Latent profiles as predictors of response to instruction for students with reading difficulties.

The program code developed by others is appropriately cited in the text and listed in the references section. The raw and processed data on which study conclusions are based are not available. The statistical syntax needed to reproduce analyses in the article is available upon request. The methods section provides references for the materials described therein. We report how we determined our sample size, all data exclusions, all manipulations, and all measures in the study, and we follow APA Style Journal Article Reporting Standards. This study's design, hypotheses, and data analytic plan were not pre-registered. Prior research supports the need for elementary-aged students with reading difficulties (RD) to receive explicit systematic small group evidence-based reading instruction. Yet for many students, simply receiving an evidence-based reading instruction in a small group setting is insufficient to reach the progress milestones needed to meet grade level reading standards. The current study examined whether: (1) elementary school students with RD constitute a homogeneous or heterogeneous groups when considering their basic language and cognitive skills (using a latent profile analysis), and (2) if latent profiles are predictive of response to reading comprehension instruction (using a mixed modeling approach). The sample consisted of 335 students, including students with RD and typical students (n = 57). The results revealed heterogeneity within students with RD - there were two distinct profiles, with one having higher basic language (reading fluency and decoding) and cognitive (verbal domain productivity, cognitive flexibility, working memory) skills and lower attention skills, and the other having stronger attention skills and lower basic language and cognitive skills. The findings also suggested that latent profiles were predictive of response to reading comprehension instruction. Our results provide a convincing argument for leading the field in the direction of developing customized interventions. It is conceivable, but remains to be further examined, that researchers and educators could potentially improve reading outcomes through providing a customized reading intervention to a student based on their cognitive-language profile.

The crystal structures of the low-temperature and high-pressure polymorphs of nitric acid.

A new high-pressure phase of pure nitric acid (HNO(3)) has been characterised at 1.6 GPa at room temperature by high-pressure neutron powder and X-ray single-crystal diffraction techniques. This is the first crystalline phase obtained upon compression of liquid nitric acid at room temperature and appears to be the stable phase up to pressures of at least 4 GPa. The crystal structure of this new phase shows some similarities to that of the low-temperature phase of nitric acid at ambient pressure, which has been redetermined as part of this study. Both structures share a herringbone packing of hydrogen-bonded molecular catemers, although the presence of disorder within the hydrogen bonds within one of the catemers of the low-temperature phase makes its structure comparatively more complex.

Comparison of the effects of caudal pole hemi-meniscectomy and complete medial meniscectomy in the canine stifle joint.

OBJECTIVE: To compare the effects of caudal pole hemi-meniscectomy (CPHM) and complete medial meniscectomy (MM), specifically with respect to development of secondary osteoarthritis, in the stifle joints of clinically normal dogs. ANIMALS: 14 large-breed dogs. PROCEDURE: Unilateral CPHM (7 dogs) or MM (7) was performed, and the left stifle joints served as untreated control joints. Gait was assessed in all dogs before surgery and at 4, 8, 12, and 16 weeks postoperatively. After euthanasia, joints were evaluated grossly; Mankin cartilage scores, subchondral bone density assessment, and articular cartilage proteoglycan extraction and western blot analyses of 3B3(-) and 7D4 epitopes were performed. RESULTS: Weight distribution on control limbs exceeded that of treated limbs at 4 and 16 weeks after surgery in the CPHM group and at 4 and 8 weeks after surgery in the MM group; weight distribution was not significantly different between the 2 groups. After 16 weeks, incomplete meniscal regeneration and cartilage fibrillation on the medial aspect of the tibial plateau and medial femoral condyle were detected in treated joints in both groups. Mankin cartilage scores, subchondral bone density, and immunoexpression of 3B3(-) or 7D4 in articular cartilage in CPHM- or MM-treated joints were similar; 7D4 epitope concentration in synovial fluid was significantly greater in the MM-treated joints than in CPHM-treated joints. CONCLUSIONS AND CLINICAL RELEVANCE: Overall severity of secondary osteoarthritis induced by CPHM and MM was similar. Investigation of 7D4 epitope concentration in synovial fluid suggested that CPHM was associated with less disruption of chondrocyte metabolism.

Erk2 signaling and early embryo stem cell self-renewal.

Differentiation of the mammalian blastocyst generates two distinct cell lineages: the trophectoderm, which contributes to the trophoblast layers of the placenta, and the inner cell mass, which forms the embryo. We and others recently demonstrated that the MAP kinase ERK2 is essential for trophoblast development. Erk2 mutant embryos fail to form extra-embryonic ectoderm and the ectoplacental cone, suggesting a role for ERK2 activation in the proliferation of trophoblast stem (TS) cells. Previous studies have documented that ERK1/2 activity is dispensable for proliferation of embryonic stem (ES) cells and rather interferes with self-renewal. Thus, signaling by the ERK1/2 MAP kinase pathway appears to be critical for the regulation of self-renewal and propagation of early embryo stem cell populations.

An essential function of the mitogen-activated protein kinase Erk2 in mouse trophoblast development.

The closely related mitogen-activated protein kinase isoforms extracellular signal-regulated kinase 1 (ERK1) and ERK2 have been implicated in the control of cell proliferation, differentiation and survival. However, the specific in vivo functions of the two ERK isoforms remain to be analysed. Here, we show that disruption of the Erk2 locus leads to embryonic lethality early in mouse development after the implantation stage. Erk2 mutant embryos fail to form the ectoplacental cone and extra-embryonic ectoderm, which give rise to mature trophoblast derivatives in the fetus. Analysis of chimeric embryos showed that Erk2 functions in a cell-autonomous manner during the development of extra-embryonic cell lineages. We also found that both Erk2 and Erk1 are widely expressed throughout early-stage embryos. The inability of Erk1 to compensate for Erk2 function suggests a specific function for Erk2 in normal trophoblast development in the mouse, probably in regulating the proliferation of polar trophectoderm cells.

Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks.

The anterior visceral endoderm plays a pivotal role in establishing anterior-posterior polarity of the mouse embryo, but the molecular nature of the signals required remains to be determined. Here, we demonstrate that Cerberus-like(-/-);Lefty1(-/-) compound mutants can develop a primitive streak ectopically in the embryo. This defect is not rescued in chimeras containing wild-type embryonic, and Cerberus-like(-/-);Lefty1(-/-) extraembryonic, cells but is rescued in Cerberus-like(-/-); Lefty1(-/-) embryos after removal of one copy of the Nodal gene. Our findings provide support for a model whereby Cerberus-like and Lefty1 in the anterior visceral endoderm restrict primitive streak formation to the posterior end of mouse embryos by antagonizing Nodal signaling. Both antagonists are also required for proper patterning of the primitive streak.

Mapping of receptive language cortex in bilingual volunteers by using magnetic source imaging.

OBJECT: There are conflicting claims in the functional imaging literature concerning whether different languages are represented by distinct brain mechanisms in individuals who are proficient in more than one language. This interesting theoretical issue has practical implications when functional imaging methods are used for presurgical language mapping. To address this issue the authors compared the location and extent of receptive language cortex specific to English and Spanish in neurologically intact bilingual volunteers by using magnetic source imaging. METHODS: Areas of the cortex that were specialized for receptive language functions were identified separately for each language in 11 healthy adults who were bilingual in English and Spanish. The authors performed exactly the same procedures used routinely for presurgical receptive language mapping. In each bilingual individual, the receptive language-specific map always encompassed the posterior portion of the superior temporal gyrus. In every case, however, substantial differences in the receptive language maps were also observed for the two languages, regardless of whether each participant's first language was English or Spanish. CONCLUSIONS: Although the reasons for such differences and their ultimate significance in identifying the cerebral mechanisms of language are subject to continuing investigation, their presence is noteworthy and has practical implications for the surgical management of patients with lesions in the temporal and parietal regions of the dominant hemisphere.

Measures of information processing in rapid automatized naming (RAN) and their relation to reading.

The letters, numbers, and objects subtests of the Rapid Automatized Naming Tests (RAN) were given to 50 first- and second-grade students. Student performance on the three RAN subtests were audiotaped and subjected to postacquisition processing to distinguish articulation and interarticulation pause times. This study investigated (1) the relations between the articulation and pause durations associated with the 50 stimuli of each RAN subtest and (2) the relations between the pause and articulation latencies of the three RAN subtests and reading. For both first- and second-grade students, pause and articulation times for RAN letters and objects were not found to be reliably related, in contrast to RAN numbers articulation and pause durations. RAN subtest pause durations were differentially related to reading; however, articulation was rarely related to reading. The RAN letters pause time was the most robust predictor of decoding and reading comprehension, consistently predicting all first- and second-grade measures. Analysis supported the view that reading is predicted by speed of processing associated with letters, not general processing speed.

Prenatal cocaine exposure and prematurity: neurodevelopmental growth.

The consequences of prematurity and prenatal cocaine exposure on early neurobehavior and physical growth were examined longitudinally in a sample of 20 cocaine-exposed and 20 non-exposed preterm neonates. The magnitude of the difference in physical growth acceleration related to prenatal cocaine exposure increased with increasing birth gestational age, whereas growth rate differences in irritability decreased. In contrast, prenatal cocaine exposure, independent of prematurity, was related to reduced attention skills at 36 weeks conceptional age and increased rates of neurobehavioral change. The effects of prenatal cocaine exposure differed with respect to the degree of prematurity, depending on the nature of the outcome examined, suggesting differing windows of vulnerability for different outcome domains. The usefulness of a developmental growth perspective was demonstrated.

Persistence of dyslexia: the Connecticut Longitudinal Study at adolescence.

OBJECTIVE: The outcome in adolescence of children diagnosed as dyslexic during the early years of school was examined in children prospectively identified in childhood and continuously followed to young adulthood. This sample offers a unique opportunity to investigate a prospectively identified sample of adolescents for whom there is no question of the childhood diagnosis and in whom highly analytic measures of reading and language can be administered in adolescence. DESIGN: Children were recruited from the Connecticut Longitudinal Study, a cohort of 445 children representative of those children entering public kindergarten in Connecticut in 1983. Two groups were selected when the children were in grade 9: children who met criteria for persistent reading disability in grades 2 through 6 (persistently poor readers [PPR]; n = 21) and a comparison group of nondisabled children, subdivided into average readers (n = 35) and superior readers (n = 39). In grade 9, each child received a comprehensive assessment of academic, language, and other cognitive skills. RESULTS: Measures of phonological awareness (but not orthographic awareness) were most significant in differentiating the 3 reading groups, with smaller contributions from measures of word finding and digit-span. Academic measures that best separated good from poor readers were decoding and spelling, whereas measures of math and reading comprehension did not. Measures of phonological awareness, followed next by teacher rating of academic skills were the best predictors of decoding, reading rate, and reading accuracy. In contrast, the best predictor of reading comprehension was word finding, with digit span and socioeconomic status also contributing significantly. Using a growth curve model (quadratic model of growth to a plateau) all 3 groups demonstrated similar patterns of growth over time, with the superior group outperforming the average group, and the average group outperforming the PPR group. There was no evidence that the children in the PPR group catch up in their reading skills. CONCLUSIONS: Deficits in phonological coding continue to characterize dyslexic readers even in adolescence; performance on phonological processing measures contributes most to discriminating dyslexic and average readers, and average and superior readers as well. These data support and extend the findings of previous investigators indicating the continuing contribution of phonological processing to decoding words, reading rate, and accuracy and spelling. Children with dyslexia neither spontaneously remit nor do they demonstrate a lag mechanism for catching up in the development of reading skills. In adolescents, the rate of reading as well as facility with spelling may be most useful clinically in differentiating average from poor readers.

Identification of sulfated oligosaccharide-based inhibitors of tumor growth and metastasis using novel in vitro assays for angiogenesis and heparanase activity.

Inhibitors of tumor angiogenesis and metastasis are rapidly emerging as important new drug candidates for cancer therapy. To facilitate the identification of such drugs, we recently developed novel and rapid in vitro assays for human angiogenesis and for the extracellular matrix-degrading enzyme heparanase, which has been implicated in tumor metastasis. In this study, sulfated oligosaccharides, which are structural mimics of heparan sulfate, were investigated as drug candidates because these compounds may interfere with heparan sulfate recognition by many angiogenic growth factors and may inhibit cleavage of heparan sulfate by heparanase. In the preliminary screening studies, it was found that inhibitory activity in both assay systems was critically dependent on chain length and degree of sulfation, highly sulfated linear oligosaccharides of five or more monosaccharides in length being the most active. However, two sulfated oligosaccharides stood out as potential antitumor drugs, phosphomannopentaose sulfate (PI-88) and maltohexaose sulfate, both of these compounds having the important property of simultaneously being potent inhibitors of in vitro angiogenesis and heparanase activity. Due to the ease of manufacture of the starting material, phosphomannopentaose, PI-88 was studied in more detail. PI-88 was shown to inhibit the primary tumor growth of the highly invasive rat mammary adenocarcinoma 13762 MAT by approximately 50%, inhibit metastasis to the draining popliteal lymph node by approximately 40%, and reduce the vascularity of tumors by approximately 30%, all of these effects being highly significant. Acute hematogenous metastasis assays also demonstrated that PI-88 was a potent (>90%) inhibitor of blood-borne metastasis. Thus, by the use of novel in vitro screening procedures, we have identified a promising antitumor agent.

Memory functions in children with early hydrocephalus.

Children with arrested, shunted, and no hydrocephalus were compared on verbal and nonverbal memory tasks assessing multiple components of memory. A gradient of severity was hypothesized, with the shunted hydrocephalus group expected to exhibit the most significant memory impairments and the arrested group expected to perform more poorly than children with no hydrocephalus. Etiologies of prematurity, spina bifida, and aqueductal stenosis were represented by 157 participants. Results supported the hypothesis; the shunted hydrocephalus group performed poorer on all memory measures. Differences for the arrested group were less frequently statistically significant relative to children with no hydrocephalus. Irrespective of etiology, the shunted hydrocephalus group exhibited a pattern of performance suggestive of encoding and retrieval deficits on both verbal and nonverbal tasks, showing a pervasive disturbance of memory processes.

The foundations of literacy: learning the sounds of letters.

Learning the sounds of letters is an important part of learning to read and spell. To explore the factors that make some letter-sound correspondences easier for children to learn than others, we first analyzed knowledge of letters' sounds (and names) by 660 children between 3 1/2 and 7 1/2 years old. A second study examined pre-schoolers' (M age 4 years, 11 months) ability to learn various sound-letter mappings. Together, the results show that an important determinant of letter-sound knowledge is whether the sound occurs in the name of the letter and, if so, whether it is at the beginning or the end. The properties of the sound itself (consonant versus vowel, sonorant versus obstruent, stop versus continuant) appear to have little or no influence on children's learning of basic letter-sound correspondences. The findings show that children use their knowledge of letters' names when learning the letters' sounds rather than memorizing letter-sound correspondences as arbitrary pairings.

Effects of intraventricular hemorrhage and hydrocephalus on the long-term neurobehavioral development of preterm very-low-birthweight infants.

Measures of intelligence, neuropsychological functions, academic skills, and behavioral adjustment were obtained at school-age from children born preterm with no hydrocephalus (N=29), arrested hydrocephalus (N=19), and shunted hydrocephalus (N=17), and a term comparison group (N=23). Most children also received concurrent neurological examinations and MRI brain scans. Results revealed significantly poorer neurobehavioral development in all four domains in preterm children with shunted hydrocephalus. Despite abnormal MRI findings in virtually all children with arrested hydrocephalus, significant differences between preterm children with arrested hydrocephalus and those with no hydrocephalus were largely in areas involving attentional and academic skills. Preterm children with no hydrocephalus tended to show poorer motor development relative to term children. Neurological abnormalities were restricted to children with spasticity in the arrested (N=2) and shunted (N=10) groups. These results highlight the importance of separating cases according to residual neurological and neuroimaging abnormalities in accounting for variations in the neurobehavioral development of preterm, low-birth-weight infants.

Psychometric properties of family members' reports of parental physical aggression toward clinic-referred children.

This study examined (a) differences among mothers', fathers', and children's reports of parental physical aggression toward children; (b) the reliability and validity of family members' reports of aggression using confirmatory factor analysis; and (c) the discriminant validity of the constructs of mother-child and father-child aggression. Participants were 72 dual-parent families in which the parents were seeking clinical services for their children's (ages 7-9 years) conduct behavior problems. Each participant completed the parent-child version of the Conflict Tactics Scale (P-CTS). Results indicate that children reported lower levels of mother-child and father-child aggression than either mothers or fathers reported. Although the reliability (total systematic variance accounted for by observed variables) of family members' reports on the P-CTS ranged from moderate to high, convergent validity was generally low. The constructs of mother-child and father-child aggression were highly correlated but could be distinguished from each other when relationships among rater effects were considered.

Longitudinal neuropsychological outcome in infants and preschoolers with traumatic brain injury.

Neuropsychological outcome was evaluated in a prospective, longitudinal follow-up study of children age 4 months to 7 years at injury with either mild-to-moderate (N = 35) or severe (N = 44) traumatic brain injury (TBI). Age-appropriate tests were administered at baseline, 6 months, 12 months, and 24 months after the injury. Performance was compared on (1) Composite IQ and motor, (2) Receptive and expressive language, and (3) Verbal and Perceptual-Performance IQ scores. In comparison to mild-to-moderate TBI, severe TBI in infants and preschoolers produced deficits in all areas. Interactions between task and severity of injury were obtained. Motor scores were lower than IQ scores, particularly after severe TBI. Both receptive and expressive scores were reduced following severe TBI. Expressive language scores were lower than receptive language scores for children sustaining mild-to-moderate TBI. While severe TBI lowered both Verbal and Perceptual-Performance IQ scores, Verbal IQ scores were significantly lower than Perceptual-Performance IQ scores after mild-to-moderate TBI. Mild injuries may produce subtle linguistic changes adversely impacting estimates of Verbal IQ and expressive language. Within the limited age range evaluated within this study, age at injury was unrelated to test scores: The impact of TBI was comparable in children ages 4 to 41 months versus 42 to 72 months at the time of injury. All neuropsychological scores improved significantly from baseline to the 6-month follow-up. However, no further change in scores was observed from 6 to 24 months after the injury. The persistent deficits and lack of catch-up over time suggest a reduction in the rate of acquisition of new skills after severe TBI. Methodological issues in longitudinal studies of young children were discussed.

Cognitive correlates of long-term cannabis use in Costa Rican men.

BACKGROUND: Cognitive correlates of long-term cannabis use have been elusive. We tested the hypothesis that long-term cannabis use is associated with deficits in short term memory, working memory, and attention in a literate, westernized culture (Costa Rica) in which the effects of cannabis use can be isolated. METHODS: Two cohorts of long-term cannabis users and nonusers were studied. Within each cohort, users and nonusers were comparable in age and socioeconomic status. Polydrug users and users who tested positive for the use of cannabis at the time of cognitive assessment after a 72-hour abstention period were excluded. The older cohort (whose age was approximately 45 years) had consumed cannabis for an average of 34 years, and comprised 17 users and 30 nonusers, who had been recruited in San José, Costa Rica, and had been observed since 1973. The younger cohort (whose age was approximately 28 years) had consumed cannabis for an average of 8 years, and comprised 37 users and 49 nonusers. Short-term memory, working memory, and attentional skills were measured in each subject. RESULTS: Older long-term users performed worse than older nonusers on 2 short-term memory tests involving learning lists of words. In addition, older long-term users performed worse than older nonusers on selective and divided attention tasks associated with working memory. No notable differences were apparent between younger users and nonusers. CONCLUSION: Long-term cannabis use was associated with disruption of short-term memory, working memory, and attentional skills in older long-term cannabis users.

Correlation of medical and neurosurgical events with neuropsychological status in children at diagnosis of astrocytoma: utilization of a neurological severity score.

Neuropsychological studies of children who have brain tumors have yielded diverse results with respect to identifying factors that contribute to poor intellectual outcome. The purpose of this study was to evaluate the relationship between pre- and perioperative events, tumor-related factors, and the neuropsychological status of children diagnosed with astrocytoma. Events that could potentially be detrimental to neuropsychological outcome were quantified utilizing a new "neurological severity score." The Neurological Severity Score was developed as a research tool to test our hypothesis that ultimate intellectual outcome is a result of cumulative, interactive insults on the central nervous system. This study constitutes a first step in examining the predictive value of the Neurological Severity Score by evaluating its correlation with baseline neuropsychological status. Fifty-nine children who had astrocytoma (36 supratentorial and 23 infratentorial) received complete neurological and neuropsychological evaluations within 3 months of diagnosis. Each child's neurological history and examination results were scored by an independent observer using the Neurological Severity Score. Neuroimages obtained at diagnosis and at the time of neuropsychological testing were evaluated as well. For the group as a whole, memory, attention, and motor abilities were significantly below age-appropriate norms, whereas intelligence, language, and academic skills were preserved. Patterns of deficits were identified and related to tumor site. There were no significant differences in mean neuropsychological domain scores between groups based on gender, pre-versus post-operative status, ethnicity, tumor grade, or abnormalities on magnetic resonance imaging (MRI). The Neurological Severity Score was significantly inversely correlated with visual-spatial skills, memory, attention, performance IQ, and global IQ. In conclusion, among all the medical and neurological factors present at diagnosis, the neurological severity score had the highest correlation with neuropsychological scores. This instrument has promise as a research tool in investigations of the psychological effects of cancer and its treatment on children.

Neuropsychologic effects of chemotherapy on children with cancer: a longitudinal study.

PURPOSE: A prospective study was conducted to assess the effects of chemotherapy for cancer on children's long-term neuropsychologic status. PATIENTS AND METHODS: Ninety-nine children who received no cranial radiation therapy (CRT) completed four annual neuropsychologic assessments. Fifty-one patients received intrathecal (IT) chemotherapy (ITC); 48 received no CNS treatment. These two groups were compared using repeated-measures analysis of variance on IQ, memory, language, freedom from distractibility, academic achievement, executive functions, and fine-motor, perceptual-motor, and tactile-spatial skills. In addition, 51 of the sample of 99 patients had been examined 5 to 11 years after diagnosis. Their data were analyzed to evaluate the longer-term effects of chemotherapy. The predictability of demographic and medical variables on neuropsychologic outcome at 3-year and long-term follow-up study were assessed using multiple regression techniques. RESULTS: Overall, the effects of chemotherapy in the absence of CRT appear to be slight. Patients who received ITC and intravenous (IV) methotrexate declined slightly on perceptual-motor skills, but were still well within the normal range. Both groups, regardless of treatment, declined on academic achievement tests, although not to a statistically significant degree. Age effects were found on performance IQ (PIQ) and perceptual-motor skills. Socioeconomic status (SES) correlated with a large number of variables. Sex effects were not significant. CONCLUSION: The present results are largely consistent with previous findings for nonirradiated groups. Treatment effects from ITC are slightly more apparent 5 to 11 years after diagnosis than at 3-year follow-up evaluation but this does not constitute a clinically meaningful difference. More noticeable are academic declines among all groups, regardless of treatment.

Regional brain tissue composition in children with hydrocephalus. Relationships with cognitive development.

OBJECTIVE: To determine whether children with shunted hydrocephalus show variations in regional brain tissue composition that relate to cognitive functions. DESIGN: Nonequivalent control group. PATIENTS AND METHODS: Magnetic resonance imaging (MRI) and cognitive skills assessments were obtained on 28 children, 6 to 9 years of age, with shunted hydrocephalus and 13 normal control subjects comparable in age, gender, ethnicity, and socioeconomic status. Three consecutive MRI slices below the vertex were segmented using a fuzzy clustering algorithm to separate pixels into gray matter, white matter, and cerebrospinal fluid (CSF) in quadrants representing left and right anterior and posterior brain regions. The cognitive skills assessments included the Wechsler Intelligence Scale for Children-Revised verbal and performance IQ scores, neuropsychological composites of language and visuospatial skills, a measure of visuomotor dexterity, and 2 measures of problem-solving abilities. The MRI data were analyzed in a group x tissue x hemisphere x region analysis of variance. Spearman rho correlations were computed within the hydrocephalus group between the MRI and cognitive measures. RESULTS: Children with hydrocephalus showed reductions in overall gray matter percentages and corresponding increased CSF percentages that were more pronounced in posterior than anterior regions of both hemispheres. White matter percentages were reduced in children with hydrocephalus only in the left posterior quadrant. Correlations of posterior, but not anterior, CSF and gray matter percentages were significant with verbal and performance IQ scores and language, visuospatial, and visuomotor dexterity skills, but not with problem-solving abilities. Children with hydrocephalus who had proportionately greater posterior than anterior CSF percentages had significantly poorer visuomotor dexterity and visuospatial skills than did hydrocephalic children with proportionate CSF percentages. CONCLUSION: Regional variations in brain tissue composition in children with shunted hydrocephalus correlate with a variety of cognitive and visuomotor functions.