Automatic threshold determination for a local approach of change detection in long-term signal recordings

CUSUM (cumulative sum) is a well-known method that can be used to detect changes in a signal when the parameters of this signal are known. This paper presents an adaptation of the CUSUM-based change detection algorithms to long-term signal recordings where the various hypotheses contained in the signal are unknown. The starting point of the work was the dynamic cumulative sum (DCS) algorithm, previously developed for application to long-term electromyography (EMG) recordings. DCS has been improved in two ways. The first was a new procedure to estimate the distribution parameters to ensure the respect of the detectability property. The second was the definition of two separate, automatically determined thresholds. One of them (lower threshold) acted to stop the estimation process, the other one (upper threshold) was applied to the detection function. The automatic determination of the thresholds was based on the Kullback-Leibler distance which gives information about the distance between the detected segments (events). Tests on simulated data demonstrated the efficiency of these improvements of the DCS algorithm

Parasites of the Deep-Sea Smelt Bathylagus euryops (Argentiniformes: Microstomatidae) from the Charlie-Gibbs Fracture Zone (CGFZ)

The deep-sea smelt Bathylagus euryops, caught in July 2004 at the Charlie-Gibbs Fracture Zone (CGFZ) of the Mid-Atlantic Ridge (North Atlantic), was studied for metazoan parasites and diet composition. A total of 86 specimens with standard lengths between 6.4 and 22.1 cm (mean 13.6 cm) were examined. The parasite fauna consisted of five species: three Digenea, one Cestoda and one Nematoda. The predominant parasites were Lecithaster sp. (Digenea) and an unidentified bothriocephalidean cestode. The only nematode, Anisakis sp., occurred with a low prevalence. Bathylagus euryops at CGFZ serves as final host for the three digeneans, and as intermediate host for the cestodes and Anisakis sp. Stomach content analysis revealed a mesozooplankton crustacean diet, while 95.3% of the stomachs contained unidentified tissue

Non-overshooting stabilisation via state and output feedback

The concept of “strong stability” of LTI systems has been introduced in a recent paper [KHP2]. This is a stronger notion of stability compared to alternative definitions (e.g. stability in the sense of Lyapunov, asymptotic stability), which allows the analysis and design of control systems with non-overshooting response in the state-space for arbitrary initial conditions. The paper reviews the notion of “strong stability” [KHP2] and introduces the problem of non-overshooting stabilization. It is shown that non-overshooting stabilization under dynamic and static output feedback are, in a certain sense, equivalent problems. Thus, we turn our attention to static non-overshooting stabilization problems under state-feedback, output injection and output feedback. After developing a number of preliminary results, we give a geometric interpretation to the problem in terms of the intersection of an affine hyperplane and the interior of an open convex cone. A solution to the problem is finally obtained via Linear Matrix Inequalities, along with the complete parametrization of the optimal solution set

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. METHODS: This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. RESULTS: STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). CONCLUSION: A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy

How Do Home and Clinic Blood Pressure Readings Compare in Pregnancy?: A Systematic Review and Individual Patient Data Meta-Analysis

Hypertensive disorders during pregnancy result in substantial maternal morbidity and are a leading cause of maternal deaths worldwide. Self-monitoring of blood pressure (BP) might improve the detection and management of hypertensive disorders of pregnancy, but few data are available, including regarding appropriate thresholds. This systematic review and individual patient data analysis aimed to assess the current evidence on differences between clinic and self-monitored BP through pregnancy. MEDLINE and 10 other electronic databases were searched for articles published up to and including July 2016 using a strategy designed to capture all the literature on self-monitoring of BP during pregnancy. Investigators of included studies were contacted requesting individual patient data: self-monitored and clinic BP and demographic data. Twenty-one studies that utilized self-monitoring of BP during pregnancy were identified. Individual patient data from self-monitored and clinic readings were available from 7 plus 1 unpublished articles (8 studies; n=758) and 2 further studies published summary data. Analysis revealed a mean self-monitoring clinic difference of ≤1.2 mm Hg systolic BP throughout pregnancy although there was significant heterogeneity (difference in means, I2 >80% throughout pregnancy). Although the overall population difference was small, levels of white coat hypertension were high, particularly toward the end of pregnancy. The available literature includes no evidence of a systematic difference between self and clinic readings, suggesting that appropriate treatment and diagnostic thresholds for self-monitoring during pregnancy would be equivalent to standard clinic thresholds

The Snail repressor recruits EZH2 to specific genomic sites through the enrollment of the lncRNA HOTAIR in epithelial-to-mesenchymal transition

The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.260

Early Detection of Diabetic Peripheral Neuropathy: A Focus on Small Nerve Fibres

Diabetic peripheral neuropathy (DPN) is the most common complication of both type 1 and 2 diabetes. As a result, neuropathic pain, diabetic foot ulcers and lower-limb amputations impact drastically on quality of life, contributing to the individual, societal, financial and healthcare burden of diabetes. DPN is diagnosed at a late, often pre-ulcerative stage due to a lack of early systematic screening and the endorsement of monofilament testing which identifies advanced neuropathy only. Compared to the success of the diabetic eye and kidney screening programmes there is clearly an unmet need for an objective reliable biomarker for the detection of early DPN. This article critically appraises research and clinical methods for the diagnosis or screening of early DPN. In brief, functional measures are subjective and are difficult to implement due to technical complexity. Moreover, skin biopsy is invasive, expensive and lacks diagnostic laboratory capacity. Indeed, point-of-care nerve conduction tests are convenient and easy to implement however questions are raised regarding their suitability for use in screening due to the lack of small nerve fibre evaluation. Corneal confocal microscopy (CCM) is a rapid, non-invasive, and reproducible technique to quantify small nerve fibre damage and repair which can be conducted alongside retinopathy screening. CCM identifies early sub-clinical DPN, predicts the development and allows staging of DPN severity. Automated quantification of CCM with AI has enabled enhanced unbiased quantification of small nerve fibres and potentially early diagnosis of DPN. Improved screening tools will prevent and reduce the burden of foot ulceration and amputations with the primary aim of reducing the prevalence of this common microvascular complication

Higher-order multipole amplitudes in charmonium radiative transitions

Using 24 million $\psi' \equiv \psi(2S)$ decays in CLEO-c, we have searched for higher multipole admixtures in electric-dipole-dominated radiative transitions in charmonia. We find good agreement between our data and theoretical predictions for magnetic quadrupole (M2) amplitudes in the transitions $\psi' \to \gamma \chi_{c1,2}$ and $\chi_{c1,2} \to \gamma J/\psi$, in striking contrast to some previous measurements. Let $b_2^J$ and $a_2^J$ denote the normalized M2 amplitudes in the respective aforementioned decays, where the superscript $J$ refers to the angular momentum of the $\chi_{cJ}$. By performing unbinned maximum likelihood fits to full five-parameter angular distributions, we determine the ratios $a_2^{J=1}/a_2^{J=2} = 0.67^{+0.19}_{-0.13}$ and $a_2^{J=1}/b_2^{J=1} = -2.27^{+0.57}_{-0.99}$, where the theoretical predictions are independent of the charmed quark magnetic moment and are $a_2^{J=1}/a_2^{J=2} = 0.676 \pm 0.071$ and $a_2^{J=1}/b_2^{J=1} = -2.27 \pm 0.16$.Comment: 32 pages, 7 figures, acceptance updat

Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al