Newborn screening for mucopolysaccharidosis type II: Lessons learned.

We describe our experience with population-based newborn screening for mucopolysaccharidosis type II (MPS II) in 586,323 infants by measurement of iduronate-2-sulfatase activity in dried blood spots between December 12, 2017 and April 30, 2022. A total of 76 infants were referred for diagnostic testing, 0.01% of the screened population. Of these, eight cases of MPS II were diagnosed for an incidence of 1 in 73,290. At least four of the eight cases detected had an attenuated phenotype. In addition, cascade testing revealed a diagnosis in four extended family members. Fifty-three cases of pseudodeficiency were also identified, for an incidence of 1 in 11,062. Our data suggest that MPS II may be more common than previously recognized with a higher prevalence of attenuated cases.

Clinical Evaluation of BD Veritor SARS-CoV-2 and Flu A+B Assay for Point-Of-Care System.

Differential diagnosis of COVID-19 and/or influenza (flu) at point of care is critical for efficient patient management and treatment of both these diseases. The study presented here characterizes the BD Veritor System for Rapid Detection of SARS-CoV-2 and Flu A+B ("Veritor SARS-CoV-2/Flu") triplex assay. The performance for SARS-CoV-2 detection was determined using 298 specimens from patients reporting COVID-19 symptoms within 7 days from symptom onset (DSO) in comparison with the Lyra SARS-CoV-2 RT-PCR (reverse transcriptase PCR) assay ("Lyra SARS-CoV-2") as the reference. The performance for flu A and flu B detection was determined using 75 influenza-positive and 40 influenza-negative retrospective specimens in comparison with the previously FDA-cleared BD Veritor System for Rapid Detection of Flu A+B assay ("Veritor Flu") as the reference. The Veritor SARS-CoV-2/Flu assay met the FDA EUA acceptance criteria (86.7%; 95% confidence interval [95% CI]: 75.8 to 93.1) for SARS-CoV-2 testing compared to Lyra SARS-CoV-2. The Veritor SARS-CoV-2/Flu assay also demonstrated 100% agreement with the Veritor Flu for Flu A+B assay. For flu A detection, the lower bound of the 95% CI was 91.2%; for flu B detection, the lower bound was 90.0%. The dual detection capability of Veritor SARS-CoV-2/Flu for the etiologic agents causing COVID-19 and flu will allow efficient differentiation between the two illnesses, inform disease management, and facilitate optimal treatment. IMPORTANCE COVID-19 and flu are two respiratory illnesses which share similar clinical symptoms. The BD Veritor SARS-CoV-2/Flu assay has high sensitivity and specificity for detecting the SARS-CoV-2 and influenza A/B, the two etiologic agents causing COVID-19 and flu, respectively. This dual detection capability is critical when overlap occurs between the COVID-19 pandemic and the flu season. This triplex assay will allow efficient differentiation between the two respiratory illnesses and support a point-of-care physician diagnosis to facilitate the proper treatment and disease management for patients exhibiting overlapping symptoms.

Examining the role of COVID-19 testing availability on intention to isolate: A Randomized hypothetical scenario.

BACKGROUND: Little information exists on how COVID-19 testing influences intentions to engage in risky behavior. Understanding the behavioral effects of diagnostic testing may highlight the role of adequate testing on controlling viral transmission. In order to evaluate these effects, simulated scenarios were conducted evaluating participant intentions to self-isolate based on COVID-19 diagnostic testing availability and results. METHODS: Participants from the United States were recruited through an online survey platform (Amazon Mechanical Turk) and randomized to one of three hypothetical scenarios. Each scenario asked participants to imagine having symptoms consistent with COVID-19 along with a clinical diagnosis from their physician. However, scenarios differed in either testing availability (testing available v. unavailable) or testing result (positive v. negative test). The primary outcome was intention to engage in high-risk COVID-19 behaviors, measured using an 11-item mean score (range 1-7) that was pre-registered prior to data collection. Multi-variable linear regression was used to compare the mean composite scores between conditions. The randomized survey was conducted between July 23rd to July 29th, 2020. RESULTS: A total of 1400 participants were recruited through a national, online, opt-in survey. Out of 1194 respondents (41.6% male, 58.4% female) with a median age of 38.5 years, participants who had no testing available in their clinical scenario showed significantly greater intentions to engage in behavior facilitating COVID-19 transmission compared to those who received a positive confirmatory test result scenario (mean absolute difference (SE): 0.14 (0.06), P = 0.016), equating to an 11.1% increase in mean score risky behavior intentions. Intention to engage in behaviors that can spread COVID-19 were also positively associated with male gender, poor health status, and Republican party affiliation. CONCLUSION: Testing availability appears to play an independent role in influencing behaviors facilitating COVID-19 transmission. Such findings shed light on the possible negative externalities of testing unavailability. TRIAL REGISTRATION: Effect of Availability of COVID-19 Testing on Choice to Isolate and Socially Distance, NCT04459520, https://clinicaltrials.gov/ct2/show/NCT04459520.

Multicenter Comparison of Nucleic Acid Amplification Tests for the Diagnosis of Rectal and Oropharyngeal Chlamydia trachomatis and Neisseria gonorrhoeae Infections.

Research using nucleic acid amplification tests (NAATs) have repeatedly found rectal and oropharyngeal infections with Chlamydia trachomatis and Neisseria gonorrhoeae to be common and potentially more difficult to treat than genital infections. Unfortunately, public health and patient care efforts have been hampered by the lack of FDA-cleared NAATs with claims for anorectal or oropharyngeal samples. At the time of the initiation of this study, no commercially available assays had these claims. We formed a novel partnership among academic institutions and diagnostic manufacturers to address this public health need. From May 2018 through August 2019, we recruited 1108 women, 1256 men, and 26 transgender persons each of whom provided 3 anal and 3 oropharyngeal swab specimens. The 3 anal swabs were pooled into a single transport tube as were the 3 oropharyngeal swabs. The performance of each of three study assays was estimated by comparison to the composite result and relative to one another. Percent positivity for chlamydia was 5.9 and 1.2% from anal and oropharyngeal specimens, respectively, compared to 4.2 and 4.1% for gonorrhea. Sensitivity for chlamydia detection ranged from 81.0 to 95.1% and 82.8 to 100% for anal and oropharyngeal specimens, respectively. Gonorrhea sensitivity ranged from 85.9 to 99.0% and 74.0 to 100% for anal and oropharyngeal samples, respectively. Specificity estimates were ≥ 98.9% for all assays, organisms, and sample types. Although there was heterogeneity between sensitivity estimates, these assays offer better ability to detect extragenital infections than culture and potential solutions for providing appropriate sexual health care for populations in which these infections are of concern.

A Medial Subvastus Approach for Lateral Unicompartmental Knee Arthroplasty: Technique Description and Early Outcome Results.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) treats arthritis involving only one compartment of the knee. Lateral UKA is mainly performed through medial parapatellar or lateral parapatellar approaches to the knee. This technique article introduces a medial subvastus approach to lateral UKA, discusses the clinical rationale behind its use, and offers a preliminary retrospective study on short-term outcomes of lateral UKAs using the lateral vs medial subvastus approaches. METHODS: A description of the medial subvastus approach is included. In addition, we reviewed 32 and 30 lateral UKAs performed using the lateral and medial subvastus approaches, respectively. Minimum follow-up duration was 1 year. Knee injury and osteoarthritis outcome score for joint replacement (KOOS, JR) knee scores were used for comparison. RESULTS: Age and body mass index were similar between the 2 cohorts. Mean KOOS, JR. scores for the subvastus approach group were significantly higher than those for the lateral approach group at 81.41 ± 2.0 for medial subvastus and 74.19 ± 2.9 for lateral (P = .02). One deep infection and 2 revision total knee arthroplasties occurred in the lateral approach group. Neither occurred in the subvastus group. The mean follow-up duration was significantly longer for the lateral approach group than that for the subvastus group at 749 vs 410 days (P < .001). Literature on time-dependence of patient-reported outcomes supports usage of the data, despite follow-up discrepancies. CONCLUSIONS: A subvastus approach for lateral UKA may offer improved visualization, easier conversion to total knee arthroplasty, and faster recovery, based on clinical observation. Preliminary results suggest improved short-term knee scores compared to a lateral approach.

Newborn Screening for Pompe Disease in Illinois: Experience with 684,290 Infants.

Statewide newborn screening for Pompe disease began in Illinois in 2015. As of 30 September 2019, a total of 684,290 infants had been screened and 395 infants (0.06%) were screen positive. A total of 29 cases of Pompe disease were identified (3 infantile, 26 late-onset). While many of the remainder were found to have normal alpha-glucosidase activity on the follow-up testing (234 of 395), other findings included 62 carriers, 39 infants with pseudodeficiency, and eight infants who could not be given a definitive diagnosis due to inconclusive follow-up testing.

De Novo and Bi-allelic Pathogenic Variants in NARS1 Cause Neurodevelopmental Delay Due to Toxic Gain-of-Function and Partial Loss-of-Function Effects.

Aminoacyl-tRNA synthetases (ARSs) are ubiquitous, ancient enzymes that charge amino acids to cognate tRNA molecules, the essential first step of protein translation. Here, we describe 32 individuals from 21 families, presenting with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia, with de novo heterozygous and bi-allelic mutations in asparaginyl-tRNA synthetase (NARS1). We demonstrate a reduction in NARS1 mRNA expression as well as in NARS1 enzyme levels and activity in both individual fibroblasts and induced neural progenitor cells (iNPCs). Molecular modeling of the recessive c.1633C>T (p.Arg545Cys) variant shows weaker spatial positioning and tRNA selectivity. We conclude that de novo and bi-allelic mutations in NARS1 are a significant cause of neurodevelopmental disease, where the mechanism for de novo variants could be toxic gain-of-function and for recessive variants, partial loss-of-function.

Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7.

PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. METHODS: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. RESULTS: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. CONCLUSION: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies.

Abnormally increased carotid intima media-thickness and elasticity in patients with Morquio A disease.

BACKGROUND: Cardiovascular disease frequently causes morbidity and mortality in mucopolysaccharidoses (MPS); however, cardiovascular anatomy and dysfunction in MPS IVA (Morquio A disease) is not well described. Consequently, the study aimed to compare carotid artery structure and elasticity of MPS IVA patients with other MPS patients and healthy control subjects, and quantitate frequency of MPS IVA cardiac structural and functional abnormalities. METHODS: Prospective, multi-center echocardiogram and carotid ultrasound evaluations of 12 Morquio A patients were compared with other MPS and healthy control subjects. Average differences between groups were adjusted for age, sex, and height with robust variance estimation for confidence intervals and P-values. RESULTS: Morquio A patients demonstrated significantly higher (P < 0.001) adjusted carotid intima-media thickness (cIMT), mean (SD) of 0.56 mm (0.03) compared to control subjects, 0.44 mm (0.04). The Morquio A cohort had significantly greater adjusted carotid elasticity (carotid cross-sectional compliance + 43%, P < 0.001; carotid incremental elastic modulus - 33%, P = 0.003) than control subjects and other MPS patients. Aortic root dilatation was noted in 56% of the Morquio A cohort, which also had highly prevalent mitral (73%) and aortic (82%) valve thickening, though hemodynamically significant valve dysfunction was less frequent (9%). CONCLUSIONS: Increased carotid elasticity in Morquio A patients is an unexpected contrast to the reduced elasticity observed in other MPS. These Morquio A cIMT findings corroborate MPS IVA arterial post-mortem reports and are consistent with cIMT of other MPS. Aortic root dilatation in Morquio A indicates arterial elastin dysfunction, but their carotid hyperelasticity indicates other vascular intima/media components, such as proteoglycans, may also influence artery function. Studying MPS I and IVA model systems may uniquely illuminate the function of glycosaminoglycan-bearing proteoglycans in arterial health.

Population-Based Newborn Screening for Mucopolysaccharidosis Type II in Illinois: The First Year Experience.

OBJECTIVES: To assess the outcome of population-based newborn screening for mucopolysaccharidosis type II (MPS II) during the first year of screening in Illinois. STUDY DESIGN: Tandem mass spectrometry was used to measure iduronate-2-sulfatase (I2S) activity in dried blood spot specimens obtained from 162 000 infant samples sent to the Newborn Screening Laboratory of the Illinois Department of Public Health in Chicago. RESULTS: One case of MPS II and 14 infants with pseudodeficiency for I2S were identified. CONCLUSIONS: Newborn screening for MPS II by measurement of I2S enzyme activity was successfully integrated into the statewide newborn screening program in Illinois.

Prevalence of Postoperative Periprosthetic Femur Fractures Between Two Different Femoral Component Designs Used in Direct Anterior Total Hip Arthroplasty.

BACKGROUND: Periprosthetic femur fractures are a well-documented complication following direct anterior uncemented total hip arthroplasty. The purpose of this study is to compare the prevalence of postoperative periprosthetic femur fractures between 2 different femoral component designs used in direct anterior total hip arthroplasty. METHODS: Beginning in February 2015, a single fellowship-trained adult reconstruction surgeon performed 361 consecutive direct anterior total hip replacements using a flat, single-taper, wedged femoral implant. In June 2016, that same surgeon, using the exact same surgical technique and postoperative weight-bearing protocol, began using a dual-taper, hydroxyapatite-coated implant for 789 consecutive hips. The patients were carefully monitored for 3 months after surgery to identify the frequency of periprosthetic femur fractures. A Fisher's exact test was used to determine if the prevalence of periprosthetic femur fractures differed between the 2 implant designs. RESULTS: Five of 361 (1.4%) patients sustained proximal femur fractures at an average of 19.6 days postoperatively in the first group, all demonstrating a Vancouver type B2 periprosthetic fracture and requiring femoral revision. No patients (0/789, 0%) in the second cohort sustained a postoperative, periprosthetic fracture (P = .006). CONCLUSION: In this comparison of 2 consecutive cohorts, the dual-taper, hydroxyapatite-coated implant had a statistically significant lower postoperative periprosthetic fracture rate than a flat, single-taper, wedged design.

Errors on a computer task and subclinical symptoms of attention-deficit/hyperactivity disorder (ADHD).

Previous reports have found increased error rate for children with attention-deficit/hyperactivity disorder (ADHD) on response time (RT) computer tasks. Here we attempt the conceptual replication and extension of two studies that examined error rate in a general population of children (N = 203). Study 1 followed Johnstone and Galletta but considered associations between scores on a dimensional measure of ADHD symptoms (rather than comparing those with or without an ADHD diagnosis) and the frequency of commission and omission errors. Study 2 followed Shiels, Tamm & Epstein and examined post-error adjustment in the same group of children as for Study 1. Study 1 did not replicate previous findings of no increase in errors of commission in those with higher ADHD symptoms (Johnstone & Galletta). Instead, we found that younger children with lower ADHD symptoms were more likely to make commission errors, while omission errors did not vary with age. Study 2 replicated the previous finding of less RT slowing in children with more ADHD symptoms, extending this finding to a general population of children. Namely, as ADHD symptoms increase, RT slowing is less likely, putting children with higher ADHD symptoms at risk of additional errors. Overall, we extend previous ADHD research to typically developing children with ADHD symptoms.

Continuous Venovenous Hemodialysis Via Extracorporeal Membrane Oxygenation Pump for Treatment of Hyperammonemia Secondary to Propionic Acidemia in Monochorionic Diamniotic Twin Boys.

Late-preterm twins with propionic acidemia developed severe hyperammonemic encephalopathy at 5 days of age. Continuous venovenous hemodialysis was performed successfully for both infants via extracorporeal membrane oxygenation pump, and both rapidly improved. They were taken off continuous venovenous hemodialysis and extracorporeal membrane oxygenation and discharged with dietary therapy. At 3 years of age, neurodevelopment showed globally delayed milestones.

Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis.

Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic condition characterized by ocular, cutaneous, and central nervous system anomalies. Key clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, and central nervous system lipomas. Seizures, spasticity, and intellectual disability can be present, although affected individuals without seizures and with normal intellect have also been reported. Given the patchy and asymmetric nature of the malformations, ECCL has been hypothesized to be due to a post-zygotic, mosaic mutation. Despite phenotypic overlap with several other disorders associated with mutations in the RAS-MAPK and PI3K-AKT pathways, the molecular etiology of ECCL remains unknown. Using exome sequencing of DNA from multiple affected tissues from five unrelated individuals with ECCL, we identified two mosaic mutations, c.1638C>A (p.Asn546Lys) and c.1966A>G (p.Lys656Glu) within the tyrosine kinase domain of FGFR1, in two affected individuals each. These two residues are the most commonly mutated residues in FGFR1 in human cancers and are associated primarily with CNS tumors. Targeted resequencing of FGFR1 in multiple tissues from an independent cohort of individuals with ECCL identified one additional individual with a c.1638C>A (p.Asn546Lys) mutation in FGFR1. Functional studies of ECCL fibroblast cell lines show increased levels of phosphorylated FGFRs and phosphorylated FRS2, a direct substrate of FGFR1, as well as constitutive activation of RAS-MAPK signaling. In addition to identifying the molecular etiology of ECCL, our results support the emerging overlap between mosaic developmental disorders and tumorigenesis.

Fabry disease in infancy and early childhood: a systematic literature review.

PURPOSE: Fabry disease is a pan-ethnic, progressive, X-linked genetic disorder that commonly presents in childhood and is caused by deficient activity of the lysosomal enzyme alpha-galactosidaseA (α-gal A). Symptoms of Fabry disease in the pediatric population are well described for patients over five years of age; however, data are limited for infancy and early childhood. The purpose of this article is to delineate the age of detection for specific Fabry symptoms in early childhood. METHODS: A systematic retrospective analysis of PubMed indexed, peer-reviewed publications and case reports in the pediatric Fabry population was performed to review symptoms in patients reported before 5 years of age. RESULTS: The most frequently reported symptom in all age groups under 5 years was acroparesthesias/neuropathic pain, reported in 9 children, ranging in age from 2.0-4.0 years. Also notable is the frequency of gastrointestinal issues reported in 6 children aged 1.0-4.1 years of age. CONCLUSION: This article finds clear evidence that symptoms can occur in early childhood, before age 5 years. Given early presenting symptoms and the ability to monitor these disease hallmarks, a timely referral to a medical geneticist or other specialty clinician experienced in managing children with Fabry disease is strongly indicated.

Reported communication ability of persons with trisomy 18 and trisomy 13.

OBJECTIVE: The aim of this study was to describe the communication ability of individuals with trisomy 18 and trisomy 13 syndromes. METHODS: Parents reported on children's potential communication acts, words, spontaneous gesture, and augmentative and alternative communication (AAC) using a parent report inventory (n = 32; age range 3-35 years). Potential communicative acts are defined as behaviors produced by an individual that may be interpreted by others to serve communicative functions. RESULTS: Potential communicative acts categorized as body movement displayed the highest median rank for reported occurrence followed by vocalization and facial expression. Although symbolic forms were ranked lower, more than half of the parents (66%) reported that their children produced at least one word, gesture or AAC form. Challenging behaviors or stereotypic movement displayed lowest median ranks. CONCLUSIONS: Results are discussed in terms of communication potential and the need to address AAC in trisomy 18 and 13.

Combined immunodeficiency in a 3-year-old boy with 16p11.2 and 20p12.2-11.2 chromosomal duplications.

We report for the first time on a 3-year-old boy with paternally inherited 212.85 kb-16p11.2 and 7.8 Mb-20p12.2-11.23 interstitial microduplications associated with having congenital cardiac defect, dysmorphic facial features, and combined T-, B-, and NK cell immunodeficiency. In addition the 7.8 Mb-20p12.2-11.23 microduplication is unique showing novel breakpoints among all partial trisomy/duplication 20p reported to date, narrowing down the critical region for trisomy 20p syndrome.

Tracking clinical genetic services for newborns identified through newborn dried bloodspot screening in the United States-lessons learned.

To determine how US newborn dried bloodspot screening (NDBS) programs obtain patient-level data on clinical genetic counseling services offered to families of newborns identified through newborn NDBS and the extent to which newborns and their families receive these services. These data should serve to inform programs and lead to improved NDBS follow-up services. Collaborations were established with three state NDBS programs that reported systematically tracking genetic counseling services to newborns and their families identified through NDBS. A study protocol and data abstraction form were developed and IRB approvals obtained. Data from three state NDBS programs on a total of 151 patients indicated that genetic services are documented systematically only by metabolic clinics, most often by genetic counselors. Data from 69 endocrinology patients indicated infrequent referrals for genetic services; as expected higher for congenital adrenal hyperplasia than congenital hypothyroidism. Endocrinology patients were often counseled by physicians. While systematic tracking of genetic counseling services may be desirable for quality assurance of NDBS follow-up services, current systems do not appear conducive to this practice. Clinical records are not typically shared with NDBS programs and tracking of follow-up clinical genetic services has not been generally defined as a NDBS program responsibility. Rather, tracking of clinical services, while recognized as useful data, has been viewed by NDBS programs as a research project. The associated IRB requirements for patient-related research may pose an additional challenge. National guidance for NDBS programs that define quality genetic service indicators and monitoring responsibilities are needed. US experiences in this regard may provide information that can assist developing programs in avoiding tracking issues.

Relational and social-cognitive correlates of early adolescents' forgiveness of parents.

This study examined how mother and father-child relationship quality and marital forgiveness were related to early adolescents' forgiveness of mothers and fathers. Adolescents' social-cognitive skills (empathy and emotional regulation) and parents' forgiveness of child were examined as mediators. Mother, father, and child self-reported questionnaires and observational data were taken from Time 1 and Time 3 (two years later) of the Flourishing Families Project, and included 334 two-parent families with an early adolescent (M age at Time 1 = 11.24; 51% male; 76% Caucasian). Using path analyses via structure equation modeling, mother-child relationship quality and adolescents' own social-cognitive skills were salient correlates of adolescents' forgiveness toward parents. The unique contributions of mothers and fathers, differences by reporter, and the importance of studying forgiveness within the parent-child relationship are discussed.

Parenting in emerging adulthood: an examination of parenting clusters and correlates.

The changing nature of the transition to adulthood in western societies, such as the United States, may be extending the length of time parents are engaged in "parenting" activities. However, little is known about different approaches parents take in their interactions with their emerging-adult children. Hence, this study attempted to identify different clusters of parents based on the extent to which they exhibited both extremes of control (psychological control, punishment, verbal hostility, indulgence) and responsiveness (knowledge, warmth, induction, autonomy granting), and to examine how combinations of parenting were related to emerging adult children's relational and individual outcomes (e.g. parent-child relationship quality, drinking, self-worth, depression). The data were collected from 403 emerging adults (M age = 19.89, SD = 1.78, range = 18-26, 62% female) and at least one of their parents (287 fathers and 317 mothers). Eighty-four percent of participants reported being European American, 6% Asian American, 4% African American, 3% Latino, and 4% reported being of other ethnicities. Data were analyzed using hierarchical cluster analysis, separately for mothers and fathers, and identified three similar clusters of parents which we labeled as uninvolved (low on all aspects of parenting), controlling-indulgent (high on both extremes of control and low on all aspects of responsiveness), and authoritative (high on responsiveness and low on control). A fourth cluster was identified for both mothers and fathers and was labeled as inconsistent for mothers (mothers were above the mean on both extremes of control and on responsiveness) and average for fathers (fathers were at the mean on all eight aspects of parenting). The discussion focuses on how each of these clusters effectively distinguished between child outcomes.