Safety and efficacy of physiologist-led dobutamine stress echocardiography: experience from a tertiary cardiac centre

Background: Dobutamine stress echocardiography (DSE) services have traditionally been medically led. In some UK institutions, DSE lists are led by physiologists with medical support. In our tertiary cardiac centre at New Cross Hospital (NCH), the DSE service was established by a consultant echocardiographer. Following intensive training and assessment, the Trust approved drug administration by named senior cardiac physiologists. We believe this is the first report of a cardiac physiologist-managed DSE service, including physiologist drug administration. We have assessed the feasibility, safety and validity of this physiologist-led DSE service. Methods: Retrospective analysis of 333 patients undergoing stress echocardiogram for inducible reversible ischaemia, myocardial viability and valvular heart disease over 6 months. Patients’ case notes review after 18–24 months. Results: Overall, 92% of all cases (306) were performed by physiologists. In 300 studies, dobutamine was administered. The majority of the referrals were for coronary artery disease (CAD) assessment (281). In 235 cases, the study was uncomplicated. Sixty-seven patients developed dobutamine-related side effects. In 16 cases, complications led to early termination of the study. In two cases, urgent medical review was needed. Of the 281 studies for CAD assessment, 239 were negative for ischaemia, 28 were positive and 14 inconclusive. In 5 out of 28 cases with echocardiogram, evidence of inducible ischaemia, coronary angiography revealed unobstructed coronary arteries. Conclusion: This study demonstrates the safety and effectiveness of this practice and provides potential for the expansion of the physiologists’ role and physiologist-led DSE services in other hospitals

Comparative Analysis of Pyrosequencing and a Phylogenetic Microarray for Exploring Microbial Community Structures in the Human Distal Intestine

Background Variations in the composition of the human intestinal microbiota are linked to diverse health conditions. High-throughput molecular technologies have recently elucidated microbial community structure at much higher resolution than was previously possible. Here we compare two such methods, pyrosequencing and a phylogenetic array, and evaluate classifications based on two variable 16S rRNA gene regions. Methods and Findings Over 1.75 million amplicon sequences were generated from the V4 and V6 regions of 16S rRNA genes in bacterial DNA extracted from four fecal samples of elderly individuals. The phylotype richness, for individual samples, was 1,400–1,800 for V4 reads and 12,500 for V6 reads, and 5,200 unique phylotypes when combining V4 reads from all samples. The RDP-classifier was more efficient for the V4 than for the far less conserved and shorter V6 region, but differences in community structure also affected efficiency. Even when analyzing only 20% of the reads, the majority of the microbial diversity was captured in two samples tested. DNA from the four samples was hybridized against the Human Intestinal Tract (HIT) Chip, a phylogenetic microarray for community profiling. Comparison of clustering of genus counts from pyrosequencing and HITChip data revealed highly similar profiles. Furthermore, correlations of sequence abundance and hybridization signal intensities were very high for lower-order ranks, but lower at family-level, which was probably due to ambiguous taxonomic groupings. Conclusions The RDP-classifier consistently assigned most V4 sequences from human intestinal samples down to genus-level with good accuracy and speed. This is the deepest sequencing of single gastrointestinal samples reported to date, but microbial richness levels have still not leveled out. A majority of these diversities can also be captured with five times lower sampling-depth. HITChip hybridizations and resulting community profiles correlate well with pyrosequencing-based compositions, especially for lower-order ranks, indicating high robustness of both approaches. However, incompatible grouping schemes make exact comparison difficult

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Report from the Annual Conference of the British Society of Echocardiography, November 2017, Edinburgh International Conference Centre, Edinburgh

No abstract available

The DNA sequence of the human X chromosome

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence