A meta-analysis of the association between Caesarean section and childhood asthma

Background: Children born by Caesarean section have modified intestinal bacterial colonization and consequently may have an increased risk of developing asthma under the hygiene hypothesis. The results of previous studies that have investigated the association between Caesarean section and asthma have been conflicting.

Objective: To review published literature and perform a meta-analysis summarizing the evidence in support of an association between children born by Caesarean section and asthma.

Methods: MEDLINE, Web Science, Google Scholar and PubMed were searched to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were calculated for each study from the reported prevalence of asthma in children born by Caesarean section and in control children. Meta-analysis was then used to derive a combined OR and test for heterogeneity in the findings between studies.

Results: Twenty-three studies were identified. The overall meta-analysis revealed an increase in the risk of asthma in children delivered by Caesarean section (OR=1.22, 95% CI 1.14, 1.29). However, in this analysis, there was evidence of heterogeneity (I2=46%) that was statistically significant (P<0.001). Restricting the analysis to childhood studies, this heterogeneity was markedly decreased (I2=32%) and no longer attained statistical significance (P=0.08). In these studies, there was also evidence of an increase (P<0.001) in the risk of asthma after Caesarean section (OR=1.20, 95% CI 1.14, 12.6).

Conclusion: In this meta-analysis, we found a 20% increase in the subsequent risk of asthma in children who had been delivered by Caesarean section.

Adaptive automated construction of hybrid heuristics for exam timetabling and graph colouring problems

In this paper, we present a random iterative graph based hyper-heuristic to produce a collection of heuristic sequences to construct solutions of different quality. These heuristic sequences can be seen as dynamic hybridisations of different graph colouring heuristics that construct solutions step by step. Based on these sequences, we statistically analyse the way in which graph colouring heuristics are automatically hybridised. This, to our knowledge, represents a new direction in hyper-heuristic research. It is observed that spending the search effort on hybridising Largest Weighted Degree with Saturation Degree at the early stage of solution construction tends to generate high quality solutions. Based on these observations, an iterative hybrid approach is developed to adaptively hybridise these two graph colouring heuristics at different stages of solution construction. The overall aim here is to automate the heuristic design process, which draws upon an emerging research theme on developing computer methods to design and adapt heuristics automatically. Experimental results on benchmark exam timetabling and graph colouring problems demonstrate the effectiveness and generality of this adaptive hybrid approach compared with previous methods on automatically generating and adapting heuristics. Indeed, we also show that the approach is competitive with the state of the art human produced methods.

Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant

AIMS
The aim of this study was to investigate the in?uence of genetic polymorphisms in ABCB1 on the incidence of nephrotoxicity and tacrolimus dosage-requirements in paediatric patients following liver transplantation.
METHODS
Fifty-one paediatric liver transplant recipients receiving tacrolimus were genotyped for ABCB1 C1236>T, G2677>T and C3435>T polymorphisms. Dose-adjusted tacrolimus trough concentrations and estimated glomerular ?ltration rates (EGFR) indicative of renal toxicity were determined and correlated with the corresponding genotypes.
RESULTS
The present study revealed a higher incidence of the ABCB1 variant-alleles examined among patients with renal dysfunction (30% reduction in EGFR) at 6 months post-transplantation (1236T allele: 63.3% vs 37.5% in controls,P = 0.019; 2677T allele: 63.3% vs. 35.9%, p = 0.012; 3435T allele: 60% vs. 39.1%,P = 0.057). Carriers of the G2677->T variant allele also had a signi?cant reduction (%) in EGFR at 12 months post-transplant (mean difference = 22.6%; P = 0.031). Haplotype analysis showed a signi?cant association between T-T-T haplotypes and an increased incidence of nephrotoxicity at 6 months post-transplantation (haplotype-frequency = 52.9% in nephrotoxic patients vs 29.4% in controls; P = 0.029). Furthermore, G2677->T and C3435->T polymorphisms and T-T-T haplotypes were signi?cantly correlated with higher tacrolimus dose-adjusted pre-dose concentrations at various time points examined long after drug initiation.
CONCLUSIONS
These ?ndings suggest that ABCB1 polymorphisms in the native intestine signi?cantly in?uence tacrolimus dosage-requirement in the stable phase after transplantation. In addition, ABCB1 polymorphisms in paediatric liver transplant recipients may predispose them to nephrotoxicity over the ?rst year posttransplantation. Genotyping future transplant recipients for ABCB1 polymorphisms, therefore, could have the potential to individualize better tacrolimus immunosuppressive therapy and enhance drug safety