Regional patient transfer patterns matter for the spread of hospital-acquired pathogens.

Pathogens typically responsible for hospital-acquired infections (HAIs) constitute a major threat to healthcare systems worldwide. They spread via hospital (or hospital-community) networks by readmissions or patient transfers. Therefore, knowledge of these networks is essential to develop and test strategies to mitigate and control the HAI spread.

Transmission of drug-resistant bacteria in a hospital-community model stratified by patient risk.

A susceptible-infectious-susceptible (SIS) model for simulating healthcare-acquired infection spread within a hospital and associated community is proposed. The model accounts for the stratification of in-patients into two susceptibility-based risk groups. The model is formulated as a system of first-order ordinary differential equations (ODEs) with appropriate initial conditions.

Diversity and inclusion for rodents: how animal ethics committees can help improve translation.

Translation failure occurs when a treatment shown to be safe and effective in one type of population does not produce the same result in another. We are currently in a crisis involving the translatability of preclinical studies to human populations. Animal trials are no better than a coin toss at predicting the safety and efficacy of drugs in human trials, and the high failure rate of drugs entering human trials suggests that most of the suffering of laboratory animals is futile, creating no commensurate benefit for human patients.

Clarifying the Ethics and Oversight of Chimeric Research.

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human-nonhuman chimeric research.

The effect of re-directed patient flow in combination with targeted infection control measures on the spread of multi-drug-resistant Enterobacteriaceae in the German health-care system: a mathematical modelling approach.

Objective: The introduction of multi-drug-resistant Enterobacteriaceae (MDR-E) by colonized patients transferred from high-prevalence countries has led to several large outbreaks of MDR-E in low-prevalence countries, with the risk of propagated spread to the community. The goal of this study was to derive a strategy to counteract the spread of MDR-E at the regional health-care network level.

Methods: We used a hybrid ordinary differential equation and network model built based on German health insurance data to evaluate whether the re-direction of patient flow in combination with targeted infection control measures can counteract the spread of MDR-E in the German health-care system.

Application of Inspiratory Muscle Training to Improve Physical Tolerance in Older Patients with Ischemic Heart Failure.

Regardless of the management regime for heart failure (HF), there is strong evidence supporting the early implementation of exercise-based cardiac rehabilitation (CR). Respiratory therapy is considered to be an integral part of such secondary prevention protocols. The aim of the study was to evaluate the effect of inspiratory muscle training (IMT) on exercise tolerance and the functional parameters of the respiratory system in patients with heart failure involved in cardiac rehabilitation.

Effects of incomplete inter-hospital network data on the assessment of transmission dynamics of hospital-acquired infections.

In the year 2020, there were 105 different statutory insurance companies in Germany with heterogeneous regional coverage. Obtaining data from all insurance companies is challenging, so that it is likely that projects will have to rely on data not covering the whole population. Consequently, the study of epidemic spread in hospital referral networks using data-driven models may be biased.

Relevance of intra-hospital patient movements for the spread of healthcare-associated infections within hospitals - a mathematical modeling study.

The aim of this study is to analyze patient movement patterns between hospital departments to derive the underlying intra-hospital movement network, and to assess if movement patterns differ between patients at high or low risk of colonization. For that purpose, we analyzed patient electronic medical record data from five hospitals to extract information on risk stratification and patient intra-hospital movements. Movement patterns were visualized as networks, and network centrality measures were calculated.

Research guidelines for embryoids.

Human embryo models formed from stem cells-known as embryoids-allow scientists to study the elusive first stages of human development without having to experiment on actual human embryos. But clear ethical guidelines for research involving embryoids are still lacking. Previously, a handful of researchers put forward new recommendations for embryoids, which they hope will be included in the next set of International Society for Stem Cell Research guidelines.

Modelling pathogen spread in a healthcare network: Indirect patient movements.

Inter-hospital patient transfers (direct transfers) between healthcare facilities have been shown to contribute to the spread of pathogens in a healthcare network. However, the impact of indirect transfers (patients re-admitted from the community to the same or different hospital) is not well studied. This work aims to study the contribution of indirect transfers to the spread of pathogens in a healthcare network.

Rethinking the oversight conditions of human-animal chimera research.

New discoveries are improving the odds of human cells surviving in host animals, prompting regulatory and funding agencies to issue calls for additional layers of ethical oversight for certain types of human-animal chimeras. Of interest are research proposals involving chimeric animals with humanized brains. But what is motivating the demand for additional oversight? I locate two, not obviously compatible, motivations, each of which provides the justificatory basis for paying special attention to different sets of human-animal chimeras.

Avoiding the potentiality trap: thinking about the moral status of synthetic embryos.

Research ethics committees must sometimes deliberate about objects that do not fit nicely into any existing category. This is currently the case with the "gastruloid," which is a self-assembling blob of cells that resembles a human embryo. The resemblance makes it tempting to group it with other members of that kind, and thus to ask whether gastruloids really are embryos.

Why is an Egg Donor a Genetic Parent, but not a Mitochondrial Donor?

As new ways of reproducing emerge, advancing technologies are forcing us to rethink our old ideas of what it means to be a genetic parent. Why should some processes qualify as "reproduction" and others should not? To illustrate the practical impact of providing a defensible account of reproduction, the author examines the case of mitochondrial donation (mtDNA) and calls for a philosophical argument to bring clarity to exactly what we mean by 'reproduction.'

A mathematical model describes the malignant transformation of low grade gliomas: Prognostic implications.

Gliomas are the most frequent type of primary brain tumours. Low grade gliomas (LGGs, WHO grade II gliomas) may grow very slowly for the long periods of time, however they inevitably cause death due to the phenomenon known as the malignant transformation. This refers to the transition of LGGs to more aggressive forms of high grade gliomas (HGGs, WHO grade III and IV gliomas).

Preface.

This volume was inspired by the topics presented at the international conference "Micro and Macro Systems in Life Sciences" which was held on Jun 8-12, 2015 in Będlewo, Poland. System biology is an approach which tries to understand how micro systems, at the molecular and cellular levels, affect macro systems such as organs, tissue and populations. Thus it is not surprising that a major theme of this volume evolves around cancer and its treatment.

Deterministic and Stochastic Study for a Microscopic Angiogenesis Model: Applications to the Lewis Lung Carcinoma.

Angiogenesis modelling is an important tool to understand the underlying mechanisms yielding tumour growth. Nevertheless, there is usually a gap between models and experimental data. We propose a model based on the intrinsic microscopic reactions defining the angiogenesis process to link experimental data with previous macroscopic models.

A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge.

Transferring morality to human-nonhuman chimeras.

Human-nonhuman chimeras have been the focus of ethical controversies for more than a decade, yet some related issues remain unaddressed. For example, little has been said about the relationship between the origin of transferred cells and the morally relevant capacities to which they may give rise. Consider, for example, a developing mouse fetus that receives a brain stem cell transplant from a human and another that receives a brain stem cell transplant from a dolphin.

A simple model of carcinogenic mutations with time delay and diffusion.

In the paper we consider a system of delay differential equations (DDEs) of Lotka-Volterra type with diffusion reflecting mutations from normal to malignant cells. The model essentially follows the idea of Ahangar and Lin (2003) where mutations in three different environmental conditions, namely favorable, competitive and unfavorable, were considered. We focus on the unfavorable conditions that can result from a given treatment, e.

Gompertz model with delays and treatment: mathematical analysis.

In this paper we study the delayed Gompertz model, as a typical model of tumor growth, with a term describing external interference that can reflect a treatment, e.g. chemotherapy.

Model of tumour angiogenesis -- analysis of stability with respect to delays.

In the paper we consider the model of tumour angiogenesis process proposed by Bodnar and Fory (2009). The model combines ideas of Hahnfeldt et al. (1999) and Agur et al.

A numerical model of EMT6/Ro spheroid dynamics under irradiation: calibration and estimation of the underlying irradiation-induced cell survival probability.

We present extensions to our quasi-2D cellular automata spheroid model that add a cellular kinetics module together with an irradiation and repair module. Significantly, our approach is not based on the Linear Quadratic (LQ) model, instead, we propose a simple two-parameter, algorithmic model which captures the essential biological features of irradiation-induced cell death, repair and associated cell cycle delays. This approach allows us to estimate directly the underlying irradiation-induced cell survival probability.