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IntroductionYoung children with type 1 diabetes (T1D) may be at particularly high risk of cognitive decline following diabetic ketoacidosis (DKA). However, studies of cognitive functioning in T1D typically examine school-age children. The goal of this study was to examine whether a single experience of DKA is associated with lower cognitive functioning in young children. We found that recently diagnosed 3- to 5-year-olds who experienced one DKA episode, regardless of its severity, exhibited lower IQ scores than those with no DKA exposure.MethodsWe prospectively enrolled 46 3- to 5-year-old children, who presented with DKA at the onset of T1D, in a randomized multi-site clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 22 children and mild in 24 children. Neurocognitive function was assessed once 2-6 months after the DKA episode. A comparison group of 27 children with T1D, but no DKA exposure, was also assessed. Patient groups were matched for age and T1D duration at the time of neurocognitive testing.ResultsChildren who experienced DKA, regardless of its severity, exhibited significantly lower IQ scores than children who did not experience DKA, F(2, 70) = 6.26, p = .003, partial η2  = .15. This effect persisted after accounting for socioeconomic status and ethnicity.ConclusionsA single DKA episode is associated with lower IQ scores soon after exposure to DKA in young children.

ObjectivesInvestigating empirical relationships among laboratory measures in children with diabetic ketoacidosis (DKA) can provide insights into physiological alterations occurring during DKA. We determined whether alterations in laboratory measures during DKA conform to theoretical predictions.MethodsWe used Pearson correlation statistics and linear regression to investigate correlations between blood glucose, electrolytes, pH and PCO2 at emergency department presentation in 1,681 pediatric DKA episodes. Among children with repeat DKA episodes, we also assessed correlations between laboratory measures at the first vs. second episode.ResultspH and bicarbonate levels were strongly correlated (r=0.64), however, pH and PCO2 were only loosely correlated (r=0.17). Glucose levels were correlated with indicators of dehydration and kidney function (blood urea nitrogen (BUN), r=0.44; creatinine, r=0.42; glucose-corrected sodium, r=0.32). Among children with repeat DKA episodes, PCO2 levels tended to be similar at the first vs. second episode (r=0.34), although pH levels were only loosely correlated (r=0.19).ConclusionsElevated glucose levels at DKA presentation largely reflect alterations in glomerular filtration rate. pH and PCO2 are weakly correlated suggesting that respiratory responses to acidosis vary among individuals and may be influenced by pulmonary and central nervous system effects of DKA.

ObjectiveFluid replacement to correct dehydration, acidosis, and electrolyte abnormalities is the cornerstone of treatment for diabetic ketoacidosis (DKA), but little is known about optimal fluid infusion rates and electrolyte content. The objective of this study was to evaluate whether different fluid protocols affect the rate of normalization of biochemical derangements during DKA treatment.Research design and methodsThe current analysis involved moderate or severe DKA episodes (n = 714) in children age

ObjectiveThis study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes and whether the same is true in children who had previously been diagnosed after accounting for variations in glycemic control and other relevant factors.Research design and methodsWe prospectively enrolled 758 children, 6-18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled.ResultsAmong all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (β = -0.12, P < 0.001), item-color recall (β = -0.08, P = 0.010), and forward digit span (β = -0.06, P = 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β = -0.08, P = 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA1c were independently associated with lower IQ (β = -0.10 and β = -0.09, respectively, P < 0.01) and higher HbA1c was associated with lower item-color recall (β = -0.10, P = 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for.ConclusionsA single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.

ObjectivesTo characterize hemodynamic alterations occurring during diabetic ketoacidosis (DKA) in a large cohort of children and to identify clinical and biochemical factors associated with hypertension.Study designThis was a planned secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a randomized clinical trial of fluid resuscitation protocols for children in DKA. Hemodynamic data (heart rate, blood pressure) from children with DKA were assessed in comparison with normal values for age and sex. Multivariable statistical modeling was used to explore clinical and laboratory predictors of hypertension.ResultsAmong 1258 DKA episodes, hypertension was documented at presentation in 154 (12.2%) and developed during DKA treatment in an additional 196 (15.6%), resulting in a total of 350 DKA episodes (27.8%) in which hypertension occurred at some time. Factors associated with hypertension at presentation included more severe acidosis, (lower pH and lower pCO2), and stage 2 or 3 acute kidney injury. More severe acidosis and lower Glasgow Coma Scale scores were associated with hypertension occurring at any time during DKA treatment.ConclusionsDespite dehydration, hypertension occurs in a substantial number of children with DKA. Factors associated with hypertension include greater severity of acidosis, lower pCO2, and lower Glasgow Coma Scale scores during DKA treatment, suggesting that hypertension might be centrally mediated.

BACKGROUND:Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades. METHODS:We conducted a 13-center, randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of

To investigate the genetic etiology of anophthalmia and microphthalmia, we used exome sequencing in a Caucasian female with unilateral microphthalmia and coloboma, bilateral optic nerve hypoplasia, ventricular and atrial septal defects, and growth delays. We found two sequence variants in SALL4 - c.[575C>A], predicting p.(Ala192Glu), that was paternally inherited, and c.[2053G>C], predicting p.(Asp685His), that was maternally inherited. Haploinsufficiency for SALL4 due to nonsense or frameshift mutations has been associated with acro-renal ocular syndrome that is characterized by eye defects including Duane anomaly and coloboma, in addition to radial ray malformations and renal abnormalities. Our report is the first description of structural eye defects associated with two missense variants in SALL4 inherited in trans; the absence of reported findings in both parents suggests that both sequence variants are hypomorphic mutations and that both are needed for the ocular phenotype. SALL4 is expressed in the developing lens and regulates BMP4, leading us to speculate that altered BMP4 expression was responsible for the eye defects, but we could not demonstrate altered BMP4 expression in vitro after using small interfering RNAs (siRNAs) to reduce SALL4 expression. We conclude that SALL4 hypomorphic variants may influence eye development.

The article "AUCTION HOUSES IN BRITAIN AND CHINA: THE HISTORY AND THE LAW" discusses the historical development of art auctions in Britain and China. In Britain, art auctions have a long history dating back to the seventeenth and eighteenth centuries, reflecting the rise of the middle class during the industrial revolution. In contrast, art auctions in China are a more recent phenomenon, emerging in the late 1980s and early 1990s after the country's transition to a market economy. Both English and Chinese laws protect auction houses from claims brought by buyers, emphasizing the principle of caveat emptor. The legal obligations of auction houses in both countries are similar, with courts often finding auction houses not liable for claims brought by buyers. The article highlights the complexities and uncertainties surrounding the art market, emphasizing the subjective nature of attributions and the challenges of tracing authenticity over time. [Extracted from the article]

We previously reported that tacrolimus (TAC) trough blood concentrations for African American (AA) kidney allograft recipients were lower than those observed in white patients. Subtherapeutic TAC troughs may be associated with acute rejection (AR) and AR-associated allograft failure. This variation in TAC troughs is due, in part, to differences in the frequency of the cytochrome P450 CYP3A5*3 allele (rs776746, expresses nonfunctional enzyme) between white and AA recipients; however, even after accounting for this variant, variability in AA-associated troughs is significant. We conducted a genomewide association study of TAC troughs in AA kidney allograft recipients to search for additional genetic variation. We identified two additional CYP3A5 variants in AA recipients independently associated with TAC troughs: CYP3A5*6 (rs10264272) and CYP3A5*7 (rs41303343). All three variants and clinical factors account for 53.9% of the observed variance in troughs, with 19.8% of the variance coming from demographic and clinical factors including recipient age, glomerular filtration rate, anticytomegalovirus drug use, simultaneous pancreas-kidney transplant and antibody induction. There was no evidence of common genetic variants in AA recipients significantly influencing TAC troughs aside from the CYP3A gene. These results reveal that additional and possibly rare functional variants exist that account for the additional variation.

Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing with the ACE Exome(TM) (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 cases) to sequence 28 patients with A/M and four patients with varied developmental eye defects. In the 28 patients with A/M, we identified de novo mutations in three patients (OTX2, p.(Gln91His), RARB, p.Arg387Cys and GDF6, p.Ala249Glu) and inherited mutations in STRA6 in two patients. In patients with developmental eye defects, a female with cataracts and cardiomyopathy had a de novo COL4A1 mutation, p.(Gly773Arg), expanding the phenotype associated with COL4A1 to include cardiomyopathy. A male with a chorioretinal defect, microcephaly, seizures and sensorineural deafness had two PNPT1 mutations, p.(Ala507Ser) and c.401-1G>A, and we describe eye defects associated with this gene for the first time. Exome sequencing was efficient for identifying mutations in pathogenic genes for which there is no clinical testing available and for identifying cases that expand phenotypic spectra, such as the PNPT1 and COL4A1-associated disorders described here.

This commentary reviews and summarises the strides which neuroscience has made in our present understanding of the development of literacy and numeracy in children. Specifically, it draws attention to key insights from studies which have elucidated the possible neural mechanisms that may account for difficulties in the development of these fundamental learning abilities. It also discusses the possible future applications of neuroscience in providing early detection of these learning difficulties in children, and in guiding the design of appropriate interventions aimed at mitigating these difficulties. Finally, it identifies challenges that will arise as the field of educational neuroscience matures. Importantly, it emphasises that educational neuroscience research must be considered in tandem with research in other fields in order to develop a holistic understanding of the process of learning.

As an increasing number of emerging adults enter university as undergraduate students, and the relationship between higher education and the graduate employment market becomes ever more interconnected, it is critical to examine how this population can navigate their career development effectively in today's ever-changing world. This paper draws attention to the influence of uncertainty on the career development of emerging adults as undergraduate students. Three critical challenges that are related to uncertainty are examined, including: (a) ambiguity in the external environment; (b) inadequate management of uncertainty due to executive function deficits; and (c) mental health implications -- specifically, anxiety--that arise from uncertainty. Then, I address these challenges with three postmodern career development approaches and their related interventions, including the Chaos Theory of Careers, the narrative approach, and the spiritual approach.

Objectives: The aims of this study were to examine the effects of group cognitive-behavior therapy (CBT) on improving anxiety symptoms and enhancing personal growth among adolescents at risk of developing anxiety disorders in school settings in Hong Kong. Method: A total of 26 participants received an eight-session CBT group and 20 received treatment as usual in the waitlist control condition. Instruments measuring anxiety symptoms, types of anxiety in children, dysfunctional thoughts, and personal growth were used to assess the changes in severity of anxiety symptoms, dysfunctional thoughts, and personal growth among the participants. Results: A 2 × 2 mixed model analyses of variance were employed, results demonstrated significantly greater improvements in overall anxiety symptoms, generalized anxiety symptoms, and personal growth--use of resources in the participants of the CBT group compared to the control group. Conclusion: Group CBT may potentially improve anxiety symptoms of adolescents in school settings in Hong Kong. [Paper presented at the Stockholm Conference on Behavioral and Social Intervention Research, 11-12 May, 2017.]

Purpose: Immature auditory processing has been proposed to underlie language impairments in children with developmental language disorder (DLD; also known as "specific language impairment"). Using newly available normative auditory evoked potential (AEP) waveforms, we estimated AEP maturity in individual children with DLD and explored whether this maturational index was related to their language abilities. Method: AEPs were elicited by 225 trials of a 490-Hz pure tone. Using intraclass correlation and our previously established normative AEP waveforms of 7- to 10-year-old children with typical development, we estimated the age equivalent of the AEPs (AEP-age) from 21 children with DLD. The relation between AEP maturity and language was explored through regression analysis. Results: AEP-age predicted 31% of the variance in the language abilities of children with DLD. The AEP-age of children with mild DLD was similar to their chronological age, whereas children with moderate-severe DLD showed, on average, a 1.3-year delay in their neural responses. AEP-age predicted receptive, but not expressive, language performance. Conclusion: Maturation in auditory neural responses is a significant predictor of language ability, particularly in children with moderate-severe DLD.

Wnt signaling, which encompasses multiple biochemical pathways that regulate neural development downstream of extracellular Wnt glycoprotein ligands, has been suggested to contribute to major psychiatric disorders including autism spectrum disorders (ASD). We used next-generation sequencing and Sequenom genotyping technologies to resequence 10 Wnt signaling pathway genes in 198 ASD patients and 240 matched controls. Results for single-nucleotide polymorphisms (SNPs) of interest were confirmed in a second set of 91 ASD and 144 control samples. We found a significantly increased burden of extremely rare missense variants predicted to be deleterious by PolyPhen-2, distributed across seven genes in the ASD sample (3.5% in ASD vs 0.8% in controls; Fisher's exact test, odds ratio (OR)=4.37, P=0.04). We also found a missense variant in WNT1 (S88R) that was overrepresented in the ASD sample (8 A/T in 267 ASD (minor allele frequency (MAF)=1.69%) vs 1 A/T in 377 controls (MAF=0.13%), OR=13.0, Fisher's exact test, P=0.0048; OR=8.2 and P=0.053 after correction for population stratification). Functional analysis revealed that WNT1-S88R is more active than wild-type WNT1 in assays for the Wnt/β-catenin signaling pathway. Our findings of a higher burden in ASD of rare missense variants distributed across 7 of 10 Wnt signaling pathway genes tested, and of a functional variant at the WNT1 locus associated with ASD, support that dysfunction of this pathway contributes to ASD susceptibility. Given recent findings of common molecular mechanisms in ASD, schizophrenia and affective disorders, these loci merit scrutiny in other psychiatric conditions as well.

This study investigated the differential influences of maternal and paternal factors on Chinese children's English as a foreign language development. It took into account both behavioral (i.e. parental home literacy practices, HLP; and children's vocabulary knowledge) and emotional (i.e. parental and children's foreign language reading anxiety, FLRA) aspects of home literacy environment and children's language outcomes. Forty-eight Chinese first graders were tested individually on English vocabulary knowledge. Subsequently, both parents of participating children completed a questionnaire rating their HLP on English as a foreign language, their FLRA and their child's FLRA. Results from hierarchical regression analysis showed that paternal HLP predicted children's English vocabulary knowledge and paternal FLRA predicted children's FLRA, after controlling for children's age, family income and parental education level. However, when the effects of maternal factors were accounted for, these paternal factors did not uniquely contribute to children's English vocabulary knowledge or FLRA. In contrast, maternal HLP and FLRA explained unique variance in both children's English vocabulary knowledge and FLRA, even after paternal factors were accounted for. These results have provided a more comprehensive picture of how home literacy environment contributes to children's foreign language development, by indicating maternal and paternal contributions both behaviorally and emotionally.

Purpose: The study aims to examine the effectiveness of a positive psychology group-based intervention program, incorporating elements of hope and gratitude, in decreasing depression and increasing life satisfaction among primary school students in Hong Kong. Method: A total of 68 children, with the Depression score of Chinese Hospital Anxiety and Depression Scale from 9 to 11, were randomly assigned to the intervention and control groups. An eight-session intervention group-based program was conducted in five primary schools. Results: Participants of the intervention groups showed a significant decrease in depression and significant increase in life satisfaction, partially mediated by hope and gratitude, after the intervention when compared with those of the control groups. Discussion: As positive psychology intervention teaches children ways to increase their positive cognition, emotions, and behaviors, it may help children cope with current emotional problems and enhance their capability to deal with future stress and adversities.

Based on the responses of 5,557 Chinese secondary students in Hong Kong, the relationships among perceived hopelessness, family functioning, and suicidal ideation were examined. Results showed that suicidal ideation was positively related to hopelessness, but negatively related to parent-adolescent communication. Compared with father-adolescent communication, mother-adolescent communication generally had a stronger association with adolescent suicidal ideation. It was further found that the linkage between hopelessness and adolescent suicidal ideation was stronger under a low parent-adolescent communication condition, thus suggesting the moderating effect of parent-adolescent communication on the effect of hopelessness on suicidal ideation. The theoretical and practical implications of the findings are discussed.

Based on the family ecological model, personal (hopelessness, social problem solving, emotional competence) and family (parent-adolescent communication, family functioning) quality of life measures related to adolescent suicidal ideation were examined in 5,557 Secondary 1 to Secondary 4 students in Hong Kong. Results showed that suicidal ideation was positively related to adolescent hopelessness but negatively related to emotional competence, social problem solving, father-adolescent communication, mother-adolescent communication and family functioning. Multiple regression analyses showed that hopelessness was the most important predictor of adolescent suicidal ideation, followed by mother-adolescent communication, family functioning, social problem solving, father-adolescent communication, and emotional competence. Path analyses with and without direct effects showed that hopelessness mediated the effect of personal and family correlates on adolescent suicidal ideation. Theoretical and practice implications of the findings are discussed.

Lutein and zeaxanthin are important anti-oxidant nutrients obtained only from foods that are essential for good eye health. The purpose of this study was to assess food choices rich in lutein/zeaxanthin and compare the amount of lutein/zeaxanthin intake amongst college students and their live-in parents. Three-day dietary records from 95 undergraduate college students were reviewed and compared with the records of an equal number of their live-in parents. The study included 76 African Americans (AA) (38 young AA, 38 old AA) and 114 Caucasian Americans (57 young Caucasians, 57 old Caucasians). Individuals in this study had an average of 2.5 servings of fruits and vegetables a day. It was calculated that they consumed approximately 2 mg per day of lutein/zeaxanthin from their regular diets. The statistical analyses of ethnic, gender, and age subgroups were performed. There were no statistical differences in food consumption and lutein/zeaxanthin intakes between ethnic, age and gender groups in this study. Both the recommended daily consumption of 5 to 9 servings of fruits/vegetables and the daily intake of 6 mg/day of lutein/zeaxanthin were unmet by all subjects in this study. Great effort in educating the public is therefore needed for eye health. (Contains 4 figures and 6 tables.)