Path Signatures for Seizure Forecasting

Forecasting the state of a system from an observed time series is the subject of research in many domains, such as computational neuroscience. Here, the prediction of epileptic seizures from brain measurements is an unresolved problem. There are neither complete models describing underlying brain dynamics, nor do individual patients exhibit a single seizure onset pattern, which complicates the development of a `one-size-fits-all' solution. Based on a longitudinal patient data set, we address the automated discovery and quantification of statistical features (biomarkers) that can be used to forecast seizures in a patient-specific way. We use existing and novel feature extraction algorithms, in particular the path signature, a recent development in time series analysis. Of particular interest is how this set of complex, nonlinear features performs compared to simpler, linear features on this task. Our inference is based on statistical classification algorithms with in-built subset selection to discern time series with and without an impending seizure while selecting only a small number of relevant features. This study may be seen as a step towards a generalisable pattern recognition pipeline for time series in a broader context

An atom efficient, single-source precursor route to plasmonic CuS nanocrystals

The synthesis of colloidal semiconductor nanocrystals (NCs) from single-source precursors offers simplified manufacturing processes at the cost of reduced atom efficiency. Self-capping routes have the potential to maximise this efficiency although investigation has so far been limited to organic solvents. Here we present the synthesis of copper sulfide NCs via the decomposition of a copper dithiocarbamate complex in water. Nanocrystalline covellite particles were prepared without the need for additional capping ligand and exhibited a hollow nanosphere morphology. Mass spectrometry of the water-stable NCs indicated the presence of a number of surface ligands, including a small amine fragment of the single-source precursor (SSP) complex. A broad plasmon resonance in the near-infrared (NIR) at 990 nm was also observed and the photothermal effect of this demonstrated. Cytotoxicity experiments indicated cell viability remained above 95% for NC concentrations up to 1 mg mL(−1), indicating high biocompatibility

Importance of the alternative NF-κB activation pathway in inflammation-associated gastrointestinal carcinogenesis

Chronic inflammation is a common factor in the development of many gastrointestinal malignancies. Examples include inflammatory bowel disease predisposing to colorectal cancer, Barrett's esophagus as a precursor of esophageal adenocarcinoma, and Helicobacter pylori-induced gastric cancer. The classical activation pathway of NF-κB signaling has been identified as regulating several sporadic and inflammation-associated gastrointestinal tract malignancies. Emerging evidence suggests that the alternative NF-κB signaling pathway also exerts a distinct influence on these processes. This review brings together current knowledge of the role of the alternative NF-κB signaling pathway in the gastrointestinal tract, with a particular emphasis on inflammation-associated cancer development. members of the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) family were initially described as transcription factors in B lymphocytes in 1986 (68). Since then, they have been shown to be widely expressed and are conserved across both vertebrates and invertebrates (5, 27). The conventional model of NF-κB signaling proposes two main arms of the pathway. These share similar features but are triggered independently and activate different target genes (76). The classical (canonical) NF-κB activation pathway is triggered by Th1 cytokines and is typified by the action of reticuloendotheliosis viral oncogene homolog A (RelA) (p65)-NF-κB1(p50) heterodimers, whereas the alternative (noncanonical) activation pathway signals through the adaptor protein NF-κB-inducing kinase (NIK). Activation of this mechanism leads to nuclear translocation of transcriptionally active v-rel avian reticuloendotheliosis viral oncogene homolog B (RelB)-NF-κB2(p52) heterodimers. Signaling through either pathway can influence multiple different cellular functions and can exert effects that may appear contradictory. For example, both pro- and anti-apoptotic effects, as well as proliferation (18) and senescence (70) signals, have been attributed to the classical activation pathway of NF-κB signaling. Because of the wide variation in outcomes following pathway activation, it is difficult to extrapolate the effects of NF-κB signaling from one context to another. Classical pathway NF-κB signaling has been identified as a key regulator of inflammation-associated carcinogenesis in several tissues since the early 2000s when Greten et al. demonstrated increased sensitivity to colitis-associated carcinogenesis in mice lacking IKK-β in intestinal epithelial cells (31), and, almost simultaneously Pikarsky et al. identified a similar increase in tumor burden in Mdr2 mice lacking IKK-β in hepatocytes (60). More recent evidence has established that alternative activation pathway NF-κB signaling is also important during the development of several gastrointestinal pathologies in mouse and humans. This article seeks to review this evidence and to establish questions for future research

Colonic epithelial ion transport is not affected in patients with diverticulosis

<p>Abstract</p> <p>Background</p> <p>Colonic diverticular disease is a bothersome condition with an unresolved pathogenesis. It is unknown whether a neuroepithelial dysfunction is present. The aim of the study was two-fold; (1) to investigate colonic epithelial ion transport in patients with diverticulosis and (2) to adapt a miniaturized Modified Ussing Air-Suction (MUAS) chamber for colonic endoscopic biopsies.</p> <p>Methods</p> <p>Biopsies were obtained from the sigmoid part of the colon. 86 patients were included. All patients were referred for colonoscopy on suspicion of neoplasia and they were without pathological findings at colonoscopy (controls) except for diverticulosis in 22 (D-patients). Biopsies were mounted in MUAS chambers with an exposed area of 5 mm². Electrical responses to various stimulators and inhibitors of ion transport were investigated together with histological examination. The MUAS chamber was easy to use and reproducible data were obtained.</p> <p>Results</p> <p>Median basal short circuit current (SCC) was 43.8 μA·cm^-2(0.8 – 199) for controls and 59.3 μA·cm^-2(3.0 – 177.2) for D-patients. Slope conductance was 77.0 mS·cm^-2(18.6 – 204.0) equal to 13 Ω·cm²for controls and 96.6 mS·cm^-2(8.4 – 191.4) equal to 10.3 Ω·cm²for D-patients. Stimulation with serotonin, theophylline, forskolin and carbachol induced increases in SCC in a range of 4.9 – 18.6 μA·cm^-2, while inhibition with indomethacin, bumetanide, ouabain and amiloride decreased SCC in a range of 6.5 – 27.4 μA·cm^-2, and all with no significant differences between controls and D-patients. Histological examinations showed intact epithelium and lamina propria before and after mounting for both types of patients.</p> <p>Conclusion</p> <p>We conclude that epithelial ion transport is not significantly altered in patients with diverticulosis and that the MUAS chamber can be adapted for studies of human colonic endoscopic biopsies.</p

Using systems medicine to identify a therapeutic agent with potential for repurposing in inflammatory bowel disease

ObjectiveInflammatory bowel diseases cause significant morbidity and mortality. Aberrant NF-κB signalling is strongly associated with these conditions, and several established drugs influence the NF-κB signalling network to exert their effect. This study aimed to identify drugs which alter NF-κB signalling and may be repositioned for use in inflammatory bowel disease.DesignThe SysmedIBD consortium established a novel drug-repurposing pipeline based on a combination of in-silico drug discovery and biological assays targeted at demonstrating an impact on NF-kappaB signalling, and a murine model of IBD.ResultsThe drug discovery algorithm identified several drugs already established in IBD, including corticosteroids. The highest-ranked drug was the macrolide antibiotic Clarithromycin, which has previously been reported to have anti-inflammatory effects in aseptic conditions. Clarithromycin's effects were validated in several experiments: it influenced NF-κB mediated transcription in murine peritoneal macrophages and intestinal enteroids; it suppressed NF-κB protein shuttling in murine reporter enteroids; it suppressed NF-κB (p65) DNA binding in the small intestine of mice exposed to LPS, and it reduced the severity of dextran sulphate sodium-induced colitis in C57BL/6 mice. Clarithromycin also suppressed NF-κB (p65) nuclear translocation in human intestinal enteroids.ConclusionsThese findings demonstrate that in-silico drug repositioning algorithms can viably be allied to laboratory validation assays in the context of inflammatory bowel disease; and that further clinical assessment of clarithromycin in the management of inflammatory bowel disease is required