Impact of Asthma on Educational Attainment in a Socioeconomically Deprived Population: A Study Linking Health,Education and Social Care Datasets

Background

Asthma has the potential to adversely affect children''s school examination performance, and hence longer term life chances. Asthma morbidity is especially high amongst UK ethnic minority children and those experiencing social adversity, populations which also have poor educational outcomes. We tested the hypothesis that asthma adversely affects performance in national school examinations in a large cohort from an area of ethnic diversity and social deprivation.

Methods and Findings

With a novel method (using patient and address-matching algorithms) we linked administrative and clinical data for 2002–2005 for children in east London aged 5–14 years to contemporaneous education and social care datasets. We modelled children''s performance in school examinations in relation to socio-demographic and clinical variables.The dataset captured examination performance for 12,136 children who sat at least one national examination at Key Stages 1–3. For illustration, estimates are presented as percentage changes in Key Stage 2 results. Having asthma was associated with a 1.1% increase in examination scores (95%CI 0.4 to 1.7)%,p = 0.02. Worse scores were associated with Bangladeshi ethnicity −1.3%(−2.5 to −0.1)%,p = 0.03; special educational need −14.6%(−15.7 to −13.5)%,p = 0.02; mental health problems −2.5%(−4.1 to −0.9)%,p = 0.003, and social adversity: living in a smoking household −1.2(−1.7 to −0.6)%,p<0.001; living in social housing −0.8%(−1.3 to −0.2)% p = 0.01, and entitlement to free school meals −0.8%(−1.5 to −0.1)%,p<0.001.

Conclusions

Social adversity and ethnicity, but not asthma, are associated with poorer performance in national school examinations. Policies to improve educational attainment in socially deprived areas should focus on these factors.     

JOCB Bulletin

JOCB Bulletin

JOCB Bulletin     

Pharmacological concentrations of ascorbate radiosensitize glioblastoma multiforme primary cells by increasing oxidative DNA damage and inhibiting G2/M arrest

Glioblastoma multiforme (GBM) has a very poor prognosis because of its chemo- and radiation therapy resistance. Here we investigated the ability of pharmacological concentrations of ascorbate to radiosensitize primary cells isolated from six GBM patients, mouse astrocytoma cells, and mouse astrocytes. We measured cell viability by trypan blue exclusion, generation of double-stranded DNA breaks by H2AX phosphorylation using fluorescently labeled antibodies and FACS analysis, apoptosis by annexin V/propidium iodide staining, inhibition of autophagy by 3-methyladenine, and cell cycle progression by propidium iodide staining of permeabilized cells. We showed that 5 mM ascorbate in combination with 6 Gy radiation killed more GBM primary cells by generating significantly more double-stranded breaks than either treatment alone (p<0.05). Combined treatment affected viability and double-stranded break generation in normal astrocytes to a much smaller extent. Radiation, but not 5 mM ascorbate, caused G2/M arrest in GBM cells and ascorbate prevented radiation-induced G2/M arrest in combined treatment. Cell death in response to 5 mM ascorbate or combination treatment was not mediated by apoptosis or autophagy. In conclusion, pharmacological concentrations of ascorbate radiosensitize GBM primary cells to a much greater extent than astrocytes; this large therapeutic ratio may be of clinical significance in radiation-resistant cancers.     

Preimplantation genetic diagnosis: State of the ART 2011

For the last 20 years, preimplantation genetic diagnosis (PGD) has been mostly performed on cleavage stage embryos after the biopsy of 1–2 cells and PCR and FISH have been used for the diagnosis. The main indications have been single gene disorders and inherited chromosome abnormalities. Preimplantation genetic screening (PGS) for aneuploidy is a technique that has used PGD technology to examine chromosomes in embryos from couples undergoing IVF with the aim of helping select the chromosomally ‘best’ embryo for transfer. It has been applied to patients of advanced maternal age, repeated implantation failure, repeated miscarriages and severe male factor infertility. Recent randomised controlled trials (RCTs) have shown that PGS performed on cleavage stage embryos for a variety of indications does not improve delivery rates. At the cleavage stage, the cells biopsied from the embryo are often not representative of the rest of the embryo due to chromosomal mosaicism. There has therefore been a move towards blastocyst and polar body biopsy, depending on the indication and regulations in specific countries (in some countries, biopsy of embryos is not allowed). Blastocyst biopsy has an added advantage as vitrification of blastocysts, even post biopsy, has been shown to be a very successful method of cryopreserving embryos. However, mosaicism is also observed in blastocysts. There have been dramatic changes in the method of diagnosing small numbers of cells for PGD. Both array-comparative genomic hybridisation and single nucleotide polymorphism arrays have been introduced clinically for PGD and PGS. For PGD, the use of SNP arrays brings with it ethical concerns as a large amount of genetic information will be available from each embryo. For PGS, RCTs need to be conducted using both array-CGH and SNP arrays to determine if either will result in an increase in delivery rates.     

The effect of staining on the immunoreactivity of nitrocellulose bound proteins

It was found that Coomassie blue staining of proteins electroblotted onto nitrocellulose resulted in a significant decrease in subsequent immunoreactivity, relative to unstained proteins. This was not uniform, and resulted in distortion of the pattern detected by immunoreaction as well as an overall decrease in sensitivity. Staining with amido black resulted in no such alteration. Additionally, it was observed that amido black is completely leached from the nitrocellulose strip during immunoreaction, whereas no leaching is apparent with Coomassie blue. This may contribute to the observed effect of staining on immunoreactivity.     

Comprehensive quality assessment approach for flow cytometric immunophenotyping of human lymphocytes

Flow cytometric immunophenotypic (IPT) evaluation has become an important adjunct to clinical patient management and epidemiological studies. This has precipitated a need for stringent quality assessment (QA) procedures to ascertain data integrity. We evaluated a QA approach to monitor all elements of the immunophenotyping process, inclusive of blood collection and processing procedures as well as of staining reagent and instrument performance. Central to our approach was preparation each day, in parallel with clinical analytes, of lymphocytes from healthy donors, selected from a 15 donor panel. IPT parameters evaluated over a 19 month period included frequencies of CD3+, CD4+, CD8+, and CD20+ lymphocytes and the ratio of CD4+ to CD8+ lymphocytes. The sensitivity for analytical error detection was reflected by median coefficients of variation of these parameters within individual panel donors, which were 4.1%, 4.5%, 3.9%, 8.2%, and 10.1%, respectively. IPT parameter values were determined each day for two of the panel donors, then averaged and standardized to obtain a quality or Q variate, which was the basis of QA. Error detection sensitivity decreased 0.6-1.7% and the number of false rejections increased 1.2-3.3% when one panel donor rather than two was used daily for QA. This study also illuminated important aspects of what constitutes the norm for longitudinal IPT parameter variation in healthy individuals including: 1) a generally low degree of temporal parameter variation within individual donors, but 2) significant differences between donors with respect to variance estimates for CD3+ and CD8+ lymphocyte frequencies and CD4+/CD8+ lymphocyte ratios, and 3) an apparent seasonal pattern of variation in CD4+ T-cell frequencies.