinicaltrials.gov as NCT02620943.

Abstract This study aimed to investigate the diagnostic accuracy of the Baptista Depression Scale adult and screening versions (EBADEP-A and EBADEP-screening) for discrimination of people with a major depressive episode (MDE) or major depressive disorder (MDD) and to compare discriminative capacities. Participants were 187 people, 52 patients, and 135 non-clinical individuals. Results indicated sensitivity equal to 0.92 and specificity equal to 0.88 for EBADEP-A (cut-off = 54), and 0.96 and 0.82, respectively, for EBADEP-screening (cut-off = 17). Findings suggest equivalence between the two versions of EBADEP to discriminate people with MDE or MDD. Results indicate that the two versions can provide a correct diagnostic indicative for MDE and MDD.

The article discusses the use of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for the early detection and diagnosis of acute kidney injury (AKI). AKI is a syndrome characterized by an increase in serum creatinine levels and a decrease in urine output. NGAL is a kidney biomarker that can indicate early damage and predict prognosis. The article highlights the need for standardized NGAL cutoffs and further research on alternative methods and classification systems for AKI diagnosis and risk assessment. [Extracted from the article]

Purpose: Immunotherapy is regarded as the most promising treatment for cancer. However, immune checkpoint inhibitors (ICIs) are not effective for all patients. Herein, we conducted a systematic review and meta-analysis to explore whether tumor mutational burden (TMB) can be used as a potential prognostic biomarker for cancer patients treated with ICIs. Methods: We systematically retrieved relevant literature published in the PubMed, Embase, Web of Science, and Cochrane databases up to December 28, 2020. All cohort studies and clinical trials that reported hazard ratios (HRs) for overall (OS) and progression-free survival (PFS), as well as the corresponding 95% confidence intervals (CIs) of high and low TMB patients, were included. All statistical analyses were performed using the R software. Results: Pooled results from a total of 32 studies with 6,131 participants showed significantly increased OS (HR: 0.61, 95% CI: 0.53–0.71; P < 0.01) and PFS (HR: 0.51, 95% CI: 0.44–0.60; P < 0.01) for the high TMB group receiving ICIs as compared to the low TMB group. Particularly, results were found to be more significant in studies with larger sample sizes (≥30), Western patients, higher TMB cutoff values (≥20 mut/Mb), anti–PD-1 therapy, and when the sample source was tissue and tumor type was either melanoma, small cell lung cancer, or gastric cancer. Conclusion: TMB is a promising independent prognostic biomarker for cancer patients receiving ICIs, which could provide a new potential therapeutic strategy for high TMB patients who have failed traditional therapy. Furthermore, consistency in the key aspects of TMB assessment is expected in the future. Systematic Review Registration: [ https://www.crd.york.ac.uk/PROSPERO ], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42021229016. [ABSTRACT FROM AUTHOR]

We study the convergence to stationarity for random walks on dynamic random digraphs with given degree sequences. The digraphs undergo full regeneration at independent geometrically distributed random time intervals with parameter α. Relaxation to stationarity is the result of an interplay of regeneration and mixing on the static digraph. When the number of vertices n tends to infinity and the parameter α tends to zero, we find three scenarios according to whether α log n converges to zero, infinity or to some finite positive value: when the limit is zero, relaxation to stationarity occurs in two separate stages, the first due to mixing on the static digraph, and the second due to regeneration; when the limit is infinite, there is not enough time for the static digraph to mix and the relaxation to stationarity is dictated by the regeneration only; finally, when the limit is a finite positive value we find a mixed behavior interpolating between the two extremes. A crucial ingredient of our analysis is the control of suitable approximations for the unknown stationary distribution. [ABSTRACT FROM AUTHOR]

Maternal exposure to air pollution during pregnancy is associated with adverse outcomes in the offspring, but limited studies focused on the impacts of gaseous air pollution on newborn congenital hypothyroidism (CH). Therefore, a national data-based analysis was conducted to explore the association between maternal exposure to gaseous air pollution and the incidence of CH in China. Annual average exposure levels of SO2, NO2, CO, and O3 from January 1, 2014, to December 30, 2014, were acquired from the Chinese Air Quality Online Monitoring and Analysis Platform. The annual incidence of newborn CH from October 1, 2014, to September 30, 2015, was collected from the Chinese Maternal and Child Health Surveillance Network. Temperature and toxic metal in wastewater in 2014 were also collected as covariates. Maternal exposure to O3 and NO2 in 1 μg/m3 level increment was positively associated with newborn CH, with an OR of 1.055 (95% CI 1.011, 1.102) and 1.097 (95% CI 1.019, 1.182) after adjusting for covariates completely. Compared with the lowest level of O3, maternal exposure to the 4th quartile of O3 was positively associated with newborn CH (OR 1.393, 95% CI 1.081, 1.794) after adjusting for covariates completely. And the 3rd and 4th quartiles of NO2 were associated positively with CH (OR 1.576, 95% CI 1.025, 2.424, and OR 1.553, 95% CI 0.999, 2.414, respectively) compared with the lowest level of NO2. By fitting the ROC curve, 93.688 μg/m3 in O3 might be used as cutoff to predict the incidence of newborn CH in China. [ABSTRACT FROM AUTHOR]

PurposeImmunotherapy is regarded as the most promising treatment for cancer. However, immune checkpoint inhibitors (ICIs) are not effective for all patients. Herein, we conducted a systematic review and meta-analysis to explore whether tumor mutational burden (TMB) can be used as a potential prognostic biomarker for cancer patients treated with ICIs.MethodsWe systematically retrieved relevant literature published in the PubMed, Embase, Web of Science, and Cochrane databases up to December 28, 2020. All cohort studies and clinical trials that reported hazard ratios (HRs) for overall (OS) and progression-free survival (PFS), as well as the corresponding 95% confidence intervals (CIs) of high and low TMB patients, were included. All statistical analyses were performed using the R software.ResultsPooled results from a total of 32 studies with 6,131 participants showed significantly increased OS (HR: 0.61, 95% CI: 0.53–0.71; P

Introduction: Total bilirubin (TB) is a major prognosis predictor representing liver failure in patients with acute on chronic liver failure (ACLF). However, the cutoff value of TB for liver failure and whether the same cutoff could be applied in both cirrhotic and non-cirrhotic patients remain controversial. There is a need to obtain the quantitative correlation between TB and short-term mortality via evidence-based methods, which is critical in establishing solid ACLF diagnostic criteria.Methods: Patients hospitalized with cirrhosis or advanced fibrosis (FIB-4 > 1.45) were studied. TB and other variables were measured at baseline. The primary outcome was 90-day transplantation-free mortality. Multi-variable Cox proportional hazard model was used to present the independent risk of mortality due to TB. Generalized additive model and second derivate (acceleration) were used to plot the “TB-mortality correlation curves.” The mathematical (maximum acceleration) and clinical (adjusted 28-day transplantation-free mortality rate reaching 15%) TB cutoffs for liver failure were both calculated.Results: Among the 3,532 included patients, the number of patients with cirrhosis and advanced fibrosis were 2,592 and 940, respectively, of which cumulative 90-day mortality were 16.6% (430/2592) and 7.4% (70/940), respectively. Any increase of TB was found the independent risk factor of mortality in cirrhotic patients, while only TB >12 mg/dL independently increased the risk of mortality in patients with advanced fibrosis. In cirrhotic patients, the mathematical TB cutoff for liver failure is 14.2 mg/dL, with 23.3% (605/2592) patients exceeding it, corresponding to 13.3 and 25.0% adjusted 28- and 90-day mortality rate, respectively. The clinical TB cutoff for is 18.1 mg/dL, with 18.2% (471/2592) patients exceeding it. In patients with advanced fibrosis, the mathematical TB cutoff is 12.1 mg/dL, 33.1% (311/940) patients exceeding it, corresponding to 2.9 and 8.0% adjusted 28- and 90-day mortality rate, respectively; the clinical TB cutoff was 36.0 mg/dL, 1.3% (12/940) patients above it.Conclusion: This study clearly demonstrated the significantly different impact of TB on 90-day mortality in patients with cirrhosis and advanced fibrosis, proving that liver failure can be determined by TB alone in cirrhosis but not in advanced fibrosis. The proposed TB cutoffs for liver failure provides solid support for the establishment of ACLF diagnostic criteria.

It is not clear whether D-dimer can be an independent predictor of coronavirus disease 2019 (COVID-19) mortality, and the cut-off of D-dimer for clinical use remains to be determined. Therefore, a comprehensive analysis is still necessary to illuminate the clinical significance of plasma D-dimer in COVID-19 mortality. We searched PubMed, Embase, Cochrane Library, and Scopus databases until November 2020. STATA software was used for all the statistical analyses. The identifier of systematic review registration was PROSPERO CRD42020220927. A total of 66 studies involving 40,614 COVID-19 patients were included in our meta-analysis. Pooled data showed that patients in high D-dimer group had poor prognosis than those in low D-dimer group [OR = 4.52, 95% CI = (3.61, 5.67), P < 0.001; HR = 2.81, 95% CI = (1.85, 4.27), P < 0.001]. Sensitivity analysis, pooled data based on different effect models and the Duval and Tweedie trim-and-fill method did not change the conclusions. Subgroup analyses stratified by different countries, cutoffs, sample size, study design, and analysis of OR/HR still keep consistent conclusions. D-dimer was identified as an independent predictor for COVID-19 mortality. A series of values including 0.5 μg/ml, 1 μg/ml, and 2 μg/ml could be determined as cutoff of D-dimer for clinic use. Measurement and monitoring of D-dimer might assist clinicians to take immediate medical actions and predict the prognosis of COVID-19.

Background Calf circumference (CC) is used in geriatric studies as a simple and practical skeletal muscle (SM) marker for diagnosing low SM and sarcopenia. Currently applied CC cutoff points were developed in samples including older participants; values representative of the full adult lifespan are lacking. Objectives We aimed to develop CC cutoff points and to identify relevant confounding factors from the large and diverse NHANES 1999–2006 population sample. Methods Demographic, anthropometric, and imaging data (DXA, appendicular lean mass) from the adult (age ≥18 y) NHANES sample were partitioned into subgroups according to sex, age, ethnicity, and race. Adults aged 18–39 y and BMI (in kg/m2) 18.5–24.9 were set as a reference population; CC cutoff points were derived at 1 and 2 SDs below the mean. Results The sample included 17,789 participants, 51.3% males and 48.7% females, with respective ages (mean ± SD) of 43.3 ± 16.1 y and 45.5 ± 16.9 y. CC was strongly correlated with appendicular lean mass, r  = 0.84 and 0.86 for males and females (both P  < 0.001), respectively. Significant differences in mean CC were present across sex, ethnic, self-reported race, and BMI groups. Adjusting CC for adiposity using BMI revealed a decrease in CC beginning after the second decade in males and third decade in females. Rounded CC cutoff values for moderately and severely low CC were 34 cm and 32 cm (males), and 33 cm and 31 cm (females), respectively. Our findings support the use of BMI-adjusted CC values for participants outside the normal-weight BMI range (18–24.9). Conclusions This study defined CC values in a diverse population sample along with a BMI-adjustment approach that helps to remove the confounding effects of adiposity and thereby improves CC as a useful clinical estimate of SM mass. [ABSTRACT FROM AUTHOR]

Establishing the virological cutoff point, during epidemics, such as the COVID-19 Pandemic, is crucially important as inadequate standardization and the false qualitative results, have enormous clinical and economic consequences when screening for SARS-CoV-2. Moreover, a cutoff point is a crucial step in ensuring a minimal risk of clinical misclassification. Therefore complying with such statutory requirements is an essential part of obligatory good laboratory and clinical practices. In this concise report, we propose a novel methodology for establishing cutoff points for all samples exhibiting detectable levels of the measured parameter, even those from the disease-free group. Based on target specificity and sensitivity levels of 100 % and 95 %, a value of 1209 A is identified as the "best cutoff". In fact, the ROC decision matrixes play a crucial role in determining optimal cutoff points. The most effective discriminators are those that meet specified accuracy criteria. The selection process is influenced by finding the right clinical sensitivity/specificity trade-off. [ABSTRACT FROM AUTHOR]

Abstract Background While it is widely acknowledged that family burden can be ameliorated with effective psycho-social interventions, how to measure family burden and define a valid cutoff to identify family caregivers in need of such interventions remains a key question. The purpose of the present study was to determine a statistically valid cutoff score for the Family Burden Interview Schedule (FBIS), using the cutoff scores of the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale (GAD-7) as the reference. Methods The FBIS, PHQ-9, and GAD-7 were administered to a representative community sample of 327 family caregivers of schizophrenia patients. A FBIS cutoff score was determined using three different statistical methods: tree-based modeling, K-means clustering technique and linear regression. Contingency analysis was conducted to compare the FBIS cutoff with depression and anxiety scale scores. Results Findings proposed a cutoff score of 23 for the FBIS, with sensitivity being 76% for PHQ-9 and 74% for GAD-7, specificity being 68% for PHQ-9 and 67% for GAD-7. Conclusion This cutoff score would enable health care providers to assess family caregivers at risk and provide necessary interventions to improve their quality of life.

Abstract Background The eighth TNM classification for gastric cancer categorizes N3 as N3a and N3b in the final pathologic stage. The cutoff for N3a/N3b is defined as 15 metastatic lymph nodes, but the rationale for this cutoff remains unclear. This study aimed to determine the optimal N3a/N3b cutoff and evaluate its prognostic significance. Methods An international database was constructed by combining data from patients with N3 gastric cancer and complete five-year follow-up data from the Surveillance, Epidemiology, and End Results program database (n = 1833) and the Fujian Medical University Union Hospital database (n = 920) (total n = 2753). A log-rank test was performed to determine the optimal N3a/N3b cutoff, and its prognostic significance was confirmed in a two-step multivariate analysis and compared to that of the eighth TNM. Results A cut-point analysis performed at each metastatic lymph node number identified the greatest survival difference between N3a and N3b at 13 metastatic lymph nodes (χ2 = 157.671, P = 3.65 × 10− 36). In patients with 14–15 metastatic lymph nodes, prognoses were significantly worse than those in patients with 7–13 metastatic lymph nodes (P 15 metastatic lymph nodes (P = 0.078). Therefore, patients with 14–15 metastatic lymph nodes were incorporated into a modified N3b classification. In the two-step multivariate analysis, the eighth N3 classification fell out of the model, while the modified N3 classification remained intact (HR 1.51, P

To date, the Child and Adolescent Mindfulness Measure (CAMM) has been translated into several languages, including Chinese. This study aimed to explore the reliability and validity of the Chinese version of the CAMM and to identify the appropriate cutoff score among Chinese primary school students. A total of 1283 participants (52.2% males; 11.52 ± 0.78 years of age) completed a series of questionnaires to evaluate their mental health, including mindfulness, subjective well-being, positive youth development (PYD), depression, and anxiety. Item analysis, Confirmatory Factor Analysis (CFA), Exploratory Structural Equation Modeling (ESEM), criterion-related validity analysis, Receiver Operating Characteristic (ROC) analysis, and reliability analysis were performed. The results show that the Chinese version of the CAMM had acceptable item–scale correlation (r = 0.405–0.775, p < 0.001) and was the best fit for the two-factor ESEM model (χ2 = 168.251, p < 0.001, df = 26, TLI = 0.910, CFI = 0.948, RMSEA = 0.065, SRMR = 0.033) among Chinese primary school students. Additionally, the total score of the Chinese version of the CAMM was significantly associated with subjective well-being and PYD (r = 0.287–0.381, p < 0.001), and negatively associated with depression, and anxiety (r = −0.612–−0.542, p < 0.001). Moreover, a cutoff score of 22 or higher revealed a significant predictive power for all the included criteria. Finally, the Chinese version of the CAMM had good internal consistency (Cronbach’s α = 0.826, McDonald’s ω = 0.826). Altogether, the Chinese version of the CAMM had satisfactory psychometric properties, and it can be applied to Chinese children.

Background: Patient-reported outcome measures are widely utilized to assess health-related quality of life (HRQOL) in patients with adolescent idiopathic scoliosis (AIS). However, the association between HRQOL and curve severity is mostly unknown. The aim of this study is to clarify the association between HRQOL and curve severity, and to determine the optimal cutoff values of patient-reported outcomes for major curve severity in female patients with AIS.Methods: Female patients with AIS treated conservatively were recruited. The patients' HRQOL outcomes were examined using the revised Scoliosis Research Society-22 (SRS-22r) and the Scoliosis Japanese Questionnaire-27 (SJ-27). The correlations of the SRS-22r and SJ-27 scores with the major Cobb angle were assessed using Spearman's correlation coefficient analysis. The association between HRQOL issues in the SJ-27 and the major Cobb angle was evaluated by calculating Akaike's Information Criterion (AIC). Furthermore, the optimal cutoff values of the SRS-22r and SJ-27 scores for the major Cobb angle were determined by AIC analysis.Results: The study cohort comprised 306 female patients with AIS. The SRS-22r and SJ-27 scores were significantly correlated with the major Cobb angle. Questions in the SJ-27 regarding discomfort when wearing clothes showed a lower AIC value in patients with severe scoliosis. The optimal cutoff values were a SRS-22r score of 3.2 for the discrimination of severe scoliosis (Cobb angle ≥48°), and a SJ-27 score of 32 for the discrimination of moderate scoliosis (Cobb angle ≥33°).Conclusion: Discomfort when wearing clothes was the most important HRQOL problem caused by severe scoliosis. The SRS-22r and SJ-27 scores are useful for the discrimination of clinical status in female patients with severe scoliosis or moderate scoliosis. [ABSTRACT FROM AUTHOR]

We consider a random walk on the hyperoctahedral group Bn generated by the signed permutations of the forms (i,n) and (-i,n) for 1≤i≤n. We call this the flip-transpose top with random shuffle on Bn. We find the spectrum of the transition probability matrix for this shuffle. We prove that the mixing time for this shuffle is of order nlogn. We also show that this shuffle exhibits the cutoff phenomenon. In the appendix, we show that a similar random walk on the demihyperoctahedral group Dn also has a cutoff at (n-1/2)logn. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the diagnostic accuracy of the Baptista Depression Scale adult and screening versions (EBADEP-A and EBADEP-screening) for discrimination of people with a major depressive episode (MDE) or major depressive disorder (MDD) and to compare discriminative capacities. Participants were 187 people, 52 patients, and 135 non-clinical individuals. Results indicated sensitivity equal to 0.92 and specificity equal to 0.88 for EBADEP-A (cut-off = 54), and 0.96 and 0.82, respectively, for EBADEP-screening (cut-off = 17). Findings suggest equivalence between the two versions of EBADEP to discriminate people with MDE or MDD. Results indicate that the two versions can provide a correct diagnostic indicative for MDE and MDD. [ABSTRACT FROM AUTHOR]