Frequency of cytokine gene promoter polymorphisms in the Northern Ireland Cystic Fibrosis population

It has been postulated that cytokine allele frequencies are gender and perhaps geographically-specific. Cytokine release is crucial in the regulation of the type and magnitude of the immune response. This study observed no differences in the frequency of cytokine promoter polymorphisms associated with variant levels of expression in patients with CIF and a non-CF population of Northern Ireland. (c) 2007 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa. Heredity (2010) 104, 148-154; doi:10.1038/hdy.2009.84; published online 29 July 2009

Data-driven optimal filtering for phase and frequency of noisy oscillations: Application to vortex flow metering

A method for measuring the phase of oscillations from noisy time series is proposed. To obtain the phase, the signal is filtered in such a way that the filter output has minimal relative variation in the amplitude over all filters with complex-valued impulse response. The argument of the filter output yields the phase. Implementation of the algorithm and interpretation of the result are discussed. We argue that the phase obtained by the proposed method has a low susceptibility to measurement noise and a low rate of artificial phase slips. The method is applied for the detection and classification of mode locking in vortex flow meters. A measure for the strength of mode locking is proposed.

The UK Renal Registry Advanced CKD Study: frequency of incorrect reporting of date of start of RRT

Background: A preliminary review of the UK Renal Registry (UKRR) pre-RRT study data revealed results suggesting that, for some patients, the date of start of renal replacement therapy (RRT), as reported to the UKRR, was incorrect and often significantly later than the true date of start. A more detailed study then aimed to validate a set of criteria to identify patients with an incorrect start date. Methods: Pre-RRT laboratory data were electronically extracted from 8,810 incident RRT patients from 9 UK renal centres. Any patient with a low urea (<15 mmol/L) at the start of RRT or with a substantial improvement in kidney function (either a fall in urea >10 mmol/L or rise in eGFR >2 ml/min/1.73 m) within the two months prior to RRT were considered to potentially have an incorrect date of start. In 4
selected centres, the electronic patient records of all patients flagged were reviewed to validate these criteria.
Results: Of 8,810 patients, 1,616 (18.3%) were flagged by the identification criteria as having a potentially incorrect date of start of RRT, although a single centre accounted for 41% of the total flagged cohort. Of these flagged patients, 61.7% had been assigned an incorrect date of start of haemodialysis (HD), 5.7% had evidence of acute RRT being given before the reported date of start of HD
and 9.2% had evidence of starting peritoneal dialysis exchanges prior to the reported date of start. Of
those flagged, 10.7% had a correct date of start of RRT.
Conclusions: Accurate reporting of RRT episodes is vital for the analysis of time dependent studies such as survival or time to transplantation. A proportion of patients starting RRT were assigned an incorrect start date. In order to improve the accuracy of this reporting the UK Renal Registry
must work with renal centres and clinical staff on improving data input for the start of RRT.

An investigation of the changes in the natural frequency of a Pile affected by Scour

Scour around bridge foundations is one of the leading causes of bridge failure. Up until recently, the monitoring of this phenomenon was primarily based around using underwater instrumentation to monitor the progression of scour holes as they develop around foundation systems. Vibration-based damage detection techniques have been used to detect damage in bridge beams. The application of these vibration based methods to the detection of scour has come to the fore in research in recent years. This paper examines the effect that scour has on the frequency response of a driven pile foundation system, similar to those used to support road and rail bridges. The effect of scour on the vibration characteristics of the pile is examined using laboratory and field testing. It is clear that there is a very clear reduction in the natural frequency of the pile as the severity of scour increases. It is shown that by combining state-of-the-art geotechnical techniques with relatively simple finite element modelling approaches, it is possible to accurately predict the natural frequency of the pile for a given scour depth. Therefore, the paper proposes a method that would allow the estimation of scour depth for a given observed pile frequency.

Rifampicin and sodium fusidate reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) isolation in adults with cystic fibrosis and chronic MRSA infection

Nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) to patients with cystic fibrosis (CF) frequently results in chronic respiratory tract carriage. This is an increasing problem, adds to the burden of glycopeptide antibiotic use in hospitals, and represents a relative contraindication to lung transplantation. The aim of this study was to determine whether it is possible to eradicate MRSA with prolonged oral combination antibiotics, and whether this treatment is associated with improved clinical status. Adult CF patients (six male, one female) with chronic MRSA infection were treated for six months with rifampicin and sodium fusidate. Outcome data were examined for six months before treatment, on treatment and after treatment. The patients had a mean age of 29.3 (standard deviation=6.3) years and FEV(1) of 36.1% (standard deviation=12.7) predicted. The mean duration of MRSA isolation was 31 months. MRSA isolates identified in these patients was of the same lineage as the known endemic strain at the hospital when assessed by pulsed-field gel electrophoresis. Five of the seven had no evidence of MRSA during and for at least six months after rifampicin and sodium fusidate. The proportion of sputum samples positive for MRSA was lower during the six months of treatment (0.13) and after treatment (0.19) compared with before treatment (0.85) (P<0.0001). There was a reduction in the number of days of intravenous antibiotics per six months with 20.3+/-17.6 on treatment compared with 50.7 before treatment and 33.0 after treatment (P=0.02). There was no change in lung function. Gastrointestinal side effects occurred in three, but led to therapy cessation in only one patient. Despite the use of antibiotics with anti-staphylococcal activity for treatment of respiratory exacerbation, MRSA infection persists. MRSA can be eradicated from the sputum of patients with CF and chronic MRSA carriage by using rifampicin and sodium fusidate for six months. This finding was associated with a significant reduction in the duration of intravenous antibiotic treatment during therapy.