Evaluating the association of TRPA1 gene polymorphisms with pain sensitivity: a protocol for an adaptive recall by genotype study

Background Pain is a complex polygenic trait whose common genetic underpinnings are relatively ill-defined due in part to challenges in measuring pain as a phenotype. Pain sensitivity can be quantified, but this is difficult to perform at the scale required for genome wide association studies (GWAS). Existing GWAS of pain have identified surprisingly few loci involved in nociceptor function which contrasts strongly with rare monogenic pain states. This suggests a lack of resolution with current techniques. We propose an adaptive methodology within a recall-by-genotype (RbG) framework using detailed phenotyping to screen minor alleles in a candidate ‘nociceptor’ gene in an attempt to estimate their genetic contribution to pain. Methods/design Participants of the Avon Longitudinal Study of Parents and Children will be recalled on the basis of genotype at five common non-synonomous SNPs in the ‘nociceptor’ gene transient receptor potential ankylin 1 (TRPA1). Those homozygous for the common alleles at each of the five SNPs will represent a control group. Individuals homozygous for the minor alleles will then be recruited in a series of three sequential test groups. The outcome of a pre-planned early assessment (interim) of the current test group will determine whether to continue recruitment or switch to the next test group. Pain sensitivity will be assessed using quantitative sensory testing (QST) before and after topical application of 10% cinnamaldehyde (a TRPA1 agonist). Discussion The design of this adaptive RbG study offers efficiency in the assessment of associations between genetic variation at TRPA1 and detailed pain phenotypes. The possibility to change the test group in response to preliminary data increases the likelihood to observe smaller effect sizes relative to a conventional multi-armed design, as well as reducing futile testing of participants where an effect is unlikely to be observed. This specific adaptive RbG design aims to uncover the influence of common TRPA1 variants on pain sensation but can be applied to any hypothesis-led genotype study where costly and time intensive investigation is required and / or where there is large uncertainty around the expected effect size. Trial registration: ISRCTN, ISRCTN16294731. Retrospectively registered 25th November 2021.

Feasibility Study on Electrical Properties of 20 kV Polymeric Insulator Dry Test and Rainwater Test

Insulator is a very important equipment in an electric power system. Ceramic insulators have been widely used to support conductors in 20 kV power lines. The problem of ceramic insulators is that they are heavy, easily contaminated on the surface and require a lot of energy in the manufacturing process. Therefore, polymer insulators were developed. This paper presents the design of an epoxy resin polymer insulator with Titanium Dioxide (TiO2) as a nanofiller. The leakage current test was carried out in a high voltage laboratory by applying an AC high voltage of 50 Hz to the insulator dry conditions and the insulator wetted by rainwater contaminants. The results of the leakage current test in dry conditions are 487.6 μA, rainwater contaminated conditions are 594.93 μA, insulation resistance in dry conditions is 2.07 G-Ohms, and contaminated conditions are 1.41 G-Ohms. Based on the test results show that the insulator leakage current increases up to 22% when the surface of the insulator is contaminated with rainwater. Meanwhile, the insulation resistance decreased by up to 32% in conditions contaminated with rainwater. The value of leakage current and insulation resistance indicates that the epoxy resin insulator with TiO2 as filler is electrically feasible to use.

Development of an Eddy Current Test Configuration for Welded Carbon Steel Pipes under the Change in Physical Properties

Carbon steel pipe is used in various industries, including nuclear power plants. Due to the daily cyclic operation of the pipe over time, environmental influences, and extreme working conditions, the probability of developing small fine cracks in the welded areas of the pipes increases. For that reason, it requires earlier assessment, and providing adequate inspection and evaluation of the weld area of the pipes used in such an installation is crucial to increase the safety level. In this paper, two different probe configurations were used to assess the integrity of the girth weld of the SA106 carbon steel pipe welded by gas tungsten arc welding. The conventional eddy current probe was initially used, but as it had some limitations, a new probe configuration was proposed to overcome these constraints. Numerical simulations using the finite element method were performed, based on the real measurement of the physical properties of the specimen, to complement the experimental data. In addition, the experimental results were successfully reproduced by the simulations. Simulation and experimental results show that the proposed probe configuration allows adequate inspection.

Molecular Detection of SARS-Cov-2 in Exhaled Breath Using a Portable Sampler

The SARS-CoV-2 pandemic has highlighted the need for improved technologies to help control the spread of contagious pathogens. While rapid point-of-need testing plays a key role in strategies to rapidly identify and isolate infectious patients, a cornerstone for any disease-control strategy, current test approaches have significant shortcomings related to assay limitations and sample type. Direct quantification of viral shedding in exhaled particles may offer a better rapid testing approach, since SARS-CoV-2 is believed to spread mainly by aerosols. It potentially measures contagiousness directly, the sample is easy to obtain, its production can be standardized between patients, and the limited sample volume lends itself to a fast and sensitive analysis. In view of these benefits, we developed and tested an approach where exhaled particles are efficiently sampled using inertial impaction in a micromachined silicon chip, followed by an in-situ RT-qPCR molecular assay to detect SARS-CoV-2 shedding. We demonstrate that sampling subjects using a one-minute breathing protocol, yields sufficient viral RNA to detect infections with a sensitivity comparable to standard sampling methods. A longitudinal study revealed clear differences in the temporal dynamics of viral load for nasopharyngeal swab, saliva, breath, and antigen tests. Overall, after an infection, the breath-based test is the first to consistently report a negative result, putatively signaling the end of contagiousness and further emphasizing the potential of this tool to help manage the spread of airborne respiratory infections.

Detection of Root Physiological Parameters and Potassium and Calcium Currents in the Rhizoplane of the Apple Rootstock Superior Line 12-2 With Improved Apple Replant Disease Resistance

The cultivation of resistant rootstocks is one of the more effective ways to mitigate apple replant disease (ARD). We performed an ion current test, a pot experiment, and a pathogen infection test on the apple rootstocks 12-2 (self-named), T337, and M26. The ion current test showed that exposure to ARD soil extract for 30 min had a significant effect on K+ ion currents at the meristem, elongation, and mature zones of the M26 rhizoplane and on Ca2+ currents in the meristem and elongation zones. ARD also had a significant effect on Ca2+ currents in the meristem, elongation, and mature zones of the T337 rhizoplane. Exposure to ARD soil extract for 5 min had a significant effect on K+ currents in the meristem, elongation, and mature zones of 12-2 and on the Ca2+ currents in the elongation and mature zones. Compared to a 5-min exposure, a 30-min exposure to ARD extract had a less pronounced effect on K+ and Ca2+ currents in the 12-2 rhizoplane. The pot experiment showed that ARD soil had no significant effect on any root architectural or physiological parameters of 12-2. By contrast, ARD soil significantly reduced some root growth indices and the dry and fresh weights of T337 and M26 compared with controls on sterilized soil. ARD also had a significant effect on root metabolic activity, root antioxidant enzyme activity (except superoxide dismutase for T337), and malondialdehyde content of T337 and M26. Pathogen infection tests showed that Fusarium proliferatum MR5 significantly affected the root structure and reduced the root metabolic activity of T337 and M26. It also reduced their root antioxidant enzyme activities (except catalase for T337) and significantly increased the root malondialdehyde content, reactive oxygen levels, and proline and soluble sugar contents. By contrast, MR5 had no such effects on 12-2. Based on these results, 12-2 has the potential to serve as an important ARD-resistant rootstock.

Older Adults’ Experiences Participating in Aging Strong 2020 Programs

User satisfaction assessments are integral to demonstrating intervention efficacy. Towards that end, older participants across the Aging Strong 2020 suite of offerings participated in semi-structured interviews (n = 248) to provide feedback about their experiences in the program and resulting satisfaction. Overall, most participants were satisfied with the Aging Strong 2020 interventions and reported gaining new skills, tools, or coping strategies. Participants endorsed program features that facilitated social interaction, community building, and social support. Program content specifically adapted for older adults and appropriate life stage concerns and/or areas of interest were considered especially helpful. Results demonstrate that the current test and learn model offers an opportunity for participant feedback to refine and improve future iterations of project offerings. Participant feedback led to key improvements in subsequent versions of the Aging Strong 2020 programs and their contributions to successful aging among older adults.

Moisture Accumulation in Building Façades Exposed to Accelerated Artificial Climatic Ageing—A Complementary Analysis to NT Build 495

Building façades must endure severe climatic exposure throughout their lifetimes. To prevent damage and expensive repairs, ageing tests are used in durability assessments. The NT Build 495 describes an artificial ageing procedure to address building material and component resistance to ultraviolet (UV) light, heat, water, and frost using a climate simulator. The test has been used for decades to investigate exterior surface materials and façade products but has only recently been adopted for multi-layered systems. This study investigates moisture accumulation in a façade system for retrofitting based on concrete and thermal insulation. Hygrothermal simulations of the façade system subjected to ageing were conducted. Moisture accumulation was considered theoretically for the current test procedure and compared to a modified setup in which the interior climate was controlled at 21 °C. Physical measurements were performed in the climate simulator to determine the boundary conditions. Results showed that moisture accumulation in the thermal insulation was largely affected by the type of concrete, that applying a water-repellent surface treatment reduced moisture accumulation, and that the current setup resulted in less moisture accumulation compared to the modified setup. The latter implicates accelerated degradation with the modified setup.

Development of Portable AIDS Diagnosis Device

It is estimated that there are 40 million people with AIDS worldwide, with most cases occurring mainly in developing countries. HIV, the virus that causes AIDS, is infected with CD4+ T cells in the blood and gradually destroys CD4+ T cells for several months to 10 years, thereby lowering the patient's immune function. AIDS patients who have weakened immunity in this way will die from various diseases. The current method for counting the number of CD4+ T cells is usually performed by flow cytometry. The flow cytometry method has the advantage of high accuracy, but it is difficult to use in developing countries because it requires skilled professionals and equipment is expensive. As a result of this study, a device for AIDS screening was developed by capturing leukocytes from a small amount of 5 ㎕ blood through a microfilter and analyzing CD4+ T cells and CD8+ T cells from the captured cells. cheaper and easier to carry and use than current test equipment.

Public nudity and the right to freedom of expression: Balancing competing interests

<p>With little case law concerning nudity and the right to freedom of expression, this paper aims to uncover the appropriate frameworks to be used to determine the following questions: (a) when is public nudity “expression” for the purposes of s 14 of the New Zealand Bill of Rights Act 1990, and (b) in what circumstances involving “expressive” public nudity would it be reasonable and demonstrably justifiable to limit the right to freedom of expression using s 4(1)(a), as per s 5 of the Bill of Rights Act? As regards the first of these questions, this paper critiques the current test in use in New Zealand for determining whether conduct is expression – the test developed by the Canadian Supreme Court in Irwin Toy Ltd v Attorney-general (Quebec) – and advocates for the adoption of a purposive approach to determining the scope of the right to freedom of expression. As for the second of these questions, this paper advocates for the adoption of “the modified Hansen sequence” proposed by Professor Claudia Geiringer. This paper then uses recent examples of public nudity involving naturists and protestors to test these frameworks and to illustrate how they would operate in practice.</p>

Public nudity and the right to freedom of expression: Balancing competing interests

<p>With little case law concerning nudity and the right to freedom of expression, this paper aims to uncover the appropriate frameworks to be used to determine the following questions: (a) when is public nudity “expression” for the purposes of s 14 of the New Zealand Bill of Rights Act 1990, and (b) in what circumstances involving “expressive” public nudity would it be reasonable and demonstrably justifiable to limit the right to freedom of expression using s 4(1)(a), as per s 5 of the Bill of Rights Act? As regards the first of these questions, this paper critiques the current test in use in New Zealand for determining whether conduct is expression – the test developed by the Canadian Supreme Court in Irwin Toy Ltd v Attorney-general (Quebec) – and advocates for the adoption of a purposive approach to determining the scope of the right to freedom of expression. As for the second of these questions, this paper advocates for the adoption of “the modified Hansen sequence” proposed by Professor Claudia Geiringer. This paper then uses recent examples of public nudity involving naturists and protestors to test these frameworks and to illustrate how they would operate in practice.</p>