Associations of psychotic symptom dimensions with clinical and developmental variables in twin and general clinical samples.

BACKGROUND: Positive, negative and disorganised psychotic symptom dimensions are associated with clinical and developmental variables, but differing definitions complicate interpretation. Additionally, some variables have had little investigation. AIMS: To investigate associations of psychotic symptom dimensions with clinical and developmental variables, and familial aggregation of symptom dimensions, in multiple samples employing the same definitions. METHOD: We investigated associations between lifetime symptom dimensions and clinical and developmental variables in two twin and two general psychosis samples. Dimension symptom scores and most other variables were from the Operational Criteria Checklist. We used logistic regression in generalised linear mixed models for combined sample analysis (n = 875 probands). We also investigated correlations of dimensions within monozygotic (MZ) twin pairs concordant for psychosis (n = 96 pairs). RESULTS: Higher symptom scores on all three dimensions were associated with poor premorbid social adjustment, never marrying/cohabiting and earlier age at onset, and with a chronic course, most strongly for the negative dimension. The positive dimension was also associated with Black and minority ethnicity and lifetime cannabis use; the negative dimension with male gender; and the disorganised dimension with gradual onset, lower premorbid IQ and substantial within twin-pair correlation. In secondary analysis, disorganised symptoms in MZ twin probands were associated with lower premorbid IQ in their co-twins. CONCLUSIONS: These results confirm associations that dimensions share in common and strengthen the evidence for distinct associations of co-occurring positive symptoms with ethnic minority status, negative symptoms with male gender and disorganised symptoms with substantial familial influences, which may overlap with influences on premorbid IQ.

Internal Standard Triggered-Parallel Reaction Monitoring Mass Spectrometry Enables Multiplexed Quantification of Candidate Biomarkers in Plasma.

Despite advances in proteomic technologies, clinical translation of plasma biomarkers remains low, partly due to a major bottleneck between the discovery of candidate biomarkers and costly clinical validation studies. Due to a dearth of multiplexable assays, generally only a few candidate biomarkers are tested, and the validation success rate is accordingly low. Previously, mass spectrometry-based approaches have been used to fill this gap but feature poor quantitative performance and were generally limited to hundreds of proteins. Here, we demonstrate the capability of an internal standard triggered-parallel reaction monitoring (IS-PRM) assay to greatly expand the numbers of candidates that can be tested with improved quantitative performance. The assay couples immunodepletion and fractionation with IS-PRM and was developed and implemented in human plasma to quantify 5176 peptides representing 1314 breast cancer biomarker candidates. Characterization of the IS-PRM assay demonstrated the precision (median % CV of 7.7%), linearity (median R2 > 0.999 over 4 orders of magnitude), and sensitivity (median LLOQ < 1 fmol, approximately) to enable rank-ordering of candidate biomarkers for validation studies. Using three plasma pools from breast cancer patients and three control pools, 893 proteins were quantified, of which 162 candidate biomarkers were verified in at least one of the cancer pools and 22 were verified in all three cancer pools. The assay greatly expands capabilities for quantification of large numbers of proteins and is well suited for prioritization of viable candidate biomarkers.

Taxonomic Reclassification of the Fungal Pathogen Causing Dry Berry Disease of Caneberries into the Division Ascomycota as Monilinia rubi.

As molecular genetic techniques improve and sequence data becomes available for more fungal species, taxonomic classifications historically based upon growth morphology alone are being revisited and occasionally reclassified. Herein, we present such an instance for the fungal pathogen that causes dry berry disease of caneberries. The organism was previously described as the basidiomycete fungus Rhizoctonia rubi based upon the pathogen's production of Rhizoctonia-like angular branching hyphae. Utilizing molecular genetic techniques unavailable when the pathogen was first characterized in 1959, three housekeeping gene regions (ITS, ß-tubulin, and G3PDH) were sequenced across 13 contemporary dry berry isolates, as well as the original 1959 R. rubi type strain, CBS382.59. The resulting neighbor-joining, maximum likelihood, and Bayesian phylogenies for single and multilocus sequences provide strong evidence that the dry berry pathogen was misclassified. This data, in addition to revisiting in vivo macroscopic and microscopic growth morphology, again comparing contemporary dry berry isolates to the CBS382.59 type strain, suggests that the causal organism is a new species within the genus Monilinia that we propose be classified as Monilinia rubi. A transition from designation as a basidiomycete fungus to an ascomycete fungus could have implications on chemical management decisions, as well as the assumptions made about cell structure and the pathogen's putative life cycle.

The Helicobacter pylori cell shape promoting protein Csd5 interacts with the cell wall, MurF, and the bacterial cytoskeleton.

Chronic infection with Helicobacter pylori can lead to the development of gastric ulcers and stomach cancers. The helical cell shape of H. pylori promotes stomach colonization. Screens for loss of helical shape have identified several periplasmic peptidoglycan (PG) hydrolases and non-enzymatic putative scaffolding proteins, including Csd5. Both over and under expression of the PG hydrolases perturb helical shape, but the mechanism used to coordinate and localize their enzymatic activities is not known. Using immunoprecipitation and mass spectrometry we identified Csd5 interactions with cytosolic proteins CcmA, a bactofilin required for helical shape, and MurF, a PG precursor synthase, as well as the inner membrane spanning ATP synthase. A combination of Csd5 domain deletions, point mutations, and transmembrane domain chimeras revealed that the N-terminal transmembrane domain promotes MurF, CcmA, and ATP synthase interactions, while the C-terminal SH3 domain mediates PG binding. We conclude that Csd5 promotes helical shape as part of a membrane associated, multi-protein shape complex that includes interactions with the periplasmic cell wall, a PG precursor synthesis enzyme, the bacterial cytoskeleton, and ATP synthase.

Carbonyl reduction by YmfI in Bacillus subtilis prevents accumulation of an inhibitory EF-P modification state.

Translation elongation factor P (EF-P) in Bacillus subtilis is required for a form of surface migration called swarming motility. Furthermore, B. subtilis EF-P is post-translationally modified with a 5-aminopentanol group but the pathway necessary for the synthesis and ligation of the modification is unknown. Here we determine that the protein YmfI catalyzes the reduction of EF-P-5 aminopentanone to EF-P-5 aminopentanol. In the absence of YmfI, accumulation of 5-aminopentanonated EF-P is inhibitory to swarming motility. Suppressor mutations that enhanced swarming in the absence of YmfI were found at two positions on EF-P, including one that changed the conserved modification site (Lys 32) and abolished post-translational modification. Thus, while modification of EF-P is thought to be essential for EF-P activity, here we show that in some cases it can be dispensable. YmfI is the first protein identified in the pathway leading to EF-P modification in B. subtilis, and B. subtilis encodes the first EF-P ortholog that retains function in the absence of modification.

Genome-Assisted Development of a Diagnostic Protocol for Distinguishing High Virulence Pseudomonas syringae pv. tomato Strains.

A severe outbreak of bacterial speck of tomato, caused by Pseudomonas syringae pv. tomato, occurred in central New York in 2009. Isolate 09150, collected from this outbreak and subsequently named NYS-T1, was found to be highly virulent on tomato. To better understand the relationship of 09150 to other P. syringae strains and develop a diagnostic assay for aggressive strains of this pathogen, the 09150 genome was sequenced. Genome comparison revealed it to be highly similar to a previously sequenced isolate, T1. Genetic factors linked to host interaction including type III effectors, toxin biosynthetic genes, and elicitors of host innate immunity were identified. Type III effector repertoires were compared with other strains in the high virulence T1-like subgroup and lower virulence DC3000/P. syringae pv. maculicola subgroup within P. syringae phylogenetic Group I. Primers for conventional PCR were developed using sequences for avrA, hopW, conserved in the former subgroup and hopN, present in the latter. These were tested on isolates in the two subgroups, other pseudomonads, and other bacterial pathogens of tomato. Primers developed for avaA and hopW were diagnostic for more virulent strains of P. syringae pv. tomato while primers for hopN were diagnostic for P. syringae pv. tomato DC3000 and related P. syringe pv. maculicola strains. Primers designed against hopR distinguished both of these P. syringae subgroups from other P. syringae strains.

UV light inactivation of human and plant pathogens in unfiltered surface irrigation water.

Fruit and vegetable growers continually battle plant diseases and food safety concerns. Surface water is commonly used in the production of fruits and vegetables and can harbor both human- and plant-pathogenic microorganisms that can contaminate crops when used for irrigation or other agricultural purposes. Treatment methods for surface water are currently limited, and there is a need for suitable treatment options. A liquid-processing unit that uses UV light for the decontamination of turbid juices was analyzed for its efficacy in the treatment of surface waters contaminated with bacterial or oomycete pathogens, i.e., Escherichia coli, Salmonella enterica, Listeria monocytogenes, Clavibacter michiganensis subsp. michiganensis, Pseudomonas syringae pv. tomato, and Phytophthora capsici. Five-strain cocktails of each pathogen, containing approximately 10(8) or 10(9) CFU/liter for bacteria or 10(4) or 10(5) zoospores/liter for Ph. capsici, were inoculated into aliquots of two turbid surface water irrigation sources and processed with the UV unit. Pathogens were enumerated before and after treatment. In general, as the turbidity of the water source increased, the effectiveness of the UV treatment decreased, but in all cases, 99.9% or higher inactivation was achieved. Log reductions ranged from 10.0 to 6.1 and from 5.0 to 4.2 for bacterial pathogens and Ph. capsici, respectively.

Plant-pathogenic oomycetes, Escherichia coli strains, and Salmonella spp. Frequently found in surface water used for irrigation of fruit and vegetable crops in New York State.

In the United States, surface water is commonly used to irrigate a variety of produce crops and can harbor pathogens responsible for food-borne illnesses and plant diseases. Understanding when pathogens infest water sources is valuable information for produce growers to improve the food safety and production of these crops. In this study, prevalence data along with regression tree analyses were used to correlate water quality parameters (pH, temperature, turbidity), irrigation site properties (source, the presence of livestock or fowl nearby), and precipitation data to the presence and concentrations of Escherichia coli, Salmonella spp., and hymexazol-insensitive (HIS) oomycetes (Phytophthora and Pythium spp.) in New York State surface waters. A total of 123 samples from 18 sites across New York State were tested for E. coli and Salmonella spp., of which 33% and 43% were positive, respectively. Additionally, 210 samples from 38 sites were tested for HIS oomycetes, and 88% were found to be positive, with 10 species of Phytophthora and 11 species of Pythium being identified from the samples. Regression analysis found no strong correlations between water quality parameters, site factors, or precipitation to the presence or concentration of E. coli in irrigation sources. For Salmonella, precipitation (≤ 0.64 cm) 3 days before sampling was correlated to both presence and the highest counts. Analyses for oomycetes found creeks to have higher average counts than ponds, and higher turbidity levels were associated with higher oomycete counts. Overall, information gathered from this study can be used to better understand the food safety and plant pathogen risks of using surface water for irrigation.

Muskelin acts as a substrate receptor of the highly regulated Drosophila CTLH E3 ligase during the maternal-to-zygotic transition.

The maternal-to-zygotic transition (MZT) is a conserved developmental process where the maternally-derived protein and mRNA cache is replaced with newly made zygotic gene products. We have previously shown that in Drosophila the deposited RNA-binding proteins ME31B, Cup, and Trailer Hitch (TRAL) are ubiquitylated by the CTLH E3 ligase and cleared. However, the organization and regulation of the CTLH complex remain poorly understood in flies. In particular, Drosophila lacks an identifiable substrate adaptor, and the mechanisms restricting degradation of ME31B and its cofactors to the MZT are unknown. Here, we show that the developmental specificity of the CTLH complex is mediated by multipronged regulation, including transcriptional control by the transcription factor OVO and autoinhibition of the E3 ligase. One major regulatory target is the subunit Muskelin, which we demonstrate acts as a substrate adaptor for the Drosophila CTLH complex. Although conserved, Muskelin has structural roles in other species, suggesting a surprising functional plasticity. Finally, we find that Muskelin has few targets beyond the three known RNA binding proteins, showing exquisite target specificity. Thus, multiple levels of integrated regulation restrict the activity of the embryonic CTLH complex to early embryogenesis, seemingly with the goal of regulating three important RNA binding proteins.

Overcoming immune evasion from post-translational modification of a mutant KRAS epitope to achieve TCR-T cell-mediated antitumor activity.

T cell receptor (TCR)-T cell immunotherapy, in which T cells are engineered to express a TCR targeting a tumor epitope, is a form of adoptive cell therapy (ACT) that has exhibited promise against various tumor types. Mutants of oncoprotein KRAS, particularly at glycine-12 (G12), are frequent drivers of tumorigenicity, making them attractive targets for TCR-T cell therapy. However, class I-restricted TCRs specifically targeting G12-mutant KRAS epitopes in the context of tumors expressing HLA-A2, the most common human HLA-A allele, have remained elusive despite evidence an epitope encompassing such mutations can bind HLA-A2 and induce T cell responses. We report post-translational modifications (PTMs) on this epitope may allow tumor cells to evade immunologic pressure from TCR-T cells. A lysine side chain-methylated KRAS G12V peptide, rather than the unmodified epitope, may be presented in HLA-A2 by tumor cells and impact TCR recognition. Using a novel computationally guided approach, we developed by mutagenesis TCRs that recognize this methylated peptide, enhancing tumor recognition and destruction. Additionally, we identified TCRs with similar functional activity in normal repertoires from primary T cells by stimulation with modified peptide, clonal expansion, and selection. Mechanistically, a gene knockout screen to identify mechanism(s) by which tumor cells methylate/demethylate this epitope unveiled SPT6 as a demethylating protein that could be targeted to improve effectiveness of these new TCRs. Our findings highlight the role of PTMs in immune evasion and suggest identifying and targeting such modifications should make effective ACTs available for a substantially greater range of tumors than the current therapeutic landscape. One-sentence summary: Tumor cell methylation of KRAS G12V epitope in HLA-A2 permits immune evasion, and new TCRs were generated to overcome this with engineered cell therapy.

Immunodepletion plasma proteomics by tripleTOF 5600 and Orbitrap elite/LTQ-Orbitrap Velos/Q exactive mass spectrometers.

Plasma proteomic experiments performed rapidly and economically using several of the latest high-resolution mass spectrometers were compared. Four quantitative hyperfractionated plasma proteomics experiments were analyzed in replicates by two AB SCIEX TripleTOF 5600 and three Thermo Scientific Orbitrap (Elite/LTQ-Orbitrap Velos/Q Exactive) instruments. Each experiment compared two iTRAQ isobaric-labeled immunodepleted plasma proteomes, provided as 30 labeled peptide fractions, and 480 LC-MS/MS runs delivered >250 GB of data in 2 months. Several analysis algorithms were compared. At 1% false discovery rate, the relative comparative findings concluded that the Thermo Scientific Q Exactive Mass Spectrometer resulted in the highest number of identified proteins and unique sequences with iTRAQ quantitation. The confidence of iTRAQ fold-change for each protein is dependent on the overall ion statistics (Mascot Protein Score) attainable by each instrument. The benchmarking also suggested how to further improve the mass spectrometry parameters and HPLC conditions. Our findings highlight the special challenges presented by the low abundance peptide ions of iTRAQ plasma proteome because the dynamic range of plasma protein abundance is uniquely high compared with cell lysates, necessitating high instrument sensitivity.

Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression.

OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD. METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system. RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD. CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).

Phenotype evaluation and genomewide linkage study of clinical variables in schizophrenia.

Genetic factors are likely to influence clinical variation in schizophrenia, but it is unclear which variables are most suitable as phenotypes and which molecular genetic loci are involved. We evaluated clinical variable phenotypes and applied suitable phenotypes in genome-wide covariate linkage analysis. We ascertained 170 affected relative pairs (168 sibling-pairs and two avuncular pairs) with DSM-IV schizophrenia or schizoaffective disorder from the United Kingdom. We defined psychotic symptom dimensions, age at onset (AAO), and illness course using the OPCRIT checklist. We evaluated phenotypes using within sibling-pair correlations and applied suitable phenotypes in multipoint covariate linkage analysis based on 372 microsatellite markers at ∼10 cM intervals. The statistical significance of linkage results was assessed by simulation. The positive and disorganized symptom dimensions, AAO, and illness course qualified as suitable phenotypes. There were no genome-wide significant linkage results. There was suggestive evidence of linkage for the positive dimension on chromosomes 2q32, 10q26, and 20q12; the disorganized dimension on 8p21 and 17q21; and illness course on 2q33 and 22q11. The linkage peak for disorganization on 17q21 remained suggestive after correction for multiple testing. To our knowledge, this is the first study to integrate phenotype evaluation and genome-wide covariate linkage analysis for symptom dimensions and illness history variables in sibling-pairs with schizophrenia. The significant within-pair correlations strengthen the evidence that some clinical variables within schizophrenia are suitable phenotypes for molecular genetic investigations. At present there are no genome-wide significant linkage results for these phenotypes, but a number of suggestive findings warrant further investigation.

ARTEMIS: A Novel Mass-Spec Platform for HLA-Restricted Self and Disease-Associated Peptide Discovery.

Conventional immunoprecipitation/mass spectroscopy identification of HLA-restricted peptides remains the purview of specializing laboratories, due to the complexity of the methodology, and requires computational post-analysis to assign peptides to individual alleles when using pan-HLA antibodies. We have addressed these limitations with ARTEMIS: a simple, robust, and flexible platform for peptide discovery across ligandomes, optionally including specific proteins-of-interest, that combines novel, secreted HLA-I discovery reagents spanning multiple alleles, optimized lentiviral transduction, and streamlined affinity-tag purification to improve upon conventional methods. This platform fills a middle ground between existing techniques: sensitive and adaptable, but easy and affordable enough to be widely employed by general laboratories. We used ARTEMIS to catalog allele-specific ligandomes from HEK293 cells for seven classical HLA alleles and compared results across replicates, against computational predictions, and against high-quality conventional datasets. We also applied ARTEMIS to identify potentially useful, novel HLA-restricted peptide targets from oncovirus oncoproteins and tumor-associated antigens.

Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk.

Studies in post-mortem human brain tissue have associated major depressive disorder (MDD) with cortical transcriptomic changes, whose potential in vivo impact remains unexplored. To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing 'depression-like' shifts in cortical gene expression. Here, we used a non-clinical sample of young adults (n = 482, Duke Neurogenetics Study: 53% women; aged 19.8 ± 1.2 years) to map T-PRS onto brain morphology measures, including Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index, as well as broad MDD risk, indexed by self-reported family history of depression. We conducted side-by-side comparisons with a PRS independently derived from a Psychiatric Genomics Consortium (PGC) MDD GWAS (PGC-PRS), and sought to link T-PRS with diagnosis and symptom severity directly in PGC-MDD participants (n = 29,340, 59% women; 12,923 MDD cases, 16,417 controls). T-PRS was associated with smaller amygdala volume in women (t = -3.478, p = 0.001) and lower prefrontal gyrification across sexes. In men, T-PRS was associated with hypergyrification in temporal and occipital regions. Prefrontal hypogyrification mediated a male-specific indirect link between T-PRS and familial depression (b = 0.005, p = 0.029). PGC-PRS was similarly associated with lower amygdala volume and cortical gyrification; however, both effects were male-specific and hypogyrification emerged in distinct parietal and temporo-occipital regions, unassociated with familial depression. In PGC-MDD, T-PRS did not predict diagnosis (OR = 1.007, 95% CI = [0.997-1.018]) but correlated with symptom severity in men (rho = 0.175, p = 7.957 × 10-4) in one cohort (N = 762, 48% men). Depression-like shifts in cortical gene expression have sex-specific effects on brain morphology and may contribute to broad depression vulnerability in men.

Validation of self-report depression rating scales in Huntington's disease.

The aim of this study was to assess the criterion validity of three self-report measures of depression in a sample of patients with Huntington's disease (HD). Fifty patients with HD completed the Beck Depression Inventory-II (BDI-II), the Hospital Anxiety and Depression Scale (HADS), and the Depression Intensity Scale Circles (DISCs). Current psychiatric status was assessed using the schedules for clinical assessment in neuropsychiatry (SCAN), and ICD-10 diagnosis was used as the gold standard. Receiver operating characteristics (ROC) curves were obtained and the sensitivity, specificity, positive, and negative predictive values were calculated for different cut-off scores on each rating scale. Twelve patients (24%) met ICD-10 criteria for depressive disorder. The depression sub-scale of the HADS (HADS-D) at an optimal cut-off of 6/7 was found to discriminate maximally between depressed and nondepressed patients in this population. The DISCs at a cut-off of 1/2 also performed well at detecting possible "cases" of depression, whereas the BDI-II performed the least satisfactorily of all scales. The HADS-D and DISCs are good screening measures for depression in the HD population and the DISCs may be particularly useful in those patients with more severe communicative and cognitive deficits.

Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.

BACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4). RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99). CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

Development of a battery of functional tests for low vision.

PURPOSE: We describe the development and evaluation of a battery of tests of functional visual performance of everyday tasks intended to be suitable for assessment of low vision patients. METHODS: The functional test battery comprises-Reading rate: reading aloud 20 unrelated words for each of four print sizes (8, 4, 2, & 1 M); Telephone book: finding a name and reading the telephone number; Medicine bottle label: reading the name and dosing; Utility bill: reading the due date and amount due; Cooking instructions: reading cooking time on a food package; Coin sorting: making a specified amount from coins placed on a table; Playing card recognition: identifying denomination and suit; and Face recognition: identifying expressions of printed, life-size faces at 1 and 3 m. All tests were timed except face and playing card recognition. Fourteen normally sighted and 24 low vision subjects were assessed with the functional test battery. Visual acuity, contrast sensitivity, and quality of life (National Eye Institute Visual Function Questionnaire 25 [NEI-VFQ 25]) were measured and the functional tests repeated. Subsequently, 23 low vision patients participated in a pilot randomized clinical trial with half receiving low vision rehabilitation and half a delayed intervention. The functional tests were administered at enrollment and 3 months later. RESULTS: Normally sighted subjects could perform all tasks but the proportion of trials performed correctly by the low vision subjects ranged from 35% for face recognition at 3 m, to 95% for the playing card identification. On average, low vision subjects performed three times slower than the normally sighted subjects. Timed tasks with a visual search component showed poorer repeatability. In the pilot clinical trial, low vision rehabilitation produced the greatest improvement for the medicine bottle and cooking instruction tasks. CONCLUSIONS: Performance of patients on these functional tests has been assessed. Some appear responsive to low vision rehabilitation.

Accommodation, acuity, and their relationship to emmetropization in infants.

PURPOSE: To evaluate the relationship between accommodation, visual acuity, and emmetropization in human infancy. METHODS: Defocus at distance and near (57 cm) was assessed using Mohindra and dynamic retinoscopy, respectively, in 262 normal birthweight infants at 3, 9, and 18 months of age. Preferential looking provided acuity data at the same ages. The spherical equivalent refractive error was measured by cycloplegic retinoscopy (cyclopentolate 1%). RESULTS: Univariate linear regression analyses showed no associations between the change in refractive error and defocus at distance or near. Change in refractive error was linearly related to the accommodative response at distance (R = 0.17, p < 0.0001) and near (R = 0.13, p < 0.0001). The ten subjects with the poorest emmetropization relative to the change predicted by the linear effects of their refractive error had higher average levels of hyperopic defocus at distance and near (p < 0.043). Logistic regression showed a decrease in the odds of reaching +2.00 diopter or less hyperopia by 18 months with increasing levels of hyperopia at 3 months, or if Mohindra retinoscopy was myopic combined with acuity better than the median level of 1.25 logMAR [area under the receiver operating characteristic curve = 0.78 (95% CI = 0.68 to 0.88)]. CONCLUSIONS: The level of cycloplegic refractive error was the best single factor for predicting emmetropization by 18 months of age, with smaller contributions from visual acuity and Mohindra retinoscopy. The lack of correlation between defocus and change in refractive error does not support a simple model of emmetropization in response to the level of hyperopic defocus. Infants were capable of maintaining accurate average levels of accommodation across a range of moderate hyperopic refractive errors at 3 months of age. The association between the change in refractive error and accommodative response suggests that accommodation is a plausible visual signal for emmetropization.

Randomized trial of the effect of contact lens wear on self-perception in children.

PURPOSE: To determine whether contact lens wear affects children's self-perceptions. METHODS: The Adolescent and Child Health Initiative to Encourage Vision Empowerment Study was a randomized, single-masked trial conducted at five clinical centers in the United States. Subjects were 8- to 11-year-old myopic children randomly assigned to wear spectacles (n = 237) or soft contact lenses (n = 247) for 3 years. The primary endpoint was the Self-Perception Profile for Children Global Self-Worth scale. Secondary outcomes included the Physical Appearance, Athletic Competence, Scholastic Competence, Behavioral Conduct, and Social Acceptance Self-Perception Profile for Children scales. RESULTS: Global self-worth was not affected by contact lens wear [analysis of variance (ANOVA), difference = 0.06; 95% CI, -0.004 to 0.117]. Physical appearance (ANOVA, difference = 0.15; 95% CI, 0.07 to 0.22), athletic competence (ANOVA, difference = 0.08; 95% CI, 0.01 to 0.15), and social acceptance (ANOVA, difference = 0.10; 95% CI, 0.03 to 0.17) were all greater for contact lens wearers. CONCLUSIONS: Although contact lens wear does not affect global self-perceptions of 8- to 11-year-old myopic children their physical appearance, athletic competence, and social acceptance self-perceptions are likely to improve with contact lens wear. Eye care practitioners should consider the social and visual benefits of contact lens wear when choosing the most appropriate vision correction modality for children as young as 8 years of age.