bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the laser fluence and wavelength dependence in surface‐assisted laser desorption/ionization mass spectrometry using gold nanoparticles
Authors: Müller Wendy H. , Potthoff Alexander , Dreisewerd Klaus , Soltwisch Jens
Published: August 2024

Rationale

Surface‐assisted laser desorption/ionization (SALDI) mass spectrometry (MS) builds on the use of nanostructured surfaces (e.g., coatings of colloidal nanoparticles) to promote analyte desorption and ionization. The SALDI process is believed to occur mainly through thermal processes, resulting from heating of the nanosubstrate upon absorption of the photon energy, and by assisting ionization steps. Mostly due to the accessibility of the respective hardware, the majority of SALDI‐MS studies use standard laser wavelengths for MALDI (i.e., 337 or 355 nm), even though peak absorption of the SALDI nanosubstrate might completely differ from these values.

Methods

Here, we investigated the wavelength dependence in SALDI‐MS to determine if wavelength adjustment would be beneficial, and to provide new experimental data for a better understanding of the SALDI mechanism. To this end, gold nanoparticles (AuNPs) sprayed onto microscope glass slides were employed as SALDI nanosubstrates and L‐arginine as a model analyte. In addition, we used 2,5‐dihydroxyacetophenone (2,5‐DHAP) for classical MALDI‐MS using the same experimental setup. Arginine ion signals were recorded as a function of laser wavelength and laser fluence. Mass spectra were acquired in the wavelength range between 310 and 630 nm, including the absorption maximum of the sprayed AuNPs around 550 nm and that of 2,5‐DHAP around 380 nm.

Results

Laser fluence thresholds for the generation of arginine ions were found to be dependent on the laser wavelength and to inversely correlate with the absorbance profiles of the deposited AuNPs and 2,5‐DHAP, respectively. Very differently to MALDI, in SALDI ionization efficiency was found to strictly linearly decrease with increasing laser wavelength.

Conclusions

Our results, therefore, corroborate the general assumption that material ejection in SALDI‐MS is mainly driven by thermal processes in the low laser fluence range and add new evidence that the ionization process is directly influenced by photon energy when AuNPs are employed as nanosubstrates.
Role of Gut Microbiota in Dengue
Authors: Pedreañez Adriana , Carrero Yenddy , Vargas Renata , Hernandez‐Fonseca Juan P. , Hernandez‐Fonseca Hugo , Mosquera Jesús A.
Published: August 2024

Dengue is a disease caused by a flavivirus (DENV) and transmitted by the bite of a mosquito, primarily the Aedes aegypti and Aedes albopictus species. Previous studies have demonstrated a relationship between the host gut microbiota and the evolution of dengue. It seems to be a bidirectional relationship, in which the DENV can affect the microbiota by inducing alterations related to intestinal permeability, leading to the release of molecules from microbiota dysbiosis that can influence the evolution of dengue. The role of angiotensin II (Ang II) in the microbiota/dengue relationship is not well understood, but it is known that the renin‐angiotensin system (RAS) is present in the intestinal tract and interacts with the gut microbiota. The possible effect of Ang II on the microbiota/Ang II/dengue relationship can be summarised as follows: the presence of Ang II induced hypertension, the increase in angiotensinogen, chymase, and microRNAs during the disease, the induction of vascular dysfunction, the production of trimethylamine N‐oxide and the brain/microbiota relationship, all of which are elements present in dengue that could be part of the microbiota/Ang II/dengue interactions. These findings suggest the potential use of Ang II synthesis blockers and the use of AT1 receptor antagonists as therapeutic drugs in dengue.
Extracellular enzyme activity and stoichiometry reveal P limitation in the wild panda habitat of the Qinling Mountains
Authors: Chang Shun , Li Chunyue , Miao Yu , Wang Yi , Zhang Wenting , Li Qianxue , Kou Zhaoyang , Zeng Xiaomin , Chen Ji
Published: August 2024

Soil microbial extracellular enzymes play crucial roles in soil carbon and nutrient cycling by catalyzing soil biochemical processes. However, the activity and stoichiometry of enzymes involved in the carbon, nitrogen, and phosphorus cycles in the environment with the highest density of wild giant pandas on the southern slopes of the Qinling Mountains is unknown. We have established eight research areas at an elevation of 1090–2621 m. The β‐1,4‐glucosidase (BG), β‐1,4‐N‐acetylglucosaminidase (NAG), and acid phosphatase (APase) in soil samples were measured. We used redundancy analysis and structural equation model to evaluate the driving factors of metabolic restriction of soil microorganisms along the elevational gradient, and four models were used to cross‐evaluate the nutrient restriction status of soil microorganisms. The results showed that most soil physiochemical properties, soil microbial biomass, and microbial extracellular enzymes exhibited a hump‐shaped trend with increasing elevation. Elevation indirectly affected soil enzyme activity and stoichiometry by C, N, and P status. Microorganisms are limited by C at lower and higher elevations but limited by N at medium elevations. These results could help strengthen the conservation and management of the wild panda's natural habitat.
Promoting sustainable development goals through generative artificial intelligence in the digital supply chain: Insights from Chinese tourism SMEs
Authors: Wang Shaofeng , Zhang Hao
Published: August 2024

Interdisciplinary advancements, such as generative artificial intelligence (AI) and digital supply chains, can significantly contribute to achieving sustainable development goals (SDGs), particularly within tourism. This paper illuminates how it works well, focusing on the underexplored area of Environmental, Social, and Governance (ESG) performance within small and medium‐sized tourism enterprises (SMEs) in China. Through a survey of 429 international SMEs, we apply the Resource‐Based View and Dynamic Capabilities Theory to investigate how generative AI, such as ChatGPT, in digital supply chains can enhance innovation, collaboration, and, ultimately, ESG performance. The empirical findings underscore the pivotal role of generative AI in augmenting ESG performance via bolstering innovation and collaboration within digital supply chains. Additionally, the moderating effect of customer involvement positively influences the relationship between the digital supply chain and ESG performance. By demonstrating these relations, our study contributes to theoretical and practical efforts toward sustainable tourism and the broader achievement of the SDGs.
Numerical Simulation of Molten Steel Flow Field in a Ladle Induced by Low‐Frequency High‐Power Ultrasound
Authors: Guo Qing , Chen Min , Xu Lei , Cheng Weihao
Published: August 2024

To encourage the use of ultrasound in the calcium treatment of molten steel, this study utilizes the volume‐of‐fluid (VOF) method combined with a mixture model to analyze the distribution of the flow field in molten steel when ultrasound is applied. The effects of low‐frequency, high‐power ultrasound on the pressure field, volume fraction of cavitation bubbles, velocity distribution, and turbulence intensity are investigated. The results reveal a pattern of alternating positive and negative pressure in the pressure field during each cycle, with the lowest pressure measuring −9.63 × 104 Pa at 96 kW. The cavitation bubbles are concentrated in the intense cavitation area beneath the ultrasonic probe, exhibiting a maximum volume fraction of 2.50 × 10−2. The axial velocity peaks at the central axis, whereas the radial velocity is negligible. The maximum axial velocity increases from 0.36 m/s at 48 kW to 0.82 m/s at 120 kW. This velocity trend mirrors the turbulence intensity distribution, with the highest turbulence intensity of 276 at 96 kW. These findings provide a theoretical basis for low‐frequency, high‐power ultrasound to improve the calcium treatment of molten steel. The outcomes of the numerical simulation closely align with the experimental results, substantiating their reliability through a comparison with published studies.
Prevalence and associated risk factors of hydatidosis in cattle slaughtered at Wolaita Sodo municipality abattoir
Authors: Endale Habtamu , Mathewos Mesfin
Published: August 2024

Background

Hydatidosis, caused by the larval stage of the tapeworm Echinococcus granulosus, affect cattle by forming hydatid cyst in thier lungs, livers and pose great financial loss in animal production and country's economy by both direct and indirect effect. Despite its great economic and health importance, there is an absence of current information on cystic echinococcosis in cattle slaughtered at Wolaita Sodo municipality abattoir in Ethiopia.

Objectives

Current investigation determines the prevalence, organ distribution and fertility of hydatid cysts in cattle slaughtered at the Wolaita Sodo municipality abattoir in Ethiopia.

Methods

A cross‐sectional study was conducted from February, 2023, to October, 2023, at Wolaita Sodo municipality abattoir in southern Ethiopia, through regular meat examinations and cyst characterisation to determine the prevalence, organ distribution and fertility of hydatid cysts.

Results

The overall prevalence of hydatidosis recorede in current study was 17.9% (69/384) and has shown a statistically significant association (p < 0.05) with the body condition of cattle. However, there was no statistically significant association (p > 0.05) between the prevalence of hydatidosis and other risk factors such as sex, breed, production system and origin of animals. This study showed that the lungs and liver were the most affected organs in cattle, followed by the spleen and kidneys. On cyst characterisation, the majority of hydatid cysts were found sterile (55.4%) followed by fertile (38.8%) and calcified (8.7%) cysts. Out of 125 fertile hydatid cysts tested for survival, 18.8% (58/321) were viable and 20% (67/321) were nonviable.

Conclusion

The finding of this study shows that cystic echinococcus was important health threat of the cattle and widespread in the internal organs of affected cattle causing significant economic loss by condemning edible organs that are not suitable for human consumption. Therefore, urgent and integreted preventive action is needed to disrupt the life cycle of cystic echinococcosis to tackle subsequent financial loss and risk of zoonosis to humans in the study area.
Real-Time GNSS Integrated Water Vapor Sensing Based on Time Series Correction Deep Learning Models
Authors: Wang Duo , Yuan Peng , Kutterer Hansjörg
Published: August 2024

In the past three decades, GNSS-based Integrated Water Vapor (IWV) retrieval has been intensively investigated, and its products have been widely used in meteorology like severe weather event monitoring. The physical model for the inversion of IWV from the tropospheric Zenith Total Delay (ZTD) requires meteorological data at the location of the GNSS station, such as the surface pressure and the atmospheric weighted mean temperature. However, real-time acquisition of the meteorological data is a very challenging task for most GNSS stations. While proposed empirical models such as Global Pressure and Temperature 3 (GPT3) can provide the meteorological data based on their historical information, larger estimation distortions are found in specific mid- and high-latitude regions. Moreover, we analyzed the seasonal variations in GPT3 prediction errors. In view of the above-mentioned problems, this study implements an IWV conversion model based on a feedforward Deep artificial Neural Network (DNN) and Long Short-Term Memory Network (LSTM) network, which learns historical data from GNSS stations and allows real-time ZTD to IWV conversion without the need of actual meteorological observation but of values only GPT3. Results at four selected mid- and high-latitude GNSS stations show that the Root Mean Square Error (RMSE) of the proposed deep learning method decreases from an average of 3.97 mm to 2.84 mm compared to GNSS IWV retrieved from GPT3. The proposed model provides a broad applicability in real-time GNSS IWV prediction without the availability of real-time measured meteorological data.
11 Accelerating Diagnostic Innovation for Pandemic Control
Authors: Gilliland C. Taylor , Heetderks William , Juluru Krishna , Kirilusha Anthony , Lash Tiffani B. , Merchak Todd , Qashu Felicia , Sheeley Douglas M. , Snyder Mark , Weitz Andrew , Wolfson Michael , Tromberg Bruce
Published: August 2024

Any serious outbreak of a novel infectious disease requires rapid innovation in testing technologies that can efficiently and accurately screen and diagnose active infection on both the individual and population levels. Delays in diagnostic testing imperil containment of an outbreak and delay control of a pandemic. In response to the dearth of diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the outset of the coronavirus disease 2019 (COVID-19) pandemic, the U.S. National Institutes of Health (NIH) launched the Rapid Acceleration of Diagnostics (RADx) initiative. RADx comprises a suite of programs to support the development, production scale-up, and deployment of SARS-CoV-2 tests across the country. RADx helped create a diagnostic testing ecosystem that is dynamic, distributed, and accessible, and that extends diagnostic testing to the point of care (POC) and into homes, schools, and places of business. This chapter describes the approach and lessons learned through one of the components of RADx, RADx Technology, that sped innovation in the development, commercialization, and implementation of COVID-19 testing. RADx Tech, led by the NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB), used an innovation funnel methodology to compress the diagnostic technology development timeline from years to months. This was accomplished by employing expert teams in parallel to address technical, regulatory, clinical, and commercialization requirements and to support the validation, de-risking, scale-up, manufacturing, and deployment of novel SARS-CoV-2 tests. RADx Tech and its partner programs enabled dozens of testing technologies to obtain regulatory authorization, delivered billions of tests into the market, and catalyzed a fundamental shift toward the acceptance and widespread use of self-testing. This program represents a new paradigm by which the NIH, and the federal government writ large, can catalyze medical technology development during a public health emergency.
12 Vaccine Candidates for Novel Pathogens
Authors: Bok Karin
Published: August 2024

This chapter reviews recent progress in developing vaccine platforms and other techniques to formulate vaccine candidates, especially in actual and potential pandemic emergencies. Innovative medical countermeasure (MCM) designs and manufacturing technologies currently in use to combat COVID-19 are primary examples, along with future approaches. Better understanding of viral structure and self-assembly, intended target proteins, and conserved but vulnerable viral epitopes, as well as immune system reactions to viral infection, is foundational to preparedness for the emergence of novel or variant pathogens and rapid development of new MCMs. The prototype pathogen approach to MCM development promotes advance development of vaccine candidates incorporating critical, innovative safety and immunogenicity features into designs based on a well-informed target product profile.
15.1 In Practice: Leveraging an Integrated National Health System for Research Response—The UK National Institute for Health Research Respiratory Translational Research Collaboration
Authors: Lemoine Nick R. , Chinnery Patrick F. , Taylor Charlotte H.
Published: August 2024

This chapter describes the efforts and strategies that allowed the United Kingdom (UK) to lead the world in coronavirus disease 2019 (COVID-19) research, inform government policy, and provide its National Health Service (NHS) and social care systems with tools needed to prevent and treat COVID-19. The UK National Institute for Health Research (NIHR) minimized fragmentation of research efforts between countries in the UK, guided the prioritization of resources across the system in the UK, and focused efforts on therapeutics most likely to be effective against severe acute respiratory system coronavirus 2 (SARS-CoV-2), which causes COVID-19. The Urgent Public Health (UPH) process treated research as a crucial, prioritized component of the COVID-19 response from the start of the pandemic and assembled a portfolio of platform trials spanning first-in-human (Phase I) through Phase III safety and efficacy trials on medical countermeasures (MCMs). The impartial, scientifically driven UK Covid Therapeutics Advisory Panel (UK-CTAP) was established to identify, prioritize, and recommend drugs to be tested through national trial platforms while avoiding duplication of effort. Treatment recommendations were made through an open submission system approach based on three layers of scrutiny to guard against conscious and subconscious bias. A Therapeutics Taskforce coordinated government efforts and ensured that high-quality research was delivered at pace, providing patients with timely access to safe and effective COVID-19 treatments. These successes have helped save the lives of millions around the world, and NIHR continues to support critical research that enables treatments and vaccines for all.
18 Good Participatory Practice: Social Mobilization, Communications, and Community Engagement
Authors: Sorenson Robert A. , Delph Yvette , Wilson Bartholomew , Fallah Mosoka P. , Higgs Elizabeth S.
Published: August 2024

Good participatory practice (GPP) is a set of procedures to ensure all stakeholders in a clinical trial have a voice in the research process. It is rooted in the ethical imperative to treat people as ends in themselves, rather than mere means. It is also a necessity for research programs to engender participant and community trust in clinical research and ultimately in the safety and efficacy of medical countermeasures (MCMs) validated by clinical trials. GPP requires systematically reaching out to all stakeholders who are affected by or can influence the research in question, listening to them, and making changes to the way the trial team interacts with stakeholders if needed. Genuine dialogue with stakeholders about the principles of clinical research and why it is being conducted in their community is the basic principle. As well as GPP, this sort of engagement is known by different names in various places: in sub-Saharan Africa, it is often referred to as social mobilization, communication, and community engagement (SMC).

While GPP/SMC should be part of all clinical research efforts, it must be part of an emergency research response. When populations are under stress from an emerging infectious disease and its disruptive social consequences, their active participation in the research; their understanding of its purpose, goals, and process; and their confidence in research integrity, ethics, and oversight are pragmatic as well as normative requirements. Without community backing, a research program may not be feasible, and if the research identifies an MCM as safe and efficacious but it is not used for lack of confidence, then it does little good. GPP must be tailored to circumstances, including the pathogen causing the outbreak, the dynamics of the disease, and the type of study. It should be responsive to feedback from stakeholders so as to refine messaging content and format, adjust procedures, and effectively communicate both successes and obstacles. Fruitful dialogue requires understanding the communities, languages, and cultures involved. Effective GPP strengthens those communities and other stakeholders and contributes to enhanced healthcare and research capacity. To illustrate these themes, this chapter explores some common patterns evident in different times and places, such as the 2014–2016 Ebola outbreak in West Africa and the coronavirus disease 2019 (COVID-19) epidemic.
18.1 In Practice: Building Community Engagement for Clinical Research Response
Authors: Andrasik Michele , Broder Gail , Oseso Linda , Segura Patricia , Baepanye Kagisho , Kamel Luciana , Michael Nelson
Published: August 2024

This in-practice text provides examples of progressive community engagement that lays the groundwork for an emergency clinical research response in case of need. Community engagement via good participatory practice (GPP) enables sharing information and perspectives among community members, researchers, research sponsors, and other stakeholders throughout the clinical trial lifecycle. It builds and maintains relationships and partnerships between the research team and the wider community through bidirectional communication and reciprocity. Real-world examples of community engagement include the Transcrições Art Project for fostering relationships with transgender women in Rio de Janeiro, which played a role during the COVID-19 pandemic, and the CEPAD HIV testing center in Buenos Aires. Real-world examples of meaningful community involvement also include the COVID-19 Prevention Network (CoVPN), with clinical research sites in South and Central America, southern Africa, and the United States. The sites have been active in reducing misinformation and disinformation about COVID-19. In the United States, southern Africa, and South America, full-time network staff provide technical assistance and capacity building to sustain community engagement efforts at clinical research sites. GPP is vital to preparedness and requires additional attention and support if it is to be optimized for pandemic response, as shown by the examples given.
18.2 18.2 In Practice: Adapting Social Analytics for Research Response
Authors: O’Neill Rhys , Cyprian David , Higgs Elizabeth S.
Published: August 2024

Social analytics had its genesis in the defense and communication sectors. At the outset of the 2014–2016 West Africa Ebola outbreak, social analytics techniques were adapted and modified to support social mobilization, communication, and community engagement (SMC) efforts in Liberia. The experience demonstrated that social analytics provides a powerful tool for understanding community beliefs, identifying trusted sources of information, monitoring rumors, and public understanding (or not) of research and response interventions. Utilization of social analytics techniques has been increasing; for example, supporting the Democratic Republic of the Congo (DRC) during the large 2018–2020 Ebola virus disease (EVD) outbreak in its eastern provinces, as well as in COVID-19 vaccination efforts, and more recently in support of WHO AFRO.

Social analytics can often be misconstrued as social media monitoring, but effective social analytics requires comprehensive “listening”; a holistic approach to available social data, including online content, news and broadcast content, field research; and, perhaps most distinctively, local, on-the-ground experts knowledgeable about the social and cultural context. Social analytics must thus be used to gather and analyze data close to operational teams. Societal and community beliefs can vary between neighboring communities, and it should never be assumed that one community will react to events or messages the same way as others. Beliefs and attitudes also change throughout a health emergency. Therefore, social analytics must be geographically precise and updated weekly to stay current and inform effective disinformation countermeasures and risk communications. What began as work with NIAID on a single outbreak in West Africa has evolved into a powerful tool for informing communication, messaging, and dialogue with communities and broader populations during health emergencies. Social analytics is now an established, powerful tool for assisting social mobilization committee (SMC) pillars, research sponsors, and host governments as they respond to health emergencies.
19 Understanding and Reporting the Natural History of an Infectious Disease
Authors: Crozier Ian
Published: August 2024

Accurate characterization of the natural history of a disease is often inadequate in outbreaks of novel or re-emerging infectious diseases. Through the lens of the host–pathogen–care interface, the stages, outcomes, and determinants of the natural history are considered, with emphasis on how the natural history might suggest interventions to improve acute and convalescent outcomes. Understanding the natural history directly informs not only clinical care but also preclinical development and discovery of medical countermeasures and sets the stage for design of high-quality clinical trials of the same. Conducting optimal natural history studies is challenging during an infectious disease emergency; strategies to enhance understanding and report natural history as part of the emergency research response are discussed.
21 Epidemiologic Research in the Setting of Outbreak Response
Authors: Reingold Arthur
Published: August 2024

The highest priority during the response to an outbreak or epidemic is to limit morbidity and mortality by preventing new cases and improving outcomes in those who are affected. Epidemiologic research is an essential component of such a response. Well-designed and rapidly executed observational epidemiologic studies, often done in conjunction with laboratory and environmental investigations and informed by relevant behavioral and social sciences knowledge, can help guide the development and implementation of interventions that ameliorate the current outbreak, as well as contribute to more effective and earlier responses to future outbreaks. While generic, “off the shelf” protocols for studies of some recurring, outbreak-prone infectious diseases (e.g., cholera and influenza) may help expedite such studies, they are no substitute for well-trained, experienced epidemiologists who are available for rapid deployment wherever and whenever they are needed to plan and carry out such studies. Experience with recent epidemics and pandemics caused by a wide range of infectious disease agents (e.g., Ebola, Zika, severe acute respiratory syndrome [SARS or SARS-1], influenza, and coronavirus disease 2019 [COVID-19]) illustrates the central contribution of observational epidemiologic studies to enhanced understanding of and improved response to both new and old infectious disease threats. Following the COVID-19 pandemic, there will be considerable investment, at least in the short term, in accelerating outbreak response research, including its epidemiologic dimensions. Assuring that such research is thoughtfully designed and carefully implemented is a high priority.
22 Vaccine Trial Designs
Authors: Kahn Rebecca , Villar Sofia S. , Dean Natalie E. , Lipsitch Marc
Published: August 2024

Vaccine efficacy trials conducted during epidemics of emerging infectious diseases have three main objectives: (1) to test the null hypothesis in a rigorous fashion, (2) to estimate the efficacy of the vaccine candidate, and (3) to maximize the trial’s public health impact. All of these objectives create urgency for planning and implementing vaccine trials. Ideally, a preferred design choice, based on the anticipated aims of a trial, should be chosen as early as possible. Here we discuss five key choices that must be made in trial design: (1) randomization unit, (2) comparator intervention, (3) trial population, (4) trial implementation, and (5) primary endpoint. We examine each of these choices in the context of each of the three objectives. We also describe the opportunities and challenges of employing adaptive designs for vaccine trials. Where possible, simple, familiar designs should be chosen to make the trial easier to conduct, results easier to interpret, and authorization or approval easier to obtain. However, in some circumstances, innovative designs may be called for, and having preapproved protocols with adaptive elements incorporated can help expedite such trials during an outbreak. The contrast between vaccine trial conditions and choices during the West African Ebola outbreak and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a reminder of the unique challenges arising in each infectious disease emergency and the importance of these conditions in guiding trial design.
22.1 In Focus: Ring Trial Design
Authors: Dean Natalie E. , Longini Ira M.
Published: August 2024

This focus article explains the origins, design, and rationale behind the ring trial design for clinical medical countermeasure (MCM) research, especially in an emergency response setting. In a ring trial, individuals linked to a newly diagnosed infectious disease case are recruited and randomized as a cluster or individually within the ring to an intervention such as vaccination or a control arm. The advantages and disadvantages of the ring trial design are outlined, and the Ebola ça Suffit! vaccine ring trial in Guinea is provided as an illustration. Considerations for an appropriate study design and potential modifications to the design, such as amending the definition of a ring, are described. The ring trial design has great potential for future applications to evaluate fast-acting interventions in settings where spatiotemporal disease incidence is highly unpredictable and infection is relatively rare. Such an approach has the potential to accelerate the accrual of critical results in emergency response research.
23 Data and Safety Monitoring of Clinical Trials During Public Health Emergencies
Authors: Proschan Michael A. , Grund Birgit
Published: August 2024

Public health emergencies present special challenges in the monitoring of clinical trials. There is tremendous pressure to find effective treatments as quickly as possible without jeopardizing the integrity of results. Frequent early monitoring from an experienced data and safety monitoring board (DSMB) is required to ensure patient safety, especially when novel or repurposed interventions may be tested earlier than they would be in a nonemergency setting. This chapter begins by reviewing general monitoring, including the purpose, composition, and operation of DSMBs, efficacy monitoring boundaries, tools such as conditional power and predicted interval plots for judging whether continuation of a trial is futile, and practical aspects of monitoring clinical trials. We offer important historical examples, like the Cardiac Arrhythmia Suppression Trial (CAST), as well as more recent examples specific to infectious disease, such as the Adaptive COVID-19 Treatment Trial (ACTT-1). We highlight the special challenges posed by monitoring clinical trials in public health emergencies and illustrate these with a case study of the Partnership for Research on Ebola Vaccines in Liberia (PREVAIL-I) vaccine trial in West Africa. We conclude with important lessons learned.
24 Mathematical Modeling for Emergency Response: Using Models to Inform and Direct Response Priorities and Shape the Research Agenda
Authors: Greening Bradford , Meltzer Martin I.
Published: August 2024

Mathematical modeling has become an essential component of planning for and responding to infectious disease outbreaks and other threats. Modeling can provide insights into possible scenarios when there are insufficient data for statistical analysis to produce solid guidance for decision-makers, allowing them to, for example, undertake immediate response for the most likely outcomes and begin contingency planning for worst-case scenarios. Good modeling depends on using experience and well-tested models and bringing in new data as they become available in a continuous process of refinement. Modeling can provide a sense of the interventions needed, the magnitude of required response, and what leadership needs to convey to the health care system and the broader population. An introduction to the main types of models used in infectious disease response follows, along with a summary of how to communicate the results to decision-makers. A worked example allows readers to follow along with the development of a modeling and information process. Modeling cannot produce predictions in the absence of essential data, but it can provide guidance on what could happen, and do so with increasing reliability as more data on the complex interactions between a pathogen and human populations become available.
28 Financing Emergency Research Response During Infectious Disease Outbreaks: Lessons from the World Bank and Other International Financial Institutions
Authors: Pate Muhammad Ali , Bali Sulzhan
Published: August 2024

Recent infectious disease outbreaks have stimulated multiple institutional and operational efforts by governments, international organizations, and the private sector to ensure the world is better prepared to respond to epidemics. One of the critical advances has been the greater engagement of international financial institutions (IFIs) in supporting preparedness for and response to emerging and re-emerging infectious diseases (EIDs) with epidemic potential. Despite progress on preparedness and response, including the launch of initiatives such as the Coalition for Epidemic Preparedness Initiatives (CEPI), the world is not well prepared for the next pandemic, and research and development (R&D) for medical countermeasures against EIDs requires more attention, coordination, and investment. IFI investments in health security have so far focused primarily on disease surveillance, laboratory capacity, outbreak readiness, and human resources for health security, under initiatives that have not so far included sufficient focus on R&D for preparedness and accelerated development of new vaccines, therapeutics, and diagnostics (VTD) against novel pathogens.

This chapter examines how IFIs can better contribute to the advancement of EID preparedness and response. It describes IFI initiatives, including those by the World Bank, that complement other global efforts to galvanize emergency research during EID outbreaks. IFI initiatives seek to strengthen national and regional infectious disease response systems. Through IFI financial management expertise, leveraging IFIs’ comparative advantage in fund management services and their use of development lending, IFIs also seek to bolster core capacity at the intersection of health systems and clinical research. This chapter also notes some constraints faced by IFIs in financing clinical research and examines lessons and opportunities for IFIs to accelerate investment in emergency research.
30 Organizational Partnerships for Preparedness and Response to Emerging and Re-emerging Infectious Diseases
Authors: Yazdanpanah Yazdan , Madelaine Claire , Pulik Nicolas , Souteyrand Yves
Published: August 2024

International crises demand active formation of health research partnerships, which are collaborative relationships between two or more parties for the common goal of improving the health of populations through mutually agreed functions and principles and sharing of risks and benefits. Key partnership players include communities, national authorities and health systems, research organizations, academic centers, non-governmental organizations (NGOs), pharmaceutical companies, international funders, policymakers, and the World Health Organization (WHO). The greatest strength of these partnerships is their ability to combine the complementary strengths of different stakeholders to achieve common objectives. To improve pandemic preparedness and the capacity for prompt responses to emerging infectious diseases, the chapter recommends enhancing partnerships, embedding international R&D efforts into national health systems; providing appropriate research funding; developing and strengthening human resources, communication, infrastructures, and surveillance; and translating science into policy decisions.
30.2 In Practice: Building and Maintaining Preparedness for a Rapid Research Response in Indonesia
Authors: Lau Chuen-Yen , Grue Louis , Neal Aaron , Karyana Muhammad
Published: August 2024

Existing international research partnerships, bilateral or multilateral, are a crucial building block of research response preparedness. The long-standing partnership between the Indonesia Ministry of Health and the U.S. National Institute of Allergy and Infectious Diseases, known as INA-RESPOND, demonstrated the value of such preparedness through its early contributions to the diagnosis of and research on coronavirus disease 2019 (COVID-19) in early 2020. Building on such partnerships is essential preparation for the next potential pandemic, especially in parts of the world where animal species diversity; close contact among humans, livestock, and wild fauna; and land use changes make the spillover of novel zoonotic pathogens most likely. INA-RESPOND has also demonstrated its capacity to work with other partners, like the World Health Organization and universities in Australia, thus making it an internationally linked node in a global framework that may be the best hope for preventing the next pandemic.
4.1 In Practice: Vaccine Efficacy and Safety Testing—An Ethical Case for Individual Randomization
Authors: Eyal Nir , Lipsitch Marc
Published: August 2024

A scientific trial has individually randomized control when the intervention or control status for each participant is independently chosen at random at the start of the trial. That is in contrast to cluster randomization, where this status is determined for groups of participants, and in contrast to trials without randomization and to non-trial methods of assessing experimental interventions. The individually randomized controlled trial is generally the most effective and thus the most ethical trial design for assessing the safety and efficacy of candidate vaccines against infectious disease. With this trial design, all study participants benefit by receiving protections that other people at similar risk of infection often do not receive. These benefits include close monitoring, enhanced clinician–patient ratios, and the opportunity to be randomized to the preferred arm of the study. Furthermore, individually randomized trials for emergency response usually reach any given level of statistical confidence before alternative designs with group randomization. Individual randomization is also compatible with delayed or active control trial designs, parallel or stepped rollout, a variety of primary endpoint trial population choices, and either environmental or challenge exposure to the pathogen.
33.3 In Practice: Capacity Building for Research Ethics Review in Low- and Middle-Income Countries
Authors: Sina Barbara , Tierney John
Published: August 2024

All research with human participants must undergo ethical review by a research ethics committee with jurisdiction over the location of a proposed research study. Recent global infectious disease outbreaks have exposed shortcomings even in otherwise well-functioning ethical review systems in developed countries when they must meet the urgent demands of outbreak research. Moreover, relatively little global health research funding and resources have supported development of research ethics review system capacities in low- and middle-income countries. Countries with less robust ethics review systems and limited current support, less pertinent expertise, and lower administrative capabilities have been even more affected by emergency outbreaks. To be better prepared for the next outbreak or other public health emergencies, research partners must make every effort to support sustainable development of local resources and institutions, oversight of ongoing research, and review of new research proposals. This chapter will concentrate on three areas: (1) evaluation of existing research ethics review capacity, (2) partnering and exchange to immediately address gaps and needs, and (3) developing future research infrastructure and capacity to ensure epidemic ethics preparedness.
37 Supply and Logistics for Clinical Research in Low-Resource Settings
Authors: Baseler Beth , Proffitt Calvin , Sandrus Jen , Marchand Jonathan , Stavale Eric
Published: August 2024

Providing continuous logistical support for clinical research sites is a critical function of any clinical research study, one that is substantially more challenging for an emergency research response in a resource-limited setting. This chapter provides an overview of the planning considerations involved, as well as a discussion of specific functions like partnership development, export and import, transportation, supply and equipment management, and hiring in-country staff to provide logistical support. The chapter includes multiple potential solutions, since more than one approach, as well as flexibility and creativity, are generally needed to keep a scientific research operation running in an infectious disease emergency—especially where resources are scarce and the populace distressed by fear and concern for themselves and their families.
38 Pharmaceutical Management
Authors: Kirchoff Matthew Carl
Published: August 2024

Clinical research pharmacists at remote research sites in low-resource nations face many of the same challenges as their colleagues in better-equipped environments but more acutely. These problems can include shortages, facility shortcomings, language difficulties, storage issues, regulatory questions, and logistical demands—from initial anticipation of requirements to the special considerations involved in handling investigational medicinal products and the ultimate disposition of biohazardous material. This chapter provides an overview of standard clinical research requirements, potential obstacles in a low-resource setting, and ways to overcome them, focusing on considerations that one might overlook when responding to an outbreak in a high-pressure, unfamiliar, and resource-constrained setting. It includes references to the most authoritative guidelines and frequently used manuals for ensuring that the pharmaceutical operation in a research program supports an expedited, scientifically and ethically rigorous research program in response to an infectious disease emergency.
41 Management of Security for Clinical Trials During Emergencies
Authors: Muyisa Billy Sivahera , de Sainte Fare Eric Barte , Aboulhab Jamila
Published: August 2024

Virtually all emergency clinical research in infectious disease outbreaks involves risks—ranging from suspicion and resentment on the part of local populations, and sometimes local officials, to operations amid violent conflict, as in the northeastern Democratic Republic of the Congo (DRC) during the 2018–2020 Ebola outbreak. Before any such research can begin, project planners must assess the threat environment and organize and implement protective measures. In general, such strategies should include establishing and rehearsing security procedures for all staff so that everyone knows where they should be and what they should be doing in an emergency, and arranging to guard research sites at all times, especially areas where pharmaceuticals and valuable equipment are held. Information and communications security is also vital to operations.
5 Health Emergency Research amid Global Inequities: Some Considerations for Researchers
Authors: Greco Dirceu
Published: August 2024

Even under the pressure of a worldwide pandemic, urgent international medical research must be ethically planned and conducted, particularly in lower-income countries, to avoid the appearance or the reality of exploitation. Over the past few decades, a number of international research ethic codes have been developed to protect the rights of individual research participants—sometimes even to the point of guaranteeing them access to the fruits of the research years after the trial in which they took part has ended. Among these are the Declaration of Helsinki, the UNESCO Universal Declaration on Bioethics and Human Rights, and the frequently updated ethics guidelines by the Council for International Organizations of Medical Sciences (CIOMS). However, these codes, and often the research institutions that comply with them, miss a crucial point. They do not come to grips with the broader societal context in which emergency research on emerging or re-emerging infectious diseases is carried out. The Ebola outbreak in 2014–2016 and the COVID-19 pandemic that exploded in 2020 revealed deep disparities between wealthy and lower-income countries in health, medical care, and the social and economic conditions that lay at the heart of their impoverishment. World Health Organization (WHO) Director General Tedros Adhanom Ghebreyesus declared that the coronavirus disease 2019 (COVID-19) pandemic has hit the poorest countries in the world hardest and “instead of solidarity, the pandemic has been marred by inequity.” The international health, research, and ethics communities—and their home countries—must work together to correct these inequities.
Private Sector Engagement Policies in South Korea: Challenges and Policy Recommendations
Authors: Kim Eunju
Published: August 2024

The Korean government recently announced a strategy for engaging the private sector in international development. There are expectations that this will attract innovative solutions with more financial resources, but, on the other hand, there are concerns that private companies will only focus on pursuing commercial interests without paying attention to the normative legitimacy such as private sector development in partner countries. There are also concerns that fragmentation will further deepen as ODA funds are divided due to mutual non-interference among various actors. Finally, this study discusses policy implications for Korean private companies to be development agents which are derived from the case of German private sector engagement.
The Political Economy of German and Korean Sustainability Transitions
Authors: Kalinowski Thomas
Published: August 2024

Germany and the Republic of Korea (hereafter referred to as Korea) have ambitious goals for a green transformation but follow distinct paths that both have their strengths and weaknesses. Germany is more advanced in emission reduction, energy efficiency and environmental conscious behaviour, while Korea leads in investment in green infrastructure and industries. These distinct traits can be explained by path-dependent political economies. In Germany this created a market-oriented approach that adds an ecological dimension to the German “social market economy”. Korea, on the other hand, follows the path of its “developmental state”, which sees the ecological transformation as an opportunity to achieve industrial development and export leadership in green industries. Both strategies offer important insights for mutual learning as well as lessons for developed and developing countries alike.
Introduction: The Massacre That Changed Ukraine and the World
Authors: Katchanovski Ivan
Published: August 2024

The chapter describes importance of the Maidan massacre of the police and the Maidan protesters in Kyiv in Ukraine on February 18–20, 2014, and its role in the overthrow of the Ukrainian government and ultimately in the start of the war in Donbas, the Russian annexation of Crimea, and conflicts of Russia with Ukraine and the West that Russia escalated dramatically by launching the illegal war with Ukraine on February 24, 2022. The question is whether the Yanukovych government, the Maidan opposition, in particular, the far-right, or any “third force,” such as Russia, was involved in the mass killing of protesters and the police.
Conflicting Narratives of the Maidan Massacre in Ukraine
Authors: Katchanovski Ivan
Published: August 2024

This chapter examines different narratives concerning the Maidan massacre of the Maidan activists and the police on February 18–20, 2014, and previous scholarly studies of this massacre. The dominant narrative promoted by the Ukrainian and Western governments and with some exceptions the media attributed the Maidan massacre of the protesters to the Yanukovych government and his security forces and Berkut anti-riot police.
Forensic Ballistic and Medical Examinations by Ukrainian Government Experts
Authors: Katchanovski Ivan
Published: August 2024

This chapter analyzes results of forensic ballistic and medical examinations and investigative experiments by government experts for the Ukrainian government investigation and the Maidan massacre trial.