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.

Effectiveness, Explainability and Reliability of Machine Meta-Learning Methods for Predicting Mortality in Patients with COVID-19: Results of the Brazilian COVID-19 Registry

The majority prognostic scores proposed for early assessment of coronavirus disease 19 (COVID-19) patients are bounded by methodological flaws. Our group recently developed a new risk score - ABC2SPH - using traditional statistical methods (least absolute shrinkage and selection operator logistic regression - LASSO). In this article, we provide a thorough comparative study between modern machine learning (ML) methods and state-of-the-art statistical methods, represented by ABC2SPH, in the task of predicting in-hospital mortality in COVID-19 patients using data upon hospital admission. We overcome methodological and technological issues found in previous similar studies, while exploring a large sample (5,032 patients). Additionally, we take advantage of a large and diverse set of methods and investigate the effectiveness of applying meta-learning, more specifically Stacking, in order to combine the methods' strengths and overcome their limitations. In our experiments, our Stacking solutions improved over previous state-of-the-art by more than 26% in predicting death, achieving 87.1% of AUROC and MacroF1 of 73.9%. We also investigated issues related to the interpretability and reliability of the predictions produced by the most effective ML methods. Finally, we discuss the adequacy of AUROC as an evaluation metric for highly imbalanced and skewed datasets commonly found in health-related problems.

Neutrophil-lymphoycyte-ratio, platelet-lymphocyte-ratio and procalcitonin for early assessment of prognosis in patients undergoing VA-ECMO

The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasing, but mortality remains high. Early assessment of prognosis is challenging and valid markers are lacking. This study aimed to investigate Neutrophil–Lymphocyte Ratio (NLR), Platelet-Lymphocyte-Ratio (PLR) and Procalcitonin (PCT) for early assessment of prognosis in patients undergoing VA-ECMO. This retrospective single-center cohort study included 344 consecutive patients ≥ 18 years who underwent VA-ECMO due to cardiogenic shock. Main exposures were NLR, PLR and PCT measured within 24 h after VA-ECMO initiation. The primary endpoint was all-cause in-hospital mortality. In total, 92 patients were included into final analysis (71.7% male, age 57 ± 14 years). In-hospital mortality rate was 48.9%. Receiver operating characteristics (ROC) curve revealed an area under the curve (AUC) of 0.65 [95% confidence interval (CI) 0.53–0.76] for NLR. The AUCs of PLR and PCT were 0.47 [95%CI 0.35–0.59] and 0.54 [95%CI 0.42–0.66], respectively. Binary logistic regression showed an adjusted odds ratio of 3.32 [95%CI 1.13–9.76] for NLR, 1.0 [95%CI 0.998–1.002] for PLR and 1.02 [95%CI 0.99–1.05] for PCT. NLR is independently associated with in-hospital mortality in patients undergoing VA-ECMO. However, discriminative ability is weak. PLR and PCT seem not to be suitable for this purpose.

A Novel Scoring System for Early Assessment of the Risk of the COVID-19-associated Mortality in Hospitalized Patients: COVID-19 BURDEN

Background: Corona Virus Disease 2019 (COVID-19) presentation resembles common flu or can be more severe; it can result in hospitalization with significant morbidity and/or mortality. We made an attempt to develop a predictive model and a scoring system to improve the diagnostic efficiency for COVID-19 mortality via analysis of clinical features and laboratory data on admission. Methods: We retrospectively enrolled 480 consecutive adult patients, aged 21-95, who were admitted to Faghihi Teaching Hospital. Clinical and laboratory features were extracted from the medical records and analyzed using multiple logistic regression analysis. Results: A novel mortality risk score (COVID-19 BURDEN) was calculated, incorporating risk factors from this cohort. CRP (> 73.1 mg/L), O2 saturation variation (greater than 90%, 84-90%, and less than 84%), increased PT (>16.2s), diastolic blood pressure (≤75 mmHg), BUN (>23 mg/dL), and raised LDH (>731 U/L) are the features comprising the scoring system. The patients are triaged to the groups of low- (score <4) and high-risk (score ≥ 4) groups. The area under the curve, sensitivity, and specificity for predicting non-response to medical therapy with scores of ≥ 4 were 0.831, 78.12%, and 70.95%, respectively. Conclusion: Using this scoring system in COVID-19 patients, the severity of the disease will be determined in the early stages of the disease, which will help to reduce hospital care costs and improve its quality and outcome.

A New Method to Estimate Peak Signal to Noise Ratio for Least Significant Bit Modification Audio Steganography

Audio steganography is implemented based on three main features: capacity, robustness, and imperceptibility, but simultaneously implementing them is still a challenge. Embedding data at the Least Significant Bit (LSB) of the audio sample is one of the most implemented audio steganography methods because the method will give high capacity and imperceptibility. However, LSB has the lowest robustness among all common methods in audio steganography. To cater to this problem, researchers increased the depth of the embedding level from fourth to sixth and eighth LSB level to improve its robustness feature. However, consequently, the imperceptibility feature, which is commonly measured by Peak Signal to Noise Ratio (PSNR), is reduced due to the trade-off between imperceptibility and robustness. Currently, the lack of study on the estimation of the PSNR for audio steganography has caused the early assessment of the imperceptibility-robustness trade-off difficult. Therefore, a method to estimate PSNR, known as PSNR Estimator (PE), is introduced to enable early evaluation of imperceptibility feature for each stego-file produced by the audio steganography, which is important for the utilisation of embedding. The proposed PE estimates the PSNR based on the pattern collected from the embedment at different levels. From the evaluation, the proposed method has 99.9% of accuracy in estimating PSNR values at different levels. In comparison with the Mazdak Method, the proposed method performs better in all situations. In conclusion, the proposed PE can be used as a reference for embedding and further reducing the calculation complexity in finding the feasible value to minimise the trade-off between robustness and imperceptibility.

Evaluation of the meat quality of chickens of the egg-meat direction of productivity, for promising use in organic production

Purpose: studying the features of the formation of signs of meat productivity in chickens of the egg-meat direction in the juvenile period in ontogenesis and fixing the most informative age for early assessment of meat qualities.Materials and methods. Young grew in group cells of a 3-tier cellular battery. The dynamics of growth and the development of exterior and interior indicators, characterizing meat productivity in ontogenesis in the young of the Pushkin breed of chickens, which refers to an egg-meat type on productivity through periodic (every 2 weeks) weighing and taking protections of the physique in 100 heads of young people. On 21 heads, an anatomical cutting was carried out at which the mass of the heart, liver, two parts of the stomach (muscular, iron), the sum of the muscles (femur, crus, metatisium) took into account. The development of meat forms of the physique to determine the age and individual characteristics was determined using exterior articles of industrial (the length of the body, the length of the keel, the gripping of the chest, the length of the leg, hips, plus). Prombs were taken from the entire experienced livestock, together with weighing, every 2 weeks. In order to find the most informative age for an early estimate of meat quality, which would characterize meat productivity at an older age, the correlation was calculated between the industrial over the age periods and the mass of muscles at 16 weeks.Results. The dynamics of the average daily growth of the living mass and the mass of the carved carcass in the roosters was uneven. Until 8-week age, the average daily increase increased, then began to decline until 14 weeks of age, during 16-week aged an average increase increased dramatically. The dynamics of average daily growths in the roosters of individual muscles was similar, namely, from 4 to 8-week age, high rates of average daily growth were noted, and from 8 to 14 months of age there is a decrease, and then again activation of growth. Studies have shown that the growth of the skeleton is slowed down by 14 weeks. The dynamics of the average daily growth of internal organs in the roosters in the juvenile period occurs asynchronously. The greatest intensity of the growth of the heart, liver and stomach was observed on a 8-week age. Studies have shown that the stomach is most intensively developing up to 8 weeks, then development is braked sharply.Conclusion. Based on the data obtained, it can be concluded that for the preliminary selection of chickens of the egg-meat direction of cultivation with the best genetic potential for meat productivity, it is possible at 8 weeks old, but the final rating should be carried out no earlier than 14-week age. The estimation of meat qualities in a 14-week age should be carried out on the basis of live masses and industrial, namely, the oblique length of the body, the girth plus, the length of the leg, the preliminary estimate can be done in such a precursor, as the slanting the length of the body, the length of the leg and girth plus.

Assessing the Risks and Success Factors of Telehealth Development Projects in an Academic Setting

The development of a telehealth technology in an academic setting is a complex project that faces several obstacles. The early assessment of the project risks plays a critical role in the translation of promising telehealth innovations into healthcare practice. This paper presents a decision support tool based on Failure Mode and Effects Analysis (FMEA) and Quality Function Deployment (QFD) techniques to associate the project risks to relevant success factors. Certain modifications in both techniques are applied to deploy them for project risk assessment. The project risks and success factors used in the tool are identified from the literature. The proposed decision support tool enables researchers to manage the risks in their telehealth development projects and identify action items to overcome such risks. The application of the proposed tool is illustrated with a telehealth development project for virtual physical therapy.

Assessment of Substrate and TBC Damage Effects on Resonance Frequencies for Blade Health Monitoring

The reliability of critical aircraft components continues to shift towards onboard monitoring to optimize maintenance scheduling, economy efficiency and safety. Therefore, the present study investigates changes in dynamic behavior of turbine blades for the detection of defects, with focus on substrate cracks and TBC spallation as they relate to vibration modes 1 to 6. Two‐dimensional and three-dimensional finite element simulation is used. The results indicate that TBC spallation reduces natural frequencies due to the ensuing hot spot and overall increase in temperature, leading to drops in blade stiffness and strength. Cracks cause even larger frequency shifts due to local plastic deformation at the crack that changes the energy dissipation behavior. Mode 1 vibration shows the largest shifts in natural frequencies that best correlate to the size of defects and their position. As such, it may be most appropriate for the early assessment of the severity and location of defects.

Role of C-reactive protein in predicting the outcome of acute pancreatitis

Background: Acute pancreatitis is one of the most commonly encountered clinical entities in surgical practice and controversy still exists regarding the clinical features of acute pancreatitis. An early diagnosis, however, is regarded as mandatory for successful treatment. Over the years many Authors have proposed different scoring systems for the early assessment of the clinical evolution of acute pancreatitis. The most widely used scoring systems are often cumbersome and difficult to use in clinical practice because of their multi factorial nature. Thus, a number of unifactorial prognostic indices have been employed in routine hospital practice, such as C-reactive protein (CRP), serum amylase and serum lipase. These serum enzymes are easy to obtain in normal clinical practice and many authors consider them as reliable as multi factorial scoring systems.Methods: A hospital based observational prospective study was done with 30 patients to measure C reactive protein levels in patients of acute pancreatitis and evaluate if CRP levels predict the severity of pancreatitis.Results: In cases where CRP was raised >100 mg/dl on day 7 and beyond showed either a complication or increased duration of stay and delayed recovery. This correspondence of CRP with the clinical outcome co related well with other parameters like blood counts, serum lipase and amylase levels too.Conclusions: Hence, CRP can be a very useful uni factorial tool in assessing and thereby predicting the outcome in a case of pancreatitis.

Noninvasive Multi-Disciplinary Management of Ectodermal Dysplasia with Hyposalivation – A Case Report

Ectodermal dysplasia (ED) is a rare genetic condition with nearly 200 documented traits. As the name states, ED targets tissues derived from ectoderms, such as hair, skin, nails, sweat glands, and teeth. Other orofacial structures might be affected, such as salivary glands and hard palate. Lack of teeth and diminished facial height can impact negatively on child growth and psychological well-being. Therefore, assessment and an interdisciplinary management plan of orofacial components of ED children should be installed as early as possible. Here we report an early assessment and multi-disciplinary management of ED child’s orofacial structures, which allow restoration of facial height and dental function and saliva reduction by the least invasive restorative approach in the form of the composite build-up of microdont and overdentures. It also highlights the importance of periodic evaluation of growth and treatment plan adjustment as an integral part of the transitional management until the age of a definite dental treatment.