Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

Background: The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy.\ud Design/Methods: We will conduct a non-inferiority andomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm,participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely.This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation.\ud Outcomes/Follow-up: The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal\ud symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day

Biliary Bicarbonate Secretion Constitutes a Protective Mechanism against Bile Acid-Induced Injury in Man

Background: Cholangiocytes expose a striking resistance against bile acids: while other cell types, such as hepatocytes, are susceptible to bile acid-induced toxicity and apoptosis already at micromolar concentrations, cholangiocytes are continuously exposed to millimolar concentrations as present in bile. We present a hypothesis suggesting that biliary secretion of HCO(3)(-) in man serves to protect cholangiocytes against bile acid-induced damage by fostering the deprotonation of apolar bile acids to more polar bile salts. Here, we tested if bile acid-induced toxicity is pH-dependent and if anion exchanger 2 (AE2) protects against bile acid-induced damage. Methods: A human cholangiocyte cell line was exposed to chenodeoxycholate (CDC), or its glycine conjugate, from 0.5 mM to 2.0 mM at pH 7.4, 7.1, 6.7 or 6.4, or after knockdown of AE2. Cell viability and apoptosis were determined by WST and caspase-3/-7 assays, respectively. Results: Glycochenodeoxycholate (GCDC) uptake in cholangiocytes is pH-dependent. Furthermore, CDC and GCDC (pK(a) 4-5) induce cholangiocyte toxicity in a pH-dependent manner: 0.5 mM CDC and 1 mM GCDC at pH 7.4 had no effect on cell viability, but at pH 6.4 decreased viability by >80% and increased caspase activity almost 10- and 30-fold, respectively. Acidification alone had no effect. AE2 knockdown led to 3- and 2-fold enhanced apoptosis induced by 0.75 mM CDC or 2 mM GCDC at pH 7.4. Discussion: These data support our hypothesis of a biliary HCO(3)(-) umbrella serving to protect human cholangiocytes against bile acid-induced injury. AE2 is a key contributor to this protective mechanism. The development and progression of cholangiopathies, such as primary biliary cirrhosis, may be a consequence of genetic and acquired functional defects of genes involved in maintaining the biliary HCO(3)(-) umbrella. Copyright (C) 2011 S. Karger AG, Base

Casting Light on Dark Matter

The prospects for detecting a candidate supersymmetric dark matter particle at the LHC are reviewed, and compared with the prospects for direct and indirect searches for astrophysical dark matter. The discussion is based on a frequentist analysis of the preferred regions of the Minimal supersymmetric extension of the Standard Model with universal soft supersymmetry breaking (the CMSSM). LHC searches may have good chances to observe supersymmetry in the near future - and so may direct searches for astrophysical dark matter particles, whereas indirect searches may require greater sensitivity, at least within the CMSSM.Comment: 16 pages, 13 figures, contribution to the proceedings of the LEAP 2011 Conferenc

Comparing the Bacterial Diversity of Acute and Chronic Dental Root Canal Infections

This study performed barcoded multiplex pyrosequencing with a 454 FLX instrument to compare the microbiota of dental root canal infections associated with acute (symptomatic) or chronic (asymptomatic) apical periodontitis. Analysis of samples from 9 acute abscesses and 8 chronic infections yielded partial 16S rRNA gene sequences that were taxonomically classified into 916 bacterial species-level operational taxonomic units (OTUs) (at 3% divergence) belonging to 67 genera and 13 phyla. The most abundant phyla in acute infections were Firmicutes (52%), Fusobacteria (17%) and Bacteroidetes (13%), while in chronic infections the dominant were Firmicutes (59%), Bacteroidetes (14%) and Actinobacteria (10%). Members of Fusobacteria were much more prevalent in acute (89%) than in chronic cases (50%). The most abundant/prevalent genera in acute infections were Fusobacterium and Parvimonas. Twenty genera were exclusively detected in acute infections and 18 in chronic infections. Only 18% (n = 165) of the OTUs at 3% divergence were shared by acute and chronic infections. Diversity and richness estimators revealed that acute infections were significantly more diverse than chronic infections. Although a high interindividual variation in bacterial communities was observed, many samples tended to group together according to the type of infection (acute or chronic). This study is one of the most comprehensive in-deep comparisons of the microbiota associated with acute and chronic dental root canal infections and highlights the role of diverse polymicrobial communities as the unit of pathogenicity in acute infections. The overall diversity of endodontic infections as revealed by the pyrosequencing technique was much higher than previously reported for endodontic infections

Improving SIEM for critical SCADA water infrastructures using machine learning

Network Control Systems (NAC) have been used in many industrial processes. They aim to reduce the human factor burden and efficiently handle the complex process and communication of those systems. Supervisory control and data acquisition (SCADA) systems are used in industrial, infrastructure and facility processes (e.g. manufacturing, fabrication, oil and water pipelines, building ventilation, etc.) Like other Internet of Things (IoT) implementations, SCADA systems are vulnerable to cyber-attacks, therefore, a robust anomaly detection is a major requirement. However, having an accurate anomaly detection system is not an easy task, due to the difficulty to differentiate between cyber-attacks and system internal failures (e.g. hardware failures). In this paper, we present a model that detects anomaly events in a water system controlled by SCADA. Six Machine Learning techniques have been used in building and evaluating the model. The model classifies different anomaly events including hardware failures (e.g. sensor failures), sabotage and cyber-attacks (e.g. DoS and Spoofing). Unlike other detection systems, our proposed work helps in accelerating the mitigation process by notifying the operator with additional information when an anomaly occurs. This additional information includes the probability and confidence level of event(s) occurring. The model is trained and tested using a real-world dataset

Pro-active Meeting Assistants: Attention Please!

This paper gives an overview of pro-active meeting assistants, what they are and when they can be useful. We explain how to develop such assistants with respect to requirement definitions and elaborate on a set of Wizard of Oz experiments, aiming to find out in which form a meeting assistant should operate to be accepted by participants and whether the meeting effectiveness and efficiency can be improved by an assistant at all. This paper gives an overview of pro-active meeting assistants, what they are and when they can be useful. We explain how to develop such assistants with respect to requirement definitions and elaborate on a set of Wizard of Oz experiments, aiming to find out in which form a meeting assistant should operate to be accepted by participants and whether the meeting effectiveness and efficiency can be improved by an assistant at all

3D thermal analysis of a permanent magnet motor with cooling fans

Overheating of permanent magnet (PM) machines has become a major technical challenge as it gives rise to magnet demagnetization, degradation of insulation materials, and loss of motor efficiency. This paper proposes a state-of-the-art cooling system for an axial flux permanent magnet (AFPM) machine with the focus on its structural optimization. A computational fluid dynamics (CFD) simulation with thermal consideration has been shown to be an efficient approach in the literature and is thus employed in this work. Meanwhile, a simplified numerical approach to the AFPM machine with complex configuration in 3D consisting of conduction, forced convection, and conjugate heat transfer is taken as a case study. Different simplification methods (including configuration and working conditions) and two optimized fans for forced convection cooling are designed and installed on the AFPM machine and compared to a natural convection cooling system. The results show that the proposed approach is effective for analyzing the thermal performance of a complex AFPM machine and strikes a balance between reasonable simplification, accuracy, and computational resource

Quantum control of proximal spins using nanoscale magnetic resonance imaging

Quantum control of individual spins in condensed matter systems is an emerging field with wide-ranging applications in spintronics, quantum computation, and sensitive magnetometry. Recent experiments have demonstrated the ability to address and manipulate single electron spins through either optical or electrical techniques. However, it is a challenge to extend individual spin control to nanoscale multi-electron systems, as individual spins are often irresolvable with existing methods. Here we demonstrate that coherent individual spin control can be achieved with few-nm resolution for proximal electron spins by performing single-spin magnetic resonance imaging (MRI), which is realized via a scanning magnetic field gradient that is both strong enough to achieve nanometric spatial resolution and sufficiently stable for coherent spin manipulations. We apply this scanning field-gradient MRI technique to electronic spins in nitrogen-vacancy (NV) centers in diamond and achieve nanometric resolution in imaging, characterization, and manipulation of individual spins. For NV centers, our results in individual spin control demonstrate an improvement of nearly two orders of magnitude in spatial resolution compared to conventional optical diffraction-limited techniques. This scanning-field-gradient microscope enables a wide range of applications including materials characterization, spin entanglement, and nanoscale magnetometry.Comment: 7 pages, 4 figure

Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice

Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+) and IgA(+) antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge