The field of optimal design of linear elastic structures has seen many exciting successes that resulted in new architected materials and designs. With the availability of cloud computing, including high-performance computing, machine learning, and simulation, searching for optimal nonlinear structures is now within reach. In this study, we develop two convolutional neural network models to predict optimized designs for a given set of boundary conditions, loads, and volume constraints. The first convolutional neural network model is for the case of materials with a linear elastic response while the second developed model is for hyperelastic response where material and geometric nonlinearities are involved. For the nonlinear elastic case, the neo-Hookean model is utilized. For this purpose, we generate datasets, composed of the optimized designs paired with the corresponding boundary conditions, loads, and constraints, using topology optimization framework to train and validate both models. The developed models are capable of accurately predicting the optimized designs without requiring an iterative scheme and with negligible computational time. The suggested pipeline can be generalized to other nonlinear mechanics scenarios and design domains.

Precipitation hardening stainless steel 17-7PH with modified chemical composition was heat treated by modified RH950 condition. In this paper is presented the results of tests of microstructure and mechanical properties of precipitation hardened stainless steel 17-7PH with modified chemical composition, heat treated in modificated RH950 conditions. Regression analysis showed which variables are statistically significant in predicting the value of mechanical properties of the steel 17-7PH chemically modified composition.

One of the frequently occurring tasks during the development of a warehouse management system is the implementation of a routing algorithm of some kind. Whether it is for guiding workers during order picking, routing delivery vehicles or for routing company representatives, this task has proven to be challenging in the technical as well as the social sense. In other words, the task is heavily dependent on various company-specific constraints and it directly dictates the way employees should do their job. This paper describes a strategic approach to the development and gradual integration process of such algorithms which makes sure that all constraints are satisfied and, more importantly, ensures that route suggestions are viewed by the employees as a helpful tool rather than a threat to their job. Described through a real-world case study in a medium-to-large warehouse, the routing efficiency is almost doubled in comparison to the previous approach and critical factors are analysed and discussed throughout different stages of the process.

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Increased usage of genomic risk assessment assays suggests increased reliance on data provided by these assays to guide therapy decisions. The current study aimed to assess the change in treatment decision and physician confidence based on the 70-gene risk of recurrence signature (70-GS, MammaPrint) and the 80-gene molecular subtype signature (80-GS, BluePrint) in early stage breast cancer patients. IMPACt, a prospective, case-only study, enrolled 452 patients between November 2015 and August 2017. The primary objective population included 358 patients with stage I-II, hormone receptor-positive, HER2-negative breast cancer. The recommended treatment plan and physician confidence were captured before and after receiving results for 70-GS and 80-GS. Treatment was started after obtaining results. The distribution of 70-GS High Risk (HR) and Low Risk (LR) patients was evaluated, in addition to the distribution of 80-GS compared to IHC status. The 70-GS classified 62.5% (n = 224/358) of patients as LR and 37.5% (n = 134/358) as HR. Treatment decisions were changed for 24.0% (n = 86/358) of patients after receiving 70-GS and 80-GS results. Of the LR patients initially prescribed CT, 71.0% (44/62) had CT removed from their treatment recommendation. Of the HR patients not initially prescribed CT, 65.1% (41/63) had CT added. After receiving 70-GS results, CT was included in 83.6% (n = 112/134) of 70-GS HR patient treatment plans, and 91.5% (n = 205/224) of 70-GS LR patient treatment plans did not include CT. For patients who disagreed with the treatment recommended by their physicians, most (94.1%, n = 16/17) elected not to receive CT when it was recommended. For patients whose physician-recommended treatment plan was discordant with 70-GS results, discordance was significantly associated with age and lymph node status. The IMPACt trial showed that treatment plans were 88.5% (n = 317/358) in agreement with 70-GS results, indicating that physicians make treatment decisions in clinical practice based on the 70-GS result. In clinically high risk, 70-GS Low Risk patients, there was a 60.0% reduction in treatment recommendations that include CT. Additionally, physicians reported having greater confidence in treatment decisions for their patients in 72% (n = 258/358) of cases after receiving 70-GS results. “Measuring the Impact of MammaPrint on Adjuvant and Neoadjuvant Treatment in Breast Cancer Patients: A Prospective Registry” (NCT02670577) retrospectively registered on Jan 27, 2016.

Sore throat is a common reason for seeking medical help [1]. It can have infectious and non-infectious etiology [2]. The term “sore throat” is usually associated with an infectious agent (bacteria, viruses, and less commonly fungi) [1,3,4]. The terms “throat discomfort“, “throat irritation“, or “functional dysphonia due to the occupational diseases“ (which represents voice disorder) are often used in the same sense as non-infectious sore throat [2,3]. It is identified by the exclusion of infectious etiology symptoms accompanied with persistent sore throat symptoms (tingling and scratching sensation in the throat, hoarseness or muffled voice, foreign body sensation in the throat, coughing, and difficulty in swallowing accompanied by pain) [2,5]. Various factors can lead to non-infectious sore throat. The most important are: environmental (exposure to smog and irritants), individual risk factors (smoking, alcohol and excessive caffeine consumption, incorrect technique of using voice, and snoring), existence of other diseases (allergies, hormonal disorders, gastroesophageal refluxes, and anxiety disorders), and the use of some medications [2,6]. Epidemiological studies for non-infectious sore throat are rare. In a study performed on 1326 adults in the USA, it was found that 6.6% of respondents had current voice disorders while lifetime prevalence was 29.9% [6]. Professions more susceptible to non-infectious sore throat have high demands on vocal performance (for example, teachers, singers, sports coaches, receptionists, television and radio presenters, lawyers, touristic tour guides, and politicians) [2,3,7]. In modern societies, about one-third of the working population belongs to occupations in which the voice is the primary tool [8]. Teaching is a high-risk occupation for developing voice disorders. In a study performed on 2531 adults in the USA, teachers had higher prevalence of lifetime voice disorders (57.7%) as compared to other professions (28.8%) [5]. Voice problems may lead to a lower quality of teaching and a serious personal and emotional burden. This can have detrimental effects on the career of teachers, with negative consequences on pupils and employers [9]. Despite the adverse impact of non-infectious sore throat on professional performance and reduced quality of life, only a small number of teachers is seeking professional medical help [10]. This can be due to a low level of awareness on this topic. Although exact mechanisms of non-infectious sore throat development vary with etiology, inflammation can be found in the majority of cases [2], with elevated pro-inflammatory cytokines such as interleukin (IL)-6, IL-β, and tumor necrosis factor-α (TNF-α) [2,11,12]. There has been little systematic assessment of treatments for non-infectious sore throat. The field lacks objective outcomes, with most studies relying on subjective (self-reported) endpoints [2]. Although there is no unique doctrine in the treatment, anti-inflammatory medicines and antiseptics are usually used. Inflammation is the pathophysiological mechanism of both infectious and non-infectious sore throat, so similar anti-inflammatory therapies have beneficial effects in both etiologies [2]. Few studies showed positive effects of non-steroidal anti-inflammatory medicines, paracetamol, and steroids [13]. Various herbal formulations and antiseptic lozenges, sprays, and mouthwashes (with or without the addition of an anesthetic or analgesic) are most commonly used [2,12]. Lysozyme is natural enzybiotic with properties that could be beneficial in the treatment of non-infectious sore throat. Different types of lysozymes can be found in nature. They have similar structures and share the ability to hydrolyze bacterial cell wall peptidoglycan [14]. Lysozyme is a significant part of the immune system. In humans, it can be found in body secretions, mucosal surfaces, liver, blood, and immune cells [14]. Human milk is rich in lysozyme, which plays an important role in our immunity from the first days of life [15]. The pharmaceutical industry is mainly using hen egg white lysozyme in products for treatment of certain infectious and inflammatory diseases [16]. Besides its direct antibacterial activity, lysozyme has immunomodulatory and anti-inflammatory effects. Immunomodulatory effects have been demonstrated in cancer patients after chemotherapy, where it improved the recovery of CD4+/CD8+ lymphocyte ratio [17]. One of the proposed mechanisms is through the release of immunomodulatory Lysozyme in the treatment of non-infectious sore throat

Instructions for administering some drugs and indications for their use raise certain dilemmas and controversies questioning the appropriateness of the treatment in this way. In this article, some controversies regarding the prescribing of statins in patients whose blood cholesterol level is normal and the use of anticoagulants in the elderly patients without blood clots prior to the treatment are described. Also, it is discussed about some controversies regarding the use of the insulin analogues in the treatment of patients with diabetes mellitus.

Stable isotopically labelled organisms have found wide application in life science research including plant physiology, plant stress and defense as well as metabolism related sciences. Therefore, the reproducible production of plant material enriched with stable isotopes such as 13C and 15N is of considerable interest. A high degree of enrichment (> 96 atom %) with a uniformly distributed isotope (global labelling) is accomplished by a continuous substrate supply during plant growth/cultivation. In the case of plants, 13C-labelling can be achieved by growth in 13CO2(g) atmosphere while global 15N-labelling needs 15N- containing salts in the watering/nutrient solution. Here, we present a method for the preparation of 13C and 15N-labelled plants by the use of closed growth chambers and hydroponic nutrient supply. The method is exemplified with durum wheat. In total, 330 g of globally 13C- and 295 g of 15N-labelled Triticum durum wheat was produced during 87 cultivation days. For this, a total of 3.88 mol of 13CO2(g) and 58 mmol of 15N were consumed. The degree of enrichment was determined by LC-HRMS and ranged between 96 and 98 atom % for 13C and 95–99 atom % for 15N, respectively. Additionally, the isotopically labelled plant extracts were successfully used for metabolome-wide internal standardisation of native T.durum plants. Application of an isotope-assisted LC-HRMS workflow enabled the detection of 652 truly wheat-derived metabolites out of which 143 contain N. A reproducible cultivation which makes use of climate chambers and hydroponics was successfully adapted to produce highly enriched, uniformly 13C- and 15N-labelled wheat. The obtained plant material is suitable to be used in all kinds of isotope-assisted research. The described technical equipment and protocol can easily be applied to other plants to produce 13C-enriched biological samples when the necessary specific adaptations e.g. temperature and light regime, as well as nutrient supply are considered. Additionally, the 15N-labelling method can also be carried out under regular glasshouse conditions without the need for customised atmosphere.

E-learning is considered a leading application of digital technologies in educational systems. The aim of the paper is to explore the utilization and impact of digital technologies on an e-learning platform. For this purpose, research was conducted at the Moodle learning management system. Data from the e-learning platform were empirically evaluated in order to find key indicators of student performance in different courses. Student success with the e-learning system was evaluated using a mixed-method: Social Network Analysis, K-Means Clustering, and Multiple Linear Regression. The research was conducted at the University of Novi Sad, Faculty of Technical Sciences, Serbia. The results indicate a significant relationship between the performance of students and the use of digital educational resources from the e-learning platform.