Exploring Stakeholder Value Models via Interactive Visualization

AbstractIn the design of complex systems, models can be used to predict a future system's performance as well as approximate stakeholder preferences on performance. This paper examines the problem of model truthfulness and the challenge of trusting models, with a focus on value models and how they are used to predict stakeholder preferences. A framework is proposed for the analysis of these issues (truthfulness and trust), which is used to discuss the relationship between models and decision outcomes. Interactive visualization is proposed as an efficient and effective method for increasing model truthfulness and model trust, and hence making better decisions. An interactive visualization tool is also presented, and an application of the tool to a complex decision case is discussed

Delineation of the healthy rabbit heart by immunohistochemistry - A technical note

Heart failure poses a big health problem and may result from obesity, smoking, alcohol and/or growing age. Studying pathological heart tissue demands accurate histological and immunohistochemical stainings in animal models, including chromogenic and fluorescent approaches. Moreover, a reliable set of healthy heart stainings and labeling are required, in order to provide a reference for the pathological situation. Heart and brain tissue of a healthy rabbit were collected, and different histological key steps were compared, such as paraffin embedding after formalin fixation versus cryopreservation; an antigen retrieval (AR) step in processing paraffin sections versus the same procedure without AR; or a chromogenic with a fluorescent detection system, respectively. Using serial sections, we stained the same morphological structure with classic approaches (HE, Masson Goldner Trichrome (GT) and Elastica van Gieson (EL)) and with different markers, including collagen I, collagen III, fibronectin, α-SMA, protease-activated receptor-2 (PAR-2) which is an inflammation-related marker, and ki67 for proliferating cells. Differences between conditions were quantitatively assessed by measuring the color intensity. Generally, cryosections exhibited a more prominent signal intensity in immunohistochemically labeled sections than in paraffin sections, but the strong staining was slurry, which sometimes impeded proper identification of morphological structures, particularly at higher magnifications. In addition, the advantage of an AR step was observed when compared to the condition without AR, where signal intensities were significantly lower. Different stainings of the heart arteries and the myocardium revealed a clear distribution of extracellular matrix components, with prominent collagen III in the artery wall, but an absence of collagen III in the myocardium. Moreover, paraffin-embedded sections provided more distinct structures compared to cryosections after collagen III, ki67, fibronectin, and α-SMA labeling. As for the Purkinje cells that were depicted in the heart and the cerebellum (Purkinje neurons), we found GT staining most suitable to depict them in the heart, while HE as well as EL staining was ideal to depict Purkinje neurons in the cerebellum. In sum, we provide useful reference images with different stainings for researchers using the rabbit heart or brain model. Such images can help to decide which of the immunohistochemical protocols are valuable to reach a specific aim. Recommendations are given for the best visualization of the target structures and specific (immunohistochemical) staining

Patterns of cross-sectional and predictive physical activity in Swiss adults aged 52+: results from the SAPALDIA cohort

Non-communicable diseases (NCDs) account for the vast majority of deaths in Switzerland. Insufficient physical activity (PA) is an established NCD risk factor and PA is known to be beneficial for physical and mental wellbeing. Sedentary behaviour (SB) is an additional, independent risk factor and associated with frailty in older adults. This study aimed at describing cross-sectional PA patterns in a general population sample of subjects aged 52 years and older (52+) from eight areas across different language regions of Switzerland. Additionally, the predictive association of self-reported PA for objectively measured PA was tested.; Participants 52+ of the Swiss Cohort Study on Air Pollution And Lung and Heart Disease In Adults (SAPALDIA) who completed accelerometer data collection at the most recent follow-up (SAPALDIA4 in 2017/18) and provided information on determinants of interest (sex, age, body mass index [BMI], language region, education, employment status, civil status, smoking) were included in the analysis (n = 1314). The accelerometer-derived average time spent in different PA intensities (SB, light PA [LPA], moderate-to-vigorous PA [MVPA]) was estimated according to participant characteristics with control for season and wear time using multiple linear regressions. In further analyses, the predictive effect of changes in self-reported PA over roughly ten years between SAPALDIA2 (2001/02) and SAPALDIA3 (2010/11) (remaining inactive [RI]; becoming inactive [BI]; becoming active [BA]; remaining active [RA]) on the objectively measured SB, LPA and MVPA obtained seven years later by accelerometry (SAPALDIA4), was assessed using multiple linear regression models.; Overall, 21.7% of 52+ participants met the Swiss recommendations for subjectively assessed PA. Obese participants, 75+ year-olds, smokers and subjects living alone spent more time in SB and less time in LPA and MVPA compared with participants with a BMI below 25 kg/m2, between 52 and 64 years old, not smoking and being married, respectively. Residents living in the French-speaking part of Switzerland were less likely to engage in MVPA compared with residents from the German-speaking part and thus were less likely to meet the PA recommendations. A trend for increasing PA and decreasing SB was observed consistently across the four groups (RI, BI, BA, RA) of predictive self-reported PA patterns with participants remaining active over the course of roughly ten years showing highest levels of PA and lowest levels of SB measured objectively at SAPALDIA4.; The high proportion of SB points to the need of physical activity promotion for the older part of the population in Switzerland. According to our data, behavioural changes in PA are possible and sustainable as we can see in the group of participants becoming active and this is essential for health promotion recommendations

Molecular mechanism of enzymatic chlorite detoxification: insights from structural and kinetic studies

The heme enzyme chlorite dismutase (Cld) degrades chlorite to chloride and dioxygen. Although the structure and steady-state kinetics of pentameric Clds have been elucidated, many questions remain, such as the mechanism of chlorite cleavage and the pH dependence of the reaction. Here, we present high resolution X-ray crystal structures of a dimeric Cld at pH 6.5 and 8.5, its fluoride and isothiocyanate complexes and the neutron structure at pH 9.0 together with the pH dependence of the Fe(III)/Fe(II) couple and the UV-vis and resonance Raman spectral features. We demonstrate that the distal Arg127 cannot act as proton acceptor and is fully ionized even at pH 9.0 ruling out its proposed role in dictating the pH dependence of chlorite degradation. Stopped-flow studies show that (i) Compound I and hypochlorite cannot recombine and (ii) Compound II is the immediately formed redox intermediate that dominates during reaction. Homolytic cleavage of chlorite is propose

First report in italy of the exotic mosquito species Aedes (Finlaya) koreicus, a potential vector of arboviruses and filariae

BACKGROUND: In the Veneto region (north-eastern Italy) an entomological surveillance system has been implemented since the introduction of the Asian tiger mosquito (Aedes albopictus) in 1991. During the routine monitoring activity in a tiger mosquito-free area, an unexpected mosquito was noticed, which clearly did not belong to the recorded Italian fauna. FINDINGS: At the end of May 2011, twelve larvae and pupae were collected in a small village in Belluno province (Veneto region) from a single manhole. Ten adults reared in the laboratory were morphologically and genetically identified as Aedes (Finlaya) koreicus (Edwards, 1917), a species native to Southeast Asia. The subsequent investigations carried out in the following months in the same village provided evidence that this species had become established locally. Entomological and epidemiological investigations are currently ongoing in the surrounding area, to verify the eventual extension of the species outside the village and to trace back the route of entry into Italy. CONCLUSIONS: This is the first report in Italy of the introduction of the exotic mosquito Ae. koreicus. This species has been shown experimentally to be competent in the transmission of the Japanese encephalitis virus and of the dog heartworm Dirofilaria immitis and is considered a potential vector of other arboviruses. Thus, the establishment of this species may increase the current risk or pose new potential threats, for human and animal health. This finding considerably complicates the entomological monitoring of the Asian tiger mosquito Ae. albopictus in Italy and stresses the importance of implementing the entomological surveillance for the early detection of and the rapid response against invasive mosquito species

From chlorite dismutase towards HemQ -the role of the proximal H-bonding network in haeme binding

Synopsis Chlorite dismutase (Cld) and HemQ are structurally and phylogenetically closely related haeme enzymes differing fundamentally in their enzymatic properties. Clds are able to convert chlorite into chloride and dioxygen, whereas HemQ is proposed to be involved in the haeme b synthesis of Gram-positive bacteria. A striking difference between these protein families concerns the proximal haeme cavity architecture. The pronounced H-bonding network in Cld, which includes the proximal ligand histidine and fully conserved glutamate and lysine residues, is missing in HemQ. In order to understand the functional consequences of this clearly evident difference, specific hydrogen bonds in Cld from 'Candidatus Nitrospira defluvii' (NdCld) were disrupted by mutagenesis. The resulting variants (E210A and K141E) were analysed by a broad set of spectroscopic (UV-vis, EPR and resonance Raman), calorimetric and kinetic methods. It is demonstrated that the haeme cavity architecture in these protein families is very susceptible to modification at the proximal site. The observed consequences of such structural variations include a significant decrease in thermal stability and also affinity between haeme b and the protein, a partial collapse of the distal cavity accompanied by an increased percentage of low-spin state for the E210A variant, lowered enzymatic activity concomitant with higher susceptibility to self-inactivation. The high-spin (HS) ligand fluoride is shown to exhibit a stabilizing effect and partially restore wild-type Cld structure and function. The data are discussed with respect to known structure-function relationships of Clds and the proposed function of HemQ as a coprohaeme decarboxylase in the last step of haeme biosynthesis in Firmicutes and Actinobacteria

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants