bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity of discharge projections to potential evapotranspiration estimation in Northern Tunisia
Authors: Dakhlaoui Hamouda , Seibert Jan , Hakala Kirsti
Published: March 2020

Tunisia has a long history of coping with water scarcity, and the quantification of climate change impacts on runoff is important for future water management. A major requirement for such studies is an estimation of potential evapotranspiration (PET), which is challenging as many regions often lack the observational data needed for physically based PET equations. In this study, different PET estimation approaches were used to study the impact of PET estimation on discharge projections for catchments in Northern Tunisia. Discharge was simulated for five catchments using three rainfall-runoff models (RRMs): HBV, GR4 and IHACRES. A general differential split sample test (GDSST) was used for an RRM robustness evaluation based on subperiods with contrasting climatic conditions for the 1970–2000 period. Three cases with varying PET were considered: (1) daily calculated PET, (2) long-term daily mean PET with the same values for calibration and validation periods (calculated over the calibration period) and (3) long-term daily mean PET varying between calibration and validation periods (calculated over the calibration and validation period separately). Over the historical period, the comparison between cases 1 and 3 showed little impact of reduced PET information on the RRM performance and robustness. The comparison of cases 2 and 3 indicated a limited impact of varying PET between calibration and validation on the RRM results. The impact of varying levels of PET information on hydrological projections was also analysed over two future 30-year periods: mid-term period (2040–2070) and long-term period (2070–2100), with two representative concentration pathway scenarios (RCPs 4.5 and 8.5), by comparing cases 1 and 2. The projected discharge with constant PET (case 2) was generally lower than the projected discharge with variable PET (case 1) but the difference in volume change did not exceed 9% for both the time period and the RCP scenario considered. While PET slightly increased under the different climate change scenarios, actual evapotranspiration (AET) was found to decrease. These opposite trends of PET and AET can be attributed to the projected decrease in precipitation. Overall, our results demonstrate that discharge, in semi-arid regions like Northern Tunisia, is not sensitive to PET estimates since AET is mainly controlled by the availability of soil moisture. This finding is useful for performing studies of climate change impact on hydrological cycles in arid regions, as our study shows that simple PET estimation is a valid approach for such studies.
Promises, Rights, and Deontic Control
Authors: Molina Crescente
Published: March 2020

This article argues that the notion of a promissory right captures a central feature of the morality of promising which cannot be explained by the notion of promissory obligation alone: the fact that the promisee acquires a full range of control over the promisor’s obligation. It defends two main claims. First, it argues that promissory rights are distinctively grounded in our interest in controlling others’ deontic world. Second, it proposes a version of the ‘Interest Theory’ of rights (the ‘Deontic Interest Theory’) that incorporates our interest in purely deontic forms of control into the various human interests that constitute the grounds of our rights.
Conceptualizing Corruption in Public Private Partnerships
Authors: Schomaker Rahel M.
Published: March 2020

This article conceptualizes the vulnerability of the different stages of Public-Private Partnership (PPP) models for corruption against the backdrop of contract theory, principal-agent theory and transaction cost economics, and discusses potential control mechanisms. The article’s contribution to the debate on PPPs is twofold: first, an issue widely neglected by the pertinent literature is conceptualized. Second, as these PPPs are used not only in developed countries whose legal order may shield them sufficiently, but also in developing countries, carving out the vulnerable points in PPP arrangements may enable decision makers to install appropriate control mechanisms, if need be on project level.
What Can We Weave? Authority, Reconstructing, and Negotiating Heritages Through Archaeological Open-Air Museums
Authors: Montgomery Ramírez Paul Edward
Published: March 2020

The construction of heritage is an ongoing process, with numerous voices involved in it. Physical remains of the past frequently—though not always—play a significant role as focal points that heritage narratives attach to. As resources, these remains can be used to draw both domestic and foreign tourism, providing economic benefit to states and providing a platform from which heritage narratives may be told. Such narratives can be economically, socially, and politically powerful. They have been previously examined through the authorized heritage discourse, wherein only certain ‘pasts’ are explored, or as heritage brands. In a world of change in society and in tourism, the authority of archaeologist/historian/scholar, governing bodies, tourism agencies, passionate ‘non-specialists’, and multiple publics over heritages is one of contestation. Each is a weaver of heritage. This article examines the creation of archaeological open-air museums (AOAMs) as renewable resources for tourism within a fragmenting market. It explores the authorities and threads of heritage that result in different capacities to actively address visitor perceptions of the ‘past’ and present they are touring. This paper concludes with viewing the use of an AOAM as a location of contestation, as any other heritage property can become, though one more malleable to the changing needs of heritage weavers due to its existence in conflict with understandings of linear time.
Recent Advances in the Noninvasive Prenatal Testing for Chromosomal Abnormalities Using Maternal Plasma DNA
Authors: Lau Tze Kin , Zhu Xiaofan , Kwok Yvonne Ka Yin , Leung Tak Yeung , Choy Kwong Wai
Published: March 2020

No single invention in the past has created such a rapid and massive impact on clinical obstetric practice as the introduction of noninvasive prenatal screening (NIPS) for chromosomal abnormalities using cell-free DNA in maternal plasma. However, the technology of NIPS which has also been called noninvasive prenatal testing (NIPT) is rapidly evolving. Most clinicians may not be able to fully understand this new technology to enable good clinical practice. This review will be focused on issues that have important clinical implications. NIPT/S is only a screening test and all positive cases must be confirmed by invasive diagnostic techniques. Although NIPT/S is being expanded rapidly to cover other chromosomes and large chromosomal structural abnormalities, the detection rate is still uncertain, and the positive predictive value is expected to be lower. Pregnant women who are at risk of chromosomal abnormalities other than common trisomies should be offered a diagnostic test instead of NIPT/S. The use of NIPT/S as a primary Down syndrome screening test should not replace the 11–13 weeks scan.
The slope creep law for a soft rock in an open-pit mine in the Gobi region of Xinjiang, China
Authors: Zhao Hongze , Tian Yu , Guo Qingyong , Li Meijie , Wu Jianwen
Published: March 2020

The lithology of the strata in the Gobi region of the Xinjiang autonomous region of China is mainly composed of mudstone, silty mudstone, and other soft rocks. Because of the low strength of the rock mass and the serious effects of physical weathering in this area, the slope stability in open-pit mines is poor, and creep deformation and instability can readily occur. Taking the Dananhu No. 2 open-pit mine as a typical example, the creep test of a mudstone sample under different stress levels was studied. Then, based on a bottom friction experiment and a FLAC3D numerical simulation, the deformation and failure processes of the slope were analyzed. The stress–displacement curve and the displacement–time curve for the monitoring points were plotted to obtain the relationship between the stress and displacement for the slope of the soft rock. The results showed that the long-term strength of the mudstone was between 8.0 and 8.8 MPa, and that stable creep occurred when the slope was under low stress. The potential failure mode for this type of slope is that the front edge creeps along the weak layer and then a crack is formed at the trailing edge of the slope. When the crack penetrates the weak layer, cutting bedding and bedding sliding occur. The deformation process of the stable creep slope includes an initial deformation stage, an initial creep stage, a constant velocity creep stage and a deceleration creep stage.
The impact of culture on FDI disentangled: separating the “level” and the “distance” effects
Authors: Kapás Judit , Czeglédi Pál
Published: March 2020

The most important concern of this paper centers on the question of whether the difference in inward FDI across countries is a result of the fact that destination countries have different cultures, or the fact that they are more distant culturally from the origin country than others? We argue that answering this question requires disentangling the impact of culture, which consists of separating two effects: the “level” (the former) and the “distance” effect (the latter), which are mixed in the literature, leading in this way to biased conclusions in relation to how cultural distance matters for FDI. In this paper we propose an econometric method to separate the two effects of the culture, in which the key is that cultural distance does not depend on the origin country’s culture. Our empirical results indicate a “strong” level effect in the sense that it is a working effect in the case of all the three cultural values we use, and its size is economically significant, as well. The distance effect, however, is at best as important as the level effect but very probably less so, accordingly, it seems that the literature has “overemphasized” the impact of cultural distance.
Moralische Probleme und ethische Fragen von Lehrenden der Erwachsenen- und Weiterbildung – Ein Modell für die Forschung zur erwachsenenpädagogischen Bereichsethik
Authors: Bernhardsson-Laros Nils
Published: March 2020

Die Kompetenz, ethisch-moralisch zu handeln, wird im Rahmen von Kompetenzkatalogen für Lehrkräfte der Erwachsenen- und Weiterbildung als wichtiges Lernfeld ausgewiesen. Allerdings fehlt bisher Forschung, welche die Perspektive von Lehrenden auf eine Berufsethik für die Erwachsenen- und Weiterbildung genauer beleuchtet. Gegenstand des Beitrags ist eine qualitative Interviewstudie, welche Fragen nach ethisch relevanten Handlungssituationen, konkreten ethischen Fragen, pädagogisch-ethischen Überzeugungen und ethischen Orientierungen von Lehrkräften der Erwachsenen- und Weitbildung nachgeht. Um das Forschungsfeld zu erschließen, wird auf Basis der Studienergebnisse ein vierdimensionales Modell moralischer Probleme entwickelt.
The Embeddedness of Inter-Merchant Relations in France, 1750–1850: A Revolution in the World of Commerce?
Authors: Bartolomei Arnaud , de Oliveira Matthieu , Eloire Fabien , Lemercier Claire , Sougy Nadège
Published: March 2020

The grand narratives of modernization often describe the period between 1750 and 1850 as marking a transition from embedded economic relationships (relying on kinship or community ties) to impersonal market transactions supported by legal arrangements. This article questions these narratives by studying three corpora of tools employed by early modern and modern merchants on a daily basis: initial-contact letters, circulars, and notarized proxy forms. Systematic quantitative and qualitative analysis of these documents reveals few traces of a revolution or even a consistent linear evolution. To the contrary, it challenges the opposition between embedded and completely disembedded relationships. Indeed, there is strong evidence that personal and impersonal supports for economic transactions complemented rather than substituted one another. In addition, other types of embeddedness also played an important role: on the one hand, repeated interactions and relational chains involving intermediaries; on the other, a homophilic sociability among merchants that was partly based on the shared language of commerce.
Latina/o and non-latina/o brain injury and dementia patients’ and caregivers’ health: An actor/partner interdependence model
Authors: Linton Kristen Faye
Published: March 2020

Background:

The interdependence between patient and caregivers’ health, which is when the patients’ and informal caregivers’ emotion, cognition and/or behavior affects that of the other person is well documented among dyads experiencing cancer and heart disease, but scant research has assessed interdependence among those with brain injuries or dementia and Latina/o populations. This study aimed to assess the interdependence of patient and caregiver depression, patient functional independence and caregiver burden among non-Latina/o and Latina/o and patients with brain injuries and dementia and their caregivers.

Methods:

Patients and caregiver dyads (n = 96) were recruited from a trauma hospital. Participants completed measures on patient and caregiver depression, patient functional independence and caregiver burden. Participants provided written informed consent. Patient inclusion criteria included: (1) diagnosis with a brain injury or dementia, (2) minimum age of 12, (3) community dwelling and (4) ability to verbally communicate and complete study measures. Caregivers were only included if they were informal, unpaid, family or a friend. Nonparametric Spearman’s Rho correlations were conducted to test the study hypotheses.

Discussion:

There was consistently a statistically significant positive relationship between caregiver depression and caregiver burden for all groups. For non-Latina/o patient and caregiver dementia dyads, there were associations between patient depression and caregiver depression. For non-Latina/o dementia dyads, functional ability was only associated with patient depression. For Latina/o patient and caregiver brain injury and dementia dyads, the only statistically significant relationship was between caregiver depression and caregiver burden. Health services should embrace family-focused mental health and respite interventions.
Antiseptic efficacy of an innovative perioperative surgical skin preparation: A confirmatory FDA phase 3 analysis
Authors: Edmiston Charles E. , Lavin Philip , Spencer Maureen , Borlaug Gwen , Seabrook Gary R. , Leaper David
Published: March 2020

Background:

An innovative approach to perioperative antiseptic skin preparation is warranted because of potential adverse skin irritation, rare risk of serious allergic reaction, and perceived diminished clinical efficacy of current perioperative antiseptic agents. The results of a confirmatory US Food and Drug Administration (FDA) phase 3 efficacy analysis of a recently approved innovative perioperative surgical skin antiseptic agent are discussed.

Methods:

The microbial skin flora on abdominal and groin sites in healthy volunteers were microbiologically sampled following randomization to either ZuraGard, a 2% chlorhexidine/70% isopropyl alcohol preparation (Chloraprep), or a control vehicle (alcohol-free ZuraGard). Mean log10reduction of colony-forming units (CFU) was assessed at 30 seconds, 10 minutes, and 6 hours.

Results:

For combined groin sites (1,721 paired observations) at all time points, the mean log10CFU reductions were significantly greater in the ZuraGard group than in the Chloraprep group (P< .02). Mean log10CFU reductions across combined abdominal and groin sites at all time points (3,277 paired observations) were significantly greater in the ZuraGard group than in the Chloraprep group (P< .02).

Conclusions:

A confirmatory FDA phase 3 efficacy analysis of skin antisepsis in human volunteers documented that ZuraGard was efficacious in significantly reducing the microbial burden on abdominal and groin test sites, exceeding that of Chloraprep. No significant adverse reactions were observed following the application of ZuraGard.

Trial registration:

ClinicalTrials.govidentifiers: NCT02831998 and NCT02831816.
Transhumance, Climate Change and Conflicts: Reflections on the Legal Implications of Grazing Reserves and Ruga Settlements in Nigeria
Authors: Ele Millicent N
Published: March 2020

In recent times, clash after clash has arisen between herdsmen and farmers in Nigeria. These conflicts were linked to the effects of climate change in northern Nigeria, but have been exacerbated by other factors including ethno-religious sentiments. Herdsmen forced to migrate southwards face intense competition for arable and grazing land with the farmers in Nigeria's middle belt. This invariably leads to conflicts, often resulting in gruesome murder and carnage. Thousands have died, many more have been maimed and millions displaced because of this crisis. As a solution, the Nigerian government proposes to set up grazing reserves and rural grazing area settlements in all states of the federation. The problem with this proposal is how and where to obtain the land. This article reflects on the legal implications of the proposal and argues in favour of grazing reserves and ranching on the basis of a private freehold / leasehold tenure arrangement, not through the compulsory acquisition of land by the government.
Ideas, Interests, and the Transition to a Floating Exchange System
Authors: KI YOUN , JEUNG YONGWOO
Published: March 2020

Milton Friedman’s idea of flexible exchange rates was heresy for Americans until the mid-1960s. However, by the late 1970s the idea became embedded in academic thought, policymaking, and business practices. This article analyzes how floating currencies, once eschewed, became embraced as legitimate in the US through the late 1960s and early 1970s. It demonstrates how business leaders’ economic interests and laissez-faire economists’ framework for causes of and solutions to business hardships contributed to society’s acceptance of currency flexibility. Increasing societal support of flexible currencies strengthened the power of float-advocates within the US government, facilitating the transition of the international monetary system from fixed exchange rates to floating. This study highlights how material interests and policy discourses contributed to America’s new policy orientation. It also addresses the origins of the neoliberal international financial order by documenting how American elites reconstituted the state-market balance in global finance while navigating monetary crises.
Pre-operative neutrophil–lymphocyte ratio predicts low cardiac output in children after cardiac surgery
Authors: Iliopoulos Ilias , Alder Matthew N. , Cooper David S. , Villarreal Enrique G. , Loomba Rohit , Sahay Rashmi D. , Fei Lin , Steele Paul E. , Flores Saul
Published: March 2020

Neutrophil–lymphocyte ratio has been associated with clinical outcomes in several groups of cardiac patients, including patients with coronary artery disease, cardiac failure, and cardiac transplant recipients. We hypothesised that pre- and/or post-operative haematological cell counts are associated with clinical outcomes in children undergoing cardiac surgery for CHD. We performed a post hoc analysis of data collected as part of a prospective observational cohort study (n = 83, data available n = 47) of children evaluated for glucocorticoid receptor levels after cardiac surgery (July 2015–January 2016). The association of neutrophil–lymphocyte ratio with low cardiac output syndrome, time to inotrope free, and vasoactive-inotropic score was examined using proportional odds analysis, cox regression, and linear regression models, respectively. A majority (80%) of patients were infants (median/interquartile range 4.1/0.2–7.6 months) with conotruncal (36%) and left-sided obstructed lesions (28%). Two patients required mechanical circulatory support and three died. Higher pre-operative neutrophil–lymphocyte ratio was associated with higher cumulative odds of severe/moderate versus mild low cardiac output on post-operative day 1 (odds ratio 2.86; 95% confidence interval 1.18–6.93; p = 0.02). Pre-operative neutrophil–lymphocyte ratio was not significantly associated with time to inotrope free or vasoactive-inotrope score. Post-operative neutrophil–lymphocyte ratio was also not associated with outcomes. In children after congenital heart surgery, higher pre-operative neutrophil–lymphocyte ratio was associated with a higher chance of low cardiac output in the early post-operative period. Pre-operative neutrophil–lymphocyte ratio maybe a useful prognostic marker in children undergoing congenital heart surgery.
Nutrition status in adult Chilean population: economic, ethnic and sex inequalities in a post-transitional country
Authors: Mujica-Coopman María F , Navarro-Rosenblatt Deborah , López-Arana Sandra , Corvalán Camila
Published: March 2020

Objective:

To assess the relationship between malnutrition, socioeconomic status (SES) and ethnicity in Chilean adult population.

Design:

Nationally representative survey (ENS) conducted in 2016–2017. Sociodemographic information, weight, height and hemoglobin (Hb) were measured (2003 ENS). Excess weight was defined as BMI ≥25 kg/m2. Undernutrition included underweight (BMI <18·5 kg/m2), short stature (height <1·49 m in women and <1·62 m in men) or anaemia (Hb <12 g/l). Education and household income level were used as indicators of SES; ethnicity was self-reported. We applied linear combinations of estimators to compare the prevalence of excess weight and undernutrition by SES and ethnicity.

Setting:

Chile.

Participants:

In total, 5082 adults ≥20 years (64 % women) and 1739 women ≥20 years for anaemia analyses.

Results:

Overall, >75 % of women and men had excess weight. Low SES women either by income or education had higher excess weight ((82·0 (77·1, 86·1) v. 65·0 (54·8, 74·1)) by income; (85·3 (80·6, 89·0) v. 68·2 (61·6, 74·1) %) by education) and short stature (20–49 years; 31(17·9, 48·2) v. 5·2 (2·2,11·4) by education); obesity was also more frequent among indigenous women (20–49 years; 55·8 (44·4, 66·6) v. 37·2 (32·7, 42·0) %) than non-indigenous women. In men, excess weight did not significantly differ by SES or ethnicity, but short stature concentrated in low SES (20–49 years; 47·6 (24·6, 71·6) v. 4·5 (2·1, 9·5) by education) and indigenous men (21·5 (11·9, 5·5, 11·9) v. 8·2 (5·5, 11·9)) (P < 0·05 for all).

Conclusions:

In Chile, malnutrition is disproportionately concentrated among women of low SES and indigenous origin; these inequalities should be considered when implementing prevention policies.
The Structure of Climate Variability Across Scales
Authors: Franzke Christian L. E. , Barbosa Susana , Blender Richard , Fredriksen Hege‐Beate , Laepple Thomas , Lambert Fabrice , Nilsen Tine , Rypdal Kristoffer , Rypdal Martin , Scotto Manuel G, , Vannitsem Stéphane , Watkins Nicholas W. , Yang Lichao , Yuan Naiming
Published: March 2020

One of the most intriguing facets of the climate system is that it exhibits variability across all temporal and spatial scales; pronounced examples are temperature and precipitation. The structure of this variability, however, is not arbitrary. Over certain spatial and temporal ranges, it can be described by scaling relationships in the form of power laws in probability density distributions and autocorrelation functions. These scaling relationships can be quantified by scaling exponents which measure how the variability changes across scales and how the intensity changes with frequency of occurrence. Scaling determines the relative magnitudes and persistence of natural climate fluctuations. Here, we review various scaling mechanisms and their relevance for the climate system. We show observational evidence of scaling and discuss the application of scaling properties and methods in trend detection, climate sensitivity analyses, and climate prediction.
Large Earthquakes Driven by Fluid Overpressure: The Apennines Normal Faulting System Case
Authors: Chiarabba C. , Buttinelli M. , Cattaneo M. , De Gori P.
Published: March 2020

Fluid overpressure is a primary mechanism behind fault interaction and earthquakes triggering. The Apennines section within the young Alpine mobile belt is a key locus to investigate the interplay between fluids and faults. Here, seismicity develops along the extending mountain belt and the key role of fluids has been invoked in past large earthquake sequences. In this study, we use seismological data to get improved images of the Apennines normal faulting system, trying to catch evidences for the involvement of fluids in the preparatory phase of large earthquakes. We observe that extension preferentially reutilizes inherited fragments of faults which were assembled during the Mio‐Pliocene contraction, with steep segments that floor on a regional‐scale gently east dipping plane. We find evidences for wide volumes of overpressured fluids at the base of the seismogenic layer, which are connected to the activation of the recent large earthquakes. The recognition of fluids compartments with overpressuring and diffusion molding seismicity is a key to understand faulting processes and possibly develop forecasts scenarios.
Feedback Between Reservoir Operation and Floodplain Development: Implications for Reservoir Benefits and Beneficiaries
Authors: Wallington Kevin , Cai Ximing
Published: March 2020

Currently, reservoir operation researchers and decision makers weigh the trade‐off between water conservation and flood control at the event and seasonal scales but have neglected the role of socioeconomic dynamics which unfold over longer time scales. However, ongoing advances in understanding human‐flood interactions provide an exemplary opportunity to diverge from this traditional treatment and instead incorporate feedbacks from downstream floodplain development in reservoir operation decisions. To do so, we modify and couple existing mathematical frameworks for optimal reservoir operation and leveed floodplain dynamics. The new coupled model demonstrates that, where reservoir operation persistently maximizes event‐ to seasonal‐scale benefits (i.e., the status quo), most reservoir‐floodplain systems will coevolve toward states of high preference for flood protection and highly developed floodplains. Further, under the status quo operation strategy, less benefits can be achieved as time goes on, benefits shift from water conservation consumers to floodplain inhabitants, and risk is transferred from floodplain inhabitants to water conservation consumers. We compare the status quo operation strategy to a strategy which stabilizes the floodplain development level and show that allowing excess (i.e., more than is optimal at the seasonal scale) flooding now preserves future water conservation benefits by disincentivizing floodplain development. Finally, we illustrate this coevolution and its ramifications at two U.S. reservoir‐floodplain systems where floodplain development has seemingly undermined hydropower production. The insights from this study fill a knowledge gap for floodplain managers and reservoir operators tasked with achieving economically efficient use of floodplains and reservoir storage.
Silencing of circRACGAP1 sensitizes gastric cancer cells to apatinib via modulating autophagy by targeting miR-3657 and ATG7
Authors: Ma Ling , Wang Zhangding , Xie Mengyan , Quan Yunlin , Zhu Weiyou , Yang Fengming , Zhao Chenhui , Fan Yu , Fang Na , Jiang Huning , Wang Qiang , Wang Shouyu , Zhou Jianwei , Chen Xiaofeng , Shu Yongqian
Published: March 2020

The positive results of the apatinib phase III trial have cast new light on treatment for patients with advanced gastric cancer (GC). However, in terms of safety, apatinib toxicities may lead to a dose modification or treatment interruption. Therefore, proper intervention is urgently needed to help patients benefit from apatinib treatment. In this study, we found that apatinib promoted autophagy activation via upregulation of ATG7 expression and autophagy inhibition enhanced apatinib-induced apoptosis. With microRNA and circular RNA-sequencing analyses of GC xenograft models, we demonstrated that circRACGAP1 functioned as an endogenous sponge for miR-3657 to inhibit its activity and further upregulate ATG7 expression. Silencing of circRACGAP1 inhibited apatinib-induced autophagy, which was rescued by miR-3657. Moreover, knockdown of circRACGAP1 sensitized GC cells to apatinib via autophagy inhibition in vitro and in vivo. These findings provided the first evidence that the circRACGAP1-miR-3657-ATG7 axis mediates a novel regulatory pathway critical for the regulation of apatinib sensitivity in GC. Thus, specific blockage of circRACGAP1 may be a potential therapeutic strategy to reduce the toxicities of apatinib and enhance its therapeutic effect in human GC.
Emerging strategies to bridge the gap between pharmacogenomic research and its clinical implementation
Authors: Lauschke Volker M. , Ingelman-Sundberg Magnus
Published: March 2020

The genomic inter-individual heterogeneity remains a significant challenge for both clinical decision-making and the design of clinical trials. Although next-generation sequencing (NGS) is increasingly implemented in drug development and clinical trials, translation of the obtained genomic information into actionable clinical advice lags behind. Major reasons are the paucity of sufficiently powered trials that can quantify the added value of pharmacogenetic testing, and the considerable pharmacogenetic complexity with millions of rare variants with unclear functional consequences. The resulting uncertainty is reflected in inconsistencies of pharmacogenomic drug labels in Europe and the United States. In this review, we discuss how the knowledge gap for bridging pharmacogenomics into the clinics can be reduced. First, emerging methods that allow the high-throughput experimental characterization of pharmacogenomic variants combined with novel computational tools hold promise to improve the accuracy of drug response predictions. Second, tapping of large biobanks of therapeutic drug monitoring data allows to conduct high-powered retrospective studies that can validate the clinical importance of genetic variants, which are currently incompletely characterized. Combined, we are confident that these methods will improve the accuracy of drug response predictions and will narrow the gap between variant identification and its utilization for clinical decision-support.
Quantifying Human Engagement into Playful Activities
Authors: Reguera David , Colomer-de-Simón Pol , Encinas Iván , Sort Manel , Wedekind Jan , Boguñá Marián
Published: March 2020

Engaging in playful activities, such as playing a musical instrument, learning a language, or performing sports, is a fundamental aspect of human life. We present a quantitative empirical analysis of the engagement dynamics into playful activities. We do so by analyzing the behavior of millions of players of casual video games and discover a scaling law governing the engagement dynamics. This power-law behavior is indicative of a multiplicative (i.e., “happy- get-happier”) mechanism of engagement characterized by a set of critical exponents. We also find, depending on the critical exponents, that there is a phase transition between the standard case where all individuals eventually quit the activity and another phase where a finite fraction of individuals never abandon the activity. The behavior that we have uncovered in this work might not be restricted only to human interaction with videogames. Instead, we believe it reflects a more general and profound behavior of how humans become engaged in challenging activities with intrinsic rewards.
Resistant starch from five Himalayan rice cultivars and Horse chestnut: Extraction method optimization and characterization
Authors: Gani Adil , Ashwar Bilal Ahmad , Akhter Gazalla , Gani Asir , Shah Asima , Masoodi Farooq Ahmad , Wani Idrees Ahmed
Published: March 2020

In this study resistant starch (RS) was extracted from five Himalayan rice cultivars and Indian Horse chestnut (HCN) using porcine pancreatin enzyme following which it was subsequently characterized for its physicochemical, structural and functional properties. In vitro digestibility test showed that RS content of the rice cultivars and HCN was in the range of 85.5 to 99.5%. The RS extracted from the rice cultivars and HCN showed significant difference in the apparent amylose content (AAC), ranging between 31.83 to 40.68% for rice and 45.79% for HCN. Water absorption capacity (WAC), swelling and solubility index of RS ranged from 112–133.9%, 5.28–7.25 g/g and 0.033–0.044 g/g, respectively. The rice RS granules were polyhedral and irregular shaped with granular length in the range of 4.8–5.9 µm. The HCN RS granule morphology showed smooth surfaced, round, elliptical, irregular and oval shapes with average granular length of 21 µm. Pasting behavior also varied significantly between rice RS and HCN RS with later showing the lower values of pasting properties. Thermal properties (T0, Tp, Tc) and ΔH gel also varied considerably between the rice RS and HCN RS, wherein the highest values for peak gelatinization temperature and gelatinization enthalpy were seen for CH-1039. X-ray diffraction pattern of rice RS and HCN RS showed the characteristic A type of pattern in consonance with cereal starches.
Kraft pulp mill dregs and grits as permeable reactive barrier for removal of copper and sulfate in acid mine drainage
Authors: Farage Rogério M. P. , Quina Margarida J. , Gando-Ferreira Licínio , Silva Cláudio M. , de Souza José João L. L. , Torres Caio M. M. E.
Published: March 2020

Mining is an essential human activity, but results in several environmental impacts, notably the contamination of ground and surface water through the presence of toxic substances such as metals and sulfates in mine drainage. Permeable reactive barriers (PRB) have been applied to remediate this environmental impact, but the high costs associated with the maintenance of this system are still a challenge. The main objective of this study was to evaluate the use of kraft pulp mill alkaline residues, known as dregs and grits, as material for PRB, and to determine their capacity for retaining copper and sulfate. The work was carried out in laboratory adsorption kinetics assays, batch assays and column tests. Tests for elemental characterization, point of zero charge, acid neutralization capacity, total porosity, bulk density and moisture of the dregs and grits were conducted. The results showed high retention of Cu due to a chemical precipitation mechanism, notably for dregs (99%) at 5 min in adsorption kinetics. The grits presented similar results after 180 min for the same assay. Sulfate retention was effective at pH below 5, with an efficiency of 79% and 89% for dregs and grits, respectively. Dregs presented the best results for acid drainage remediation, notably with a solid:liquid (S:L) ratio of 1:10.
Matching Graft Quality to Recipient’s Disease Severity Based on the Survival Benefit in Liver Transplantation
Authors: Winter Audrey , Féray Cyrille , Antoine Corinne , Azoulay Daniel , Daurès Jean-Pierre , Landais Paul
Published: March 2020

Persistent shortage and heterogeneous quality of liver grafts encourages the optimization of donor-recipient matching in liver transplantation (LT). We explored whether or not there was a survival benefit (SB) of LT according to the quality of grafts assessed by the Donor Quality Index (DQI) and recipients’ disease severity, using the Model for End-Stage Liver Disease (MELD) in 8387 French patients wait-listed between 2009 and 2014. SB associated with LT was estimated using the sequential stratification method in different categories of MELD and DQI. For each transplantation, a stratum was created that matched one transplanted patient with all eligible control candidates. Strata were thereafter combined, and a stratified Cox model, adjusted for covariates, was fitted in order to estimate hazard ratios that qualified the SB according to each MELD and DQI sub-group. A significant SB was observed for all MELD and DQI sub-groups, with the exception of high MELD patients transplanted with “high-risk” grafts. More specifically, in decompensated-cirrhosis patients, “high-risk” grafts did not appear to be detrimental in medium MELD patients. Interestingly, in hepatocellular-carcinoma (HCC) patients, a significant SB was found for all MELD-DQI combinations. For MELD exceptions no SB was found. In terms of SB, “low-risk” grafts appeared appropriate for most severe patients (MELD > 30). Conversely, low/medium MELD and HCC patients presented an SB while allocated “high-risk” grafts. Thus, SB based matching rules for LT candidates might improve the survival of the LT population as a whole.
Relationship between environmental radiation and radioactivity and childhood thyroid cancer found in Fukushima health management survey
Authors: Toki H. , Wada T. , Manabe Y. , Hirota S. , Higuchi T. , Tanihata I. , Satoh K. , Bando M.
Published: March 2020

Environmental radioactive contamination caused by the Fukushima Dai-ichi Nuclear Power Plant accident has aroused great concern regarding a possible increase in the incidence of childhood thyroid cancer. The ultrasound examinations were conducted immediately after the accident as part of the Fukushima Health Management Survey (FHMS), which is divided into the preliminary baseline survey (PBLS) and the full-scale survey (FSS). Some of their outcomes are reported regularly and made available to the public. We have detailed measurements of the air-dose rates and radioactive elements in soil in many places all over the Fukushima prefecture. To study the dose-response relationship, we begin with the assumption that the external and internal doses are correlated with the air-dose rate and the amount of131I in soil, respectively. We then investigate the relationship between these estimated doses and the PBLS and FSS thyroid cancer cases. Our analysis shows that the dose-response curve with the FSS data clearly differs from that with the PBLS data. Finally, we consider the potential mitigating effects of evacuation from highly contaminated areas in both external and internal exposure scenarios.
The evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates
Authors: Sun Ao , Xu Ke , Liu Haifeng , Li Hua , Shi Yaohuang , Zhu Xiaoyan , Liang Tao , Li Xinyue , Cao Xianxia , Ji Yanhong , Jiang Taijiao , Xu Chenqi , Liu Xiaolong
Published: March 2020

The recombination activating gene (RAG or RAG1/RAG2 complex)-mediated adaptive immune system is a hallmark of jawed vertebrates. It has been reported that RAG originated in invertebrates. However, whether RAG further evolved once it arose in jawed vertebrates remains largely unknown. Here, we found that zebrafish RAG (zRAG) had a lower activity than mouse RAG (mRAG). Intriguingly, the attenuated stability of zebrafish RAG2 (zRAG2), but not zebrafish RAG1, caused the reduced V(D)J recombination efficiency compared to mRAG at 37 °C which are the body temperature of most endotherms except birds. Importantly, the lower temperature 28 °C, which is the best temperature for zebrafish growth, made the recombination efficiency of zRAG similar to that of mRAG by improving the stability of zRAG2. Consistent with the prementioned observation, the V(D)J recombination ofRag2KI/KImice, which zRAG2 was substituted for mRAG2, was also severely impaired. Unexpectedly,Rag2KI/KImice developed cachexia syndromes accompanied by premature death. Taken together, our findings illustrate that the evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates.
Costs of exploratory behavior: the energy trade-off hypothesis and the allocation model tested under caloric restriction
Authors: Peña-Villalobos Isaac , Casanova-Maldonado Ignacio , Lois Pablo , Palma Verónica , Sabat Pablo
Published: March 2020

In order to maintain the energy balance, animals often exhibit several physiological adjustments when subjected to a decrease in resource availability. Specifically, some rodents show increases in behavioral activity in response to food restriction; a response regarded as a paradox because it would imply an investment in locomotor activity, despite the lack of trophic resources. Here, we aim to explore the possible existence of trade-offs between metabolic variables and behavioral responses when rodents are faced to stochastic deprivation of food and caloric restriction. Adult BALB/c mice were acclimatized for four weeks to four food treatments: two caloric regimens (ad libitum and 60% restriction) and two periodicities (continuous and stochastic). In these mice, we analyzed: exploratory behavior and home-cage behavior, basal metabolic rate, citrate synthase and cytochrome oxidase c enzyme activity (in liver and skeletal muscle), body temperature and non-shivering thermogenesis. Our results support the model of allocation, which indicates commitments between metabolic rates and exploratory behavior, in a caloric restricted environment. Specifically, we identify the role of thermogenesis as a pivotal budget item, modulating the reallocation of energy between behavior and basal metabolic rate. We conclude that brown adipose tissue and liver play a key role in the development of paradoxical responses when facing decreased dietary availability.
An investigation of the metabolic activity, isozyme contribution, species differences and potential drug–drug interactions of PI-103, and the identification of efflux transporters for PI-103-O-glucuronide in HeLa1A9 cells
Authors: Gao Li , Qin Zifei , Zhang Beibei , Yin Zhao , Zhang Xiaojian , Yang Jing
Published: March 2020

Metabolic activity and disposition characteristics of PI-103.
Approach to solve multi‐criteria group decision‐making problems by exponential operational law in generalised spherical fuzzy environment
Authors: Haque Tipu Sultan , Chakraborty Avishek , Mondal Sankar Prasad , Alam Shariful
Published: March 2020

The construction of generalised spherical fuzzy number (GSFN) is a reliable philosophy to design and understanding of vagueness and impreciseness. In this study, at first, the authors have defined the generalised spherical fuzzy set and discussed its several properties. Then, a new score and accuracy functions have been introduced in the generalised spherical fuzzy environment which leads to a new method of conversion of fuzzy number into a crisp number. New exponential operational law has been defined for GSFNs where the bases are positive real numbers & components are GSFNs and its various algebraic properties have been studied explicitly. Using this exponential operational law, a generalised spherical weighted exponential averaging operator has been proposed, which is used to develop a multi‐criteria group decision‐making (MCGDM) method in the generalised spherical fuzzy environment. The newly developed MCGDM has been demonstrated through a real‐life problem and its effectiveness and rationality have been shown through sensitivity analysis.
Stellar wind models of central stars of planetary nebulae
Authors: Krtička J. , Kubát J. , Krtičková I.
Published: March 2020

Context. Fast line-driven stellar winds play an important role in the evolution of planetary nebulae, even though they are relatively weak.

Aims. We provide global (unified) hot star wind models of central stars of planetary nebulae. The models predict wind structure including the mass-loss rates, terminal velocities, and emergent fluxes from basic stellar parameters.

Methods. We applied our wind code for parameters corresponding to evolutionary stages between the asymptotic giant branch and white dwarf phases for a star with a final mass of 0.569 M⊙. We study the influence of metallicity and wind inhomogeneities (clumping) on the wind properties.

Results. Line-driven winds appear very early after the star leaves the asymptotic giant branch (at the latest for Teff ≈ 10 kK) and fade away at the white dwarf cooling track (below Teff = 105 kK). Their mass-loss rate mostly scales with the stellar luminosity and, consequently, the mass-loss rate only varies slightly during the transition from the red to the blue part of the Hertzsprung–Russell diagram. There are the following two exceptions to the monotonic behavior: a bistability jump at around 20 kK, where the mass-loss rate decreases by a factor of a few (during evolution) due to a change in iron ionization, and an additional maximum at about Teff = 40−50 kK. On the other hand, the terminal velocity increases from about a few hundreds of km s−1 to a few thousands of km s−1 during the transition as a result of stellar radius decrease. The wind terminal velocity also significantly increases at the bistability jump. Derived wind parameters reasonably agree with observations. The effect of clumping is stronger at the hot side of the bistability jump than at the cool side.

Conclusions. Derived fits to wind parameters can be used in evolutionary models and in studies of planetary nebula formation. A predicted bistability jump in mass-loss rates can cause the appearance of an additional shell of planetary nebula.
Application of discrete damage mechanics for determination of the crack density in composite laminates
Authors: Žmindák Milan , Kormaníková Eva , Novák Pavol , Soukup Josef , Kotrasová Kamila
Published: March 2020

The finite element method (FEM) is one of the most widely and most popular numerical methods for analyzing damage of composite structures, In this paper discrete damage mechanics (DDM) is used to predict inter-laminar transverse and shear damage initiation and evolution in terms of the fracture toughness of the laminate. ANSYS commercial software is used for analysis of layered plate composite structure reinforced with long unidirectional fibers with Carbon/Epoxy material. Because ANSYS does not have a built-in capability for calculating crack density, we have to use plagin. A methodology for determination of the fracture toughness is based on fitting DDM model and these data are obtained from literature. Also, prediction of modulus vs. applied strain is contrasted with ply discount results and the effect of in situ correction of strength is highlighted. Evaluation of matrix cracking detected in lamina has been solved using return mapping algorithm.
The fatigue stress on laser welded joints of DC06EK steel
Authors: Mihaliková Mária , Špegarová Anna , Petrik Jozef , Babič Matej
Published: March 2020

The paper analyses the influence of the fatigue characteristics of laser welding steels sheets. The combination of laser welded steel sheets DC06EK has been subjected to fatigue stress testing. To assess the condition of the material under the cyclic stress and to determine the material characteristics such as fatigue or resp. fatigue time limit was performed according to STN 42 0363. Fatigue tests were performed on the test piece. The experimental material had a laser weld with a rough surface. The test specimens were subjected to a pulsating positive disappearing thrust at a constant value of the coefficient of unbalance of 0‹R‹1 and a frequency of 25 Hz. The fatigue limit was determined at 260 MPa. The analysis of fracture surfaces showed on the sides of the weld joint the formation of a de-cohesive fracture. The resulting test values graphically presents stress-number curve.
Parametric simulation of ceiling panels exposed to aggressive environments
Authors: Hegedüsová Iveta , Priganc Sergej
Published: March 2020

The subject matter of the contribution is findings obtained from a parametric simulation of ceiling panels behaviour under a change of determined parameters. The optional parameters included concrete strength, reinforcement cross-section area, and concrete covering. The experiment investigated an impact of the given parameters changes onto the element resistance which was evaluated on the basis of the ultimate state of usability, namely from the point of view of crack checking and deflection measuring. Panel behaviour was presented by a load-deflection relation and crack topography