Postantibiotic effect of roxithromycin, erythromycin, and clindamycin against selected Gram-positive bacteria and Haemophilus influenzae

Recent experimental work has shown that a so-called PAE (postantibiotic effect, i.e. persistent suppression of regrowth after short exposure of bacteria to the study drug in vitro) is a feature of most current antibiotics. However, marked quantitative differences were found between different types of antibiotics and also between Gram-positive and Gram-negative organisms studied. A PAE has not yet been demonstrated for roxithromycin, a new macrolide antibiotic. Therefore, we compared the PAE of roxithromycin, erythromycin, and clindamycin against laboratory strains and clinical isolates of Staphylococcus aureus, Streptococcus pyogenes, Str.pneumoniae, and Haemophilus influenzae in vitro. Identical multiples of the MIC and identical exposure times resulted in similar PAEs for the three study drugs tested. Good correlations could be found between the area under the in-vitro concentration-vs-time curve (AUC) and PAEs. The longest PAE of 9.6 h was observed after exposure of Str. pneumoniae to 1.9 mg/l of roxithromycin for 6

THE PREVALENCE OF PALPABLE FINGER JOINT NODULES IN DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS (DISH). A CONTROLLED STUDY

The presence of clinically palpable finger joint nodules a(Heberden's and Bouchard's nodes) was documented in 123 consecutive cases with diffuse idiopathic skeletal hyperostosis (DISH) of the thoracic spine and 191 matched DISH negative controls. The prevalence of palpable finger joint nodules was almost twice as frequent in cases with spinal DISH compared to controls (46% versus 31%, X2 = 7.67, P<0.01; multivariate adjusted odds ratio OR = 1.84; 95% CI: 1.14-2.98). This increase was most marked at the proximal interphalangeal joint, in males and in patients up to the age of 65 years. In addition and independent of other variables such as hyperostotic features, age and sex, the prevalence of palpable finger joint nodules was about twice as high in probands with a history of physically heavy work compared to those without (43% ver sus 26%, X = 9.18, P<0.005; multivariate adjusted odds ratio OR = 2.10; 95% CI: 1.26-3.52). From these results we con clude that DISH should be considered as an independent risk factor in the development of finger joint nodule

DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS (DISH) OF THE SPINE: A CAUSE OF BACK PAIN? A CONTROLLED STUDY

This is the first controlled study of the frequency of back pain in a European caucasian population with diffuse idiopathic skeletal hyperostosis (DISH). Elderly patients admitted to hospital for reasons other than back pain were assessed for the presence of spinal DISH using the routine lateral chest radiograph films. A total of 106 probands (82 males, 24 females) with a mean age of 70 years fulfilled the criteria for DISH as defined previously. One hundred and seventyeight patients (117 males, 61 females) not meeting these criteria were used as controls. The prevalence of back pain was assessed by a blinded interviewer using a structured questionnaire. Our primary hymthesis was that spinal DISH positive probands had not had back pain more often than controls. The controlled study showed no statistically significant difference in pain frequency between spinal DISH positive probands and controls at any spinal level. We conclude that back pain does not occur more often in radiographically defined DISH positive probands than in controls. The radiological finding of spinal DISH, as far as it does not lead to stenosis of the spinal canal or dysphagia, thus seems to be a finding without clinical relevanc

DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS (DISH) OF THE SHOULDER: A CAUSE OF SHOULDER PAIN?

Shoulder pain is a common complaint and shoulder hyperostosis a frequent radiological condition. However, little is known about the association between the clinical and radiological findings. To evaluate the clinical relevance of shoulder hyperostosis we performed a controlled, blind study of 99 hospitalized probands with and without thoracospinal hyperostosis on lateral chest X-rays. The study included grading of the shoulder hyperostosis on the basis of three bilateral standard radiographs, assessing shoulder pain in a standardized way by an interviewer and recording extraskeletal causes of shoulder pain. The prevalence of shoulder hyperostosis was doubled in probands with thoracospinal hyperostosis compared to controls (X2= 5.90, F>0.025, n = 99). Shoulder hyperostosis, irrespective of thoracospinal hyperostosis, predisposed to shoulder pain (40% versus 18%, x2 = 4.06, F>0.05, n = 74). Shoulder hyperostosis in combination with thoracospinal hyperostosis (shoulder DISH) predisposed to shoulder pain to an even greater extent (46% versus 12%, x2 = 6.64, P>0.01, n = 47). We conclude that shoulder hyperostosis is a radiological finding of potential clinical relevanc

Vortex pinning by natural defects in thin films of YBa2Cu3O7−δ

Although vortex pinning in laser-ablated YBa2Cu3O7−δ films on (100) SrTiO3 is dominated by threading dislocations, many other natural pinning sites are present. To identify the contribution from twin planes, surface corrugations and point defects, we manipulate the relative densities of all defects by post-annealing films with various as-grown dislocation densities, ndisl. While a universal magnetic field B dependence of the transport current density js(B, T) is observed (independently of ndisl, temperature T and the annealing treatment), the defect structure changes considerably. Correlating the microstructure to js(B, T), it becomes clear that surface roughness, twins and point defects are not important at low magnetic fields compared to linear defect pinning. Transmission electron microscopy indicates that threading dislocations are not part of grain boundaries nor are they related to the twin domain structure. We conclude that js(B, T) is essentially determined by pinning along threading dislocations, naturally induced during the growth process. Even in high magnetic fields, where the vortex density outnumbers ndisl, it appears that linear defects stabilize the vortex lattice by means of the vortex–vortex interaction.

Strong Pinning in High Temperature Superconductors

Detailed measurements of the critical current density jc of YBa2Cu3O7 films grown by pulsed laser deposition reveal the increase of jc as function of the filmthickness. Both this thickness dependence and the field dependence of the critical current are consistently described using a generalization of the theory of strong pinning of Ovchinnikov and Ivlev [Phys. Rev. B 43, 8024 (1991)]. From the model, we deduce values of the defect density (10^21 m^-3) and the elementary pinning force, which are in good agreement with the generally accepted values for Y2O3-inclusions. In the absence of clear evidence that the critical current is determined by linear defects or modulations of the film thickness, our model provides an alternative explanation for the rather universal field dependence of the critical current density found in YBa2Cu3O7 films deposited by different methods.Comment: 11 pages; 8 Figures; Published Phys. Rev. B 66, 024523 (2002

Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich Ataxia

Copyright © 2014 Anjomani Virmouni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Background - Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC) transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats), YG8R (90 and 190 GAA repeats) and YG22R (190 GAA repeats). Methodology/Principal Findings - We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH) analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R. Conclusions/Significance - Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.European Union, Ataxia UK and FARA

DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS (DISH) OF THE ELBOW: A CAUSE OF ELBOW PAIN? A CONTROLLED STUDY

Elbow pain is a common complaint and elbow hyperostosis a frequent radiological condition. However, little is known about the association between the clinical and radiological findings. To evaluate the relationship between spinal and extraspinal hyperostotic features and the clinical relevance of elbow hyperostosis we have performed the first controlled, double-blinded study of 85 hospitalized probands, 33 with and 52 without thoracospinal hyperostosis on lateral chest X-ray. Elbow and shoulder hyperostosis were graded on bilateral standard radiographs. Elbow pain was assessed by an interviewer using a standardized questionnaire and extraskeletal causes of elbow pain were recorded. The prevalence of elbow hyperostosis was increased in cases with thoracospinal hyperostosis compared to controls (82% versus 58%, X2 = 5.32, P<0.025, n = 85, odds ratio (OR) 3.30 (95% Cl 1.16-9.35)). Similarly, the prevalence of elbow hyperostosis was increased in cases with shoulder hyperostosis compared to controls (83% versus 60%, x2 = 4.51, P<0.05, n = 84, OR = 3.20 (95% CI 1.06-9.66)), emphasizing the multifocal nature of hyperostotic features. Elbow pain was only slightly more prevalent in cases with elbow hyperostosis compared to controls (21% versus l3%, x2 = 0.75, NS, OR = 1.84 (95% CI 0.46-7.44)). We conclude that elbow hyperostosis is a radiological finding of doubtful clinical relevanc

Nanomechanical sensors: Measuring a response in blood

Nanomechanical cantilevers can determine the concentration of active drugs in human serum

Sequential Quasi-Monte Carlo

We derive and study SQMC (Sequential Quasi-Monte Carlo), a class of algorithms obtained by introducing QMC point sets in particle filtering. SQMC is related to, and may be seen as an extension of, the array-RQMC algorithm of L'Ecuyer et al. (2006). The complexity of SQMC is $O(N \log N)$, where $N$ is the number of simulations at each iteration, and its error rate is smaller than the Monte Carlo rate $O_P(N^{-1/2})$. The only requirement to implement SQMC is the ability to write the simulation of particle $x_t^n$ given $x_{t-1}^n$ as a deterministic function of $x_{t-1}^n$ and a fixed number of uniform variates. We show that SQMC is amenable to the same extensions as standard SMC, such as forward smoothing, backward smoothing, unbiased likelihood evaluation, and so on. In particular, SQMC may replace SMC within a PMCMC (particle Markov chain Monte Carlo) algorithm. We establish several convergence results. We provide numerical evidence that SQMC may significantly outperform SMC in practical scenarios.Comment: 55 pages, 10 figures (final version