932 research outputs found
rRNA sequencing in molecular microbiological diagnosis of bacterial infections in the autopsy setting
Diagnosing the aetiology of infectious diseases at autopsy, such as pneumonia, meningitis, sepsis or SUDI, is complicated due to issues including post mortem contamination, difficulty culturing fastidious organisms and subjective interpretation of polymicrobial cultures. Death of organisms may also occur post mortem, especially if antibiotics were given to the patient, but residual DNA from non-viable organisms, amenable to molecular detection, may remain. The 16S rRNA gene is present in all bacteria with conserved and hyper-variable regions along its length, allowing amplification and sequencing of all bacterial 16S sequences present in a sample. 16S sequencing offers potential advantages over culture-based diagnostics and is increasingly used in clinical practice. It has been used to identify bacteria in formalin fixed paraffin embedded (FFPE) surgical pathology specimens but its use has not been reported in autopsy diagnosis. This talk will summarise a study aimed to assess the utility of 16S sequencing as an adjunctive microbiological test in the autopsy. Our preliminary work has used post mortem lung tissue samples from children dying with pneumonia as part of the Pneumonia Etiology Research for Child Health (PERCH) project. The technique has identified known pathogens in some cases and provided additional diagnostic information in others. The presentation will discuss the technical aspects of 16S sequencing from FFPE and autopsy material, and the issues surrounding its application to diagnosis in comparison with standard culture based diagnostics on surgical/autopsy material
High frequency diffraction of an electromagnetic plane wave by an imperfectly conducting rectangular cylinder
Copyright @ 2011 IEEEWe shall consider the the problem of determining the scattered far wave field produced when a plane E-polarized wave is incident on an imperfectly conducting rectangular cylinder. By using the the uniform asymptotic solution for the problem of the diffraction of a plane wave by a right-angled impedance wedge, in conjunction with Keller's method, the a high frequency far field solution to the problem is given
A bifurcation analysis of a modified neural field model: conductance-based synapses act as an anti-epileptic regulatory mechanism
The effect of network structure on epileptic dynamics: analysis of the synchronisation properties of an inter-network of cortical columns
Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth.
The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2-29.8) mm; P = 0.004; n = 361]. Significant associations were also found between the maternally inherited African-specific SNP 28 (rs5506) allele and post-natal weight gain [effect size 0.19 (0.05-0.32) z score points/year; P = 0.005; n = 728). These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits
The perturbation response and power spectrum of a mean-field of IF neurons with inhomogeneous inputs
Massive migration from the steppe is a source for Indo-European languages in Europe
We generated genome-wide data from 69 Europeans who lived between 8,000-3,000
years ago by enriching ancient DNA libraries for a target set of almost four
hundred thousand polymorphisms. Enrichment of these positions decreases the
sequencing required for genome-wide ancient DNA analysis by a median of around
250-fold, allowing us to study an order of magnitude more individuals than
previous studies and to obtain new insights about the past. We show that the
populations of western and far eastern Europe followed opposite trajectories
between 8,000-5,000 years ago. At the beginning of the Neolithic period in
Europe, ~8,000-7,000 years ago, closely related groups of early farmers
appeared in Germany, Hungary, and Spain, different from indigenous
hunter-gatherers, whereas Russia was inhabited by a distinctive population of
hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By
~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred
throughout much of Europe, but in Russia, the Yamnaya steppe herders of this
time were descended not only from the preceding eastern European
hunter-gatherers, but from a population of Near Eastern ancestry. Western and
Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded
Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya,
documenting a massive migration into the heartland of Europe from its eastern
periphery. This steppe ancestry persisted in all sampled central Europeans
until at least ~3,000 years ago, and is ubiquitous in present-day Europeans.
These results provide support for the theory of a steppe origin of at least
some of the Indo-European languages of Europe
Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G
Background:
The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised.
Methodology/Principal Findings:
We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy.
Conclusions/Significance:
We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality
Proctors exploit three-dimensional ghost tools during clinical-like training scenarios: a preliminary study
Selection of Medical Diagnostic Codes for Analysis of Electronic Patient Records. Application to Stroke in a Primary Care Database
BACKGROUND: Electronic patient records from primary care databases are increasingly used in public health and health services research but methods used to identify cases with disease are not well described. This study aimed to evaluate the relevance of different codes for the identification of acute stroke in a primary care database, and to evaluate trends in the use of different codes over time.METHODS: Data were obtained from the General Practice Research Database from 1997 to 2006. All subjects had a minimum of 24 months of up-to-standard record before the first recorded stroke diagnosis. Initially, we identified stroke cases using a supplemented version of the set of codes for prevalent stroke used by the Office for National Statistics in Key health statistics from general practice 1998 (ONS codes). The ONS codes were then independently reviewed by four raters and a restricted set of 121 codes for 'acute stroke' was identified but the kappa statistic was low at 0.23.RESULTS: Initial extraction of data using the ONS codes gave 48,239 cases of stroke from 1997 to 2006. Application of the restricted set of codes reduced this to 39,424 cases. There were 2,288 cases whose index medical codes were for 'stroke annual review' and 3,112 for 'stroke monitoring'. The frequency of stroke review and monitoring codes as index codes increased from 9 per year in 1997 to 1,612 in 2004, 1,530 in 2005 and 1,424 in 2006. The one year mortality of cases with the restricted set of codes was 29.1% but for 'stroke annual review,' 4.6% and for 'stroke monitoring codes', 5.7%.CONCLUSION: In the analysis of electronic patient records, different medical codes for a single condition may have varying clinical and prognostic significance; utilisation of different medical codes may change over time; researchers with differing clinical or epidemiological experience may have differing interpretations of the relevance of particular codes. There is a need for greater transparency in the selection of sets of codes for different conditions, for the reporting of sensitivity analyses using different sets of codes, as well as sharing of code sets among researchers
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