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Aims: Heart failure (HF) has become an epidemic and constitutes a major medical, social, and economic problem worldwide. Despite advances in medical treatment, HF prognosis remains poor. The development of efficient therapies is hampered by the lack of appropriate animal models in which HF can be reliably determined, particularly in mice. The development of HF in mice is often assumed based on the presence of cardiac dysfunction, but HF itself is seldom proved. Lung ultrasound (LUS) has become a helpful tool for lung congestion assessment in patients at all stages of HF. We aimed to apply this non-invasive imaging tool to evaluate HF in mouse models of both systolic and diastolic dysfunction. Methods and results: We used LUS to study HF in a mouse model of systolic dysfunction, dilated cardiomyopathy, and in a mouse model of diastolic dysfunction, diabetic cardiomyopathy. LUS proved to be a reliable and reproducible tool to detect pulmonary congestion in mice. The combination of LUS and echocardiography allowed discriminating those mice that develop HF from those that do not, even in the presence of evident cardiac dysfunction. The study showed that LUS can be used to identify the onset of HF decompensation and to evaluate the efficacy of therapies for this syndrome. Conclusions: This novel approach in mouse models of cardiac disease enables for the first time to adequately diagnose HF non-invasively in mice with preserved or reduced ejection fraction, and will pave the way to a better understanding of HF and to the development of new therapeutic approaches. ; This study was supported by grants from the Spanish Ministerio de Economia y Competitividad (SAF2015-65722-R), Comunidad Autonoma de Madrid (2010-BMD2321, FIBROTEAM Consortium), European Union's FP7 (CardioNeT-ITN-289600, CardioNext-ITN-608027) and the Spanish Instituto de Salud Carlos III (CPII14/00027 to E.L-P, RD12/0042/0054 to B.I. and RD12/0042/066 to P.G.-P. and E.L-P). This work was also supported by the Plan Estatal de I+D+I 2013-2016 - European Regional Development Fund (FEDER) "A way of making Europe", Spain. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MINECO) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). ; Sí

An increasing percentage of people have or are at risk to develop non-alcoholic fatty liver disease (NAFLD) worldwide. NAFLD comprises different stadia going from isolated steatosis to non-alcoholic steatohepatitis (NASH). NASH is a chronic state of liver inflammation that leads to the transformation of hepatic stellate cells to myofibroblasts. These cells produce extra-cellular matrix that results in liver fibrosis. In a normal situation, fibrogenesis is a wound healing process that preserves tissue integrity. However, sustained and progressive fibrosis can become pathogenic. This process takes many years and is often asymptomatic. Therefore, patients usually present themselves with end-stage liver disease e.g., liver cirrhosis, decompensated liver disease or even hepatocellular carcinoma. Fibrosis has also been identified as the most important predictor of prognosis in patients with NAFLD. Currently, only a minority of patients with liver fibrosis are identified to be at risk and hence referred for treatment. This is not only because the disease is largely asymptomatic, but also due to the fact that currently liver biopsy is still the golden standard for accurate detection of liver fibrosis. However, performing a liver biopsy harbors some risks and requires resources and expertise, hence is not applicable in every clinical setting and is unsuitable for screening. Consequently, different non-invasive diagnostic tools, mainly based on analysis of blood or other specimens or based on imaging have been developed or are in development. In this review, we will first give an overview of the pathogenic mechanisms of the evolution from isolated steatosis to fibrosis. This serves as the basis for the subsequent discussion of the current and future diagnostic biomarkers and anti-fibrotic drugs. ; The Ph.D. authors of this paper are part of the Limburg Clinical Research Center (LCRC), supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish government, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. ; Francque, S (corresponding author), Antwerp Univ Hosp, Dept Gastroenterol & Hepatol, Antwerp, Belgium ; Univ Antwerp, Fac Med & Hlth Sci, Lab Expt Med & Paediat, Antwerp, Belgium. sven.francque@uza.be

Article ; Cet article analyse une distinction faite fréquemment dans les situations de communication en neurosciences : l'emploi des termes "invasif" ou "non-invasif" pour qualifier les techniques d'observation du cerveau. Un jugement de valeur implicite ou explicite accompagnant ces termes, l'adjectif de "non-invasif" a pu être utilisé à des fins de promotion du progrès technique, en particulier à propos des nouvelles techniques d'imagerie apparues ces dernières décennies. Nous étudions ici les interactions entre experts scientifiques et la sphère politique. L'analyse porte sur plusieurs rapports d'expertise concernant les neurosciences, issus de différents comités en France. Nous montrons que la signification des termes "invasif" et "non-invasif" varie selon le contexte, c'est-à-dire en fonction de la nature du discours, des techniques en comparaison ou des parties engagées dans la discussion. La définition de ce qui est à concevoir comme invasif ou non-invasif devient un enjeu stratégique et peut ainsi changer selon les méthodes privilégiées par les experts participants à ces comités ou conseils. ; This paper analyzes a common distinction in neuroscience communication: the labels "invasive" and "non-invasive" attributed to brain-observation technologies. Because an implicit or explicit value judgment accompanies the term "non-invasive," it has been used to promote technological progress, especially new brain-imaging techniques that have appeared in recent decades. This study's material comes from interactions between some expert scientists and the political sphere. Expert reports on neuroscience from different advisory bodies in the French public sector have been collected and analyzed for use of the distinction between invasive and non-invasive. The paper shows that the meaning of these widely used labels varies according to the context, e.g., status of discourse, technologies compared, or stakeholders engaged in the discussion. The definition of what is understood as invasive or non-invasive becomes a strategic issue and can thus vary according to the methodologies favoured by experts participating in national advisory boards or councils.

Although estimates vary, there is a broad agreement that invasive species impose major costs on the U.S. economy, as well as posing risks to nonmarket environmental goods and services and to public health. The domestic effort to manage risks associated with invasive species is coordinated by the National Invasive Species Council (NISC), which is charged with developing a science‐based process to evaluate risks associated with the introduction and spread of invasive species. Various international agreements have also elevated invasive species issues onto the international policy agenda. The World Trade Organization (WTO) Sanitary and Phytosanitary (SPS) Agreement establishes rights and obligations to adhere to the discipline of scientific risk assessment to ensure that SPS measures are applied only to the extent required to protect human, animal, and plant health, and do not constitute arbitrary or unjustifiable technical barriers to trade. Currently, however, the field of risk assessment for invasive species is in its infancy. Therefore, there is a pressing need to formulate scientifically sound methods and approaches in this emerging field, while acknowledging that the demand for situation‐specific empirical evidence is likely to persistently outstrip supply. To begin addressing this need, the Society for Risk Analysis Ecological Risk Assessment Specialty Group and the Ecological Society of America Theoretical Ecology Section convened a joint workshop to provide independent scientific input into the formulation of methods and processes for risk assessment of invasive species to ensure that the analytic processes used domestically and internationally will be firmly rooted in sound scientific principles.

Increased global trade and travel have led to a rise in the number of invasive alien species (IAS), i.e. species introduced by humans in geographic areas where are not naturally found, worldwide. Despite the recognized role of wildlife, as well as of wildlife translocations, in the emergence and re-emergence of infections of public health significance, IAS remain mainly studied for their environmental impacts, and their disease risk towards humans and animals is still largely neglected by health professionals. The main aim of this thesis is therefore to cover this gap by setting the ground for a new "invasion epidemiology" field, and this has been done through two main steps: the review and analysis of both the mechanisms underlying IAS disease risk and the information available in literature on IAS pathogens, and the development of a standardized qualitative disease risk assessment method, applicable to different geographic contexts, to assess the risk of mammal IAS to impact on human and animal health. First, I reviewed the existing biological and ecological literature on IAS to identify the main mechanisms by which animal IAS may affect disease risk in their area of release. IAS resulted to potentially affect disease risk both directly, by acting as hosts of infectious agents, thus possibly leading to the introduction of new pathogens, and/or the amplification of endemic ones, or indirectly, by altering the ecosystem equilibrium, through competitive and trophic interactions with native host species or the modification of local habitats. This literature review highlighted how IAS may have important health implications, which should be better acknowledged by people working in the human and animal health field, and how the mechanisms underlying the sanitary outcome of a biological invasion, and in particular indirect ones, are extremely complex, being the product of multiple factors. Acknowledging the important limitations of our current ability to predict possible health impacts driven by indirect mechanisms, I decided to address the issue of IAS disease risk by focusing specifically on IAS possible role as infectious agents' host. As information on IAS pathogens is not systematized, preventing from knowing the amount and quality of available data to inform possible disease risk assessment procedures, I systematically reviewed the literature on the infectious agents of the main mammal species of European Union concern. Current knowledge on the pathogens harbored by mammal IAS was evaluated through different statistical approaches: the identification of the main factors associated with research intensity and the observed pathogen species richness, the estimation of the true helminth species richness, and a meta-analysis of prevalence of the pathogens of public and animal health significance. Results highlighted the existence of strong information gaps and biases in the way research on mammal IAS pathogens is carried out, the current underestimation of the amount of pathogens harbored by these species and high levels of uncertainty in the pooled prevalence of pathogens of public and animal health significance. However, the review confirmed that mammal IAS harbor pathogens of human and animal health significance, and therefore, the need to identify high-risk species. Considering that the existing knowledge gaps would have resulted in strong limitations in informing a risk assessment procedure, I developed a qualitative disease risk assessment methodology informed by expert opinion. This tool is specifically aimed at assessing IAS disease risk towards humans, domestic animal populations, and/or wildlife populations and allows to obtain a list of the pathogens of animal and human health significance that mammal IAS could transmit to a population of interest (directly or through the communities of local hosts), each with the related level of risk and uncertainty. Key features of the tool are its flexibility, being applicable to different contexts and for different purposes, and the high resolution of the mechanisms under assessment, which make possible for risk managers identifying the most critical pathogens and mechanisms involved in disease risk, allowing them to direct targeted actions and surveillance plans. Finally, the need to combine multiple likelihood estimates deriving from several pathways in an overall risk estimate led me to tackle a methodological aspect of qualitative risk assessment procedures, and I proposed a standardized method applicable in such cases, to reduce the subjectivity that relies in the different ways multiple estimates are currently combined.

During operational activities, military personnel face extremely demanding circumstances, which when combined lead to severe fatigue, influencing both their well-being and performance. Physical exertion is the main condition leading to fatigue, and its continuous tracking would help prevent its effects. This review aimed to investigate the up-to-date progress on non-invasive physiological monitoring to evaluate situations of physical exertion as a pre-condition to fatigue in military populations, and determine the potential associations between physiological responses and fatigue, which can later result in decision-making indicators to prevent health-related consequences. Adhering to the PRISMA Statement, four databases (Scopus, Science Direct, Web of Science and PubMed) were used for a literature search based on combinations of keywords. The eligibility criteria focused on studies monitoring physiological variables through non-invasive objective measurements, with these measurements being developed in military field, combat, or training conditions. The review process led to the inclusion of 20 studies. The findings established the importance of multivariable assessments in a real-life context to accurately characterise the effects of military practices. A tendency for examining heart rate variables, thermal responses, and actigraphy measurements was also identified. The objectives and experimental protocols were diverse, but the effectiveness of non-invasive measurements in identifying the most fatigue-inducing periods was demonstrated. Nevertheless, no assessment system for standardised application was presented. Future work may include the development of assessment methods to translate physiological recordings into actionable information in real-time and mitigate the effects of fatigue on soldiers' performance accurately.

With climate change and increasing globalisation of trade and travel, the risks presented by invasive pests and pathogens to natural environments, agriculture and economies have never been greater, and are only increasing with time. Governments world-wide are responding to these increased threats by strengthening quarantine and biosecurity. This book presents a comprehensive review of risk-based techniques that help policy makers and regulators protect national interests from invasive pests and pathogens before, at, and inside national borders. Selected from the research corpus of the Centre of Excellence for Biosecurity Risk Analysis at the University of Melbourne, this book provides solutions that reflect scientific rigour coupled with practical, hands-on applications. Focusing on surveillance, stochastic modelling, intelligence gathering, decision making and risk communication, the contents combine the strengths of risk analysts, mathematicians, economists, biologists and statisticians. The book presents tested scientific solutions to the greatest challenges faced by quarantine and biosecurity policy makers and regulators today

Background Invasive non-typhoidal Salmonella (iNTS) disease is a well-described cause of mortality in children and human immunodeficiency virus (HIV)-infected adults in sub-Saharan Africa. Additionally, there is an ill-defined burden of iNTS disease in Southeast Asia. Methods Aiming to investigate the causative serovars of non-invasive and iNTS disease and their associated antimicrobial susceptibility profiles in the Lao People's Democratic Republic, we performed multilocus sequence typing and antimicrobial susceptibility profiling on 168 NTS (63 blood and 105 faecal) organisms isolated in Lao between 2000 and 2012. Results Six different serovars were isolated from blood; Salmonella enterica serovar Enteritidis (n=28), S. enterica serovar Typhimurium (n=19) and S. entericaserovar Choleraesuis (n=11) accounted for >90% (58/63) of the iNTS disease cases. In contrast, the isolates from diarrhoeal faeces were comprised of 18 different serovars, the mostly commonly identified being S. entericaTyphimurium (n=28), S. enterica Weltevreden (n=14) and S. enterica Stanley (n=15). S. enterica Enteritidis and S. enterica Choleraesuis were significantly more associated with systemic disease than diarrhoeal disease in this patient group (p<0.001). Conclusions We find a differing distribution of Salmonella sequence types/serovars between those causing iNTS disease and non-invasive disease in Lao. We conclude that there is a small but not insignificant burden of iNTS disease in Lao. Further clinical and epidemiological investigations are required to assess mortality and the role of comorbidities such as HIV.

Background: Invasive non-typhoidal Salmonella (iNTS) disease is a well-described cause of mortality in children and human immunodeficiency virus (HIV)-infected adults in sub-Saharan Africa. Additionally, there is an ill-defined burden of iNTS disease in Southeast Asia. Methods: Aiming to investigate the causative serovars of non-invasive and iNTS disease and their associated antimicrobial susceptibility profiles in the Lao People's Democratic Republic, we performed multilocus sequence typing and antimicrobial susceptibility profiling on 168 NTS (63 blood and 105 faecal) organisms isolated in Lao between 2000 and 2012. Results: Six different serovars were isolated from blood; Salmonella enterica serovar Enteritidis (n=28), S. enterica serovar Typhimurium (n=19) and S. enterica serovar Choleraesuis (n=11) accounted for >90% (58/63) of the iNTS disease cases. In contrast, the isolates from diarrhoeal faeces were comprised of 18 different serovars, the mostly commonly identified being S. enterica Typhimurium (n=28), S. enterica Weltevreden (n=14) and S. enterica Stanley (n=15). S. enterica Enteritidis and S. enterica Choleraesuis were significantly more associated with systemic disease than diarrhoeal disease in this patient group (p<0.001). Conclusions: We find a differing distribution of Salmonella sequence types/serovars between those causing iNTS disease and non-invasive disease in Lao. We conclude that there is a small but not insignificant burden of iNTS disease in Lao. Further clinical and epidemiological investigations are required to assess mortality and the role of comorbidities such as HIV.

Background: Invasive non-typhoidal Salmonella (iNTS) disease is a well-described cause of mortality in children and human immunodeficiency virus (HIV)-infected adults in sub-Saharan Africa. Additionally, there is an ill-defined burden of iNTS disease in Southeast Asia. Methods: Aiming to investigate the causative serovars of non-invasive and iNTS disease and their associated antimicrobial susceptibility profiles in the Lao People's Democratic Republic, we performed multilocus sequence typing and antimicrobial susceptibility profiling on 168 NTS (63 blood and 105 faecal) organisms isolated in Lao between 2000 and 2012. Results: Six different serovars were isolated from blood; Salmonella enterica serovar Enteritidis (n=28), S. enterica serovar Typhimurium (n=19) and S. enterica serovar Choleraesuis (n=11) accounted for >90% (58/63) of the iNTS disease cases. In contrast, the isolates from diarrhoeal faeces were comprised of 18 different serovars, the mostly commonly identified being S. enterica Typhimurium (n=28), S. enterica Weltevreden (n=14) and S. enterica Stanley (n=15). S. enterica Enteritidis and S. enterica Choleraesuis were significantly more associated with systemic disease than diarrhoeal disease in this patient group (p<0.001). Conclusions: We find a differing distribution of Salmonella sequence types/serovars between those causing iNTS disease and non-invasive disease in Lao. We conclude that there is a small but not insignificant burden of iNTS disease in Lao. Further clinical and epidemiological investigations are required to assess mortality and the role of comorbidities such as HIV.