bluuebunny/crossref_metadata_2025 huggingface dataset:
Grappling with uncertainties in physical climate impact projections of water resources
Authors: Dankers Rutger , Kundzewicz Zbigniew W.
Published: October 2020

This paper reviews the sources of uncertainty in physical climate impact assessments. It draws on examples from related fields such as climate modelling and numerical weather prediction in discussing how to interpret the results of multi-model ensembles and the role of model evaluation. Using large-scale, multi-model simulations of hydrological extremes as an example, we demonstrate how large uncertainty at the local scale does not preclude more robust conclusions at the global scale. Finally, some recommendations are made: climate impact studies should be clear about the questions they want to address, transparent about the uncertainties involved, and honest about the assumptions being made.
Blended Learning Adoption and Implementation in Higher Education: A Theoretical and Systematic Review
Authors: Anthony Bokolo , Kamaludin Adzhar , Romli Awanis , Raffei Anis Farihan Mat , Phon Danakorn Nincarean A. L. Eh , Abdullah Aziman , Ming Gan Leong
Published: October 2020

Technological innovations such as blended learning (BL) are rapidly changing teaching and learning in higher education, where BL integrates face to face teaching with web based learning. Thus, as polices related to BL increases, it is required to explore the theoretical foundation of BL studies and how BL were adopted and implemented in relation to students, lecturers and administration. However, only fewer studies have focused on exploring the constructs and factors related to BL adoption by considering the students, lecturers and administration concurrently. Likewise, prior research neglects to explore what practices are involved for BL implementation. Accordingly, this study systematically reviews, synthesizes, and provides meta-analysis of 94 BL research articles published from 2004 to 2020 to present the theoretical foundation of BL adoption and implementation in higher education. The main findings of this study present the constructs and factors that influence students, lecturers and administration towards adopting BL in higher education. Moreover, findings suggest that the BL practices to be implemented comprises of face-to-face, activities, information, resources, assessment, and feedback for students and technology, pedagogy, content, and knowledge for lecturers. Besides, the review reveals that the ad hoc, technology acceptance model, information system success model, the unified theory of acceptance and use of technology, and lastly diffusion of innovations theories are the mostly employed theories employed by prior studies to explore BL adoption. Findings from this study has implications for student, lecturers and administrators by providing insights into the theoretical foundation of BL adoption and implementation in higher education.
Correction to: Enterprising Women in Southern Africa: When Does Land Ownership Matter?
Authors: Brixiová Zuzana , Kangoye Thierry , Tregenna Fiona
Published: October 2020

The article “Enterprising Women in Southern Africa: When Does Land Ownership Matter?”, written by “Zuzana Brixiová, Thierry Kangoye, Fiona Tregenna”, was originally published Online First without Open Access.
Fungal Volatiles as Olfactory Cues for Female Fungus Gnat, Lycoriella ingenua in the Avoidance of Mycelia Colonized Compost
Authors: Kecskeméti Sándor , Szelényi Magdolna Olívia , Erdei Anna Laura , Geösel András , Fail József , Molnár Béla Péter
Published: October 2020

The chemical signatures emitted by fungal substrates are key components for mycophagous insects in the search for food source or for suitable oviposition sites. These volatiles are usually emitted by the fruiting bodies and mycelia. The volatiles attract fungivorous insects, like flowers attract pollinators; certain flowers mimic the shape of mushroom fruiting bodies and even produce a typical mushroom odor to exploit on fungus-insect mutualism. There are numerous insects which are mycophagous or eat fungi additionally, but only a few are considered a threat in agriculture. Lycoriella ingenua is one of the most serious pests in mushroom cultivation worldwide. Here we attempt to examine the role of environmental volatiles upon behavioral oviposition preference. In two-choice bioassays, fungus gnats preferred uncolonized compost compared to colonized compost but preferred colonized compost against nothing. However, when colonized compost was paired against distilled water, no significant choice was observed. The comparison of fresh casing material and mycelium colonized casing material resulted in no significant preference. From colonized compost headspace, three antennally active volatiles were isolated by gas chromatography coupled with electroantennography and subsequently identified with gas chromatography coupled mass spectrometry as 1-hepten-3-ol, 3-octanone and 1-octen-3-ol. In behavioral assays the addition of said synthetic volatiles to uncolonized compost separately and in combination to mimic colonized compost resulted in avoidance. We thus partially elucidate the role of fungal volatiles in the habitat seeking behavior of Lycoriella ingenua.
Open data governance: civic hacking movement, topics and opinions in digital space
Authors: Maretti Mara , Russo Vanessa , del Gobbo Emiliano
Published: October 2020

The expression ‘open data’ relates to a system of informative and freely accessible databases that public administrations make generally available online in order to develop an informative network between institutions, enterprises and citizens. On this topic, using the semantic network analysis method, the research aims to investigate the communication structure and the governance of open data in the Twitter conversational environment. In particular, the research questions are: (1) Who are the main actors in the Italian open data infrastructure? (2) What are the main conversation topics online? (3) What are the pros and cons of the development and use (reuse) of open data in Italy? To answer these questions, we went through three research phases: (1) analysing the communication network, we found who are the main influencers; (2) once we found who were the main actors, we analysed the online content in the Twittersphere to detect the semantic areas; (3) then, through an online focus group with the main open data influencers, we explored the characteristics of Italian open data governance. Through the research, it has been shown that: (1) there is an Italian open data governance strategy; (2) the Italian civic hacker community plays an important role as an influencer; but (3) there are weaknesses in governance and in practical reuse.
A multi-center psychometric evaluation of the Severity Indices of Personality Problems 118 (SIPP-118): Do we really need all those facets?
Authors: Paap Muirne C. S. , Hummelen Benjamin , Braeken Johan , Arnevik Espen A. , Walderhaug Espen , Wilberg Theresa , Berghuis Han , Hutsebaut Joost , Pedersen Geir
Published: October 2020

Purpose

The Severity Indices of Personality Problems 118 (SIPP-118) is a self-report questionnaire that aims to measure core components of (mal)adaptive personality functioning that can change over time. In this study, we aimed to assess the facet strength of the 16 facets across three large clinical samples.

Methods

Data from Norwegian and Dutch psychiatric patients were analyzed in this international multi-center study (N1 = 2814, N2 = 4751, N3 = 2217). Bi-factor modeling was used to assess to what degree the SIPP items tap into an overall general factor. The incremental value (distinctiveness) of the facets was studied using proportional reduction in mean squared error (PRMSE) based statistics.

Results

The estimated model showed adequate fit. The explained common variance (ECV) attributable to the general factor equaled 50% for all three samples. All but two facets (stable self-image and frustration tolerance) showed sufficient levels of distinctiveness. The findings were observed to be comparable across the three samples.

Conclusion

Our findings showed that the general factor was relatively weak, and the facets had a clear incremental value.
Male and female entrepreneurs’ employment growth ambitions: the contingent role of regulatory efficiency
Authors: Darnihamedani Pourya , Terjesen Siri
Published: October 2020

Entrepreneurs start and grow their ventures in a widely varying set of institutional contexts. One differentiator is a country’s regulatory efficiency which encompasses the freedom to start and to run a business without excessive government interventions around registering, hiring, and firing employees, and price controls on currency. The efficiency of regulations varies substantially among countries and imposes additional costs and risks on entrepreneurs’ activities. We integrate insights from institutional theory and recent literature on gender and entrepreneurship to better understand how a country’s regulatory efficiency affects male and female entrepreneurs’ employment growth ambitions. We explore three aspects of regulatory efficiency: business freedom (e.g., to start, operate, and close a venture), labor freedom (e.g., laws around minimum wage, layoffs, severance), and monetary freedom (e.g., price stability) using data from over 47,000 entrepreneurs in 68 countries. We find that entrepreneurs’ growth ambitions are higher in countries with more efficient regulations, particularly those countries characterized by fewer labor law restrictions and greater monetary freedoms. These findings are further exacerbated by gender by such that, relative to their female counterparts, male entrepreneurs have significantly greater venture growth ambitions. Our paper contributes to the discussion on how formal institutions influence women and men entrepreneurs in distinct ways.
Biomarkers of iron metabolism in chronic kidney disease
Authors: Tomasz Glogowski , Ewa Wojtaszek , Jolanta Malyszko
Published: October 2020

Iron is the most abundant transition metal in the human body and an essential element required for growth and survival. Our understanding of the molecular control of iron metabolism has increased dramatically over the past 20 years due to the discovery of hepcidin, which regulates the uptake of dietary iron and its mobilization from macrophages and hepatic stores. Anemia and iron deficiency are common in chronic kidney disease. The pathogenesis of anemia of chronic kidney disease is multifactorial. Correction of anemia requires two main treatment strategies: increased stimulation of erythropoiesis, and maintenance of an adequate iron supply to the bone marrow. However, there are still many uncertainties in regard to iron metabolism in patients with chronic kidney disease and in renal replacement therapy. The aim of this review was to summarize the current knowledge on iron metabolism in this population, including new biomarkers of iron status. There is an area of uncertainty regarding diagnostic utility of both erythroferrone (ERFE) and hepcidin in end-stage renal disease (ESRD) patients. Higher concentration of hepcidin in oligoanuric patients may reflect decreased renal clearance. Furthermore, the hepcidin-lowering effect of ERFE in ESRD patients treated with erythropoiesis-stimulating agents (ESAs) may be blunted by underlying inflammation and concomitant iron treatment. Thus, future studies should validate the use of ERFE as a biomarker of erythropoiesis and predictor of response to iron and ESA therapy in dialysis-dependent patients.
Impact of Force Function Formulations on the Numerical Simulation of Centre-Based Models
Authors: Mathias Sonja , Coulier Adrien , Bouchnita Anass , Hellander Andreas
Published: October 2020

Centre-based or cell-centre models are a framework for the computational study of multicellular systems with widespread use in cancer modelling and computational developmental biology. At the core of these models are the numerical method used to update cell positions and the force functions that encode the pairwise mechanical interactions of cells. For the latter, there are multiple choices that could potentially affect both the biological behaviour captured, and the robustness and efficiency of simulation. For example, available open-source software implementations of centre-based models rely on different force functions for their default behaviour and it is not straightforward for a modeller to know if these are interchangeable. Our study addresses this problem and contributes to the understanding of the potential and limitations of three popular force functions from a numerical perspective. We show empirically that choosing the force parameters such that the relaxation time for two cells after cell division is consistent between different force functions results in good agreement of the population radius of a two-dimensional monolayer relaxing mechanically after intense cell proliferation. Furthermore, we report that numerical stability is not sufficient to prevent unphysical cell trajectories following cell division, and consequently, that too large time steps can cause geometrical differences at the population level.
Selective Targeting of Non-nuclear Estrogen Receptors with PaPE-1 as a New Treatment Strategy for Alzheimer’s Disease
Authors: Wnuk Agnieszka , Przepiórska Karolina , Rzemieniec Joanna , Pietrzak Bernadeta , Kajta Małgorzata
Published: October 2020

Alzheimer’s disease (AD) is a multifactorial and severe neurodegenerative disorder characterized by progressive memory decline, the presence of Aβ plaques and tau tangles, brain atrophy, and neuronal loss. Available therapies provide moderate symptomatic relief but do not alter disease progression. This study demonstrated that PaPE-1, which has been designed to selectively activate non-nuclear estrogen receptors (ERs), has anti-AD capacity, as evidenced in a cellular model of the disease. In this model, the treatment of mouse neocortical neurons with Aβ (5 and 10 μM) induced apoptosis (loss of mitochondrial membrane potential, activation of caspase-3, induction of apoptosis-related genes and proteins) accompanied by increases in levels of reactive oxygen species (ROS) and lactate dehydrogenase (LDH) as well as reduced cell viability. Following 24 h of exposure, PaPE-1 inhibited Aβ-evoked effects, as shown by reduced parameters of neurotoxicity, oxidative stress, and apoptosis. Because PaPE-1 downregulated Aβ-induced Fas/FAS expression but upregulated that of Aβ-induced FasL, the role of PaPE-1 in controlling the external apoptotic pathway is controversial. However, PaPE-1 normalized Aβ-induced loss of mitochondrial membrane potential and restored the BAX/BCL2 ratio, suggesting that the anti-AD capacity of PaPE-1 particularly relies on inhibition of the mitochondrial apoptotic pathway. These data provide new evidence for an anti-AD strategy that utilizes the selective targeting of non-nuclear ERs with PaPE-1.
Protein Concentrations of Thrombospondin-1, MIP-1β, and S100A8 Suggest the Reflection of a Pregnancy Clock in Mid-Trimester Amniotic Fluid
Authors: Viklund Felicia , Hallingström Maria , Kacerovsky Marian , Cobo Teresa , Skogstrand Kristin , Hougaard David M. , Sävman Karin , Carlsson Ylva , Tsiartas Panagiotis , Juodakis Julius , Nilsson Staffan , Jacobsson Bo
Published: October 2020

The development of immunoassays enables more sophisticated studies of the associations between protein concentrations and pregnancy outcomes, allowing early biomarker identification that can improve neonatal outcomes. The aim of this study was to explore associations between selected mid-trimester amniotic fluid proteins and (1) overall gestational duration and (2) spontaneous preterm delivery. A prospective cohort study, including women undergoing mid-trimester transabdominal genetic amniocentesis, was performed in Gothenburg, Sweden, 2008–2016 (n = 1072). A panel of 27 proteins related to inflammation was analyzed using Meso-Scale multiplex technology. Concentrations were adjusted for gestational age at sampling, experimental factors, year of sampling, and covariates (maternal age at sampling, parity (nulliparous/multiparous), smoking at first prenatal visit, and in vitro fertilization). Cox regression analysis of the entire cohort was performed to explore possible associations between protein concentrations and gestational duration. This was followed by Cox regression analysis censored at 259 days or longer, to investigate whether associations were detectable in women with spontaneous preterm delivery (n = 47). Finally, linear regression models were performed to analyze associations between protein concentrations and gestational duration in women with spontaneous onset of labor at term (n = 784). HMG-1, IGFBP-1, IL-18, MIP-1α, MIP-1β, S100A8, and thrombospondin-1 were significantly associated with gestational duration at term, but not preterm. Increased concentrations of thrombospondin-1, MIP-1β, and S100A8, respectively, were significantly associated with decreased gestational duration after the Holm-Bonferroni correction in women with spontaneous onset of labor at term. This adds to the concept of a pregnancy clock, where our findings suggest that such a clock is also reflected in the amniotic fluid at early mid-trimester, but further research is needed to confirm this.
Ruth Macrides: an appreciation
Authors: Herrin Judith
Published: October 2020

The anniversary of Ruth's death and the funeral at St Andrews has just passed, reminding me how much I miss her and how profoundly she is admired by many medievalists, not just those specializing in Byzantine Studies, for a wide range of exciting studies not often brought together.
Theophilus of Edessa on the death of Constans II
Authors: Woods David
Published: October 2020

It is argued that Theophanes the Confessor derives his information concerning the name of the baths where Constans II was allegedly assassinated from Theophilus of Edessa. It is further argued that Theophilus’ claim that Andrew deliberately killed Constans by hitting him with a bucket is rather unconvincing and may represent the hypothetical reconstruction of the event by an imperial administration that could not accept that the emperor had died as a result of an unfortunate accident.
Performance and subversion under the Colonels’ gaze: changing notions of identity in the different editions of Dido Sotiriou's Οι νɛκροί πɛριμένουν
Authors: Camatsos Efrosini
Published: October 2020

This article examines the different editions of Dido Sotiriou's first novel Οι νɛκροί πɛριμένουν, whose first edition was published in 1959 and the definitive edition, one hundred pages shorter, in 1971, when the military junta ruled Greece and strict censorship was being exercised. The first edition depicts details of the resistance movement against the Axis powers, whereas this has been cut from the definitive edition, which ends just as Greece enters the war against Italy. It will be argued that the revisions, on the one hand, address criticisms of the first edition, in an attempt to improve the novel. On the other hand, the omission of descriptions of resistance against a tyrant (something the colonels resented, for fear of comparisons being drawn to their regime) and the shifting depiction of identities of two main characters, from one that is stable (1959 edition) to one that is subtly performative (1971 edition), also inform discussions of censorship and identity during the years of the military regime.
The Production of theMuselmannand the Singularity of Auschwitz: A Critique of Adriana Cavarero's Account of the “Auschwitz Event”
Authors: Riep Leonhard
Published: October 2020

Feminist philosopher Adriana Cavarero claims in her bookHorrorism: Naming Contemporary Violencethat the core of the horror of Auschwitz is constituted by the figure of theMuselmann. I argue that Cavarero's lack of an accurate historical engagement with this figure in particular and with Auschwitz in general leads her to a speculative turn, thereby universalizing the phenomenon of theMuselmannby making ittheexample of Auschwitz, and moreover, the key factor to explain its singularity. I show that the phenomenon of theMuselmann, although a particular horrible effect of Auschwitz, is not limited to this concentration and extermination camp system. Consequently, the characteristic that makes Auschwitz aunicumcannot be found in theMuselmann. Rather, as I elucidate, the singularity of Auschwitz and the Shoah in general must be understood in relation to the true goal of this camp: the final extermination of European Jewry.
Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019
Authors: Janssen Rob , Visser Margot P. J. , Dofferhoff Anton S. M. , Vermeer Cees , Janssens Wim , Walk Jona
Published: October 2020

Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.
FOREIGN INVESTORS’ RESPONSIBILITIES AND CONTRIBUTORY FAULT IN INVESTMENT ARBITRATION
Authors: Marcoux Jean-Michel , Bjorklund Andrea K.
Published: October 2020

Some investment arbitration tribunals have relied upon the principle of contributory fault to conclude that claimants have contributed to their own loss and should accordingly receive less compensation. The principle has not, however, been coherently applied. After analysing the use of contributory fault by tribunals and identifying factors contributing to an incoherent approach, the authors conclude that carefully crafted treaty provisions can improve the consistency of international investment arbitration by fostering a more coherent approach to both contributory fault and foreign investors’ responsibilities.
Appropriate use of echocardiography for palpitations in paediatric cardiology clinics
Authors: Sheth Saloni , Fares Munes , Kikano Sandra , Snyder Christopher , Dodgen Andrew , Wilhelm Carolyn M.
Published: October 2020

Objectives:

Identify diagnostic yield and frequency of echocardiograms for palpitation-related indications at outpatient paediatric cardiology clinics in relation to the 2014 ACC/AAP/AHA/ASE/HRS/SCAI/SCCT/SCMR/SOPE appropriate use criteria for Initial Transthoracic Echocardiography in Outpatient Paediatric Cardiology.

Study design:

A single-centre, retrospective study of children presenting for evaluation of a chief complaint of palpitations to outpatient paediatric cardiology clinics from 2015 to 2017. Palpitations were defined as an unpleasant sensation of rapid, irregular, and/or forceful beating of the heart. Indications for echocardiogram in patients were retrospectively classified based on the appropriate use criteria as “appropriate,” “may be appropriate,” or “rarely appropriate.” The incidence of abnormal and incidental echocardiographic findings for each category was determined.

Results:

A total of 286 patients presented with palpitations, with 128 (52% female) meeting inclusion criteria. Exclusion criteria included patients with additional cardiac complaints, prior echocardiogram, or history of congenital heart disease. Echocardiograms were performed on 36 (28%) patients. The appropriate use criteria were retrospectively applied, and indications for their performance were classified as “appropriate” (n = 4), “may be appropriate” (n = 17), or “rarely appropriate” (n = 15). Minor echocardiographic abnormalities were present in 22% (n = 8) of echocardiograms obtained for all appropriate use criteria classifications. No moderate or severe echocardiographic abnormalities were found. Incidental findings were noted in eight echocardiograms.

Conclusion:

Echocardiography in the evaluation of “rarely appropriate” and “may be appropriate” palpitation-related indications is of low diagnostic yield.
An Important Dilemma: Fibrinolytic Treatment in Bleeding Diathesis
Authors: Canakci Mustafa Emin , Ercan Volkan , Acar Nurdan , Efe Serdar
Published: October 2020

Pulmonary embolism is a clinical condition with high mortality rates in all age groups. The treatment includes anticoagulation and fibrinolytic therapy, and clinical management is challenging in cases of bleeding diathesis. Sepsis-induced coagulopathy (SIC), which has been recently defined to cause disruption of coagulation cascade accompanied by organ dysfunctions, is regarded as a major cause of mortality. It is noteworthy that there is no decrease in fibrinogen levels, unlike disseminated intravascular coagulopathy (DIC). This study aimed to present the management of a 70-year-old female patient who was admitted to emergency department with atypical complaints and diagnosed with pulmonary embolism due to deep vein thrombosis and septic shock. The clinical success of fibrinolytic therapy following the administration of fresh frozen plasma (FFP), although the patient had elevated international normalized ratio (INR), is presented in this case report. Since elevated INR and thrombocytopenia, which are observed in SIC, are caused by the inhibition of fibrinolysis, fibrinolytic therapy can be a rational treatment choice considering the profit/loss rate.
B-vitamins and metabolic syndrome in Mesoamerican children and their adult parents
Authors: Villatoro-Santos Claudia R , Ramirez-Zea Manuel , Villamor Eduardo ,   for the Nine Mesoamerican Countries Metabolic Syndrome (NiMeCoMeS) Study Group
Published: October 2020

Objective:

To examine the associations between vitamins of the methionine-homocysteine (Hcys) cycle (B6, B12 and folate) and Hcys with metabolic syndrome (MetS) among Mesoamerican children and their adult parents.

Design:

We conducted a cross-sectional study. Exposures were plasma vitamins B6 and B12 concentrations, erythrocyte folate and plasma Hcys. In children, the outcome was a continuous metabolic risk score calculated through sex- and age standardisation of waist circumference, the homoeostatic model assessment for insulin resistance, mean arterial pressure (MAP), serum HDL-cholesterol and serum TAG. In parents, the outcome was the prevalence of MetS according to the Adult Treatment Panel III Criteria. We estimated mean differences in the metabolic risk score and prevalence ratios of MetS between quartiles of the exposures using multivariable-adjusted linear and Poisson regression models, respectively.

Setting:

Capital cities of Belize, Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica and Chiapas State in Mexico.

Participants:

In total, 237 school-aged children and 524 parents.

Results:

Among children, vitamin B12 was inversely associated with the metabolic risk score (quartiles 4–1 adjusted difference = –0·13; 95 % CI: –0·21, –0·04; Ptrend = 0·008) through MAP, HDL-cholesterol and TAG. In contrast, folate was positively associated with the metabolic risk score (quartiles 4–1 adjusted difference = 0·11; 95 % CI: 0·01, 0·20; Ptrend = 0·02). In adults, vitamin B6 was inversely associated with MetS prevalence, whereas vitamin B12 and folate were positively related to this outcome.

Conclusions:

Vitamins of the methionine-Hcys cycle are associated with MetS in different directions. The associations differ between children and adults.
Evaluating the effect of the initiative ‘Caring for the Newborn and the Mother at Home’ in Mexico
Authors: Unar-Munguía Mishel , González de Cosío Teresita , Escalante-Izeta Ericka Ileana , Ferré-Eguiluz Isabel , Sachse-Aguilera Matthias , Herrera Carolina
Published: October 2020

Objective:

The WHO and UNICEF recommend home visits to improve health outcomes for mothers and newborns. We evaluated the effect of home visits by community volunteers during pregnancy and postpartum on breast-feeding practices, women’s knowledge about benefits, beliefs and myths of breast-feeding, obstetric and neonatal warning signs, preparation for childbirth and initial care for newborns, and diarrhoea and respiratory diseases in children.

Design:

Community quasi-experimental design. We estimated difference-in-difference models with fixed effects at the community level weighted by propensity score and investigated implementation barriers through focus groups and semi-structured interviews.

Setting:

Poor rural communities in Mexico; 48 intervention and 29 control.

Participants:

Baseline and follow-up information were reported from two independent cross-sectional samples of women with babies aged between 6 and 18 months (baseline: 292 control, 320 intervention; follow-up: 292 control, 294 intervention).

Results:

The intervention increased reports of exclusive breast-feeding in the first 6 months by 24·4 percentage points (pp) (95 % CI: 13·4, 35·4), mothers’ knowledge of obstetric warning signs by 23·4 pp (95 % CI: 9·2, 37·5) and neonatal warning signs by 26·2 pp (95 % CI: 15·2, 37·2) compared to the control group. A non-linear dose–response relation with the number of home visits was found. Diarrhoea and respiratory diseases among children decreased in the interventionv. control group but were not statistically significant.

Conclusions:

Home visits should be implemented as a complementary strategy to the provision of prenatal and postnatal care in rural communities due to their potential positive effects on the health of mothers and their children.
Just war theory after colonialism and the war on terror: reexamining non-combatant immunity
Authors: Mares Gabriel
Published: October 2020

I challenge a recent trend in just war theory – that civilians might be complicit with terrorists and lose non-combatant immunity – by reversing the gun sights and asking whether colonizing populations complicit with empire might compromise their non-combatant status. Employing colonial settlers as a thought experiment, I demonstrate the logic of expanded civilian culpability that has been proposed in the wake of the War on Terror would be unacceptable in other scenarios, and that these revisionist proposals are in service of ends incompatible with just war. In the process, I identify an important ambiguity regarding the performativity of non-combatant status, and show how this is used to aggressively expand civilian culpability for violence.
The epigenetic role of breastfeeding in mammary differentiation
Authors: Santiano Flavia E. , Campo Verde Arboccó Fiorella , Bruna Flavia A. , Zyla Leila E. , Sasso Corina V. , Gómez Silvina , Pistone-Creydt Virginia , López-Fontana Constanza M. , Carón Rubén W.
Published: October 2020

Maternal milk consumption can cause changes in the mammary epithelium of the offspring that result in the expression of molecules involved in the induction of differentiation, reducing the risk of developing mammary cancer later in life. We previously showed that animals that maintained a higher intake of maternal milk had a lower incidence of mammary cancer. In the present study, we evaluated one of the possible mechanisms by which the consumption of maternal milk could modify the susceptibility to mammary carcinogenesis. We used Sprague Dawley rats reared in litters of 3 (L3), 8 (L8), or 12 (L12) pups per mother in order to generate a differential consumption of milk. Whole mounts of mammary glands were performed to analyze the changes in morphology. Using real-time polymerase chain reaction (PCR), we analyzed the expression of mammary Pinc, Tbx3, Stat6, and Gata3 genes. We use the real-time methylation-specific polymerase chain reaction method to assess the methylation status of Stat6 and Gata3 CpG sites. Our findings show an increase in the size of the epithelial tree and a smaller number of ducts called terminal end buds in L3 vs. L12. We observed an increased expression of mRNA of Stat6, Gata3, Tbx3, and a lower expression of Pinc in L3 with respect to L12. Stat6 and Gata3 are more methylated in the CpG islands of the promoter analyzed in L12 vs. L3. In conclusion, the increased consumption of maternal milk during the postnatal stage generates epigenetic and morphological changes associated with the differentiation of the mammary gland.
Projected Strengthening of the Extratropical Surface Impacts of the Stratospheric Quasi‐Biennial Oscillation
Authors: Rao Jian , Garfinkel Chaim I. , White Ian P.
Published: October 2020

Using state‐of‐the‐art models with a spontaneous quasi‐biennial oscillation (QBO) from the Coupled Model Intercomparison Project Phases 5 and 6 (CMIP5/6), this study explores projected changes in the Holton‐Tan (HT) relationship and the near‐surface response to the QBO. Most models project an enhanced surface response to the QBO via a strengthened HT relationship in the future. Specifically, the North Atlantic Oscillation‐like response is projected to double and shift eastward in the future in the high‐end emission scenarios compared with the historical simulation. This strengthening occurs even as the amplitude of the QBO in the tropical stratosphere weakens from the historical simulation to the future projections. The seemingly contradictory projections of future changes in the QBO and the HT relationship might imply that the HT relationship changes nonlinearly with the QBO intensity, and the coherent changes in the background circulation structure should also be highlighted.
Treatments after progression to first-line FOLFOXIRI and bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies by GONO
Authors: Rossini Daniele , Lonardi Sara , Antoniotti Carlotta , Santini Daniele , Tomasello Gianluca , Ermacora Paola , Germani Marco Maria , Bergamo Francesca , Ricci Vincenzo , Caponnetto Salvatore , Moretto Roberto , Zaniboni Alberto , Pietrantonio Filippo , Buonadonna Angela , Ritorto Giuliana , Masi Gianluca , Latiano Tiziana Pia , Rapisardi Stefania , Falcone Alfredo , Cremolini Chiara
Published: October 2020

Background

FOLFOXIRI/bevacizumab (bev) is a first-line regimen of proven activity and efficacy in metastatic colorectal cancer. The upfront exposure to three cytotoxics raises concerns about the efficacy of treatments after progression.

Methods

We performed a pooled analysis of treatments after progression to upfront FOLFOXIRI/bev in patients enrolled in two randomised Phase 3 studies (TRIBE and TRIBE2) that compared FOLFOXIRI/bev to doublets (FOLFOX or FOLFIRI)/bev. Response rate, progression-free survival (2nd PFS) and overall survival (2nd OS) during treatments after progression were assessed. The RECIST response in first line and the oxaliplatin and irinotecan-free interval (OIFI) were investigated as potential predictors of benefit from FOLFOXIRI ± bev reintroduction.

Results

Longer 2nd PFS was reported in patients receiving FOLFOXIRI ± bev reintroduction compared to doublets ± bev or other treatments (6.1 versus 4.4 and 3.9 months, respectively, P = 0.013), and seems limited to patients achieving a response during first line (6.9 versus 4.2 and 4.7 months, respectively, P = 0.005) and an OIFI ≥ 4 months (7.2 versus 6.5 and 4.6 months, respectively, P = 0.045).

Conclusions

First-line FOLFOXIRI/bev does not impair the administration of effective second-line therapies. First-line response and longer OIFI seem associated with improved response and 2nd PFS from FOLFOXIRI ± bev reintroduction, without impacting 2nd OS.
Long noncoding RNA HOTAIR regulates the invasion and metastasis of prostate cancer by targeting hepaCAM
Authors: Li Ting , Liu Nanjing , Gao Yingying , Quan Zhen , Hao Yanni , Yu Chaowen , Li Luo , Yuan Mengjuan , Niu Lingfang , Luo Chunli , Wu Xiaohou
Published: October 2020

Background

The role of HOX transcript antisense RNA (HOTAIR) has been proven to be important in tumorigenesis. However, how this molecule promotes metastasis and invasion in PCa is still unclear.

Methods

The relationship between HOTAIR and hepatocellular adhesion molecule (hepaCAM) in PCa was identified by immunohistochemistry, immunofluorescence, plasmid transfection, quantitative real-time PCR and immunoblotting. The regulatory effects of HOTAIR on hepaCAM and MAPK signalling and their key roles in PCa metastasis were investigated in vitro.

Results

The expression of HOTAIR was inversely correlated with hepaCAM in the blood and tissue of PCa patients. Here, hepaCAM was identified as a novel target gene of HOTAIR and was critical for the invasiveness of PCa. HOTAIR recruited PRC2 to the hepaCAM promoter, resulting in high levels of H3K27me3 and the absence of hepaCAM with an abnormally activated MAPK pathway. Both HOTAIR depletion and EZH2 inhibition could induce hepaCAM re-expression with inhibitory MAPK signalling and decrease the invasive and metastatic capabilities of PCa cells.

Conclusions

This study demonstrates that HOTAIR promotes invasion and metastasis of PCa by decreasing the inhibitory effect of hepaCAM on MAPK signalling. Therefore, the HOTAIR/hepaCAM/MAPK axis may provide a new avenue towards therapeutic strategies and prognostic indicators for advanced prostate cancer.
Artificial selection for host resistance to tumour growth and subsequent cancer cell adaptations: an evolutionary arms race
Authors: Ibrahim-Hashim Arig , Luddy Kimberly , Abrahams Dominique , Enriquez-Navas Pedro , Damgaci Sultan , Yao Jiqiang , Chen Tingan , Bui Marilyn M. , Gillies Robert J. , O’Farrelly Cliona , Richards Christina L. , Brown Joel S. , Gatenby Robert A.
Published: October 2020

Background

Cancer progression is governed by evolutionary dynamics in both the tumour population and its host. Since cancers die with the host, each new population of cancer cells must reinvent strategies to overcome the host’s heritable defences. In contrast, host species evolve defence strategies over generations if tumour development limits procreation.

Methods

We investigate this “evolutionary arms race” through intentional breeding of immunodeficient SCID and immunocompetent Black/6 mice to evolve increased tumour suppression. Over 10 generations, we injected Lewis lung mouse carcinoma cells [LL/2-Luc-M38] and selectively bred the two individuals with the slowest tumour growth at day 11. Their male progeny were hosts in the subsequent round.

Results

The evolved SCID mice suppressed tumour growth through biomechanical restriction from increased mesenchymal proliferation, and the evolved Black/6 mice suppressed tumour growth by increasing immune-mediated killing of cancer cells. However, transcriptomic changes of multicellular tissue organisation and function genes allowed LL/2-Luc-M38 cells to adapt through increased matrix remodelling in SCID mice, and reduced angiogenesis, increased energy utilisation and accelerated proliferation in Black/6 mice.

Conclusion

Host species can rapidly evolve both immunologic and non-immunologic tumour defences. However, cancer cell plasticity allows effective phenotypic and population-based counter strategies.
Evening types have social jet lag and metabolic alterations in school-age children
Authors: Martínez-Lozano Nuria , Barraco Gloria Maria , Rios Rafael , Ruiz Maria José , Tvarijonaviciute Asta , Fardy Paul , Madrid Juan Antonio , Garaulet Marta
Published: October 2020

Chronotype has been mostly assessed with subjective scales. Objective assessment has been undertaken with actigraphy, although problems may occur in classifying chronotype. The aims of the study were to assess chronotype in school-age children using a novel integrative measurement (TAP) derived from non-invasive assessments of wrist temperature (T) physical activity (A) and body position (P) and to explore associations between chronotype, sleep disturbances, and metabolic components. Four-hundred-thirty-two children of 8–12 years were recruited from a Mediterranean area of Spain. Measurements were: (a) Chronotype objectively (7-day-rhythms of TAP) and subjectively measured (Munich-chronotype-self-reported questionnaire); (b) sleep rhythms and light exposition; (c) 7-day-diaries of food intake; (d) anthropometry and metabolic parameters; (e) academic scores. TAP acrophase was able to assess eveningness. As compared to more morning-types, more evening-types displayed lower amplitude in temperature rhythms, increased physical activity in the evening, delayed sleep and midpoint of intake and had more frequent social jet lag (P < 0.05). More evening-types had higher light intensity at 2 h before sleep and lower melatonin values (01:00 h). Eveningness associated with higher BMI and metabolic risk (higher values of insulin, glucose, triglycerides and cholesterol). Evening-types presented better grades in art. In conclusion, more evening-types, as objectively assessed, presented sleep alterations, social jet lag, obesity and higher metabolic risk.
Heterogeneous groups cooperate in public good problems despite normative disagreements about individual contribution levels
Authors: Otten Kasper , Buskens Vincent , Przepiorka Wojtek , Ellemers Naomi
Published: October 2020

Norms can promote human cooperation to provide public goods. Yet, the potential of norms to promote cooperation may be limited to homogeneous groups in which all members benefit equally from the public good. Individual heterogeneity in the benefits of public good provision is commonly conjectured to bring about normative disagreements that harm cooperation. However, the role of these normative disagreements remains unclear because they are rarely directly measured or manipulated. In a laboratory experiment, we first measure participants’ views on the appropriate way to contribute to a public good with heterogeneous returns. We then use this information to sort people into groups that either agree or disagree on these views, thereby manipulating group-level disagreement on normative views. Participants subsequently make several incentivized contribution decisions in a public goods game with peer punishment. We find that although there are considerable disagreements about individual contribution levels in heterogeneous groups, these disagreements do not impede cooperation. While cooperation is maintained because low contributors are punished, participants do not use punishment to impose their normative views on others. The contribution levels at which groups cooperate strongly relate to the average normative views of these groups.
Waist-to-height ratio and skipping breakfast are predictive factors for high blood pressure in adolescents
Authors: Aparicio-Cercós C. , Alacreu M. , Salar L. , Moreno Royo L.
Published: October 2020

The purpose of this study was to estimate the prevalence of high blood pressure (HBP) in adolescents of the Valencian Autonomous Community (VC) in Spain. Besides, its association with other risk factors related to cardiovascular disease (CVD) or arterial hypertension (AHT) in order to increase our knowledge of public health and to provide advice about healthy diets. We conducted a multicentre, observational, cross-sectional, epidemiological study in a sample of 4402 adolescents from 15 schools during the 2015–2016 school year. The participants were aged between 11 and 18 years, and any individuals already diagnosed with AHT were excluded. In addition to the Physical Activity Questionnaire for Adolescents (PAQ-A), Evaluation of the Mediterranean Diet Quality Index (KIDMED), a lifestyle habits survey, the waist-to-height ratio (WtHR), and body mass index (BMI) were calculated for each participant. Informed Consent was obtained from Parents of the adolescents involved in the current study. The study received approval from the University ethics committee and all procedures were conducted in accordance with the tenets of the Declaration of Helsinki. Chi-squared, Student t-tests, and ANOVA statistical analyses showed that 653 (14.8%) adolescents had previously undiagnosed HBP and that was significantly associated with male sex (p < 0.001), age over 15 years (p < 0.05), and height, weight, waist circumference, WtHR, BMI, and skipping breakfast. Based on the data we obtained in this study, the modifiable factors that influence HBP in adolescents were WtHR, BMI, and skipping breakfast.
Knotless seton for perianal fistulas: feasibility and effect on perianal disease activity
Authors: Stellingwerf Merel E. , Bak Michiel T. J. , de Groof E. Joline , Buskens Christianne J. , Molenaar Charlotte B. H. , Gecse Krisztina B. , Nerkens Willem , Horeman Tim , Bemelman Willem A.
Published: October 2020

Patients with perianal fistulas are frequently treated by a knotted seton which is well-known for causing complaints. We aimed to assess the feasibility of the knotless SuperSeton and advantages with respect to perianal disease activity. In a prospective cohort study, we included all consecutive adult patients with a knotted seton in situ or a perianal fistula requiring new seton drainage. Primary endpoint was seton feasibility (maintenance of the connection for minimally three months). Secondary endpoints included improvement of the Perianal Disease Activity Index (PDAI), complications and re-interventions within three months of follow-up. PDAI scores of patients with a knotted seton were crossover compared to PDAI scores after knotless seton replacement. Sixty patients (42% male, mean age 42 (SD 13.15), 41 with Crohn’s disease) were included between August 2016 and April 2018. Of 79 knotless setons, 69 (87.3%) stayed connected for ≥ 3 months. Overall, the knotless seton significantly decreased discharge (P = 0.001), pain (P < 0.001) and induration (P < 0.001) measured by the PDAI when compared to baseline. In patients with a knotted seton, replacement by the knotless seton significantly decreased discharge (P = 0.005) and pain (P < 0.001) measured by the PDAI. Furthermore, 71% of patients reported fewer cleaning problems compared to the knotted seton. Ten patients developed a perianal abscess, and five patients required a re-intervention. This study supports the feasibility of the knotless seton with promising short-term results. The knotless seton might be preferred over the knotted seton in terms of perianal disease activity.