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Kaonic atoms are an extremely efficient tool to investigate the strong interaction at the low energy Frontier, since they provide direct access to the K−N interaction at threshold, eliminating the necessity for extrapolation, unlike in the case of scattering experiments. During the 1970s and 1980s, extensive studies were performed on kaonic atoms spanning across a broad spectrum of elements in the periodic table, ranging from lithium to uranium. These measurements provided inputs and constraints for the theoretical description of the antikaon-nuclei interaction potential. Nevertheless, the existing data suffer from significant experimental uncertainties, and numerous measurements have been found to be inconsistent with more recent measurements that utilize advanced detector technology. Furthermore, there remain numerous transitions of kaonic atoms that have yet to be measured. For these reasons, a new era of kaonic atoms studies is mandatory. The DAΦNE electron-positron collider at the INFN Laboratory of Frascati (INFN-LNF) stands out as a unique source of low-energy kaons, having been utilized by Collaborations such as DEAR, SIDDHARTA, and AMADEUS for groundbreaking measurements of kaonic atoms and kaon-nuclei interactions. Presently, the SIDDHARTA-2 experiment is installed at DAΦNE, aiming to perform the first-ever measurement of the 2p → 1s x-ray transition in kaonic deuterium, a crucial step towards determining the isospin-dependent antikaon-nucleon scattering lengths. Based on the experience gained with the SIDDHARTA experiment, which performed the most precise measurement of the kaonic hydrogen 2p → 1s x-ray transition, the SIDDHARTA-2 setup is now fully equipped for the challenging kaonic deuterium measurement. In this paper, we present a comprehensive description of the SIDDHARTA-2 setup and of the first kaonic atoms measurements performed during the commissioning phase of the DAΦNE collider. We also outline a proposal for future measurements of kaonic atoms at DAΦNE beyond SIDDHARTA-2, which is intended to stimulate discussions within the broad scientific community performing research, directly or indirectly, related to this field.

The World Health Organization estimates that 71 million people worldwide have chronic hepatitis C viral infection. A major challenge is overall lack of public awareness of hepatitis C, particularly among infected people of their infection status. Chronic hepatitis C infection is associated with advanced liver disease, is the main cause of hepatocellular carcinoma and causes many extra-hepatic manifestations. The existence of seven viral genotypes complicates targeting of treatment. Recent years have seen the approval of many direct acting antivirals targeted at hepatitis C virus non-structural proteins. These have revolutionized therapy as they allow achievement of extremely high sustained virologic responses. Of great significance is the development of pan-genotypic drug combinations, including the NS3/4A-NS5A inhibitor combinations sofosbuvir–velpatasvir and glecaprevir–pibrentasvir. However, resistance-associated mutations can result in failure of these treatments in a small number of patients. This, combined with the high costs of treatment, highlights the importance of continued research into effective anti-hepatitis C therapies, for example aimed at viral entry. Recent developments include identification of the potential of low-cost anti-histamines for repurposing as inhibitors of hepatitis C viral entry. In this review we focus on molecular biology of hepatitis C virus, and the new developments in hepatitis C treatment. Keywords: Hepatitis, Direct-acting antiviral, Sofosbuvir, Resistance-associated variant, NS5A

Introduction: Increasing prevalence of antimicrobial resistance is a major concern especially in light of lack of new antimicrobial agents. Here, we present antibiotic resistance pattern of gram-negative bacteria (GNB) over six years (2013–2018) in a hospital in Saudi Arabia. Materials and Methods: The study included a report of the cumulative antibiogram of GNB. Interpretation of the antibacterial susceptibility tests was based on the Clinical and Laboratory Standards Institute guidelines and VITEK® 2 system. Results: There was a total of 32,890 GNB isolates and the most common were: Escherichia coli (69.8%), Klebsiella pneumoniae (17.2%) and Pseudomonas aeruginosa (12.8%). Antimicrobial susceptibility of P. aeruginosa and E. coli did not change overtime, however, susceptibility to ceftazidime decreased from 92% to 85% in P. aeuroginosa. Yearly antimicrobial susceptibility did not change significantly overtime for K. pneumoniae. ESBL isolates among K. peumoniae and E. coli was about 26% and 20%, respectively (p = 0.0068). For ESBL E. coli, the least effective antibiotics were ciprofloxacin (26%) and trimethoprim-sulfamethoxazole (34%). For ESBL K. pneumoniae, gentamicin, ciprofloxacin, trimethoprim-sulfamethoxazole, and nitrofurantoin had poor activity. For K. pneumoniae, both ciprofloxacin (90%) and trimethoprim-sulfamethoxazole (86%) had better coverage than for E. coli. K. pneumoniae showed less susceptibility to nitrofurantoin than E. coli (20% vs. 92%). Conclusion: Antibiotic resistance among P. aeruginosa and E. coli did not change overtime (2013–2018) and the rate of ESBL-producing E. coli and K. pneumoniae was high. Thus, continued surveillance is needed. Keywords: Antibiotic resistance, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa

Rapid tests to diagnose tuberculosis relies on molecular detection of the M. tuberculosis. GeneXpert MTB/RIF test identifies M. tuberculosis and rifampicin resistance. We present a case of simultaneous coinfection with M. tuberculosis and M. avium. M. tuberculosis was detected in the sputum by PCR GeneXpert method. Unrecognized coexistence of M. tuberculosis and M. avium modified the results of drug susceptibility tests making the primary identification of M. tuberculosis as multi-drug resistant strain. We performed in vitro experiments to investigate the effect of the coexistence of M. avium with M. tuberculosis on the results of GeneXpert method, and drug susceptibility test. Keywords: Tuberculosis, Mycobacterium avium, GeneXpert

Ventricular fibrillation (VF) is a life-threatening electromechanical dysfunction of the heart associated with complex spatiotemporal dynamics of electrical excitation and mechanical contraction of the heart muscle. It has been hypothesized that VF is driven by three-dimensional rotating electrical scroll waves, which can be characterized by filamentlike electrical phase singularities or vortex filaments, but visualizing their dynamics has been a long-standing challenge. Recently, it was shown that rotating excitation waves during VF are associated with rotating waves of mechanical deformation. Three-dimensional mechanical scroll waves and mechanical filaments describing their rotational core regions were observed in the ventricles by using high-resolution ultrasound. The findings suggest that the spatiotemporal organization of cardiac fibrillation may be assessed from waves of mechanical deformation. However, the complex relationship between excitation and mechanical waves during VF is currently not understood. Here, we study the fundamental nature of mechanical phase singularities, their spatiotemporal organization, and their relation with electrical phase singularities. We demonstrate the existence of two fundamental types of mechanical phase singularities: “paired singularities,” which are colocalized with electrical phase singularities, and “unpaired singularities,” which can form independently. We show that the unpaired singularities emerge due to the anisotropy of the active force field, generated by fiber anisotropy in cardiac tissue, and the nonlocality of elastic interactions, which jointly induce strong spatiotemporal inhomogeneities in the strain fields. The inhomogeneities lead to the breakup of deformation waves and create mechanical phase singularities, even in the absence of electrical singularities, which are typically associated with excitation wave break. We exploit these insights to develop an approach to discriminate paired and unpaired mechanical phase singularities, which could potentially be used to locate electrical rotor cores from a mechanical measurement. Our findings provide a fundamental understanding of the complex spatiotemporal organization of electromechanical waves in the heart and a theoretical basis for the analysis of high-resolution ultrasound data for the three-dimensional mapping of heart rhythm disorders.

Objectives: The influenza A(H1N1)pdm09 virus caused a worldwide pandemic in 2009–2010 and has since remained in seasonal circulation. This study was conducted to determine any variations in the influenza A(H1N1)pdm09 status according to sex, age group, sample type, or location within the Eastern Province of the Kingdom of Saudi Arabia. Methods: Samples from 749 patients with suspected Middle East respiratory coronavirus who presented to Johns Hopkins Aramco Healthcare facilities in the Eastern Province of Saudi Arabia were tested reflexively for influenza A/H1N1 2009 by the Ministry of Health using the RealTime ready Influenza A/H1N1 Detection Set for real-time PCR. The sample types included nasopharyngeal swabs (n = 677), expectorated deep cough sputum (n = 32), induced sputum (n = 17), and tracheal aspirates (n = 23). Results: The incidence of influenza A(H1N1)pdm09 was higher among younger patients; 27.94% of patients in the 0–19-year age group tested positive compared to only 3.51% of patients in the ≥80-year age group. The incidence of influenza A(H1N1)pdm09 was higher in Ras Tanura city compared to other locations in the Eastern Province. Conclusions: Younger individuals in the Eastern Province of the Kingdom of Saudi Arabia had a relatively higher risk of influenza A(H1N1)pdm09 infection. Additionally, an outbreak of influenza A(H1N1)pdm09 may have occurred in Ras Tanura city between April 2015 and February 2016. Keywords: Influenza A(H1N1)pdm09, Saudi Arabia, Eastern Province, Ras Tanura, Real-time PCR

Abstract The VIolation of Pauli exclusion principle -2 experiment, or VIP-2 experiment, at the Laboratori Nazionali del Gran Sasso searches for X-rays from copper atomic transitions that are prohibited by the Pauli exclusion principle. Candidate direct violation events come from the transition of a 2p electron to the ground state that is already occupied by two electrons. From the first data taking campaign in 2016 of VIP-2 experiment, we determined a best upper limit of $$3.4~\times ~10^{-29}$$ 3.4×10-29 for the probability that such a violation exists. Significant improvement in the control of the experimental systematics was also achieved, although not explicitly reflected in the improved upper limit. By introducing a simultaneous spectral fit of the signal and background data in the analysis, we succeeded in taking into account systematic errors that could not be evaluated previously in this type of measurements.

GeneXpert MRSA kits (Cepheid) are based on a multiplex, real-time PCR method for methicillin-resistant Staphylococcus aureus (MRSA) detection, with primers to detect each SCCmec type and the chromosomal orfX-SCCmec junction. Modifications in recent kit versions were proposed to help overcome false-positive issues in earlier kit versions. The main objective of this study was to determine whether use of any version of the GeneXpert MRSA multiplex, real-time PCR kits yielded higher than expected MRSA+ results. We also estimated the level of MRSA in our healthcare facility as a proportion of total S. aureus between 2010 and 2015. We examined results from five generations of the kits used between 2008 and 2015. Results were from nasal swab samples from 16,431 patients in the Johns Hopkins Aramco Healthcare facility in Saudi Arabia. The percentage of isolates scored as MRSA+ for the original Xpert MRSA kit was 18.57%, compared to 6.93 ± 1.12% (mean ± SD) for the other four kits. The Xpert MRSA-SA Nasal kit yielded 6.48% Invalid results, compared to 0.73 ± 0.28% for the other four kits. The succeeding Xpert MRSA-SA Nasal G3 and Xpert MRSA-SA Nasal Complete G3 kits yielded Invalid results rates of 0.29% and 1.04% respectively. Levels of MRSA-positive isolates as a percentage of total S. aureus-containing samples ranged between 19.81% and 26.74%. In conclusion, the original Xpert MRSA kit yielded higher than expected rates of MRSA+. Issues with over-estimation of MRSA+ and/or numerous Invalid results have been overcome in the most recent modified kits. Keywords: MRSA, Staphylococcus aureus, GeneXpert, Real-time PCR

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging disease with a relatively high case fatality rate. Most cases have been reported from Saudi Arabia, and the disease epidemic potential is considered to be limited. However, human–human transmission has occurred, usually in the context of healthcare facility-associated outbreaks. The scientific and medical community depends on timely publication of epidemiological information on emerging diseases during outbreaks to appropriately target public health responses. In this review, we considered the academic response to four MERS CoV outbreaks that occurred in Al-Hasa in 2013, Jeddah in 2014 and Riyadh in 2014 and 2015. We analysed 68 relevant epidemiology articles. For articles for which submission dates were available, six articles were submitted during the course of an outbreak. One article was published within a month of the Al-Hasa outbreak, and one each was accepted during the Jeddah and Riyadh outbreaks. MERS-CoV epidemiology articles were cited more frequently than articles on other subjects in the same journal issues. Thus, most epidemiology articles on MERS-CoV were published with no preferential advantage over other articles. Collaboration of the research community and the scientific publishing industry is needed to facilitate timely publication of emerging infectious diseases. Keywords: Middle East Respiratory Syndrome Coronavirus, Outbreak, Epidemiology, Publication, Saudi Arabia, MERS-CoV

Effective implementation of infection prevention and control in healthcare facilities depends on training, awareness and compliance of healthcare workers. In Saudi Arabia recent significant hospital outbreaks, including Middle East Respiratory Syndrome Coronavirus (MERS-CoV), have resulted from lack of, or breakdown in, infection prevention and control procedures. This study was designed to assess attitudes to, and awareness of, infection prevention and control policies and guidelines among healthcare workers of different professions and institution types in Saudi Arabia. A questionnaire was administered to 607 healthcare workers including physicians (n = 133), nurses (n = 162), laboratory staff (n = 233) and other staff (n = 79) in government hospitals, private hospitals and poly clinics. Results were compared using Chi square analysis according to profession type, institution type, age group and nationality (Saudi or non-Saudi) to assess variability. Responses suggested that there are relatively high levels of uncertainty among healthcare workers across a range of infection prevention and control issues, including institution-specific issues, surveillance and reporting standards, and readiness and competence to implement policies and respond to outbreaks. There was evidence to suggest that staff in private hospitals and nurses were more confident than other staff types. Carelessness of healthcare workers was the top-cited factor contributing to causes of outbreaks (65.07% of total group), and hospital infrastructure and design was the top-cited factor contributing to spread of infection in the hospital (54.20%), followed closely by lack and shortage of staff (53.71%) and no infection control training program (51.73%). An electronic surveillance system was considered the most effective by staff (81.22%). We have identified areas of concern among healthcare workers in Saudi Arabia on infection prevention and control which vary between institutions and among different professions. This merits urgent multi-factorial actions to try to ensure outbreaks such as MERS-CoV can be minimized and contained. Keywords: Saudi Arabia, Infection prevention, Infection control, Healthcare workers, MERS-CoV

Summary: Matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry facilitates rapid and accurate identification of pathogens, which is critical for sepsis patients.In this study, we assessed the accuracy in identification of both Gram-negative and Gram-positive bacteria, except for Streptococcus viridans, using four rapid blood culture methods with Vitek MALDI-TOF-MS. We compared our proposed lysis centrifugation followed by washing and 30% acetic acid treatment method (method 2) with two other lysis centrifugation methods (washing and 30% formic acid treatment (method 1); 100% ethanol treatment (method 3)), and picking colonies from 90 to 180 min subculture plates (method 4). Methods 1 and 2 identified all organisms down to species level with 100% accuracy, except for Streptococcus viridans, Streptococcus pyogenes, Enterobacter cloacae and Proteus vulgaris. The latter two were identified to genus level with 100% accuracy. Each method exhibited excellent accuracy and precision in terms of identification to genus level with certain limitations. Keywords: MALDI-TOF, Gram-negative, Gram-positive, Sepsis, Blood culture

Summary: Compared to routine isolated colony-based methods, direct testing of bacterial pellets from positive blood cultures reduces turnaround time for reporting of antibiotic susceptibility.The aim of this study was to compare the accuracy, and precision, of a rapid method for direct identification and susceptibility testing of blood cultures with the routine method used in our laboratory, using Vitek 2. A total of 60 isolates were evaluated using the candidate and the routine method. The candidate method had 100% accuracy for the identification of Gram negative bacteria, Staphylococcus and Enterococcus, 50% for Streptococcus and 33.3% for Corynebacterium species. Susceptibility testing of Gram negative isolates yielded 98–100% essential agreement. For Staphylococcus and Enterococcus isolates, essential agreement was 100% for 17 antibiotics except for moxifloxacin. Direct testing of blood culture samples with Vitek 2 produced reliable identification and susceptibility results 18–24 h sooner for aerobic/anaerobic facultative Gram-negative bacteria and Gram-positive Staphylococcus and Enterococcus strains. Keywords: Blood culture, Microbial identification, Susceptibility, Vitek II

This study presents a novel fully distributed and cooperative demand side management framework based on adaptive diffusion strategy. In this approach, each customer autonomously and without any need for the global information, minimises his incommodity function. The proposed framework has ability to track drifts resulting from the changes in the customer preferences and conditions or any rapidly changing price parameter coming from the wholesale market. In this scenario, the customers aim at maximising their individual utility functions; while the utility company aims at minimising the smart grid total payment (i.e. maximisation of the social welfare). The authors show that there is no need for the utility company to participate in the scheduling program for maximising social welfare. This measurement is maximised adaptively when the customers minimise their incommodity. Moreover, the authors provide a detailed analysis of the robustness of the proposed strategy in the presence of imperfect communication/computation conditions. Numerical results show that the proposed framework performs well, is scale free, and can achieve lower peak-to-average ratio of the total energy demand compared with that achieved by the game theoretical methods.

The current Zika virus outbreak in the Americas and the proposed link to increases in microcephaly and neurological disorders have prompted the World Health Organization to declare a Public Health Emergency of International Concern on February 1, 2016. The virus is transmitted by Aedes mosquitoes and potentially by transfusion, perinatal and sexual transmission. The potential for spread into countries where Aedes mosquitoes are endemic is high. Previously, cases tended to be sporadic and associated with mild, non-specific symptoms. Prior outbreaks occurred in Yap Island in Micronesia in 2007, the first time Zika arose outside of Africa and Asia, and in French Polynesia in 2013. A birth data review has confirmed that the latter outbreak was followed by an increase in microcephaly cases. A coordinated international response is needed to address mosquito control; expedite development of diagnostic tests, vaccines and specific treatments for Zika; and address the proposed link to microcephaly and neurological diseases. Keywords: ZIKV, Zika infection, Epidemiology, Transmission, Control measures, Diagnostic test

Summary: Active surveillance cultures for multidrug-resistant (MDR) gram-negative bacteria is one strategy to control outbreaks. The objectives of the study are to evaluate the prevalence of Acinetobacter colonization and to compare conventional culture and in-house developed PCR based method. Swabs were collected from patients transferred from another organization or were admitted to the intensive care units. Swabs were cultured by conventional method and were tested using in-house LightCycler® 2.0 real-time PCR method. Of 449 tested samples, the majority came from cardiac step down unit (188, 42%), male medical floor (80; 18%), and coronary care unit (66; 13.4%). Of the total specimens, 14 (3%) were positive by PCR and 12 (2.6%) were positive by routine cultures. The positivity rates among wounds, respiratory, perineal, and nasal samples were 3.2%, 9.7%, 4.6% and 0.8% respectively. Two positive samples by PCR were negative by routine culture. The overall concordance rate was 99.5% and the positive concordance rate was 85.7%. The current study revealed a low prevalence of MDR Acinetobacter among the studied population. The LightCycler® 2.0 PCR produced comparable positive results to routine cultures. Keywords: Acinetobacter, Surveillance, Epidemiology

Summary: Panton-Valentine leukocidin (PVL) is a two-component toxin associated with the toxicity and virulence of Staphylococcus aureus. The presence of PVL is well documented in community-acquired methicillin-resistant S. aureus (CA-MRSA) and is observed in methicillin-susceptible S. aureus (MSSA) with variable prevalence. We assessed the prevalence of PVL in a sample of 93 MSSA patients in a healthcare facility in Eastern Saudi Arabia using real-time PCR for lukSF-PV genes. The presence or absence of PVL was correlated with age, gender, hospitalization status, infection site and antibiotic resistance. PVL was detected in 28 (30%) patient samples. PVL was associated with a greater likelihood of resistance to trimethoprim–sulfamethoxazole (a resistance of 39.2% of PVL-positive isolates compared to 6.1% of PVL-negative isolates) (p

Fusarium infections in solid-organ transplant recipients are rare and carry high mortality. We report a case of a kidney transplant recipient who developed infection with Fusarium species. The patient received treatment with oral voriconazole for five months with good response.

Demand side energy consumption scheduling is a well-known issue in the smart grid research area. However, there is lack of a comprehensive method to manage the demand side and consumer behavior in order to obtain an optimum solution. The method needs to address several aspects, including the scale-free requirement and distributed nature of the problem, consideration of renewable resources, allowing consumers to sell electricity back to the main grid, and adaptivity to a local change in the solution point. In addition, the model should allow compensation to consumers and ensurance of certain satisfaction levels. To tackle these issues, this paper proposes a novel autonomous demand side management technique which minimizes consumer utility costs and maximizes consumer comfort levels in a fully distributed manner. The technique uses a new logarithmic cost function and allows consumers to sell excess electricity (e.g. from renewable resources) back to the grid in order to reduce their electric utility bill. To develop the proposed scheme, we first formulate the problem as a constrained convex minimization problem. Then, it is converted to an unconstrained version using the segmentation-based penalty method. At each consumer location, we deploy an adaptive diffusion approach to obtain the solution in a distributed fashion. The use of adaptive diffusion makes it possible for consumers to find the optimum energy consumption schedule with a small number of information exchanges. Moreover, the proposed method is able to track drifts resulting from changes in the price parameters and consumer preferences. Simulations and numerical results show that our framework can reduce the total load demand peaks, lower the consumer utility bill, and improve the consumer comfort level.

The excellent quality kaon beam provided by the DAΦNE collider of LNF-INFN (Italy) together with SIDDHARTA/SIDDHARTA-2 new experimental techniques, as very precise and fast-response X-ray detectors, allow to perform unprecedented measurements on light kaonic atoms crucial for a deeper understanding of the low-energy quantum chromodynamics (QCD) in the strangeness sector. In this paper an overview of the main results obtained by the SIDDHARTA collaboration, as well as the future plans related to the SIDDHARTA-2 experiment, are discussed.