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.

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.

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.

The increased global demand for weapons is growing fast both military and civilian grade equipment. The defense industry is experiencing an increase in its trades and production over the globe. Currently global market trade of arms is about US$ 1.9 trillion, with a trend of increase. This paper investigates global trends in defense through analysis of global defense spending and R&D activities with the focus to Bosnian defense industry perspectives. It was observed that Bosnian defense industry has potential to be one of the key players of the national innovation system through which the national R&D output would make notable positive impact on the national economic performances.

Abstract To explore driver behavior in highly automated vehicles (HAVs), independent researchers are mainly conducting short experiments. This limits the ability to explore drivers’ behavioral changes over time, which is crucial when research has the intention to reveal human behavior beyond the first-time use. The current paper shows the methodological importance of repeated testing in experience and behavior related studies of HAVs. The study combined quantitative and qualitative data to capture effects of repeated interaction between drivers and HAVs. Each driver (n=8n=8) participated in the experiment on two different occasions (∼90 minutes) with one-week interval. On both occasions, the drivers traveled approximately 40 km on a rural road at AstaZero proving grounds in Sweden and encountered various traffic situations. The participants could use automated driving (SAE level 4) or choose to drive manually. Examples of data collected include gaze behavior, perceived safety, as well as interviews and questionnaires capturing general impressions, trust and acceptance. The analysis shows that habituation effects were attenuated over time. The drivers went from being exhilarated on the first occasion, to a more neutral behavior on the second occasion. Furthermore, there were smaller variations in drivers’ self-assessed perceived safety on the second occasion, and drivers were faster to engage in non-driving related activities and become relaxed (e. g., they spent more time glancing off road and could focus more on non-driving related activities such as reading). These findings suggest that exposing drivers to HAVs on two (or more) successive occasions may provide more informative and realistic insights into driver behavior and experience as compared to only one occasion. Repeating an experiment on several occasions is of course a balance between the cost and added value, and future research should investigate in more detail which studies need to be repeated on several occasions and to what extent.

Animal cognition research aims to understand animal minds by using a diverse range of methods across an equally diverse range of species. Throughout its history, the field has sought to mitigate various biases that occur when studying animal minds, from experimenter effects to anthropomorphism. Recently, there has also been a focus on how common scientific practices might affect the reliability and validity of published research. Usually, these issues are discussed in the literature by a small group of scholars with a specific interest in the topics. This study aimed to survey a wider range of animal cognition researchers to ask about their attitudes towards classic and contemporary issues facing the field. Two-hundred and ten active animal cognition researchers completed our survey, and provided answers on questions relating to bias, replicability, statistics, publication, and belief in animal cognition. Collectively, researchers were wary of bias in the research field, but less so in their own work. Over 70% of researchers endorsed Morgan’s canon as a useful principle but many caveated this in their free-text responses. Researchers self-reported that most of their studies had been published, however they often reported that studies went unpublished because they had negative or inconclusive results, or results that questioned “preferred” theories. Researchers rarely reported having performed questionable research practices themselves—however they thought that other researchers sometimes (52.7% of responses) or often (27.9% of responses) perform them. Researchers near unanimously agreed that replication studies are important but too infrequently performed in animal cognition research, 73.0% of respondents suggested areas of animal cognition research could experience a ‘replication crisis’ if replication studies were performed. Consistently, participants’ free-text responses provided a nuanced picture of the challenges animal cognition research faces, which are available as part of an open dataset. However, many researchers appeared concerned with how to interpret negative results, publication bias, theoretical bias and reliability in areas of animal cognition research. Collectively, these data provide a candid overview of barriers to progress in animal cognition and can inform debates on how individual researchers, as well as organizations and journals, can facilitate robust scientific research in animal cognition.

Abstract Rationale: Pentalogy of Cantrell (POC) is an extremely rare syndrome with an estimated incidence of 1:65,000 to 200,000 live births. Its complete form includes a midline epigastric abdominal wall defect, defects affecting the lower sternum, anterior diaphragm, diaphragmatic pericardium, and various intracardiac defects. Patient concerns: We report a case of complete POC affecting only the first-born of a set of premature dizygotic twins. Diagnosis: A giant omphalocele with an eviscerated liver and bowel on prenatal, obstetric ultrasonography at 24 gestational weeks was observed. At birth, physical examination confirmed a massive (10 × 8 cm) epigastric omphalocele in which a significant part of the liver was seen. A postnatal echocardiogram revealed the presence of an ostium secundum atrial septal defect, perimembranous ventricular septal defect, and moderate pulmonary stenosis. X-ray showed an abnormal intrathoracic positioned stomach, which was confirmed with a plain x-ray of the upper intestinal tract with hydrosoluble contrast. Computed tomography (CT) scan revealed the sternum's absence and a close connection between the pericardial sac and the stomach wall. Interventions: The patient underwent surgical intervention at 18 days of age. Outcomes: Despite adequate and appropriate postoperative treatment, the baby rapidly deteriorated and died 72 hours after surgery. Lessons: POC is a complex, high-mortality syndrome whose management requires a multidisciplinary approach and meticulous planning. Despite all efforts, POC carries a poor prognosis, particularly in patients affected by its complete form.

Interactive image-guided surgery technologies enable accurate target localization while preserving critical nearby structures in many surgical interventions. Current state-of-the-art interfaces largely employ traditional anatomical cross-sectional views or augmented reality environments to present the actual spatial location of the surgical instrument in preoperatively acquired images. This work proposes an alternative, simple, minimalistic visual interface intended to assist during real-time surgical target localization. The estimated 3D pose of the interventional instruments and their positional uncertainty are intuitively presented in a visual interface with respect to the target point. A usability study with multidisciplinary participants evaluates the proposed interface projected in surgical microscope oculars against cross-sectional views. The latter was presented on a screen both stand-alone and combined with the proposed interface. The instruments were electromagnetically navigated in phantoms. The usability study demonstrated that the participants were able to detect invisible targets marked in phantom imagery with significant enhancements for localization accuracy and duration time. Clinically experienced users reached the targets with shorter trajectories. The stand-alone and multi-modal versions of the proposed interface outperformed cross-sectional views-only navigation in both quantitative and qualitative evaluations. The results and participants’ feedback indicate potential to accurately navigate users toward the target with less distraction and workload. An ongoing study evaluates the proposed system in a preclinical setting for auditory brainstem implantation.

Complexity and complexity economics are relatively new fields of science, both of which started at the beginning of the 1980s. As it had emerged, questions have been raised regarding complexity’s applicability on human-involved systems and its predictive powers. Economics has been in the spotlight in recent years within the framework of complexity, since economics is one of the most well-established fields in social sciences. Within this framework, the field is referred to as complexity economics. While in its early years, complexity economics research had distanced itself from the reductionist neoclassic tradition of economics that has been identified by its use of, and reliance on, descriptive equations. One of the salient feature of complexity economics is its somewhat unorthodox approach to economic systems, as in its emphasis on non-equilibria. However in recent years, the proponents have become more assertive that complexity economics needs to be more modest and symbiotically co-exist with well-established mainstream economics. Although we focus on economics under the prism of complexity, our underlying interest is in the investigation of how other disciplines, such as industrial engineering and operations research, may benefit from a similar complexity-oriented perspective. Keywords: Complexity, complexity economics, mainstream economics, equation-based economics, non-equilibrium