How Global Collaboration Can Improve the Medical Countermeasure Life Cycle for Infectious Disease Outbreaks.

Infectious disease outbreaks have become increasingly common and require global partnership for adequate preparedness and response. During outbreaks, medical countermeasures (MCMs)-vaccines, therapeutics, and diagnostics-need to reach patients quickly. Recent outbreaks exemplify that products with regulatory approval can expand access and reach patients quicker than investigational products. Unfortunately, insufficient funding globally and differences in funders' prioritization puts gains and future efforts at risk. Of primary concern is (1) lack of a feasible regulatory path and clinical capability to achieve regulatory approval for new MCMs for many diseases; and (2) the need for partners with the mandate, funding, and capabilities to support long-term sustainment of manufacturing capability and stockpiling of licensed products. Without collaboration, the global community runs the risk of losing the capabilities built through years of investment and being underprepared to combat future threats. Synergies between funders are critical to create long-term sustainment of products to ensure access.

Project NextGen: Developing the Next Generation of COVID-19 Vaccines and Therapeutics to Respond to the Present and Prepare for the Future.

Coronavirus disease 2019 (COVID-19) epidemiology and product landscapes have changed considerably since onset of the pandemic. Safe and effective vaccines and therapeutics are available, but the continual emergence of severe acute respiratory syndrome coronavirus 2 variants introduce limitations in our ability to prevent and treat disease. Project NextGen is a collaboration between the Biomedical Advanced Research and Development Authority, part of the Administration for Strategic Preparedness and Response, and the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, that is leveraging public-private partnerships to address gaps in the nation's COVID-19 vaccine and therapeutic capabilities. Targeted investments will advance promising next-generation candidates through the most difficult phases of clinical development to encourage further private sector interest for later stage development and commercial availability. New commercial vaccines and therapeutics that are more durable and effective across variants will improve our fight against COVID-19 and transform our response to future threats.

Crimean-Congo Hemorrhagic Fever Virus for Clinicians-Diagnosis, Clinical Management, and Therapeutics.

Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread tickborne viral infection worldwide and has a fatality rate of up to 62%. Despite its widespread range and high fatality rate, no vaccines or treatments are currently approved by regulatory agencies in the United States or Europe. Supportive treatment remains the standard of care, but the use of antiviral medications developed for other viral infections have been considered. We reviewed published literature to summarize the main aspects of CCHFV infection in humans. We provide an overview of diagnostic testing and management and medical countermeasures, including investigational vaccines and limited therapeutics. CCHFV continues to pose a public health threat because of its wide geographic distribution, potential to spread to new regions, propensity for genetic variability, potential for severe and fatal illness, and limited medical countermeasures for prophylaxis and treatment. Clinicians should become familiar with available diagnostic and management tools for CCHFV infections in humans.

Low-dose X-ray radiation induces an adaptive response: A potential countermeasure to galactic cosmic radiation exposure.

Space exploration involves many dangers including galactic cosmic radiation (GCR). This class of radiation includes high-energy protons and heavy ionizing ions. NASA has defined GCR as a carcinogenic risk for long-duration space missions. To date, no clear strategy has been developed to counter chronic GCR exposure. We hypothesize that preconditioning cells with low levels of radiation will be protective from subsequent higher radiation exposures. H9C2 cells were pretreated with 0.1 to 1.0 Gy X-rays. The challenge radiation exposure consisted of either 8 Gy X-rays or 75 cGy of GCR, using a five-ion GCRsim protocol. A cell doubling time assay was used to determine cell viability. An 8 Gy X-ray challenge alone significantly (P < 0.05) increased cell doubling time compared to the no-radiation control group. Low-dose radiation pre-treatment ameliorated the 8 Gy X-ray-induced increases in cell doubling time. A 75 cGy GCR challenge alone significantly increased cell doubling time compared to the no-radiation group. Following the 75 cGy challenge, only the 0.5 and 1.0 Gy pre-treatment ameliorated the 75 cGy-induced increases in cell doubling time. DNA damage or pathological oxidant stress will delay replicative functions and increase cell doubling time. Our results suggested that pretreatment with low-dose X-rays induced an adaptive response which offered a small but significant protection against a following higher radiation challenge. Although perhaps not a practical countermeasure, these findings may serve to offer insight into cell signalling pathways activated in response to low-dose irradiation and targeted for countermeasure development.

The disaster liaison for pediatric and perinatal medicine: A new system in Japan.

BACKGROUND: Worldwide, children, newborns, and pregnant or postpartum women are vulnerable to disasters and emergency situations, and providing support to this population is of great concern. Japan is located in a disaster-prone area, so disaster response and risk reduction strategies are important priorities. METHODS: We introduce a system called the Disaster Liaison for Pediatric and Perinatal Medicine (DLPPM). This was created with a specific focus on perinatal children and pregnant women in Japan. We report the details of its activities, discuss its challenges, and draw on lessons learned for the further development of perinatal support systems, particularly for children. RESULTS: The lessons learned from the activities of the DLPPM include the following: (1) establish a support system for emergency specialists beyond those with pediatric and perinatal specialties; (2) mitigate the risk of indirect damage caused by primary disasters; and (3) establish a networking function linked to existing pediatric and perinatal medicine facilities. CONCLUSIONS: By establishing similar systems, we believe that it will be feasible to address pediatric and perinatal care needs in disaster response contexts in other countries and regions around the world.

Protecting FPGA-Based Cryptohardware Implementations from Fault Attacks Using ADCs.

The majority of data exchanged between connected devices are confidential and must be protected against unauthorized access. To ensure data protection, so-called cryptographic algorithms are used. These algorithms have proven to be mathematically secure against brute force due to the key length, but their physical implementations are vulnerable against physical attacks. The physical implementation of these algorithms can result in the disclosure of information that can be used to access confidential data. Some of the most powerful hardware attacks presented in the literature are called fault injection attacks. These attacks involve introducing a malfunction into the normal operation of the device and then analyzing the data obtained by comparing them with the expected behavior. Some of the most common methods for injecting faults are the variation of the supply voltage and temperature or the injection of electromagnetic pulses. In this paper, a hardware design methodology using analog-to-digital converters (ADCs) is presented to detect attacks on cryptocircuits and prevent information leakage during fault injection attacks. To assess the effectiveness of the proposed design approach, FPGA-based ADC modules were designed that detect changes in temperature and supply voltage. Two setups were implemented to test the scheme against voltage and temperature variations and injections of electromagnetic pulses. The results obtained demonstrate that, in 100% of the cases, when the correct operating voltage and temperature range were established, the detectors could activate an alarm signal when the cryptographic module was attacked, thus avoiding confidential information leakage and protecting data from being exploited.

Multi-level decisions for addressing trade-off in the cross-regional water-environment-agriculture interactive system under constraint of water ecological carrying capacity.

The complex-enhanced hierarchical relationship among multiple stakeholders in the water-environment-agriculture interactive system has been overlooked. This study develops a leader-follower-enhanced framework (named as FCMLP) that integrates variable-weight combination prediction model, multi-level programming, and fuzzy credibility constrained programming, which can effectively address the above problems under uncertainties. Five water ecological carrying capacity (WECC) statuses are treated as a critical constraint into the modeling framework to improve the accuracy of decision-making. An interactive fuzzy satisfaction algorithm is advanced for solving this multi-level problem, in which COD discharge minimization, economic benefits maximization, and grain yield maximization are taken as the upper-, middle-, and lower-level goals, respectively. The framework is applied to plan the cross-regional water-environment-agriculture interactive system in the Beijing-Tianjin-Hebei and Yangtze River Economic Belt. Solutions reveal that increased WECC status and credibility level would decrease 1.40%-1.74%, 0.71%-9.61%, and 1.63%-2.26% of water resources allocation, COD emissions, and economic benefits, respectively. Crop area and grain yield would dramatically decline by 4.13%-4.46% and 4.03%-4.67% when a credibility level increases from 0.8 to 1, respectively. The overall satisfactory degree would range from 0.58 to 0.70, which illustrates interactive decision-making process of multiple stakeholders. Significant differences can be observed in the optimized schemes of water resources allocation and environmental-economic-agricultural performances among various models. The amounts of allocated water resources, pollutant discharge, and economic output from the FCMLP model would be respectively 11.30%-13.45%, 14.90%-15.21%, and 73.12%-73.48% higher than those from the environment- and agriculture-oriented schemes, yet 13.81%, 32.05%, and 15.29% lower than those from the economy-oriented scheme. Some water adaptability countermeasures are given for ensuring the scientific operation of the South-to-North Water Transfer Project and alleviating conflicts between water source and receiving areas. Further exploration of the optimization scheme of water-environment-energy-agriculture system driven by climate change is still required for guaranteeing the dynamic balance of regional resources.

The Arenaviridae Family: Knowledge Gaps, Animal Models, Countermeasures, and Prototype Pathogens.

Lassa virus (LASV), Junin virus (JUNV), and several other members of the Arenaviridae family are capable of zoonotic transfer to humans and induction of severe viral hemorrhagic fevers. Despite the importance of arenaviruses as potential pandemic pathogens, numerous gaps exist in scientific knowledge pertaining to this diverse family, including gaps in understanding replication, immunosuppression, receptor usage, and elicitation of neutralizing antibody responses, that in turn complicates development of medical countermeasures. A further challenge to the development of medical countermeasures for arenaviruses is the requirement for use of animal models at high levels of biocontainment, where each model has distinct advantages and limitations depending on, availability of space, animals species-specific reagents, and most importantly the ability of the model to faithfully recapitulate human disease. Designation of LASV and JUNV as prototype pathogens can facilitate progress in addressing the public health challenges posed by members of this important virus family.

[Research progress and countermeasures of cancer risk in police officers].

The people's police of public security organs shoulder the important mission of maintaining social security and stability, and ensuring the well-being of people. However, the working environment exposed to a variety of adverse factors has significantly increased the risk of cancer and cancer mortality of public security police, such as bladder cancer, prostate cancer, colon cancer, melanoma cancer, etc. Police related cancer risk research is a noteworthy issue. This article provides a review of existing research on the types and carcinogenic factors of cancer among domestic and foreign police officers, and analyzes various factors that may lead to their cancer based on the actual work situation of Chinese public security police. Corresponding response strategies are proposed to provide a scientific basis for reducing the risk of cancer among public security police.

[The current situation of occupational health in the Internet industry and countermeasures].

As an important force in promoting the transformation and upgrading of the national economy, the occupational health of the Internet industry's employees has received widespread attention. This paper examines the current situation of occupational health risks and management in the Internet industry at home and abroad, and on this basis reveals the physical and mental health problems of Internet industry employees. Combining the existing regulations, policies and standard documents at home and abroad, countermeasures are proposed to improve the relevant laws and regulations and their guidelines, implement relevant job design requirements, build a healthy working environment, optimise the work management system and carry out workplace health promotion, in order to provide ideas to accelerate the improvement of occupational health issues in the Internet industry.

[Countermeasures and enlightenment of occupational health assistance for small and medium-sized enterprises at domestic and international].

China attaches great importance to the occupational health assistance for small and medium-sized enterprises, but many efforts are still needed. Through the research and comparative analysis of the policies and measures of occupational health assistance for small and medium-sized enterprises at domestic and international, this paper finds that there are still some problems in the occupational health assistance for small and medium-sized enterprises in China, such as imperfect policies, lack of safeguard measures, support platforms and resources, and puts forward that China can promote the occupational health assistance for small and medium-sized enterprises from the aspects of perfecting the support system, strengthening safeguard measures, building relevant platforms and enriching resources.

Protein biomarkers for radiation injury and testing of medical countermeasure efficacy: promises, pitfalls, and future directions.

INTRODUCTION: Radiological/nuclear accidents, hostile military activity, or terrorist strikes have the potential to expose a large number of civilians and military personnel to high doses of radiation resulting in the development of acute radiation syndrome and delayed effects of exposure. Thus, there is an urgent need for sensitive and specific assays to assess the levels of radiation exposure to individuals. Such radiation exposures are expected to alter primary cellular proteomic processes, resulting in multifaceted biological responses. AREAS COVERED: This article covers the application of proteomics, a promising and fast developing technology based on quantitative and qualitative measurements of protein molecules for possible rapid measurement of radiation exposure levels. Recent advancements in high-resolution chromatography, mass spectrometry, high-throughput, and bioinformatics have resulted in comprehensive (relative quantitation) and precise (absolute quantitation) approaches for the discovery and accuracy of key protein biomarkers of radiation exposure. Such proteome biomarkers might prove useful for assessing radiation exposure levels as well as for extrapolating the pharmaceutical dose of countermeasures for humans based on efficacy data generated using animal models. EXPERT OPINION: The field of proteomics promises to be a valuable asset in evaluating levels of radiation exposure and characterizing radiation injury biomarkers.

Results of the Cologne Corona Surveillance (CoCoS) study - a cross-sectional study: survey data on risk factors of SARS-CoV-2 infection in adults.

BACKGROUND: The personal, environmental, and behavioral risk factors that play an important role in the spread of SARS-CoV-2 are still largely unclear. At the same time, there is limited evidence on the effectiveness of specific countermeasures for SARS-CoV-2. As a first approach to these questions, we use data from the Cologne Corona Surveillance (CoCoS) study, a large cross-sectional study conducted in Cologne, Germany, in June 2021. METHODS: This study was conducted in Cologne, Germany. Six thousand randomly selected Cologne residents who were 18 years of age or older were invited to participate in this study. Participant information was obtained via an online survey. Previous SARS-CoV-2 infections were recorded using self-reports. Sociodemographic and environmental information such as age, sex, living situation were collected. Potential SARS-CoV-2 risk behaviors were captured (workplace situation, adherence to hygiene regulations, and regular use of public transportation). Adherence to hygiene regulations was surveyed by determining the compliance with the 'AHA'-rules (German acronym that stands for keeping a distance of 1.5 m from fellow citizens, hand disinfection, and wearing a face mask). Binary logistic regression analysis was used to identify risk factors for SARS-CoV-2 infection. RESULTS: A sample of 2,433 study participants provided information. Comparison of the sample with the general population showed representativeness for most sociodemographic characteristics with a preference for higher level of education in the study sample. Younger age, as well as living with minor children (under 18 years) in the same household were associated with a higher number of self-reported SARS-CoV-2 infections. Adherence to hygiene regulations was associated with fewer self-reported SARS-CoV-2 infections in adults. Gender, size of living space per person, workplace situation (work from home versus working with contact to colleagues/customers), and regular use of public transportation showed no significant association with self-reported SARS-CoV-2 infections in multivariable analysis. CONCLUSION: The presented results provide initial indications of which sociodemographic and behavioral factors may be associated with SARS-CoV-2 infection. However, the fact that these factors were recorded without exact dates and could have changed accordingly during the pandemic or after infection limits the strength of the results. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Research on Interrupted Sampling Repeater Jamming Performance Based on Joint Frequency Shift/Phase Modulation.

Interrupted sampling repeater jamming (ISRJ) is a classic active coherent jamming. Due to its structural limitations, it has inherent defects such as a discontinuous time-frequency (TF) distribution, strong distribution regularity of pulse compression results, limited jamming amplitude, and strong false targets lagging behind the real target. These defects have not been fully resolved yet due to the limitation of the theoretical analysis system. Based on the analysis of the influence factors of ISRJ on the interference performance for linear-frequency-modulated (LFM) and phase-coded signals, this paper proposes an improved ISRJ method based on the joint subsection frequency shift and two-phase modulation. The coherent superposition of jamming signals at different positions for LFM signals is achieved by controlling the frequency shift matrix and the phase modulation parameters to form a strong pre-lead false target or multiple positions and ranges of blanket jamming areas. For the phase-coded signal, the pre-lead false targets are generated through code prediction and the two-phase modulation of the code sequence, resulting in similar noise interference. The simulation results show that this method can overcome the inherent defects of ISRJ.

Security of Cryptocurrencies: A View on the State-of-the-Art Research and Current Developments.

[Context] The goal of security is to protect digital assets, devices, and services from being disrupted, exploited or stolen by unauthorized users. It is also about having reliable information available at the right time. [Motivation] Since the inception in 2009 of the first cryptocurrency, few studies have been undertaken to analyze and review the state-of-the-art research and current developments with respect to the security of cryptocurrencies. [Purpose] We aim to provide both theoretical and empirical insights into the security landscape, in particular focusing on both technical solutions and human-related facets. [Methodology] We used an integrative review which could help in building science and scholarly research, the basis for conceptual and empirical models. [Results] Successful defense against cyberattacks depends on technical measures on the one hand, as well as on self-education and training with the aim to develop competence, knowledge, skills and social abilities, on the other. [Contribution] Our findings provide a comprehensive review for the major achievements and developments of the recent progress on the security of cryptocurrencies. [Future research] Since there is increasing interest in adoption of the current solutions within the central bank digital currencies, the future research should explore the development and inception of effective measures against social engineering attacks, which still remain the main concern.

A Critical Cybersecurity Analysis and Future Research Directions for the Internet of Things: A Comprehensive Review.

The emergence of the Internet of Things (IoT) technology has brought about tremendous possibilities, but at the same time, it has opened up new vulnerabilities and attack vectors that could compromise the confidentiality, integrity, and availability of connected systems. Developing a secure IoT ecosystem is a daunting challenge that requires a systematic and holistic approach to identify and mitigate potential security threats. Cybersecurity research considerations play a critical role in this regard, as they provide the foundation for designing and implementing security measures that can address emerging risks. To achieve a secure IoT ecosystem, scientists and engineers must first define rigorous security specifications that serve as the foundation for developing secure devices, chipsets, and networks. Developing such specifications requires an interdisciplinary approach that involves multiple stakeholders, including cybersecurity experts, network architects, system designers, and domain experts. The primary challenge in IoT security is ensuring the system can defend against both known and unknown attacks. To date, the IoT research community has identified several key security concerns related to the architecture of IoT systems. These concerns include issues related to connectivity, communication, and management protocols. This research paper provides an all-inclusive and lucid review of the current state of anomalies and security concepts related to the IoT. We classify and analyze prevalent security distresses regarding IoT's layered architecture, including connectivity, communication, and management protocols. We establish the foundation of IoT security by examining the current attacks, threats, and cutting-edge solutions. Furthermore, we set security goals that will serve as the benchmark for assessing whether a solution satisfies the specific IoT use cases.

Guidance Framework for Developing IoT-Enabled Systems' Cybersecurity.

Internet of Things (IoT) faces security concerns different from existing challenges in conventional information systems connected through the Internet because of their limited resources and heterogeneous network setups. This work proposes a novel framework for securing IoT objects, the key objective of which is to assign different Security Level Certificates (SLC) for IoT objects according to their hardware capabilities and protection measures implemented. Objects with SLCs, therefore, will be able to communicate with each other or with the Internet in a secure manner. The proposed framework is composed of five phases, namely: classification, mitigation guidelines, SLC assignment, communication plan, and legacy integration. The groundwork relies on the identification of a set of security attributes, termed security goals. By performing an analysis on common IoT attacks, we identify which of these security goals are violated for specific types of IoT. The feasibility and application of the proposed framework is illustrated at each phase using the smart home as a case study. We also provide qualitative arguments to demonstrate how the deployment of our framework solves IoT specific security challenges.

Securing Cloud-Assisted Connected and Autonomous Vehicles: An In-Depth Threat Analysis and Risk Assessment.

As threat vectors and adversarial capabilities evolve, Cloud-Assisted Connected and Autonomous Vehicles (CCAVs) are becoming more vulnerable to cyberattacks. Several established threat analysis and risk assessment (TARA) methodologies are publicly available to address the evolving threat landscape. However, these methodologies inadequately capture the threat data of CCAVs, resulting in poorly defined threat boundaries or the reduced efficacy of the TARA. This is due to multiple factors, including complex hardware-software interactions, rapid technological advancements, outdated security frameworks, heterogeneous standards and protocols, and human errors in CCAV systems. To address these factors, this study begins by systematically evaluating TARA methods and applying the Spoofing, Tampering, Repudiation, Information disclosure, Denial of service, and Elevation of privileges (STRIDE) threat model and Damage, Reproducibility, Exploitability, Affected Users, and Discoverability (DREAD) risk assessment to target system architectures. This study identifies vulnerabilities, quantifies risks, and methodically examines defined data processing components. In addition, this study offers an attack tree to delineate attack vectors and provides a novel defense taxonomy against identified risks. This article demonstrates the efficacy of the TARA in systematically capturing compromised security requirements, threats, limits, and associated risks with greater precision. By doing so, we further discuss the challenges in protecting hardware-software assets against multi-staged attacks due to emerging vulnerabilities. As a result, this research informs advanced threat analyses and risk management strategies for enhanced security engineering of cyberphysical CCAV systems.

Drowsiness Mitigation Through Driver State Monitoring Systems: A Scoping Review.

OBJECTIVE: To explore the scope of available research and to identify research gaps on in-vehicle interventions for drowsiness that utilize driver monitoring systems (DMS). BACKGROUND: DMS are gaining popularity as a countermeasure against drowsiness. However, how these systems can be best utilized to guide driver attention is unclear. METHODS: A scoping review was conducted in adherence to PRISMA guidelines. Five electronic databases (ACM Digital Library, Scopus, IEEE Xplore, TRID, and SAE Mobilus) were systematically searched in April 2022. Original studies examining in-vehicle drowsiness interventions that use DMS in a driving context (e.g., driving simulator and driver interviews) passed the screening. Data on study details, state detection methods, and interventions were extracted. RESULTS: Twenty studies qualified for inclusion. Majority of interventions involved warnings (n = 16) with an auditory component (n = 14). Feedback displays (n = 4) and automation takeover (n = 4) were also investigated. Multistage interventions (n = 12) first cautioned the driver, then urged them to take an action, or initiated an automation takeover. Overall, interventions had a positive impact on sleepiness levels, driving performance, and user evaluations. Whether interventions effective for one type of sleepiness (e.g., passive vs. active fatigue) will perform well for another type is unclear. CONCLUSION: Literature mainly focused on developing sensors and improving the accuracy of DMS, but not on the driver interactions with these technologies. More intervention studies are needed in general and for investigating their long-term effects. APPLICATION: We list gaps and limitations in the DMS literature to guide researchers and practitioners in designing and evaluating effective safety systems for drowsy driving.

Natural Scene Virtual Reality as a Behavioral Health Countermeasure in Isolated, Confined, and Extreme Environments: Three Isolated, Confined, Extreme Analog Case Studies.

INTRODUCTION: Isolated, confined, extreme (ICE) environments are accompanied by a host of stress-inducing circumstances: operational pressure, interpersonal dynamics, limited communication with friends and family, and environmental hazards. We evaluated the effectiveness of attention-restoration-therapy-based immersive Virtual Reality (VR) in three ICE environments: the Canadian Forces Station-Alert (CFS Alert), the 12-month HI-SEAS IV expedition, and the 8-month HI-SEAS V expedition. METHODS: Thirty-one individuals (29 male, 2 female) at CFS Alert, and 12 total crewmembers (7 male, 5 female, six crewmembers per sessions) at HI-SEAS participated. All participants viewed immersive VR scenes, but scene content varied by deployment. Data collection included pre- and post-intervention surveys and semi-structured post-mission interviews. Survey data were analyzed by scene content within each analog using nonparametric approaches. RESULTS: Acceptability and desirability of the VR content varied significantly by ICE analog, as well as by participants within a given analog. The two initial exploratory protocols enabled a more directed study in HI-SEAS V to identify the importance of differences in scene content. DISCUSSION: Use and perceived utility of the VR varied considerably across participants, indicating that psychological support needs to be individualized. Overall, natural scene VR was broadly considered restorative, but after long periods of isolation, dynamic and familiar scenes including those with people were also appealing. Immersive, nature-based VR was highly valued by some, but not all participants, suggesting that this intervention tool holds promise for use in ICE settings but needs to be tailored to the setting and individual.