Electrochemical communication with the inside of cells using micro-patterned vertical carbon nanofibre electrodes

With the rapidly increasing demands for ultrasensitive biodetection, the design and applications of new nano-scale materials for development of sensors based on optical and electrochemical transducers have attracted substantial interest. In particular, given the comparable sizes of nanomaterials and biomolecules, there exist plenty of opportunities to develop functional nanoprobes with biomolecules for highly sensitive and selective biosensing, shedding new light on cellular behaviour. Towards this aim, herein we interface cells with patterned nano-arrays of carbon nanofibers forming a nanosensor-cell construct. We show that such a construct is capable of electrochemically communicating with the intracellular environment.This work was supported by the Leverhulme Trust [grant numbers F/00 094/BD, ECF/2013-603]; the Biotechnology and Biological Sciences Research Council [grant number BB/L017059/1]; the European Research Council [Consolidator Grant, number 614787], the Engineering and Physical Sciences Research Council [EP/K027263/1]; and the NC3Rs [grant number NC/L00058X/1]

A Special Homotopy Continuation Method For A Class of Polynomial Systems

A special homotopy continuation method, as a combination of the polyhedral homotopy and the linear product homotopy, is proposed for computing all the isolated solutions to a special class of polynomial systems. The root number bound of this method is between the total degree bound and the mixed volume bound and can be easily computed. The new algorithm has been implemented as a program called LPH using C++. Our experiments show its efficiency compared to the polyhedral or other homotopies on such systems. As an application, the algorithm can be used to find witness points on each connected component of a real variety

Epidemiological associations between brachycephaly and upper respiratory tract disorders in dogs attending veterinary practices in England

Background: Brachycephalic dog breeds are increasingly common. Canine brachycephaly has been associated with upper respiratory tract (URT) disorders but reliable prevalence data remain lacking. Using primary-care veterinary clinical data, this study aimed to report the prevalence and breed-type risk factors for URT disorders in dogs. Results: The sampling frame included 170,812 dogs attending 96 primary-care veterinary clinics participating within the VetCompass Programme. Two hundred dogs were randomly selected from each of three extreme brachycephalic breed types (Bulldog, French Bulldog and Pug) and three common small-to medium sized breed types (moderate brachycephalic: Yorkshire Terrier and non-brachycephalic: Border Terrier and West Highland White Terrier). Information on all URT disorders recorded was extracted from individual patient records. Disorder prevalence was compared between groups using the chi-squared test or Fisher’s test, as appropriate. Risk factor analysis used multivariable logistic regression modelling. During the study, 83 (6.9 %) study dogs died. Extreme brachycephalic dogs (median longevity: 8.6 years, IQR: 2.4-10.8) were significantly younger at death than the moderate and non-brachycephalic group of dogs (median 12.7 years, IQR 11.1-15.0) (P \u3c 0.001). A higher proportion of deaths in extreme brachycephalic breed types were associated with URT disorders (4/24 deaths, 16.7 %) compared with the moderate and non-brachycephalic group (0/59 deaths, 0.0 %) (P = 0.001). The prevalence of having at least one URT disorder in the extreme brachycephalic group was higher (22.0 %, 95 % confidence interval (CI): 18.0-26.0) than in the moderate and non-brachycephalic group (9.7 %, 95 % CI: 7.1-12.3, P \u3c 0.001). The prevalence of URT disorders varied significantly by breed type: Bulldogs 19.5 %, French Bulldogs 20.0 %, Pugs 26.5 %, Border Terriers 9.0 %, West Highland White Terriers 7.0 % and Yorkshire Terriers 13.0 % (P \u3c 0.001). After accounting for the effects of age, bodyweight, sex, neutering and insurance, extreme brachycephalic dogs had 3.5 times (95 % CI: 2.4-5.0, P \u3c 0.001) the odds of at least one URT disorder compared with the moderate and non-brachycephalic group. Conclusions: In summary, this study reports that URT disorders are commonly diagnosed in Bulldog, French Bulldog, Pug, Border Terrier, WHWT and Yorkshire Terrier dogs attending primary-care veterinary practices in England. The three extreme brachycephalic breed types (Bulldog, French Bulldog and Pug) were relatively short-lived and predisposed to URT disorders compared with three other small-to-medium size breed types that are commonly owned (moderate brachycephalic Yorkshire Terrier and non-brachycephalic: Border Terrier and WHWT). Conclusions: In summary, this study reports that URT disorders are commonly diagnosed in Bulldog, French Bulldog, Pug, Border Terrier, WHWT and Yorkshire Terrier dogs attending primary-care veterinary practices in England. The three extreme brachycephalic breed types (Bulldog, French Bulldog and Pug) were relatively short-lived and predisposed to URT disorders compared with three other small-to-medium size breed types that are commonly owned (moderate brachycephalic Yorkshire Terrier and non-brachycephalic: Border Terrier and WHWT)

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations

Pain coping skills training for African Americans with osteoarthritis (STAART): study protocol of a randomized controlled trial

Background: African Americans bear a disproportionate burden of osteoarthritis (OA), with higher prevalence rates, more severe pain, and more functional limitations. One key barrier to addressing these disparities has been limited engagement of African Americans in the development and evaluation of behavioral interventions for management of OA. Pain Coping Skills Training (CST) is a cognitive-behavioral intervention with shown efficacy to improve OA-related pain and other outcomes. Emerging data indicate pain CST may be a promising intervention for reducing racial disparities in OA symptom severity. However, there are important gaps in this research, including incorporation of stakeholder perspectives (e.g. cultural appropriateness, strategies for implementation into clinical practice) and testing pain CST specifically among African Americans with OA. This study will evaluate the effectiveness of a culturally enhanced pain CST program among African Americans with OA. Methods/Design: This is a randomized controlled trial among 248 participants with symptomatic hip or knee OA, with equal allocation to a pain CST group and a wait list (WL) control group. The pain CST program incorporated feedback from patients and other stakeholders and involves 11 weekly telephone-based sessions. Outcomes are assessed at baseline, 12 weeks (primary time point), and 36 weeks (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include self-efficacy, pain coping, pain interference, quality of life, depressive symptoms, and global assessment of change. Linear mixed models will be used to compare the pain CST group to the WL control group and explore whether participant characteristics are associated with differential improvement in the pain CST program. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Boards of the University of North Carolina at Chapel Hill, Durham Veterans Affairs Medical Center, East Carolina University, and Duke University Health System. Discussion: This culturally enhanced pain CST program could have a substantial impact on outcomes for African Americans with OA and may be a key strategy in the reduction of racial health disparities.Funded by Patient-Centered Outcomes Research Institute (PCORI) Award (AD-1408-19519)