Postoperative Innate Immune Dysregulation, Proteomic, and Monocyte Epigenomic Changes After Colorectal Surgery: A Substudy of a Randomized Controlled Trial.

BACKGROUND: Colorectal surgery is associated with moderate-to-severe postoperative complications in over 25% of patients, predominantly infections. Monocyte epigenetic alterations leading to immune tolerance could explain postoperative increased susceptibility to infections. This research explores whether changes in monocyte DNA accessibility contribute to postoperative innate immune dysregulation. METHODS: Damage-associated molecular patterns (DAMPs) and ex vivo cytokine production capacity were measured in a randomized controlled trial (n = 100) in colorectal surgery patients, with additional exploratory subgroup proteomic (proximity extension assay; Olink) and epigenomic analyses (Assay for Transposase-Accessible Chromatin [ATAC sequencing]). Monocytes of healthy volunteers were used to study the effect of high-mobility group box 1 (HMGB1) and heat shock protein 70 (HSP70) on cytokine production capacity in vitro. RESULTS: Plasma DAMPs were increased after surgery. HMGB1 showed a mean 235% increase from before- (preop) to the end of surgery (95% confidence interval [CI] [166 - 305], P < .0001) and 90% increase (95% CI [63-118], P = .0004) preop to postoperative day 1 (POD1). HSP70 increased by a mean 12% from preop to the end of surgery (95% CI [3-21], not significant) and 30% to POD1 (95% CI [18-41], P < .0001). Nuclear deoxyribonucleic acid (nDNA) increases by 66% (95% CI [40-92], P < .0001) at the end of surgery and 94% on POD1 (95% CI [60-127], P < .0001). Mitochondrial DNA (mtDNA) increases by 370% at the end of surgery (95% CI [225-515], P < .0001) and by 503% on POD1 (95% CI [332-673], P < .0001). In vitro incubation of monocytes with HSP70 decreased cytokine production capacity of tumor necrosis factor (TNF) by 46% (95% CI [29-64], P < .0001), IL-6 by 22% (95% CI [12-32], P = .0004) and IL-10 by 19% (95% CI [12-26], P = .0015). In vitro incubation with HMGB1 decreased cytokine production capacity of TNF by 34% (95% CI [3-65], P = .0003), interleukin 1ß (IL-1ß) by 24% (95% CI [16-32], P < .0001), and IL-10 by 40% (95% CI [21-58], P = .0009). Analysis of the inflammatory proteome alongside epigenetic shifts in monocytes indicated significant changes in gene accessibility, particularly in inflammatory markers such as CXCL8 (IL-8), IL-6, and interferon-gamma (IFN-γ). A significant enrichment of interferon regulatory factors (IRFs) was found in loci exhibiting decreased accessibility, whereas enrichment of activating protein-1 (AP-1) family motifs was found in loci with increased accessibility. CONCLUSIONS: These findings illuminate the complex epigenetic modulation influencing monocytes' response to surgical stress, shedding light on potential biomarkers for immune dysregulation. Our results advocate for further research into the role of anesthesia in these molecular pathways and the development of personalized interventions to mitigate immune dysfunction after surgery.

Fifteen years later: Enhancing the classification accuracy of the performance validity module of the Advanced Clinical Solutions.

OBJECTIVE: The study was designed to evaluate the performance validity module of Advanced Clinical Solutions (ACS) against external criterion measures and compare two alternative aggregation methods for its five components. METHOD: The ACS was evaluated against psychometrically defined criterion groups in a sample of 93 outpatients with TBI. In addition to the default method, the component performance validity tests (PVTs) were either dichotomized along a single cutoff (VI-ACS) or recoded to capture various degrees of failure (EI-ACS). RESULTS: The standard ACS model correctly classified 75-83% of the sample. The alternative aggregation methods produced superior overall correct classification: 80-91% (VI-ACS) and 86-91% (EI-ACS). Mild TBI was associated with higher failure rates than moderate/severe TBI. Failing just one of the five ACS components resulted in a 3- to 8-fold increase in the likelihood of failing criterion PVTs. CONCLUSIONS: Results support the use of the standard PVT module for ACS: it is an effective measure of performance validity that is robust to moderate-to-severe TBI. Post-publication research on individual ACS components and methodological advances in PVT research provide an opportunity to enhance the overall classification accuracy of the ACS model. Passing stringent multivariate PVT cutoffs does not indicate valid performance.

Base rates of failure on various performance validity tests as a function of age in adults referred for neuropsychological assessment.

This study aimed to investigate the relationship between age and base rates of failure (BRFail) on various performance validity tests (PVTs) administered in medical-legal settings. Archival data were analyzed from 3,297 adults (Mage = 42.3 years; Meducation = 11.2) referred for psychological or neuropsychological assessments in a medical-legal or forensic civil disability context who passed the Word Memory Test. BRFail on 10 PVTs (three freestanding and seven embedded) were reported at multiple cutoffs across five age groups ranging from 16 years to 69 years. BRFail increased with age on most embedded PVTs, with a couple of notable exceptions. Reliable Digit Span was unrelated to age at ≤6 but produced elevated BRFail among older examinees at ≤7. Within freestanding PVTs, a positive relationship emerged between age and BRFail on most instruments/cutoffs. Older age is associated with an increased risk of false positive errors on many embedded PVTs that rely on raw scores. Although freestanding PVTs tend to be more resistant to the effects of age, several commonly used cutoffs may still produce increased false positive rates in older examinees. Taken together, results suggest that PVT scores should be interpreted in the context of patient characteristics, in an evidence-based manner, rather than by rigidly applying omnibus cutoffs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The classification accuracy of Warrington's recognition memory test (words) as a performance validity Test in a neurorehabilitation setting.

This study was designed to evaluate the classification accuracy of the Warrington's Recognition Memory Test (RMT) in 167 patients (97 or 58.1% men; MAge = 40.4; MEducation= 13.8) medically referred for neuropsychological evaluation against five psychometrically defined criterion groups. At the optimal cutoff (≤42), the RMT produced an acceptable combination of sensitivity (.36-.60) and specificity (.85-.95), correctly classifying 68.4-83.3% of the sample. Making the cutoff more conservative (≤41) improved specificity (.88-.95) at the expense of sensitivity (.30-.60). Lowering the cutoff to ≤40 achieved uniformly high specificity (.91-.95) but diminished sensitivity (.27-.48). RMT scores were unrelated to lateral dominance, education, or gender. The RMT was sensitive to a three-way classification of performance validity (Pass/Borderline/Fail), further demonstrating its discriminant power. Despite a notable decline in research studies focused on its classification accuracy within the last decade, the RMT remains an effective free-standing PVT that is robust to demographic variables. Relatively low sensitivity is its main liability. Further research is needed on its cross-cultural validity (sensitivity to limited English proficiency).

Compassion Versus Accuracy: Lenient Scoring of the Spatial Orientation Items on the Mini-mental State Exam Lowers Sensitivity.

The Mini-mental State Examination (MMSE) is a commonly used screening tool for cognitive impairment. Lenient scoring of spatial orientation errors (SOEs) on the MMSE is common and negatively affects its diagnostic utility. We examined the effect of lenient SOE scoring on MMSE classification accuracy in a consecutive case series of 103 older adults (age 60 or above) clinically referred for neuropsychological evaluation. Lenient scoring of SOEs on the MMSE occurred in 53 (51.4%) patients and lowered the sensitivity by 7% to 18%, with variable gains in specificity (0% to 11%) to psychometrically operationalized cognitive impairment. Results are consistent with previous reports that lenient scoring is widespread and attenuates the sensitivity of the MMSE. Given the higher clinical priority of correctly detecting early cognitive decline over specificity, a warning against lenient scoring of SOEs (on the MMSE and other screening tools) during medical education and in clinical practice is warranted.

A chromatin-regulated biphasic circuit coordinates IL-1ß-mediated inflammation.

Inflammation is characterized by a biphasic cycle consisting initially of a proinflammatory phase that is subsequently resolved by anti-inflammatory processes. Interleukin-1ß (IL-1ß) is a master regulator of proinflammation and is encoded within the same topologically associating domain (TAD) as IL-37, which is an anti-inflammatory cytokine that opposes the function of IL-1ß. Within this TAD, we identified a long noncoding RNA called AMANZI, which negatively regulates IL-1ß expression and trained immunity through the induction of IL37 transcription. We found that the activation of IL37 occurs through the formation of a dynamic long-range chromatin contact that leads to the temporal delay of anti-inflammatory responses. The common variant rs16944 present in AMANZI augments this regulatory circuit, predisposing individuals to enhanced proinflammation or immunosuppression. Our work illuminates a chromatin-mediated biphasic circuit coordinating expression of IL-1ß and IL-37, thereby regulating two functionally opposed states of inflammation from within a single TAD.

Dual-Pathway Inhibition with Rivaroxaban and Low-Dose Aspirin Does Not Alter Immune Cell Responsiveness and Distribution in Patients with Coronary Artery Disease.

INTRODUCTION: Cardiovascular diseases (CVD) are the leading cause of death globally. Inflammation is an important driver of CVD where tissue damage may lead to the formation of deadly thrombi. Therefore, antithrombotic drugs, such as platelet inhibitors, are crucial for secondary risk prevention in coronary artery disease (CAD) and peripheral artery disease (PAD). For severe forms of the disease, dual-pathway inhibition (DPI) where low-dose aspirin is combined with rivaroxaban has shown improved efficacy in reducing cardiovascular mortality. METHODS: Given this greater improvement in mortality, and the importance of inflammation in driving atherosclerosis, the potential for off-target inflammation-lowering effects of these drugs was evaluated by looking at the change in immune cell distribution and responsiveness to ex vivo lipopolysaccharide (LPS) stimulation after 3 months of DPI in patients with CAD. RESULTS: We observed no changes in whole blood or peripheral blood mononuclear cell (PBMC) immune cell responsiveness to LPS after 3 months of DPI. Additionally, we did not observe any changes in the distribution of total white blood cells, monocytes, neutrophils, lymphocytes, or platelets during the study course. Signs of systemic inflammation were studied using Olink proteomics in 33 patients with PAD after 3 months of DPI. No changes were observed in any of the inflammatory proteins measured after the treatment period, suggesting that the state of chronic inflammation was not altered in these subjects. CONCLUSION: Three months of DPI does not result in any meaningful change in immune cell responsiveness and distribution in patients with CAD or PAD. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05210725.

Replicating the classification accuracy of the Verbal Paired Associates and Visual Reproduction recognition trials as embedded performance validity tests.

OBJECTIVE: This study was designed to replicate previous research on the clinical utility of the Verbal Paired Associates (VPA) and Visual Reproduction (VR) subtests of the WMS-IV as embedded performance validity tests (PVTs) and perform a critical item (CR) analysis within the VPA recognition trial. METHOD: Archival data were collected from a mixed clinical sample of 119 adults (MAge = 42.5, MEducation = 13.9). Classification accuracy was computed against psychometrically defined criterion groups based on the outcome of various free-standing and embedded PVTs. RESULTS: Age-corrected scaled scores ≤ 6 were specific (.89-.98) but had variable sensitivity (.36-.64). A VPA recognition cutoff of ≤ 34 produced a good combination of sensitivity (.46-.56) and specificity (.92-.93), as did a VR recognition cutoff of ≤ 4 (.48-.53 sensitivity at .86-.94 specificity). Critical item analysis expanded the VPA's sensitivity by 3.5%-7.0% and specificity by 5%-8%. Negative learning curves (declining output on subsequent encoding trials) were rare but highly specific (.99-1.00) to noncredible responding. CONCLUSIONS: Results largely support previous reports on the clinical utility of the VPA and VR as embedded PVTs. Sample-specific fluctuations in their classification accuracy warrant further research into the generalizability of the findings. Critical item analysis offers a cost-effective method for increasing confidence in the interpretation of the VPA recognition trial as a PVT. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Biomarkers of sustained systemic inflammation and microvascular dysfunction associated with post-COVID-19 condition symptoms at 24 months after SARS-CoV-2-infection.

Introduction: Comprehensive studies investigating sustained hypercoagulability, endothelial function, and/or inflammation in relation to post-COVID-19 (PCC) symptoms with a prolonged follow-up are currently lacking. Therefore, the aim of this single-centre cohort study was to investigate serum biomarkers of coagulation activation, microvascular dysfunction, and inflammation in relation to persisting symptoms two years after acute COVID-19. Methods: Patients diagnosed with acute SARS-CoV-2 infection between February and June 2020 were recruited. Outcome measures included the CORona Follow-Up (CORFU) questionnaire, which is based on an internationally developed and partially validated basic questionnaire on persistent PCC symptoms. Additionally, plasma biomarkers reflecting coagulation activation, endothelial dysfunction and systemic inflammation were measured. Results: 167 individuals were approached of which 148 (89%) completed the CORFU questionnaire. At 24 months after acute infection, fatigue was the most prevalent PCC symptom (84.5%). Over 50% of the patients experienced symptoms related to breathing, cognition, sleep or mobility; 30.3% still experienced at least one severe or extreme (4 or 5 on a 5-point scale) PCC symptom. Multiple correlations were found between several PCC symptoms and markers of endothelial dysfunction (endothelin-1 and von Willebrand factor) and systemic inflammation (Interleukin-1 Receptor antagonist). No positive correlations were found between PCC symptoms and coagulation complexes. Discussion: In conclusion, this study shows that at 24 months after acute COVID-19 infection patients experience a high prevalence of PCC symptoms which correlate with inflammatory cytokine IL-1Ra and markers of endothelial dysfunction, especially endothelin-1. Our data may provide a rationale for the selection of treatment strategies for further clinical studies. Trial registration: This study was performed in collaboration with the CORona Follow-Up (CORFU) study (NCT05240742, https://clinicaltrials.gov/ct2/show/ NCT05240742).

Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells.

Immunoparalysis is a compensatory and persistent anti-inflammatory response to trauma, sepsis or another serious insult, which increases the risk of opportunistic infections, morbidity and mortality. Here, we show that in cultured primary human monocytes, interleukin-4 (IL4) inhibits acute inflammation, while simultaneously inducing a long-lasting innate immune memory named trained immunity. To take advantage of this paradoxical IL4 feature in vivo, we developed a fusion protein of apolipoprotein A1 (apoA1) and IL4, which integrates into a lipid nanoparticle. In mice and non-human primates, an intravenously injected apoA1-IL4-embedding nanoparticle targets myeloid-cell-rich haematopoietic organs, in particular, the spleen and bone marrow. We subsequently demonstrate that IL4 nanotherapy resolved immunoparalysis in mice with lipopolysaccharide-induced hyperinflammation, as well as in ex vivo human sepsis models and in experimental endotoxemia. Our findings support the translational development of nanoparticle formulations of apoA1-IL4 for the treatment of patients with sepsis at risk of immunoparalysis-induced complications.

Dimethyl itaconate induces long-term innate immune responses and confers protection against infection.

Itaconate is an immunomodulatory metabolite produced by immune cells under microbial stimulation and certain pro-inflammatory conditions and triggers antioxidant and anti-inflammatory responses. We show that dimethyl itaconate, a derivative of itaconate previously linked to suppression of inflammation and widely employed as an alternative to the endogenous metabolite, can induce long-term transcriptional, epigenomic, and metabolic changes, characteristic of trained immunity. Dimethyl itaconate alters glycolytic and mitochondrial energetic metabolism, ultimately leading to increased responsiveness to microbial ligand stimulation. Subsequently, mice treated with dimethyl itaconate present increased survival to infection with Staphylococcus aureus. Additionally, itaconate levels in human plasma correlate with enhanced ex vivo pro-inflammatory cytokine production. Collectively, these findings demonstrate that dimethyl itaconate displays short-term anti-inflammatory characteristics and the capacity to induce long-term trained immunity. This pro-and anti-inflammatory dichotomy of dimethyl itaconate is likely to induce complex immune responses and should be contemplated when considering itaconate derivatives in a therapeutic context.

Geographic variability in limited English proficiency: A cross-cultural study of cognitive profiles.

OBJECTIVE: This study was designed to evaluate the effect of limited English proficiency (LEP) on neurocognitive profiles. METHOD: Romanian (LEP-RO; n = 59) and Arabic (LEP-AR; n = 30) native speakers were compared to Canadian native speakers of English (NSE; n = 24) on a strategically selected battery of neuropsychological tests. RESULTS: As predicted, participants with LEP demonstrated significantly lower performance on tests with high verbal mediation relative to US norms and the NSE sample (large effects). In contrast, several tests with low verbal mediation were robust to LEP. However, clinically relevant deviations from this general pattern were observed. The level of English proficiency varied significantly within the LEP-RO and was associated with a predictable performance pattern on tests with high verbal mediation. CONCLUSIONS: The heterogeneity in cognitive profiles among individuals with LEP challenges the notion that LEP status is a unitary construct. The level of verbal mediation is an imperfect predictor of the performance of LEP examinees during neuropsychological testing. Several commonly used measures were identified that are robust to the deleterious effects of LEP. Administering tests in the examinee's native language may not be the optimal solution to contain the confounding effect of LEP in cognitive evaluations.

Video-Based Elevated Skin Temperature Detection.

In this work, we propose a non-contact video-based approach that detects when an individual's skin temperature is elevated beyond the normal range. The detection of elevated skin temperature is critical as a diagnostic tool to infer the presence of an infection or an abnormal health condition. Detection of elevated skin temperature is typically achieved using contact thermometers or non-contact infrared-based sensors. The ubiquity of video data acquisition devices such as mobile phones and computers motivates the development of a binary classification approach, the Video-based TEMPerature (V-TEMP) to classify subjects with non-elevated/elevated skin temperature. We leverage the correlation between the skin temperature and the angular reflectance distribution of light, to empirically differentiate between skin at non-elevated temperature and skin at elevated temperature. We demonstrate the uniqueness of this correlation by 1) revealing the existence of a difference in the angular reflectance distribution of light from skin-like and non-skin like material and 2) exploring the consistency of the angular reflectance distribution of light in materials exhibiting optical properties similar to human skin. Finally, we demonstrate the robustness of V-TEMP by evaluating the efficacy of elevated skin temperature detection on subject videos recorded in 1) laboratory controlled environments and 2) outside-the-lab environments. V-TEMP is beneficial in two ways; 1) it is non-contact-based, reducing the possibility of infection due to contact and 2) it is scalable, given the ubiquity of video-recording devices.

Logical memory, visual reproduction, and verbal paired associates are effective embedded validity indicators in patients with traumatic brain injury.

OBJECTIVE: This study was design to evaluate the potential of the recognition trials for the Logical Memory (LM), Visual Reproduction (VR), and Verbal Paired Associates (VPA) subtests of the Wechsler Memory Scales-Fourth Edition (WMS-IV) to serve as embedded performance validity tests (PVTs). METHOD: The classification accuracy of the three WMS-IV subtests was computed against three different criterion PVTs in a sample of 103 adults with traumatic brain injury (TBI). RESULTS: The optimal cutoffs (LM ≤ 20, VR ≤ 3, VPA ≤ 36) produced good combinations of sensitivity (.33-.87) and specificity (.92-.98). An age-corrected scaled score of ≤5 on either of the free recall trials on the VPA was specific (.91-.92) and relatively sensitive (.48-.57) to psychometrically defined invalid performance. A VR I ≤ 5 or VR II ≤ 4 had comparable specificity, but lower sensitivity (.25-.42). There was no difference in failure rate as a function of TBI severity. CONCLUSIONS: In addition to LM, VR, and VPA can also function as embedded PVTs. Failing validity cutoffs on these subtests signals an increased risk of non-credible presentation and is robust to genuine neurocognitive impairment. However, they should not be used in isolation to determine the validity of an overall neurocognitive profile.

From "below chance" to "a single error is one too many": Evaluating various thresholds for invalid performance on two forced choice recognition tests.

This study was designed to empirically evaluate the classification accuracy of various definitions of invalid performance in two forced-choice recognition performance validity tests (PVTs; FCRCVLT-II and Test of Memory Malingering [TOMM-2]). The proportion of at and below chance level responding defined by the binomial theory and making any errors was computed across two mixed clinical samples from the United States and Canada (N = 470) and two sets of criterion PVTs. There was virtually no overlap between the binomial and empirical distributions. Over 95% of patients who passed all PVTs obtained a perfect score. At chance level responding was limited to patients who failed ≥2 PVTs (91% of them failed 3 PVTs). No one scored below chance level on FCRCVLT-II or TOMM-2. All 40 patients with dementia scored above chance. Although at or below chance level performance provides very strong evidence of non-credible responding, scores above chance level have no negative predictive value. Even at chance level scores on PVTs provide compelling evidence for non-credible presentation. A single error on the FCRCVLT-II or TOMM-2 is highly specific (0.95) to psychometrically defined invalid performance. Defining non-credible responding as below chance level scores is an unnecessarily restrictive threshold that gives most examinees with invalid profiles a Pass.

Replicating a Meta-Analysis: The Search for the Optimal Word Choice Test Cutoff Continues.

This study was designed to expand on a recent meta-analysis that identified ≤42 as the optimal cutoff on the Word Choice Test (WCT). We examined the base rate of failure and the classification accuracy of various WCT cutoffs in four independent clinical samples (N = 252) against various psychometrically defined criterion groups. WCT ≤ 47 achieved acceptable combinations of specificity (.86-.89) at .49 to .54 sensitivity. Lowering the cutoff to ≤45 improved specificity (.91-.98) at a reasonable cost to sensitivity (.39-.50). Making the cutoff even more conservative (≤42) disproportionately sacrificed sensitivity (.30-.38) for specificity (.98-1.00), while still classifying 26.7% of patients with genuine and severe deficits as non-credible. Critical item (.23-.45 sensitivity at .89-1.00 specificity) and time-to-completion cutoffs (.48-.71 sensitivity at .87-.96 specificity) were effective alternative/complementary detection methods. Although WCT ≤ 45 produced the best overall classification accuracy, scores in the 43 to 47 range provide comparable objective psychometric evidence of non-credible responding. Results question the need for designating a single cutoff as "optimal," given the heterogeneity of signal detection environments in which individual assessors operate. As meta-analyses often fail to replicate, ongoing research is needed on the classification accuracy of various WCT cutoffs.

Vascular Function, Systemic Inflammation, and Coagulation Activation 18 Months after COVID-19 Infection: An Observational Cohort Study.

INTRODUCTION: Among its effect on virtually all other organs, COVID-19 affects the cardiovascular system, potentially jeopardizing the cardiovascular health of millions. Previous research has shown no indication of macrovascular dysfunction as reflected by carotid artery reactivity, but has shown sustained microvascular dysfunction, systemic inflammation, and coagulation activation at 3 months after acute COVID-19. The long-term effects of COVID-19 on vascular function remain unknown. MATERIALS AND METHODS: This cohort study involved 167 patients who participated in the COVAS trial. At 3 months and 18 months after acute COVID-19, macrovascular dysfunction was evaluated by measuring the carotid artery diameter in response to cold pressor testing. Additionally, plasma endothelin-1, von Willebrand factor, Interleukin(IL)-1ra, IL-6, IL-18, and coagulation factor complexes were measured using ELISA techniques. RESULTS: The prevalence of macrovascular dysfunction did not differ between 3 months (14.5%) and 18 months (11.7%) after COVID-19 infection (p = 0.585). However, there was a significant decrease in absolute carotid artery diameter change, 3.5% ± 4.7 vs. 2.7% ± 2.5, p-0.001, respectively. Additionally, levels of vWF:Ag were persistently high in 80% of COVID-19 survivors, reflecting endothelial cell damage and possibly attenuated endothelial function. Furthermore, while levels of the inflammatory cytokines interleukin(IL)-1RA and IL-18 were normalized and evidence of contact pathway activation was no longer present, the concentrations of IL-6 and thrombin:antithrombin complexes were further increased at 18 months versus 3 months (2.5 pg/mL ± 2.6 vs. 4.0 pg/mL ± 4.6, p = 0.006 and 4.9 µg/L ± 4.4 vs. 18.2 µg/L ± 11.4, p < 0.001, respectively). DISCUSSION: This study shows that 18 months after COVID-19 infection, the incidence of macrovascular dysfunction as defined by a constrictive response during carotid artery reactivity testing is not increased. Nonetheless, plasma biomarkers indicate sustained endothelial cell activation (vWF), systemic inflammation (IL-6), and extrinsic/common pathway coagulation activation (FVII:AT, TAT) 18 months after COVID-19 infection.

Multivariate models provide an effective psychometric solution to the variability in classification accuracy of D-KEFS Stroop performance validity cutoffs.

ObjectiveThe study was designed to expand on the results of previous investigations on the D-KEFS Stroop as a performance validity test (PVT), which produced diverging conclusions. Method The classification accuracy of previously proposed validity cutoffs on the D-KEFS Stroop was computed against four different criterion PVTs in two independent samples: patients with uncomplicated mild TBI (n = 68) and disability benefit applicants (n = 49). Results Age-corrected scaled scores (ACSSs) ≤6 on individual subtests often fell short of specificity standards. Making the cutoffs more conservative improved specificity, but at a significant cost to sensitivity. In contrast, multivariate models (≥3 failures at ACSS ≤6 or ≥2 failures at ACSS ≤5 on the four subtests) produced good combinations of sensitivity (.39-.79) and specificity (.85-1.00), correctly classifying 74.6-90.6% of the sample. A novel validity scale, the D-KEFS Stroop Index correctly classified between 78.7% and 93.3% of the sample. Conclusions A multivariate approach to performance validity assessment provides a methodological safeguard against sample- and instrument-specific fluctuations in classification accuracy, strikes a reasonable balance between sensitivity and specificity, and mitigates the invalid before impaired paradox.

Limited English proficiency inhibits auditory verbal learning in cognitively healthy young adults - exploring culturally responsive diagnostic and educational safeguards.

This study was designed to examine the effect of limited English proficiency (LEP) on the Hopkins Verbal Learning Test-Revised (HVLT-R). The HVLT-R was administered to 28 undergraduate student volunteers. Half were native speakers of English (NSE), half had LEP. The LEP sample performed significantly below NSE on individual acquisition trials and delayed free recall (large effects). In addition, participants with LEP scored 1.5-2 SDs below the normative mean. There was no difference in performance during recognition testing. LEP status was associated with a clinically significant deficit on the HVLT-R in a sample of cognitively healthy university students. Results suggest that low scores on auditory verbal learning tests in individuals with LEP should not be automatically interpreted as evidence of memory impairment or learning disability. LEP should be considered as grounds for academic accommodations. The generalizability of the findings is constrained by the small sample size.

Take Their Word for It: The Inventory of Problems Provides Valuable Information on Both Symptom and Performance Validity.

This study was designed to compare the validity of the Inventory of Problems (IOP-29) and its newly developed memory module (IOP-M) in 150 patients clinically referred for neuropsychological assessment. Criterion groups were psychometrically derived based on established performance and symptom validity tests (PVTs and SVTs). The criterion-related validity of the IOP-29 was compared to that of the Negative Impression Management scale of the Personality Assessment Inventory (NIMPAI) and the criterion-related validity of the IOP-M was compared to that of Trial-1 on the Test of Memory Malingering (TOMM-1). The IOP-29 correlated significantly more strongly (z = 2.50, p = .01) with criterion PVTs than the NIMPAI (rIOP-29 = .34; rNIM-PAI = .06), generating similar overall correct classification values (OCCIOP-29: 79-81%; OCCNIM-PAI: 71-79%). Similarly, the IOP-M correlated significantly more strongly (z = 2.26, p = .02) with criterion PVTs than the TOMM-1 (rIOP-M = .79; rTOMM-1 = .59), generating similar overall correct classification values (OCCIOP-M: 89-91%; OCCTOMM-1: 84-86%). Findings converge with the cumulative evidence that the IOP-29 and IOP-M are valuable additions to comprehensive neuropsychological batteries. Results also confirm that symptom and performance validity are distinct clinical constructs, and domain specificity should be considered while calibrating instruments.