Vocabulary knowledge and reading comprehension account for SES-differences in how school-aged children infer word meanings from sentences.

Socioeconomic status (SES)-related language gaps are known to widen throughout the course of the school years; however, not all children from lower SES homes perform worse than their higher SES peers on measures of language. The current study uses mediation and moderated mediation to examine how cognitive and language abilities (vocabulary, reading, phonological processing, working memory) account for individual differences in a children's ability to infer a novel word's meaning, a key component in word learning, in school-aged children from varying SES backgrounds. Vocabulary and reading comprehension mediated the relationship between SES and accuracy when inferring word meanings. The relationship between SES, vocabulary, and inferring word meaning was moderated by age, such that the influence of vocabulary on task performance was strongest in young children. The reading pathway did not interact with age effects, indicating reading is an important contributor to SES-related differences in how children infer a word's meaning throughout grade school. These findings highlight different paths by which children's trajectories for inferring word meanings may be impacted.

Neural oscillations reveal differences in the process of word learning among school-aged children from lower socioeconomic status backgrounds.

Building a robust vocabulary in grade school is essential for academic success. Children from lower socioeconomic status (SES) households on average perform below their higher SES peers on word learning tasks, negatively impacting their vocabulary; however, significant variability exists within this group. Many children from low SES homes perform as well as, or better than, their higher SES peers on measures of word learning. The current study addresses what processes underlie this variability, by comparing the neural oscillations of 44 better versus worse word learners (ages 8-15 years) from lower SES households as they infer the meaning of unknown words. Better word learners demonstrated increases in theta and beta power as a word was learned, whereas worse word learners exhibited decreases in alpha power. These group differences in neural oscillatory engagement during word learning indicate there may be different strategies employed based on differences in children's skills. Notably, children with greater vocabulary knowledge are more likely to exhibit larger beta increases; a strategy which is associated with better word learning. This sheds new light on the mechanisms that support word learning in children from low SES households.

The changing incidence of childhood-onset type 1 diabetes in Wales: Effect of gender and season at diagnosis and birth.

AIMS: Determinants of the changing incidence of childhood-onset type 1 diabetes remain uncertain. We determined the recent time-trend of type 1 diabetes incidence in Wales and explored the role of vitamin D by evaluating the influence of season both at diagnosis and at birth. METHODS: Data from all Welsh paediatric units 1990-2019, and from primary care to determine ascertainment. RESULTS: Log-linear modelling indicated a non-linear secular trend in incidence with peak and subsequent decline. The peak occurred around June 2010: 31∙3 cases/year/100,000 children aged < 15y. It occurred earlier in children younger at diagnosis and earlier in boys. There were more cases in males aged <2y and >12y but more in females aged 9-10 y. More were diagnosed in winter. Also, children born in winter had less risk of future diabetes. CONCLUSIONS: The risk of developing type 1 diabetes before age 15y in Wales is no longer increasing. The data on season are consistent with a preventative role for vitamin D both during pregnancy and later childhood. Metereological Office data shows increasing hours of sunlight since 1980 likely to increase vitamin D levels with less diabetes. Additional dietary supplementation with vitamin D might further reduce the incidence of type 1 diabetes.

Reporting and analysis of open-label extension studies of anti-epileptic drugs.

PURPOSE: Open-label extension studies, or follow-on randomised controlled trials (FORCTs) are widely believed to be prone to patient selection biases which may inflate effect estimates. This study investigates the reporting and analysis of efficacy outcomes in FORCTs and critically evaluates the associated underlying assumptions. We propose an alternative method of analysis, in line with that recommended in the analysis of RCTs, the intention to treat (ITT) approach, in which it is assumed that all patients who discontinue treatment are non-responders. METHODS: A systematic review of FORCTs and randomised controlled trials (RCT) of topiramate, levetiracetam and gabapentin as adjuvant therapy in refractory adult epilepsy was conducted. Sample sizes and numbers of responders, along with reported outcomes were extracted. To evaluate the feasibility of the assumptions underlying the various methods of analysis, the most common causes of discontinuation were evaluated. For each FORCT, we compared the reported outcome to the proposed ITT analysis. RESULTS: The 10 FORCT reports identified all excluded from the analysis patients who dropped out of the RCT. Adverse events or inefficacy were the main reasons for treatment discontinuation. Analysis based on the ITT method, led to smaller effect estimates than those reported. For example, a FORCT of levetiracetam reported a responder rate of 43%, which reduced to 28% under an ITT analysis, comparable to an ITT analysis outcome of 26% for the parent RCT. CONCLUSIONS: FORCTs can provide important information about long-term efficacy and tolerability of newer therapies. However, current reporting methods are likely to be misleading as outcomes are reported for the subset of patients continuing with treatment at the end of the FORCT. Since the majority of patients who discontinue treatment do so for reasons associated with inefficacy, an analysis based on the ITT approach more closely reflects the outcomes of the patients.

Overwhelming heterogeneity in systematic reviews of observational anti-epileptic studies.

PURPOSE: Observational studies may provide important information on the long-term effects of treatments for epilepsy, but systematic reviews of observational studies may be more prone to heterogeneity and biases. These issues were investigated in a systematic review of non-randomised add-on anti-epileptic drug studies. METHODS: Searches of MEDLINE (1966-2006), EMBASE (1974-2006), CINAHL (1982-2006), the Cochrane database of systematic reviews, the Cochrane Controlled Trials register, the DARE database and hand-searching congress proceedings were conducted. Randomised controlled trials, follow-on randomised controlled trials and prospective and retrospective cohort studies of gabapentin, topiramate, or levetiracetam as add-on therapy in adults (>12 years old) were identified. Outcomes were 50% responders and proportion seizure free. RESULTS: Thirty-eight non-randomised gabapentin studies, 82 topiramate and 84 levetiracetam studies were identified. There was marked heterogeneity of effect estimates from observational studies which prohibited the pooling of estimates in random effects models. Median effect estimates were larger and more varied for observational studies than randomised placebo-controlled trials (RCTs). For example, the median value (10th and 90th percentile) for 50% responders for gabapentin was 36% (15 and 71%) compared to 23% (19 and 38%) for gabapentin RCTs. Patient and study covariates in meta-regression models could not explain the vast heterogeneity. Publication bias was evident and a sensitivity analysis, allowing for the effects of publication bias, showed that effect estimates could increase by up to 6% for seizure freedom rates. DISCUSSION: Reports of observational anti-epileptic studies give limited information on patient selection and characteristics. Systematic reviews of observational studies are prone to significant heterogeneity and bias which cannot adequately be explained by reported study characteristics. Reporting standards for observational studies of anti-epileptic drugs could be improved by following guidelines for reporting non-randomised studies of interventions.

Synthesis and secretion of selenoprotein P by cultured rat astrocytes.

Selenoprotein P is an extracellular protein that has been postulated to have an oxidant defense function. It has survival-promoting properties for cultured neurons and its mRNA is present in the brain. This study sought to determine the primary structure of rat brain selenoprotein P and to assess its production by cultured brain cells. The cDNA of selenoprotein P was isolated from a rat brain cDNA library and was found to encode the same peptide sequence as rat liver cDNA. Thus the primary structure of brain selenoprotein P is the same as selenoprotein P from liver. Astrocytes and a cerebellar granule cell preparation (CGC) were obtained from rat brains and established in culture. The CGC was estimated to contain up to 5% glial cells. Both preparations were shown to contain selenoprotein P mRNA. During incubation with (75)Se-labeled selenite, both cell preparations secreted a (75)Se-labeled protein into the medium that corresponded in size to selenoprotein P. Also, the (75)Se-labeled protein could be precipitated from both media with an antiserum to selenoprotein P. This shows that astrocytes and the CGC secrete selenoprotein P. Selenoprotein P is made in the brain and may have an oxidant defense function there.

The development of allergy in high-risk children.

BACKGROUND: It is uncertain as to what extent the development of allergic disease in childhood is predictable during early infancy. A number of environmental factors have been suspected of increasing the risk of acquiring allergy, but the evidence is conflicting. OBJECTIVE: To observe the development of atopy and allergic disease in a cohort of high-risk children so as to determine the importance of certain environmental factors and to study the relationship between early and later manifestations. METHODS: A cohort of infants, all at high risk of allergy, was followed up from birth to the age of 7 years. In half, selected at random, cow's milk protein was avoided for 4 months. Skin-prick tests were performed and serum IgE measured in infancy and at 7 years, when an AlaTOP test was also performed. RESULTS: Skin sensitivity to egg in the first year of life was strongly associated with eczema, asthma, mite sensitivity and serum IgE at the age of 7 years, when mother's atopic history was associated with AlaTOP status, father's atopic history with skin sensitivity, and male sex with both. Maternal smoking during pregnancy was associated positively with IgE at 3 months and negatively with skin sensitivity at 7 years. The development of allergy was unrelated to infant feeding method or number of older siblings. CONCLUSION: Allergic disease in childhood is to a large degree determined before birth or during infancy.

The effect of monovalent cations on the self-association of cytidylyl-(3-5')-guanosine and guanylyl-(3'5')-cytidine in aqueous solution.

The hydrogen-bonding, base stacking, and formation of extended aggregates has been investigated for salts of guanylyl-3'-5')-cytidine, GpC, and cytidylyl-(3'-5')- guanosine, CpG, in which the cation was Na+, K+, or tetramethylammonium (TMA+). Variable temperature studies were done at 2-70 degrees C on aqueous solutions at pD4 and 8 using 1H NMR and FTIR. At low temperatures it has been found that at pD 8 both GpC and CpG form Watson-Crick dimers which stack upon each other to form larger species. A slight cation effect is observed below 35 degrees C which has the order: TMA+ > Na+ > K+. This order suggests that the cations are interacting with the phosphate and interactions with the bases are unlikely. The 1H NMR spectrum for TMACpG at pD 4 has been assigned and exhibits chemical shift differences from those at pD 8 which are consistent with protonation of the N3 of the cytidine residue. Based on NMR line broadening, CpG at pD 4 has a greater degree of self-association at low temperature than it or GpC have at pD 8. A different type of hydrogen bonding and self-association occur in CpG at pD 4 compared to pD 8, but the structures are uncertain. Due to hemi-protonation of the cytidine N3, parallel G-G/C-C+ base paired dimers or G-tetrads may be forming.

Infant feeding, wheezing, and allergy: a prospective study.

The determinants of wheezing and allergy were investigated in 453 children with a family history of allergic disease. A randomised controlled trial examined the effects of withholding cows' milk protein during the first three months of life and replacing cows' milk with soya milk. The children were followed up to the age of 7 years. Withholding cows' milk did not reduce the incidence of allergy or wheezing. Children who had ever been breast fed had a lower incidence of wheeze than those who had not (59% and 74% respectively). The effect persisted to age 7 years in the non-atopics only, the risk of wheeze being halved in the breast fed children after allowing for employment status, sex passive smoking, and overcrowding. Allergic disease was not associated with exposure to tobacco smoke, house dust mite antigen, or cats. Breast feeding may confer long term protection against respiratory infection.

Interstitial deletion of 17p11.2: case report and review.

A child with mental retardation and multiple congenital abnormalities, including brachycephaly, an unusual facies, brachydactyly, clinodactyly and bilateral talipes valgus, was found to have a small interstitial deletion of the short arm of chromosome 17. The clinical features and cytogenetic observations are compared with those in previously reported cases.

Cytological detection of the basis of uniparental inheritance of plastid DNA in Chlamydomonas moewusii.

By using the fluorochrome 4'-6-diamidino-2-phenylindole (DAPI) to stain DNA one can follow the pattern of events affecting plastid DNA which occur in the formation and maturation of individual zygotes of the green flagellate Chlamydomonas moewusii. This species, like C. reinhardi, expresses uniparental inheritance of plastid DNA characters among zygote progeny, and is particularly favorable for cytological observation because the locale of the contribution of each gamete can still be recognized in mature zygotes. Gametes contribute equal numbers of DNA nucleoids, and amounts of plastid DNA (as measured by DAPI-DNA micro spectrofluorometry), to the zygote at fusion. Starting at nine hours, coincident with the further fusion of cell contents, plastid DNA disappears from the plastid contributed by one gamete. Further slow coalescence of nucleoids leads to a final nucleoid number per zygote approximately 1/3 of the sum of the 2 gametes.The DNA loss from one gamete plastid may require plastid contact to be initiated. Both light and nutrient availability affect the final number and distribution of plastid DNA nucleoids in the mature zygote. These observations are related to known genetic and biochemical data on uniparental inheritance of plastid characters.

Mithramycin- and 4'-6-diamidino-2-phenylindole (DAPI)-DNA staining for fluorescence microspectrophotometric measurement of DNA in nuclei, plastids, and virus particles.

The properties of two DNA-specific fluorochromes, 4'-6-diamidino-2-phenylindole (DAPI) and mithramycin, have been analyzed as reagents to quantitate cellular DNA by fluorescence microspectrophotometry. Optimal staining conditions and concentrations, and the effects of other cellular materials to which the dyes bind, have been evaluated in measurements of the DNA of rat, chick, and yeast nuclei, Gonyostomum chloroplasts, and T4 particles. Use of either fluorochrome permits a high degree of resolution of different DNA quantities in nuclei and in cell organelles, and the DAPI-DNA complex is sufficiently fluorescent to permit quantitation of the DNA content in genomes as small as those of individual T4 bacteriophage particles. Fluorescence of mithramycin- or DAPI-stained DNA is proportional to DNA quantity when DNA of the same has composition is compared. Quantitation does not appear to be affected discernably by the state of the DNA, whether in different stages of the cell cycle, in condensed chromosomes, or in noncycling, differentiated nuclei. The use of chicken red blood cells is recommended as an internal monitor for variations in staining conditions.

Amoxycillin injection in the treatment of pyogenic meningitis in children.

An open trial of the use of amoxycillin injection in the treatment of pyogenic meningitis in children showed similar results to previous trials here of penicillin-chloramphenicol combinations. It is felt that, in developing countries at least, treatment of pyogenic meningitis in children should be with the latter combination, but where rapid and accurate bacteriology is available amoxycillin may be valuable non-toxic alternative to chloramphenicol with similar activity to ampicillin.

Empyema in children in tropics.

Thirty-six cases of empyema were diagnosed in children over a two year period, giving an overall incidence of 0.11% of the total hospital admissions. Many of them had measles bronchopneumonia and most were malnourished. 16 children had penicillin resistant staphylococcal infection. 29 of them were treated with closed tube drainage. Thirteen died during the course of treatment, the majority within three days of admission. The rest were followed up over a period of up to six months and showed good recovery. Six of these patients developed pneumothorax during the course of treatment. Various combinations of Ampicillin, Cloxacillin, Gentamycin and Cotrimoxazole parenterally were used. Supportive treatment with blood transfusion was found to be beneficial.

Intra- thecal antitetanus serum in the management of tetanus neonatorum.

Eleven neonates have treated with intra-thecal antitetanus serum in addition to other standard measures. Five survived. The results were judged promising.