Threats to the integrity of psychological assessment: The misuse of test raw data and materials.

In the practice of psychological assessment there have been warnings for decades by the American Psychological Association (APA), the National Academy of Neuropsychology (NAN), other associations, and test vendors, against the disclosure of test raw data and test materials. Psychological assessment occurs across several different practice environments, and test raw data is a particularly sensitive aspect of practice considering what it implicitly represents about a client/patient, and this concept is further developed in this paper. Many times, test materials are intellectual property protected by copyrights and user agreements. It follows that improper management of the release of test raw data and test materials threatens the scientific integrity of psychological assessment. Here the matters of test raw data, test materials, and different practice environments are addressed to highlight the challenges involved with improper releases and to offer guidance concerning good-faith efforts to preserve the integrity of psychological assessment and legal agreements. The unique demands of forensic practice are also discussed, including attorneys' needs for cross-examination and discovery, which may place psychologists (and other duly vetted evaluators) in conflict with their commitment to professional ethical codes and legal agreements. To this end, important threats to the proper use of test raw data and test materials include uninformed professionals and compromised evaluators. In this paper, the mishandling of test raw data and materials by both psychologists and other evaluators is reviewed, representative case examples, including those from the literature, are provided, pertinent case law is discussed, and practical stepwise conflict resolutions are offered.

Ecological validity of the Meyers Neuropsychological Battery.

Neuropsychologists are increasingly being asked to apply neuropsychological test results to real world functioning; however, neuropsychological tests are not usually constructed to do so, but instead are more concerned with diagnostic accuracy than with prediction of daily functioning. Using samples of 5,460 patients that did self-ratings and 2791 patients that had family ratings plus the Meyers Neuropsychological Battery (MNB), it was found that the family ratings were better predicted by neuropsychological test data than were self-ratings on the 38 item Patient Competency Rating Scale (PCRS). The R values for family ratings on the 36 regression equations ranged from .236 to .763. The results show that the ratings given patients by family members could be predicted by the neuropsychological test results. These findings can help the clinician to make broad statements regarding likely real-life functioning and also support the ecological validity of the tests that make up the MNB.

Objective methods for matching neuropsychological patterns: Formulas and comparisons.

INTRODUCTION: Objective neuropsychology test score pattern matching methods can help to identify data similarities and differences with comparison groups which can help the clinician in diagnosis and in identifying treatment options. MATERIALS AND METHODS: The current study examines five methods of matching a data set: Correlation, Configuration, Kullback-Leibler (KL) Divergence, Pooled Effect Size (Cohen's d), and a new method called MNB (Meyers Neuropsychological Battery) Code. Thirty data sets diagnosed with Traumatic Brain Injury (TBI) were compared with four Comparison Group data sets consisting of TBI, Depression, Anxiety and Attention Deficit/Hyperactivity Disorder. RESULTS: The Correlation Method was correct 90% (27/30) and Configuration was correct 86% (26/30). The KL Divergence was correct 76% (23/30) and the MNB Code was correct 73% (22/30). The Effect Size Method was correct 70% (21/30). When using a simple majority of all the matching methods, the classification rate was 90+ percent. CONCLUSIONS: The results of this study demonstrate that there are statistical methods that can identify patterns of cognitive strengths and weaknesses. Multiple matching methods and a simple majority of agreement between the different comparisons suggests the best matching profile for diagnosis. In some cases, more than one pattern may be present.

Physician norms for the Automated Neuropsychological Assessment Metrics (ANAM).

INTRODUCTION: The development of population specific norms for the Automated Neuropsychological Assessment Metrics (ANAM) is to help expand the utility for use with other population groups. Currently, normative data are available for general military, special operations, athletic, and community populations. The current study provides normative reference values for use in assessing physicians. MATERIALS AND METHODS: Retrospective data from a sample of 2,288 physicians who completed the ANAM were examined. The data were gathered from practicing civilian physicians serving in the National Guard or Reserves who completed the assessment as part of the mandated Department of Defense clinical testing policy. The effects of age and sex on performance were examined for all subtests. Normative tables were stratified by age (23-29, 30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, 65-79) and sex. Base rates of low scores among the physician population were also examined. RESULTS: Older age was associated with lower performance on all subtests with small-to-medium effect sizes. A mixed pattern of performance was observed as a factor of sex with females scoring better on one subtest and males scoring better on three subtests. However, effects sizes associated with sex were small and likely of minimal clinical significance. A total of 11.3% of the physician sample scored below average on two or more tests in the battery. CONCLUSIONS: This study provides normative data for practicing physicians that can be used to help inform clinical decision-making.

A Validity Measure for the Automated Neuropsychological Assessment Metrics.

The Automated Neuropsychological Assessment Metrics (ANAM) is one of the most widely used and validated neuropsychological instruments for assessing cognition. The ANAM Test System includes a reporting tool, the ANAM Validity Indicator Report that generates scores for the embedded effort measure, the ANAM Performance Validity Index (APVI). The current study seeks to develop a proxy for the APVI, using raw subtest summary test scores. This would be useful for situations where the APVI score is unavailable (e.g., validity report not generated at the time of the assessment) or when the item level data needed to generate this score are inaccessible. ANAM scores from a large data set of 1,000,000+ observations were used for this retrospective analysis. Results of linear regression analysis suggest that the APVI can be reasonably estimated from the raw subtest summary test scores that are presented on the ANAM Performance Report. Clinically, this means that an important step in the interpretation process, checking the validity of test data, can still be performed even when the APVI is not available.

Expression and characterization of SARS-CoV-2 spike proteins.

The severe acute respiratory syndrome coronavirus 2 spike protein is a critical component of coronavirus disease 2019 vaccines and diagnostics and is also a therapeutic target. However, the spike protein is difficult to produce recombinantly because it is a large trimeric class I fusion membrane protein that is metastable and heavily glycosylated. We recently developed a prefusion-stabilized spike variant, termed HexaPro for six stabilizing proline substitutions, that can be expressed with a yield of >30 mg/L in ExpiCHO cells. This protocol describes an optimized workflow for expressing and biophysically characterizing rationally engineered spike proteins in Freestyle 293 and ExpiCHO cell lines. Although we focus on HexaPro, this protocol has been used to purify over a hundred different spike variants in our laboratories. We also provide guidance on expression quality control, long-term storage, and uses in enzyme-linked immunosorbent assays. The entire protocol, from transfection to biophysical characterization, can be completed in 7 d by researchers with basic tissue cell culture and protein purification expertise.

Discovery of Sisunatovir (RV521), an Inhibitor of Respiratory Syncytial Virus Fusion.

RV521 is an orally bioavailable inhibitor of respiratory syncytial virus (RSV) fusion that was identified after a lead optimization process based upon hits that originated from a physical property directed hit profiling exercise at Reviral. This exercise encompassed collaborations with a number of contract organizations with collaborative medicinal chemistry and virology during the optimization phase in addition to those utilized as the compound proceeded through preclinical and clinical evaluation. RV521 exhibited a mean IC50 of 1.2 nM against a panel of RSV A and B laboratory strains and clinical isolates with antiviral efficacy in the Balb/C mouse model of RSV infection. Oral bioavailability in preclinical species ranged from 42 to >100% with evidence of highly efficient penetration into lung tissue. In healthy adult human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a significant reduction in viral load and symptoms compared to placebo.

Tuning π-Acceptor/σ-Donor Ratio of the 2-Isocyanoazulene Ligand: Non-Fluorinated Rival of Pentafluorophenyl Isocyanide and Trifluorovinyl Isocyanide Discovered.

Isocyanoazulenes (CNAz) constitute a relatively new class of isocyanoarenes that offers rich structural and electronic diversification of the organic isocyanide ligand platform. This article considers a series of 2-isocyano-1,3-X2-azulene ligands (X = H, Me, CO2Et, Br, and CN) and the corresponding zero-valent complexes thereof, [(OC)5Cr(2-isocyano-1,3-X2-azulene)]. Air- and thermally stable, X-ray structurally characterized 2-isocyano-1,3-dimethylazulene may be viewed as a non-benzenoid aromatic congener of 2,6-dimethyphenyl isocyanide (2,6-xylyl isocyanide), a longtime "workhorse" aryl isocyanide ligand in coordination chemistry. Single crystal X-ray crystallographic {Cr-CNAz bond distances}, cyclic voltametric {E1/2(Cr0/1+)}, 13C NMR {δ(13CN), δ(13CO)}, UV-vis {dπ(Cr) → pπ*(CNAz) Metal-to-Ligand Charge Transfer}, and FTIR {νN≡C, νC≡O, kC≡O} analyses of the [(OC)5Cr(2-isocyano-1,3-X2-azulene)] complexes provided a multifaceted, quantitative assessment of the π-acceptor/σ-donor characteristics of the above five 2-isocyanoazulenes. In particular, the following inverse linear relationships were documented: δ(13COtrans) vs. δ(13CN), δ(13COcis) vs. δ(13CN), and δ(13COtrans) vs. kC≡O,trans force constant. Remarkably, the net electron withdrawing capability of the 2-isocyano-1,3-dicyanoazulene ligand rivals those of perfluorinated isocyanides CNC6F5 and CNC2F3.

Structure-based design of prefusion-stabilized SARS-CoV-2 spikes.

The coronavirus disease 2019 (COVID-19) pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and difficult to produce recombinantly. We characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial substitutions resulted in the identification of HexaPro, a variant with six beneficial proline substitutions exhibiting higher expression than its parental construct (by a factor of 10) as well as the ability to withstand heat stress, storage at room temperature, and three freeze-thaw cycles. A cryo-electron microscopy structure of HexaPro at a resolution of 3.2 angstroms confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Structure-based Design of Prefusion-stabilized SARS-CoV-2 Spikes.

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has led to accelerated efforts to develop therapeutics, diagnostics, and vaccines to mitigate this public health emergency. A key target of these efforts is the spike (S) protein, a large trimeric class I fusion protein that is metastable and difficult to produce recombinantly in large quantities. Here, we designed and expressed over 100 structure-guided spike variants based upon a previously determined cryo-EM structure of the prefusion SARS-CoV-2 spike. Biochemical, biophysical and structural characterization of these variants identified numerous individual substitutions that increased protein yields and stability. The best variant, HexaPro, has six beneficial proline substitutions leading to ~10-fold higher expression than its parental construct and is able to withstand heat stress, storage at room temperature, and multiple freeze-thaws. A 3.2 Å-resolution cryo-EM structure of HexaPro confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for SARS-CoV-2.

Time estimation: Close your eyes and tell me when a minute goes by.

The 1-minute estimation test is a relatively new task. This article is an initial offering showing normative data for children from age six up through adulthood (age =76). The task is quite simple, the individual was simply asked to estimate the passage of time for 1 minute. The normative data indicate that children's data needs to be stratified by age, whereas adult data did not need to be stratified by age. Demographic variables such as handedness, gender and ethnicity were not significantly related to 1-minute estimation performance. In looking at a comparison between Traumatic Brain Injured (TBI) patients and Normal Controls, there was a significant effect suggesting that the 1-minute estimation is sensitive to cognitive impairment. Further investigation is needed; however, investigation must begin with the availability of adequate norms so that comparisons can be made. This article provides the needed normative data.

Premorbid estimates of neuropsychological functioning for diverse groups.

One of the basic tasks performed by a neuropsychologist is to identify the difference between current performance and the premorbid expected performance. Baseline expected performance for Intellectually Impaired (n = 21), Developmentally Delayed (n = 40), Attention Deficit Disorder (n = 98), Learning Disability (n = 42), and "Normal" groups (n = 75) were developed along with a demographically corrected prediction of premorbid functioning and a word reading based prediction of premorbid functioning. We utilized a subset of this data pool for development (n = 107) and validation (n = 108) of premorbid functioning estimates. Findings show that a combination of three methods (baseline, demographic, and reading) were superior to any individual method. The effect size (Cohen's d) calculations show that differences in the prediction of domain level performances were small and likely not clinically meaningful, indicating that the premorbid estimates would be usable as a prediction of expected performance at the domain level. However, the motor domains were not well predicted.

Long-Term Test-Retest Stability of ANAM in a Large Military Sample.

OBJECTIVE: This paper examines the long-term stability of the Automated Neuropsychological Assessment Metrics (ANAM) over 1-year, 3-year, and 5-year time periods. METHODS: The sample was drawn from active duty military personnel. All individuals were administered the ANAM and were re-administered the ANAM a second time, either 1 year, 3 years, or 5 years later. All individuals had no reported cognitive problems or concussion or any traumatic brain injury between the first and second assessments and had no intervening contact with the ANAM. All were assessed using the military standard approach with trained proctors. RESULTS: The results for (n = 19,997) individuals who were tested 1 year apart showed an intra-class correlation (ICC) of .6 for simple reaction time and simple reaction time repeat and .7 and above for all other scales. For the sample with 3 years between testings (n = 9,166), the ICC was similar to the 1-year sample. When the 5 year between testings data was examined (n = 2,270), the ICCs for all scales except the simple reaction time and simple reaction time repeat showed ICCs of .7 and.8. The simple reaction time and simple reaction time repeat showed ICCs of .596. CONCLUSIONS: These results indicate that the use of the ANAN baseline for comparison can be done even if the baseline is up to 5 years old.

Use of multiple performance and symptom validity measures: Determining the optimal per test cutoff for determination of invalidity, analysis of skew, and inter-test correlations in valid and invalid performance groups.

Objective: Discrimination of patients passing vs. failing the Word Memory Test (WMT) by performance on 11 performance and symptom validity tests (PVTs, SVTs) from the Meyers Neuropsychological Battery (MNB) at per-test false positive cutoffs ranging from 0 to 15%. PVT and SVT intercorrelation in subgroups passing and failing the WMT, as well as the degree of skew of the individual PVTs and SVT in the pass/fail subgroups, were also analyzed. Method: In 255 clinical and forensic cases, 100 failed and 155 passed the WMT, at a base-rate of invalid performance of 39.2%. Performance was contrasted on 10 PVTs and 1 SVT from the MNB, using per-test false positive rates of 0.0%, 3.3%, 5.0%, 10.0%, and 15.0% in discriminating WMT pass and WMT fail groups. These two WMT groups were also contrasted using the 10 PVTs and 1 SVT as continuous variables in a logistic regression. Results: The per-PVT false positive rate of 10% yielded the highest WMT pass/fail classification, and more closely approximated the classification obtained by logistic regression than other cut scores. PVT and SVT correlations were higher in cases failing the WMT, and data were more highly skewed in those passing the WMT. Conclusions: The optimal per-PVT and SVT cutoff is at a false positive rate of 10%, with failure of ≥3 PVTs/SVTs out of 11 yielding sensitivity of 61.0% and specificity of 90.3%. PVTs with the best classification had the greatest degree of skew in the WMT pass subgroup.

Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients.

In December 2017, the National Academy of Neuropsychology convened an interorganizational Summit on Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients in Denver, Colorado. The Summit brought together representatives of a broad range of stakeholders invested in the care of older adults to focus on the topic of cognitive health and aging. Summit participants specifically examined questions of who should be screened for cognitive impairment and how they should be screened in medical settings. This is important in the context of an acute illness given that the presence of cognitive impairment can have significant implications for care and for the management of concomitant diseases as well as pose a major risk factor for dementia. Participants arrived at general principles to guide future screening approaches in medical populations and identified knowledge gaps to direct future research. Key learning points of the summit included: recognizing the importance of educating patients and healthcare providers about the value of assessing current and baseline cognition; emphasizing that any screening tool must be appropriately normalized and validated in the population in which it is used to obtain accurate information, including considerations of language, cultural factors, and education; and recognizing the great potential, with appropriate caveats, of electronic health records to augment cognitive screening and tracking of changes in cognitive health over time.

Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients.

In December 2017, the National Academy of Neuropsychology convened an interorganizational Summit on Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients in Denver, Colorado. The Summit brought together representatives of a broad range of stakeholders invested in the care of older adults to focus on the topic of cognitive health and aging. Summit participants specifically examined questions of who should be screened for cognitive impairment and how they should be screened in medical settings. This is important in the context of an acute illness given that the presence of cognitive impairment can have significant implications for care and for the management of concomitant diseases as well as pose a major risk factor for dementia. Participants arrived at general principles to guide future screening approaches in medical populations and identified knowledge gaps to direct future research. Key learning points of the summit included: recognizing the importance of educating patients and healthcare providers about the value of assessing current and baseline cognition;emphasizing that any screening tool must be appropriately normalized and validated in the population in which it is used to obtain accurate information, including considerations of language, cultural factors, and education; andrecognizing the great potential, with appropriate caveats, of electronic health records to augment cognitive screening and tracking of changes in cognitive health over time.

Presidential Address National Academy of Neuropsychology Conference Boston 2017.

This presidential address attempts to predict the future directions of neuropsychology. Predicting the future is always a difficult thing. By examining population trends such as aging and demographics, a clearer picture becomes visible. The population is getting older and more ethnically diverse. Also, examination of the spending trends in health care indicates that neuropsychology needs to be able to adapt to working with larger population-based patient care as well as individual patient care. Shifts in the demographics of neuropsychology, in that the profession previously was 70% male dominate and now is >70% female dominant are also discussed. Trends in NAN's speaker and leader demographics are examined as well as the need to stay current in the trends and latest neuropsychological research lest we become dinosaurs in the next 5-10 years. Recommendations for new neuropsychologists and post-doctoral fellows are also presented.

An Unusual Triple-Decker Variant of the Tetragonal BaAl4-Structure Type: Synthesis, Structural Characterization, and Chemical Bonding of Sr3Cd8Ge4 and Eu3Cd8Ge4.

Reported are the synthesis and the crystal structures of the new ternary phases Sr3Cd8Ge4 and Eu3Cd8Ge4. The structures of both compounds have been established by single-crystal and powder X-ray diffraction methods. They crystallize in the tetragonal space group I4/mmm (No. 139, own structure type, Pearson symbol tI30) with Z = 2, and lattice parameters as follows: a = 4.4941(14) Å; c = 35.577(7) Å for Sr3Cd8Ge4, and a = 4.4643(12) Å; c = 35.537(9) Å for Eu3Cd8Ge4, respectively. The most prominent feature of the structure is the complex [Cd2Ge] polyanionic framework, derived by unique ordering of the Cd and Ge atoms in fragments that bear resemblance to the BaAl4 structure type. Temperature dependent DC magnetization measurements indicate that Eu3Cd8Ge4 displays Curie-Weiss paramagnetic behavior with no sign of magnetic ordering in the measured range. Theoretical considerations of the electronic structure on the basis of the tight-binding linear muffin-tin orbital (TB-LMTO-ASA) method are also presented and discussed.