Cardiac output measurement in children: comparison of Aesculon® cardiac output monitor and thermodilution

Background We compared cardiac output (CO) measurements by the non-invasive electrical velocimetry (Aesculon®) monitor with the pulmonary artery catheter (PAC) thermodilution method in children. Methods CO values using the Aesculon® monitor and PAC thermodilution were simultaneously recorded during cardiac catheterization in children. Measurements were performed under general anaesthesia. To compare, three consecutive measurements for each patient within 3 min were obtained. The means of the three values were compared using simple regression and Bland-Altman analysis. Data were presented as mean (sd). A mean percentage of <30% was defined to indicate clinical useful reliability of the Aesculon® monitor. Results A total of 50 patients with a median (range) age of 7.5 (0.5-16.5) yr were enrolled in the study. Mean CO values were 3.7 (1.5) litre min−1 (PAC thermodilution) and 3.1 (1.7) litre min−1 (Aesculon® monitor). Analysis for CO measurement showed a good correlation between the two methods (r=0.894; P<0.0001). The bias between the two methods was 0.66 litre min−1 with a precision of 1.49 litre min−1. The mean percentage error for CO measurements was 48.9% for the Aesculon® monitor when compared with PAC thermodilution. Conclusions Electrical velocimetry using the Aesculon® monitor did not provide reliable CO values when compared with PAC thermodilution. Whether the Aesculon® monitor can be used as a CO trend monitor has to be assessed by further investigations in patients with changing haemodynamic

Tracheal tube-tip displacement in children during head-neck movement—a radiological assessment

Background. Aims of this study were to assess the maximum displacement of tracheal tube tip during head-neck movement in children, and to evaluate the appropriateness of the intubation depth marks on the Microcuff Paediatric Endotracheal Tube regarding the risk of inadvertent extubation and endobronchial intubation. Methods. We studied children, aged from birth to adolescence, undergoing cardiac catheterization. The patients' tracheas were orally intubated and the tracheal tubes positioned with the intubation depth mark at the level of the vocal cords. The tracheal tube tip-to-carina distances were fluoroscopically assessed with the patient supine and the head-neck in 30° flexion, 0° neutral position and 30° extension. Results. One hundred children aged between 0.02 and 16.4 yr (median 5.1 yr) were studied. Maximum tracheal tube-tip displacement after head-neck 30° extension and 30° flexion demonstrated a linear relationship to age [maximal upward tube movement (mm)=0 0.71×age (yr)+9.9 (R2=0.893); maximal downward tube movement (mm)=0.83×age (yr)+9.3 (R2=0.949)]. Maximal tracheal tube-tip downward displacement because of head-neck flexion was more pronounced than upward displacement because of head-neck extension. Conclusions. The intubation depth marks were appropriate to avoid inadvertent tracheal extubation and endobronchial intubation during head-neck movement in all patients. However, during head-neck extension the tracheal tube cuff may become positioned in the subglottic region and should be re-adjusted when the patient remains in this position for a longer tim

Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistance

Trypanosoma brucei rhodesiense (Tbr) and T. b. gambiense (Tbg), causative agents of Human African Trypanosomiasis (sleeping sickness) in Africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (TLFs), components of innate immunity in human serum that protect against infection by other African trypanosomes. In Tbr, lytic activity is suppressed by the Tbr-specific serum-resistance associated (SRA) protein. The mechanism in Tbg is less well understood but has been hypothesized to involve altered activity and expression of haptoglobin haemoglobin receptor (HpHbR). HpHbR has been shown to facilitate internalization of TLF-1 in T.b. brucei (Tbb), a member of the T. brucei species complex that is susceptible to human serum. By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1) and not found in related taxa, which are either human serum susceptible (Tbb) or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2). We hypothesize that this single substitution contributes to reduced uptake of TLF and thus may play a key role in conferring serum resistance to Tbg group 1. In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR functio

Population genetic structure of Schistosoma haematobium and Schistosoma haematobium x Schistosoma bovis hybrids among school-aged children in Côte d'Ivoire

While population genetics of Schistosoma haematobium have been investigated in West Africa, only scant data are available from Cote d'Ivoire. The purpose of this study was to analyze both genetic variability and genetic structure among S. haematobium populations and to quantify the frequency of S. haematobium x S. bovis hybrids in school-aged children in different parts of Cote d'Ivoire. Urine samples were subjected to a filtration method and examined microscopically for Schistosoma eggs in four sites in the western and southern parts of Cote d'Ivoire. A total of 2692 miracidia were collected individually and stored on Whatman((R)) FTA cards. Of these, 2561 miracidia were successfully genotyped for species and hybrid identification using rapid diagnostic multiplex mitochondrial cox1 PCR and PCR Restriction Fragment Length Polymorphism (PCR-RFLP) analysis of the nuclear ITS2 region. From 2164 miracidia, 1966 (90.9%) were successfully genotyped using at least 10 nuclear microsatellite loci to investigate genetic diversity and population structure. Significant differences were found between sites in all genetic diversity indices and genotypic differentiation was observed between the site in the West and the three sites in the East. Analysis at the infrapopulation level revealed clustering of parasite genotypes within individual children, particularly in Duekoue (West) and Sikensi (East). Of the six possible cox1-ITS2 genetic profiles obtained from miracidia, S. bovis cox1 x S. haematobium ITS2 (42.0%) was the most commonly observed in the populations. We identified only 15 miracidia (0.7%) with an S. bovis cox1 x S. bovis ITS2 genotype. Our study provides new insights into the population genetics of S. haematobium and S. haematobium x S. bovis hybrids in humans in Cote d'Ivoire and we advocate for researching hybrid schistosomes in animals such as rodents and cattle in Cote d'Ivoire

Population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci

African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda) and Southern (Malawi) Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics

"It's making contacts" : notions of social capital and implications for widening access to medical education

Acknowledgements Our thanks to the Medical Schools Council (MSC) of the UK for funding Study A; REACH Scotland for funding Study B; and Queen Mary University of London, and to the medical school applicants and students who gave their time to be interviewed. Our thanks also to Dr Sean Zhou and Dr Sally Curtis, and Manjul Medhi, for their help with data collection for studies A and B respectively. Our thanks also to Dr Lara Varpio, Uniformed Services University of the USA, for her advice and guidance on collating data sets and her comments on the draft manuscript.Peer reviewedPublisher PD

Phylogeography and Taxonomy of Trypanosoma brucei

Trypanosoma brucei, the parasite causing human African trypanosomiasis (sleeping sickness) across sub-Saharan Africa is traditionally split into three subspecies: T. b. gambiense (Tbg), causing a chronic form of human disease in West and Central Africa; T. b. rhodesiense (Tbr), causing an acute form of human disease in East and Southern Africa; and T. b. brucei (Tbb), which is restricted to animals. Tbg is further split into Tbg group 1 and Tbg group 2. Better understanding the evolutionary relationships between these groups may help to shed light on the epidemiology of sleeping sickness. Here, we used three different types of genetic markers to investigate the phylogeographic relationships among the four groups across a large portion of their range. Our results confirm the distinctiveness of Tbg group 1 while highlighting the extremely close relationships among the other three taxa. In particular, Tbg group 2 was closely related to Tbb, while Tbr appeared to be a variant of Tbb, differing only in its phenotype of human infectivity. The wide geographic distribution of the gene conferring human infectivity (SRA) and the fact that it is readily exchanged among lineages of T. brucei in eastern Africa suggests that human-infective trypanosomes have access to an extensive gene pool with which to respond to selective pressures such as drugs

Credit bureaus between risk-management, creditworthiness assessment and prudential supervision

"This text may be downloaded for personal research purposes only. Any additional reproduction for other purposes, whether in hard copy or electronically, requires the consent of the author. If cited or quoted, reference should be made to the full name of the author, the title, the working paper or other series, the year, and the publisher."This paper discusses the role and operations of consumer Credit Bureaus in the European Union in the context of the economic theories, policies and law within which they work. Across Europe there is no common practice of sharing the credit data of consumers which can be used for several purposes. Mostly, they are used by the lending industry as a practice of creditworthiness assessment or as a risk-management tool to underwrite borrowing decisions or price risk. However, the type, breath, and depth of information differ greatly from country to country. In some Member States, consumer data are part of a broader information centralisation system for the prudential supervision of banks and the financial system as a whole. Despite EU rules on credit to consumers for the creation of the internal market, the underlying consumer data infrastructure remains fragmented at national level, failing to achieve univocal, common, or defined policy objectives under a harmonised legal framework. Likewise, the establishment of the Banking Union and the prudential supervision of the Euro area demand standardisation and convergence of the data used to measure debt levels, arrears, and delinquencies. The many functions and usages of credit data suggest that the policy goals to be achieved should inform the legal and institutional framework of Credit Bureaus, as well as the design and use of the databases. This is also because fundamental rights and consumer protection concerns arise from the sharing of credit data and their expanding use

Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The three sub-species of &lt;i&gt;Trypanosoma brucei&lt;/i&gt; are important pathogens of sub-Saharan Africa. &lt;i&gt;T. b. brucei&lt;/i&gt; is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. &lt;i&gt;T. b. rhodesiense&lt;/i&gt; and &lt;i&gt;T. b. gambiense&lt;/i&gt; are able to resist lysis by TLF. There are two distinct sub-groups of &lt;i&gt;T. b. gambiense&lt;/i&gt; that differ genetically and by human serum resistance phenotypes. Group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (&lt;i&gt;HpHbR&lt;/i&gt;)) gene. Here we investigate if this is also true in group 2 parasites.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology:&lt;/b&gt; Isogenic resistant and sensitive group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the &lt;i&gt;HpHbR&lt;/i&gt; gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to &lt;i&gt;T. b. brucei&lt;/i&gt;. Both resistant and sensitive group 2, as well as group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt;, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data indicate that, despite group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of &lt;i&gt;HpHbR&lt;/i&gt;. Thus there are differences in the mechanism of human serum resistance between &lt;i&gt;T. b. gambiense&lt;/i&gt; groups 1 and 2.&lt;/p&gt

Multiple evolutionary origins of Trypanosoma evansi in Kenya

Trypanosoma evansi is the parasite causing surra, a form of trypanosomiasis in camels and other livestock, and a serious economic burden in Kenya and many other parts of the world. Trypanosoma evansi transmission can be sustained mechanically by tabanid and Stomoxys biting flies, whereas the closely related African trypanosomes T. brucei brucei and T. b. rhodesiense require cyclical development in tsetse flies (genus Glossina) for transmission. In this study, we investigated the evolutionary origins of T. evansi. We used 15 polymorphic microsatellites to quantify levels and patterns of genetic diversity among 41 T. evansi isolates and 66 isolates of T. b. brucei (n = 51) and T. b. rhodesiense (n = 15), including many from Kenya, a region where T. evansi may have evolved from T. brucei. We found that T. evansi strains belong to at least two distinct T. brucei genetic units and contain genetic diversity that is similar to that in T. brucei strains. Results indicated that the 41 T. evansi isolates originated from multiple T. brucei strains from different genetic backgrounds, implying independent origins of T. evansi from T. brucei strains. This surprising finding further suggested that the acquisition of the ability of T. evansi to be transmitted mechanically, and thus the ability to escape the obligate link with the African tsetse fly vector, has occurred repeatedly. These findings, if confirmed, have epidemiological implications, as T. brucei strains from different genetic backgrounds can become either causative agents of a dangerous, cosmopolitan livestock disease or of a lethal human disease, like for T. b. rhodesiense