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Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

The present study explored preschoolers' internal state language and resolution strategies in sad stories that shifted to a positive emotional tone. Fifty-four 3-, 4-, and 5-year-olds attending a laboratory preschool shared stories about 'a time when you were happy/sad.' Stories were audio-recorded, transcribed, and coded for internal state language, emotional tone shift, and resolutions. Consistent with past work, children reported more internal states in sad (v. happy) stories. Children who shifted their sad stories to a positive emotional tone compared to those whose stories remained sad included more emotion talk and cognitive states, and used a variety of resolution strategies. Descriptive analysis suggested that the distribution of strategies differed by age of the child, with 5-year-olds utilising more strategies, and strategies more cognitively complex compared to younger children. Findings provide new insight into the ways preschoolers make meaning out of and resolve sad experiences through personal narratives.

Anterior segment dysgeneses (ASDs) comprise a spectrum of developmental disorders affecting the anterior segment of the eye. Here, we describe three unrelated families affected by a previously unclassified form of ASD. Shared ocular manifestations include bilateral iris hypoplasia, ectopia lentis, corectopia, ectropion uveae, and cataracts. Whole-exome sequencing and targeted Sanger sequencing identified mutations in CPAMD8 (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 8) as the cause of recessive ASD in all three families. A homozygous missense mutation in the evolutionarily conserved alpha-2-macroglobulin (A2M) domain of CPAMD8, c.4351T>C (p. Ser1451Pro), was identified in family 1. In family 2, compound heterozygous frameshift, c.2352_2353insC (p.Arg785Glnfs∗23), and splice-site, c.4549-1G>A, mutations were identified. Two affected siblings in the third family were compound heterozygous for splice-site mutations c.700+1G>T and c.4002+1G>A. CPAMD8 splice-site mutations caused aberrant pre-mRNA splicing in vivo or in vitro. Intriguingly, our phylogenetic analysis revealed rodent lineage-specific CPAMD8 deletion, precluding a developmental expression study in mice. We therefore investigated the spatiotemporal expression of CPAMD8 in the developing human eye. RT-PCR and in situ hybridization revealed CPAMD8 expression in the lens, iris, cornea, and retina early in development, including strong expression in the distal tips of the retinal neuroepithelium that form the iris and ciliary body, thus correlating CPAMD8 expression with the affected tissues. Our study delineates a unique form of recessive ASD and defines a role for CPAMD8, a protein of unknown function, in anterior segment development, implying another pathway for the pathogenicity of ASD.

Raising young children has always been hard, but evidence suggests that it may be getting harder. The isolation of the pandemic, the pressures to fulfill exacting parenting standards, and the explosion of "expert" parenting advice on social media have fueled the rise of "gentle parenting," an approach that pivots away from older, discipline-heavy parenting typologies and which promises the development of happier, healthier children. Despite the popularity of gentle parenting, it has received no empirical scrutiny. The current study represents the first systematic investigation of what gentle parenting entails. Data were gathered from a sample (N = 100) of parents of at least one child between the ages of 2 and 7 from the Midwest, Southeast, and Southwest. Approximately half (n = 49) of the sample identified as "gentle parents." Inductive analyses identified this approach as one that emphasizes high levels of parental affection and parents' and children's emotion regulation. Gentle parenting appears to be distinct from other established measures of parenting approaches in its emphasis on boundaries, yet the enactment of those boundaries is not uniform. Overall, gentle parents reported high levels of parenting satisfaction and efficacy, but a subset of gentle parents who were highly critical of themselves reported significantly lower levels of efficacy than the rest of the sample. Statements of parenting uncertainty and burnout were present in over one-third of the gentle parent sample. Implications are discussed for future research and increased support for those who identify as gentle parents. [ABSTRACT FROM AUTHOR]

PurposeTo characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical trials of gene therapy.DesignCross-sectional study.ParticipantsForty subjects with ACHM.MethodsAll subjects underwent spectral domain optical coherence tomography (SD-OCT), microperimetry, and molecular genetic testing. Foveal structure on SD-OCT was graded into 5 distinct categories: (1) continuous inner segment ellipsoid (ISe), (2) ISe disruption, (3) ISe absence, (4) presence of a hyporeflective zone (HRZ), and (5) outer retinal atrophy including retinal pigment epithelial loss. Foveal and outer nuclear layer (ONL) thickness was measured and presence of hypoplasia determined.Main outcome measuresPhotoreceptor appearance on SD-OCT imaging, foveal and ONL thickness, presence of foveal hypoplasia, retinal sensitivity and fixation stability, and association of these parameters with age and genotype.ResultsForty subjects with a mean age of 24.9 years (range, 6-52 years) were included. Disease-causing variants were found in CNGA3 (n = 18), CNGB3 (n = 15), GNAT2 (n = 4), and PDE6C (n = 1). No variants were found in 2 individuals. In all, 22.5% of subjects had a continuous ISe layer at the fovea, 27.5% had ISe disruption, 20% had an absent ISe layer, 22.5% had an HRZ, and 7.5% had outer retinal atrophy. No significant differences in age (P = 0.77), mean retinal sensitivity (P = 0.21), or fixation stability (P = 0.34) across the 5 SD-OCT categories were evident. No correlation was found between age and foveal thickness (P = 0.84) or between age and foveal ONL thickness (P = 0.12).ConclusionsThe lack of a clear association of disruption of retinal structure or function in ACHM with age suggests that the window of opportunity for intervention by gene therapy is wider in some individuals than previously indicated. Therefore, the potential benefit for a given subject is likely to be better predicted by specific measurement of photoreceptor structure rather than simply by age. The ability to directly assess cone photoreceptor preservation with SD-OCT and/or adaptive optics imaging is likely to prove invaluable in selecting subjects for future trials and measuring the trials' impact.

The present study explored developmental differences in preschoolers' use of reported speech and internal state language in personal narratives. Three-, four-, and five-year-olds attending a laboratory preschool shared 204 stories about 'a time when you were happy/sad'. Stories were audio-recorded, transcribed, and coded for reported speech (direct, indirect, narrativized) and internal state language (cognitive states, total emotion terms, unique emotion terms). Personal narratives told by five-year-olds included more cognitive states and more narrativized speech than those told by three- and four-year-olds, even when accounting for children's vocabulary skills, and that reported speech (narrativized, direct) were positively correlated with cognitive state talk. These findings highlight distinct shifts in children's use of cognitive state talk and reported speech in personal narratives told at age five. Associations between reported speech and internal state language are both informed by and support Vygotsky's (1978) fundamental claim that psychological processes are socially mediated by language. [ABSTRACT FROM AUTHOR]

This study was undertaken to investigate the prevalence of sequence variants in LCA5 in patients with Leber congenital amaurosis (LCA), early-onset retinal dystrophy (EORD), and autosomal recessive retinitis pigmentosa (arRP); to delineate the ocular phenotypes; and to provide an overview of all published LCA5 variants in an online database. Patients underwent standard ophthalmic evaluations after providing informed consent. In selected patients, optical coherence tomography (OCT) and fundus autofluorescence imaging were possible. DNA samples from 797 unrelated patients with LCA and 211 with the various types of retinitis pigmentosa (RP) were screened by Sanger sequence analysis of all LCA5 exons and intron/exon junctions. Some LCA patients were prescreened by APEX technology or selected based on homozygosity mapping. In silico analyses were performed to assess the pathogenicity of the variants. Segregation analysis was performed where possible. Published and novel LCA5 variants were collected, amended for their correct nomenclature, and listed in a Leiden Open Variation Database (LOVD). Sequence analysis identified 18 new probands with 19 different LCA5 variants. Seventeen of the 19 LCA5 variants were novel. Except for two missense variants and one splice site variant, all variants were protein-truncating mutations. Most patients expressed a severe phenotype, typical of LCA. However, some LCA subjects had better vision and intact inner segment/outer segment (IS/OS) junctions on OCT imaging. In two families with LCA5 variants, the phenotype was more compatible with EORD with affected individuals displaying preserved islands of retinal pigment epithelium. One of the families with a milder phenotype harbored a homozygous splice site mutation; a second family was found to have a combination of a stop mutation and a missense mutation. This is the largest LCA5 study to date. We sequenced 1,008 patients (797 with LCA, 211 with arRP) and identified 18 probands with LCA5 mutations. Mutations in LCA5 are a rare cause of childhood retinal dystrophy accounting for ∼2% of disease in this cohort, and the majority of LCA5 mutations are likely null. The LCA5 protein truncating mutations are predominantly associated with LCA. However, in two families with the milder EORD, the LCA5 gene analysis revealed a homozygous splice site mutation in one and a stop mutation in combination with a missense mutation in a second family, suggesting that this milder phenotype is due to residual function of lebercilin and expanding the currently known phenotypic spectrum to include the milder early onset RP. Some patients have remaining foveal cone structures (intact IS/OS junctions on OCT imaging) and remaining visual acuities, which may bode well for upcoming treatment trials.

Writing assessments have attended to the mechanics of writing, reflecting a value on the teaching of writing conventions. One quality of writing rarely assessed is authorial voice, a personal style that communicates the author's stance toward events reported and the author's relationship to the audience. The authors explore associations among authorial voice, writing mechanics, and academic performance. In the fall and spring of 1 academic year, 115 third- through fifth-grade students wrote personal narratives that were coded for 2 measures of mechanics and 4 measures of authorial voice. Students and teachers completed measures of academic performance. Mechanics, but not voice, predicted academic performance. The authors suggest that mechanics-focused state standards discourage authorial voice, and they propose attention to voice as a springboard to develop other writing skills.

This study examined patterns of mothers' and fathers' acceptance and youths' friendship intimacy among 246 Mexican-origin 7th graders. Three patterns were identified using mixture modeling: (a) low mother and father acceptance, and average friendship intimacy (Low Parent Profile); (b) average mother acceptance, high father acceptance and friendship intimacy (Positive Profile); and (c) high mother acceptance, average father acceptance, and low friendship intimacy (Low Friend Profile). Profiles differed with respect to cultural characteristics and youth adjustment. Findings demonstrated the benefit of a person-oriented approach to illuminate how parental and peer experiences are connected in different ways for different youth and are linked with youth adjustment. Results highlighted the need for research to attend to the unique cultural experiences of minority youth. (Contains 4 tables.)

The primary aims of the present longitudinal study were to examine (a) patterns of early transition relatedness with teachers and peers in 6th grade, (b) whether pre-transition behavior in 5th grade predicted early transition relatedness in 6th grade, and (c) how unique indicators of early transition relatedness with teachers and peers and patterns of early transition relatedness were associated with school adjustment among 383 rural, lower- to middle-class, White youth. Results suggest that behavioral characteristics in elementary school may contribute to early transition patterns of relatedness with teachers and peers in middle school. Findings also indicate that having a pattern of poor relationships with the primary social partners in the school context is negatively associated with adjustment above and beyond the independent indicators of relatedness. Implications for school practice are discussed. (Contains 5 tables and 1 figure.)

Cross-age peer mentoring programs, in which teenagers mentor younger children, have proliferated in recent years, yet there is disagreement about the effectiveness of such programs. This study tested whether teen mentors' attitudes about children interact with their mentees' characteristics to moderate outcomes of cross-age peer mentoring. The sample included 221 high school volunteers, 205 mentees, and 182 control group youth. Latent profile analyses yielded two profiles of students who were labeled "academically connected" or "disconnected." Analyses revealed that the academically disconnected mentees who were paired with mentors holding relatively positive attitudes toward youth were more emotionally engaged in the mentoring relationship (than disconnected mentees with more negative mentors) and, subsequently, reported stronger relationships with their teachers at year's end (than did the similarly disconnected children in the control group). Conversely, there was evidence of iatrogenic effects of matching negative mentors with academically connected mentees. Implications for mentor selection and training are discussed. (Contains 4 tables and 3 figures.)