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Abstract Background Emotional problems can be evaluated using categorical approaches to guide treatment choices focused on targeting specific disorders, or dimensional approaches to reduce symptom severity. Moreover, recent evidence points out the need to intervene in patients’ quality of life (QoL), which often remains low even after the remission of emotional problems. Thus, assessment instruments are needed to provide information on diagnosis, symptom severity, and QoL. The present study aimed to provide diagnostic and QoL cutoffs for the Inventory of Depression and Anxiety Symptoms-II (IDAS-II). Methods 273 patients recruited from mental health services in Huelva (Spain) completed the IDAS-II, Mini International Neuropsychiatric Interview, and Short Form-36 Health Survey. Receiver operating characteristic curve analyses were used to establish cutoff values. Diagnostic, balanced, and screening cutoffs were provided for each IDAS-II scale to detect corresponding diagnoses and poor QoL. Results The specific IDAS-II scales Suicidality, Panic, Social Anxiety, Claustrophobia, and Traumatic Intrusions showed adequate discrimination values for their corresponding diagnoses (suicidal behavior disorder, panic disorder, social anxiety disorder, agoraphobia, and post-traumatic stress disorder, respectively). Both the General Depression and Dysphoria scales showed adequate ability to detect major depressive disorder. The IDAS-II scales showed a higher discrimination ability for Mental Health-related QoL, than for General Health-related QoL. Conclusions The diagnostic and QoL cutoffs expand the clinical utility of the IDAS-II in clinical practice and research, making it a comprehensive, detailed, and versatile self-report tool. The IDAS-II allows for the assessment of emotional problems consistent with the dimensional, categorical, transdiagnostic, and QoL approaches.

Despite the popularity of traditional fit index cutoffs like RMSEA ≤.06 and CFI ≥.95, several studies have noted issues with overgeneralizing traditional cutoffs. Computational methods have been proposed to avoid overgeneralization by deriving cutoffs specifically tailored to the characteristics of the model being evaluated. Simulations show favorable performance of these methods; however, these methods support a narrow set of scenarios (e.g., certain models or response scales) and the interpretation of cutoffs is not always standardized, which affects empirical researchers' ability to confidently and broadly adopt these methods to evaluate model fit. In this paper, we propose an extension to one recently developed computational method—dynamic fit index cutoffs—that (a) permits application to any covariance structure model (e.g., CFA, mediation, bifactor), (b) standardizes interpretation of cutoffs across any covariance structure model, and (c) supports normal, nonnormal, categorical, and missing data. Software is provided to facilitate implementation of the method. [ABSTRACT FROM AUTHOR]

Background: In the era of disease-modifying therapies, empowering the clinical neuropsychologist's toolkit for timely identification of mild cognitive impairment (MCI) is crucial. Objective: Here we examine the clinimetric properties of the Montreal Cognitive Assessment (MoCA) for the early diagnosis of MCI due to Alzheimer's disease (MCI-AD). Methods: Data from 48 patients with MCI-AD and 47 healthy controls were retrospectively analyzed. Raw MoCA scores were corrected according to the conventional Nasreddine's 1-point correction and demographic adjustments derived from three normative studies. Optimal cutoffs were determined while previously established cutoffs were diagnostically reevaluated. Results: The original Nasreddine's cutoff of 26 and normative cutoffs (non-parametric outer tolerance limit on the 5th percentile of demographically-adjusted score distributions) were overly imbalanced in terms of Sensitivity (Se) and Specificity (Sp). The optimal cutoff for Nasreddine's adjustment showed adequate clinimetric properties (≤23.50, Se = 0.75, Sp = 0.70). However, the optimal cutoff for Santangelo's adjustment (≤22.85, Se = 0.65, Sp = 0.87) proved to be the most effective for both screening and diagnostic purposes according to Larner's metrics. The results of post-probability analyses revealed that an individual testing positive using Santangelo's adjustment combined with a cutoff of 22.85 would have 84% post-test probability of receiving a diagnosis of MCI-AD (LR+ = 5.06). Conclusions: We found a common (mal)practice of bypassing the applicability of normative cutoffs in diagnosis-oriented clinical practice. In this study, we identified optimal cutoffs for MoCA to be allocated in secondary care settings for supporting MCI-AD diagnosis. Methodological and psychometric issues are discussed. [ABSTRACT FROM AUTHOR]

Background: Emotional problems can be evaluated using categorical approaches to guide treatment choices focused on targeting specific disorders, or dimensional approaches to reduce symptom severity. Moreover, recent evidence points out the need to intervene in patients' quality of life (QoL), which often remains low even after the remission of emotional problems. Thus, assessment instruments are needed to provide information on diagnosis, symptom severity, and QoL. The present study aimed to provide diagnostic and QoL cutoffs for the Inventory of Depression and Anxiety Symptoms-II (IDAS-II). Methods: 273 patients recruited from mental health services in Huelva (Spain) completed the IDAS-II, Mini International Neuropsychiatric Interview, and Short Form-36 Health Survey. Receiver operating characteristic curve analyses were used to establish cutoff values. Diagnostic, balanced, and screening cutoffs were provided for each IDAS-II scale to detect corresponding diagnoses and poor QoL. Results: The specific IDAS-II scales Suicidality, Panic, Social Anxiety, Claustrophobia, and Traumatic Intrusions showed adequate discrimination values for their corresponding diagnoses (suicidal behavior disorder, panic disorder, social anxiety disorder, agoraphobia, and post-traumatic stress disorder, respectively). Both the General Depression and Dysphoria scales showed adequate ability to detect major depressive disorder. The IDAS-II scales showed a higher discrimination ability for Mental Health-related QoL, than for General Health-related QoL. Conclusions: The diagnostic and QoL cutoffs expand the clinical utility of the IDAS-II in clinical practice and research, making it a comprehensive, detailed, and versatile self-report tool. The IDAS-II allows for the assessment of emotional problems consistent with the dimensional, categorical, transdiagnostic, and QoL approaches. [ABSTRACT FROM AUTHOR]

The performance of individual biomarkers in discriminating between two groups, typically the healthy and the diseased, may be limited. Thus, there is interest in developing statistical methodologies for biomarker combinations with the aim of improving upon the individual discriminatory performance. There is extensive literature referring to biomarker combinations under the two-class setting. However, the corresponding literature under a three-class setting is limited. In our study, we provide parametric and nonparametric methods that allow investigators to optimally combine biomarkers that seek to discriminate between three classes by minimizing the Euclidean distance from the receiver operating characteristic surface to the perfection corner. Using this Euclidean distance as the objective function allows for estimation of the optimal combination coefficients along with the optimal cutoff values for the combined score. An advantage of the proposed methods is that they can accommodate biomarker data from all three groups simultaneously, as opposed to a pairwise analysis such as the one implied by the three-class Youden index. We illustrate that the derived true classification rates exhibit narrower confidence intervals than those derived from the Youden-based approach under a parametric, flexible parametric, and nonparametric kernel-based framework. We evaluate our approaches through extensive simulations and apply them to real data sets that refer to liver cancer patients. [ABSTRACT FROM AUTHOR]

Globally, liver cancer is the third most frequent etiology of cancer death, with the rates of occurrence of both new cases and mortality estimated to increase. Given the availability of multiple treatments, interdisciplinary management of the patient is crucial. Moreover, the diagnostic assessment of patients with severe liver fibrosis is essential for the staging of HCC and liver cirrhosis and early diagnosis of HCC. In this context, non-invasive evaluation plays a critical role in identifying prognostic factors of clinical application for the surveillance of the occurrence or recurrence of HCC. The new frontiers of transient elastography have become a useful tool to assess the risk of HCC occurrence and recurrence. There has been a major increase in studies investigating the cutoff liver stiffness value that best predicts the need for monitoring for the onset of HCC. Therefore, this review discusses the new advances that have occurred in the last four years on HCC, highlighting the new frontiers of non-invasive evaluation of HCC subjects, with particular attention regarding the clinical application of liver stiffness assessment for de novo HCC and predicting recurrence in patients with chronic HCV achieving sustained virological response after treatment with direct antiviral agents. [ABSTRACT FROM AUTHOR]

Globally, liver cancer is the third most frequent etiology of cancer death, with the rates of occurrence of both new cases and mortality estimated to increase. Given the availability of multiple treatments, interdisciplinary management of the patient is crucial. Moreover, the diagnostic assessment of patients with severe liver fibrosis is essential for the staging of HCC and liver cirrhosis and early diagnosis of HCC. In this context, non-invasive evaluation plays a critical role in identifying prognostic factors of clinical application for the surveillance of the occurrence or recurrence of HCC. The new frontiers of transient elastography have become a useful tool to assess the risk of HCC occurrence and recurrence. There has been a major increase in studies investigating the cutoff liver stiffness value that best predicts the need for monitoring for the onset of HCC. Therefore, this review discusses the new advances that have occurred in the last four years on HCC, highlighting the new frontiers of non-invasive evaluation of HCC subjects, with particular attention regarding the clinical application of liver stiffness assessment for de novo HCC and predicting recurrence in patients with chronic HCV achieving sustained virological response after treatment with direct antiviral agents.

Background: Early identification of response to neoadjuvant chemotherapy (NAC) is instrumental in predicting patients prognosis. However, since a fixed criterion with high accuracy cannot be generalized to molecular subtypes, our study first aimed to redefine grades of clinical response to NAC in invasive breast cancer patients (IBC). And then developed a prognostic model based on clinical features and ultrasound semantics. Methods: A total of 480 IBC patients were enrolled who underwent anthracycline and taxane-based NAC between 2018 and 2020. The decrease rate of the largest diameter was calculated by ultrasound after NAC and their cut-off points were determined among subtypes. Thereafter, a nomogram was constructed based on clinicopathological and ultrasoundrelated data, and validated using the calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and clinical impact curve (CIC). Results: The optimal cut-off points for predicting pCR were 53.23%, 51.56%, 41.89%, and 53.52% in luminal B-like (HER2 negative), luminal B-like (HER2 positive), HER2 positive, and triple-negative, respectively. In addition, time interval, tumor size, molecular subtypes, largest diameter decrease rate, and change of blood perfusion were significantly associated with pCR (all p < 0.05). The prediction model based on the above variables has great predictive power and clinical value. Conclusion: Taken together, our data demonstrated that calculated cut-off points of tumor reduction rates could be reliable in predicting pathological response to NAC and developed nomogram predicting prognosis would help tailor systematic regimens with high precision. [ABSTRACT FROM AUTHOR]

Tests and scales measuring psychological disorders should provide information about how scores relate to other constructs such as quality of life or functional impairment. Such information is necessary to allow that their scores contribute to clinical decision making. The current study analyzes the clinical utility of the Spanish version of the Inventory for Depression and Anxiety Symptoms (IDAS-II) to discriminate between different levels of functional impairment and identify the IDAS-II scales that contribute most to explaining impairment. The total sample (N = 1390) consists of two subsamples: a community sample of the general population (n = 1072) selected by random sampling; and a sample of patients (n = 318) from public and private mental health services. The Spanish IDAS-II for measuring internalizing symptoms and WHODAS 2.0 for measuring impairment were administered to all participants. All scales show statistically significant higher scores in the patient sample, with Cohen's d effect sizes values greater than 0.30, except for well-being (d = 0.19). The cutoff values and their confidence intervals do not overlap with the means of either the community or patient sample. AUC values for most of the scales are above.70, except for appetite gain, ordering, euphoria, cleaning, and well-being. Multiple linear regression model using IDAS-II scales explain 57.1% of the variance of the WHODAS 2.0 (F12.1377 = 155.305; p <.001). Cutoff values provided allow us to reliably differentiate between the patients and community samples. Spanish IDAS-II scores show greater sensitivity and specificity in detecting those with greater impairment. General Depression, Lassitude, Panic and Claustrophobia contribute to impairment in a greater extent. Knowledge of which symptoms are most related with impairment, allows healthcare providers to improve treatment planning based on empirical evidence. [ABSTRACT FROM AUTHOR]

Purpose: To establish reference ranges for four most commonly used diagnostic measures of craniocervical instability (CCI) in three cervical sagittal positions. This necessitated development of a reliable measurement protocol using upright, dynamic MRI (udMRI), to determine differences in the extent of motion between positions, and whether age and sex correlate with these measures. Materials and Methods: Deidentified udMRIs of 50 adults, referred for reasons other than CCI, were captured at three positions (maximal flexion, maximal extension and neutral). Images were analyzed, providing measures of basion-axial interval, basion-axial angle, basion-dens interval (BDI) and the Grabb–Oakes line (GOL) for all three positions (12 measures per participant). All measures were independently recorded by a radiologist and neurosurgeon to determine their reliability. Descriptive statistics, correlations, paired and independent t-tests were used. Mean (± 2 SD) identified the reference range for all four measures at each craniocervical position. Results: The revised measurement protocol produced inter-rater reliability indices of 0.69–0.97 (moderate–excellent). Fifty adults' (50% male; mean age 41.2 years (± 9.7)) reference ranges for all twelve measures were reported. Except for the BDI and GOL when moving between neutral and full flexion, significant extents of movement were identified between the three craniocervical positions for all four measures (p ≤ 0.005). Only a minor effect of age was found. Conclusions: This is the first study to provide a rigorous standardized protocol for four diagnostic measures of CCI. Reference ranges are established at mid and ends of sagittal cervical range corresponding to where exacerbations of signs and symptoms are commonly reported. [ABSTRACT FROM AUTHOR]

Factor analysis is often used to model scales created to measure latent constructs, and internal structure validity evidence is commonly assessed with indices like RMSEA, and CFI. These indices are essentially effect size measures and definitive benchmarks regarding which values connote reasonable fit have been elusive. Simulations from the 1990s suggesting possible benchmark values are among the most highly cited methodological papers across any discipline. However, simulations have suggested that fixed benchmarks do not generalize well – fit indices are systematically impacted by characteristics like the number of items and the magnitude of the loadings, so fixed benchmarks can confound misfit with model characteristics. Alternative frameworks for creating customized, model-specific benchmarks have recently been proposed to circumvent these issues but they have not been systematically evaluated. Motivated by two empirical applications where different methods yield inconsistent conclusions, two simulation studies are performed to assess the ability of three different approaches to correctly classify models that are correct or misspecified across different conditions. Results show that dynamic fit indices and equivalence testing both improved upon the traditional Hu & Bentler benchmarks and dynamic fit indices appeared to be least confounded with model characteristics in the conditions studied. [ABSTRACT FROM AUTHOR]

Background The 5-repetition chair stand test (CST) is increasingly being used to assess locomotion capacity in older adults. However, there is a lack of age-stratified cutoffs for adults aged ≥70 validated against a higher risk of functional loss. Methods We used 2 population-based studies (Study on global AGEing and adult health in Mexico [SAGE Mexico] and Toledo Study for Healthy Aging [TSHA]) and receiver operating characteristic (ROC) analyses to develop and cross-validate age-stratified chair stand cutoffs with activities of daily living (ADL) disability as the outcome. Then, we used data from an randomized controlled trial (RCT) (Multidomain Alzheimer Preventive Trial [MAPT]) and a frailty day-hospital for external validation with cross-sectional and longitudinal measures of ADL disability. The merged sample of SAGE Mexico and TSHA was n = 1 595; sample sizes for external validation were: MAPT n = 1 573 and Frailty day-hospital n = 2 434. The Cox models for incident disability in MAPT had a mean follow-up of 58.6 months. Results Cutoffs obtained were 14 second (ages 70–79) and 16 second (ages 80+). Those cutoffs identified older adults at higher odds of incident ADL disability odds ratio (OR) = 1.72 (95% confidence interval [CI] 1.06; 2.78) for ages 70–79 and odds ratio (OR) = 2.27 (95% CI 1.07; 4.80) in those aged 80+. Being a slow chair stander according to the cut points was associated with ADL disability in cross-sectional and longitudinal measures. Conclusions Fourteen- and 16-second cut points for the CST are suitable to identify people at higher risk of functional decline among older adults in Mexico and Toledo, Spain. Adjusting the cut point from 14 to 16 second generally improved the psychometric properties of the test. The validation of these cutoffs can facilitate the screening for limited mobility and the implementation of the Integrated Care for Older People program. [ABSTRACT FROM AUTHOR]

Background/Purpose: Hypertension is a risk factor of incident diabetes. In 2017, the ACC/AHA updated the definition of hypertension to above 130/80 mmHg, while the 2018 ESC/ESH guideline and the JNC7 criteria remained the cutoff of 140/90 mmHg. This study was aimed to investigate how different cutoffs of hypertension affect the association of hypertension to incident diabetes and the progression of insulin resistance. Methods: A total of 1177 subjects without diabetes at baseline were followed for 4.5 years. Diabetes was diagnosed by the results of oral glucose tolerance tests and hemoglobin A1c, or if anti-diabetic agents were used. Results: Hypertension by both criteria was associated with incident diabetes. Change of HOMA2-IR every 5 years (ΔHOMA2-IR/5 yr) was higher in subjects with hypertension than those without (adjusted p = 0.044). Subjects with treated hypertension had the highest risk of diabetes (HR 2.98, p

Background: Population-derived cutoffs for low skeletal muscle mass, skeletal muscle strength, and frailty among Indians are lacking. Studies describing sarcopenia and frailty among patients with chronic liver diseases have used cutoffs derived from Caucasian populations giving erroneous results. Aims: We aimed to derive gender-specific cutoffs for low skeletal muscle mass and skeletal muscle strength from healthy Indians. Methods: Healthy Indian population consisted of two groups. Group 1 (Gp I) included 242 healthy liver donors and group 2 (Gp II) 272 healthy health care workers. Skeletal muscle index (SMI) was calculated from computed tomography (CT) abdomen performed prior to donor hepatectomy only in Gp I. Liver frailty index (LFI) was computed using the online calculator, after recording hand grip strength (HGS), chair stand-up test (CSUT), and balance test in both groups. HGS was measured using the Smedley handgrip dynamometer. CSUT was noted as time to complete 5 chair stand-ups with subjects' arms folded across the chest. Gender-specific cutoffs of SMI and HGS were derived as <5th percentile of the distribution values and as >95th percentile for CSUT and LFI values. Results: The SMI was measured from Gp I subjects (n=242; 120 males [mean age 31.13] and 122 females [mean age 36.60]). The HGS, CSUT, and LFI were measured in Gp I and Gp II subjects (n=514; 272 males [mean age 34.30] and 242 females [mean age 37.52]). The cutoffs for SMI, HGS, CSUT, and LFI were <27.72 cm2/m2, <25.63 kg, >10 s, and >3.49, respectively for healthy males. The corresponding cutoffs for healthy females were <24.4 cm2/m2, <16.7 kg, > 10 s, and >3.68, respectively. Conclusions: We derived gender-specific cutoffs for SMI, HGS, CSUT, and LFI from healthy adult Indian population, which can be used to detect sarcopenia and frailty among patients with liver diseases, as well as other conditions. [ABSTRACT FROM AUTHOR]

Abstract Background Fall risk assessment and determination of older adults’ individual risk profiles are crucial elements in fall prevention. As such, it is essential to establish cutoffs and reference values for high and low risk according to key risk factor outcomes. This study main objective was to determine the key physical fitness, body composition, physical activity, health condition and environmental hazard risk outcome cutoffs and interval reference values for stratified fall risk assessment in community-dwelling older adults. Methods Five-hundred community-dwelling Portuguese older adults (72.2 ± 5.4 years) were assessed for falls, physical fitness, body composition, physical (in) activity, number of health conditions and environmental hazards, and sociodemographic characteristics. Results The established key outcomes and respective cutoffs and reference values used for fall risk stratification were multidimensional balance (low risk: score > 33, moderate risk: score 32–33, high risk: score 30–31, and very high: score 44 kg, moderate risk: 42–44 kg, high risk: 39–41 kg, and very high: 42%); total physical activity (low risk: > 2800 Met-min/wk., moderate risk: 2300–2800 Met-min/wk., high risk: 1900–2300 Met-min/wk., and very high: 5 h/day); health conditions (low risk: n 5); and environmental hazards (low risk: n 8). Conclusions Assessment of community-dwelling older adults’ fall risk should focus on the above outcomes to establish individual older adults’ fall risk profiles. Moreover, the design of fall prevention interventions should manage a person’s identified risks and take into account the determined cutoffs and respective interval values for fall risk stratification.

Lowland coastal plain rivers are important for navigation and ecosystems, having unique concerns regarding water and sediment management. The Apalachicola River in Florida, the lower end of the ACF (Apalachicola–Chattahoochee–Flint) system, had historical modifications beginning in the 1800s. Most impacts are attributable to the Apalachicola Navigation Project in the latter half of the 20th century, which included dredging, disposal, rock and snag removal, artificial cutoffs, and wing‐dike building. As one of few studies using paired hydrographic surveys over a long reach and time (170 km, 50 years), we defined four zones of bed elevation change between 1960 and 2010 based on the cumulative thalweg elevation plots. The river has four bed change zones: (1) uppermost, marked degradation from river mile (RM) 106 to 85 because of dam construction; (2) middle, minimal degradation from RM 85 to 34; (3) artificial cutoff zone, highest degradation, from RM 34 to 27; and (4) lowermost zone, aggradation from RM 27 to Apalachicola Bay because of upstream bed and bank sediment disturbances. Artificial cutoffs and lithology influence lateral migration, with rates being highest in cutoff zones and least in areas with some bedrock upstream and finer sediments downstream. Length changes from 1941 to 2019 are stable, except for the middle reach, which lengthened nearly 10%, and the lower non‐tidal reach, where length shortened with cutoffs then regained in subsequent decades. Minimizing disturbance has led to 18% of the sand bar area revegetating since a decade of dredging ended. This framework helps in understanding historic and ongoing human activities, notably upstream water consumption, connectivity changes, sediment inputs, and climate change, that will affect the water and sediment management of the river, its floodplain, and bay, thus varying approaches for restoration. [ABSTRACT FROM AUTHOR]

Introduction: The educational background and size of the elderly population are undergoing significant changes in Finland during the 2020s. A similar process is likely to occur also in several European countries. For cognitive screening of early Alzheimer's disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy. The aim of the present study was to examine the effects of education, age, and gender on the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-nb) in a large register-based, clinical sample of patients with mild AD and nondemented at-risk persons from the general population (controls) and to examine whether corrected cutoff scores would increase the accuracy of differentiation between the 2 groups. Methods: CERAD-nb scores were obtained from AD patients (n = 389, 58% women, mean age 74.0 years) and from controls (n = 1,980, 52% women, mean age 68.5 years). The differences in CERAD-nb performance were evaluated by univariate GLM. Differentiation between the 2 groups was evaluated using a receiver operating characteristic (ROC) curve, where a larger area under the ROC curve represents better discrimination. Youden's J was calculated for the overall performance and accuracy of each of the measures. Results: Of the demographic factors, education was the strongest predictor of CERAD-nb performance, explaining more variation than age or gender in both the AD patients and the controls. Education corrected cutoff scores had better diagnostic accuracy in discriminating between the AD patients and controls than existing uncorrected scores. The highest level of discrimination between the 2 groups overall was found for two CERAD-nb total scores. Conclusions: Education-corrected cutoff scores were superior to uncorrected scores in differentiating between controls and AD patients especially for the highest level of education and should therefore be used in clinical cognitive screening, also as the proportion of the educated elderly is increasing substantially during the 2020s. Our results also indicate that total scores of the CERAD-nb are better at discriminating AD patients from controls than any single subtest score. A digital tool for calculating the total scores and comparing education-based cutoffs would increase the efficiency and usability of the test. [ABSTRACT FROM AUTHOR]

Background/purpose: Hypertension is a risk factor of incident diabetes. In 2017, the ACC/AHA updated the definition of hypertension to above 130/80 mmHg, while the 2018 ESC/ESH guideline and the JNC7 criteria remained the cutoff of 140/90 mmHg. This study was aimed to investigate how different cutoffs of hypertension affect the association of hypertension to incident diabetes and the progression of insulin resistance.Methods: A total of 1177 subjects without diabetes at baseline were followed for 4.5 years. Diabetes was diagnosed by the results of oral glucose tolerance tests and hemoglobin A1c, or if anti-diabetic agents were used.Results: Hypertension by both criteria was associated with incident diabetes. Change of HOMA2-IR every 5 years (ΔHOMA2-IR/5 yr) was higher in subjects with hypertension than those without (adjusted p = 0.044). Subjects with treated hypertension had the highest risk of diabetes (HR 2.98, p < 0.001) and ΔHOMA2-IR/5 yr, compared with subjects with normal blood pressure. However, the associations of hypertension, HR of incident diabetes and ΔHOMA2-IR/5 yr were attenuated by the 2017 ACC/AHA criteria, as compared with that by the JNC7 and 2018 ESC/ESH criteria.Conclusion: Hypertension by both criteria is associated with incident diabetes and accelerated progression of insulin resistance, and the associations are attenuated by the 2017 ACC/AHA criteria. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (ICI) therapies can achieve meaningful tumor responses in a subset of patients with most types of cancer that have been investigated. However, the majority of patients treated with these drugs do not experience any clinical benefit. Because not all patients benefit from ICIs, and some may experience more meaningful tumor response if treated with chemotherapy or other treatments, there is a compelling need for predictive biomarkers to facilitate more informed selection of therapy. Tumor mutational burden (TMB) is one feature of a tumor that has predictive value for ICI therapy across multiple cancer types. In a pan-cancer analysis of over 1,600 patients, higher TMB was associated with longer survival and higher response rates with ICI therapy. While this effect was seen in the majority of cancer types, indicating that TMB underlies fundamental aspects of immune-mediated tumor rejection, the optimal predictive cut-point varied widely by histology, suggesting that there is unlikely to be one tissue-agnostic definition of high TMB that is useful for predicting ICI response. More comprehensive predictive models integrating TMB with other factors – including genetic, immunologic, and clinicopathologic markers – will be needed to potentially achieve a tissue-agnostic predictor of benefit from ICIs.

Background: Fall risk assessment and determination of older adults' individual risk profiles are crucial elements in fall prevention. As such, it is essential to establish cutoffs and reference values for high and low risk according to key risk factor outcomes. This study main objective was to determine the key physical fitness, body composition, physical activity, health condition and environmental hazard risk outcome cutoffs and interval reference values for stratified fall risk assessment in community-dwelling older adults.Methods: Five-hundred community-dwelling Portuguese older adults (72.2 ± 5.4 years) were assessed for falls, physical fitness, body composition, physical (in) activity, number of health conditions and environmental hazards, and sociodemographic characteristics.Results: The established key outcomes and respective cutoffs and reference values used for fall risk stratification were multidimensional balance (low risk: score > 33, moderate risk: score 32-33, high risk: score 30-31, and very high: score < 30); lean body mass (low risk: > 44 kg, moderate risk: 42-44 kg, high risk: 39-41 kg, and very high: < 39 kg); fat body mass (low risk: < 37%, moderate risk: 37-38%, high risk: 39-42%, and very high: > 42%); total physical activity (low risk: > 2800 Met-min/wk., moderate risk: 2300-2800 Met-min/wk., high risk: 1900-2300 Met-min/wk., and very high: < 1900 Met-min/wk); rest period weekdays (low risk: < 4 h/day, moderate risk: 4-4.4 h/day, high risk: 4.5-5 h/day, and very high: > 5 h/day); health conditions (low risk: n < 3, moderate risk: n = 3, high risk: n = 4-5, and very high: n > 5); and environmental hazards (low risk: n < 5, moderate risk: n = 5, high risk: n = 6-8, and very high: n > 8).Conclusions: Assessment of community-dwelling older adults' fall risk should focus on the above outcomes to establish individual older adults' fall risk profiles. Moreover, the design of fall prevention interventions should manage a person's identified risks and take into account the determined cutoffs and respective interval values for fall risk stratification. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer with a 5‐year survival rate of less than 5%. As in many other diseases, its diagnosis might involve progressive stages. It is common that in biomarker studies referring to PDAC, recruitment involves three groups: healthy individuals, patients that suffer from chronic pancreatitis, and PDAC patients. Early detection and accurate classification of the state of the disease are crucial for patients' successful treatment. ROC analysis is the most popular way to evaluate the performance of a biomarker and the Youden index is commonly employed for cutoff derivation. The so‐called generalized Youden index has a drawback in the three‐class case of not accommodating the full data set when estimating the optimal cutoffs. In this article, we explore the use of the Euclidean distance of the ROC to the perfection corner for the derivation of cutoffs in trichotomous settings. We construct an inferential framework that involves both parametric and nonparametric techniques. Our methods can accommodate the full information of a given data set and thus provide more accurate estimates in terms of the decision‐making cutoffs compared with a Youden‐based strategy. We evaluate our approaches through extensive simulations and illustrate them on a PDAC biomarker study. [ABSTRACT FROM AUTHOR]

The assessment of prognostic markers is key to the improvement of therapeutic strategies for cancer patients. Some promising markers may fail to be applied in clinical practice, or some useless markers may be applied, because of misleading results ensuing from inadequate planning of the study and/or from an oversimplified statistical analysis. This commentary illustrates and discusses the main issues involved in planning an effective clinical study and the subsequent statistical analysis for the prognostic evaluation of a cancer marker. Another aim is to extend the most applied statistical models (ie, those using Kaplan-Meier and Cox) to enable the choice of the best-suited methods for study endpoints. Specifically, for tumor-centered endpoints like tumor recurrence, the issue of competing risks is highlighted. For markers measured on a continuous numerical scale, a loss of relevant prognostic information may occur by setting arbitrary cutoffs; thus, the methods to analyze the original scale are explained. Furthermore, because the P -value is not a sufficient criterion to assess the usefulness of a marker in clinical practice, measures for evaluating the ability of the marker to discriminate between "good" and "bad" prognoses are illustrated. Several tumor markers are considered both in human and veterinary medicine. Given the similarity between markers for human breast cancer and canine mammary cancer, an application of the statistical methods discussed within the article to a public dataset from human breast cancer patients is shown. [ABSTRACT FROM AUTHOR]

Abstract Background Iron deficiency is highly prevalent in chronic kidney disease (CKD) patients. In clinical practice, iron deficiency is defined based on a combination of two commonly used markers, ferritin and transferrin saturation (TSAT). However, no consensus has been reached which cutoffs of these parameters should be applied to define iron deficiency. Hence, we aimed to assess prospectively which cutoffs of ferritin and TSAT performed optimally for outcomes in CKD patients. Methods We meticulously analyzed 975 CKD community dwelling patients of the Prevention of Renal and Vascular Endstage Disease prospective study based on an estimated glomerular filtration rate 30 mg/24 h, or albumin-to-creatinine ratio ≥ 30 mg/g. Cox proportional hazard regression analyses using different sets and combinations of cutoffs of ferritin and TSAT were performed to assess prospective associations with all-cause mortality, cardiovascular mortality, and development of anemia. Results Of the included 975 CKD patients (62 ± 12 years, 64% male with an estimated glomerular filtration rate of 77 ± 23 ml/min/1.73m2), 173 CKD patients died during a median follow-up of 8.0 (interquartile range 7.5–8.7) years of which 70 from a cardiovascular cause. Furthermore, 164 CKD patients developed anemia. The highest risk for all-cause mortality (hazard ratio, 2.83; 95% confidence interval, 1.53–5.24), cardiovascular mortality (4.15; 1.78–9.66), and developing anemia (3.07; 1.69–5.57) was uniformly observed for a TSAT

Scientific Centre for Family Health and Human Reproduction Problems (ul. Timiryazeva 16, Irkutsk 664003, Russian Federation) Problems of pathogenesis, diagnosis, and treatment of obesity are actively discussed. The annual increase in the incidence requires improved approaches to prevention, diagnosis, and drug-free treatment of this pathological condition. Modern estimates of obesity ignore modern concepts of the heterogeneity of the disease, the role of visceral fat depots, metabolic phenotypes, and the individual cardiometabolic risk in a patient is not fully assessed. The prevalence of obesity is increasing among Asian adults due to rapid economic development and lifestyle. Obesity significantly elevates the risk of CVD (cardiovascular disease), diabetes, insulin resistance and other metabolic disorders. BMI is a widely used anthropometric index for measuring body fatness in clinical practice and epidemiological studies; Asian people are more likely to have a higher percentage of body fat at lower BMI and WC than Europeans, a number of researches were to determine the associations of BM1, waist circumference (WC) and waist-height ratio (WHtR) with CVD risk factors and to evaluate the optimal cut-offvalues to define overweight or obesity in Asian adults. In this review the major pathological factors connected to obesity are generalized. It has not been established which specific measures of obesity might be most appropriate for predicting CVD risk in Asians.

The Broca formula was developed in 1871 by Pierre Paul Broca (a French Army Doctor) to help establish ideal body weight or normal body weight. Initially, the Broca Index (BI) was used to work out the normal weight but was later expanded to ideal Body Weight. Ideal Body weight (kg) = [Height (cm)-100]. The common methods used to explore the levels of adiposity include body mass index (BMI), waist circumference, skinfolds, bioelectrical impedance analysis, dual energy x-ray absorptiometry (DEXA), computerized tomography (CT) and magnetic resonance imaging (MRI). Even though there have been several anthropometric measurements discoveries to assess obesity, BMI is still widely used in many clinic centers around the world. It remains simple and relatively inexpensive to measure and easily obtainable in non-laboratory settings. In this review, we will summarize the common methods used to measure body fat and their limitations. Second, we will show the correlation that may exist between Broca Index and BMI cutoffs. Last, we will underline some potential clinical usefulness that may present Broca index in assessing body fat. [ABSTRACT FROM AUTHOR]

Data for urine cotinine and hydroxycotinine became available for the first time in the 2013–2014 cycle of the National Health and Nutrition Examination Survey administered by the US Centers for Disease Control and Prevention. Cutoffs to classify smokers and nonsmokers for both cotinine and hydroxycotinine for US adults aged ≥ 20 years were developed by using receiver operating characteristic curve methodology. The optimality criterion used to determine cutoffs simultaneously maximized both specificity and sensitivity. Cutoffs were determined for the total population, males, females, non-Hispanic whites, non-Hispanic blacks, Hispanics, and non-Hispanic Asians. Cutoffs for both cotinine and hydroxycotinine were determined with a minimum sensitivity of 95.5% and with a minimum specificity of 95.4%. For the total population, cutoff for urine cotinine was 91.7 ng/mL estimated with a specificity as well as a sensitivity of 97.1%. The cutoff for the total population for urine hydroxycotinine was 128.0 ng/mL estimated with a specificity as well as a sensitivity of 96.5%. The order in which cutoffs were observed for cotinine was non-Hispanic blacks (283.0 ng/mL) > non-Hispanic whites (111.0 ng/mL) > males (109.0 ng/mL) > females (91.7 ng/mL) > total population (91.7 ng/mL) > Hispanics (20.8 ng/mL) > non-Hispanic Asians (7.39 ng/mL). The order in which cutoffs were observed for hydroxycotinine was non-Hispanic blacks (530.0 ng/mL) > non-Hispanic whites (180.0 ng/mL) > females (97.0 ng/mL) > total population (96.5 ng/mL) > males (95.9 ng/mL) > Hispanics (20.6 ng/mL) > non-Hispanic Asians (13.8 ng/mL). Thus, the largest cutoffs were observed for non-Hispanic blacks and the lowest cutoffs were observed for non-Hispanic Asians. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: A wide variety of reference lines and landmarks have been used in imaging studies to diagnose and quantify posterior vaginal wall prolapse without consensus. We sought to determine which is the best system to (1) identify posterior vaginal wall prolapse and its appropriate cutoff values and (2) assess the prolapse size. Methods: This was a secondary analysis of sagittal maximal Valsalva dynamic MRI scans from 52 posterior-predominant prolapse cases and 60 comparable controls from ongoing research. All eight existing measurement lines and a new parameter, the exposed vaginal length, were measured. Expert opinions were used to score the prolapse sizes. Simple linear regressions, effect sizes, area under the curve, and classification and regression tree analyses were used to compare these reference systems and determine cutoff values. Linear and ordinal logistic regressions were used to assess the effectiveness of the prolapse size. Results: Among existing parameters, "the perineal line-internal pubis," a reference line from the inside of the pubic symphysis to the front tip of the perineal body (cutoff value 0.9 cm), had the largest effect size (1.61), showed the highest sensitivity and specificity to discriminate prolapse with area under the curve (0.91), and explained the most variation (68%) in prolapse size scores. The exposed vaginal length (cutoff value 2.9) outperformed all the existing lines, with the largest effect size (2.09), area under the curve (0.95), and R-squared value (0.77). Conclusions: The exposed vaginal length performs slightly better than the best of the existing systems, for both diagnosing and quantifying posterior prolapse size. Performance characteristics and evidence-based cutoffs might be useful in clinical practice. [ABSTRACT FROM AUTHOR]

Rationing is an unavoidable mechanism for reining in healthcare costs. It entails establishing cutoff points that distinguish between what is and is not offered or available to patients. When the resource to be distributed is defined by vague and indeterminate terms such as "beneficial," "effective," or even "futile," the ability to draw meaningful boundary lines that are both ethically and medically sound is problematic. In this article, I draw a parallel between the challenges posed by this problem and the ancient Greek philosophical conundrum known as the "sorites paradox." I argue, like the paradox, that the dilemma is unsolvable by conventional means of logical analysis. However, I propose another approach that may offer a practical solution that could be applicable to real-life situations in which cutoffs must be decided (such as rationing). [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to present the prevalence and concentrations of drugs in blood samples of drivers involved in road traffic accidents (RTAs) and to discuss the effects of adopting different concentration cutoff values proposed or applied in other European countries on the number of driving under the influence of drugs (DUID) offenses.Methods: Blood samples from drivers involved in RTAs in Padova province from 2014 to 2017 were analyzed for the presence of alcohol and drugs. The prevalence of positive subjects was reported for each substance adopting the limits of quantification (LOQs) of our laboratory and the concentration cutoff values proposed and/or used in other European countries. The reduction of cases of driving under the influence of illicit drugs in applying different cutoffs was calculated.Results: Four thousand four hundred forty-three blood samples were analyzed: 23.7% were positive for alcohol and 19.9% for psychoactive drugs, with prevalences of polydrug and alcohol-drug abuse of 4.5 and 6%, respectively. The most frequently detected drugs were cannabinoids (9.7%) and cocaine (7.2%), followed by benzodiazepines (4.1%), opiates (1.9%), and other opioids (1.7%). Barbiturates, amphetamines, and ketamine were identified in a much smaller number of cases. The overall decrease in DUID cases when adopting different cutoffs with respect to cases above the LOQs was between 8 and 84%. The adoption of high LOQs such as those used in the European Union's research project on Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) decreases the hypothetical number of DUID offenses by a quarter, and per se limits proposed as broadly equivalent to a blood alcohol concentration (BAC) between 0.2 and 0.8 g/L dramatically reduce the cases of DUID (cocaine -81%, cannabis -79%, opioids -97%, opiates -96%, and amphetamines -77%); no ketamine-positive samples were above the cutoff.Conclusions: The implementation of high analytical limits or per se limits based on impairing concentrations in the Italian legislation could result in the prosecution of a much lower number of drugged drivers involved in RTAs, with a decrease from 25% to more than 80% depending on the limits. [ABSTRACT FROM AUTHOR]

Abstract We consider products of ergodic Markov chains and discuss their cutoffs in total variation. Our framework is general in that rates to pick up coordinates are not necessary equal, and different coordinates may correspond to distinct chains. We give necessary and sufficient conditions for cutoffs of product chains in terms of those of coordinate chains under certain conditions. A comparison of mixing times between the product chain and its coordinate chains is made in detail as well. Examples are given to show that neither cutoffs for product chains nor for coordinate chains imply others in general. [ABSTRACT FROM AUTHOR]

Introduction: We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort. Methods: Cutoffs for Elecsys amyloid‐β1–42 (Aβ), total tau/Aβ(1–42), and phosphorylated tau/Aβ(1–42) were defined against [18F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [18F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646). Clinical progression in patients with mild cognitive impairment (n = 619) was studied. Results: CSF total tau/Aβ(1–42) and phosphorylated tau/Aβ(1–42) ratios were highly concordant with PET classification in BioFINDER (overall percent agreement: 90%; area under the curve: 94%). The CSF biomarker statuses established by predefined cutoffs were highly concordant with PET classification in Alzheimer's Disease Neuroimaging Initiative (overall percent agreement: 89%–90%; area under the curves: 96%) and predicted greater 2‐year clinical decline in patients with mild cognitive impairment. Strikingly, tau/Aβ ratios were as accurate as semiquantitative PET image assessment in predicting visual read–based outcomes. Discussion: Elecsys CSF biomarker assays may provide reliable alternatives to PET in Alzheimer's disease diagnosis. [ABSTRACT FROM AUTHOR]

Background: Limited information is available on the cutoffs of waist circumference (WC) for predicting type 2 diabetes mellitus (T2DM). We aimed to define the optimal WC cutoffs for predicting T2DM among rural Chinese people.Methods: A cohort of 11 968 participants (732 new-onset T2DM) from a rural area in China with age 18 to 87 years was established at baseline during July to August of 2007 and 2008 and followed up during July to August of 2013 and 2014. Scatterplot, X-tile plot, and receiver operating characteristic (ROC) curve analyses were used to determine WC cutoffs for predicting T2DM.Results: The WC cutoffs for males and females were 84 and 86 cm (scatterplot), 83 and 88 cm (X-tile plot), and 87 and 88 cm (ROC curve). According to the highest risk score, the optimal WC cutoffs were 87 cm for males and 88 cm for females. With the optimal WC cutoffs, the sensitivity, specificity, positive likelihood ratio, area under the ROC curve, and population-attributable risk proportions were 67.9%, 67.0%, 2.06%, 0.70%, and 46%, respectively, for males and 52.5%, 75.0%, 2.10%, 0.69%, and 34%, respectively, for females; the corresponding adjusted hazard ratio for WC predicting T2DM was 3.66 (95% confidence interval 2.80-4.78) for males and 2.55 (2.08-3.12) for females.Conclusions: The optimal WC cutoffs for predicting T2DM were similar between males and females. As well, the criteria of WC for central obesity are no longer practical for predicting T2DM. [ABSTRACT FROM AUTHOR]

Background: Body fat redistribution and metabolic abnormalities found in HIV patients receiving highly active antiretroviral therapy (HAART) contribute to an atherogenic profile, increasing cardiovascular disease risk. Objective: We aimed to evaluate adiposity measures/indexes and propose cutoffs associated with predictors of cardiovascular disease risk in HIV patients on HAART. Design: To evaluate cardiovascular disease risk in this crosssectional study, we conducted electrocardiogram exams and stress electrocardiography, measured the ankle brachial index and blood pressure arterial hypertension, conducted lipid biochemical tests, and measured blood glucose.We measured circumferences [waist (WC), hip, thigh, calf, neck, trunk] and skinfold thicknesses (biceps, triceps, subscapular, suprailiac), conducted bioelectrical impedance analysis (BIA), and calculated indexes [body mass index, waist-to-hip ratio, waist-to-thigh ratio, waist-to-calf ratio, waist-to-height ratio (WHtR), trunk-to-arm ratio, body mass index corrected for body fat mass, Body Adiposity Index, conicity index, body shape index, fat mass (percentage), and phase angle]. For evaluating the performance of all adiposity measures/indexes, we used receiver operating characteristic (ROC) curves. Results: Measures of central adiposity WC and WHtR showed the best performances--WC area under the curve (AUC) for men: 0.83 (95% CI: 0.78, 0.89; P < 0.05); WC AUC for women: 0.86 (95% CI: 0.81, 0.91; P < 0.05); WHtR AUC for men: 0.83 (95% CI: 0.78, 0.88; P < 0.05); and WHtR AUC for women: 0.85 (95% CI: 0.80, 0.91; P < 0.05). All adiposity measures/indexes presented different cutoffs from those proposed for the HIV seronegative population. The cutoffs for WC were 87.75 cm (sensitivity: 82.2%; specificity: 75.5%) for men and 90.5 cm (sensitivity: 84.0%; specificity: 73.0%) for women. Conclusions: The measures/indexes of central adiposity presented excellent associations with predictors of cardiovascular disease risk, and the use of the cutoffs proposed in the present study aims to contribute to the early identification of increasing risk of cardiovascular diseases, enabling interventions. This trial was registered at the Brazilian clinical trials registry Registro brasileiro de ensaios clínicos (Rebec) as RBR-9rcxbq. [ABSTRACT FROM AUTHOR]

Determination of iron status in pregnancy and in young children is essential for both clinical and public health practice. Clinical diagnosis of iron deficiency (ID) through sampling of bone marrow to identify the absence of body iron stores is impractical in most cases. Serum ferritin (SF) concentrations are the most commonly deployed indicator for determining ID, and low SF concentrations reflect a state of iron depletion. However, there is considerable variation in SF cutoffs recommended by different expert groups to diagnose ID. Moreover, the cutoffs used in different clinical laboratories are heterogeneous. There are few studies of diagnostic test accuracy to establish the sensitivity and specificity of SF compared with key gold standards (such as absent bone marrow iron stores, increased intestinal iron absorption, and hemoglobin response to SF) among noninflamed, outpatient populations. The limited data available suggest the commonly recommended SF cutoff of, 15 mg/L is a specific but not sensitive cutoff, although evidence is limited. Data from women during pregnancy or from young children are especially uncommon. Most data are from studies conducted .30 y ago, do not reflect ethnic or geographic diversity, and were performed in an era for which laboratory methods no longer reflect present practice. Future studies to define the appropriate SF cutoffs are urgently needed and would also provide an opportunity to compare this indicator with other established and emerging iron indexes. In addition, future work would benefit from a focus on elucidating cutoffs and indexes relevant to iron adequacy. [ABSTRACT FROM AUTHOR]

Background: In clinical and epidemiological studies, cutoffs of patient-reported outcome measures can be used to classify patients into groups of statistical and clinical relevance. However, visual analog scale (VAS) cutoffs in MASK-air have not been tested., Objective: To calculate cutoffs for VAS global, nasal, ocular, and asthma symptoms., Methods: In a cross-sectional study design of all MASK-air participants, we compared (1) approaches based on the percentiles (tertiles or quartiles) of VAS distributions and (2) data-driven approaches based on clusters of data from 2 comparators (VAS work and VAS sleep). We then performed sensitivity analyses for individual countries and for VAS levels corresponding to full allergy control. Finally, we tested the different approaches using MASK-air real-world cross-sectional and longitudinal data to assess the most relevant cutoffs., Results: We assessed 395,223 days from 23,201 MASK-air users with self-reported allergic rhinitis. The percentile-oriented approach resulted in lower cutoff values than the data-driven approach. We obtained consistent results in the data-driven approach. Following the latter, the proposed cutoff differentiating "controlled" and "partly-controlled" patients was similar to the cutoff value that had been arbitrarily used (20/100). However, a lower cutoff was obtained to differentiate between "partly-controlled" and "uncontrolled" patients (35 vs the arbitrarily-used value of 50/100)., Conclusions: Using a data-driven approach, we were able to define cutoff values for MASK-air VASs on allergy and asthma symptoms. This may allow for a better classification of patients with rhinitis and asthma according to different levels of control, supporting improved disease management., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

We study the problem of verifying role-based multi-agent systems, where the number of components cannot be determined at design time. We give a semantics that captures parameterised, generic multi-agent systems and identify three notable classes that represent different ways in which the agents may interact among themselves and with the environment. While the verification problem is undecidable in general we put forward cutoff procedures for the classes identified. The methodology is based on the existence of a notion of simulation between the templates for the agents and the template for the environment in the system. We show that the cutoff identification procedures as well as the general algorithms that we propose are sound; for one class we show the decidability of the verification problem and present a complete cutoff procedure. We report experimental results obtained on MCMAS-P , a novel model checker implementing the parameterised model checking methodologies here devised. [ABSTRACT FROM AUTHOR]

Background: Early identification of response to neoadjuvant chemotherapy (NAC) is instrumental in predicting patients prognosis. However, since a fixed criterion with high accuracy cannot be generalized to molecular subtypes, our study first aimed to redefine grades of clinical response to NAC in invasive breast cancer patients (IBC). And then developed a prognostic model based on clinical features and ultrasound semantics., Methods: A total of 480 IBC patients were enrolled who underwent anthracycline and taxane-based NAC between 2018 and 2020. The decrease rate of the largest diameter was calculated by ultrasound after NAC and their cut-off points were determined among subtypes. Thereafter, a nomogram was constructed based on clinicopathological and ultrasound-related data, and validated using the calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and clinical impact curve (CIC)., Results: The optimal cut-off points for predicting pCR were 53.23%, 51.56%, 41.89%, and 53.52% in luminal B-like (HER2 negative), luminal B-like (HER2 positive), HER2 positive, and triple-negative, respectively. In addition, time interval, tumor size, molecular subtypes, largest diameter decrease rate, and change of blood perfusion were significantly associated with pCR (all p < 0.05). The prediction model based on the above variables has great predictive power and clinical value., Conclusion: Taken together, our data demonstrated that calculated cut-off points of tumor reduction rates could be reliable in predicting pathological response to NAC and developed nomogram predicting prognosis would help tailor systematic regimens with high precision., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Meng, Yu, Cai, Wang, Cao and Ge.)

Context Depression is common among patients with advanced disease but often difficult to detect. Objectives To assess the Palliative care Outcome Scale (POS) (10 items) against the Geriatric Depression Scale (GDS)-10 total score and the Hospital Anxiety and Depression Scale (HADS)-Depression subscale total score and determine if the POS has appropriate items to screen for depression among people with advanced disease. Methods This was a secondary analysis performed on five studies. Four psychometric properties were assessed: data quality, scaling assumptions, acceptability, and internal consistency (reliability). Receiver operating characteristic (ROC) curves were used to determine the area under the curve. Sensitivity, specificity, positive and negative predictive values, false positive and negative rates, and positive and negative likelihood ratios were computed. Results The overall sample had 416 patients from Germany and England: 144 had cancer and 267 had nonmalignant conditions. Prevalence of depression across the sample was 17.5%. Floor and ceiling effects were rare. Cronbach's alpha coefficients for POS items 7 and 8 summed, GDS-10 and HADS-Depression items varied: 0.61 (heart failure) and 0.80 (cancer). Two items combined (Item 7—feeling depressed and Item 8—feeling good about yourself) consistently presented the highest area under the ROC curve, ranging from 0.76 (95% CI 0.60, 0.93) (Germany, lung cancer) to 0.97 (95% CI 0.91, 1.0) (heart failure), highest negative predictive value, and lowest false negative rate. For the overall sample, the cutoff 2/3 presented a negative predictive value of 89.4% (95% CI 84.7, 92.8) and false negative rate of 10.6 (95% CI 7.2, 15.3). Conclusion POS items 7 and 8 summed are potentially useful to screen for depression in advanced disease populations. [ABSTRACT FROM AUTHOR]

Large numbers of perennial rivers flowing through steep gradient has made Nepal an ideal place for hydropower development. Development of hydropower project in most economical way possible is the first prerequisite to get maximum benefit from harnessing water resources. The maximum benefit can be achieved only through optimal design of the project. Each project component must be designed considering the required level of factor of safety, performance standards of each component and economy. On this backdrop, this paper intends to optimize the location of cutoffs in headworks to get maximum benefits from use of it in terms of safety and economy. Improper placement of cutoff not only reduces the factor of safety against piping but also curtails the project benefits due to excessive seepage flow. Piping (internal erosion of soil particles under structure) is associated with high exit gradient. It threatens the structural stability and ultimately leads to failure of structure while as excessive seepage flow limits the availability of flow for power generation and reduces the project benefits. So, the optimal design of headworks is an attempt to identify the best location of cutoff to control seepage flow and reduce exit gradient. Five different cases representing different location of cutoff were analyzed and their roles in controlling seepage flow and reducing exit gradient was evaluated to optimize the cutoff location. 2D Finite Element Method (FEM) was used for the seepage analysis. The analysis showed that cutoffs are essential to control seepage flow when dam/weir is founded in pervious soil. However, the best location to place cutoff must be adroitly identified to reap maximum benefit from use of cutoff. The analysis reveals that the role of central cutoff in controlling seepage flow and reducing exit gradient is very limited. Likewise, the u/s cutoff has minimum effect in reducing exit gradient but the d/s cutoff seemed very effective in reducing exit gradient resulting increased factor of safety against piping. Hence, this paper concludes that the d/s end is the optimal location to place cutoff to improve safety and economy of the project. In addition, the use of both u/s and d/s cutoffs extend positive roles both in controlling seepage flow and reducing exit gradient. However, in author's opinion the construction cost of two cutoffs must be compared with benefit added by use of two cutoffs over use of single d/s cutoff. [ABSTRACT FROM AUTHOR]