Clinical prediction models

Objective!#!The aim of this study was to evaluate the validity of a semiautomated volumetric approach (5DCNS+) for the detailed assessment of the fetal brain in a clinical setting.!##!Methods!#!Stored 3D volumes of > 1100 consecutive 2nd and 3rd trimester pregnancies (range 15-36 gestational weeks) were analyzed using a workflow-based volumetric approach 5DCNS+, enabling semiautomated reconstruction of diagnostic planes of the fetal central nervous system (CNS). All 3D data sets were examined for plane accuracy, the need for manual adjustment, and fetal-maternal characteristics affecting successful plane reconstruction. We also examined the potential of these standardized views to give additional information on proper gyration and sulci formation with advancing gestation.!##!Results!#!Based on our data, we were able to show that gestational age with an OR of 1.085 (95% CI 1.041-1.132) and maternal BMI with an OR of 1.022 (95% CI 1.041-1.054) only had a slight impact on the number of manual adjustments needed to reconstruct the complete volume, while maternal age and fetal position during acquisition (p = 0.260) did not have a significant effect. For the vast majority (958/1019; 94%) of volumes, using 5DCNS+ resulted in proper reconstruction of all nine diagnostic planes. In less than 1% (89/9171 planes) of volumes, the program failed to give sufficient information. 5DCNS+ was able to show the onset and changing appearance of CNS folding in a detailed and timely manner (lateral/parietooccipital sulcus formation seen in < 65% at 16-17 gestational weeks vs. 94.6% at 19 weeks).!##!Conclusions!#!The 5DCNS+ method provides a reliable algorithm to produce detailed, 3D volume-based assessments of fetal CNS integrity through a standardized reconstruction of the orthogonal diagnostic planes. The method further gives valid and reproducible information regarding ongoing cortical development retrieved from these volume sets that might aid in earlier in utero recognition of subtle structural CNS anomalies

Opening and closure of intraventricular neuroendoscopic procedures in infants under 1 year of age: institutional technique, case series and review of the literature

Purpose: Intraventricular neuroendoscopic techniques, particularly third ventriculostomy, are employed increasingly in the management of infantile hydrocephalus. However, surgical access to the ventricular cavities is associated with a risk of post-operative cerebrospinal fluid (CSF) leak. Here, we describe a structured, multi-layered approach to wound opening and closure which aims to maximise the natural tissue barriers against CSF leakage. We present a series of patients undergoing this technique and subsequently review the literature regarding opening and closure techniques in paediatric intraventricular neuroendoscopic procedures. Methods: We performed a retrospective case series analysis of patients under 1 year of age who underwent intraventricular neuroendoscopic procedures in a single institution over a 5-year period. Patients were identified from an institutional operative database, and operation notes and clinical records were subsequently reviewed. Results: 28 patients fulfilled the inclusion criteria for this study. The mean age at operation was 9 weeks. 27 patients underwent endoscopic third ventriculostomy whilst 1 underwent endoscopic septostomy, and all patients underwent our structured, multi-layered opening and closure technique. Follow-up ranged from 4 months to 5 years. There were no cases of post-operative CSF leak, infection or wound breakdown. 12 patients remained shunt-free at the last follow-up, with the remaining 16 requiring shunt insertion for progressive hydrocephalus at a mean of 24 days post-operatively. Conclusion: Various methods aiming to prevent post-operative CSF leak have been reported in the literature. We propose that our institutional technique may be of benefit in minimising this risk in infants undergoing endoscopic third ventriculostomy and similar intraventricular neuroendoscopic procedures

The landscape of inherited and de novo copy number variants in a plasmodium falciparum genetic cross

<p>Abstract</p> <p>Background</p> <p>Copy number is a major source of genome variation with important evolutionary implications. Consequently, it is essential to determine copy number variant (CNV) behavior, distributions and frequencies across genomes to understand their origins in both evolutionary and generational time frames. We use comparative genomic hybridization (CGH) microarray and the resolution provided by a segregating population of cloned progeny lines of the malaria parasite, <it>Plasmodium falciparum</it>, to identify and analyze the inheritance of 170 genome-wide CNVs.</p> <p>Results</p> <p>We describe CNVs in progeny clones derived from both Mendelian (i.e. inherited) and non-Mendelian mechanisms. Forty-five CNVs were present in the parent lines and segregated in the progeny population. Furthermore, extensive variation that did not conform to strict Mendelian inheritance patterns was observed. 124 CNVs were called in one or more progeny but in neither parent: we observed CNVs in more than one progeny clone that were not identified in either parent, located more frequently in the telomeric-subtelomeric regions of chromosomes and singleton <it>de novo </it>CNVs distributed evenly throughout the genome. Linkage analysis of CNVs revealed dynamic copy number fluctuations and suggested mechanisms that could have generated them. Five of 12 previously identified expression quantitative trait loci (eQTL) hotspots coincide with CNVs, demonstrating the potential for broad influence of CNV on the transcriptional program and phenotypic variation.</p> <p>Conclusions</p> <p>CNVs are a significant source of segregating and <it>de novo </it>genome variation involving hundreds of genes. Examination of progeny genome segments provides a framework to assess the extent and possible origins of CNVs. This segregating genetic system reveals the breadth, distribution and dynamics of CNVs in a surprisingly plastic parasite genome, providing a new perspective on the sources of diversity in parasite populations.</p