Severity of injuries in different modes of transport, expressed with disability-adjusted life years (DALYS)

Background: Health impact assessment (HIA) studies are increasingly predicting the health effects of mode shifts in traffic. The challenge for such studies is to combine the health effects, caused by injuries, with the disease driven health effects, and to express the change in the health with a common health indicator. Disability-adjusted life year (DALY) combines years lived disabled or injured (YLD) and years of life lost (YLL) providing practical indicator to combine injuries with diseases. In this study, we estimate the average YLDs for one person injured in a transport crash to allow easy to use methods to predict health effects of transport injuries. Methods: We calculated YLDs and YLLs for transport fatalities and injuries based on the data from the Swedish Traffic Accident Data Acquisition (STRADA). In STRADA, all the fatalities and most of the injuries in Sweden for 2007–2011 were recorded. The type of injury was recorded with the Abbreviated Injury Scale (AIS) codes. In this study these AIS codes were aggregated to injury types, and YLDs were calculated for each victim by multiplying the type of injury with the disability weight and the average duration of that injury. YLLs were calculated by multiplying the age of the victim with life expectancy of that age and gender. YLDs and YLLs were estimated separately for different gender, mode of transport and location of the crash. Results: The average YLDs for injured person was 14.7 for lifelong injuries and 0.012 for temporal injuries. The average YLDs per injured person for lifelong injuries for pedestrians, cyclists and car occupants were 9.4, 12.8 and 18.4, YLDs, respectively. Lifelong injuries sustained in rural areas were on average 31% more serious than injuries in urban areas. Conclusions: The results show that shifting modes of transport will not only change the likelihood of injuries but also the severity of injuries sustained, if injured. The results of this study can be used to predict DALY changes in HIA studies that take into account mode shifts between different transport modes, and in other studies predicting the health effects of traffic injuries

Czynniki wpływające na skuteczne wdrożenie nowego produktu w przemyśle meblarskim

Centralization company activities around: new products, new processes and new materials application it is still the priority issue for most manufacturers. Therefore, this article focuses on the factors that affect the implementation of a new product with greater efficiency, such as: the analysis of market requirements, product planning and the role of senior management. However, the literature of the product management, little attention is paid to the recognition of the so-called new product success factors in specific industries. Polish furniture industry over the last 60 years established itself as one of the leaders of the global trade in furniture and has become an important branch of the national economy. For this reason, the problem of determining the factors that influence the success of a new product in the furniture industry was taken up. Research were carried out in three large furniture manufacturers (employing more than 250 people). The conducted studies revealed that there is a big area to make improvements in the development of a new furniture collection. It was indicated that only about 60% of the considered success factors are used in the chosen companiesScentralizowanie działań firmy wokół: nowych produktów, nowych procesów i zastosowania nowych materiałów to wciąż dla większości producentów kwestie priorytetowe. Dlatego w niniejszym artykule skupiono się na czynnikach, które wpływają na wdrożenie nowego produktu z większą skutecznością, jak np. analiza wymagań rynkowych, planowanie produktu i rola kierownictwa wyższego szczebla. Jednak w literaturze poświęconej zarządzaniu produktem niewiele uwagi skupiono na rozpoznaniu, tzw. czynników sukcesu nowego produktu w konkretnych branżach. Polski przemysł meblarski na przestrzeni ostatnich 60 lat wypracował sobie pozycję jednego z liderów światowego handlu meblami oraz stał się ważną gałęzią gospodarki narodowej. Z tego powodu podjęto problem określenia czynników mających wpływ na powodzenie nowego produktu w przemyśle meblarskim. Z badań przeprowadzonych u trzech dużych producentów mebli (tj. zatrudniających powyżej 250 osób) wynika, że istnieje znaczny obszar do wprowadzania usprawnień w procesie rozwoju nowej kolekcji mebli. Stwierdzono bowiem występowanie jedynie ok. 60% z rozpatrywanych czynników sukces

Severity of injuries in different modes of transport, expressed with disability-adjusted life years (DALYs).

BACKGROUND: Health impact assessment (HIA) studies are increasingly predicting the health effects of mode shifts in traffic. The challenge for such studies is to combine the health effects, caused by injuries, with the disease driven health effects, and to express the change in the health with a common health indicator. Disability-adjusted life year (DALY) combines years lived disabled or injured (YLD) and years of life lost (YLL) providing practical indicator to combine injuries with diseases. In this study, we estimate the average YLDs for one person injured in a transport crash to allow easy to use methods to predict health effects of transport injuries. METHODS: We calculated YLDs and YLLs for transport fatalities and injuries based on the data from the Swedish Traffic Accident Data Acquisition (STRADA). In STRADA, all the fatalities and most of the injuries in Sweden for 2007-2011 were recorded. The type of injury was recorded with the Abbreviated Injury Scale (AIS) codes. In this study these AIS codes were aggregated to injury types, and YLDs were calculated for each victim by multiplying the type of injury with the disability weight and the average duration of that injury. YLLs were calculated by multiplying the age of the victim with life expectancy of that age and gender. YLDs and YLLs were estimated separately for different gender, mode of transport and location of the crash. RESULTS: The average YLDs for injured person was 14.7 for lifelong injuries and 0.012 for temporal injuries. The average YLDs per injured person for lifelong injuries for pedestrians, cyclists and car occupants were 9.4, 12.8 and 18.4, YLDs, respectively. Lifelong injuries sustained in rural areas were on average 31% more serious than injuries in urban areas. CONCLUSIONS: The results show that shifting modes of transport will not only change the likelihood of injuries but also the severity of injuries sustained, if injured. The results of this study can be used to predict DALY changes in HIA studies that take into account mode shifts between different transport modes, and in other studies predicting the health effects of traffic injuries.We would like to thank Jan Ifver from the Swedish Transport agency for providing us the STRADA data and Tomasz Szreniawski from the Systems Research Institute, Poland, for helping with the data organizing. The work is part of the European-wide project Transportation Air pollution and Physical ActivitieS: an integrated health risk assessment progamme of climate change and urban policies (TAPAS)(http://www.tapas-program.org/), which has partners in Barcelona, Basel, Copenhagen, Paris, Prague and Warsaw. TAPAS is a four year project (partly) funded by the Coca-Cola Foundation, AGAUR, and CREAL. The funders have no role in the planning of study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. All authors are independent from the funders. The work was undertaken under the auspices of the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence which is funded by the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust. MT’s work has also been funded by the Ministry of Science and Higher Education through the Iuventus Plus project number IP2011 055871.This is the final published version, which is also available from BMC Public Health at http://www.biomedcentral.com/1471-2458/14/765

Renin-Angiotensin-Aldosterone System in Heart Failure: Focus on Nonclassical Angiotensin Pathways as Novel Upstream Targets Regulating Aldosterone

Aldosterone plays an important role in the regulation of blood pressure, body fluid, and electrolyte homeostasis. Overactivation of aldosterone/mineralocorticoid receptor (MR) pathway leads to hypertension, atherosclerosis, vascular damage, heart failure, and chronic kidney disease and is involved in many other diseases associated with endothelial dysfunction, inflammation, fibrosis, and metabolic disorders. Aldosterone is a final product of the renin-angiotensin-aldosterone system (RAAS), and its production is activated by angiotensin II, while angiotensin-(1–7) negatively regulates angiotensin II-mediated aldosterone production and in some experimental models inhibits aldosterone-induced damage in target tissues. In fact, the aldosterone/mineralocorticoid receptor-dependent pathway is regulated upstream by at least two major axes of RAAS: classical axis (ACE/Ang II) and nonclassical axis (ACE2/Ang-(1–7)). The relative balance between these two axes determines aldosterone production and activity. To better understand the regulation of aldosterone activity in physiology and diseases, it is important to analyze the role of aldosterone/mineralocorticoid receptor-dependent pathways in the context of upstream angiotensin pathways as some of the recently described mechanisms of RAAS represent possible novel upstream targets to inhibit aldosterone/mineralocorticoid receptor-dependent responses. In this review, we highlight the complexity of angiotensin pathways focusing on their role in various tissues in heart failure, with particular emphasis on nonclassical pathways including protective ACE2/Ang-(1–7) axis and detrimental Ang-(1–12)/chymase/Ang II axis

Structure/reaction directed analysis for LC-MS based untargeted analysis

The final publication is available at Elsevier via https://doi.org/10.1016/j.aca.2018.10.062. © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/In LC-MS based untargeted analysis, data is collected at the peak or ion level, although the investigated biochemistry processes occur at the compound or reaction level. To this end, the presence of redundancy peaks such as co-eluted peaks, multi-chargers, adducts, neutral loss, isotopologues, and fragments ions often muddle subsequent statistical data analysis. In order to fill this gap, between peaks and compounds/reactions, independent components must first be found at the peak level, then evaluated at the compound or reaction levels. Based on paired mass distances (PMD), the algorithm GlobalStd, based on retention time hierarchical cluster analysis and global analysis of PMDs within clusters, is here proposed to extract independent peaks from raw LC-MS data. Following its application, a structure/reaction directed analysis can then be used to evaluate compounds at the structure or biochemistry reaction level, based on similar PMDs among different retention times clusters. As a proof-of-concept, the developed statistical method was applied to data obtained for in vivo SPME sampling on fish. In total, 277 independent peaks were demonstrated to stand for most of the variances found for the total 1459 ions detected via LC-MS. Following, both known homologous series or biological reactions along with unknown bio-processes, which may involve oxidation/reduction reactions or homologous series, were analyzed via a structure/reaction directed analysis. The findings of this analysis yielded interesting information regarding the data, for instance denoting the possible occurrence of a biosynthesis process involving l-Carnitine and its precursor 4-Trimethylammoniobutanoic acid. Such PMD relationships could also aid in the screening of annotation results. To this end, semi-quantitative analysis based on structure/reaction directed analysis is also here proposed for further investigation of unknown patterns or for removal of contaminants in metabolomics studies. The developed data-driven algorithm has been included in a PMD package with a GUI interactive document, and is freely available online (https://github.com/yufree/pmd).This research was financially supported by the Industrial Research Chair of the National Sciences and Engineering Research Council of Canada (NSERC-IRC)

Functional and biochemical endothelial profiling in vivo in a murine model of endothelial dysfunction : comparison of effects of 1-methylnicotinamide and angiotensin-converting enzyme inhibitor

Although it is known that 1-methylnicotinamide (MNA) displays vasoprotective activity in mice, as yet the effect of MNA on endothelial function has not been demonstrated in vivo. Here, using magnetic resonance imaging (MRI) we profile the effects of MNA on endothelial phenotype in mice with atherosclerosis (ApoE/LDLR(-/-)) in vivo, in comparison to angiotensin (Ang) -converting enzyme (ACE) inhibitor (perindopril), with known vasoprotective activity. On a biochemical level, we analyzed whether MNA- or perindopril-induced improvement in endothelial function results in changes in ACE/Ang II-ACE2/Ang-(1–7) balance, and L-arginine/asymmetric dimethylarginine (ADMA) ratio. Endothelial function and permeability were evaluated in the brachiocephalic artery (BCA) in 4-month-old ApoE/LDLR(-/-) mice that were non-treated or treated for 1 month or 2 months with either MNA (100 mg/kg/day) or perindopril (10 mg/kg/day). The 3D IntraGate(®)FLASH sequence was used for evaluation of BCA volume changes following acetylcholine (Ach) administration, and for relaxation time (T(1)) mapping around BCA to assess endothelial permeability using an intravascular contrast agent. Activity of ACE/Ang II and ACE2/Ang-(1–7) pathways as well as metabolites of L-arginine/ADMA pathway were measured using liquid chromatography/mass spectrometry-based methods. In non-treated 6-month-old ApoE/LDLR(-/-) mice, Ach induced a vasoconstriction in BCA that amounted to –7.2%. 2-month treatment with either MNA or perindopril resulted in the reversal of impaired Ach-induced response to vasodilatation (4.5 and 5.5%, respectively) and a decrease in endothelial permeability (by about 60% for MNA-, as well as perindopril-treated mice). Improvement of endothelial function by MNA and perindopril was in both cases associated with the activation of ACE2/Ang-(1–7) and the inhibition of ACE/Ang II axes as evidenced by an approximately twofold increase in Ang-(1–9) and Ang-(1–7) and a proportional decrease in Ang II and its active metabolites. Finally, MNA and perindopril treatment resulted in an increase in L-arginine/ADMA ratio by 107% (MNA) and 140% (perindopril), as compared to non-treated mice. Functional and biochemical endothelial profiling in ApoE/LDLR(-/-) mice in vivo revealed that 2-month treatment with MNA (100 mg/kg/day) displayed a similar profile of vasoprotective effect as 2-month treatment with perindopril (10 mg/kg/day): i.e., the improvement in endothelial function that was associated with the beneficial changes in ACE/Ang II-ACE2/Ang (1–7) balance and in L-arginine/ADMA ratio in plasma

Multi-omic signatures of atherogenic dyslipidaemia : pre-clinical target identification and validation in humans

Dyslipidaemia is a major risk factor for atherosclerosis and cardiovascular diseases. The molecular mechanisms that translate dyslipidaemia into atherogenesis and reliable markers of its progression are yet to be fully elucidated. To address this issue, we conducted a comprehensive metabolomic and proteomic analysis in an experimental model of dyslipidaemia and in patients with familial hypercholesterolemia (FH)

Neuron numbers link innovativeness with both absolute and relative brain size

A longstanding issue in biology is whether the intelligence of animals can be predicted by absolute or relative brain size. However, progress has been hampered by an insufficient understanding of how neuron numbers shape internal brain organization and cognitive performance. On the basis of estimations of neuron numbers for 111 bird species, we show here that the number of neurons in the pallial telencephalon is positively associated with a major expression of intelligence: innovation propensity. The number of pallial neurons, in turn, is greater in brains that are larger in both absolute and relative terms and positively covaries with longer post-hatching development periods. Thus, our analyses show that neuron numbers link cognitive performance to both absolute and relative brain size through developmental adjustments. These findings help unify neuro-anatomical measures at multiple levels, reconciling contradictory views over the biological significance of brain expansion. The results also highlight the value of a life history perspective to advance our understanding of the evolutionary bases of the connections between brain and cognition

Dynamic metabolic changes during prolonged ex situ heart perfusion are associated with myocardial functional decline

Ex situ heart perfusion (ESHP) was developed to preserve and evaluate donated hearts in a perfused beating state. However, myocardial function declines during ESHP, which limits the duration of perfusion and the potential to expand the donor pool. In this research, we combine a novel, minimally-invasive sampling approach with comparative global metabolite profiling to evaluate changes in the metabolomic patterns associated with declines in myocardial function during ESHP. Biocompatible solid-phase microextraction (SPME) microprobes serving as chemical biopsy were used to sample heart tissue and perfusate in a translational porcine ESHP model and a small cohort of clinical cases. In addition, six core-needle biopsies of the left ventricular wall were collected to compare the performance of our SPME sampling method against that of traditional tissue-collection. Our state-of-the-art metabolomics platform allowed us to identify a large number of significantly altered metabolites and lipid species that presented comparable profile of alterations to conventional biopsies. However, significant discrepancies in the pool of identified analytes using two sampling methods (SPME vs. biopsy) were also identified concerning mainly compounds susceptible to dynamic biotransformation and most likely being a result of low-invasive nature of SPME. Overall, our results revealed striking metabolic alterations during prolonged 8h-ESHP associated with uncontrolled inflammation not counterbalanced by resolution, endothelial injury, accelerated mitochondrial oxidative stress, the disruption of mitochondrial bioenergetics, and the accumulation of harmful lipid species. In conclusion, the combination of perfusion parameters and metabolomics can uncover various mechanisms of organ injury and recovery, which can help differentiate between donor hearts that are transplantable from those that should be discarded

Sociality does not drive the evolution of large brains in eusocial African mole-rats

The social brain hypothesis (SBH) posits that the demands imposed on individuals by living in cohesive social groups exert a selection pressure favouring the evolution of large brains and complex cognitive abilities. Using volumetry and the isotropic fractionator to determine the size of and numbers of neurons in specific brain regions, here we test this hypothesis in African mole-rats (Bathyergidae). These subterranean rodents exhibit a broad spectrum of social complexity, ranging from strictly solitary through to eusocial cooperative breeders, but feature similar ecologies and life history traits. We found no positive association between sociality and neuroanatomical correlates of information-processing capacity. Solitary species are larger, tend to have greater absolute brain size and have more neurons in the forebrain than social species. The neocortex ratio and neuronal counts correlate negatively with social group size. These results are clearly inconsistent with the SBH and show that the challenges coupled with sociality in this group of rodents do not require brain enlargement or fundamental reorganization. These findings suggest that group living or pair bonding per se does not select strongly for brain enlargement unless coupled with Machiavellian interactions affecting individual fitness.The Czech Science Foundation (14–2758 S, to P.N.), Grant Agency of Charles University (325515, to K.K.) and the European Social Fund and the state budget of the Czech Republic (CZ.1.07/2.3.00/30.0022, to S.O.).http://www.nature.com/srepam2018Mammal Research InstituteZoology and Entomolog