Molecular Detection of Orthohantavirus puumalaense in Plasma and Urine Samples from Hospitalized Patients Presenting with a Serologically Confirmed Acute Hantavirus Infection in France.

Molecular detection of Orthohantavirus puumalaense (PUUV) RNA during the course of the disease has been studied in blood of patients in Sweden and Slovenia. The use of urine has been poorly investigated. The aims of this work were to study PUUV RNA detection in plasma from a cohort of patients in France where a different PUUV lineage circulates and to assess the use of urine instead of plasma. Matched plasma and urine samples were collected daily from hospitalized patients presenting with fever, pain, and thrombocytopenia within the last 8 days and testing positive for IgM and IgG against PUUV in serum collected at inclusion and/or approximately 1 month after release. RNA was extracted from samples, and PUUV RNA was detected using real-time reverse transcription-PCR for plasma and urine samples. Sixty-seven patients presented a serologically confirmed acute hantavirus infection. At inclusion, PUUV RNA was detected in plasma from 55 of 62 patients (88.7%) sampled within the first week after disease onset, whereas it was detected in 15 of 60 (25.0%) of matched urine samples. It was then detected from 33 (71.7%) and 2 (4.4%) of 46 patients discharged from the hospital during the second week after disease onset, in plasma and urine, respectively. When PUUV RNA was detected in urine it was also detected in plasma, and not vice versa. Detection of PUUV RNA in plasma from hospitalized patients in France is similar to that observed in Sweden and Slovenia. Urine is not an appropriate sample for this detection.

Ransomware: Analysing the Impact on Windows Active Directory Domain Services.

Ransomware has become an increasingly popular type of malware across the past decade and continues to rise in popularity due to its high profitability. Organisations and enterprises have become prime targets for ransomware as they are more likely to succumb to ransom demands as part of operating expenses to counter the cost incurred from downtime. Despite the prevalence of ransomware as a threat towards organisations, there is very little information outlining how ransomware affects Windows Server environments, and particularly its proprietary domain services such as Active Directory. Hence, we aim to increase the cyber situational awareness of organisations and corporations that utilise these environments. Dynamic analysis was performed using three ransomware variants to uncover how crypto-ransomware affects Windows Server-specific services and processes. Our work outlines the practical investigation undertaken as WannaCry, TeslaCrypt, and Jigsaw were acquired and tested against several domain services. The findings showed that none of the three variants stopped the processes and decidedly left all domain services untouched. However, although the services remained operational, they became uniquely dysfunctional as ransomware encrypted the files pertaining to those services.

GLASS: A Citizen-Centric Distributed Data-Sharing Model within an e-Governance Architecture.

E-governance is a process that aims to enhance a government's ability to simplify all the processes that may involve government, citizens, businesses, and so on. The rapid evolution of digital technologies has often created the necessity for the establishment of an e-Governance model. There is often a need for an inclusive e-governance model with integrated multiactor governance services and where a single market approach can be adopted. e-Governance often aims to minimise bureaucratic processes, while at the same time including a digital-by-default approach to public services. This aims at administrative efficiency and the reduction of bureaucratic processes. It can also improve government capabilities, and enhances trust and security, which brings confidence in governmental transactions. However, solid implementations of a distributed data sharing model within an e-governance architecture is far from a reality; hence, citizens of European countries often go through the tedious process of having their confidential information verified. This paper focuses on the sinGLe sign-on e-GovernAnce Paradigm based on a distributed file-exchange network for security, transparency, cost-effectiveness and trust (GLASS) model, which aims to ensure that a citizen can control their relationship with governmental agencies. The paper thus proposes an approach that integrates a permissioned blockchain with the InterPlanetary File System (IPFS). This method demonstrates how we may encrypt and store verifiable credentials of the GLASS ecosystem, such as academic awards, ID documents and so on, within IPFS in a secure manner and thus only allow trusted users to read a blockchain record, and obtain the encryption key. This allows for the decryption of a given verifiable credential that stored on IPFS. This paper outlines the creation of a demonstrator that proves the principles of the GLASS approach.

Trusted Threat Intelligence Sharing in Practice and Performance Benchmarking through the Hyperledger Fabric Platform.

Historically, threat information sharing has relied on manual modelling and centralised network systems, which can be inefficient, insecure, and prone to errors. Alternatively, private blockchains are now widely used to address these issues and improve overall organisational security. An organisation's vulnerabilities to attacks might change over time. It is utterly important to find a balance among a current threat, the potential countermeasures, their consequences and costs, and the estimation of the overall risk that this provides to the organisation. For enhancing organisational security and automation, applying threat intelligence technology is critical for detecting, classifying, analysing, and sharing new cyberattack tactics. Trusted partner organisations can then share newly identified threats to improve their defensive capabilities against unknown attacks. On this basis, organisations can help reduce the risk of a cyberattack by providing access to past and current cybersecurity events through blockchain smart contracts and the Interplanetary File System (IPFS). The suggested combination of technologies can make organisational systems more reliable and secure, improving system automation and data quality. This paper outlines a privacy-preserving mechanism for threat information sharing in a trusted way. It proposes a reliable and secure architecture for data automation, quality, and traceability based on the Hyperledger Fabric private-permissioned distributed ledger technology and the MITRE ATT&CK threat intelligence framework. This methodology can also be applied to combat intellectual property theft and industrial espionage.

A Privacy-Preserving Healthcare Framework Using Hyperledger Fabric.

Electronic health record (EHR) management systems require the adoption of effective technologies when health information is being exchanged. Current management approaches often face risks that may expose medical record storage solutions to common security attack vectors. However, healthcare-oriented blockchain solutions can provide a decentralized, anonymous and secure EHR handling approach. This paper presents PREHEALTH, a privacy-preserving EHR management solution that uses distributed ledger technology and an Identity Mixer (Idemix). The paper describes a proof-of-concept implementation that uses the Hyperledger Fabric's permissioned blockchain framework. The proposed solution is able to store patient records effectively whilst providing anonymity and unlinkability. Experimental performance evaluation results demonstrate the scheme's efficiency and feasibility for real-world scale deployment.

Seroprevalence of Hantavirus in Forestry Workers, Northern France, 2019-2020.

We aimed to estimate the seroprevalence of Puumala orthohantavirus (PUUV) among forestry workers in northern France, and to explore sociodemographic risk factors. We conducted a random cross-sectional seroprevalence survey among 1777 forestry workers in 2019-2020. The presence of immunoglobulin G against PUUV antigens in serum was assessed using enzyme-linked immunosorbent assay and confirmed using immunofluorescence assay. Poisson regression models were used to explore factors associated with seropositivity. Weighted seroprevalence was 5% (3-6) in northeastern France, 4% (2-6) in north central France, and 1% in two regions located in the center of the country (Auvergne and Limousin). There were no seropositive workers detected in northwestern France. Seropositivity was associated with age, sex, and cumulative seniority in the forestry sector. Seroprevalence was highest in known endemic areas of the northeast and lowest in the northwest. Nevertheless, we found serological evidence of PUUV infection in two regions located in the center of the country, suggesting circulation of the virus in these regions, previously thought to be non-endemic.

Field Evaluation of Commonly Used Adult Mosquito Traps in Greece.

Background: Entomological monitoring activities are a major part of mosquito and mosquito-borne diseases surveillance. Several trapping methods are implemented worldwide, aiming to gather data on species composition and their abundance in various study areas. Methods: Several methodological modifications, such as trapping systems baited with attractants or carbon dioxide, have been proposed to increase trap efficiency. The aim of this study was to test different trap types, commonly used in Greece to collect mosquitoes, with the addition of the Biogents Sentinel lure. Moreover, traps were placed in two distinct land types and two different heights above the ground to compare their efficacy. West Nile Virus is endemic in Greece, so we also aimed to detect viral presence and circulation in selected mosquito pools. Results: Adult mosquitoes of Aedes albopictus, Culex pipiens s.l., and Culiseta longiareolata were collected in both study areas. The trap type had a significant impact on the total collections, while the trap position and interaction between trap and position did not significantly affect mosquito catches. WNV was detected in Cx. pipiens s.l. pools examined from the two study areas. Conclusion: This study emphasizes the role of trapping methods as a key component for monitoring and surveillance of adult mosquito populations, reflecting that several trap types present with different mosquito species capture and catch rates.

Deep multiple instance learning for foreground speech localization in ambient audio from wearable devices.

Over the recent years, machine learning techniques have been employed to produce state-of-the-art results in several audio related tasks. The success of these approaches has been largely due to access to large amounts of open-source datasets and enhancement of computational resources. However, a shortcoming of these methods is that they often fail to generalize well to tasks from real life scenarios, due to domain mismatch. One such task is foreground speech detection from wearable audio devices. Several interfering factors such as dynamically varying environmental conditions, including background speakers, TV, or radio audio, render foreground speech detection to be a challenging task. Moreover, obtaining precise moment-to-moment annotations of audio streams for analysis and model training is also time-consuming and costly. In this work, we use multiple instance learning (MIL) to facilitate development of such models using annotations available at a lower time-resolution (coarsely labeled). We show how MIL can be applied to localize foreground speech in coarsely labeled audio and show both bag-level and instance-level results. We also study different pooling methods and how they can be adapted to densely distributed events as observed in our application. Finally, we show improvements using speech activity detection embeddings as features for foreground detection.

Suspensions for intravenous (IV) injection: a review of development, preclinical and clinical aspects.

There has been growing interest in nanoparticles as an approach to formulate poorly soluble drugs. Besides enhanced dissolution rates, and thereby, improved bioavailability, nanoparticles can also provide targeting capabilities when injected intravenously. The latter property has led to increased research and development activities for intravenous suspensions. The first intravenously administered nanoparticulate product, Abraxane (a reformulation of paclitaxel), was approved by the FDA in 2006. Additional clinical trials have been conducted or are ongoing for multiple other indications such as oncology, infective diseases, and restenosis. This article reviews various challenges associated with developing intravenous nanosuspension dosage forms. In addition, various formulation considerations specific to intravenous nanosuspensions as well as reported findings from various clinical studies have been discussed.

Itraconazole IV nanosuspension enhances efficacy through altered pharmacokinetics in the rat.

The goal of this research was to evaluate an intravenous itraconazole nanosuspension dosage form, relative to a solution formulation, in the rat. Itraconazole was formulated as a nanosuspension by a tandem process of microcrystallization followed by homogenization. Acute toxicity, pharmacokinetics, and distribution were studied in the rat, and compared with a solution formulation of itraconazole. Efficacy was studied in an immunocompromised rat model, challenged with a lethal dose of either itraconazole-sensitive or itraconazole-resistant C. albicans. Itraconazole nanosuspension was tolerated at significantly higher doses compared with a solution formulation. Pharmacokinetics of the nanosuspension were altered relative to the solution formulation. C(max) was reduced and t(1/2) was much prolonged. This occurred due to distribution of the nanosuspension to organs of the monocyte phagocytic system (MPS), followed by sustained release from this IV depot. The higher dosing of the drug, enabled in the case of the nanosuspension, led to higher kidney drug levels and reduced colony counts. Survival was also shown to be superior relative to the solution formulation. Thus, formulation of itraconazole as a nanosuspension enhances efficacy of this antifungal agent relative to a solution formulation, because of altered pharmacokinetics, leading to increased tolerability, permitting higher dosing and resultant tissue drug levels.

Itraconazole suspension for intravenous injection: determination of the real component of complete refractive index for particle sizing by static light scattering.

The purpose of this study is to assess the impact of real refractive indices, using different itraconazole suspensions, on the associated particle size distributions. Instrumental particle size measurement remains the practical option for determining the particle size distribution of a suspension. In this study, the suspension particle size distribution was measured by static light scattering, which requires knowledge of both the real and imaginary components of the complete refractive index. The real refractive indices of micronized itraconazole raw material, as well as vacuum-dried itraconazole suspension samples obtained from different formulations, polymorphs, manufacturing methods and particle size distributions, were determined using the Becke line method. Identical samples were analyzed by two contract laboratories in order to assess consistency. For the static light scattering equipment used in this study, the complete relative refractive index (RRI = n(particte) / n(dispersant) - ik) input required for software calculation is denoted by a refractive index kernel (RRI input) comprising a relative real component and an imaginary component. The reported real refractive indices for the itraconazole raw material as well as vacuum dried itraconazole suspension samples were different, ranging from 1.608 to 1.65 (selected kernel range of 120A010I to 124A010I). The imaginary component of itraconazole suspension was determined in a previous study to be 010I. The average real refractive index was calculated to be 1.62 (122A010I). The particle size distributions obtained using 120A010I and 124A010I were in good agreement with one generated using 122A010I. Therefore, itraconazole suspensions that were produced using different manufacturing methods/formulations or exhibited different particle size distributions/polymorphic forms may use 122A010I in determining particle size distribution. The particle size distributions determined using RRI input outside the range of 120A010I to 124A010I may not be reliable. However, it is recommended that similar investigations be conducted for other drug suspensions on a case-by-case basis.

Effect of terminal sterilization by irradiation on amber Type I and Type III glass containers containing veterinary oxytetracycline suspension.

The purpose of this study is to determine the effect of terminal sterilization by gamma irradiation on 500-mL amber Type I and Type III glass containers (bottles) containing oxytetracycline (OTC) (25% W/V) suspension formulated using 20% (W/V) phospholipids syrup. The formulation was developed for veterinary parenteral administration. The results of terminal sterilization were used to assess the acceptability for this suspension product. OTC is light-sensitive and needs to be stored in amber glass containers. Amber Type I and Type III glass containers were considered for this formulation during development. Type I is a highly resistant, borosilicate glass (oxidized glass). Type III, which is soda-lime glass (reduced glass, see Materials and Methods), may also be used for parenteral products. The amber Type I and Type III glass containers, containing the suspension, were irradiated at 20-40 kGy for 150 min. In order to determine the sterility of the suspension, ampoules of the biological indicator, Bacillus pumilus, were placed in a number of bottles of the suspension. The bottles with the biological indicators were then positioned among the rest of the production bottles as per a radiation dose-mapping study conducted at the sterilization facility. Potency determination and stability evaluations for OTC were performed using high pressure liquid chromatography (HPLC). The results indicate that the gamma irradiation dose of 20-40 kGy for 150 min was able to inactivate 10(6) Bacillus pumilus spores in ampoules. After gamma sterilization, OTC concentration, pH, particle size, endotoxins, and sterility were evaluated. The assay results were comparable for the suspension in amber Type I and Type III glass containers. Sterility and pyrogenicity were measured by the USP Membrane Filtration Method and USP Bacterial Endotoxins Test, respectively. The suspension in the amber Type III glass container was also chemically (HPLC) and physically (suspension mean particle size, viscosity, density, and syringeability) stable for at least 12 months at room temperature. However, amber Type I glass darkened following irradiation, leading to a substantial reduction in glass transparency. The appearance of amber Type III glass was acceptable. Thus, the "reduced" glass, such as soda-lime, was found to be much less susceptible to darkening than the highly oxidized borosilicate amber. Due to the potential aesthetic concerns with Type I glass, the amber Type III glass container was selected for this suspension formulation.

Plasma atrial natriuretic peptide in essential hypertension after treatment with irbesartan.

The aim of this study was to evaluate the medium-term effects of the selective AT1-blocker irbesartan on atrial natriuretic peptide (ANP) levels in patients with moderate essential hypertension. The drug was given orally in a daily dose of 300 mg for 30 days. Plasma ANP levels increased by 15.7% despite the drop in blood pressure and the slight decrease of atrial and ventricular diameters. These findings indicate that AT,-blockers like irbesartan exert part of their antihypertensive action by increasing ANP plasma levels.