bluuebunny/crossref_metadata_2025 huggingface dataset:
United States
Authors: Street Debra
Published: February 2020

For decades, American discourse about the future of SocialSecurity has trumped meaningful discussion of extending working lives. Similar to patterns of public debate and policymaking elsewhere, in the US pensions and delayed retirement has received most of the policy focus with relatively little attention paid to the gendered structure of the US labour market, and the systematic disadvantages built into its retirementincome regime. Nor have debates come to grips with the real likelihood as opposed to imagined potential for most older Americans remain employed longer, given the mismatch between available jobs andolder workers’ skills, their physical capacities, and competing family careresponsibilities. Complicating the US context further is the sheer complexity arising from significant regional differences in employment prospects, interactions between federal and state policies that shape employment and retirement outcomes, and the very exceptional character of UShealthinsurance arrangements to contend with, all within an ageist and age-denying culture. This chapter explores why there has been little debate and no consensusin US policymaking about how to expand good employment opportunities that could help Americans to extend their working lives, but plenty about raising retirement ages and contribution levels for SocialSecurity.
Belgium
Authors: Burnay Nathalie , Vendramin Patricia
Published: February 2020

Belgium is characterised by a low rate of employment for older people, though recent measures taken by national and regional governments have increased this rate. However, the extension of working life generates an increase in inequalities, especially for women. Having drastically reduced the legal provisions allowing people to leave the labour market before the legal retirement age, the Belgian federal government has adopted a series of measures aimed at extending working life. These reforms target botholder workers and companies. The trade unions are trying to resist, however neo-liberal logic is gradually penetrating the Belgian framework.
Perspective for Part I
Authors: Yamagishi Hiroyuki
Published: February 2020

The lungs are the primary organs of the respiratory system in vertebrates, other than fish, that function as an efficient gas exchanger. This respiratory system is physically and physiologically connected to the cardiovascular system to extract oxygen from the atmosphere and transfer it into the bloodstream and to release carbon dioxide from the bloodstream into the atmosphere. The normal pulmonary circulation, in contrast to the systemic circulation, has low pressure because of a low-resistant vascular bed that enables highly efficient gas exchange between the millions of alveoli and capillaries. Pulmonary hypertension (PH) is a rare pulmonary arterial disease with a high mortality and morbidity although treatment options have improved in the last decades. PH is defined by a mean pulmonary artery pressure (mPAP) greater than or equal to 20 mmHg at rest and is classified into five main subgroups based on the etiology and hemodynamic criteria. Because PH is heterogeneous at the genetic and molecular levels, a deeper understanding is required for the development of more effective therapies.
Using Patient-Specific Induced Pluripotent Stem Cells to Understand and Treat Pulmonary Arterial Hypertension
Authors: Gu Mingxia
Published: February 2020

Pulmonary arterial hypertension (PAH) is characterized by endothelial cell (EC) dysfunction, loss of peripheral pulmonary arterial (PA) microvessels, and proliferation of vascular cells in proximal PAs, leading to occlusion of the lumen. Loss of function mutations in bone morphogenetic protein receptor (BMPR)2 occur in over 70% of heritable form of PAH (HPAH) patients. Intriguingly, only 20% of the mutation carriers develop clinical symptoms, suggesting that genetic variation may provide modifiers that alleviate the disease. Induced pluripotent stem cell (iPSC)-derived vascular cells provide a new opportunity to further understand the disease mechanisms in a personalized manner. In our study, we demonstrated that iPSC-derived endothelial cell (iPSC-EC) recapitulates the functional and gene expression abnormalities in native PAEC from the same PAH patients compared with healthy controls. Interestingly, PAH PAEC and iPSC-EC also respond similarly to potential PAH therapies elafin and FK506 in terms of improved angiogenesis. We then used iPSC-ECs to further understand the reduced penetrance of the BMPR2 mutation. iPSC-EC was generated from three families with unaffected mutation carriers (UMC), HPAH patients, and gender-matched controls. We identified patient-specific features of preserved function in UMC iPSC-EC attributed to the regulators of BMPR2 signaling or to cell survival gene revealed by RNA-Seq analyses. Our findings therefore highlight protective modifiers for HPAH that could help inform development of future treatment strategies. Despite the site of disease in the lung and the particular vulnerability of the PA vasculature, iPSC-EC is a good surrogate for PAH modeling and drug testing.
Risk Stratification in Paediatric Pulmonary Arterial Hypertension
Authors: Moledina Shahin
Published: February 2020

Risk stratification can be defined as clinical assessment and investigation with the purpose of determining a person’s risk of suffering a particular outcome and thereby guiding the need for preventative intervention (McGraw-Hill Concise Dictionary of Modern Medicine 2002). The need for risk stratification comes from the realisation that although the presence of pulmonary arterial hypertension significantly impairs survival, the degree of impairment can vary across the population of patients by as much as an order of magnitude.

Furthermore the understanding that therapies aimed at palliating symptoms and prolonging life has negative consequences both for the patients by way of side effects and society by way of costs and should therefore be targeted at those for whom potential benefit outweighs harm.
The Adaptive Right Ventricle in Eisenmenger Syndrome: Potential Therapeutic Targets for Pulmonary Hypertension?
Authors: Kameny Rebecca Johnson , Datar Sanjeev A. , Boehme Jason , Fineman Jeffrey R.
Published: February 2020

Pulmonary hypertension (PH) is a rare disease with significant mortality despite targeted therapies. Among patients with PH, both survival and functional class are more closely correlated with right ventricular (RV) function than with the degree of pulmonary artery pressure elevation or pulmonary vascular resistance. Unfortunately, the RV is usually exquisitely sensitive to increases in afterload associated with PH, and progressive RV failure is the typical clinical course among most patients over time. However, in the subset of PH patients with congenital heart disease and Eisenmenger syndrome, survival is prolonged and RV function is preserved compared to patients with primary PH. This functional superiority may be due to a persistent RV fetal phenotype as patients continue to have a biventricular hypertrophy pattern which mimics fetal cardiac morphology. We have utilized an ovine model of congenital heart disease to demonstrate superior RV function following acute afterload stimulus—a unique RV Anrep effect. Further, we have shown shared gene expression patterns in the fetal and CHD model RV. In the future, understanding the underlying mechanisms of RV adaptation in CHD and PH may yield novel therapeutic strategies for all patients with pulmonary hypertension.
Impaired Right Coronary Vasodilator Function in Pulmonary Hypertensive Rats Assessed by In Vivo Synchrotron Microangiography
Authors: Inagaki Tadakatsu , Tsuchimochi Hirotsugu , Pearson James T. , Schwenke Daryl O. , Umetani Keiji , Shirai Mikiyasu , Nakaoka Yoshikazu
Published: February 2020

Pulmonary hypertension (PH) causes cardiac hypertrophy in the right ventricle (RV) and eventually leads to RV failure due to persistently elevated afterload. Considerable clinical and experimental animal studies have shown that abnormalities of endothelial function represent a hallmark of heart failure. However, the relationships between right coronary endothelial dysfunction and the development of heart failure remain to be fully established especially in the right heart. Synchrotron radiation (SR) microangiography has provided the temporal and spatial resolution required to visualize microvessels of various organs in vivo [1]. Therefore, in this study, we aimed to validate a new approach for the in vivo assessment of endothelial coronary function of the rat right heart using SR microangiography.
Lung Development and Notch Signaling
Authors: Morimoto Mitsuru
Published: February 2020

The respiratory system is connected to the cardiovascular system physically and physiologically. This chapter overviews the morphogenesis and epithelial development of the lung. The airway branching structure is formed as development progresses and is controlled by reciprocal mesenchymal-epithelial interactions. During the branching process, the distal terminal buds are thought to contain a population of multipotent epithelial progenitors that are more proliferative than proximal cells. This predominant proliferation in the distal tip leads to the lung bud extension toward the distal end. As the bronchial tree extends further, descendants of these multipotent cells give rise to lineage-restricted progenitors in the conducting airways. Notch signaling is used repeatedly to organize three epithelial cell types: Club, ciliated, and neuroendocrine (NE) cells. The Notch-mediated fate selection of Club/ciliated cells and of the size of NE cell clusters is regulated by different mechanisms. The Club/ciliated cell fate decision is mediated exclusively by Notch2 in response to Jag1. In contrast, all three Notch receptors contribute to robustly regulate the NE cell-cluster size. High-resolution whole-mount imaging of the developing lung revealed that the NE cell cluster appears at the stereotypic positions at the bifurcating area of the branching airways. Moreover, the 4D imaging, 3D plus live-imaging, method for developing lung epithelial cells discovered dynamics of NE cell clustering in which NE cells appear at inter-bifurcation area as solitary cells and migrate toward the branching points to form clusters. Further analyses determined that Notch signaling regulates the number of solitary NE cells in a lateral-inhibition fashion.
Perspective for Part III
Authors: Nakanishi Toshio
Published: February 2020

The ductus arteriosus (DA) is open before birth and normally closes after birth. The unique anatomy and normal and abnormal behavior of the DA are discussed by Gittenberger, Shelton, and Sterren in this chapter.
Prostaglandin E2 Receptor EP4 Inhibition Constricts the Rat Ductus Arteriosus
Authors: Sakuma Toshiki , Akaike Toru , Minamisawa Susumu
Published: February 2020

Patent ductus arteriosus (PDA) often occurs in premature infants [1]. At present, the cyclooxygenase inhibitor indomethacin is used to treat patients with PDA by inhibiting prostaglandin E2 synthesis. However, its efficiency is frequently limited [2] and adverse effects are problematic [3]. We have demonstrated that the prostaglandin E2 receptor EP4 specifically expresses in the rat ductus arteriosus (DA) [4]. Therefore, we hypothesized that EP4 inhibition promoted closure of the DA with fewer side effects.
Dilatation of the Ductus Arteriosus by Diazoxide in Fetal and Neonatal Rats
Authors: Toyoshima Katsuaki , Momma Kazuo , Ishii Tetsuko , Nakanishi Toshio
Published: February 2020

We previously reported that ATP-sensitive potassium (KATP) channels regulate ductal constriction in response to oxygen [1]. Diazoxide is a KATP channel opener while the usefulness of diazoxide for hyperinsulinemic hypoglycemia is well established. Yoshida et al. reported DA reopening in very low-birth-weight infants [2]. The objectives of this study were to elucidate the effect of KATP channel openers on the DA in neonatal rats as well as the different effects in preterm and full-term fetal rats [3].
The Effect of Long-term Administration of Prostaglandin E1 on Morphological Changes in Ductus Arteriosus
Authors: Iwaki Ryuma , Matsuhisa Hironori , Minamisawa Susumu , Akaike Toru , Hoshino Masato , Yagi Naoto , Morita Kiyozo , Shinohara Gen , Kaneko Yukihiro , Yoshitake Syuichi , Takahashi Masashi , Tsukube Takuro , Oshima Yoshihiro
Published: February 2020

The morphological and histopathological effects of PGE1 infusion for ductus arteriosus were clarified through novel modality XPCT and immunohistochemical analyses, EP4, and LOX expression. Recognition of microstructural changes of ductal tissue induced by extended administration of PGE1 is profound to establish the safety usage of PGE1 for HLHS patients with staged Norwood repair.
Optimum Preparation of Candida albicans Cell Wall Extra (CAWE) for the Mouse Model of Kawasaki Disease
Authors: Yoshikane Yukako , Cho Tamaki , Koga Mitsuhisa , Haraoka Seiji , Ogawa Atsushi
Published: February 2020

Kawasaki disease is the most common acute systemic vasculitis of unknown etiology in children [1] and can cause inflammation of the coronary arteries leading to aneurysms. Candida albicans extract is one of the materials commonly used to induce coronary arteritis in a mouse model of Kawasaki disease [2, 3]. Here we report an optimized method for preparing C. albicans cell wall extra (CAWE).
The Endocardium as a Master Regulator of Ventricular Trabeculation
Authors: Qu Xianghu , Baldwin H. Scott
Published: February 2020

Ventricular chamber morphogenesis, characterized by trabeculae formation, is crucial for cardiac function and embryonic viability and depends on cellular interactions between the endocardium and myocardium. The ang1-Tie2 pathway is required for normal heart chamber development, but its molecular effectors are not well defined. Here we show that loss of Tie2 in endocardial cells (EC) results in mid-gestation lethality due to heart defects including hyperplastic myocardium trabeculation (fewer but thicker trabeculae), thinner compact myocardium and simplified endocardial network. The thicker trabeculae phenotype results from enhanced proliferation of trabecular cardiomyocytes. Meanwhile, endocardial loss of Tie2 reduces proliferation and production of ECs and impairs endocardial sprouting, which provides necessary support for trabecular assembly and extension, thus resulting in a dramatically simplified trabecular meshwork. These findings reveal two seemingly apposing functions of Tie2 in myocardium trabeculation: ensuring normal trabeculation by supporting EC proliferation and sprouting while preventing hypertrabeculation by inhibiting trabecular cardiomyocyte proliferation.
Cardiac Cell Specification by Defined Factors
Authors: Morita Yuika , Takeuchi Jun
Published: February 2020

Our previous study has shown that Tbx5-Gata4-Baf60c-induced functional cardiomyocytes via the ectopic expression of Nkx2-5/Islet1 in the mesodermal cells, but not in the endodermal/ectodermal cells [1, 2] (Fig. 57.1). Mesp1 is one of the major transcriptional regulators specifying the mesodermal lineage, but it also induces skeletal muscle, hematopoietic and vascular cells as well as cardiac cells [3–5]. Eomesodermin (Eomes), an upstream player of Mesp1, regulates mesodermal cell lineages, but it does not have a potential for specification of cardiac cell fate from cardiovascular lineages either [6]. Therefore, the study of cardiac cell fate specification from the embryonic stem cells by the defined factors still remains at least two major questions.
Establishment of an In Vitro LQT3 model Using Induced Pluripotent Stem Cells from LQT3 Patient-Derived Cardiomyocytes
Authors: Furutani Yoshiyuki , Hayama Emiko , Kawaguchi Nanako , Katsube Yasuhiro , Oomichi Eiko , Shimada Mitsuyo , Inai Kei , Nakanishi Toshio
Published: February 2020

Cardiomyocytes derived from induced pluripotent stem cells (iPSC) are used to evaluate the function and risk factors of genetic variations linked to congenital and adult heart diseases in human beings. Our purpose in this study was to establish an in vitro cardiac disease model from an immortalized B-cell line stock using patient-specific iPSC-derived cardiomyocytes. Long QT syndrome (LQTS) 3 is caused by a gain-of-function mutation in the SCN5A gene, resulting in a prolonged QT interval as well as the development of early after-depolarizations (EADs). We generated LQT3-iPSC lines from immortalized B-cell lines transformed from peripheral blood obtained from a 24-day-old male (patient #1) and an 11-year-old female (patient #2), both diagnosed with type-3 LQTS due to SCN5A missense mutation (patient #1: exon 28, G4868A, R1623Q; patient #2: exon 20, G3578A, R1193Q). Several control iPSC lines were also created from samples collected from healthy candidates (26–36-year-old male and female). In both the generated patient iPSC lines, mutated genes were not altered after reprogramming, and normal karyotypes were observed. The pluripotency of all these iPSC lines was proven by in vivo teratoma formation and the expression of pluripotent stem cell marker genes and proteins. To evaluate the electrophysiological properties at the multicellular level, we studied the iPSC-derived cardiac cell layers with a microelectrode array mapping system (MED 64, Alpha MED Scientific Inc.). The recorded extracellular electrograms were analyzed to measure the field-potential duration (FPD), which was normalized to account for variations in beating frequency, using Fridericia’s correction (FPDcF, analogous to the QTc interval in the electrocardiogram). FPDcF was observed to be longer in LQT3 patient-derived specimens when compared to that in healthy control specimens (patient #1: P < 0.05, N = 17 and patient #2: P < 0.0001, N = 19 when compared to healthy control N = 39). Moreover, EADs were observed in both LQT3 patient specimens after 15–30 nM of E-4031 was added exclusively to patient samples. The results indicated that LQT3 patient iPSC-derived cardiac cells expressed prolonged QT duration (a common pathophysiological feature of LQTS) and EAD development with marked arrhythmogenicity in our in vitro disease model system.
Genetic Assessments for Clinical Courses of Left Ventricle Noncompaction
Authors: Nogimori Yoshitsugu , Kato Akio , Sato Kazuhisa , Kitagawa Yosuke , Wakamiya Takuya , Ono Shin , Kim Ki-Sung , Yanagi Sadamitsu , Ueda Hideaki
Published: February 2020

Left ventricle noncompaction (LVNC) is a clinically heterogeneous disorder. Although several genetic mutations have been reported, only a little is known about its genotype–phenotype correlation. We report two cases of LVNC with different mutations and different clinical courses for each. Case 1 was a 15-year-old boy with atrial septum defect and pulmonary valve stenosis. He was diagnosed as LVNC when he was 3 years old, but his cardiac function was maintained and no medication was necessary. A 432 kb deletion in chromosome 8p 23.1, including GATA4, was found. Case 2 was a boy who was referred to our hospital at the age 6 for apparent right ventricle hypertrophy in electrocardiogram carried out for screening. We recognized severe pulmonary hypertension (PH) and LVNC with attenuated cardiac diastolic function and fair systolic function. In spite of medications for both heart failure and PH, the response was poor. A genetic investigation revealed a point mutation at exon 6 of TBX20, c.655-2A>G.
Elucidating the Pathogenesis of Congenital Heart Disease in the Era of Next-Generation Sequencing
Authors: Nakagama Yu , Inuzuka Ryo
Published: February 2020

Over the last decade, genetic screening has become increasingly available for patients with congenital heart disease (CHD). Chromosomal microarray has proved to be promising, particularly in the diagnosis of syndromic CHDs, and is now considered first-tier cytogenetic testing [1]. Whole-exome sequencing (WES) is another approach for genetic screening aimed towards identifying single-gene mutations [2]. Trio- and pedigree-based WES facilitate the identification of de novo and compound heterozygous variants throughout the entire coding region. Filtering of variants based on allele frequency, in silico predictions and segregation status, effectively narrows down the putative mutation. Thus, application of next-generation sequencing (NGS) has the potential of enhancing gene discovery in CHD pathogenesis.
Extracellular Vesicles, MicroRNAs, and Pulmonary Hypertension
Authors: Chen Tianji , Raj J. Usha
Published: February 2020

Pulmonary hypertension (PH) is a devastating disease that results in a progressive increase in pulmonary vascular resistance, right ventricular failure, and ultimately death of patients. Recent advances in our understanding of pathogenesis of diseases, including PH, have led to the study of extracellular vesicles (EV) as mediators of disease. Subsets of EV are microvesicles (MV), exosomes (Exo), and apoptotic bodies, and they are released from a variety of cell types and carry cargo such as proteins and microRNAs (miR). MicroRNAs contained within these EV play an important role in disease including in the pathogenesis of PH as well as other lung diseases.
Roles of Tbx4 in the Lung Mesenchyme for Airway and Vascular Development
Authors: Uchida Keiko , Yoshida Yu , Kodo Kazuki , Yamagishi Hiroyuki
Published: February 2020

The T-box family genes are evolutionarily conserved transcription factors. In particular, Tbx4 and Tbx5 are closely conserved and play crucial roles in development and organogenesis. Tbx4 is essential for hindlimb and allantoic vessel formation [1]. It is also highly expressed in the lung mesenchyme (Fig. 8.1), initially expressed at embryonic day (E) 9.25 and later expressed throughout murine embryogenesis [2].
Magnetic quivers, Higgs branches, and 6d $$ \mathcal{N} $$ = (1, 0) theories — orthogonal and symplectic gauge groups
Authors: Cabrera Santiago , Hanany Amihay , Sperling Marcus
Published: February 2020

Abstract

M5 branes on a D-type ALE singularity display various phenomena that introduce additional massless degrees of freedom. The M5 branes are known to fractionate on a D-type singularity. Whenever two fractional M5 branes coincide, tensionless strings arise. Therefore, these systems do not admit a low-energy Lagrangian description. Focusing on the 6-dimensional $$ \mathcal{N} $$
N
= (1, 0) world-volume theories on the M5 branes, the vacuum moduli space has two branches were either the scalar fields in the tensor multiplet or the scalars in the hypermultiplets acquire a non-trivial vacuum expectation value. As suggested in previous work, the Higgs branch may change drastically whenever a BPS-string becomes tensionless. Recently, magnetic quivers have been introduced with the aim to capture all Higgs branches over any point of the tensor branch. In this paper, the formalism is extended to Type IIA brane configurations involving O6 planes. Since the 6d $$ \mathcal{N} $$
N
= (1, 0) theories are composed of orthosymplectic gauge groups, the derivation rules for the magnetic quiver in the presence of O6 planes have to be conjectured. This is achieved by analysing the 6d theories for a single M5 brane on a D-type singularity and deriving the magnetic quivers for the finite and infinite gauge coupling Higgs branch from a brane configuration. The validity of the proposed derivation rules is underpinned by deriving the associated Hasse diagram. For multiple M5 branes, the approach of this paper provides magnetic quivers for all Higgs branches over any point of the tensor branch. In particular, an interesting infinite gauge coupling transition is found that is related to the SO(8) non-Higgsable cluster.
A R2R3-MYB gene-based marker for the non-darkening seed coat trait in pinto and cranberry beans (Phaseolus vulgaris L.) derived from ‘Wit-rood boontje’
Authors: Erfatpour M. , Pauls K. P.
Published: February 2020

Key message

The genePhvul.010G130600which codes for a MYB was shown to be tightly associated with seed coat darkening inPhaseolus vulgarisand a single nucleotide deletion in the allele in Wit-rood disrupts a transcription activation region that likely prevents its functioning in this non-darkening genotype.

The beige and white background colors of the seed coats of conventional pinto and cranberry beans turn brown through a process known as postharvest darkening (PHD). Seed coat PHD is attributed to proanthocyanidin accumulation and its subsequent oxidation in the seed coat. TheJgene is an uncharacterized classical genetic locus known to be responsible for PHD in common bean (P. vulgaris) and individuals that are homozygous for its recessive allele have a non-darkening (ND) seed coat phenotype. A previous study identified a major colorimetrically determined QTL for seed coat color on chromosome 10 that was associated with the ND trait. The objectives of this study were to identify a gene associated with seed coat postharvest darkening in common bean and understand its function in promoting seed coat darkening. Amplicon sequencing of 21 candidate genes underlying the QTL associated with the ND trait revealed a single nucleotide deletion (c.703delG) in the candidate genePhvul.010G130600in non-darkening recombinant inbred lines derived from crosses between ND ‘Wit-rood boontje’ and a regular darkening pinto genotype. In silico analysis indicated thatPhvul.010G130600encodes a protein with strong amino acid sequence identity (70%) with a R2R3-MYB-type transcription factorMtPAR, which has been shown to regulate proanthocyanidin biosynthesis inMedicago truncatulaseed coat tissue. The deletion in the ‘Wit-rood boontje’ allele ofPhvul.010G130600likely causes a translational frame shift that disrupts the function of a transcriptional activation domain contained in the C-terminus of the R2R3-MYB. A gene-based dominant marker was developed for the dominant allele ofPhvul.010G130600which can be used for marker-assisted selection of ND beans.
Functionality of primary hepatic non-parenchymal cells in a 3D spheroid model and contribution to acetaminophen hepatotoxicity
Authors: Bell Catherine C. , Chouhan Bhavik , Andersson Linda C. , Andersson Håkan , Dear James W. , Williams Dominic P. , Söderberg Magnus
Published: February 2020

In addition to hepatocytes, the liver comprises a host of specialised non-parenchymal cells which are important to consider in the development of in vitro models which are both physiologically and toxicologically relevant. We have characterized a 3D co-culture system comprising primary human hepatocytes (PHH) and non-parenchymal cells (NPC) and applied it to the investigation of acetaminophen-induced toxicity. Firstly, we titrated ratios of PHH:NPC and confirmed the presence of functional NPCs via both immunohistochemistry and activation with both LPS and TGF-β. Based on these data we selected a ratio of 2:1 PHH:NPC for further studies. We observed that spheroids supplemented with NPCs were protected against acetaminophen (APAP) toxicity as determined by ATP (up to threefold difference in EC50 at day 14 compared to hepatocytes alone) and glutathione depletion, as well as miR-122 release. APAP metabolism was also altered in the presence of NPCs, with significantly lower levels of APAP-GSH detected. Expression of several CYP450 enzymes involved in the bioactivation of APAP was also lower in NPC-containing spheroids. Spheroids containing NPCs also expressed higher levels of miRNAs which have been implicated in APAP-induced hepatotoxicity, including miR-382 and miR-155 which have potential roles in liver regeneration and inflammation, respectively. These data indicate that the interaction between hepatocytes and NPCs can have significant metabolic and toxicological consequences important for the correct elucidation of hepatic safety mechanisms.
Inhibition of IDO leads to IL-6-dependent systemic inflammation in mice when combined with photodynamic therapy
Authors: Wachowska Malgorzata , Stachura Joanna , Tonecka Katarzyna , Fidyt Klaudyna , Braniewska Agata , Sas Zuzanna , Kotula Iwona , Rygiel Tomasz Piotr , Boon Louis , Golab Jakub , Muchowicz Angelika
Published: February 2020

It was previously reported that the activation of antitumor immune response by photodynamic therapy (PDT) is crucial for its therapeutic outcome. Excessive PDT-mediated inflammation is accompanied by immunosuppressive mechanisms that protect tissues from destruction. Thus, the final effect of PDT strongly depends on the balance between the activation of an adoptive arm of immune response and a range of activated immunosuppressive mechanisms. Here, with flow cytometry and functional tests, we evaluate the immunosuppressive activity of tumor-associated myeloid cells after PDT. We investigate the antitumor potential of PDT combined with indoleamine 2,3-dioxygenase 1 (IDO) inhibitor in the murine 4T1 and E0771 orthotopic breast cancer models. We found that the expression of IDO, elevated after PDT, affects the polarization of T regulatory cells and influences the innate immune response. Our results indicate that, depending on a therapeutic scheme, overcoming IDO-induced immunosuppressive mechanisms after PDT can be beneficial or can lead to a systemic toxic reaction. The inhibition of IDO, shortly after PDT, activates IL-6-dependent toxic reactions that can be diminished by the use of anti-IL-6 antibodies. Our results emphasize that deeper investigation of the physiological role of IDO, an attractive target for immunotherapies of cancer, is of great importance.
Effectiveness and Usage Trends of Hemorrhage Control Interventions in Patients with Pelvic Fracture in Shock
Authors: Matsumoto Shokei , Funabiki Tomohiro , Hayashida Kei , Yamazaki Motoyasu , Ebihara Takayuki , Moriya Takashi
Published: February 2020

Background

Hemorrhage control for pelvic fractures remains challenging. There are several kinds of hemostatic interventions, including angiography/angioembolization (AG/AE), external fixation (EF), and resuscitative endovascular balloon occlusion of the aorta (REBOA). However, no large studies have been conducted for the comparative review of each intervention. In this study, we examined the usage trend of therapeutic interventions in Japan for patients with pelvic fractures in shock and the influence of these interventions on mortality.

Methods

Data of adult patients with pelvic fracture who were in shock were obtained from the Japanese Trauma Data Bank (2004–2014). The primary endpoint was the influence of each intervention (AG/AE, EF, and REBOA) on in‐hospital mortality. We also investigated the frequency of each intervention.

Results

A total of 3149 patients met all our inclusion criteria. Specifically, 1131 (35.9%), 496 (15.8%), and 256 (8.1%) patients underwent AG, EF, and REBOA interventions, respectively. Therapeutic AE was performed in 690 patients who underwent AG (61.0%). The overall mortality rate was 31.4%. Multiple regression analysis identified that AG/AE (OR 0.64, 95% CI 0.52–0.80) and EF (OR 0.75, 95% CI 0.58–0.98) were significantly associated with survival, whereas REBOA (OR 4.17, 95% CI 3.00–5.82) was significantly associated with worse outcomes.

Conclusions

In Japan, patients with pelvic fracture who were in shock had high mortality rates. AG/AE and EF were associated with decreased mortality. AG may benefit from the early detection of arterial bleeding, leading to decreased mortality of patients with pelvic fracture in shock.
Sustainability Models for Efficient Resource Use in the Context of Current Ecological and Social Pressures
Authors: Feiel Susanne
Published: February 2020

The basis of human societal existence is a complex interaction between social, environmental and industrial aspects resulting in the consumption of the environment for wealth generation. In combination with the actual scope of human industrial activity and population development this has led to a currently exceptional planetary situation, which is characterized by unprecedented environmental pressures. In order to develop a strategy on how industrial activity, especially the mineral raw materials sector and its downstream industries, can develop more sustainably, various sustainability models can combined provide orientation on where the journey should go.
Size dependency of variables influencing fire occurrence in Mediterranean forests of Eastern Spain
Authors: Peris-Llopis Marina , González-Olabarria José Ramón , Mola-Yudego Blas
Published: February 2020

Fires are among the most damaging disturbances to forests in the Mediterranean area. The study analyses the occurrence and characteristics of forest fires in Eastern Spain (1993–2015) to identify key variables related to burnt forest land, differentiating fires according to their burnt area. Data are retrieved from digital cartography, the Spanish Forest Map and data concerning fires. Based on previous research, the variables included are altitude, slope, aspect, fuel, species, population and road density. The fires are classified in small (5–50 ha), medium (50–500 ha) and large (> 500 ha). Four models are considered to explain the proportion of burnt area based on weighted generalized linear models: a general model and one per size class. The results highlight the different relations of similar variables with fires according to the size. When a single model is considered to explain all area burnt, the relationships are mainly driven by large fires. The larger area is burnt on forests with pine, bushes and small trees, whereas smaller fires tend to occur on lower altitude, low slope, high population and road densities. There are large differences in the variables according to the fire sizes, especially for the presence of pine (negative in the medium fires model but positive for the large fires model) and Pasture (which only explains the small fires). The models can be applied to analyse occurrence by fire size in Mediterranean areas, and the results can help elaborate fire prevention strategies and land-planning schemes.
Towards a relational paradigm in sustainability research, practice, and education
Authors: Walsh Zack , Böhme Jessica , Wamsler Christine
Published: February 2020

Relational thinking has recently gained increasing prominence across academic disciplines in an attempt to understand complex phenomena in terms of constitutive processes and relations. Interdisciplinary fields of study, such as science and technology studies (STS), the environmental humanities, and the posthumanities, for example, have started to reformulate academic understanding of nature-cultures based on relational thinking. Although the sustainability crisis serves as a contemporary backdrop and in fact calls for such innovative forms of interdisciplinary scholarship, the field of sustainability research has not yet tapped into the rich possibilities offered by relational thinking. Against this background, the purpose of this paper is to identify relational approaches to ontology, epistemology, and ethics which are relevant to sustainability research. More specifically, we analyze how relational approaches have been understood and conceptualized across a broad range of disciplines and contexts relevant to sustainability to identify and harness connections and contributions for future sustainability-related work. Our results highlight common themes and patterns across relational approaches, helping to identify and characterize a relational paradigm within sustainability research. On this basis, we conclude with a call to action for sustainability researchers to co-develop a research agenda for advancing this relational paradigm within sustainability research, practice, and education.
Connection between Parent–Child Religiosity: Moderated Mediation by Perceived Maternal and Paternal Warmth and Overprotection and Emerging Adult Gender
Authors: Stearns Melanie , McKinney Cliff
Published: February 2020

Previous research has shown a strong connection between parental religiosity and parenting behaviors in the transmission of religion from parent to child. Our study expanded upon previous research by examining how perceived maternal and paternal warmth and overprotection mediated the relation between parental and personal religiosity in males and females. A sample of 486 emerging adults reported maternal, paternal, and personal religiosity as well as their parents’ parenting behaviors. Results indicated that perceived paternal warmth served as a mediator for males only but neither perceived maternal nor paternal overprotection mediated the relationship between parental religiosity and emerging adult religiosity. Gender moderated the paths from perceived paternal religiosity to paternal overprotection, such that the relationship was stronger for females, and perceived paternal warmth to emerging adult religiosity, such that the relationship was stronger for males. Overall, results demonstrated that mediation effects occurred for males only, suggesting moderated mediation.
Metastasenchirurgie beim Harnblasenkarzinom: Sinn oder Unsinn
Authors: Garstka Nathalie , Shariat Shahrokh François
Published: February 2020

Das Outcome eines lymphknotenpositiven oder fernmetastasierten Urothelkarzinoms (mUC) der Harnblase ist schlecht. Eine cisplatinbasierte Chemotherapie wie Gemcitabin/Cisplatin oder akzeleriertes MVAC (Methotrexat, Vinblastin, Adriamycin und Cisplatin) bilden den Standard in der systemischen Erstlinientherapie des mUC. Alternativ kann seit 2016 in diesem Setting eine Immuntherapie angeboten werden. Somit stehen z. B. in der Erstlinie cisplatinungeeigneten Patienten die Checkpointinhibitoren Atezolizumab oder Pembrolizumab zur Verfügung, sofern sie einen positiven PD-L1-Status aufweisen. Eine Metastasen gezielte operative Therapie wird bereits erfolgreich bei verschiedenen urologischen Tumoren, wie dem Hoden- oder dem Nierenzellkarzinom, eingesetzt, um das Überleben zu verlängern und/oder die Lebensqualität zu verbessern. In diesem Artikel soll der Stellenwert der Metastasenchirurgie beim mUC der Harnblase evaluiert werden.
The approach of partial stabilisation in design of discrete-time robust guidance laws against manoeuvering targets
Authors: Shafiei M.H. , Vazirpour N.
Published: February 2020

In this paper, a robust three-dimensional guidance law against manoeuvering targets is designed using the approach of discrete-time partial stabilisation. In the proposed method, the equations of the guidance problem are divided into two subsystems where the asymptotic stability is desired only for the first one. The control input of the second subsystem is designed such that the collision to be ensured in a short time. Despite recent advances in technology and implementation of digital controllers, the design of guidance laws with the approach of discrete-time partial stabilisation has not been done, till now. One of the advantages of this paper is to design a discrete-time guidance law even with the difficulties of the discrete-time Lyapunov theorem. Moreover, the Lyapunov function is chosen based on the physics of the guidance problem (making the rate of line of sight (LOS) rotation close to zero), and it is shown that it is not possible to asymptotically stabilise the system in the case of manoeuvering targets. Nevertheless, to guarantee the collision with the target, it is enough to limit the rotation rate of LOS to a small value. Finally, simulation results are given to show the appropriate performance of the proposed guidance law.
EU Coordination of Serious Cross-Border Threats to Health: The Implications for Protection of Informed Consent in National Pandemic Policies
Authors: VAN KOLFSCHOOTEN Hannah
Published: February 2020

This article discusses the development of a more supranational EU approach to regulate risks of “serious cross-border threats to health” such as pandemic disease outbreaks. It argues that the EU’s public health measures to prevent and tackle pandemics could affect individual patients’ rights, because the rights of individual European citizens are balanced against the importance of protecting the European community as a whole. This results in a tension between public health and individual rights in the EU, especially with regard to the right to informed consent, a central right in health law. In response to the 2013–2016 Ebola outbreak in West Africa, the EU introduced several preventive and responsive measures in the Member States to prevent the pandemic from spreading to the EU. The case study analysis of Dutch pandemic policies established in reaction to this outbreak shows that national pandemic policies are substantially shaped by EU actions, which has implications for the protection of the individual right to informed consent in the Member States.
Conceptual metaphors in poetry interpretation: a psycholinguistic approach
Authors: RASSE CARINA , ONYSKO ALEXANDER , CITRON FRANCESCA M. M.
Published: February 2020

Psycholinguistic research has shown that conceptual metaphors influence how people produce and understand language (e.g., Gibbs, 1994, 2017a; Kövecses, 2015; Jacobs & Kinder, 2017). So far, investigations have mostly paid attention to non-poetic metaphor comprehension. This focus stems from the original discovery of Conceptual Metaphor Theory that much of everyday, non-poetic language is metaphorical. The present study aims to expand this focus and explores whether people access conceptual metaphors during poetry interpretation. To answer this question, we conducted a psycholinguistic experiment in which 38 participants, all native speakers of English, completed two tasks. In each task, participants read excerpts of poetry containing conceptual metaphors before selecting or rating items that indicated their implicit and explicit awareness of the conceptual metaphors. The results of both tasks show that participants retrieve conceptual metaphors when reading poetry. This provides empirical evidence in favor of the idea that crucial aspects of poetic thought and language arise from conceptual metaphor.
Ranking Dutch intensifiers: a usage-based approach
Authors: RICHTER MICHAEL , VAN HOUT ROELAND
Published: February 2020

The present approach estimates the strength of intensifiers in Dutch by computing their information values in a language corpus, that is, contextual information content (Cohen Priva, 2008; Piantadosi, Tily, & Gibson, 2011) and Shannon Information (Shannon & Weaver, 1948), to respectively explain the use value and the expressive value of intensifiers when they intensify a predicative adjective. Conflicting strength values help in understanding the high number of intensifiers commonly available in particular languages and the constant need for adding new ones. Our approach underlines the relevance of two measures of information content (IC) for ranking intensifiers: (i) IC in context: the more combinatorial or transitional options an intensifier has, the higher its contextual information content and consequently its use value; and (ii) IC in relation to all alternative intensifiers: the higher the surprisal value that the occurrence of an intensifier evokes, the higher its expressive value. We shall investigate the validity of these two measures by researching a large corpus of Dutch tweets and shall test whether the values of these two measures can predict the stacking order in sequences of intensifiers.
False Memories: The Other Side of Forgetting
Authors: Turk Katherine W. , Palumbo Rocco , Deason Rebecca G. , Marin Anna , Elshaar Ala’a , Gosselin Emma , O’Connor Maureen K. , Tripodis Yorghos , Budson Andrew E.
Published: February 2020

Objective:

To measure caregivers’ and clinicians’ perception of false memories in the lives of patients with memory loss due to Alzheimer’s disease (AD) and mild cognitive impairment (MCI) using a novel false memories questionnaire. Our hypotheses were that false memories are occurring as often as forgetting according to clinicians and family members.

Method:

This prospective, questionnaire-based study consisting of 20 false memory questions paired with 20 forgetting questions had two forms: one for clinicians and the other for family members of older subjects. In total, 226 clinicians and 150 family members of 49 patients with AD, 44 patients with MCI, and 57 healthy older controls (OCs) completed the questionnaire.

Results:

False memories occurred nearly as often as forgetting according to clinicians and family members of patients with MCI and AD. Family members of OCs and patients with MCI reported fewer false memories compared to those of the AD group. As Mini-Mental State Examination scores decreased, the mean score increased for both forgetting and false memories. Among clinicians, correlations were observed between the dementia severity of patients seen with both forgetting and false memories questionnaire scores as well as with the impact of forgetting and false memories on daily life.

Conclusion:

Patients with AD experience false memories almost as frequently as they do forgetting. Given how common false memories are in AD patients, additional work is needed to understand the clinical implications of these false memories on patients’ daily lives. The novel false memories questionnaire developed may be a valuable tool.
Seismic Attenuation and Velocity Measurements of the Uppermost Mantle Beneath the Central and Eastern United States and Implications for the Temperature of the North American Lithosphere
Authors: Yassminh Rayan , Laphim Parichat , Sandvol Eric
Published: February 2020

We constructed a detailed map of the uppermost mantle seismic structure beneath the Central and Eastern United States (CEUS) using the International Seismological Centre Bulletin and seismic waveforms from USArray. Identical Pn and Sn travel time data sets were inverted to tomographically image the uppermost mantlePwave (Pn) velocity,Swave (Sn) velocity, and the velocity ratio (VPn/VSn). Furthermore, we modified the two‐station method in order to limit the contributions of site response and estimate the effective attenuation of Sn phase (Q−1Sn).

Lower Q values generally correspond with lower velocities in terms of both Pn and Sn wave speeds (e.g., New England and the Mississippi Embayment), but some regions, including southern Georgia, eastern South Carolina, and the New Madrid Seismic Zone, show high velocity and low QSnvalues. This can be explained by scattering attenuation of the Sn phase. To estimate the uppermost mantle temperature, a constrained grid‐search algorithm was conducted using the observed VSn, VPn, and QSnwith the calculated velocities of specific compositional models. The uppermost mantle temperature result shows ~300–500 °C beneath the northern midcontinent and 1100 °C beneath New England. Although our temperature results appear to be well resolved, we found that VPn, VSn, and QSnare not enough to constrain the detailed uppermost mantle composition model. Our results highlight significant temperature heterogeneity in the uppermost mantle across the CEUS and is consistent with there not being any melt within the uppermost mantle beneath the CEUS.