Acceptable Predictive Validity Research Articles

Bioinformatics analysis and experimental validation of m6A and cuproptosis-related lncRNA NFE4 in clear cell renal cell carcinoma

PurposeThis study aimed to construct an m6A and cuproptosis-related long non-coding RNAs (lncRNAs) signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using the information acquired from The Cancer Genome Atlas (TCGA) database.MethodsFirst, the co-expression analysis was performed to identify lncRNAs linked with N6-methyladenosine (m6A) and cuproptosis in ccRCC. Then, a model encompassing four candidate lncRNAs was constructed via univariate, least absolute shrinkage together with selection operator (LASSO), and multivariate regression analyses. Furthermore, Kaplan–Meier, principal component, functional enrichment annotation, and nomogram analyses were performed to develop a risk model that could effectively assess medical outcomes for ccRCC cases. Moreover, the cellular function of NFE4 in Caki-1/OS-RC-2 cultures was elucidated through CCK-8/EdU assessments and Transwell experiments. Dataset outcomes indicated that NFE4 can have possible implications in m6A and cuproptosis, and may promote ccRCC progression.ResultsWe constructed a panel of m6A and cuproptosis-related lncRNAs to construct a prognostic prediction model. The Kaplan–Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. Furthermore, the m6A and cuproptosis-related lncRNA model indicated higher diagnostic efficiency than other clinical features. Moreover, the NFE4 function analysis indicated a gene associated with m6A and cuproptosis-related lncRNAs in ccRCC. It was also revealed that the proliferation and migration of Caki-1 /OS-RC-2 cells were inhibited in the NFE4 knockdown group.ConclusionOverall, this study indicated that NFE4 and our constructed risk signature could predict outcomes and have potential clinical value.

Pre- and intra-operative risk factors predict postoperative respiratory failure after minimally invasive oesophagectomy.

Severe pulmonary complications such as postoperative respiratory failure can occur after minimally invasive oesophagectomy. However, the risk factors have not been well identified. The goal of this study was to develop a predictive model for the occurrence of postoperative respiratory failure with a large sample. We collected data from patients with oesophageal cancer who had a minimally invasive oesophagectomy at Shanghai Chest Hospital from 2019 to 2022. Univariable and backward stepwise logistic regression analysis of 19 pre- and intra-operative factors was used before model fitting, and its performance was evaluated with the receiver operating characteristic curve. Internal validation was assessed with a calibration plot, decision curve analysis and area under the curve with 95% confidence intervals, obtained from 1000 resamples set by the bootstrap method. This study enrolled 2,386 patients, 57 (2.4%) of whom developed postoperative respiratory failure. Backward stepwise logistic regression analysis revealed that age, body mass index, cardiovascular disease, diabetes, diffusion capacity of the lungs for carbon monoxide, tumour location and duration of chest surgery ≥101.5 min were predictive factors. A predictive model was constructed and showed acceptable performance (area under the curve: 0.755). The internal validation with the bootstrap method proves the good agreement for prediction and reality. Obesity, severe diffusion dysfunction and upper segment oesophageal cancer were strong predictive factors. The established predictive model has acceptable predictive validity for postoperative respiratory failure after minimally invasive oesophagectomy, which may improve the identification of high-risk patients and enable health-care professionals to perform risk assessment for postoperative respiratory failure at the initial consultation.

Efficient measurement of writing knowledge with forced-choice tasks: Preliminary data using the student knowledge of writing tests

Much of the research that has examined the writing knowledge of school-age students has relied on interviews to ascertain this information, which is problematic because interviews may underestimate breadth and depth of writing knowledge, require lengthy interactions with participants, and do not permit a direct evaluation of a prescribed array of constituent knowledge elements. For these reasons, our goal in this study is to report the development, piloting, and field testing, using a sample of 335 students from grades 4 and 5, of four alternate versions of a writing knowledge assessment—the Student Knowledge of Writing Test (SKOWT)—that uses forced-choice responses to evaluate students’ knowledge of writing processes, genre elements, and linguistic features of written language. All versions of the SKOWT demonstrated adequate internal consistency reliability and construct validity based on exploratory factor analyses following deletion of some items. In addition, there was acceptable predictive criterion validity based on associations of SKOWT scores with subtests from the Test of Written Language-4 and measures of narrative, opinion, and informative essay quality. We discuss how the SKOWT might be used in future research and educational practice.

Thrsp Gene and the ADHD Predominantly Inattentive Presentation.

There are three presentations of attention-deficit/hyperactivity disorder (ADHD): the predominantly inattention (ADHD-PI), predominantly hyperactive-impulsive (ADHD-HI), and combined (ADHD-C) presentations of ADHD. These may represent distinct childhood-onset neurobehavioral disorders with separate etiologies. ADHD diagnoses are behaviorally based, so investigations into potential etiologies should be founded on behavior. Animal models of ADHD demonstrate face, predictive, and construct validity when they accurately reproduce elements of the symptoms, etiology, biochemistry, and disorder treatment. Spontaneously hypertensive rats (SHR/NCrl) fulfill many validation criteria and compare well with clinical cases of ADHD-C. Compounding the difficulty of selecting an ideal model to study specific presentations of ADHD is a simple fact that our knowledge regarding ADHD neurobiology is insufficient. Accordingly, the current review has explored a potential animal model for a specific presentation, ADHD-PI, with acceptable face, predictive, and construct validity. The Thrsp gene could be a biomarker for ADHD-PI presentation, and THRSP OE mice could represent an animal model for studying this distinct ADHD presentation.

Preliminary validation of the Diversion Risk Scale (DRS): Using environmental and individual factors to predict opioid-related diversion events.

The standard of care calls for the assessment of patients with chronic pain prior to the initiation of opioids, with one part of this assessment including assessment of the risk of misuse of medications. However, traditional opioid risk assessment tools focus almost entirely on individual factors and on the risk of misuse and addiction to opioids. Diversion of opioid medications has been found to be not uncommon, but to date, there have been no assessment tools specifically designed to assess the risk of diversion. In this study, we developed a measure designed specifically to assess the risk of an opioid medication ending up in the hands of someone other than the chronic pain patient to whom they were prescribed. A 15-item measure, the Diversion Risk Scale, was created and administered to 85 patients at a chronic pain practice. Results found that the measure had acceptable predictive validity. It was moderately correlated with traditional opioid risk assessment tools and showed improved ability to predict specific indicators of diversion. Diversion has been an understudied phenomenon, and the clinical value of an assessment tool that can help predict diversion in the chronic pain population is discussed.

Exploring the predictive properties of the Hayes Ability Screening Index subtest background information in identifying individuals with MBID among in-patients with SUD.

For individuals with substance use disorder (SUD), mild to borderline intellectual disability (MBID) goes undetected in treatment clinics. The Hayes Ability Screening Index (HASI) has been found to be a valid, time-saving screening instrument for MBID in SUD treatment. MBID can have significant implications for treatment planning and outcomes. Therefore, it is important to have methods for the early recognition of these comorbid conditions. Because of less sensitivity to recent or ongoing substance use, the HASI subtest background information may be particularly valuable as an early screening of MBID. The main aim was to investigate the convergent, predictive, and discriminant validity of the HASI subtest background information in identifying in-patients with SUD as MBID or non-MBID. Eighty-four in-patients with SUD aged 19-64 participated in this multicentre study. MBID was diagnosed according to the ICD-10 using WAIS-IV, Vineland II, and self-reported childhood learning difficulties. The main finding was that, among the HASI subtests, background information was the strongest predictor. A HASI background information cut between 6 and 7 showed a sensitivity of 78% and a specificity of 72%. The HASI subtest background information has acceptable convergent, predictive, and discriminant validity as a screening for MBID among in-patients in SUD treatment.

Cuproptosis-Associated lncRNA Establishes New Prognostic Profile and Predicts Immunotherapy Response in Clear Cell Renal Cell Carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all kidney cancers and has a poor prognosis. Recent studies have shown that copper-dependent, regulated cell death differs from previously known death mechanisms (apoptosis, ferroptosis, and necroptosis) and is dependent on mitochondrial respiration (Tsvetkov et al., Science, 2022, 375 (6586), 1254–1261). Studies also suggested that targeting cuproptosis may be a novel therapeutic strategy for cancer therapy. In ccRCC, both cuproptosis and lncRNA were critical, but the mechanisms were not fully understood. The aim of our study was to construct a prognostic profile based on cuproptosis-associated lncRNAs to predict the prognosis of ccRCC and to study the immune profile of clear cell renal cell carcinoma (ccRCC). Methods: We downloaded the transcriptional profile and clinical information of ccRCC from The Cancer Genome Atlas (TCGA). Co-expression network analysis, Cox regression method, and least absolute shrinkage and selection operator (LASSO) method were used to identify cuproptosis-associated lncRNAs and to construct a risk prognostic model. In addition, the predictive performance of the model was validated and recognized by an integrated approach. We then also constructed a nomogram to predict the prognosis of ccRCC patients. Differences in biological function were investigated by GO, KEGG, and immunoassay. Immunotherapy response was measured using tumor mutational burden (TMB) and tumor immune dysfunction and rejection (TIDE) scores. Results: We constructed a panel of 10 cuproptosis-associated lncRNAs (HHLA3, H1-10-AS1, PICSAR, LINC02027, SNHG15, SNHG8, LINC00471, EIF1B-AS1, LINC02154, and MINCR) to construct a prognostic prediction model. The Kaplan–Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. The cuproptosis-associated lncRNA model had higher diagnostic efficiency compared to other clinical features. The analysis of Immune cell infiltration and ssGSEA further confirmed that predictive features were significantly associated with the immune status of ccRCC patients. Notably, the superimposed effect of patients in the high-risk group and high TMB resulted in shorter survival. In addition, the higher TIDE scores in the high-risk group suggested a poorer outcome for immune checkpoint blockade response in these patients. Conclusion: The ten cuproptosis-related risk profiles for lncRNA may help assess the prognosis and molecular profile of ccRCC patients and improve treatment options, which can be further applied in the clinic.

Assessing the predictive validity of a risk assessment instrument for repeat victimization in the Netherlands using prior police contacts

The current study examined to what extent a valid instrument that predicts repeat victimization can be based on a victim's prior police contacts. Police records between 2010 and 2017 were retrieved for a sample of 68,229 victims. The data was split into a training set ( n = 34,224) and a test set ( n = 34,005). Using logistic regression analyses in the training set, three models were developed linking prior police contacts to repeat victimization. The predictive validity was assessed in the test set. Results indicated that (a) prior police contacts as victims, suspects and witnesses were associated with an elevated risk of repeat victimization and (b) the model correctly classified a majority of both repeat victims and non-repeat victims across various cut-off points. Findings demonstrated moderate to acceptable predictive validity, thereby suggesting that there is considerable room for improvement.

Validity and reliability of the novel three-item occupational violence patient risk assessment tool.

AimTo develop and psychometrically test an occupational violence (OV) risk assessment tool in the emergency department (ED).DesignThree studies were conducted in phases: content validity, predictive validity and inter‐rater reliability from June 2019 to March 2021.MethodsFor content validity, ED end users (mainly nurses) were recruited to rate items that would appropriately assess for OV risk. Subsequently, a risk assessment tool was developed and tested for its predictive validity and inter‐rater reliability. For predictive validity, triage notes of ED presentations in a month with the highest OV were assessed for presence of OV risk. Each presentation was then matched with events recorded in the OV incident register. Sensitivity and specificity values were calculated. For inter‐rater reliability, two assessors—trained and untrained—independently assessed the triage notes for presence of OV risk. Cohen's kappa was calculated.ResultsTwo rounds of content validity with a total of N = 81 end users led to the development of a three‐domain tool that assesses for OV risk using aggression history, behavioural concerns (i.e., angry, clenched fist, demanding, threatening language or resisting care) and clinical presentation concerns (i.e., alcohol/drug intoxication and erratic cognition). Recommended risk ratings are low (score = 0 risk domain present), moderate (score = 1 risk domain present) and high (score = 2–3 risk domains present), with an area under the curve of 0.77 (95% confidence interval 0.7–0.81, p < .01). Moderate risk rating had a 61% sensitivity and 91% specificity, whereas high risk rating had 37% sensitivity and 97% specificity. Inter‐rater reliability ranged from 0.67 to 0.75 (p < .01), suggesting moderate agreement.ConclusionsThe novel three‐domain OV risk assessment tool was shown to be appropriate and relevant for application in EDs. The tool, developed through a rigorous content validity process, demonstrates acceptable predictive validity and inter‐rater reliability.ImpactThe developed tool is currently piloted in a single hospital ED, with a view to extend to inpatient settings and other hospitals.

Development and Validation of the Multidimensional Procrastination Scale in Chinese

Abstract. Procrastination is a complicated phenomenon with many thoughts, behaviors, and feelings that may characterize different subgroups of procrastinators. Such phenomenon has not been well studied in an integrated theoretical framework. This study aims to establish a theory about the behavioral, cognitive, and affective aspects of procrastination and to develop and validate an operational instrument. In Study 1, we conducted qualitative research based on grounded theories and generated seven initial categories with 22 themes associated with the components in procrastination. In Study 2, we developed an instrument, the Multidimensional Procrastination Scale (MPS), and established a five-dimension structure for the MPS using explanatory factor analysis (EFA; N = 435) and confirmatory factor analysis (CFA; N = 387). In Study 3, we established construct validity and predictive validity for the MPS by building a nomological framework and predicting behavioral procrastination, respectively. The theoretical framework of procrastination included maladaptive (i.e., impulsive and unorganized, hesitation, lack of incentives, avoidance) and adaptive (i.e., arousal and rationalization) components. The MPS demonstrated acceptable reliability, factorial validity, construct validity, and predictive validity. The findings of this study have implications for further studies on the typology of procrastination and the development of tailored interventions to alleviate maladaptive aspects of procrastination.

Expected clinical utility of automatable prediction models for improving palliative and end-of-life care outcomes: Toward routine decision analysis before implementation.

ObjectiveThe study sought to evaluate the expected clinical utility of automatable prediction models for increasing goals-of-care discussions (GOCDs) among hospitalized patients at the end of life (EOL).Materials and MethodsWe built a decision model from the perspective of clinicians who aim to increase GOCDs at the EOL using an automated alert system. The alternative strategies were 4 prediction models—3 random forest models and the Modified Hospital One-year Mortality Risk model—to generate alerts for patients at a high risk of 1-year mortality. They were trained on admissions from 2011 to 2016 (70 788 patients) and tested with admissions from 2017-2018 (16 490 patients). GOCDs occurring in usual care were measured with code status orders. We calculated the expected risk difference (beneficial outcomes with alerts minus beneficial outcomes without alerts among those at the EOL), the number needed to benefit (number of alerts needed to increase benefit over usual care by 1 outcome), and the net benefit (benefit minus cost) of each strategy.ResultsModels had a C-statistic between 0.79 and 0.86. A code status order occurred during 2599 of 3773 (69%) hospitalizations at the EOL. At a risk threshold corresponding to an alert prevalence of 10%, the expected risk difference ranged from 5.4% to 10.7% and the number needed to benefit ranged from 5.4 to 10.9 alerts. Using revealed preferences, only 2 models improved net benefit over usual care. A random forest model with diagnostic predictors had the highest expected value, including in sensitivity analyses.DiscussionPrediction models with acceptable predictive validity differed meaningfully in their ability to improve over usual decision making.ConclusionsAn evaluation of clinical utility, such as by using decision curve analysis, is recommended after validating a prediction model because metrics of model predictiveness, such as the C-statistic, are not informative of clinical value.

Patient knowledge of rotator cuff related shoulder pain condition and treatment and validation of a patient-reported knowledge questionnaire.

Rotator cuff related shoulder pain (RCRSP) knowledge is an important contributor to compliance with clinical practice guidelines and providing best practice care. However, there are no validated instruments for measuring health literacy levels among people with RCRSP. This study aimed to design a valid and reliable instrument to measure RCRSP health literacy and use it to evaluate an education intervention for people with RCRSP. Development of the patient knowledge questionnaire (PKQ-RCRSP) included three phases. Phase 1 was developed based on available literature and input from expert clinicians, researchers and patients. Face validity, pilot testing andreadability assessment were also undertaken. In Phase 2, internal consistency and predictive validity were assessed in people with RCRSP and other shoulder pain diagnoses. In Phase 3, RCRSP health literacy was assessed. Face validity was acceptable and pilot testing identified minor accuracy issues that were corrected. Literacy level was rated as 'difficult to read' which reflects the medical terminology within the questionnaire. Internal consistency was very good and 81% of questions demonstrated acceptable predictive validity. Health literacy was heterogeneous depending on the question with less than 40% of respondents answering correctly for questions related to the indications, process and the known benefits of RCRSP surgery. The PKQ-RCRSP demonstrated acceptable face validity, predictive validity and reliability (internal consistency) in assessing RCRSP health literacy. Health literacy among our small sample was poor for questions related to surgery for RCRSP.

The Brief Partner Behavioral Control Scale (B-PBCS): Development and Validation

Despite the large growth of close relationships literature, partner behavioral control has been rarely the primary focus of research. It is also evident that the instruments for measuring partner behavioral control are scarce. Thus, the present study aims to develop and validate a 9-item Brief Partner Behavioral Control Scale (B-PBCS). The validity and reliability of the B-PBCS were examined in a sample of emerging adults (N = 511; 81.8% females; Rangeage = 18-25) who are currently in a premarital romantic relationship. To assess psychometric properties of the B-PBCS, we conducted a series of tests examining factor structure (exploratory and confirmatory factor analyses), measurement invariance (configural and metric invariance), reliability (internal consistency and test-retest reliability), and predictive validity. Results demonstrated that the B-PBCS has a two-factor solution (overt and covert partner behavioral control), acceptable measurement invariance, internal consistency, test-retest reliability, and predictive validity. The overt partner behavioral control at baseline assessment has been linked to romantic relationship conflict and psychological distress at 14-week follow-up assessment even after controlling for sex, age, and relationship duration. In conclusion, the B-PBCS offers a valid and brief measure for assessing partner behavioral control.

Cross-cultural modifications and measurement properties of the CHAMPS questionnaire among Chinese older adults

Background/objectiveThe Community Health Activities Model Program for Seniors questionnaires (CHAMPS-Q) is one of the most extensively used instruments in assessing physical activity among older adults. However, no study had translated the CHAMPS-Q into Chinese, and no evaluations were made on the psychometric properties of the CHAMPS-Q among the Chinese population. Considering cultural differences in perceptions of language, cultural context and living habits, this study was of necessary to 1) translate and cross-culturally adapt the original CHAMPS-Q, and 2) examine the test-retest reliability and construct/predictive validity of the Chinese version of the CHAMPS-Q. MethodsThe English CHAMPS-Q was first translated into Chinese, synthesized, back-translated, and revised by an expert committee according to the pre-test results. The Chinese CHAMPS-Q was then assessed in a cross-sectional study consisting of 101 apparently healthy older adults. Test-retest reliability test was conducted with 7 days apart. The construct validity of the Chinese CHAMPS-Q was tested against accelerometer data, and the predictive validity was assessed against physical fitness as measured by the Senior Fitness Test. ResultsThe Chinese CHAMPS-Q has moderate to excellent test-retest reliability (ICC = 0.72-.96, p < .05). Energy expenditure and duration in PA significantly correlated with all accelerometry outcomes (ρ = 0.22-.31, p < .05). All the outcomes from the CHAMPS-Q showed significant correlations with upper body muscle strength (ρ = 0.22-.34, p < .05). ConclusionThe Chinese CHAMPS-Q has excellent test-retest reliability and acceptable construct and predictive validity in assessing the physical activity of Chinese older adults.

Disability and perceived stress in primary care patients with major depression.

Major depressive disorder (MDD) is highly prevalent in the Spanish primary care (PC) setting and the leading cause of disability in Spain. The aim of this study was to evaluate several key psychometric properties of the Sheehan Disability Scale (SDS) in patients with or without MDD and varying degrees of symptom severity using the Patient Health Questionnaire-9 (PHQ-9). A total of 1,704 PC patients participating in the PsicAP clinical trial completed the SDS and PHQ-9. We evaluated the factor structure, measurement invariance across gender, internal consistency, and the discriminative and predictive validity. Confirmatory factor analyses revealed a unifactorial model of the SDS containing 4 items (SDS-4) with the best model fit (CFI: .99; GFI: .99; TLI: 96; RMSEA: .10). This model contained the three life domain items (work, family, and social life) plus perceived stress (PS) with significant loadings. The internal consistency of the SDS-4 was acceptable in patients with or without MDD, regardless of symptom severity. The SDS-4 also showed good discriminative capacity and acceptable predictive validity in all subsamples. These findings support the use of the SDS-4 to assess depression-related disability in patients at Spanish primary care centres.

Constructing Taiwan’s Active Aging Index and Applications for International Comparison

The purpose of this study is to construct Taiwan’s Active Aging Index (TAAI) based on the Active Aging Index (AAI) of the European Union (EU) and with consideration of the cultural and specific characteristics in Taiwan and to compare the result with the AAI status in the EU-28 countries. The first draft of TAAI was developed; 25 experts from the aging industry, government representatives, and academics were invited to participate in the modified Delphi method or an expert group meeting. Older adults were invited to collect opinions from the perspective of older people. The weights of the TAAI indicators were assessed by an analytical hierarchical method based on the Delphi method questionnaire. The indicators collected by a survey questionnaire were designed, pretested and modified, and then, the data were collected from a sample across four regions of Taiwan (n = 738). The TAAI indicator scores were calculated accordingly. The AAI performance of Taiwan was also compared with the performance of the EU-28 countries. The original 4 AAI domains were maintained in the framework. In TAAI, 11 indicators were added to the existing four domains and, in total, 33 indicators were suggested. The TAAI indicators showed acceptable reliability and predictive validity in self-rated health. The indicators regarding health and capacity for active aging in Taiwan were good, and social participation and economic security could be improved. The TAAI framework and indicators are suggested to be applied in the monitoring and policy making of active aging and in future research.

Validity and Reliability of the Transport Triage Tool.

Standards for interfacility transport in the United States recommend that each transport request be triaged to ensure that each patient is transported by an appropriate mechanism and by the appropriate clinicians in order to meet the patient's intratransport needs. No instrument currently exists to meet that need. The Transport Triage Tool, a novel instrument, has been designed to determine the clinician (paramedic, registered nurse, or advanced practice registered nurse) who will best meet the patient's needs during transport. To assess psychometric elements-that is, validity and reliability-of the Transport Triage Tool when used by health care professionals in determining which clinician is appropriate for interfacility transport. A 3-step process was used to initially evaluate the reliability and validity of this tool when assigning a lead clinician during transport. Content and predictive validity were evaluated. Both intrarater and interrater agreement were used to examine reliability. Predictive validity was supported by an area under the receiver operating characteristic curve of 0.847 and a Youden index of 0.31. Percentage agreement and Cohen κ were reasonable across all periods of testing. The Transport Triage Tool has acceptable predictive validity and reliability; however, this preliminary evaluation indicates that further refinement is needed. Large tertiary centers that offer variations in transport team composition may be able to use the Tool in its present form to train and evaluate individuals who make decisions regarding interfacility transport, although additional testing and evaluation are recommended.

Evidence-Based Review and Discussion Points

Evidence-Based Review and Discussion Points

Predictive models for short-term and long-term improvement in women under physiotherapy for chronic disabling neck pain: a longitudinal cohort study

ObjectivesTo develop predictive models for short-term and long-term clinically important improvement in women with non-specific chronic disabling neck pain during the clinical course of physiotherapy.DesignLongitudinal cohort study based on data...

Psychometric Properties of the Merrill-Palmer-Revised Scales of Development in Preschool Children With Autism Spectrum Disorder.

Psychometrically sound tests of intellectual ability are indispensable for research and assessment of children with autism spectrum disorder (ASD), yet few tests have been validated for use with this population. The Merrill-Palmer-Revised Scales of Development (M-P-R) is a standardized test of intellectual ability that was validated for use with typically developing preschoolers. The current study's aim was to investigate the criterion validity of the M-P-R for assessing cognitive skills in preschoolers with ASD (N = 180). Good concurrent validity was demonstrated, with a large positive correlation between the M-P-R Receptive Language domain and the PLS-4 Auditory Comprehension subscale. The Cognitive domain of the M-P-R showed a medium positive correlation with later WISC-4 scores, showing acceptable predictive validity. Cognitive strengths and weaknesses assessed using the M-P-R mirrored those described for other measures, with most children obtaining higher standard scores on the Cognitive than the Receptive Language domain. An exploratory factor analysis suggested that one factor accounted for the majority of variability in M-P-R domains.