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في هذا الكتاب، يأخذنا أوفه كلوسمان في رحلة شاملة عبر تطور أجهزة الاستخبارات من بداياتها في العصور الوسطى إلى عصر \"الحرب الإلكترونية\"، مركزا على كيفية تطور دور العملاء والمخبرين عبر الزمن. يبدأ بسرد أنشطة التجسس كفن بدائي مرتبط بالحروب الرومانية والعصور الوسطى، ثم يتناول تشكل أجهزة علاقات المخابرات المنظمة في دول أوروبية حديثة وعصر النهضة، قبل أن يعرض لكيفية تحول السرية والبيروقراطية الاستخباراتية في العالم الحديث خاصة أثناء الحربين العالميتين والحرب الباردة. ويكشف أن استخدام التكنولوجيا (كالإنترنت وكشف الاتصالات المشفرة) قد منح أجهزة مثل CIA وNSA هيمنة غير مسبوقة، وجرى تجاوز مفاهيم الخصوصية والحريات الشخصية إذ باتت القدرة على المراقبة واسعة النطاق، كما رأينا في قضايا تسريبات سنودن، بعد أن توسع النفوذ الاستخباري ليشمل كل زاوية من شبكة الإنترنت العالمية.

Crimean-Congo hemorrhagic fever (CCHF), caused by CCHF virus, is a tickborne disease that can cause a range of illness outcomes, from asymptomatic infection to fatal viral hemorrhagic fever; the disease has been described in >30 countries. We conducted a literature review to provide an overview of the virology, pathogenesis, and pathology of CCHF for clinicians. The virus life cycle and molecular interactions are complex and not fully described. Although pathogenesis and immunobiology are not yet fully understood, it is clear that multiple processes contribute to viral entry, replication, and pathological damage. Limited autopsy reports describe multiorgan involvement with extravasation and hemorrhages. Advanced understanding of CCHF virus pathogenesis and immunology will improve patient care and accelerate the development of medical countermeasures for CCHF.

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.

Crimean-Congo hemorrhagic fever (CCHF) is a tickborne infection that can range from asymptomatic to fatal and has been described in >30 countries. Early identification and isolation of patients with suspected or confirmed CCHF and the use of appropriate prevention and control measures are essential for preventing human-to-human transmission. Here, we provide an overview of the epidemiology, clinical features, and prevention and control of CCHF. CCHF poses a continued public health threat given its wide geographic distribution, potential to spread to new regions, propensity for genetic variability, and potential for severe and fatal illness, in addition to the limited medical countermeasures for prophylaxis and treatment. A high index of suspicion, comprehensive travel and epidemiologic history, and clinical evaluation are essential for prompt diagnosis. Infection control measures can be effective in reducing the risk for transmission but require correct and consistent application.

Latinx individuals, particularly immigrants, are at higher risk than non-Latinx White individuals of contracting and dying from coronavirus disease 2019 (COVID-19). Little is known about Latinx experiences with COVID-19 infection and treatment. To describe the experiences of Latinx individuals who were hospitalized with and survived COVID-19. The qualitative study used semistructured phone interviews of 60 Latinx adults who survived a COVID-19 hospitalization in public hospitals in San Francisco, California, and Denver, Colorado, from March 2020 to July 2020. Transcripts were analyzed using qualitative thematic analysis. Data analysis was conducted from May 2020 to September 2020. Themes and subthemes that reflected patient experiences. Sixty people (24 women and 36 men; mean [SD] age, 48 [12] years) participated. All lived in low-income areas, 47 participants (78%) had more than 4 people in the home, and most (44 participants [73%]) were essential workers. Four participants (9%) could work from home, 12 (20%) had paid sick leave, and 21 (35%) lost their job because of COVID-19. We identified 5 themes (and subthemes) with public health and clinical care implications: COVID-19 was a distant and secondary threat (invincibility, misinformation and disbelief, ingrained social norms); COVID-19 was a compounder of disadvantage (fear of unemployment and eviction, lack of safeguards for undocumented immigrants, inability to protect self from COVID-19, and high-density housing); reluctance to seek medical care (worry about health care costs, concerned about ability to access care if uninsured or undocumented, undocumented immigrants fear deportation); health care system interactions (social isolation and change in hospital procedures, appreciation for clinicians and language access, and discharge with insufficient resources or clinical information); and faith and community resiliency (spirituality, Latinx COVID-19 advocates). In interviews, Latinx patients with COVID-19 who survived hospitalization described initial disease misinformation and economic and immigration fears as having driven exposure and delays in presentation. To confront COVID-19 as a compounder of social disadvantage, public health authorities should mitigate COVID-19-related misinformation, immigration fears, and challenges to health care access, as well as create policies that provide work protection and address economic disadvantages.

A scalable chemical method to control phosphorothioate chirality demonstrates its impact on the efficacy of antisense oligonucleotides. Whereas stereochemical purity in drugs has become the standard for small molecules, stereoisomeric mixtures containing as many as a half million components persist in antisense oligonucleotide (ASO) therapeutics because it has been feasible neither to separate the individual stereoisomers, nor to synthesize stereochemically pure ASOs. Here we report the development of a scalable synthetic process that yields therapeutic ASOs having high stereochemical and chemical purity. Using this method, we synthesized rationally designed stereopure components of mipomersen, a drug comprising 524,288 stereoisomers. We demonstrate that phosphorothioate (PS) stereochemistry substantially affects the pharmacologic properties of ASOs. We report that S p-configured PS linkages are stabilized relative to R p, providing stereochemical protection from pharmacologic inactivation of the drug. Further, we elucidated a triplet stereochemical code in the stereopure ASOs, 3′- S p S p R p, that promotes target RNA cleavage by RNase H1 in vitro and provides a more durable response in mice than stereorandom ASOs.

Background: Outbreaks of Zaire ebolavirus are an ongoing public health threat associated with high case fatality rates. The US Advisory Committee on Immunization Practices (ACIP) recommends preexposure vaccination with rVSV∆G-ZEBOV-GP Ebola vaccine (Brand name: Ervebo), which is effective in preventing disease caused by Zaire ebolavirus, to people at high risk for occupational exposure. We describe the perceptions and desire to be vaccinated with Ervebo among a subset of eligible US healthcare workers (HCWs). Methods: We conducted a cross-sectional online anonymous survey during March-October 2024, distributed to eligible HCWs at three Regional Emerging Special Pathogen Treatment Centers (RESPTCs): NYC Health + Hospitals/Bellevue, University of Texas Medical Branch, and Denver Health & Hospital Authority. Results: There were 66 responses (40% response rate), with the majority aged 30-49 years (63%), female (65%), and either a physician (42%) or nurse (27%). The majority (56%) had received some form of education on Ebola vaccines, most commonly through informational sheets or pamphlets (60%). Thirty-four (51%) were interested in (n=30) or already vaccinated with (n=4) Ervebo. Among those interested or already vaccinated, 44% would choose to receive the vaccine immediately, while 24% would get vaccinated if there were a case of Ebola virus disease (EVD) in the US. Among those not interested or unsure (n=32), most were concerned about risks of spreading the vaccine viral vector (44%), insufficient knowledge about the vaccine (31%), and unacceptable side effects (31%). Among all respondents, the most common concerns about adverse events included potential for a serious side effect (64%) and risk of arthritis (36%). Forty seven percent of respondents were concerned about the potential for spread of the vaccine virus vector. Respondents most frequently wanted more education on potential side effects (67%) and the risk of spreading the vaccine virus vector (59%). Among those not interested in vaccination or unsure (n=32), some may be convinced to accept vaccination if there were an EVD outbreak in the US (44%), if they better understood the risks and benefits of vaccination (34%), and if they better understood the vaccine safety (31%). Conclusion: During a period with no EVD outbreaks, a majority (51%) of eligible HCWs surveyed at three US RESPTCs were interested in or had received Ervebo. A significant proportion (24%) prefer to postpone vaccination until there is a case of EVD in the US. Deployment of Ervebo to eligible US HCWs may be optimized by addressing concerns identified in this study.