The press-fit process is an efficient, low-cost method for joining parts. The parts that must be joined interfere with each other’s occupation of space; therefore, contact dimensions and their tolerances influence the quality of the assembly. The traditional method for the selection of contact dimensions and their tolerances is based on engineering experience. The idea of the research work presented in this paper is to optimize the press-fit process at an early stage of development process, involving prediction and optimization of the joining force and consequently the prediction and minimization of the rejection rate. Accordingly, several finite-element (FE) simulations of the press-fit process for predicting the joining forces were conducted, considering input-parameter variations (material properties: yield stress, hardening exponent; geometry: shaft diameter, guide diameter of the core, functional diameter of the core; friction coefficient). Based on FE simulations and 47 different input-parameter-variation results, the empirical model for predicting the joining force using the response-surface methodology (RSM) was obtained. By using RSM and a stochastic Monte Carlo simulation, the rejection rate was also determined. The predicted and the actual rejection rates for selected process parameters were 1.4 % and 1.5 %, respectively. Consequently, the press-fit process can also be optimized to reduce the rejection rate using the same Monte Carlo simulation. The results of the analysis show that the rejection rate can be reduced from 1.4 % to 0.2 %.

Physics curricula around the world recognise energy as one of the core concepts in science (Duit, 2014), as it is fundamental in development of integrated scientific understanding of phenomena (Linn et al., 2006; National Research Council, 2012; Nordine et al., 2011). Importance of the energy concept is also recognised by PISA and TIMSS studies and is reflected in many science standards (National Research Council, 2012; Next Generation Science Standards, 2013). However, research about students’ energy conceptions keeps showing that students at all educational levels have significant difficulties with the concept of energy (Goldring & Osborne, 1994; Lawson & McDermott, 1987; Neumann et al., 2013; Pride et al., 1998). Concretely, students exhibit difficulties with understanding work-energy processes (Van Huis & Van den Berg, 1993), energy degradation and energy conservation (Goldring & Osborne, 1994; Liu & McKeough, 2005; Neumann et al., 2013). Thereby, a large number of studies detected conservation of energy as the most difficult aspect of the energy concept (Lindsey et al., 2012; Neumann et al., 2013; Van Heuvelen & Zou, 2001; Van Huis & Van den Berg, 1993). In fact, only a very few students develop deeper understanding of energy conservation until the time they finish secondary school (Herrmann-Abell & DeBoer, 2018). For purposes of improving the quality of teaching about energy, it is useful to identify possible sources of above-mentioned students’ difficulties. Firstly, it is important to note that many students’ difficulties with the energy concept may be related to students’ (mis)understanding of systems (Seeley et al., 2019; Van Heuvelen & Zou, 2001; Van Huis & Van den Berg, 1993). Consequently, students should be helped to recognize the importance of carefully choosing the physical system, if one wants them to gain a functional understanding of energy conservation (Lindsey et al., 2012; Seeley et al., 2019). Such system-based Abstract. Conventional teaching about the law of conservation of mechanical energy (LCME) often results with students trying to solve problems by remembering similar problems they already covered in classes. Consequently, many students fail to transfer their knowledge to simplest real-life problems. Therefore, a pre-test – post-test quasi-experiment was conducted to evaluate the effects of an alternative, system-based approach to teaching about LCME. The study included 70 upper-secondary students from the First Bosniak Gymnasium Sarajevo, Bosnia and Herzegovina. Firstly, all students learned about energy in a conventional way. Then they wrote a test on LCME and had three additional hours of teaching about this topic, where one group of students learned in line with the forces-variant of the system approach (e.g., discussing conservative and nonconservative forces) and the other group with the process-variant of the same approach (e.g., discussing system’s states and processes like in thermodynamics). For both variants, only three hours of system-based teaching proved to substantially improve the students’ level of LCME understanding compared to the level of understanding they had after conventional teaching. It follows that the system approach may work well at the upper-secondary level, if it is introduced through the scaffolding-andfading technique.

Učbenik obravnava ergonomijo izdelkov tako z vidika razvojnega inženirja, ki mora v prvi vrsti seveda zagotoviti funkcionalnost izdelka, kot tudi z vidika oblikovalca - dizajnerja, ki naj poskrbi, da bo izdelek tudi estetsko dovršen. Namen učbenika ni podajanje empiričnih podatkov, temveč seznanitev z osnovnimi pojmi ter predstavitev medsebojnih relacij in priporočil, ki so lahko inženirjem in oblikovalcem v pomoč pri razvoju izdelkov s poudarjeno ergonomsko in estetsko vrednostjo. V drugi izdaji učbenika je dodano tudi povsem novo poglavje, ki obravnava inkluzivno oblikovanje in njegove najpomembnejše vidike. Ti v večini primerov sovpadajo z ergonomskimi vidiki razvoja izdelkov ob eni pomembni razliki. Pri razvoju izdelka s poudarjeno ergonomsko vrednostjo izdelek praviloma poskušamo kar se da prilagoditi bolj ali manj omejeni ciljni populaciji uporabnikov, cilj inkluzivnega oblikovanja pa je razvoj takšnih izdelkov, ki so primerni za čim širšo populacijo.

Objetivo: Discorrer sobre o impacto da Síndrome de Burnout em enfermeiros do setor de urgência e emergência. Metodologia: Trata-se de uma revisão integrativa da literatura, seguindo seis etapas: formação da hipótese ou indagação da pesquisa; amostragem ou busca na literatura; coleta de dados; análise dos estudos incluídos na revisão; interpretação e discussão dos resultados; apresentação da revisão integrativa. Resultados: Os 14 artigos considerados para este estudo foram descritos na tabela, contendo identificação os seguintes itens: título, autor / ano, base de dados, metodologia e resultados. Os resultados identificaram os principais sinais e sintomas de Burnout que acometem o profissional de enfermagem, bem como os fatores que causam impacto na qualidade de vida, e as características do setor de urgência e emergência que influenciam no desencadeamento da síndrome de Burnout. Conclusão: Conclui-se que, o setor de urgência e de um hospital é um local propicio as doenças psicossomáticas aos profissionais que trabalham neste ambiente.

We present an application of generalized strong complete mappings to construction of a family of mutually orthogonal Latin squares. We also determine a cycle structure of such mapping which form a complete family of MOLS. Many constructions of generalized strong complete mappings over an extension of finite field are provided.

Microwave line-of-sight radio relay (RR) systems are a constitutive part of a telecom operator transport network, as an alternative to optical transmission systems when the latter are not technically possible or rational to implement. Nowadays, RR links are quite often used in the access network for connecting mobile radio base stations, thus also enabling traffic aggregation, and so on. In this paper, we focus on a practical, real-life, five-section heterogeneous RR network, comprising classic synchronous digital hierarchy (SDH) and SDH new generation network (NGN) architecture, hybrid parallel and mutually independent transmission of native Ethernet and TDM services, and all-IP network parts. Specifically, the main task of this work is to answer whether such a diverse RR system could satisfy the quality norms for Ethernet-based services, meaning whether a tolerable RR unavailability will necessarily imply the according Ethernet quality of service (QoS) degradation. This question is addressed by the comprehensive in-service and out-of-service testing of an operational hybrid RR transmission system. After extensive practical testing and appropriate analysis of the achieved results, it came out that the impact of RR-level impairments that determine the performance prediction affected the Ethernet QoS to the extent that BER values increased to the acceptability threshold values. We believe that the preliminary results reported here could serve as a hint and a framework for a more comprehensive cross-layer test strategy in terms of both test diversity and repeating rate, which contemporary network operators need to implement in order to enable the appropriate quality of experience for users of their services.

ABSTRACT The aim of this systematic review was to determine the causal role of Erysipelatoclostridium ramosum in specific invasive infections in humans, and to assess the clinical outcome of antibiotic therapy used to treat them. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with a systemic inflammatory response syndrome (SIRS) due to E. ramosum isolated from body fluids or tissues in which it is not normally present. Only reports identifying E. ramosum as the only microorganism isolated from a patient with SIRS were included. This systematic review included 15 studies reporting 19 individual cases in which E. ramosum caused invasive infections in various tissues, mainly in immunocompromised patients. E. ramosum was most often isolated by blood cultures and identified by specific biochemical tests. Severe infections caused by E. ramosum were in most cases effectively treated with antibiotics, except in two patients, one of whom died. More than one isolate of E. ramosum exhibited 100% susceptibility to metronidazole, amoxicillin/clavulanate and piperacillin/tazobactam. On the other hand, individual resistance of this bacterium to penicillin, ciprofloxacin, clindamycin, imipenem and ertapenem was reported. This systematic review confirmed the clinical relevance of E. ramosum as a cause of a number of severe infections mainly in immunocompromised inpatients. Metronidazole and meropenem appear to be the antibiotics of choice that should be used in combination or as monotherapy to treat E. ramosum infections, depending on the type and severity of the infection.

Swallowing dysfunction, or dysphagia, occurs secondary to many underlying etiologies such as stroke and can lead to pneumonia. The upper esophageal sphincter (UES) is a major anatomical landmark that allows the passage of swallowed materials into the esophagus during swallowing. Delayed UES opening or reduced duration of opening can lead to the accumulation of pharyngeal residue, which can increase risk of aspiration. UES opening is observed through the inspection of radiographic exams, known as videofluoroscopy swallow studies (VFSSs), which expose patients to ionizing radiation and depend on subjective clinician interpretations. High resolution cervical auscultation (HRCA) is a non-invasive sensor-based technology that has been recently investigated to depict swallowing physiology. HRCA has been proposed for detecting UES opening duration through a deep learning framework. However, the proposed framework was only validated over swallows from patients. For such an algorithm to be robust, it has to be proven equally reliable for the detection of UES opening duration in swallows from both patients and healthy subjects. In this study, we intend to investigate the robustness of the HRCA-based framework to detect the UES opening in signals collected from a diverse population. The framework showed comparable performance regarding the UES opening detection with an average area under the ROC curve of 95%. The results indicate that the HRCA-based UES opening detection can provide superior performance on swallows from diverse populations which demonstrates the clinical potential of HRCA as a non-invasive swallowing assessment tool.

The novel Severe Acute Respiratory Syndrome Virus 2 (SARS-CoV-2) pandemic was declared by the WHO in March 2020, with the number of new cases per day exceeding 50 000 globally. The spread of SARS-CoV-2 across the world threw the pharmaceutical industry into a race for the first COVID-19 vaccine. Since then, COVID-19 new infection rates have increased substantially with the emergence of new SARS-CoV-2 variants, notably in the United Kingdom (B.1.1.7), South Africa (S.501Y.V2), and Brazil (B.1.1.28). Despite the success in formulating several highly efficacious vaccines in such a short period of time, certain reservations remain. Public hesitancy towards vaccination is of particular concern as it undermines the strategy of herd immunity. This wide-spread hesitancy towards vaccination necessitates the availability of alternative treatment options that could be more readily accepted. More worrisome, however, is the emergence of novel SARS-CoV-2 mutations and their resulting impact on the efficiency of vaccines and spike protein directed neutralizing monoclonal antibodies (NMAb). Data presented below examines the efficacy and use of NMAbs as post-exposure prophylaxis. NMAbs function through inhibiting the viral spike protein (S-protein) which binds to host cells, and therefore, inhibition of the S-protein blocks viral entry into host cells. The S-protein consists of two subunits, S1 and S2, with the receptor binding domain (RBD) residing on the S1 subunit. The RBD binds to the transmembrane metalloprotein, angiotensin converting enzyme 2 (ACE-2), found abundantly in lung, small intestine epithelia as well as renal and arterial linings, supporting corresponding clinical presentations of COVID-19. With the consideration of public hesitancy towards vaccination, coupled with a continuous influx of newly infected COVID-19 patients, establishing a suitable therapy for post-exposure prophylaxis is essential. Countries with vaccination hesitancy rates significantly below herd immunity threshold should consider investing in options for the prompt treatment of new positive cases. Efforts have been taken to utilize the neutralization of the S-protein of SARS-CoV-2 as a method of post-exposure prophylaxis and this can occur in one of three ways: functionally mimicking ACE-2 to bind the viruses RBD and stopping the ACE-2-RBD complex (1), binding to RBD without mimicking ACE-2 (2), and binding RBD but without stopping ACE-2-RBD binding (3). When conducting a search of all clinical trials testing the efficiency of NMAbs against SARS-CoV-2 with interest placed on trial start date, phase of study, number of participants, combination therapy (Y/N), and novel SARSCoV-2 therapy (Y/N), a significant increase in the number of clinical trials testing novel NMAbs targeting SARS-CoV-2 spike protein could be demonstrated (Figure 1). The main contributors to enrolment totals initially were Regeneron's SARS-CoV-2 spike protein combination therapy REGN10933 + REGN10987 now called REGN-COV2. Since the beginning of the first novel SARS-CoV-2 NMAb trials, not only do we see initial trials progress to advanced clinical trial stages, but we also observe additional novel NMabs. This includes Astrazeneca's AZD8895, AZD1061, and Tychan's TY027 which is a fully engineered human IgG NMab stated to decrease disease severity in acutely infected COVID-19 patents. Many new NMAbs have undergone testing and some show potential. VIR-7831 is a fully humanized anti-SARS-CoV-2 NMAb characterized by S309, an antibody that is able to neutralize SARSCoV-2. Importantly, the antibody binds to a highly conserved epitope found on the spike protein, challenging mutational escape. VIR-7831 was developed from S309 and has affinity for both coronaviruses. Currently, Vir Biotechnology Inc. are investigating its use in early COVID-19 infection in non-hospitalized patients. The trial is assessing key safety, tolerability, efficacy, and PK parameters, and results are expected July 2021 (NCT04545060). Similar to VIR-7831, BRII-196/198 blocks viral entry and neutralizes SARS-CoV-2 infection in vivo by binding to a highly conserved epitope on the spike protein. Specifically, BRII-198 binds to a different site on the spike protein, and its combination with BRII-196 resulted in synergistic effects. It is now expected to continue into phase II/III clinical trials as part of the NIH's Accelerating COVID-19 Therapeutic Interventions and Vaccines program (ACTIV). Here, it will be evaluated for safety and efficacy in people with mild to moderate COVID-19 severity who are at risk of disease progression (NCT04501978). Previous ACTIV trials included Eli Lilly's LY-CoV555 (bamlanivimab) which is currently authorized for use in mild-to-moderate COVID-19 and has recently received additional authorization for its use in combination with etesevimab. NMAbs have shown to be effective in reducing viral load in both animal and human trials. However, the impact on clinical outcomes has not been described in detail. Specifically, Regeneron's REGNCOV2 reported a response in sero-negative patients with high viral load in their interim analysis, with similar safety outcomes compared to placebo group. Fuelled with preclinical success, the combination therapy NMAb had high hopes for translating the reduction of viral load into clinical impact. In a recent publication, Regeneron presented descriptive data on the impact of REGN-COV2's ability to remove post treatment healthcare visits. While the NMAb did decrease the Received: 19 January 2021 Revised: 14 March 2021 Accepted: 22 March 2021

Abstract The coronavirus disease 2019 (COVID-19) pandemic has been as unprecedented as unexpected, affecting more than 105 million people worldwide as of 8 February 2020 and causing more than 2.3 million deaths according to the World Health Organization (WHO). Not only affecting the lungs but also provoking acute respiratory distress, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to infect multiple cell types including cardiac and vascular cells. Hence a significant proportion of infected patients develop cardiac events, such as arrhythmias and heart failure. Patients with cardiovascular comorbidities are at highest risk of cardiac death. To face the pandemic and limit its burden, health authorities have launched several fast-track calls for research projects aiming to develop rapid strategies to combat the disease, as well as longer-term projects to prepare for the future. Biomarkers have the possibility to aid in clinical decision-making and tailoring healthcare in order to improve patient quality of life. The biomarker potential of circulating RNAs has been recognized in several disease conditions, including cardiovascular disease. RNA biomarkers may be useful in the current COVID-19 situation. The discovery, validation, and marketing of novel biomarkers, including RNA biomarkers, require multi-centre studies by large and interdisciplinary collaborative networks, involving both the academia and the industry. Here, members of the EU-CardioRNA COST Action CA17129 summarize the current knowledge about the strain that COVID-19 places on the cardiovascular system and discuss how RNA biomarkers can aid to limit this burden. They present the benefits and challenges of the discovery of novel RNA biomarkers, the need for networking efforts, and the added value of artificial intelligence to achieve reliable advances.