Discriminative Thresholds Research Articles

Utility of Risk Analysis Index for Assessing Morbidity in Patients Undergoing Posterior Spinal Fusion for Adult Spinal Deformity

This study investigates the predictive values of the Risk Analysis Index (RAI), the modified 5-item Frailty Index (mFI-5), and advanced age for predicting 30-day extended length of stay (LOS), 30-day complications and readmissions in patients undergoing posterior spinal fusion (PSF) for adult spinal deformity (ASD). A retrospective cohort study was performed using the 2012-2021 ACS NSQIP database. Adults undergoing posterior spinal fusion for ASD were identified using CPT and ICD codes. Using receiver operating characteristic (ROC) and multivariable analyses, we compared the discriminative thresholds and independent associations of RAI, mFI-5, and greater patient age for extended LOS, 30-day complications and readmissions. In this cohort of 3,814 patients, RAI identified 90.7% as Robust, 6.0% as Normal, and 3.3% as Frail/Very Frail, while mFI-5 classified 47.1% as Robust, 37.5% as Normal, and 15.3% as Frail/Very Frail. Multivariate analysis revealed both RAI and mFI-5 as significant predictors of extended LOS for Normal (RAI: p<0.001; mFI-5: p=0.012) and Frail/Very Frail patients (RAI: p<0.001; mFI-5: p=0.002). Additionally, RAI was a significant predictor of 30-day complication risk for Normal patients (p=0.005). Furthermore, mFI-5 was a significant predictor of 30-day readmission among Frail/Very Frail patients (p=0.002). This study highlights the utility of RAI and mFI-5 in predicting extended LOS patients undergoing PSF for ASD. RAI was found to be superior to mFI-5 for predicting 30-day readmissions, while mF-5 was greater for 30-day complications. These findings highlight the importance of incorporating frailty assessments into preoperative surgical planning.

Assessing a revised-risk analysis index for morbidity and mortality after spine surgery for metastatic spinal tumors.

Risk Analysis Index (RAI) has been increasingly used to assess surgical frailty in various procedures, but its effectiveness in predicting mortality or in-patient hospital outcomes for spine surgery in metastatic disease remains unclear. The aim of this study was to compare the predictive values of the revised RAI (RAI-rev), the modified frailty index-5 (mFI-5), and advanced age for extended length of stay, 30-day readmission, complications, and mortality among patients undergoing spine surgery for metastatic spinal tumors. A retrospective cohort study was performed using the 2012-2022 ACS NSQIP database to identify adult patients who underwent spinal surgery for metastatic spinal pathologies. Using receiver operating characteristic (ROC) and multivariable analyses, we compared the discriminative thresholds and independent associations of RAI-rev, mFI-5, and greater patient age with extended length of stay (LOS), 30-day complications, hospital readmission, and mortality. A total of 1,796 patients were identified, of which 1,116 (62.1%) were male and 1,008 (70.7%) were non-Hispanic White. RAI-rev identified 1,291 (71.9%) frail and 208 (11.6%) very frail patients, while mFI-5 identified 272 (15.1%) frail and 49 (2.7%) very frail patients. In the ROC analysis for extended LOS, both RAI-rev and mFI-5 showed modest predictive capabilities with area under the curve (AUC) values of 0.5477 and 0.5329, respectively, and no significant difference in their predictive abilities (p = 0.446). When compared to age, RAI-rev demonstrated superior prediction (p = 0.015). With respect to predicting 30-day readmission, no significant difference was observed between RAI-rev and mFI-5 (AUC 0.5394 l respectively, p = 0.354). However, RAI-rev outperformed age (p = 0.001). When assessing the risk of 30-day complications, RAI-rev significantly outperformed mFI-5 (AUC: 0.6016 and 0.5542 respectively, p = 0.022) but not age. Notably, RAI-rev demonstrated superior ability for predicting 30-day mortality compared to mFI-5 and age (AUC: 0.6541, 0.5652, and 0.5515 respectively, p < 0.001). Multivariate analysis revealed RAI-rev as a significant predictor of extended LOS [aOR: 1.96, 95% CI: 1.13-3.38, p = 0.016] and 30-day mortality [aOR: 5.27, 95% CI: 1.73-16.06, p = 0.003] for very frail patients. Similarly, the RAI-rev significantly predicted 30-day complications for frail [aOR: 2.63, 95% CI: 1.21-5.72, p = 0.015] and very frail [aOR: 3.69, 95% CI: 1.60-8.51, p = 0.002] patients. However, the RAI did not significantly predict 30-day readmission [Very Frail aOR: 1.52, 95% CI: 0.75-3.07, p = 0.245; Frail aOR: 1.46, 95% CI: 0.79-2.68, p = 0.225]. Our study demonstrates the utility of RAI-rev in predicting morbidity and mortality in patients undergoing spine surgery for metastatic spinal pathologies. Particularly, the superiority that RAI-rev has in predicting 30-day mortality may have significant implications in multidisciplinary decision making.

The association of quantitative PSMA PET parameters with pathologic ISUP grade: an international multicenter analysis.

To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.

The utility of heart rate and heart rate variability to identify limits of tolerance to moderate-intensity work in the heat: a secondary analysis.

We investigated the utility of heart rate (HR) and heart rate variability (HRV) for identifying individuals who may terminate work early due to excessive heat strain. Forty-eight men and women (median=36 years; Q1=20 years; Q3=54 years) attempted 180 min of moderate-intensity work at a fixed metabolic rate (∼200W/m2; ∼3.5 METs) in a hot environment (wet-bulb globe temperature: 32 °C). Receiver operating characteristics (ROC) curves were used to identify the ability of indices of HR (absolute HR, percentage of maximum HR, percentage of HR reserve) and HRV (root-mean-square of successive differences (RMSSD), high-frequency power, and detrended fluctuation analysis component alpha 1 (DFA α1)) to discriminate between participants who completed the 180 min work bout or terminated prematurely. Participants who terminated work prematurely (n=26) exhibited higher HR and percentage of HR measures, as well as reduced RMSSD and DFA α1 after the first hour of work compared to participants who completed the bout. The discriminative utility of HR and HRV indices was strongest within the first hour of work, with percentage of HR reserve demonstrating excellent discriminative power (ROC area under curve (AUC) of 0.8). Stratifying participants by age and sex improved ROC AUC point estimates for most indices, particularly in female participants. The study provides preliminary evidence supporting the use of noninvasive cardiac monitoring for predicting work tolerance in healthy individuals exposed to occupational heat stress. HR and percentage of HR reserve were suggested to discriminate work termination most effectively. Further investigations are warranted to explore the influence of individual factors and refine the discriminative thresholds for early identification of excessive occupational heat strain.

A comprehensive analysis of the triad of frailty, aging, and obesity in spine surgery: the risk analysis index predicted 30-day mortality with superior discrimination

BACKGROUND CONTEXTThe United States has experienced substantial shifts in its population dynamics due to an aging population and increasing obesity rates. Nonetheless, there is limited data about the interplay between the triad of frailty, aging, and obesity. PURPOSETo investigate discriminative thresholds and independent associations of the Risk Analysis Index (RAI), Modified Frailty Index-5 (mFI-5), and greater patient age. STUDY DESIGNAn observational retrospective cohort study. PATIENT SAMPLEWe analyzed 49,754 spine surgery patients from the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2020. OUTCOME MEASUREA total of 30-day postoperative mortality. METHODSUsing receiver operating characteristic (ROC) and multivariable (odds ratios [OR] and 95% confidence intervals [CI]) analyses, we compared the discriminative thresholds and independent associations of RAI, mFI-5, and greater patient age in elderly obese patients who underwent spine surgery. RESULTSThere were 49,754 spine surgery patients, with a median age of 71 years (IQR: 68–75), largely white (82.6%) and male (51.9%). The ROC analysis for 30-day postoperative mortality demonstrated superior discrimination for RAI (C–statistic 0.779, 95%CI 0.54–0.805) compared to mFI-5 (C–statistic 0.623, 95% CI 0.594–0.651) and greater patient age (C–statistic 0.627, 95% CI 0.598–0.656). Multivariable analyses revealed a dose–dependent association and a larger effect magnitude for RAI: frail patients OR: 19.52 (95% CI 18.29–20.82) and very frail patients OR: 65.81 (95% CI 62.32–69.50). A similar trend was observed in the interaction evaluating RAI–age–obesity (p<.001). CONCLUSIONOur study highlights a strong association between frailty and 30-day postoperative mortality in elderly obese spine patients, revealing a dose–dependent relationship. The RAI has superior discrimination than the mFI-5 and greater patient age in predicting 30-day postoperative mortality after spine surgery. Using the RAI in preoperative assessments may improve outcomes and help healthcare providers effectively communicate accurate surgical risks and potential benefits, set realistic recovery expectations, and enhances patient satisfaction.

Simultaneous Fault Diagnosis Based on Hierarchical Multi-Label Classification and Sparse Bayesian Extreme Learning Machine

This paper proposes an intelligent simultaneous fault diagnosis model based on a hierarchical multi-label classification strategy and sparse Bayesian extreme learning machine. The intelligent diagnosis model compares the similarity between an unknown sample to be diagnosed and each single fault mode, then outputs the probability of each fault mode occurring. First, multiple two-class sub-classifiers based on SBELM are trained by using single-fault samples to extract the correlation between various pairs of single-fault, and the sub-classifiers are integrated with the proposed hierarchical multi-label classification (HMLC) strategy to form the diagnostic model based on HMLC-SBELM. Then, samples of single faults and simultaneous faults are used to generate the optimal discriminative thresholds by using optimization algorithms. Finally, the probabilistic output generated by the HMLC-SBELM-based model is transformed into the final fault modes by using the optimal discriminative threshold. The model performance is evaluated by using actual vibration signals of the main reducer and is compared with several classical models. The contrastive results indicate that the proposed model is more accurate, efficient, and stable.

Preoperative frailty risk in deep brain stimulation patients: Risk analysis index predicts Clavien-Dindo IV complications

ObjectiveDeep brain stimulation (DBS) improves patients’ quality of life in multiple movement disorders and chronic neurodegenerative diseases. There are no published studies assessing frailty’s impact on DBS outcomes. We evaluated frailty’s impacts on DBS outcomes, comparing discriminative thresholds of the risk analysis index (RAI) to modified frailty index-5 (mFI-5) for predicting Clavien-Dindo complications (CDIV). MethodsPatients who underwent DBS between 2015 and 2019 in the ACS-NSQIP registry were included. We employed receiver operating characteristic (ROC) curve to examine the discriminative thresholds of RAI and mFI-5 and multivariable analyses for postoperative outcomes. Our primary outcome was CDIV, and secondary outcomes were discharge to higher-level care facility, unplanned reoperation within 30 days, in any hospital, for any procedure related to the index procedure, and extended length of stay. ResultsA total of 3795 patients were included. In the ROC analysis for CDIV, RAI showed superior discriminative threshold (C-statistic = 0.70, 95% CI 0.61–0.80, <0.001) than mFI-5 (C-statistic = 0.60, 95% CI 0.49–0.70, P = 0.08). On multivariable analyses, frailty stratified by RAI, had independent associations with CDIV, i.e., pre-frail 2-fold increase OR 2.04 (95% CI: 1.94–2.14) p < 0.001, and frail 39% increase OR 1.39 (95% CI: 1.27–1.53), p < 0.001. ConclusionFrailty was an independent risk-factor for CDIV. The RAI had superior discriminative thresholds than mFI-5 in predicting CDIV after DBS. Our ability to identify frail patients prior to DBS presents a novel clinical opportunity for quality improvement strategies to target this specific patient population. RAI may be a useful primary frailty screening modality for potential DBS candidates.

Semi-Quantitative [18F]FDG-PET/CT ROC-Analysis-Based Cut-Offs for Aortitis Definition in Giant Cell Arteritis.

[18F]fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) is used to diagnose large vessel vasculitis in giant cell arteritis (GCA). We aimed to define a semi-quantitative threshold for identifying GCA aortitis from aortic atheroma or the control. Contrast enhanced computed tomography (CECT) was used as the reference imaging for aortic evaluation and to define aortitis, aortic atheroma and control aortas. [18F]FDG-PET/CT was performed on 35 GCA patients and in two different control groups (aortic atheroma (n = 70) and normal control (n = 35)). Aortic semi-quantitative features were compared between the three groups. GCA patients without aortitis on CECT were excluded. Of the GCA patients, 19 (54.3%) were not on glucocorticoids (GC) prior to [18F]FDG-PET/CT. The SUVmax, TBRblood and TBRliver aortic values were significantly higher in the GCA aortitis group than in the aortic atheroma and control groups (p &lt; 0.001). Receiver operating characteristic curve analyses brought to light quantitative cut-off values allowing GCA aortitis diagnosis with optimal sensitivity and specificity versus control or aortic atheroma patients for each PET-based feature analyzed. Considering the overall aorta, a SUVmax threshold of 3.25 and a TBRblood threshold of 1.75 had a specificity of 83% and 75%, respectively, a sensitivity of 81% and 81%, respectively, and the area under the ROC curve (AUC) was 0.86 and 0.83, respectively, for aortitis detection compared to control groups in GCA cases with GC. A SUVmax threshold of 3.45 and a TBRblood threshold of 1.97 had a specificity of 90% and 93%, respectively, a sensitivity of 89% and 89%, respectively, with an AUC of 0.89 and 0.96, respectively, for aortitis detection compared to the control in GC-free GCA cases. Discriminative thresholds of SUVmax and TBRblood for the diagnosis of GCA aortitis were established using CECT as the reference imaging.

Quantification of pathological gait parameter thresholds of idiopathic normal pressure hydrocephalus patients in clinical gait analysis

The aim of the study was to distinguish the hypokinetic gait disorder in idiopathic normal pressure hydrocephalus (NPH) patients from the gait decline in the elderly population by quantifying pathological gait parameter thresholds utilizing a multiple condition gait assessment. 55 NPH patients and 55 age-matched healthy subjects underwent a standardized gait assessment with eight gait conditions. Spatiotemporal gait parameters were assessed through a pressure-sensitive carpet. Statistical analysis consisted of a binary logistic regression (BLR) model, logistic curve-fit evaluated by a Chi-square goodness-of-fit-test, receiver operating characteristic models with area under the curves (AUC), and inverse BLR. Most discriminative gait parameter thresholds were observed in pace, gait cycle, and support gait domains. The most distinct gait conditions were preferred walking speed and semantic dual task. During preferred walking speed, the most significant gait parameter thresholds were stride length ≤ 1.02 m (sensitivity 0.93/specificity 0.91/AUC 0.96), gait velocity ≤ 0.83 m/s (0.80/0.91/0.93), double support phase ≥ 27.0% (0.96/0.76/0.91), and stride length coefficient of variation ≥ 3.4% (0.93/0.72/0.90). In conclusion, the hypokinetic gait disorder in NPH can be quantitatively differentiated from gait patterns of the elderly population. In future studies, this approach may be useful to differentiate clinical entities with similar gait disorders utilizing instrumented gait analysis procedures.

Automated Pupillometry Identifies Absence of Intracranial Pressure Elevation in Intracerebral Hemorrhage Patients

IntroductionAlthough automated pupillometry is increasingly used in critical care settings, predictive value of automatically assessed pupillary parameters during different intracranial pressure (ICP) levels and possible clinical implications are unestablished.MethodsThis retrospective cohort study at the neurocritical care unit of the University of Erlangen-Nuremberg (2016–2018) included 23 nontraumatic supratentorial (intracerebral hemorrhage) ICH patients without signs of abnormal pupillary function by manual assessment, i.e., absent light reflex. We assessed ICP levels by an external ventricular drain simultaneously with parameters of pupillary reactivity [i.e., maximum and minimum apertures, light reflex latency (Lat), constriction and redilation velocities (CV, DV), and percentage change of apertures (per-change)] using a portable pupillometer (NeurOptics®). Computed tomography (CT) scans were analyzed to determine lesion location, size, intraventricular hemorrhage, hydrocephalus, midline shift, and compression or absence of the basal cisterns. We performed receiver operating characteristics analysis to investigate associations of ICP levels with pupillary parameters and to determine best cutoff values for prediction of ICP elevation. After dichotomization of assessments according to ICP values (normal: < 20 mmHg, elevated: ≥ 20 mmHg), prognostic performance of the determined cutoff parameters of pupillary function versus of CT-imaging findings was analyzed by calculating sensitivity, specificity, positive and negative predictive values (logistic regression, corresponding ORs with 95% CIs).ResultsIn 23 patients (11 women, median age 59.0 (51.0–69.0) years), 1,934 assessments were available for analysis. A total of 74 ICP elevations ≥ 20 mmHg occurred in seven patients. Best discriminative thresholds for ICP elevation were: CV < 0.8 mm/s (AUC 0.740), per-change < 10% (AUC 0.743), DV < 0.2 mm/s (AUC 0.703), and Lat > 0.3 s (AUC 0.616). Positive predictive value of all four parameters to indicate ICP elevation ranged between 7.2 and 8.3% only and was similarly low for CT abnormalities (9.1%). We found high negative predictive values of pupillary parameters [CV: 99.2% (95% CI 98.3–99.6), per-change: 98.7% (95% CI 97.8–99.2), DV: 98.0% (95% CI 97.0–98.7), Lat: 97.0% (95% CI 96.0–97.7)], and CT abnormalities [99.7% (95% CI 99.2–99.9)], providing evidence that both techniques adequately identified ICH patients without ICP elevation.ConclusionsOur data suggest an association between noninvasively detected changes in pupillary reactivity and ICP levels in sedated ICH patients. Although automated pupillometry and neuroimaging seem not sufficient to noninvasively indicate ICP elevation, both techniques, however, adequately identified ICH patients without ICP elevation. This finding may facilitate routine management by saving invasive ICP monitoring or repeated CT controls in patients with specific automated pupillometry readings.

Impact of sarcopenia in aortoiliac occlusive disease in Mediterranean population.

Background This study aims to validate the psoas muscle area and psoas muscle density as morphometric predictors in cardiovascular and cerebrovascular endpoints in patients with extensive aortoiliac peripheral arterial disease. Methods A total of 57 patients (55 males, 2 females; mean age 60±8.2 years; range, 35 to 83 years) with Trans-Atlantic Inter-Society Consensus type D lesions who underwent revascularization at two Portuguese tertiary hospitals between January 2013 and July 2019 were retrospectively analyzed. The patients with a recent (<6 months) computed tomography scan prior to the revascularization procedure were included in the study. Both centers offered to their patients open and endovascular repair of aortoiliac peripheral arterial disease. Major adverse cardiovascular and cerebrovascular events and major adverse limb events were evaluated. Results The median follow-up was 20 months. The mean survival rate was 93±3.4% at 30 days and 62.7±8.6% at 48 months. The discriminative thresholds found in this population were 2,175.8 mm2 for total psoas area and 51.75 Hounsfield unit for psoas muscle density. There was a statistically significant difference in the one-year survival rate (p=0.003 and p=0.291, respectively) and major adverse cardiovascular and cerebrovascular events (p=0.005 and p=0.206, respectively) for total psoas area compared to psoas muscle density. Conclusion Total psoas area shows a prognostic value for survival and major adverse cardiovascular and cerebrovascular events in this patient population.

Search for More Effective Microsatellite Markers for Forensics With Next-Generation Sequencing.

Published by the Combined DNA Index System (CODIS) program of the Federal Bureau of Investigation (FBI) in 1997, the 13 core short tandem repeat (STR) loci are widely adopted as genetic markers in forensic applications, e.g., identity testing and paternity testing. However, these loci may be biased and suffer from reduced sensitivities toward specific population groups. In addition, the rapid growth of entries in forensic databases raises the chance of random hits, which can cause false recognitions of criminal suspects. A solution to these problems is to introduce more effective STR markers. The availability of whole genome sequencing enables us to identify more reliable STRmarkers for forensic applicationscomputationally. In this paper, we proposed an algorithm to identify STR markers with high discriminative abilities from the next-generation sequencing data. Our algorithm could select a customized set of loci for a given population with pre-specified discriminative thresholds. We have applied the method to 320 Chinese individuals from the 1000 Genomes Project and obtained various numbers of loci, which were able to statistically identify an individualworldwide and had higher combined powers of discrimination and combined probabilities of exclusion than the existing CODIS 13 loci. For identity testing, themean frequencyofDNAprofile (FDP) with the selected 11 STRs was smaller than that with CODIS 13 STRs by student's t-test. With more loci, much smaller FDPs were obtained. The databasematching probabilities for selected loci were also lower than that for CODIS 13 STRs in a database with 10 billion entries. Moreover, the selected loci were able to provide considerably low chance of random profile matches so that statistically no false positives could occur. The selected loci also reduced the risk of random allele matches when doing the familial search, with lower random allele matching probabilities. In addition, the selected STRs were statistically better than CODIS STRs for paternity testing in our simulated data, with lower probabilities of false inclusions and exclusions.

Commentary on: Discriminative Thresholds in Facial Asymmetry: A Review of the Literature.

Commentary on: Discriminative Thresholds in Facial Asymmetry: A Review of the Literature.

Discriminative Thresholds in Facial Asymmetry: A Review of the Literature.

Facial symmetry is intimately correlated with attractiveness. Perfect facial symmetry is disconcerting and a degree of facial asymmetry is considered normal. There is a lack of data on the limits of normality across facial subunits. This systematic review aims to establish categories of facial asymmetry perception for facial aesthetic units by establishing a discriminative threshold of "deformity perception" across facial subunits and a threshold for intervention (unacceptable asymmetry). A review of the literature was performed across Medline and Embase databases using OvidSP. All prospective studies evaluating the perception of progressive facial asymmetry in laymen or clinicians using a two- or three-dimensional model were included. Studies that did not evaluate rates of perception at varying degrees of asymmetry were excluded as these did not allow for the identification of a perceptive threshold. Each facial feature possesses a unique threshold of perception defined by an abrupt, statistically significant increase in detection. Asymmetry of the eyelid position at rest is the most sensitive facial feature (perceptive threshold, 2 mm) (P < 0.02). This is followed by deviations of the oral commissure (3 mm) (P < 0.001), brow position (3.5 mm) (P < 0.001), nasal tip deviation (4 mm) (P < 0.001), and chin deviation (6 mm) (P < 0.001). Desire for surgery for worsening deformities beyond the intervention threshold is characterized by an exponential, rather than linear, correlation. Categories of facial asymmetry perception establish a framework to counsel patients with facial asymmetries, and are a valuable adjunct to clinical judgment in the management of static and dynamic facial deformities.

Multidimensional Influences on Autism Symptom Measures: Implications for Use in Etiological Research

Growing awareness that symptoms of autism spectrum disorder (ASD) transcend multiple diagnostic categories, and major advances in the identification of genetic syndromes associated with ASD, have led to widespread use of ASD symptom measures in etiologic studies of neurodevelopmental disorders. Insufficient consideration of potentially confounding factors such as cognitive ability or behavior problems can have important negative consequences in interpretation of findings, including erroneous estimation of associations between ASD and etiologic factors. Participants were 388 children 2 to 13 years old with diagnoses of ASD or another neurodevelopmental disorder without ASD. Receiver operating characteristics methods were used to assess the influence of IQ and emotional and behavioral problems on the discriminative ability of 3 widely used ASD symptom measures: the Social Responsiveness Scale (SRS), the Autism Diagnostic Interview-Revised (ADI-R), and the Autism Diagnostic Observation Schedule (ADOS). IQ influenced the discriminative thresholds of the SRS and ADI-R, and emotional and behavioral problems affected the discriminative thresholds of the SRS, ADI-R, and ADOS. This resulted in low specificity of ASD cutoffs on the SRS and ADI-R for children with intellectual disability without ASD (27-42%) and low specificity across all 3 instruments for children without ASD with increased emotional and behavioral problems (36-59%). Adjustment for these characteristics resulted in improved discriminative ability for all of the ASD measures. The findings indicate that scores on ASD symptom measures reflect far more than ASD symptoms. Valid interpretation of scores on these measures requires steps to account for the influences of IQ and emotional and behavioral problems.

TUNING THE PRECISION OF PREDICTORS TO REDUCE OVERESTIMATION OF PROTEIN DISORDER OVER LARGE DATASETS

This is a study on the precision of four known protein disorder predictors, ranked among the best-performing ones: DISOPRED2, PONDR VSL2B, IUPred and ESpritz. We address here the problem of a systematic overestimation of the number of disordered proteins recognized through the use of these predictors, considered as a standard. Some of these predictors, used with their default setting, have a low precision, implying a tendency to overestimate the occurrence of disordered proteins in genome-wide surveys. Moreover, different predictors often disagree on the evaluation of individual proteins. To cope with this problem and in order to propose a simple procedure that enhances precision based on precision-recall curves, we re-tuned the discriminative thresholds of the predictors by training and cross-validating their performance on a cured dataset. After re-tuning, both the disagreement among predictors and the tendency to overestimate the occurrence of disordered proteins are reduced. This is shown in a dedicated study over the human proteome and a set of cancer-related human proteins, with no a priori disorder annotation. Simple quantitative estimates suggest that the occurrence of disorder among cancer-related proteins and other similar large-scale surveys has been overestimated in the past.

Sensitivity and Bias in Decision-Making under Risk: Evaluating the Perception of Reward, Its Probability and Value

BackgroundThere are few clinical tools that assess decision-making under risk. Tests that characterize sensitivity and bias in decisions between prospects varying in magnitude and probability of gain may provide insights in conditions with anomalous reward-related behaviour.ObjectiveWe designed a simple test of how subjects integrate information about the magnitude and the probability of reward, which can determine discriminative thresholds and choice bias in decisions under risk.Design/MethodsTwenty subjects were required to choose between two explicitly described prospects, one with higher probability but lower magnitude of reward than the other, with the difference in expected value between the two prospects varying from 3 to 23%.ResultsSubjects showed a mean threshold sensitivity of 43% difference in expected value. Regarding choice bias, there was a ‘risk premium’ of 38%, indicating a tendency to choose higher probability over higher reward. An analysis using prospect theory showed that this risk premium is the predicted outcome of hypothesized non-linearities in the subjective perception of reward value and probability.ConclusionsThis simple test provides a robust measure of discriminative value thresholds and biases in decisions under risk. Prospect theory can also make predictions about decisions when subjective perception of reward or probability is anomalous, as may occur in populations with dopaminergic or striatal dysfunction, such as Parkinson's disease and schizophrenia.

Sleep Disorders in Machado–Joseph Disease: Frequency, Discriminative Thresholds, Predictive Values, and Correlation with Ataxia-Related Motor and Non-Motor Features

Sleep disorders are common complaints in patients with neurodegenerative diseases such as spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD)--SCA3/MJD. We evaluated the frequency of sleep disorders in SCA3/MJD patients against controls matched by age and gender, and correlated data with demographic and clinical variables. The main sleep disorders evaluated were rapid eye movement (REM) sleep behavior disorder (RBD), restless leg syndrome (RLS), and excessive daytime sleepiness (EDS). We recruited 40 patients with clinical and molecular-proven SCA3/MJD and 38 controls. We used the following clinical scales to evaluate our primary outcome measures: RBD Screening Questionnaire, International RLS Rating Scale, and Epworth Sleepiness Scale. To evaluate ataxia-related motor and non-motor features, we applied the International Cooperative Ataxia Rating Scale, the Scale for the Assessment and Rating of Ataxia, and the Unified Parkinson's Disease Rating Scale part III. Psychiatric manifestations were tested with the Hamilton Anxiety Scale, and Beck Depression Inventory. The frequency of RBD and RLS were significantly higher in the SCA3/MJD group than in the control group (p < 0.001). There was no difference between both groups with regard to EDS. The accuracy of RDBSQ to discriminate between cases and controls was considered the best area under the ROC curve (0.86). Within-SCA3/MJD group analysis showed that anxiety and depression were significantly correlated with RDB, but not with RLS. Additionally, depression was considered the best predictive clinical feature for RDB and EDS.

In Vitro Cell-Mediated Immune Responses of Human Immunodeficiency Virus-Infected and -Uninfected Individuals to Whole Cytomegalovirus Antigens and Their Subunits

The aim of this study was to optimize the ability to detect cytomegalovirus (CMV)-specfic cell-mediated immunity (CMI) in human immunodeficiency virus (HIV)-infected individuals by comparing different assays (the lymphocyte proliferation assay [LPA] and assays for gamma interferon [IFN-gamma] and interleukin-2 [IL-2] production) and CMV antigenic preparations. Thresholds discriminating positive from negative CMI results were developed with specimens from 36 CMV-seropositive and 21 CMV-seronegative healthy individuals. The analysis showed that the CMI elicited by any of the four CMV whole lysates tested in this study tended to be more robust and sensitive than the responses to the subunit antigens gB and pp65. LPA and inducible IFN-gamma but not IL-2 were highly sensitive measures of CMV-specific CMI in HIV-infected and -uninfected individuals. The ability to detect CMV-specific LPA or IFN-gamma responses in HIV-infected individuals significantly increased with higher CD4 cell numbers. Nevertheless, the proportion of HIV-infected subjects with CD4 counts of >or=500 cells/mul who had a detectable CMV-specific CMI remained significantly lower than that of healthy adults. The ability to detect CMV-specific CMI in HIV-infected individuals decreased with higher levels of HIV replication, with discriminative thresholds of 10(3) to 10(4) HIV RNA copies/ml of plasma, for LPA or inducible IFN-gamma production elicited by different antigens. The LPA responses obtained with CMV whole lysate and phytohemagglutinin were significantly correlated in HIV-infected subjects but not uninfected controls, indicating a novel characteristic of the CMI defect caused by HIV. The intrasubject variabilities of the CMV-specific CMI were similar in HIV-infected and -uninfected individuals. These data show that LPA and the inducible IFN-gamma production elicited by CMV whole lysates may be used to assess modifications of the immune competency of HIV-infected individuals.

Discriminative thresholds of cephalometric indexes in the subjective evaluation of facial asymmetry

The purpose of this study was to determine the means and the ranges of the thresholds of cephalometric indexes by which orthodontists subjectively differentiate patients needing treatment for facial asymmetry from those who do not. The study was performed at the Departments of Orthodontics and Oral and Maxillofacial Radiology, Aichi-Gakuin University School of Dentistry in Nagoya, Japan, in 2004. Ten orthodontists subjectively evaluated the frontal photographs of 100 subjects and classified them into 2 groups. The subjects in group A showed good or clinically acceptable levels of asymmetry and did not require treatment. Those in group B showed marked asymmetry, and treatment was recommended. The frontal cephalographs were also analyzed with 5 indexes related to the mandible. For each orthodontist, the threshold was determined by means of the discriminant analysis. As the number of subjects who were judged to require treatment increased, the threshold of cephalometric indexes became smaller, and the discriminant accuracy was reduced. Among the 5 indexes evaluated, the distance of menton (mean, 4.28 mm), maxillomandibular midline angle (mean, 4.31 degrees ), and the distance of L1 (mean, 2.78 mm) showed relatively high accuracy in all observers. The distance of menton, the maxillomandibular midline angle, and the distance of L1 appeared to be relevant indexes for the subjective evaluation of facial asymmetry. The thresholds determined in this study could contribute to the planning and evaluation of orthodontic treatments.