Additive manufacturing for electrochemical labs: An overview and tutorial note on the production of cells, electrodes and accessories

Additive Manufacturing (AM) is an ever-growing part of modern scientific research due to its ability to create complex features, low wastage, ever-decreasing cost of entry and rapid prototyping capabilities. Up to this point, the use of AM in electrochemical research has focused around two of the main components of the experimental setup: the working electrode, and the electrochemical cell. In this paper we highlight how researchers have utilised AM in the literature and offer our own insights into how this technology can be exploited to benefit all areas of electrochemical research. For the development of electrodes, much of the literature utilises commercially available conductive PLA filaments in conjunction with FFF printing, with only a few groups expanding into the development of their own bespoke conductive materials. AM offers huge advantages in the production of electrochemical cells, allowing users to produce bespoke designs to fit their experimental needs, rapidly producing these at low cost and easily modifying the design to improve performance. However, the use of AM in electrochemical laboratories should not stop there. We present basic designs of electrodes, cells and even accessories that can benefit all electrochemical researchers (new and experienced) in their quest for reproducible and reliable results. These designs are offered free of charge, are available to download from the Supporting Information and can be easily modified to meet any users’ specific needs. As such, we feel AM should be a staple of every laboratory and hope this work inspires people to think about all the ways that AM can benefit their research environments

Rabies screen reveals GPe control of cocaine-triggered plasticity.

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations

Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms

$\textit{Background and Purpose:}$ Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, but the relationship between AF and noncardioembolic stroke subtypes are unclear. Because AF may be unrecognized, and because AF has a substantial genetic basis, we assessed for predisposition to AF across ischemic stroke subtypes. $\textit{Methods:}$ We examined associations between AF genetic risk and Trial of Org 10172 in Acute Stroke Treatment stroke subtypes in 2374 ambulatory individuals with ischemic stroke and 5175 without from the Wellcome Trust Case-Control Consortium 2 using logistic regression. We calculated AF genetic risk scores using single-nucleotide polymorphisms associated with AF in a previous independent analysis across a range of preselected significance thresholds. $\textit{Results:}$ There were 460 (19.4%) individuals with cardioembolic stroke, 498 (21.0%) with large vessel, 474 (20.0%) with small vessel, and 814 (32.3%) individuals with strokes of undetermined cause. Most AF genetic risk scores were associated with stroke, with the strongest association ($P$=6×10$^{-4}$) attributed to scores of 944 single-nucleotide polymorphisms (each associated with AF at $P$<1×10$^{-3}$) in a previous analysis). Associations between AF genetic risk and stroke were enriched in the cardioembolic stroke subset (strongest $P$=1.2×10$^{-9}$), 944 single-nucleotide polymorphism score). In contrast, AF genetic risk was not significantly associated with noncardioembolic stroke subtypes. $\textit{Conclusions:}$ Comprehensive AF genetic risk scores were specific for cardioembolic stroke. Incomplete workups and subtype misclassification may have limited the power to detect associations with strokes of undetermined pathogenesis. Future studies are warranted to determine whether AF genetic risk is a useful biomarker to enhance clinical discrimination of stroke pathogeneses.Dr. Lubitz is supported by NIH grants K23HL114724 and a Doris Duke Charitable Foundation Clinical Scientist Development Award 2014105. Dr. Traylor is supported by a British Heart Foundation programme grant (RG/16/4/32218). Dr. Ellinor and Benjamin are supported by 1RO1HL092577, R01HL128914. Dr. Ellinor is supported by grants from the National Institutes of Health K24HL105780 and an Established Investigator Award from the American Heart Association (13EIA14220013) and by the Fondation Leducq (14CVD01). Dr. Dichgans and Dr. Malik were supported by grants from the Deutsche Forschungsgemeinschaft (CRC 1123 [B3] and Munich Cluster for Systems Neurology [SyNergy]), the German Federal Ministry of Education and Research (BMBF, e:Med programme e:AtheroSysMed), the FP7/2007-2103 European Union project CVgenes@target (grant agreement No Health-F2-2013-601456), the European Union Horizon2020 projects SVDs@target (grant agreement No 66688) and CoSTREAM (grant agreement No 667375), the Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain), the Vascular Dementia Research Foundation, and the Jackstaedt Foundation

Aspirin and non-steroidal anti-inflammatory drug use and the risk of upper aerodigestive tract cancer

Background:Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesics and preventative agents for vascular events. It is unclear whether their long-term use affects cancer risk. Data on the chemopreventative role of these drugs on the risk of the upper aerodigestive tract cancer (UADT) are insufficient and mostly refer to oesophageal cancer. The aim of this study was to investigate the effect of aspirin and other NSAIDs on the risk of UADT cancers.Methods:A nested case-control study using the Primary Care Clinical Informatics Unit (PCCIU) database. Conditional logistics regression was used for data analysis.Results:There were 2392 cases of UADT cancer diagnosed between 1996 and 2010 and 7165 age-, gender- and medical practice-matched controls from 131 general medical practices. Mean age of cases was 66 years (s.d. 12) and most were male (63%). Aspirin was prescribed in a quarter of cases and controls, COX-2 inhibitors in 4% of cases and 5% of controls and other NSAIDs in 33% of cases and 36% of controls. Aspirin prescription was associated with a nonsignificant risk reduction of cancer of UADT (adjusted OR=0.9, 95% CI=0.8, 1.0), head and neck (HN; adjusted OR=0.9, 95% CI=0.7, 1.1) or the oesophagus (adjusted OR=0.8, 95% CI=0.7, 1.0). Similar results were found for COX-2 inhibitors prescription. Prescription of other NSAIDs was associated with significantly reduced risk of cancer of UADT (adjusted OR=0.8, 95% CI=0.7, 0.9), HN (adjusted OR=0.8, 95% CI=0.7, 0.9) and the oesophagus (adjusted OR=0.8, 95% CI=0.7, 0.9). An increased volume of aspirin prescriptions was associated with a significant risk reduction (test for trend

Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

addresses: Peninsula College of Medicine and Dentistry, St Luke's Campus, University of Exeter, Exeter, UK. [email protected]: PMCID: PMC3528446types: Journal Article; Research Support, Non-U.S. Gov't© 2012 Warren et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention

Differences in Efficacy and Safety of Pharmaceutical Treatments between Men and Women: An Umbrella Review

Being male or female is an important determinant of risks for certain diseases, patterns of illness and life expectancy. Although differences in risks for and prognoses of several diseases have been well documented, sex-based differences in responses to pharmaceutical treatments and accompanying risks of adverse events are less clear. The objective of this umbrella review was to determine whether clinically relevant differences in efficacy and safety of commonly prescribed medications exist between men and women. We retrieved all available systematic reviews of the Oregon Drug Effectiveness Review Project published before January 2010. Two persons independently reviewed each report to identify relevant studies. We dually abstracted data from the original publications into standardized forms. We synthesized the available evidence for each drug class and rated its quality applying the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Findings, based on 59 studies and data of more than 250,000 patients suggested that for the majority of drugs no substantial differences in efficacy and safety exist between men and women. Some clinically important exceptions, however, were apparent: women experienced substantially lower response rates with newer antiemetics than men (45% vs. 58%; relative risk 1.49, 95% confidence interval 1.35–1.64); men had higher rates of sexual dysfunction than women while on paroxetine for major depressive disorder; women discontinued lovastatin more frequently than men because of adverse events. Overall, for the majority of drugs sex does not appear to be a factor that has to be taken into consideration when choosing a drug treatment. The available body of evidence, however, was limited in quality and quantity, confining the range and certainty of our conclusions

Effect of low-dose aspirin use on survival of patients with gastrointestinal malignancies; an observational study

Background: Previous studies suggested a relationship between aspirin use and mortality reduction. The mechanism for the effect of aspirin on cancer outcomes remains unclear. The aim of this study was to evaluate aspirin use and survival in patients with gastrointestinal tract cancer. Methods: Patients with gastrointestinal tract cancer diagnosed between 1998 and 2011 were included. The population-based Eindhoven Cancer Registry was linked to drug-dispensing data from the PHARMO Database Network. The association between aspirin use after diagnosis and overall survival was analysed using Cox regression models. Results: In total, 13 715 patients were diagnosed with gastrointestinal cancer. A total of 1008 patients were identified as aspirin users, and 8278 patients were identified as nonusers. The adjusted hazard ratio for aspirin users vs nonusers was 0.52 (95% CI 0.44-0.63). A significant association between aspirin use and survival was observed for patients with oesophageal, hepatobiliary and colorectal cancer. Conclusions: Post-diagnosis use of aspirin in patients with gastrointestinal tract malignancies is associated with increased survival in cancers with different sites of origin and biology. This adds weight to the hypothesis that the anti-cancer effects of aspirin are not tumour-site specific and may be modulated through the tumour micro-environment