To answer how epidemics end, one must ask two intersecting but separate questions: first, how particular waves of epidemics end, whether of yellow fever, cholera, plague; and second, how epidemic diseases become eradicated-either through scientific intervention, as with smallpox in the 1970s, or simply by disappearing for reasons that remain mysterious, as with the Second Plague Pandemic from ca. 1347. This article challenges two general notions on how epidemics end. First, individual waves of plagues in European municipalities or regional states (...) did not just fade into the sunset. By the late 16th century, their ends were celebrated with artistic displays, musical and poetic performances, ex-voto gifts, and bangs ranging from tambourines to military salutes. Second, the five-century Second Pandemic of plague-that is, the disease-did not end with declarations or scripted performances, but with another sort of bang. Instead of the usual assumption that epidemic diseases decline gradually over time, progressively inflicting lighter loads of virulence and mortality, the last significant plague outbreaks in most regions in Europe returned to heights of mortality not seen since the Black Death of 1347-1351. Finally, this article adds an obvious but rarely mentioned variable for understanding epidemic endings. Before widespread vaccination, the characteristics of these disappearances depended on the type of disease. (shrink)

Patterns of reproductive failure described in humans and other mammals suggest that reproductive failure may in many instances be the result of adaptations evolved to suppress reproduction under temporarily harsh conditions. By suppressing reproduction under such conditions, females are able to conserve their time and energy for reproductive opportunities in which reproduction is most likely to succeed. Such adaptations have been particularly important for female mammals, given (a) the amount of time and energy that reproduction requires, and (b) the degree (...) to which reproductive conditions can vary.The existence of conscious and unconscious mechanisms to suppress reproduction under poor conditions has several implications for obstetric/gynecologic practices. Two implications are discussed with reference to biotechnological advancements in our ability to facilitate conceptions and manage problem pregnancies: (a) potential dangers of sophisticated technologies overriding natural fertility controls; and (b) the need for greater appreciation of the association between psychosocial stress and reproductive failure in the treatment of reproductive problems. Implications for elective abortion practices are discussed as well. (shrink)

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved (...) in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed. (shrink)

Ethical theories consistent with Christian moral sensibilities must assure each neighbor's dignity and recognize his or her unique needs. While utilitarian ethics and duty-based ethics may fail to some degree in these respects, virtue ethics offers perspectives that echo more faithfully the parable of the Good Samaritan.

Experimental, theoretical, psychological, and economic barriers have caused physicians to rely on biomedical treatments for infertility at the exclusion of more environmentally oriented ones (e.g., psychosocial stress therapy). An evolutionary model is described for the origin of reproductive failure, suggesting why mammals evolved to be reproductively responsive to the environment and why psychosocial stress should have an especially strong impact on fertility problems. A study of the causal role of psychosocial stress in infertility is then summarized. The paper concludes with (...) implications for future directions for the treatment of infertility and related human reproductive problems. (shrink)

Applied Christian Ethics addresses selected themes in Christian social ethics. Part one shows the roots of contributors in the realist school; part two focuses on different levels of the significance of economics for social justice; and part three deals with both existential experience and government policy in war and peace issues.

The threat of bioterrorism, the emergence of the SARS epidemic, and a recent focus on professionalism among physicians, present a timely opportunity for a review of, and renewed commitment to, physician obligations to care for patients during epidemics. The professional obligation to care for contagious patients is part of a larger "duty to treat," which historically became accepted when 1) a risk of nosocomial infection was perceived, 2) an organized professional body existed to promote the duty, and 3) the public (...) came to rely on the duty. Physicians' responses to epidemics from the Hippocratic era to the present suggests an evolving acceptance of the professional duty to treat contagious patients, reaching a long-held peak between 1847 and the1950's. There has been some professional retrenchment against this duty to treat in the last 40 years but, we argue, conditions favoring acceptance of the duty are met today. A renewed embrace of physicians' duty to treat patients during epidemics, despite conditions of personal risk, might strengthen medicine's relationship with society, improve society's capacity to prepare for threats such as bioterrorism and new epidemics, and contribute to the development of a more robust and meaningful medical professionalism. (shrink)

��We describe a comprehensive framework for text un- derstanding, based on the representation of context. It is designed to serve as a representation of semantics for the full range of in- terpretive and inferential needs of general natural language pro- cessing. Its most distinctive feature is its uniform representation of the various simple and independent linguistic sources that play a role in determining meaning: lexical associations, syntactic re- strictions, case-role expectations, and most importantly, contextual effects. Compositional syntactic structure from a (...) shallow parsing is represented in a neural net-based associative memory, where it then interacts through a Bayesian network with semantic associa- tions and the context or “gist” of the passage carried forward from preceding sentences. Experiments with more than 2000 sentences in different languages are included. (shrink)

BackgroundGenetics and genomics research (GGR) is increasingly being conducted around the world; yet, researchers and research oversight entities in many countries have struggled with ethical challenges. A range of ethics and regulatory issues need to be addressed through comprehensive policy frameworks that integrate with local environments. While important efforts have been made to enhance understanding and awareness of ethical dimensions of GGR in Africa, including through the H3Africa initiative, there remains a need for in-depth policy review, at a country-level, to (...) inform and stimulate local policy development and revision on the continent.MethodsTo identify and characterize existing ethics-related guidelines and laws applicable to GGR across much of Africa, we conducted a scoping review of English language policy documents identified through databases, repositories, and web searches. Thirty-six documents were included and coded using a framework that contained a range of themes across five analytical categories: (1) respect, (2) beneficence, (3) justice, (4) independent oversight, and (5) bans and prohibitions. Data analysis software (NVivo 12) was used to organize, code, and tabulate information according to document characteristics and topics. Illustrative examples of policy requirements were selected for inclusion.ResultsDocuments that met inclusion criteria spanned 20 years; published between 1996 and 2018, with the majority (58%) published after 2009. About two-thirds were denoted as “guidelines,” and slightly more than half were non-exclusive to GGR. Very few (six) country-level documents identified were specific to GGR. Requirements related to the principle of “respect” appeared most often across all documents, relative to other principles and processes. The most commonly stated ban was on reproductive cloning. Other prohibitions applied to germline editing, undue inducements in research, sample use for commercial purposes, employee mandatory DNA testing, fetal sex selection, stem cell use, eugenics, and research without public health benefits.ConclusionsEnforceable policies that are indispensable to the ethical conduct and review of GGR are either deficient or missing in many African countries. Existing international, GGR-specific ethics guidelines can be used to inform GGR policy development at a country-level, in conjunction with insight from country specific ethics committees and other local stakeholders. (shrink)

Matching in observational studies faces complications when units enroll in treatment on a rolling basis. While each treated unit has a specific time of entry into the study, control units each have many possible comparison, or “pseudo-treatment,” times. Valid inference must account for correlations between repeated measures for a single unit, and researchers must decide how flexibly to match across time and units. We provide three important innovations. First, we introduce a new matched design, GroupMatch with instance replacement, allowing maximum (...) flexibility in control selection. This new design searches over all possible comparison times for each treated-control pairing and is more amenable to analysis than past methods. Second, we propose a block bootstrap approach for inference in matched designs with rolling enrollment and demonstrate that it accounts properly for complex correlations across matched sets in our new design and several other contexts. Third, we develop a falsification test to detect violations of the timepoint agnosticism assumption, which is needed to permit flexible matching across time. We demonstrate the practical value of these tools via simulations and a case study of the impact of short-term injuries on batting performance in major league baseball. (shrink)

Three traditions have influenced the idea of the state in India – the Hindu Rajah, the Islamic View and the European Secular State. From biblical and theological considerations, Christians must reject the totalism and ego-centrism of modern states and work for greater accountability and decentralised decision-making.

In a recent Target Article Naomi Scheinerman (2023a) has offered an important and compelling call to institutionalize popular participation for heritable genome engineering through the inclusion of...

Research exploring the needs of families of childhood cancer survivors is critical to improving the experiences of future families faced by this disease. However, there are numerous challenges in conducting research with this unique population, including a relatively high mortality rate. In recognition that research with cancer survivors is a relational activity, this article presents a series of cases of parents bereaved by childhood cancer who unintentionally received invitations to participate in survivorship research. We explore six ethical considerations, and compare (...) our experiences with that described previously. Our considerations include the sharing of confidential information with external parties to confirm past patients’ vital status and appropriate researcher responses to bereaved parents. The management of researchers’ emotional safety when working with illness populations and the fact that study invitations can elicit grief responses in non-bereaved families are discussed. To conclude, we argue for the benefits of inviting bereaved parents whose children died after treatment completion in survivorship research. Such parents’ early survivorship experiences will otherwise be systemically neglected. We argue that discussing complex cases can assist researchers to protect participants’ and researchers’ emotional well-being. We hope to contribute to the dearth of discussion about research operating procedures to address these issues. (shrink)

This manuscript reviews recent evidence supporting the utility of telomeres and mitochondrial DNA copy number (mtDNAcn) in detecting the biological impacts of adverse childhood experiences (ACEs) and outlines mechanisms that may mediate the connection between early stress and poor physical and mental health. Critical to interrupting the health sequelae of ACEs such as abuse, neglect, and neighborhood disorder, is the discovery of biomarkers of risk and resilience. The molecular markers of chronic stress exposure, telomere length and mtDNAcn, represent critical biological (...) links between ACEs and poor health outcomes. We examine how telomeres and mtDNAcn may exacerbate health disparities and contribute to the intergenerational transmission of trauma. Finally, we explore how these molecular markers of early stress exposure may help define the role of resilience and develop effective interventions to moderate ACE health risk impact. (shrink)

Two of the lead articles in this issue examine the emerging practice of organ procurement by normothermic regional perfusion (NRP) in terms of whether or not these patients are “dead” at the time t...